Water Quality Impacts Ionizer Performance

How Water Quality Impacts water Ionizer Performance

 

Water quality will play a significant role in how your water ionizer – in fact any water ionizer – performs and its longevity. A water ionizer requires mineral content to create those valued ionizations/ alterations in pH, ORP and to also produce molecular hydrogen H2 in water. Minerals are not only required, they are good. Calcium, potassium and magnesium all naturally occur in water and are called the “essential alkalizing minerals” because they are essential to our health.

The minerals in water are conductive. Conductivity allows for the electrical charge that produces the alterations we are seeking in alkaline, ionized water. Minerals provide a certain “vitality” to water.

Water that lacks mineral content, such as water from reverse osmosis or distillation, as no conductivity and is considered by many to be “dead” or denatured water. It is important to note that all water found in nature has some level of dissolved mineral content, so these types of “pure” waters are literally a man-made phenomenon. Our bodies are designed to drink water with minerals, to use calcium for bones and magnesium for the heart etc. and mankind has been doing so since the dawn of time. It is only in the last few decades, that we have been exposed to pure and mineral free water – often in bottles.

The more mineral content your water has, the more easily your water ionizer will alter/ionize the water and the better water ionization performance(pH,OR, H2) it will achieve and conversely. Water with a high level of mineral content is called hard water, while water with a low mineral content is called soft water.

That stated, all AlkaViva water ionizers will produce an ideal range of healthy drinking water, in both hard and soft water areas, unless used in extreme water quality situations. Please contact AlkaViva Technical Support if your water is unusually hard or soft as you will probably need pretreatment (more details below).

Hard Water Explained

 

What is Hard Water?

If you live in a hard water area, perhaps you have noticed mineral deposits on your dishes and hot water kettle, or rings of insoluble soap scum in your bathtub. These are signs of hard water. Hard water is water that contains high levels of scaling calcium, iron or magnesium mineral ions. These minerals do not pose any health threat, unless in very high amounts, but they can engage in reactions that leave deposits or scale that may damage surfaces or appliances.

Hard water mineral deposits or “scaling”, is the precipitation of minerals which form lime scale. Scale can clog pipes and can decrease the life of virtually all appliances in the home, especially those that use hot water. Scale can do the same thing to your water ionizer, decreasing water flow, water ionization performance and longevity of the water ionizer .

Signs of Hard Water

* Difficult to form lather with soap
* White mineral deposits on your glassware
* Soap scum in your bath tub
* White mineral deposits on your shower head
* White mineral deposits in your tea pot, iron, or other electrical appliance that uses water

 

Water Hardness and Water Ionizer Performance

A water ionizer requires mineral content to operate because minerals conduct electrical charge that produces the alterations found in ionized water. Water that has little or no minerals has no pathway for the electrolysis or “ionization” to occur. water Ionizers are designed to perform optimally within a specific range of mineral content in the source water; too many minerals may damage any water ionizer, too few you may experience decreased water ionization performance. With the right range of conductive minerals your water ionizer will easily alter the water and produce expected water ionization performance measurements in H2, pH and ORP.

Hard Water Treatment Solutions

To protect your investment properly, you must first determine the level of hardness in your water. You can use the Hard Water Test Kit that is supplied with every AlkaViva water ionizer, have your water tested, or get test data from your supplier. The following are AlkaViva’s recommended treatment solutions:

Extreme Water Quality Tolerances

AlkaViva does not recommend using a water ionizer without pretreatment of water that has one or more of the following measurements :

  • Hardness (or Calcium Carbonate) over 150 ppm (8.5 grains).
  • Iron over .3ppm.
  • TDS below 40ppm or over 600ppm.
  • Calcium above 50ppm.

Note: some reports will show “ppm” some will show “mg/l” – they are the same. Knowingly operating your water ionizer above these levels may void your warranty and/or decrease your water ionizer’s performance.
In no event shall AlkaViva or its dealers be liable for any direct, indirect, incidental or special consequential damages to property whatsoever, arising from use of its products with improperly treated or untreated hard water.

AlkaViva’s AquaSafe Water Quality Assurance Program

 

Many water  ionizer companies will sell you an expensive water ionizer and never mention hard water. If you live in an area that has hard water, that is like throwing money down the drain! To properly protect the investment you’ve made in your ionizer, and ensure you get the right pre-treatment at a great price, we are proud to offer our AquaSafe Water Quality Assurance Program.

AquaSafe Water Quality Assurance Program offers you two important water quality “insurance” benefits:

  • Hard Water Test Kit. Each AlkaViva water ionizer / H2 Generator includes a highly effective Hard Water Test Kit. The kit includes a simple-to-use hard water test strip which in less than a minute will determine how hard your water is (if at all). The test results fall in ranges of hardness. We include our recommended pre-treatment solution for each range.
  • The Most Complete Range Of Hard Water Solutions. The AquaSafe Water Quality Assurance Program allows you to purchase the appropriate pre-treatment solution within 30 days of purchasing your water ionizer ]

Other Considerations

 

water Softeners

AlkaViva does not recommend using a water ionizer downstream (or after) a sodium or potassium based ion-exchange water softener. If you have a sodium or potassium ion-exchange water softener, you will need to do one of the following:

  • Bypass the system (if the source water meets the above Water Quality criteria).
  • Change the plumbing connectors and install the water softener on the hot water only.
  • Install a Reverse Osmosis water prefiltration unit and water ionizer Remineralization Cartridge. The Reverse Osmosis will take out the sodium or potassium while the remineralizing cartridge will add healthy minerals back into the water.

Reverse Osmosis (RO) and water Distillers

water ionizers will not work well downstream (or after) a ReverseOsmosys or water distiller. Many homes with an ion-exchange water softening system will have an RO system. These systems remove virtually all the mineral content and leave the water with no conductivity. If you have an RO or distiller, you will need to do one of the following:

  • Bypass the reverse osmosys prefiltration system (if the source water meets the below Water Quality Tolerances).
  • Install an AlkaViva Remineralization Cartridge after the ReverseOsmosys system (an easy solution).

Soft Water Treatment Solution

Soft water is very low in mineral and dissolved solid content which gives water its conductivity. Such water would have a TDS below 40 ppm.

In areas with extremely soft water (or if using a rainwater catchment system), it may not be possible to achieve optimal water ionization performance of your AlkaViva water ionizer. In this situation, an AlkaViva Remineralization Cartridge is recommended. AlkaViva has incorporated a proprietary blend of 70+ organic and inorganic minerals into its Remineralizing Cartridge.

Well Water

The quality of well water can vary greatly and pose some health risks if not tested and mitigated. Well water needs to be tested before using with a water ionizer. Most wells are perfectly suitable for water ionizer operation; you just don’t want to be on the wrong side of that equation unwittingly.

The use of well water poses a number of questions when considering use of a water ionizer. In addition to measurements of water quality for water ionization performance and durability /longevity, health safety related issues are also important considerations when using well water.

Recommendation: Many states require a well water test report in the closing documents of a home sale. Many local governmental Health Agencies offer free testing of well water. We recommend contacting them first. AlkaViva offers at a discounted price a Professional Water Test done in a certified laboratory. More details here.

Important Notes:

  • Please contact AlkaViva if your water falls into any one of the above categories. If your situation requires additional technical assistance, AlkaViva Technical Support will work with you to find a happy solution. If your water is within 10% of two or more of the Extreme Hardness categories, you could possibly experience performance issues with your water ionizer. You may require pretreatment. Please contact Technical Support for guidance.
  • If you are uncertain of the water quality in your area, please contact your local water supplier and request the specific Water Quality information above. The appropriate phone number will be on your water bill. If using well water, contact your county or state health department to inquire about water testing services.

more reasons to chose AlkaViva

water ionizer manufacturer from AlkaViva

 
 

We don’t just say we are the #1 water ionizer company. We prove it!

 

We have sold many top brands water ionizers(Kangen Enagic, Toyo, AlkaBlue, Nexus, KYK, Tyrent, Life Ionizer EmcoTEch, BionTech) and think all the top water ionizer models(no matter the brand) make good alteration to water. The similarity ends there. The differences are in water filtration power, technology , sophistication & design(i.e.:SMART electrodes & DARC II electrode cleaning systems,AutoAdjust optimal performance with low power ), manufacturing quality and durability. Our unique focus is on the importance of clean water. AlkaViva’s UltraWater filter performance (and testing ) is unique . We are the only company who represents two top manufacturers offering water ionizer models that fill different niches. We offer you the best of the best – in water filtration, water ionizer performance, electrodeselectrode cleaning system & durability and customer experience. That is choice. That is smart.

A water  ionizer is a serious investment, so who you buy from is important. AlkaViva is the oldest direct importer in the USA. Between our two founding partners you get over 30 years of USA-specific water ionizer industry expertise. Virtually all our USA competitors started with us as dealers including Life IonizersTM, Tyent, Echo and Chanson. We have helped develop and launch major new water ionization technology that have been emulated by many others, such as MESH electrodes/plates and MARC/DARC improved electrode cleaning systems. We have been instrumental in launching and supplying water ionization components for commercial applications. Most notably, we supply Tennant Company, water cells for their Ec-H2O floor cleaning product line. Ec-H2O was the first commercially successful application of water ionization technology and has won numerous international awards.

Together, our OEM partners offer 69 years of water ionizer manufacturing. They both hold ISO 9001 and 14001 certifications, own patents too numerous to list, and have won many awards for their business practices and products. Both are firmly rooted in ongoing research and development and in quality management practices.

You can trust that our history, experience, knowledge and partnerships allow us to source top performing products from the best manufacturers in the world. Manufacturers that carry the best certifications and the latest cutting edge technology in water ionizers- ensuring you will make the best purchase.

Here is a sampling of industry-first innovations AlkaViva has brought to market:

Electrode Technology Advancements:

  • AlkaViva was the first company to launch MESH electrodes.
  • Robotically sprayed platinum coating technique that results in precise and highly uniform electrode surface.
  • Introduced the new Smart Electrodes which deliver the highest efficiency and performance in producing ORP and H2 alteration.
  • The only company to offer proprietary membrane technology.
  • introduced next Gen SMPS & AutoAdjust to optimally power the electrodes according to (changes in ) your input water

Electrode Cleaning System Advancements:

 

Water Filtration Advancements:

Independent Testing:

Other reasons to choose AlkaViva:

water ionizer performance

Water Ionizer Performance

What you need to know about water ionizers performance…

water ionizer performance is NOT absolute. It depends on three important variables: water quality, the power applied at each setting and water flow rate. In addition to these three variables, performance year-in and year-out is important and depends on how well a water ionizer’s electrode cleaning system works to keep the electrodes and membranes clean. Beware of any company or sales person who tells you “our water ionizer will do “X”. It is simply not true. What is true is that when you understand the variables, and water ionizer cleaning systems, you can make an informed choice. Learn how our AutoAdjust technology helps overcome the three variables and why DARC II cleaning keeps water ionization performance optimal over time. Be smart.

Truth: over the years, the alkaline water ionizer industry has run rife with undocumented water ionization performance claims around pH and ORP and now molecular hydrogen (H2).

Truth: many people who sell alkaline water ionizers state performance absolutes, as in our water ionizer will do “X”.

Truth: you can cut through all this. Below are four things you need to know about water ionizer’s performance metrics in ANY electric water ionizer.

Your Source Water Matters.

This first point cannot be emphasized enough. water ionization performance levels are significantly impacted by source water – whether you are talking about H2, pH and/or ORP. Any water ionizer running on hard water, or water with elevated levels of minerals or high Total Dissolved Solids (TDS), will always perform better. The harder or more mineralized the water, the better the top-end water ionization performance. Conversely, the exact same water ionizer on soft water with low mineral content will always perform lower than it can in hard water.

Comparisons are only legitimate if done using the exact same source water. Beware of importers in hard water areas who over-state performance. For example, Life Ionizers™ is located in Carlsbad, California. They have extreme TDS – over 600ppm1. To contrast, our TDS in Reno is 10% of that at between 60 – 70 ppm. Any credible water ionizer company will state a range of water ionization performance. Not absolutes.

Your water Ionizer’s Flow Rate Matters.

The second important point is that a water ionizer’s flow rate will affect water ionization performance. All things being equal, slower water flow rate will produce more water ionization performance as water will stay longer in contact with the electrodes. Some manufacturers intentionally produce water ionizers with slower flow rates to compensate for less efficient electrodes. Slowing the flow will also typically raise pH, and high pH water doesn’t taste good to most people. The vast majority of alkaline ionized water drinkers settle on lower pH ranges for regular drinking.

Electrode Power Matters.

water Ionizers offer selectable alkaline levels – typically four – that you choose with a push of a button. Each time you choose a higher level, more power is sent to the electrodes and incrementally more water ionization performance is achieved. water Ionizers that advertise high power (some go as high as 800 watts!) are ironically only advertising that they have inefficient electrodes and membrane systems. An incredibly important and often overlooked point is that water ionizers that utilize higher power will experience higher electrode heat. When electrodes get hot, the platinum plating deteriorates. Compromised plating delivers less water ionization performance over time. Many water ionizers tout higher power as the solution to water ionization performance. In the long run, it isn’t.

AutoAdjust in AlkaViva water ionizers detects the hardness of filtered water and dynamically adjusts/sets power applied on electrodes to what is required.

Electrode Cleaning is King.

The effectiveness of a water ionizer’s electrode cleaning system affects water ionization performance over time. This is also an overlooked point. You can have the perfectly mineralized water, the greatest electrodes, proper water flow rate and power, but if your water ionizer can’t eliminate scale, its water ionization performance will drop. Quickly, if you have very hard water. We have tested scaled up water ionizers that do not produce any alteration in the water. To achieve optimal water ionization performance the electrodes must be kept clean – over time. How effectively an water ionizer’s electrode cleaning system works is critical. Don’t be misled by gimmicky marketing names for electrode cleaning systems – it all boils down to the acid to alkaline cleaning ratio. When shopping, ask what the cleaning ratio is and how the system achieves that. If you do not get a lucid answer, run. Fast.

The Ultimate Solution.

While we can’t control source water, we do offer you the most advanced and effective solutions to all the other variables.

Convenience. You want a water flow rate that is fast enough, but not too fast. Super-fast flow rates will not only lower water ionization performance but they will significantly compromise water filtration. Water filters work on contact time. The faster water flow, the less contact time, especially in GAC and vitamin C water filters. The AlkaViva  H2 water ionizer Series runs at 3 lpm which is the ideal balance between great water ionization performance and great water  filtration.

Superior water Filtration. USA made UltraWater filters are the only water ionizer filters that have been independently tested against 172 contaminants and shown to reduce virtually all of them to 99.9%. Even the toughest. There is no better water filter available – because AlkaViva believes that healthy water should start by being clean.

molecular hydrogen H2 Infusion Technology. We employ the highly advanced Smart Electrode design and manufacturing. Next, we match the Smart Electrodes with our own proprietary membrane technology that is optimized to produce optimal molecular hydrogen H2 and ORP -water ionization performance.

Superior electrode cleaning means lasting water ionization & durable performance. AlkaViva H2 Series water ionizers employ our newly improved DARC II Cleaning System which previously (as DARC) was for 9 years the best cleaning system in the industry. DARC II offers the most effective 1:1 cleaning ratio using a constantly reversing polarity system controlled by a non-scaling ceramic valve.

Efficiency. AlkaViva H2 water ionizers employs the most sophisticated and advanced power delivery system. The correct current density ensures the longest electrode life and is only possible using more advanced (smaller sized) plates. You get power  efficiency and water ionization performance. While other less advanced water ionizers are required to use maxed out power of up to 800 watts to achieve water ionization performance, AlkaViva H2 water ionizers run 150 watts of peak power ensuring fantastic power density, unmatched water ionization performance and long durable  plate/electrode life. Our power supply also includes Auto Adjust which automatically adjust the background power using pulse width modification technology – optimizing water ionization performance. You get great water ionization/alteration – even at the better tasting and lower pH levels that most people drink.

Independent testing. AlkaViva is the only water ionizer company to have commissioned an EPA-certified, third party, independent laboratory to document the water performance results of different brands and prove our point about efficiency and performance. Bigger just isn’t better. When it comes to technology – including water ionizers – smaller is.

Note on molecular hydrogen H2 Performance: while we understand the basic science of how molecular H2 is produced during electrolysis, it is a new focus in our industry. No one fully understands all the unique nuances of this delicate electro-chemical process. We don’t fully know how certain properties, in addition to hardness and TDS, affect molecular  H2 performance. Apart from TDS and hardness, it is entirely possible that certain water chemistries lend to better performance, and others to less.

That is a lot of information. However, we feel these are all important points for properly informed customers to consider before simply reading – and believing – a company’s declaration that “our water ionizer does X”.

To get optimal benefits, we offer AlkaViva’s DARC II electrode cleaning and our Smart Electrodes that are perfectly powered for maximum efficiency and water ionization performance that lasts. Exactly what you want.

1) http://www.carlsbadca.gov/civicax/filebank/blobdload.aspx?BlobID=25132

 water ionizer electrodes in the water cell

water ionizer electrodes in the water cell

We drink alkaline ionized water for the healthy properties. The electrodes create the water electrolysis /ionization which deliver those benefits. When it comes to water ionizers, understanding electrodes in the water cell is like understanding the importance of your cardiac system to your overall health.

The water cell is the heart of a water ionizer. It consists of a series of electrodes (plates), each separated by a membrane. This page will explain how water ionizers electrode technologies differ and what that means to water ionizer performance and ultimately your health.

There is so much hype and misinformation about water ionizer electrodes or plates. Some say bigger plates are better. Others make you think that more plates are better. Some advertise more power applied on electrodes– like 800 watts – as if we were powering 20-inch sub-woofers. We are ionizing water. The reality is that bigger or more plates or more power means inefficient engineering and lower quality materials and manufacturing. More or bigger DOES NOT mean better water ionization performance. An often overlooked yet incredibly important point is that more power also means more heat, which means the platinum plating breaks down faster on the surface of the water ionizer electrode. This equals poor water ionization performance over time.

There is hype too around water ionizers electrode/plate type. water ionization performance is not about the electrode/ plate type, but rather the sophistication of the engineering and the quality of the materials and manufacturing.
Educate yourself on some basics and you will easily see why our Smart Electrodes offer you the most advanced engineering, along with the best materials and manufacturing. This means more efficient water ionization performance and lasting durability for electrodes/water cell/water ionizer. That is powerful. That is smart.

All things that smart shoppers look for.

Smart Electrodes

Smart Electrodes start with the highest quality materials. We use certified 99.9% pure titanium from Japan and the highest quality platinum.

The electrodes are engineered employing an advanced flat design that offers more effective surface area than slotted or mesh plates of the same size.

Then the electrodes are robotically electro-plated using a proprietary technique. A computer controlled robotic arm is used to apply the platinum, under pressure, multiple times and from different angles that allows the most precise plating application. The resulting plate surface can direct a uniform electron flow and provide the most efficient power saturation.

AlkaViva’s proprietary electroplating process and the resulting Smart Electrodes feature technological advances and enhanced water ionization performance characteristics which allow superior water ionizer performance in the following ways:

  • Superior platinum adhesion
  • Superior conductivity which allows for lower power and higher water ionization efficiency
  • Increased surface area; up to 3x the number of vertices as smooth dipped plates
  • Optimized water flow dynamics over the plate surface due to vertices (increased water ionization performance proven in independent US EPA certified testing)

When you discover more about water ionizer Electrodes, you can easily understand what puts Smart Electrodes in a league of their own.
Get your PhD in electrodes by clicking on each topic below.

Material Composition

Titanium is the base material in every water ionizer electrode/plate, because it has proven safe and effective. It is corrosion resistant, has the highest strength-to-weight ratio of any metal, is very durable, and demonstrates the ability to easily change polarity, which is critically important in the water ionization process. The best water ionizer plates are coated with platinum because it was determined in a 1992 study by the Japanese Ministry of Health, Labor and Welfare, that platinum is the only entirely safe material to use in water ionizer plating/coating.

Electrode Types

There are three basic types of plates:

  • Flat Plate/electrode: The most common, basic and simple plate design.
  • Mesh Plate/electrode: The most technically advanced configuration; also the most expensive to manufacture.
  • Slotted or “Hybrid” Plate/electrode: A less expensive and less effective version of mesh plate technology.

 

Regardless of what you read, the most critical part of an water ionizer electrode is not the type but rather how the electrodes are engineered, what materials are used and how they are applied or manufactured.

Mesh or Solid electrodes/Plates?

water ionizer electrodes
There are three, distinctly different, types of electrodes / plate designs offered in the market today and each has its own advantages or disadvantages. These are solid plates, slotted or “hybrid” electrodes / plates and mesh electrodes / plates.

These differences have a dramatic effect on power delivery inside of the cell. All three types of plates can deliver the electrical current to the water, but why are AlkaViva electrodes / plates the most efficient? Easy … our highly advanced Smart Electrode Technology!

Traditional Flat electrodes /Plates

A low quality flat plate has no way to organize or channel the current being delivered, meaning it has an inconsistent saturation of electrons. They move across the electrodes / plate finding the path of least resistance, often channeling together and are not effectively or evenly dispersed. This is like watering a garden and having the water run to the low spots and pool there. This results in an inconsistent delivery of power and less efficient / effective water ionization results.

Slotted electrodes /Plates

In contrast to a flat electrodes /plate, with slotted electrodes, there is a clear path for the electrons to travel in more predictable directions – effectively distributing the power in a consistent pattern. When we till our garden into rows and irrigate we are channeling the water to be delivered to the roots where it is needed most. The slotted electrodes /plate is more effective than the traditional flat electrode/ plate. Often has a less effective surface area, depending on the size of the slot.

Mesh electrodes /Plates

A mesh electrode /plate uses the same principle as the slotted plate, but improves upon it by providing cross-channeling to more evenly direct electron flow. The applied current more evenly saturates the plate, increasing the effective delivery of electrical current to create better alteration /ionization in your water. Can have a less effective surface area depending on the design of the mesh electrodes .

Long term research and development findings derived from a 1992 study by the Japanese Ministry of Health, Labor and Welfare indicate platinum to be the only entirely safe material for use in water ionizer plating/coating.

Two distinct methods – Plating (dipping) and Coating; are employed to apply the platinum surface to the titanium electrode/ plate:

Plating: Also known as Cladding or Dipping, plating is the process by which a titanium plate is submerged in a platinum solution. This is the most commonly used manufacturing process due to its cost efficiency.

Coating: Also known as Electroplating, coating is a technically advanced process designed to achieve a higher degree of consistency and uniformity.

The two biggest differences between plating and coating are:

  • The amount of titanium crystals produced
  • The surface coverage characteristics

The following examples visually illustrate two distinct platinum application techniques, Plating (dipping) and Coating (Electroplating).

Plating or Dipping

 

Both dust and voids are clearly visible

Plate surface from above:

Black spot represent voids

D company
Dipping method

X 6000 (Cross section):

X 6000 (Cross section)

D/H company
Dipping method

AlkaViva Coating (Electroplating)

Note the distinct vertices (peaks and valleys) and a 3-dimensional crystalline surface, as compared to the inconsistent surface of the dipped electrodes.

Plate surface from above:

No voids, thin spots or inconsistencies
water ionizer cell plating
AlkaViva plate
(coated platinum)

X 6000 (Cross section):

No voids, thin spots or inconsistencies
water ionizer plate
AlkaViva plate
(coated platinum)

 

Prevention of Titanium Leaching

AlkaViva is able to totally prevent titanium leaching on the electrodes by two methods:

  • Complete and uniform coverage. Our coating process surpasses all other processes in the water ionization industry to more completely and evenly cover the titanium plates with pure platinum, including all edges and all surfaces.
  • More efficient use of power. This means we can apply less power more efficiently which creates far less heat and stress on the water ionizer electrode/plate during the electrical load phases.

View a certified analytical test result from the United States Environmental Protection Agency Primacy Laboratory for the State of Nevada showing that there is no plate leaching.

 

Optimal water ionization Results Without Additives

AlkaViva employs proprietary technologies which are able to achieve optimal water ionization-alkalizing and acidifying results without the use of (potentially harmful) solutions such as salt enhancers.

It isn’t ALL about Electrodes: Membranes

All water ionizers employ ion-selective membranes to separate the electrodes and enable the water to “ionically separate” the water into an alkaline and acidic stream. The membrane is absolutely critical in how a waterionizer performs. You can have a well-designed electrode/plate, powered optimally but if you have poor membranes, then you have poor water ionization performance.

AlkaViva’s Infusion Membranes are made in-house and are ultrasonically pressed, rather than chemically bonded. This provides you with a distinctly superior electrode membrane, designed to work specifically with our Smart Electrodes, giving you unmatched water ionization performance-pH, -ORP, H2.

usage of more watts and amps , spreading the same input voltage over a larger surface area results in less efficiency. This does not deliver the power evenly or efficiently and must do so with greater resistance.

More power means more heat, which means the platinum plating breaks down faster on the surface of the water ionizer electrode. This equals poor water ionization  performance over time.

So now you can see that in truth, bigger electrode is not better. This is why the electronics industry (and others) has shown that when technology advances, it typically results in smaller, more powerful and devices. Why would water ionizers be any different? The truth is they are not.

Water Ionizer Cleaning Systems: Why DARC II auto cleanse is the best electrode cleanse.

https://youtube.com/watch?v=gUZfIs6QoWY

Water Ionizer Cleaning Systems: Why DARC II auto cleanse is the best electrode cleanse.

We drink alkaline ionized water to enjoy the profound benefits created from the transformation of water through created through electrolysis – or more loosely “water ionization”.

Here is the situation: Water has minerals/electrolits. Minerals build up on the electrodes and membranes and these are the two components in your water ionizer that transform the water. Scale essentially “coats” these components, compromising their ability to transform/ionize the water. This mean a decrease in pH, ORP and H2 -water ionization performance, which in turn, reduces any benefit you receive from the water – precisely what you bought your water ionizer for in the first place.

All water ionizers have cleaning systems for electrodes, but all plate cleaning systems are not created equal. Most water ionizers employ outdated plate cleaning systems that have been around for years without any advancement or technological improvement.

 

ultrawater water ionizer filtersSmart Shopper’s Shortcut 
What you need to know about water ionizer cleaning systems…Before you buy a water ionizer, it is crucial that you understand what type of electrode/plate cleaning cycle it employs. This is one of the most important considerations because it determines how well your water ionizer will perform over the long haul. If you are shopping around, ask about the type of electrode / plate cleaning system and how it works. If all the salesperson can do is quote a gimmicky cleaning system name, but can’t tell you the specific acidic to alkaline ratio in their system, or tell you specifically how it works…run. Fast! Then call us. We’ll tell you precisely how DARC II works and why it is the best  water ionizer cleaning system available.

 

The DARC Advantage.

AlkaViva set a new industry standard in 2006 when it launched the patented Dual Automatic Reverse Cleaning system (USA Patent No. 6,951,225). DARC was, and still is – thanks to the patent protection – revolutionary because it cleans the electrodes in the water cell with every use, eliminating damaging scale buildup. It accomplishes this by reversing polarity each time you use the water ionizer.

The revolutionary DARC cleaning system eliminates mineral scaling on the electrodes – protecting your investment and ensuring years of healthy water from your water ionizer. DARC is highly effective because it works in the background to clean your electrode, each time you use your water ionizer and while you are actually using it. The result is a vastly improved acidic to alkaline cleaning ratio, which is critical to keeping the electrodes cleaner than other systems that offer a 15:1 ratio or a 30:1 ratio. The Kangen Enagic™ SD501 which retails at almost $4000, only cleans using a 30:1 ratio1. The importance of this breakthrough cannot be understated.

Additionally, with the dual solenoid system that directs water flow (actually what is patented and what DARC refers to), you never have to wait while your water ionizer cleans to get your alkaline water – an industry first! AlkaViva’s Jupiter  Athena JS 205 Classic and UltraDelphi IO  400 U water ionizers  employ DARC cleaning for electrodes.

The Best just got Better: the New and Improved DARC II electrodes autoclean system .

AlkaViva once again sets a new industry standard by launching DARC II in its new H2 water ionizer series. Over the 11 years since we released DARC we have learned a few things and consequently saw how it could be substantially improved. DARC II offers you the same highly effective cleaning as the original DARC, and convenience of never waiting, but now gives you increased DURABILITY.

Because the original patented DARC solenoid system is outside the water cell, the solenoids DO NOT benefit from the acidic cleaning. The electronic solenoids in DARC contain a metal actuator that operates on a very tight tolerance. Once it gets even a hint of scale, it becomes susceptible to failure. Over 11 years since we launched DARC this was not an uncommon issue in hard water areas.

We improved DARC II by eliminating the electronic solenoid containing the metal actuators. We eliminated the potential failure of the electronic solenoid and also now employ a mechanical ceramic valve (replacing actuator) that is 100% resistant to any scaling. We did not stop there. Reversing the polarity each time you used the water ionizer did not in reality create the best possible acidic to alkaline ratio – which would be 1:1. Imagine you fill an 8 oz glass, then one liter, then a 16 oz glass, then a gallon and on and on. You don’t come close to a 1:1 ratio – even over the life of the water  ionizer. We now reverse the polarity every 5 liters – which creates a ratio much closer to 1:1, thus improving the effectiveness.

DARC II is the new standard in on-board water ionizer cleaning systems borne of experience and research and development. Another AlkaViva first.

Reverse Polarity Cleaning.

Each electrode in your water ionizer has either a positive or negative polarity. Reverse polarity cleaning is simply when your water ionizer reverses the polarity; positive electrodes become negative and conversely. When an electrode is “bathed” in alkaline water containing scaling minerals, it becomes susceptible to scaling. When the polarity is reversed, the same electrode is now exposed to acidic water which removes the scale.

All water ionizers clean using reverse polarity. However, the cleaning systems differ radically in how they trigger it, the interval at which they perform the electrode cleaning cycle, and most importantly, how effective they are.

Understanding other Cleaning Systems.

Since it is the acidic water which eats away the scale, for optimal efficacy the cleaning cycle must feature a good “acid to alkaline cleaning ratio”. The more acidic water that is run to bath the electrodes the cleaner they remain and the greater their water ionization performance and longevity.

The way a water ionizer is “programmed” to clean the electrodes is crucial in determining the electrode cleaning ratio. The most common systems have been in use many years without improvement:

  • Manual system: you must remember to reverse the polarity and initiate the electrode cleaning cycle yourself.
  • Timer system: cleans at a set-interval, such as every 15 minutes of use. After 15 minutes of run time, the next time you turn the water  ionizer on, the unit starts the cleaning cycle. Most often you must wait while it completes the electrode cleaning cycle.
  • Volume system: Similar to the timer system, but cleans based on a set volume of water (Say for example 10 gallons) passing through the water ionizer. You must also wait.
  • Post cleaning systems: while they clean after each use, the clean cycle is extremely short resulting in a poor acidic to alkaline ratio. They also use a finite amount of water to clean – only the water that is in the water cell (since the cleaning is triggered after the water ionizer is shut down). The better post-use systems drain the cell when the cycle is complete, so you do not have contaminated water in the cell that will expel into the drinking water when the water ionizer is turned on. These draining systems are prone to failure at both the PCB and drain valve level.. Not as robust, effective or durable as DARC.

Each has its draw backs: you can forget to trigger a manual cycle, the timer and volume systems have poor acidic to alkaline electride cleaning ratios. The worst drawback is that with each of the above systems you have to wait for the cycle to complete before you can receive alkaline ionized water.

In summary, we love that you have read this far! Because now you can see – emphatically – why cleaning is so important and why and how AlkaViva’s H2 water ionizer Series with its new and improved DARC II autocleanse system for electrodes is your best choice. Consider your searching over!

alkaviva h2 water ionizers
alkaviva h2 water ionizers

*1) The Kangen Enagic  SD501 water ionizer cleans for 20 seconds for each 10 gallons of use. It would take the Kangen Enagic water ionizer approximately 10 minutes of run time at 1 gpm water flow rate to produce 10 gallons. Therefore, 10 mins X 60 seconds = 600. The water ionizer plate cleaning ratio is then 600:20 or reduced is 30:1.

AlkaViva UltraWater filtration technology

AlkaViva UltraWater filtration technology 

 

Simply put, AlkaViva UltraWater filtration is the best alkaline water ionizer filter you can buy. In fact, it is the best water filter — of any type — that is currently available. Our unmatched Independent EPA / NELAP certified lab tests prove it. We often get asked how we can achieve such stunning water filtration/contaminant removal results.
ultrawater water ionizer filtersSmart Shopper’s Shortcut 
What you need to know about UltraWater filtration…AlkaViva UltraWater Filtration TechnologyWhat good is healthy water if it isn’t also clean water? Better than 0.01 micron UltraFiltration or a series of external water filters, UltraWater incorporates  Sediment shield, BioStone Booster, BioStone Carbon Block with Impregnation Plus(zeolite and silver), Bioceramic Tourmaline with Scale Guard, UltraWater Disc Technology to offer ultraclean alkaline ionized and molecular hydrogen water and most important has been tested and certified by a governmental laboratory for efficient removal of 172 water contaminants  – UltraWater filtration technology – the most thoroughly tested and safest water filtration option available.

Here’s How We Do It

Let’s start with an analogy: turbocharged gas engines. When they first came out, they combined new and existing technologies in a novel way. The result was a powerful new combination and unprecedented performance. Similarly, UltraWater filtration technology starts with the water industry’s proven top-performing media, adds in cutting edge medias in a new application, and then creates a new twist on existing manufacturing techniques. The result isn’t just a water filter. It’s a proprietary water filtration technology. This unique combination effectively “turbocharges” the media and water filtration processes, allowing better water filtration performance and better results.

What’s Inside:

sediment shield ultrawater filter

Sediment Shield

Standard GAC water filters do not offer this component. It is an electrostatic wrap comprised of polypropylene spun fiber. It is designed to provide a mechanical barrier to sediment – meaning it traps the sediments.

biostone booster ultrawater filter

Biostone Booster

Comprised of NSF certified CaSO3 slow-eluting bio-ceramic balls. They target chlorine, chloramine certain heavy metals. CaSO3 is more effective than granulated active carbon or KDF. One hundred grams (100g) of CaSO3 will outperform carbon and KDF by a factor of x2.

biostone carbon plus media

BioStone Carbon with Impregnation Plus

Our NSF certified carbon is catalyzed with an oxidizer and has the highest oxidation and adsorption pore concentration available. The carbon is impregnated with natural zeolite(vulcanic rock) and silver(antimicrobial).

The zeolite provides increased heavy metal reduction and a slight ion-exchange effect.

The silver prevents bacteria growth between uses.

We use both carbon block and loose bed applications.

Our carbon blocks are sintered and compressed under high temperature and heat (not extruded) resulting in a superior carbon block. Either way, our proprietary process greatly increases the surface area, contact time and the resulting capability.

ultrawater disc technology in filter

UltraWater Disc Technology

This leading-edge technology is the real turbocharger in UltraWater filter. It combines a high-tech NSF certified reticulated foam which is impregnated with three different medias. All are NSF certified. All offer unmatched heavy metal and organics reduction allowing us to target contaminants that other alkaline water ionizer filters can’t – such as arsenic.

bioceramic tourmaline

Bioceramic Tourmaline with Scale Guard

The tourmaline is in a very hard, slow-eluting biocermic ball from. It releases FAR infrared energy lowering surface tension. Scale Guard is a sequestering agent that is a highly effective anti-scale media. It is in a slow-eluting crystal bead form and is there to protect the water ionizer from hard water damage.

What it Does

UltraWater is the ONLY alkaline water ionizer filter tested for 172 contaminants. Independent EPA / NELAP certified lab testing shows UltraWater is the ONLY water filter that can reduce virtually all contaminants up to 99.9% — even the toughest including arsenic, chromium VI, lead, VOCs and pharmaceuticals

UltraWater filtration technology selectively reduces the bad contaminants while allowing the good, naturally occurring minerals to pass through. This alkaline water ionizer filter design is used in AlkaViva’s UltraWater electric water ionizer range to produce electric ionization.

UltraWater filtration  can also be formulated to create natural water ionization without electricity. Some of the world’s renowned sources of healing water are passively ionized by contact with certain earth alkali minerals, silicate and crystalline complexes. We have formulated an exclusive “passive water ionization” technology inside our non-electric Elita Series which contains the same type of mineral complexes. As water passes over the passive water ionization media we create increased pH, –ORP and molecular hydrogen (H2 water). While multiple beneficial minerals are dissolved, it chiefly infuses magnesium, which is shown to be absorbed best by the body when dissolved in water.

So regardless of which AlkaViva water product you choose, ultraclean and effective UltraWater is the best answer!

Available exclusively from:

ultrawater water ionizer filters

UltraWater Water Ionizer Filters – Tested for 172 Contaminants

Better water filtration Performance. Safer Water. Better Health.

Healthy water has to be clean water. Other ionizer filters simply cannot handle well known water contaminants such as lead, arsenic, chromium VI – and a host of others. Independent EPA / NELAP certified lab testing shows UltraWater reduces virtually all contaminants up to 99.9% — even the toughest including arsenic, chromium VI, lead, VOCs and pharmaceuticals.

AlkaViva testing is:

 

  • Certified & credible: All tests performed in Independent, EPA / NELAP Certified Labs
  • Thorough: we omit nothing and we show results for everything tested.
  • Real world: we tested contaminant levels in parts per million and that were as close the EPA Maximum Contaminant Level as we could get .
  • Nothing hidden or left out: we reported everything – even the toughest to remove contaminants such as arsenic, chromium VI etc.
  • Comprehensive: We tested 21 heavy metals, 65 pharmaceuticals, 3 OTC drugs, 7 Hormones, 15 pesticides and herbicides, preservatives and wastewater indicators, 45 VOCs, and 5 other anions & disinfectants – a total of 172 contaminants!
  • 16 Supercharged Medias
    Advanced Filtration Technologies.
    >See Test Results

    AlkaViva UltraWater Filter Removes

    lead in waterLead
    arsenic in waterArsenic
    drugs in waterPrescription Drugs
    chemicals in waterIndustrial Chemicals
    hormones in waterHormones
    chlorine in waterChloramine
    chemical waterTrihalomethane
    preservatives in waterPreservatives
    herbicides in waterHerbicides
    volatile chemicals in waterVolatile Organic Compounds
    Chromium VI in waterChromium VI
    chlorinated waterChlorine
    polluted waterOTC Drugs
    pesticides in waterPesticides
    heavy metals in waterHeavy Metals

    You NEED AlkaViva UltraWater Filtration

    AlkaViva free local water report

Peer Reviewed Articles on Alkaline Diet  Benefits from Increasing Alkalinity in the Body

Peer Reviewed Articles on Alkaline Diet
 Benefits from Increasing Alkalinity in the Body

 

“Alkaline water produced by a water ionizer has become the most important advancement in health care since Sir Alexander Fleming’s discovery of penicillin.”
— Dr. William Kelly, author, Cancer Cure.

Over the past decade, there has been a growing interest in alkaline diets and living an alkaline lifestyle. Part of this interest may involve drinking alkaline, ionized water from a water ionizer as a way to improve wellness, enhance performance, and prolong vitality. Alkaline, ionized water is water that has been selectively altered in a water ionizer to raise pH from neutral to pH 9 or more and also to display negative change (-ORP). Water above a pH 7 is alkaline and water below pH 7 is acidic. pH can be easily measured by using pH reagent or a meter, and ORP is measured using an ORP meter.

Life on earth depends on appropriate pH levels in and around living organisms and cells. Human life requires a tightly controlled pH level in the serum of about 7.4 (a slightly alkaline range of 7.35 to 7.45) to survive. The ability of the body to maintain this level of pH can be compromised by poor diet, lack of or excessive exercise, pollutants, dehydration, and stress. From available evidence, it would be prudent to consider the effects of alkaline water on the body and an alkaline diet to reduce morbidity and mortality from the chronic diseases that are plaguing our aging population. (www.ncbi.nlm.nih.gov/pmc/articles/PMC3195546/)

Along with this interest in all things alkaline, there have also been some unsubstantiated health claims made. Such claims give rise to pseudo-sciences that undermine the significant body of peer-reviewed, published research into how altering alkaline (pH) levels can bring about health changes. Part of the issue in studying the beneficial effects of an alkaline diet is the lack of funding available for such research coupled with the complexity in trying to isolate what factors are creating change. Indeed, a few studies failed to find health changes from altering diet, although other studies acknowledge distinct benefits. Everyone agrees that more research is needed to further investigate alkaline health benefits.

Not only do AlkaViva water ionizers produce clean, alkaline water, but they can also create a significant amount of diatomic hydrogen (H2) in the water. The peer-reviewed benefits from drinking H2 water are NOT covered in this article.

Below are excerpts from peer-reviewed, ALKALINE diet/water studies along with references as to where the full articles can be found if you wish to study further. We welcome feedback.

Alkaline water Hydration for Athleets

 

It is the position of the American College of Sports Medicine that adequate fluid replacement helps maintain hydration and, therefore, promotes the health, safety, and optimal physical performance of individuals participating in regular physical activity.
Convertino VA, Armstrong LE, Coyle EF, Mack GW, Sawka MN, Senay LC Jr, Sherman WM., American College of Sports Medicine position stand. Exercise and fluid replacement. Med Sci Sports Exerc. 1996 Jan;28(1):i-vii.

A significant difference in whole blood viscosity was detected in this study when assessing a high-pH, water versus an acceptable standard purified water during the recovery phase following strenuous exercise-induced dehydration.
Joseph Weidman, Ralph E. HolsworthJr., Bradley Brossman, Daniel J. Cho, John St.Cyr, Gregory Fridman, ffect of electrolyzed high-pH alkaline water on blood viscosity in healthy adults, Journal of the International Society of Sports Nutrition.

After using an alkalizing supplement trained Nordic skiers experienced significant changes in cardiorespiratory, blood lactate, and upper body power output measures. Studies also indicate that drinking alkaline water can enhance the body’s buffering capacity and temper the acidity, thus improving performance.
Daniel P Heil, Erik A Jacobson, and Stephanie M Howe, Influence of an alkalizing supplement on markers of endurance performance using a double-blind placebo-controlled design, J Int Soc Sports Nutr. 2012; 9: 8. Published online 2012 Mar 20. doi: 10.1186/1550-2783-9-8.

Supplementing with alkalizing minerals (calcium, magnesium, potassium) decreases cardio-respiratory stress and blood lactate responses, while improving power output in endurance athletes. Alkaline water may work similarly.
Y. Kilkian, F. Engel. P. What, J. Master, Markers of Biological Stress, https://www.researchgate.net/publication/308012779.

Consumption of alkaline water was associated with improved acid-base balance (i.e., an alkalization of the blood and urine) and hydration status when consumed under free-living conditions. In contrast, subjects who consumed the placebo bottled water showed no changes over the same period of time. These results indicate that the habitual consumption of alkaline water may be a valuable nutritional vector for influencing both acid-base balance and hydration status in healthy adults. Also, over time, the mineral content of alkalized water could help active people retain more fluid in the cardiovascular system. This might improve overall hydration status and fluid reserves.
D,. Heil, Acid-base balance and hydration status following consumption of mineral-based alkaline bottled water. Movement Science/Human Performance Laboratory, Montana State University.

The physiology of intense exercise that produces acidosis is far more complex than originally thought. In the transition to higher exercise intensity, proton release is even greater than lactate production which indicates acidosis is only partially related to production of “lactic acid.”
Robergs, R. Exercise-induced metabolic acidosis: where do the protons come from? Sport Science 5(2) sportsci.org/jour/0102/rar.thm, 2001.

The Evolution of Diet

Estimates of the net systemic load of acid in ancestral pre-agricultural diets as compared to contemporary diets reflect a mismatch between the nutrient compositions of the diet and genetically determined nutritional requirements. The result is that contemporary diets generate diet-induced metabolic acidosis in contemporary Homo Sapiens.
Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris RC Jr., Estimation of the net acid load of the diet of ancestral pre-agricultural Homo sapiens, www.ncbi.nlm.nih.gov/pubmed/12450898.

Report compiled by the World Health Organization from studies in different regions of the world on the importance of minerals in drinking water.
Ong, Choon. Minerals from drinking-water: Bioavailability for various world populations and health implications. WHO | Water Sanitation Health. World Health Organization, 17 Aug 2004.

Because of the increased incidence of obesity in our population, electrolyzed water at 2 liters/day for 2 months was given to four obese subjects. Statistical evaluation of the results of the present study suggests that electrolyzed water as used resulted in near significant weight loss and a significant loss of body fat in obese subjects.
Abraham, Guy, and Jorge Flebas. The effect of daily consumption of 2 liters of electrolyzed water for 2 months on body composition and several physiological parameters in four obese subjects: a preliminary report. Highbeam Research. Original Internist, 01 Sep 2011. Web. 2 Jul 2013. http://www.highbeam.com/doc/1G1-269433201.html.

Alkalinity/alkaline water and Muscles

As we age, there is a loss of muscle mass, which may predispose to falls and fractures. A three-year study looking at a diet rich in potassium, such as fruits and vegetables, as well as a reduced acid load, resulted in preservation of muscle mass in older men and women.
Dawson-Hughes B, Harris SS, Ceglia L. Alkaline diets favor lean tissue mass in older adults. American Journal of Clinical Nutrition. 2008;87(3):662–665.

Correction of acidosis may preserve muscle mass in conditions where muscle wasting is common such as diabetic ketosis, trauma, sepsis, chronic obstructive lung disease, and renal failure.
Gerry K. Schwalfenberg, University of Alberta, The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health? Journal of Environmental and Public Health, Volume 2012 (2012), Article ID 727630.

Chronic metabolic acidosis increases net muscle protein degradation in rat muscle tissue. Metabolic acidosis stimulates protein degradation in rat muscle by glucocorticoid-dependent mechanism.
Mitch WE, Medina R, Grieber S, May RC, England BK, Price SR, Bailey JL, Goldberg AL., University School of Medicine, Georgia,Metabolic acidosis stimulates muscle protein degradation, https://www.ncbi.nlm.nih.gov/pubmed/8182144.

Bone Loss prevention with alkaline water

The bone minerals that are wasted in the urine may not have complete compensation through intestinal absorption, which is thought to result in osteoporosis. An alkaline diet typically does improve the K/Na ratio and may benefit bone health, reduce muscle wasting, as well as mitigate other chronic diseases such as hypertension and strokes. It has been found increases in the alkali content of a diet, may attenuate bone loss in healthy older adults.
G. K. Schwalfenberg, University of Alberta, Oct 2011. www.ncbi.nlm.nih.gov/pmc/articles/PMC3195546/-.

Dietary acid charge enhances bone loss. Bicarbonate or alkaline diet decreases bone resorption in humans. We compared the effect of an alkaline mineral water, rich in bicarbonate, with that of an acid one, on bone markers, in young women with a normal calcium intake.
Wynn, E, MA Krieg, JM Aeschlimann, and P Burckhardt. Alkaline mineral water lowers bone resorption even in calcium sufficiency: alkaline mineral water and bone metabolism. Bone. Elsevier, 27 Oct 2008. Web. 1 Jul 2013. http://www.thebonejournal.com/article/S8756-3282(08)00781-3/abstract.

Excess dietary protein with high acid renal load may decrease bone density if not buffered by ingestion of supplements or foods (water) that are alkali rich.
G. K. Schwalfenberg, 2012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3195546/.

This work shows that bone depletion is absolutely dependent on extracellular acidification; these cells are inactive at pH levels above about 7.3 and show maximum stimulation at a pH of about 6.9. Bone resorption is most sensitive to changes in H+ concentration at a pH of about 7.1 (which may be close to the interstitial pH in bone). In vivo, severe systemic acidosis (pH change of about -0.05 to -0.20) often results from renal disease; milder chronic acidosis (pH change of about -0.02 to -0.05) can be caused by excessive protein intake, acid feeding, prolonged exercise, ageing, airway diseases or menopause. Acidosis can also occur locally as a result of inflammation, infection, wounds, tumors or diabetic ischemia. Cell function, including that of osteoblasts, is normally impaired by acid; the unusual stimulatory effect of acid on osteoclasts may represent a primitive ‘fail-safe’ that evolved with terrestrial vertebrates to correct systemic acidosis by ensuring release of alkaline bone mineral when the lungs and kidneys are unable to remove sufficient H+ equivalent. The present results suggest that even subtle chronic acidosis could be sufficient to cause appreciable bone loss over time.
Arnett T., Department of Anatomy and Developmental Biology, University College London, https://www.ncbi.nlm.nih.gov/pubmed/14506899.

Humans generally consume a diet that generates metabolic acids leading to a reduction in the systemic bicarbonate and a fall of pH. Chronic metabolic acidosis alters bone cell function; there is an increase in osteoclastic bone resorption and a decrease in osteoblastic bone formation. As we age, we are less able to excrete metabolic acids due to the normal decline in renal function.
Bushinski DA., Nephrology Unit, Strong Memorial Hospital, New York, https://www.ncbi.nlm.nih.gov/pubmed/11842949.

Chronic metabolic acidosis is a process whereby an excess acid load is placed on the body due to excess acid generation or diminished acid removal by normal homeostatic mechanisms. Excessive meat ingestion and aging are two clinical conditions often associated with chronic metabolic acidosis. The body’s homeostatic response to this pathology is very efficient. Therefore, the blood pH is frequently maintained within the “normal” range. However, these homeostatic responses engender pathologic consequences such as nephrolithiasis, bone demineralization, muscle protein breakdown and renal growth.
Alpern RJ1, Sakhaee K., Department of Internal Medicine, University of Texas, https://www.ncbi.nlm.nih.gov/pubmed/9016905.

Excessive dietary intake of protein with consequent increase in metabolic acid production result in compensatory mechanisms that lead to progression of kidney stones, bone disease, renal disease and a catabolic state.
Alpern, R. Trade-offs in the adaptation to acidosis, Kidney International 47: 1205-1215, 1995.

The acid load inherent in the Western diet results in mild chronic metabolic acidosis in association with a state of cortisol excess. An alkali balanced diet modulates bone resorption and the associated alterations in calcium and phosphate homeostasis.
Maurer, M.; Riesen, W.; Muser, J.; Hulter, H. and Krapf, R. Neutralization of Western diet inhibits bone resportion independently of K intake and reduces cortisol secretion in humans, American Journal of Physiology and Renal Physiology 284: F32-40, 2003.

Osteoclast activity is modulated by small pH changes and is a key determinant of bone resorption in mouse calvarial cultures.
Sajeda Meghji, Matthew S. Morrison, Brian Henderson, Timothy R. Arnett, pH Dependence of Bone Resorption American Journal of Physiology – Endocrinology and Metabolism Vol. 280 no. 1, E112-E119.

 

 

 

Alkaline Diet and Growth Hormones

It has long been known that severe forms of metabolic acidosis in children, such as renal tubular acidosis, are associated with low levels of growth hormone with resultant short stature. Correction of the acidosis increases growth hormone significantly and improved growth. Improving growth hormone levels may improve quality of life, reduce cardiovascular risk factors, improve body composition, and even improve memory and cognition.
Wass JAH, Reddy R. Growth hormone and memory. Journal of Endocrinology. 2010;207(2):125–126.

Alkaline Minerals (in water) and Back Pain

There is some evidence that chronic low back pain improves with the supplementation of alkaline minerals. With supplementation there was a slight but significant increase in blood pH and intracellular magnesium. Ensuring that there is enough intracellular magnesium allows for the proper function of enzyme systems that improves back pain and also allows for activation of vitamin D.
Gerry K. Schwalfenberg, The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health? J Environ Public Health. 2012; 2012: 727630.

Alkalinity/alkaline water and Chemotherapy

The effectiveness of chemotherapeutic agents is markedly influenced by pH. Numerous agents such as epirubicin and adriamycin require an alkaline media to be more effective. Cell death correlates with acidosis and intracellular pH shifts higher (more alkaline) after chemotherapy may reflect response to chemotherapy. It has been suggested that inducing metabolic alkalosis may be useful in enhancing some treatment regimes.
Gerry K. Schwalfenberg, The Alkaline Diet: Is There Evidence That an Alkaline pH Diet Benefits Health? J Environ Public Health. 2012; 2012: 727630.

Alkalinity/alkaline water and Cancer

Diet-induced acidosis is a potential upstream and indirect trigger in a multifactorial cascade of molecular events associated with carcinogenesis. The American Institute for Cancer Research (AICR) comprehensive global report has compiled numerous studies demonstrating associations between dietary habits and cancer risk. The findings recommend increased or regular consumption of vegetables, fruits, whole grains, and legumes, while discouraging excess consumption of sugary and energy-dense foods and drinks, red and processed meats, and salty processed foods.
Ian Forrest Robey, University of Arizona, Examining the relationship between diet-induced acidosis and cancer, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3571898/.

Oral administration of pH buffers can reduce the development of spontaneous and experimental metastases in mice, and has been proposed in clinical trials. It is notable that cancer cells maintain a high level of glucose metabolism even in the presence of oxygen, which was first documented by Warburg more than 80 years ago. This is a consistent finding across a variety of cancers, and has been recognized as a “hallmark” of cancer.
Maria de Lourdes C Ribeiro, Ariosto S. Silva, Kate M. Bailey, Nagi B. Kumar, Thomas A. Sellers, Robert A. Gatenby, Arig Ibrahim-Hashim, and Robert J. Gillies, Buffer Therapy for Cancer, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872072/.

A significant consequence of increased glucose metabolism is the production of acids, such as lactic acid, which can be an independent negative prognostic factor for cancer outcome. Prior mathematical models and empirical studies have shown that solid tumors export acid into the surrounding parenchyma. This is consistent with measurements of tumor pH in mouse models, which have shown that the extracellular pH of solid tumors is acidic. Combined, these observations have led to the generation of the “Acid Mediated Tumor Invasion” hypothesis, which proposes that fast-growing tumors export acid to surrounding stroma, and that reduced pH contributes to the tissue remodeling required for tumor invasion.
Ian F. Robey, Brenda K. Baggett, Nathaniel D. Kirkpatrick, Denise J. Roe, Julie Dosescu, Bonnie F. Sloane, Arig Ibrahim Hashim, David L. Morse, Natarajan Raghunand, Robert A. Gatenby, and Robert J. Gillies, Bicarbonate Increases Tumor pH and Inhibits Spontaneous Metastases, Cancer Res. 2009 Mar 15; 69(6): 2260–2268.

Alkalinity/alkaline water and Effects on Aging

alkalinity and aging

Changes in renal physiology and function with aging put the elderly patient at risk for adverse effect of drug therapies due to the incidence of common problems like metabolic acidosis.
Lonergan, E. Aging and the kidney: adjusting treatment to physiologic change, Geriatrics 43: 27-30, 32-33, 1998.

Authors examined peer-reviewed literature to determine whether systemic acid-base equilibrium changes with aging in normal adults humans. Using linear regression analysis, they found that with increasing age, there is a significant increase in the steady-state blood H+ indicating a progressively worsening low-level metabolic acidosis in what may reflect, in part, the normal decline of renal function with increasing age.
Frassetto, L. and Sebastian, A. Age and systemic acid-base equilibrium: analysis of published data, Journal of Gerontology, Advanced Biological Science and Medical Science, 51: B91-99, 1996.

Dietary changes over the last two centuries have resulted in a mismatch between genetically-determined nutritional requirements in humans. Excess sodium chloride, a deficiency of potassium and excess dietary acids that are not mediated by dietary bicarbonates lead to chronic low-grade metabolic acidosis that amplifies the age-related pathophysiological consequences in humans (such as loss of bone substance, increase in urinary calcium, disturbance in nitrogen metabolism, and low levels of growth hormone).
Frassetto, L.; Morris, R.; Sellmeyer, D.; Todd, K. and Sebastian, A. Diet, evolution and aging: the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet, European Journal of Nutrition 40:5 200-213, 2001.

Otherwise healthy adults manifest a low-grade, diet-dependent metabolic acidosis, the severity of which increases with age at constant rate described by an index of endogenous acid production, apparently due in part, to the normal age-related decline of renal function.
Frassetto, L.; Morris, R. and Sebastian, A. Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline, American Journal of Physiology, 271: 1114-22, 1996.

Age-induced decline in renal functions explains, at least in part, clinically important age-related conditions including metabolic acidosis.
Krapt, R. and Jehle, A. Renal function and renal disease in the elderly, Schweizerische Medizinische Wochenschrift, 130:11 398-408 2000.

Acid-base homeostasis exerts a major influence on protein function, thereby critically affecting tissue and organ performance. Deviations in body acidity can have adverse consequences and when severe, can be life-threatening.
Adrogue, H. and Madias, N. Management of life-threatening acid-base disorders, New England Journal of Medicine 338: 26-34, 1998.

Decline in the ability to adjust acid-base balance is a feature of aging. Regulation of pH ultimately depends on the kidneys and lungs, however, the ability of these organs is decreased with physiological aging. Renal insufficiency and/or chronic obstructive pulmonary disease and various drugs, such as diuretics, often affect the acid-base balance in the elderly.
Nabata, T.; Morimoto, S. and Ogihara, T. Abnormalities in acid-base balance in the elderly, Nippon Rinsho 50: 2249-53, 1992.

 

AlkaViva UltraWater is alkaline and ionized making it rich in naturally occurring beneficial minerals like calcium and magnesium that help you alkalize and maintain a HEALTHY PH BALANCE.

UltraWater filter & ionizer - life enhancement
UltraWater filter & ionizer – life enhancement

 

Alkaline ionized Water and Free Radicals

Active oxygen species or free radicals are considered to cause extensive oxidative damage to biological macromolecules. The ideal scavenger for active oxygen should be “active hydrogen”. “Active diatomic hydrogen” can be produced in reduced (alkaline) water near the cathode during electrolysis of water. Reduced (alkaline) water exhibits high pH, low dissolved oxygen (DO), extremely high dissolved molecular hydrogen (H2), and extremely negative redox potential (-ORP) values. Reduced water suppresses single-strand breakage of DNA b active oxygen species suggesting that reduced water can scavenge different types of free radicals.
Shirahata S, Kabayama S, Nakano M, Miura T, Kusumoto K, Gotoh M, Hayashi H, Otsubo K, Morisawa S, Katakura Y., EmoryElectrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage, Biochem Biophys Res Commun. 1997 May 8;234(1):269-74.

ionized water Benefits backed by research.

Over 600 PEER-REVIEWED STUDIES show that molecular hydrogen – or H2 -water / alkaline ionized water has a therapeutic benefit in every organ of the human body and positively affects over 150 disease models and health conditions.

Get your antioxidants – in your water!

Free radical damage causes oxidative stress and is one of the primary causes of aging. Oxidation causes iron or apples to “rust”. Antioxidants prevent or slow that damage. Unfortunately, anti-oxidants are non-selective neutralizing both beneficial and harmful radicals. The molecular hydrogen Hin UltraWater selectively targets only the damaging radicals – making it the “ULTIMATE” ANTIOXIDANT.

Drink more. Improve your health.

When molecular hydrogen  H2 neutralizes damaging oxygen radicals, it creates water (H2O) – increasing your CELLULAR HYDRATION.Great tasting, silky-smooth, alkaline UltraWater is also easier to drink. When you drink more, you enjoy optimal hydration and better health.

Ease your aches and pains.

Oxidative stress damages your cells, causing pain and inflammation. As we age, inflammation increases. Studies show that H₂ neutralizes the damaging radicals. Drinking UltraWater can ease chronic and acute aches and pain.

Go longer. Go stronger.

ATP powers your cells. It is the source of your energy. Research shows molecular hydrogen(water) H₂ helps INCREASE ATP PRODUCTION giving you more energy while decreasing lactic acid levels. Athlete? Exerciser? Just want more pep? UltraWater helps improve performance and recovery.

 

Molecular hydrogen water overview-definiton, benefits, research , studies  ,safety

Molecular hydrogen (water) benefits/effects in disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants

more about molecular hydrogen water

AlkaViva water ionizers& purifiers-clean , ionized alkaline water rich in molecular hidrogen H2

 

 

 

AlkaViva H2 water ionizers Certificates 

AlkaViva H2 water ionizers Certificates

AlkaViva H2 water ionizers purifiers certifications

Company Registration

Permission for medical device manufacturing item
The manufacturer of the medical device shall be examined according to the medical device technique (Article 6) for the approval of the product and the facility and quality system for the product to be manufactured.
Since receiving the manufacturing approval of No. 889 in 2000, AlkaViva’s manufacturer has obtained 28 licenses of alkaline water ionizer items as of 2017.
US food pharmacy medical device manufacturing site and device registration
The US Department of Health and Human Services (FDA) is responsible for the distribution and management of medical devices in the United States under the Ministry of Health and Welfare. Manufacturers, distributors, and importers of medical devices must be approved and certified by the FDA. AlkaViva’s manufacturer was approved in 2005 and registered all items of water ionizer equipment.
Trademark registration
The KIPO is a government agency that manages industrial property rights such as patents, utility models, designs and trademarks. When the inventors filed industrial property rights, the Korean Intellectual Property Office obtained the rights by examining them.

Management System

Medical device manufacturing and quality control certification
Good Manufacturing Practice (GMP) is a system for manufacturing and selling quality medical devices that are guaranteed by the organization, from the design of the product, the purchase of raw materials, to the manufacture, It is a standard that defines the things to be managed and maintained. AlkaViva’s manufacturer has been certified for the first time in 2005 and has maintained its effectiveness since its regular review.
Quality system
It is an international standard for quality management system enacted by the International Organization for Standardization (ISO) to evaluate and certify the quality assurance system throughout the entire production process, from products and services.
Environmental system
ISO 14001 This system evaluates the environmentally friendly management of the environment by introducing an environmental management system throughout the company’s activities. We identify the environmental hazards that occur during the production process and apply them as a method to manage the management system. AlkaViva’s manufacturer was certified in 2008.
Certificate of Origin Certification
The customs authorities shall issue a certificate of origin to the exporter who certifies that the exporter has the capability to prove that he satisfies the criteria for determining the origin of the exported goods in accordance with the Enforcement Rule of the Act on the Exemption of Customs Act for the Implementation of the FTA As a system to simplify the submission of attached documents, AlkaViva’s manufacturer has obtained certification for each item in 2013.

Electric Safety

European Community Integration Certification
It is a mandatory certification mark indicating that the product has been tested and is in conformity with the applicable EU standards for requirements relating to safety, health, environment and consumer protection in accordance with national certification schemes and technical regulations in the European Union. AlkaViva’s manufacturer was certified by product in 1998.
North American Electrical and Electronic Products Safety Certification
The NRTL program is part of the Occupational Safety and Health Administration (OSHA) guidelines to ensure that the product is safe for use in North America. Normally, when you want to export to North America, you have to obtain UL-marks for the US market, CSA-marks for the Canadian market, and NOM-marks for the Mexico region. One NRTL-marks after NAFTA (North American Free Trade Agreement) I can solve it easily. Since its acquisition of UL certification in 1998, AlkaViva’s manufacturer has obtained the 1201sus NRTL factory certification.
International electric appliance certification
It is an international electrical certification system operated by IECEE. It is a system that tests the safety of electrical and electronic products in accordance with the IEC international standard and mutually recognizes the test results internationally among the member countries. Currently, many countries, mainly in Europe, adopt the IEC standard as their own standards. AlkaViva’s manufacturer has been certified by product in 2010.
National Integrated Certification Mark KC
You can safely use it as a proven product that keeps safety standards. KC certification is made from materials that are harmless to human body, it is given after verifying that it is safe enough to maintain buoyancy and durability, so it is a product that you can trust and buy more.
Japan electric appliance type certification
It is the certification system according to the Electrical Appliance and Material Safety Law applicable to electrical and electronic products in Japan. It is compulsory certification that the customs clearance and sale in Japan are prohibited before obtaining the certification. In 2006, AlkaViva’s manufacturer certified DIAMOND PSE Certified Electrical Appliances.
Germany certified
It is an international electrical certification system operated by IECEE. It is a system that tests the safety of electrical and electronic products in accordance with IEC international standards and mutually recognizes the test settlement internationally among the member countries. Currently, many countries, mainly in Europe, adopt the IEC standard as their own standards. AlkaViva’s manufacturer has been certified by product in 2010.

Alkaline ionized water, obliterating arteritis and diabetes 

Alkaline ionized water, obliterating arteritis and diabetes – ionized alkaline water saves from amputation one leg of the patient with obliterated arteritis and diabetes

“I write these lines both for my facebook friends and for the multitude of patients suffering from diabetes and implicitly by obliterant arteritis and who sooner or later reach stents mounted in coronary, iliac, subclavicular arteries, or worse -amputation of the lower limbs.
I retired in 2002 following a myocardial infarction and since then the troubles (medical problems) have kept coming.
Due to the insulin-induced diabetes diagnosed in the 1990s, between 2002-2005, three (2-foot) surgeries were done to replace the arteries (due to massive atheroma deposits) with femoral-popliteal vascular prostheses (by-passes) at the right foot twice.
In 2011, the right foot bypass began to close (by deposition of the atheroma), which made the stenosis of the arteries under the knee (tibial and peronian) almost reach 100%. Having had major coronary problems, the doctors refused to change my right foot bypass (it would have been the third time and recommended me to make a daily infusion of “vasaprosta”(  expensive and which was distributed by CNAS with special approval) for 30 days, the procedure being considered (then) as a means of rescuing the foot from amputation.
In my case this procedure (vasaphase infusions) proved to have the effect of rubbing with “Galenica” on an acacia wood leg. As the number of infusions increased, the pain of the foot soles was increasing and the leg was all the time cold.
I informed him several times of the doctor under whose supervision these perfusions were being made, of the evolution of the disease (unbearable pain and cold leg) but not only did he not count me but he did not even take a strain on my leg. For peace reasons I do not give  the name of the doc!
After 20 days of infusions, one morning after I woke up, I noticed that my toes were black and soaked. We had the gangrene.
I turned to emergency and the surgeon at the vascular surgery department (as a day of rest) refused to interfere because they did not cut off fingers and advised emergency staff to call the surgery department for leg amputation.
I went to Bucharest and admitted to the Emergency University Hospital at the Vascular Surgery Clinic.
On December 6, 2011 I my right leg fingers were amputated . Because the gangrene continued, on December 9 I underwent a new metatarsal amputation and replaced my vascular prosthesis with a saphenous vein harvested from the amputee foot
On December 12, I had a heart attack and I was admitted to intensive care. On December 15 we made a cardiac arrest and I was intubated …
I stayed intubated for several days in incapacity, while my lungs were sucked several times a day.
After I was discharged from intensive care, I was admitted to cardiology and after a while I began to cough more and more. I was treated with bronchitis until discharge from the hospital
The cough continued after discharge and eventually I went to emergency in Constanta at the Otolaryngology section, where it was ascertained that due to intensive care suction maneuvers, after the cardiac arrest, my trachea was injured, which led to the appearance of an excrescence that finally almost obstructed my trachea.
I had surgery (post-tubal tracheostomy) and through surgery I was mounted a plastic cannula under the apple of Adam through which we breathe.
The operation of the foot has never healed.
In June 2013, I was implanted (I do not know if the term is correct) 5 stents in the coronary hearts at Fundeni Hospital.
In September 2013 (year with bad luck) the foot pain again began to amputate, having to accept a new amputation this time above the knee.
Finally, in September, three successive amputations were made at my right foot by a “great” doctor professor, but more about the professionalism and competence of the individual maybe another time.
After the third amputation, I went home with half the stools from the bumps and with my leg in the amputation area. After another month of home treatment, a nurse in surgery managed to heal my dent.
Since spring last year, my left foot, which has a femur-popliteal prosthesis since 2004 (they are guaranteed for 5-6 years) has started to hurt and the situation worsens in the beginning of 2017, with all medications, ointments and massages (including lymphatic) that have been given and done all along.
In February 2017, I did a vascular / arterial doppler exam that revealed that the bypass has a 70% stenosis, the anterior tibial is oval, the posterior tibial has 98% occlusion, and the peroneal artery has a 98% occlusion. Finally, the cardiologist who did my doppler exam, probably to encourage me,  said that in 2-3 weeks I will get to left foot amputation and showed me where they were going to amputate ….

I have a good friend and colleague from high school class, the energetic engineer GIDEA- SANDUTU VERGICA from Filiasi whom I told of my misfortune and that soon I will lose my left leg through amputation

Very relaxed and with great confidence he told me that I do not have to worry -they will not amputate my leg as he’ll help solve my problem. I replied that it was not good a joke … not to say anything else. He explained that there was no joke, that he would not allow himself to make jokes with me in the given situation and asked me if I heard anything about ALKALINE IONIZED WATER. NO, I said. I said that I do not know what it is, and that I do not think there is any drug in the world (which we also know, foolishness) that can dissolve the arteries deposits … much less a water,she would call it she-chiara, holy water or ionized alkaline water. Having realized he had no palpable arguments to convince me, he told me that this water produces absolutely nothing wrong with the body when drinking it and that he will send me water starting from the next day, having previously bought a water ionizer for producing this ionized alkaline water;he also told me that in my situation, I have two possibilities, namely:

– first, to expect the blood circulation to the leg to close definitively and reach to the gangrene and amputation,

-second  to drink at least 5 liters of ionized alkaline water daily, the water that will melt the atheroma from the arteries, the circulation of the blood going back to normal and save my foot.

I chose the second variant, knowing it was terrible it’s hard to live without a foot and get you I do not think it’s worth the pain anyway, I think it would not be worth the trouble for those around you, I would have become a calvary (I do not know if I’m wrong about that) I began to drink ionized alkaline water, sent by my friend, in the first few days 3 liters after which, I easily drank 5-6 liters a day. By then, the foot was from the kneel down, cold and white, and pains and burns, especially at night, were unbearable; I got 3-4 ketone pills per night. After 2 weeks of drinking ionized alkaline water the pains and burns diminished and in a few days they finally disappeared. 3 weeks ago his leg warmed and so remained. On March 17 we went to a private clinic in Constanta and I did (against the sum of 800 lei, CNAS funds not yet allocated) an angio CT scan of the arteries of in the pelvis and lower limbs that revealed:

– thigh amputation its right;

– 50% bypass stenosis

– 70% tibio-peronian occlusion trunk

– posterior tibial artery

– occlusion

In the meantime I was scheduled to be admitted to the Emergency University Hospital of Bucharest and on May 12, 2017, I made an arteriography revealed that the aorta and the iliac shaft are permeable, the femoropoplite bypass is permeable and permeable gambling trunk. Arteriography is an invasive artery investigation and remains the most significant in analyzing blood circulation, measurements and images being made from within the arteries.

I will express in words what I felt when the doctor who made the investigation recorded her voice with the result of viewing the monitor on which the arteriography was displayed. Never before, in my life, a word so common as  “PERMEABLE” had such GREAT significance and value.

I think the sun has appeared on my street, which is what I want. If you want to document and see that ionized alkaline water seems to be the universal medicine, you can find hundreds of sites about it and its benefits. In the meantime I bought a  ALKAVIVA water ionizer  !

I wish only good things!

.PS I WILL TALK AND ABOUT THE DIABETES SPPN …A FEW MONTHS AGO I HAD 40 MIXTARD UNITS IN THE MORNING AND 20 AT NIGHT

NOW- 20 UNITS IN THE MORNING AND 10 IN THE EVENING …

TODAY THE GLICEMIC INDEX IN THE MORNING WAS 124 AND I DID NOT HAVE ANY MIXTARD .NOW I HAVE GLYCEMIA 70 AND I HAVE NO NEED FOR MIXTARD ”

DESPRE APA ALCALINA IONIZATA Scriu aceste randuri atat pentru prietenii mei de pe…

Posted by Alexandru Bîzdîc on 18 Iunie 2017

MORE ABOUT ALKALINE IONIZED WATER/  molecular hydrogen H2- Water  AND DIABETES

MORE ABOUT ALKALINE IONIZED WATER/ molecular hydrogen H2- Water  AND BLOOD VESSELS HEALTH

 

 

Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis

Abstract

Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases.

Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.

1. Introduction

Sepsis is a systematic inflammatory response to infection. It is one of the most serious diseases in ICU, which is a worldwide challenge. Although comprehensive therapy has been developed for it, sepsis is still associated with high morbidity and mortality and costs a lot for hospitalization. In the United States, severe sepsis affects 750,000 people per year, which costs $16.7 billion annually and increases in its incidence over time of 8.7% [].

Sepsis leads to abnormal blood pressure, heart rate, and PaO2. It also influences different organs and even leads to multiple organ dysfunction syndromes (MODS). The main clinical characteristics of brain include delirium, coma, disorientation, the slowing of mental processes, and cognitive dysfunction. Sepsis leads to acute lung injury and acute respiratory distress syndrome (ARDS), whose mortality rate is as high as 30% to 50% in critically ill patients. In liver, disruption of protein synthetic function manifests as progressive disruption of blood clotting and disruption of metabolic functions leads to impaired bilirubin metabolism. The incidence of acute kidney injury is nearly 65% in critically ill patients and is able to aggravate the condition of patients with septic shock. Sepsis also decreases the blood flow of the gastrointestinal tract, which might induce severe ischemia, hypoxia, and reperfusion injury.

Recent research suggests that molecular hydrogen works as a therapeutic antioxidant activity by selectively reducing hydroxyl radicals and protects against organ damage effectively. In 2007, inhalation of  molecular hydrogen gas was found to suppress brain injury by buffering the effects of oxidative stress in an acute focal ischemia and reperfusion rat mode [].

In 2008,  molecular hydrogen therapy was found to inhibit the inflammatory reaction in the rat model of small intestinal transplantation. Contemporarily,  molecular hydrogen therapy was proved to protect against acute pancreatitis [].

In 2010, molecular hydrogen’s protective effects on sepsis and sepsis-associated organ damage were found, which mainly relied on its antioxidative property [].

There are 3 main methods of molecular hydrogen therapy: inhalation of  molecular hydrogen gas (H2), oral intake of molecular hydrogen-rich water (HRW), and injection of molecular hydrogen-saturated saline (HRS). Molecular hydrogen therapy also can be combined with other therapy such as resuscitation and oxygen therapy.

2. Oxidative Stress in Sepsis

Autoimmune injury occurs in sepsis, and the pathogenesis is very complicated, in which oxidative stress plays an important role.

The immunocyte is activated and the respiratory burst creates amount of reactive oxygen species (ROS). Oxidative stress induced by ROS can change the permeability of epithelial cells by destroying the cell membrane. The imbalance of antioxidant defense systems against oxidative stress also can damage the epithelial cells [].

3. Mechanism of Molecular Hydrogen

Molecular hydrogen is a scavenger of the hydroxyl radical. molecular hydrogen/ H2 can selectively reduce ROS in vitro; it will react with only the strongest oxidants, which means the use of molecular hydrogen H2 is mild enough having no serious side effects [].

Molecular hydrogen can suppress the release of cell adhesion molecules, as well as proinflammatory cytokines. molecular hydrogen H2 could elevate anti-inflammatory cytokine levels. molecular hydrogen H2 enhanced HO-1 expression and activity, which suggest that molecular hydrogen H2 could suppress excessive inflammatory responses and endothelial injury via an Nrf2 (nuclear factor erythroid 2 p45 related factor 2)/HO-1 pathway [].

In addition, it has been proposed that molecular hydrogen has the capabilities to affect several pathways and assist in the gene regulation or protein expression of MPO (myeloperoxidase), MCP, Caspase-3, Caspase-12, TNF (tumor necrosis factor), interleukins, Bcl-2, Bax, and Cox-2 (as shown in Figure 1 []).

Figure 1

Possible mechanisms of molecular hydrogen. Possible pathways for molecular hydrogen. It has been proposed that molecular hydrogen has the capabilities to affect the pathways mentioned and to directly or indirectly assist in the gene regulation or protein 

4. The Impact of Molecular Hydrogen on General Condition

In animal experiments, sepsis alters general condition of mice, such as mean artery pressure (MAP) decreasing and PaO2 declining.

In Liu et al.’s study, MAP decreased in 20 minutes after LPS (Lipopolysaccharide) injection. There was no significant difference in resuscitation group and resuscitation+ molecular hydrogen H2 group, while the fluid volume and usage of norepinephrine were less used in resuscitation+ molecular hydrogen H2 group []. In another study, resuscitation group needs more fluid and norepinephrine than molecular hydrogen H2 group although these two groups get to similar MAP [].

Many studies showed that sepsis makes PaO2 and PaO2/FiO2 decline, and molecular hydrogen therapy can alleviate this change. Xie et al. stated that PaO2/FiO2 ratio declined significantly in cecal ligation and puncture (CLP) group. Inhalation of molecular hydrogen H2 gas can remit the change []. PaO2 declined in Liu et al.’s study of septic mice. Resuscitation improved PaO2 to 62.34 ± 2.46 mmHg (p < 0.05), but resuscitation+ molecular hydrogen Hinhalation showed more effectivity by improving PaO2 to 88.98 ± 3.17 mmHg [].

When molecular hydrogen therapy is used alone, it is also valid. Li et al. stated that HRS increased PaO2 of 59 ± 6 mmHg to 67 ± 8 mmHg (p < 0.05) in CLP mice []. Xie et al. showed PaO2/FiO2 significantly decreased in LPS-challenged mice, which improved by molecular hydrogen H2 inhalation [].

Generally, sepsis decreased MAP, PaO2, and PaO2/FiO2. Traditional resuscitation can alleviate these changes. It works better while combined with molecular hydrogen therapy. Molecular hydrogen therapy makes it possible for using less fluid and the vasoactive agent to reach the target MAP level. Molecular hydrogen therapy also significantly improves PaO2 and PaO2/FiO2 in sepsis.

5. The Impact of Molecular Hydrogen on Different Organs

The impact of molecular hydrogen on changes of the biochemistry indicator level in different organs was summarized in Table 1.

Table 1

The impact of changes of the biochemistry indicator level.

5.1. Brain

Brain is one of the organs to be affected during early sepsis. It is strongly associated with higher mortality and lower quality of life.

Morphologic changes can be detected by pathologic examination. Brain sections were stained with H&E (hematoxylin-eosin staining). In normal condition, the hippocampal CA1 region shows tightly arranged nerve cell bodies with clear structures; cytoplasm in cells is plentiful. However, animal experiments found that most neurons in CLP-challenged mice were shrunken and stained dark; the intracellular space was enlarged. With HRS injection, the cells with eumorphism were significantly preserved. Total normal cell count in sham group was 295.50 ± 12.91, while the number in CLP group was significantly decreased. Compared with CLP group, the numbers of normal cells were much higher in HRS treatment group. This data revealed the dose-response relationship of HRS treatment []. Inhalation of molecular hydrogen H2 stated similar consequence with HRS treatment. In Liu et al.’s study, the pyramidal neurons in hippocampal CA1 region were arranged in disorder in CLP group, containing the dissolved Nissl bodies. This disorder was slighter in molecular hydrogen H2 inhalation group. A mass of apoptotic cells in hippocampal CA1 region was found in CLP group, and there were fewer apoptotic cells found in molecular hydrogen H2 inhalation group []. Zhou et al.’s study also confirmed the result [].

Both immunohistochemical staining of cleaved Caspase-3 and western blot of cleaved Caspase-3 expression in hippocampus indicate a great increase in CLP group. With HRS therapy Caspase-3 was dramatically reduced after the CLP event. The number of cleaved Caspase-3-positive cells was 223.62 ± 25.71 in CLP group, which was significantly greater than the sham group. Nevertheless, the numbers in 2.5 mg/kg and 10 mg/kg HRS treatment group were 142.26 ± 9.89 and 84.13 ± 12.48, respectively. Significant differences were found in those groups [].

 molecular hydrogen H2 treatment can attenuate blood-brain barrier disruption. Evans blue (EB) is a dye binding to serum albumin, which can seldom go through the Blood Brain Barrier (BBB). But in CLP group, obvious rise of EB quantification was observed compared with sham group; molecular hydrogen H2 treatment group showed less EB quantification compared with CLP group (p < 0.001). molecular hydrogen H2 treatment can also reduce brain water content. The brain water content was 74.85 ± 0.75 in sham group, which increased to 78.34 ± 0.82 (%) in CLP group (p < 0.001) and to 76.57 ± 0.87 (%) in molecular hydrogen H2 treatment group [].

HRS treatment and molecular hydrogen H2 treatment prevented the abnormal changes of oxidation and antioxidation. Septic mice had lower levels of SOD and higher levels of ROS and MDA (Malondialdehyde); both HRS treatment and  molecular hydrogen H2 treatment can prevent those changes. There was also a dose-response relationship showed in studies []. Moreover, activities of antioxidant enzymes (SOD and CAT) in both serum and hippocampus were significantly diminished in CLP group. On the contrary, the levels of oxidative products (MDA and 8-iso-PGF2α) were markedly increased. molecular hydrogen H2 treatment could upregulate the expression of Nrf2, which is an important transcription factor of antioxidant stress to lighten those abnormal changes. This finding may explain the antioxidant effects of molecular hydrogen therapy [].

 molecular hydrogen H2 inhalation can significantly decrease the levels of proinflammatory cytokines (TNF-α, IL-1β, and HMGB1) and increase the level of anti-inflammatory cytokines (IL-10) (p < 0.001), in both serum and hippocampus [].

Researchers measured the cognitive function of CLP-challenged mice with several methods. In Y-maze test and Fear conditioning test, molecular hydrogen H2 group showed higher cognitive function at days 3 to 14 after CLP operation []. The Morris water maze test results in cognitive impairment in CLP group; HRS injection could alleviate cognitive impairment. When the dosage of HRS boosts into 10 mL/kg, no significant difference was found between sham group and HRS treatment group. Interestingly, cognitive dysfunction recovered 10 days after the CLP event. It indicated that forced exercise may influence learning and memory.

In conclusion, sepsis can destroy the structure of brain especially hippocampus CA1 region through stimulating oxidative stress reaction and inflammatory response, which lead to impairment of cognition. However, molecular hydrogen therapy was proved to attenuate the disruption.

5.2. Lung

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are common syndromes in sepsis. When ALI occurs, the oxygenation index, lung MPO activity, lung W/D weight ratio, BAL (bronchoalveolar lavage) and total protein, lung’s histology, antioxidant enzymatic activity, and inflammatory cytokines are all different from normal conditions.

The normal lung structure has no hyperemia, neutrophil infiltration. But in sepsis, there can be found disordered alveolar structures, collapse of alveoli, incomplete alveolar wall, severe neutrophil infiltration, alveolar capillary congestion, and thickened alveolar wall by edema. Resuscitation only can reduce neutrophil accumulation and the alveolar-capillary exudate but cannot alleviate alveolar edema. When combined with molecular hydrogen H2 inhalation, the therapy significantly decreased in alveolar damage and alveolar edema as well []. In addition, HRS administration individually could also decrease infiltration of neutrophils, interstitial edema, and atelectasis []. molecular hydrogen H2 inhalation is confirmed to be effective as well to attenuate sepsis-induced lung injury in mice. 2% molecular hydrogen H2 treatment resulted in reduction of inflammatory cells infiltration and improvement in lung structure [].

Moreover, effects of molecular hydrogen H2 treatment on pulmonary cell apoptosis were investigated. Numerous lung cells were positive for TUNEL (TdT-mediated dUTP Nick-End Labeling) staining which identified apoptotic cells in LPS group. In the samples of molecular hydrogen H2 treatment group, a few of positive cells were observed. Caspase-3 detection showed the same tendency in those groups. Those data revealed LPS-induced septic stimulated pulmonary cell apoptosis and  molecular hydrogen H2 therapy would prevent this process [].

Lung W/D weight ratio is an indicator of the magnitude of pulmonary edema. Septic lung showed higher W/D ratios in all studies. Resuscitation+ molecular hydrogen H2 group showed a significant decrease in the lung W/D value compared with resuscitation group, which indicates that H2 inhalation was benefit to relieve edema []. HRS administration also decreased pulmonary W/D weight ratio []. molecular hydrogen H2 inhalation alone decreased W/D ratio as well [].

Examination of cell counts and protein concentration in BALF is a particular technique to evaluate lung effusion and its character. Animals studies mentioned that CLP or LPS increased the cell counts and protein in BALF, which could be remitted with H2 inhalation []. Xie et al. proved that molecular hydrogen H2 inhalation and HRS injection were both effective to reduce the cell counts, PMNs (Polymorphonuclears), and total protein increased by LPS [].

Antioxidant enzymatic activity in lung (SOD and CAT) was suppressed and level of oxidative products (MDA and 8-iso-PGF2α) was increased in sepsis. molecular hydrogen H2 inhalation and HRS injection both could restrain oxidative stress []. Some study presented that increased MPO in the lung of septic mice could be lightened by molecular hydrogen therapy [] but others presented that HRS injection had no effect of decreasing MPO level [].

Inflammatory cytokines (TNF-α, HMGB1, IL-1β, IL-6, and IL-8) were increased while anti-inflammatory cytokines (IL-10) were decreased, in serum and lung in sepsis patients. Molecular hydrogen therapy could reduce the level of inflammatory cytokines [] and increase the level of anti-inflammatory cytokines [] in septic mice. There are also some researchers who considered molecular hydrogen therapy had no significant effect on the level of TNF-α and IL-10 [].

Liu et al. [] combined H2 therapy with NO therapy in LPS-challenged mice and found that the combination therapy had significant interaction between the two and had more beneficial effect than H2inhalation alone.

Generally speaking, lung structure was damaged by sepsis. Lung W/D ratios, cell counts and protein concentration in BALF, level of oxidative products, and inflammatory cytokines were found increased, while antioxidative enzyme activity and anti-inflammatory cytokines were found decreased. Although there still were controversies [], most researchers regarded molecular hydrogen therapy as a valid technique to alleviate all those pathologic changes.

5.3. Liver

Liver is one of the most important organs, but also one of the first organs to be affected during sepsis. Except for degree of oxidative stress reaction and inflammatory reaction, ALT and AST (aspartate aminotransferase) can also reveal hepatic function.

Histopathological changes in liver were shown in sepsis. Animal study shows liver histologic scores significantly increased in CLP group; O2 inhalation group and  molecular hydrogenH2 inhalation group both showed much lower scores, which even had no difference to sham group [].

In addition, CLP mice developed significant liver injury, which was assessed by ALT and AST increase. H2 inhalation and HRS injection both could attenuate these abnormal changes []. Especially in Xie et al.’s study, molecular hydrogen H2 inhalation group even had no significant difference with sham group, indicating the dramatic effect of molecular hydrogen H2 therapy [].

Oxidative stress reaction and inflammatory reaction of liver were similar with lung. Inflammatory cytokines like TNF-α and HMGB1 were increased, while anti-inflammatory cytokines like IL-10 were decreased in sepsis. Antioxidant enzyme activities (SOD and CAT) were decreased and oxidative products (8-iso-PGF2α) were increased. molecular hydrogen H2 inhalation alleviated those changes [].

Studies about liver damage and hepatic function in sepsis with molecular hydrogen therapy were in a small number. Even so, these results revealed a dramatic effect of molecular hydrogen therapy. It may indicate that molecular hydrogen therapy is much more efficacious in liver protection. More research is needed in this area.

5.4. Kidney

Acute kidney injury (AKI) is a common disease in septic patients and can aggravate the condition of septic shock patients, resulting in higher mortality. Except for degree of oxidative stress reaction and inflammatory reaction, blood urea nitrogen (BUN) and creatinine (Cr) can also reveal hepatic function.

H&E staining of kidney tissues exhibited edema in renal tubular epithelial, damaged brush border, and interstitial edema with hemorrhage in septic mice. Tubular epithelial cell damage was ameliorated in molecular hydrogen Hinhalation group. The similar result showed in transmission electron microscopic analysis of glomerular filtration membrane []. Kidney histologic scores increased significantly in CLP group; it is marvelously alleviated in  molecular hydrogen H 2 inhalation group which even had no difference with sham group [].

Serum BUN and Cr were much higher in LPS or CLP group than in sham group. H2 inhalation group had significant reductions of serum BUN and Cr []. But one study revealed there was no significant difference of BUN/Cr ratio in all the groups. As BUN/Cr ratio is used to analyze whether prerenal azotemia or tubular ischemia exists in AKI, molecular hydrogen therapy may not be as effective as we thought [].

Oxidative stress reaction and inflammatory reaction of kidney were similar with lung and liver. Inflammatory cytokines (TNF-α, IL-6, and HMGB1) were increased, while anti-inflammatory cytokines (IL-10) were decreased in sepsis. Antioxidant enzyme activities (SOD and CAT) were decreased and oxidative products (MDA and 8-iso-PGF2α) were increased. H2 inhalation alleviated those changes []. However, in study of Liu et al., level of IL-10 had no change between all groups [].

In spite of some dispute, molecular hydrogen therapy was considered as a useful method to alleviate structure damage of kidney, protect renal function, and resist inflammatory reaction and oxidative reaction.

5.5. Intestine

Sepsis leads to significant decrease in blood flow of the gastrointestinal tract. Hyperperfusion induces severe ischemia, hypoxia, and reperfusion injury. Researchers also work at molecular hydrogen therapy alleviating septic damage in intestine.

In animal study, after LPS manipulating, the structure of the small intestinal mucosa was damaged. Glands of the small intestine were destroyed. Edema of mucosal villi, neutrophil infiltration, and even intestinal ulceration was also commonly observed in sepsis. Resuscitation therapy worsened the damage mentioned above while molecular hydrogen H2 inhalation reduced the damage. The histologic score of LPS group was significantly higher than sham group, but the score of molecular hydrogen H2 inhalation group was significantly decreased compared with LPS group [].

The serum diamine oxidase (DAO) activity reflects degree of intestinal mucosa epithelium cell impaired. Levels of DAO in sham group, LPS group, and H2 group were 4.32 ± 0.33 kU/L, 6.54 ± 0.68 kU/L, and 5.14 kU/L (p < 0.05), respectively []. The result demonstrated that molecular hydrogen H2 inhalation could protect epithelium cell of intestine from septic damage.

Oxidative stress reaction and inflammatory reaction of intestine were similar with lung, liver, and kidney. Inflammatory cytokines (TNF-α, IL-6, IL-8) were increased in LPS group. Antioxidant enzyme activity (SOD) was decreased and oxidative products (MDA) were increased in sepsis. molecular hydrogen H2 inhalation alleviated those changes.

The effect of molecular hydrogen therapy of intestinal damage in sepsis curing with molecular hydrogen therapy needs more research. According to the only literature of study, molecular hydrogen therapy protected intestine from sepsis.

6. The Impact of Molecular Hydrogen on Outcomes

All the research indicated molecular hydrogen therapy can improve survival rate of septic animal whatever the method of drug administration and sepsis inducing.

Zhang et al. compared 3 different ways to induce sepsis and the survival rate, respectively. The survival rates of LPS-induced septic mice at 24, 48, and 72 hr were 88.89%, 66.67%, and 66.67%. With HRS treatment, the survival rate increased to 100% (p < 0.05), 75%, and 75%, respectively. When challenged by feces injection, survival rates of mice at 24, 48, and 72 hr were 100%, 75%, and 75%. With HRS treatment, the survival rate increased to 85.71%, 85.71% (p < 0.05), and 85.71% (p < 0.05), respectively. Survival rates of CLP-induced septic mice at 24, 48, and 72 hr were 76.47%, 47.06%, and 35.23%. With HRS treatment, the survival rate increased to 72.73%, 72.73% (p < 0.01), and 54.54% (p < 0.01), respectively. The 3-day mortality rates after modeling were 33.33% (LPS model), 25% (feces model), and 64.7% (CLP model), while HRS treatment reduced them to 25%, 14.29% (p < 0.05), and 45.45% (p < 0.01), respectively []. There was still no denied data yet.

7. Safety Concerns

As mentioned before, there are 3 methods of molecular hydrogen therapy: inhalation of  molecular hydrogen (H2), oral intake of molecular hydrogen-rich water, and injection of molecular hydrogen-saturated saline. In low concentration (4.1% in pure oxygen or 4.6% in the air), molecular hydrogen is neither explosive nor dangerous. Others thought it is safer to dissolve  molecular hydrogen into water and administrate the HRS by oral or by injection.

 Once again one can benefit from molecular hydrogen  H2 regardless of the method of administration, including from drinking molecular hydrogen water wich proved to be far superior than inhaling hydrogen gas for example – read more about Modalities of molecular hydrogen administration(in water, gas or saline) to animals, humans, and plants

Molecular hydrogen-rich water is expected to be easily used in place of regular everyday drinking water and will effectively treat chronic maladies such as lifestyle-related diseases.In addition, molecular hydrogen water is both safe and easy to drink at home( we think it’s easier to drink molecular hydrogen water than injecting molecular hydrogen rich saline or inhaling molecular hydrogen gas)

8. Conclusion

Molecular hydrogen therapy has a protective effect on sepsis, which has been proved by pathological biopsy, level of inflammatory factors/anti-inflammatory factors, oxidative stress reaction, behavioral experiment, and other related indicators of organ function. Although there is a dispute of affections of molecular hydrogen therapy in liver and kidney, the mainstream view shows molecular hydrogen therapy is benefit to organs, such as brain, lung, liver, kidney, and small intestine.

Molecular hydrogen therapy combining with oxygen therapy or fluid resuscitation can reduce oxygen free radical damage, the amount of fluid and vasoactive drugs, and the overload of liquid. As a result, molecular hydrogen therapy may reduce the complications of oxygen therapy and fluid resuscitation.

However, most of the study conclusion came from animal experiment while reports of clinical research were rare. Much more clinical evidence is still demanded.

In conclusion, molecular hydrogen therapy is a promising method to alleviate organ damage, improve outcome, and reduce mortality rate in sepsis.

Competing Interests

The authors declare that they have no competing interests.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931094/

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Oxidative Medicine and Cellular Longevity
. 2016; 2016: 5806057.
Published online 2016 Jun 20. doi:  10.1155/2016/5806057
PMCID: PMC4931094
Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis

References

1. Martin G. S., Mannino D. M., Eaton S., Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. New England Journal of Medicine2003;348(16):1546–1554. doi: 10.1056/NEJMoa022139. [PubMed] [Cross Ref]
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4. Zhang J., Wu Q., Song S., et al. Effect of hydrogen-rich water on acute peritonitis of rat models. International Immunopharmacology2014;21(1):94–101. doi: 10.1016/j.intimp.2014.04.011. [PubMed][Cross Ref]
5. Xie K., Yu Y., Pei Y., et al. Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release. Shock2010;34(1):90–97. doi: 10.1097/SHK.0b013e3181cdc4ae. [PubMed] [Cross Ref]
6. Liu W., Shan L.-P., Dong X.-S., Liu X.-W., Ma T., Liu Z. Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury. World Journal of Gastroenterology2013;19(4):492–502. doi: 10.3748/wjg.v19.i4.492. [PMC free article] [PubMed] [Cross Ref]
7. Zhou J., Chen Y., Huang G.-Q., et al. Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture. Journal of Surgical Research2012;178(1):390–400. doi: 10.1016/j.jss.2012.01.041. [PubMed] [Cross Ref]
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10. Xie K., Fu W., Xing W., et al. Combination therapy with molecular hydrogen and hyperoxia in a murine model of polymicrobial sepsis. Shock2012;38(6):656–663. doi: 10.1097/SHK.0b013e3182758646.[PubMed] [Cross Ref]
11. Li G.-M., Ji M.-H., Sun X.-J., et al. Effects of hydrogen-rich saline treatment on polymicrobial sepsis. Journal of Surgical Research2013;181(2):279–286. doi: 10.1016/j.jss.2012.06.058. [PubMed] [Cross Ref]
12. Xie K., Yu Y., Huang Y., et al. Molecular hydrogen ameliorates lipopolysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis. Shock2012;37(5):548–555. doi: 10.1097/shk.0b013e31824ddc81. [PubMed] [Cross Ref]
13. Liu W., Dong X.-S., Sun Y.-Q., Liu Z. A novel fluid resuscitation protocol: provide more protection on acute kidney injury during septic shock in rats. International Journal of Clinical and Experimental Medicine2014;7(4):919–926. [PMC free article] [PubMed]
14. Chen H., Xie K., Han H., et al. Molecular hydrogen protects mice against polymicrobial sepsis by ameliorating endothelial dysfunction via an Nrf2/HO-1 signaling pathway. International Immunopharmacology2015;28(1):643–654. doi: 10.1016/j.intimp.2015.07.034. [PubMed] [Cross Ref]
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Articles from Oxidative Medicine and Cellular Longevity are provided here courtesy of Hindawi

molecular hydrogen on higher plants and in agriculture

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While the medical effects of molecular hydrogen have been broadly analyzed, research into the effects of molecular hydrogen on higher plants has often been of lesser concern. Recent studies on the botanical effects of molecular hydrogen have shown that it is involved in signal transduction pathways of plant hormones and can improve the resistance of plants to stressors, such as drought, salinity, cold and heavy metals. In addition, molecular hydrogen could delay postharvest ripening and senescence of fruits. Observational evidence has also shown that molecular hydrogen can regulate the flowering time of plants. These results indicate that molecular hydrogen may have great potential applications within agricultural production, indicating that there may be a new ‘hydrogen agricultural era’ to come.

Introduction

molecular Hydrogen is the most widely distributed element in the world, accounting for more than 75% of the mass of the universe, and it is also the most abound element of human body composition. molecular Hydrogen gas is colorless, odorless and tasteless, and was considered to be physiologically inert molecule, regarding as a potential resource for clean energy in future.

From 1930s to 1940s, some of the bacteria and algae were found capable of producing molecular hydrogen [,]. After going through more than half a century, gain little application did the industrialization of molecular hydrogen production by bacteria and algae. But in 2007, things turned the corner. Scientists from Nippon Medical University published a paper about medical protective effect of hydrogen on Nature Medicine which completely updated our knowledge about hydrogen in biology-hydrogen can not only be considered as a source of energy, but also has an therapeutic potent in disease []. In this study, the authors found that the molecular hydrogen protected cerebral ischemia-reperfusion injury by selectively reducing · OH and ONOO which are two most toxic reactive oxygen species in body. This surprising discovery immediately attracted numerous researchers all over the world, and variously new medical and biological effects of molecular hydrogen have been reported after that. It is never coming to mind that molecular hydrogen which had been implied as respiration gas in diving for its inactive in mammals now seems to become a “wonder drug” in fighting diseases. Some researchers in Japan and China have also developed variety of molecular hydrogen related health products which are warmly pursued by the public. Therefore, many researchers also believed that, with deeper digging, molecular hydrogen may play a major role in promoting human health.

Since molecular hydrogen gradually becomes the most shining star in medicine, health care and cosmetic fields, gracefully waving in agricultural production is also hydrogen. People probably did not expect that molecular hydrogen can be used not only for medical treatment and health care, but also may be widely applied to agricultural production. This may lead us to embrace the coming of “the era of molecular hydrogen agricultural”!

molecular Hydrogen production in higher plants

Early in nineteenth century, researchers had realized the bacteria and algae could synthesis molecular hydrogen. In 1931, researchers reported the first bacteria enzyme which activates molecular hydrogen []. In 1942, photochemical production of molecular hydrogen in algae was firstly found []. If most bacteria and algae could produce molecular hydrogen under certain conditions [], what about higher plants? Can higher plants produce molecular hydrogen either?

In 1947, Boichenko claimed that chloroplasts isolated from algae can release molecular hydrogen. Scientists naturally come to the assumption that higher plants whose leaves also contain chloroplasts may able to produce molecular hydrogen []. In the year of 1961, the evidence of higher plants leaves releasing and absorbing molecular hydrogen was demonstrated by Sanadze []. In 1964, Renwick and his colleges denoted that many higher plants could release molecular hydrogen and exogenous molecular hydrogen could promote the germination rate of winter rye seed []. After that hydrogenase with activity of molecular hydrogen production was isolated by Maione and Gibbs from the chloroplast of Chlamydomonas reinhardtii. They had the hypothesis that hydrogenase should also exist in some higher plants []. Then confirming evidences–release of molecular hydrogen and detection of hydrogenase activity from barley roots–published by Torres showed that the higher plants can actually release molecular hydrogen []. Since then the study on higher plants for molecular hydrogen production is ignored for a long time. One reason for that probably to get clean energy not for its biological effects was the firstly intention of investigating on hydrogen production. Another reason is that the inconvenience of molecular hydrogen collection compared with collection in bacterial and algae.

molecular Hydrogen effects on higher plants

The first finding of molecular hydrogen effects on higher plants was in 1964, when Renwick et al. found molecular hydrogen treated winter rye seeds germinate more rapidly than control []. Unfortunately, scientists have not done further study since then. molecular Hydrogen effects on higher plants have not been followed until health effects of hydrogen are generally concerned. Recently, researchers in China preliminarily studied molecular hydrogen effects on higher plants, the results show that the molecular hydrogen has important regulation effect on plant physiological function, especially plays an important role in plant resistance to abiotic stress. The study shows that molecular hydrogen has an important effect on the mung bean, rice [] and alfalfa (Medicago sativa) [] seed germination, and the molecular hydrogen H2 pretreatment can improve the rice and Arabidopsis salt stress resistance [].

Researchers at the Nanjing Agricultural University found that molecular hydrogen H2 pretreatment can induce the expression of heme oxygenase (HO-1) gene, one of Alfalfa antioxidase gene, and enhance its enzyme activity, reducing the oxidative damage caused by paraquat []. They presumed that molecular hydrogen H2 might function as an important gaseous molecule that alleviates oxidative stress via HO-1 signalling. They also found that the molecular hydrogen H2pretreatment can improve salt tolerance in rice and Arabidopsis, and the improvement of salt tolerance may be related to the reduction of reactive oxygen species (ROS) injuries []. In addition, they found that molecular hydrogen enhances the resistance of alfalfa to cadmium and aluminum due to the improvement of alfalfa antioxidant capacity induced by molecular hydrogen [,].

Researchers at the Southern China Botanical Garden, Chinese Academy of Sciences, and Second Military Medical University in Shanghai confirmed the antioxidant role of molecular hydrogen in rice seedlings, and found that antioxidant enzyme gene expression was induced by H2. In addition, upregulation of several phytohormone receptor genes and genes that encode a few key factors involved in plant signaling pathways was detected in rice seedlings treated with molecular hydrogen water. molecular hydrogen H2 production was found to be induced by abscise acid, ethylene, and jasmonate acid, salt, and drought stress and was consistent with hydrogenase activity and the expression of putative hydrogenase genes in rice seedlings. The study suggests that molecular hydrogen might be an important plant gaseous signaling molecules, which may participate in the regulation of plant hormone signaling pathways involved in plant growth and stress adaptation [].

“molecular Hydrogen agricultural era” is waving to us

A major feature of modern agriculture is the extensive use of fertilizers and pesticides. Now, the abuse of pesticides and fertilizers causes serious environmental pollution, soil degradation and food safety issues. Due to the safety of molecular hydrogen H2, the convenience and economy of molecular hydrogen water usage, the prospect of its application in agricultural production will be very attractive. Recently, some field trials done by several agricultural research institutions in China shows that molecular hydrogen and molecular hydrogen water seems to be valuable for agricultural production especially for soilless cultivation of crops, and may also have a positive effect on the nutritional value of crops. In the future, farmers may use molecular hydrogen water to replace or partially substitute for pesticide and fertilizer to enhance crop resistance to disease, insect, drought and salinity stress, and improve product quality, increase the yield. How exciting the “molecular hydrogen agricultural era” is! The application of hydrogen in agricultural production may be in the following aspects:

Seed germination

Studies show that molecular hydrogen H2 can promote the seed germination rate of winter rye and alfalfa []. This finding may promote the application of molecular hydrogen in improving the seed germination rate of plants.

Regulation of flowering time

It has been observed that roses and other plants change flowering time after treatment of molecular hydrogen water. It was also found that molecular hydrogen can regulate the expression of plant blossom related plant hormone receptor protein gene []. This finding suggests that molecular hydrogen water will have broad application prospects in horticulture.

Improvement of crop stress resistance

Drought and salinity stresses often result in crop yield reduction and even death. Studies found that molecular hydrogen water can improve the resistance ability of rice, Arabidopsis and Medicago sativa plants to salinity, drought and other stresses [,]. The crops irrigation or sprinkler irrigation using molecular hydrogen water, will improve the stress resistance of crops, to achieve the purpose of disaster prevention and reduction.

Improvement of crop resistance to disease and pests

The study have found that molecular hydrogen can regulate the expression of receptor protein genes of many plant hormone, including some plant hormones associated with disease resistance, such as salicylic acid and jasmonic acid []. Irrigation of crops by the use of molecular hydrogen water will likely improve crop resistance to pest and disease leading to substitute for pesticides or reduce the use of pesticides thus it protect environment and improve food security.

Improvement of the quality of agricultural products

molecular Hydrogen water irrigation of crops, such as vegetables and fruits, might make them much more delicious.

Reducing fertilizer use

molecular hydrogen H2 can regulate the effects of plant hormones such as auxin, cytokine. molecular Hydrogen water treatment can promote the growth of the plant. It has been observed that molecular hydrogen water has a significant effect on the growth of mung bean plants []. Therefore, in the future, molecular hydrogen water may be attractively used to irrigate crops, promoting plant growth, and reducing the use of chemical fertilizers.

Crop products preservation

The study has been shown that molecular hydrogen water treatment could delay postharvest ripening and senescence of kiwifruit. Reduction of oxidative damage was considered be one of the main mechanisms by which the molecular hydrogen water treatment delays senescence and inhibits respiration of kiwifruit []. Owing to the antioxidant properties of molecular hydrogen, molecular hydrogen or molecular hydrogen gas mixtures with other gases may contribute to the preservation of agricultural products. Due to the security of molecular hydrogen, no poison, no residue, it has a strong advantage of food safety compared with other chemical treatment of fresh agricultural products.

“molecular Hydrogen agricultural era” is desirable, but it still requires amounts of deep research and development, which firstly should be to study the mechanism of molecular hydrogen effects on higher plants, to lay a solid theoretical foundation for the application of molecular hydrogen agriculture; and secondly be to do a large scale field experiment, to figure out the precise methods of molecular hydrogen or molecular hydrogen water application in the agricultural production. We believe that, with these problems being solved gradually, “molecular hydrogen agricultural era” will step to us.

Competing interest

We are here to formly state that all the authors have no competing interest on this article.

Authors’ contribution

JZ participated in conception, designing and writing the article. ZY and XS contributed to the critical review and revision of the manuscript. All authors have seen and approved the final version of the manuscript.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177722/
. 2014; 4: 15.
Published online 2014 Aug 20. doi:  10.1186/2045-9912-4-15
Progress in the study of biological effects of hydrogen on higher plants and its promising application in agriculture

References

  • Gaffron H. Reduction of carbon dioxide with molecular hydrogen in green algae. Nature. 1939;143:204–205. doi: 10.1038/143204a0. [Cross Ref]
  • Gaffron H, Rubin J. Fermentative and photochemical production of hydrogen in algae. J Gen Physiol. 1942;26:219–240. doi: 10.1085/jgp.26.2.219. [PMC free article] [PubMed] [Cross Ref]
  • Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K. et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med. 2007;13(6):688–694. doi: 10.1038/nm1577. [PubMed] [Cross Ref]
  • Stephenson M, Stickland LH. Hydrogenase: a bacterial enzyme activating molecular hydrogen: The properties of the enzyme. Biochem J. 1931;25(1):205–214. [PMC free article] [PubMed]
  • Melis A, Melnicki MR. Integrated biological hydrogen production. Int J Hydrogen Energy. 2006;31(11):1563–1573. doi: 10.1016/j.ijhydene.2006.06.038. [Cross Ref]
  • Maione TE, Gibbs M. Hydrogenase-mediated activities in isolated chloroplasts of Chlamydomonas reinhardii. Plant Physiol. 1986;80(2):360–363. doi: 10.1104/pp.80.2.360. [PMC free article][PubMed] [Cross Ref]
  • Sanadze GA. Absorption of molecular hydrogen by green leaves in light. Fiziol Rast. 1961;8:555–559.
  • Renwick GM, Giumarro C, Siegel SM. Hydrogen metabolism in higher plants. Plant Physiol. 1964;39(3):303–306. doi: 10.1104/pp.39.3.303. [PMC free article] [PubMed] [Cross Ref]
  • Torres V, Ballesteros A, Fernández VM. Expression of hydrogenase activity in barley roots (Hordeum vulgare L.) after anaerobic stress. Arch Biochem Biophys. 1986;245:174–178. doi: 10.1016/0003-9861(86)90202-X. [PubMed] [Cross Ref]
  • Zeng J, Zhang M, Sun X. Molecular hydrogen is involved in phytohormone signaling and stress responses in plants. PLoS One. 2013;8(8):e71038. doi: 10.1371/journal.pone.0071038.[PMC free article] [PubMed] [Cross Ref]
  • Jin Q, Zhu K, Cui W, Xie Y, Han B, Shen W. Hydrogen gas acts as a novel bioactive molecule in enhancing plant tolerance to paraquat-induced oxidative stress via the modulation of heme oxygenase-1 signalling system. Plant Cell Environ. 2013;36(5):956–969. doi: 10.1111/pce.12029.[PubMed] [Cross Ref]
  • Xie Y, Mao Y, Lai D, Zhang W, Shen W. H2 enhances arabidopsis salt tolerance by manipulating ZAT10/12-mediated antioxidant defence and controlling sodium exclusion. PLoS One. 2012;7(11):e49800. doi: 10.1371/journal.pone.0049800. [PMC free article] [PubMed] [Cross Ref]
  • Chen M, Cui W, Zhu K, Xie Y, Zhang C, Shen W. Hydrogen-rich water alleviates aluminum-induced inhibition of root elongation in alfalfa via decreasing nitric oxide production. J Hazard Mater. 2014;267:40–47. [PubMed]
  • Cui W, Gao C, Fang P, Lin G, Shen W. Alleviation of cadmium toxicity in Medicago sativa by hydrogen-rich water. J Hazard Mater. 2013;260:715–724. [PubMed]
  • Hu H, Li P, Wang Y, Gu R. Hydrogen-rich water delays postharvest ripening and senescence of kiwifruit. Food Chem. 2014;156:100–109. [PubMed]

Articles from Medical Gas Research are provided here courtesy of Wolters Kluwer — Medknow Publications

Antibacterial effect of electrolyzed/ionized water on oral bacteria

Antibacterial effect of electrolyzed/ionized water on oral bacteria.

This study investigated the antibacterial effect of electrolyzed /ionized water on oral bacteria both in vitro and in vivo.

Tap water was electrolyzed in a water vessel using platinum cell technology.

The electrolyzed/ionized acidic tap water (called Puri-water) was put in contact with five major periodontopathogens or toothbrushes contaminated with these bacteria for 30 sec. In addition, Puri-water was used as a mouthwash for 30 sec in 16 subjects and the antibacterial effect on salivary bacteria was evaluated.

Puri-water significantly reduced the growth of all periodontopathogens in culture and on toothbrushes, and that of aerobic and anaerobic bacteria in saliva, when compared to the effect of tap water. It also significantly reduced mutans streptococci growing on mitis salivarius-bacitracin agar. Our results demonstrate that the electrolyzed/ionized acidic water from  tap water is effective as a mouthwash and for toothbrush disinfection.

REDUCTION WAS IMPRESSIVE TO ALMOST 10-15 PERCENT-READ FULL TEXT  FOR FREE 

PMID: 16953177
https://www.ncbi.nlm.nih.gov/pubmed/16953177

 

Antibacterial effect of electrolyzed water on oral bacteria.  , 2006. 44(4): p. 417-22.

1
Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.

 

 

molecular hydrogen treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial

Acarbose, which is clinically widely used to treat Type 2 Diabetes, is thought to act at the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing post prandial glucose excursion. The major side-effect of treatment with acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amount of molecular hydrogen.

We propose that enteric benefits of acarbose is partly attributable to be their ability to neutralise oxidative stress via increased production of molecular hydrogen H2 in the gastrointestinal tract.

CONTEXT:

The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns.

OBJECTIVE:

To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an alpha-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT).

DESIGN, SETTING, AND PARTICIPANTS:

International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years.

INTERVENTION:

Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714).

MAIN OUTCOME MEASURES:

The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (> or =140/90 mm Hg).

RESULTS:

Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P =.03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P =.02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P =.006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P =.02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P =.004) associated with acarbose treatment was still statistically significant.

CONCLUSION:

This study suggests that treating IGT patients with acarbose/molecular hydrogen is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

treatment of ulcerative colitis by increasing molecular hydrogen production

Acarbose, which is clinically widely used to treat Type 2 Diabetes, is thought to act at the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing post prandial glucose excursion. The major side-effect of treatment with acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amount of molecular hydrogen.

We propose that enteric benefits of acarbose is partly attributable to be their ability to neutralise oxidative stress via increased production of molecular hydrogen H2 in the gastrointestinal tract.

Therefore, symptoms of ulcerative colitis in human beings can be ameliorated by acarbose.

https://www.ncbi.nlm.nih.gov/pubmed/24082339-PMID: 24082339

molecular hydrogen water for patients with pressure ulcer – effects on normal human skin wounds

 

Pressure ulcer (PU) is common in immobile elderly patients, and there are some research works to investigate a preventive and curative method, but not to find sufficient effectiveness. The aim of this study is to clarify the clinical effectiveness on wound healing in patients with pressure ulcer PU by molecular hydrogen-dissolved in water (HW) intake via tube-feeding (TF). Furthermore, normal human dermal fibroblasts OUMS-36 and normal human epidermis-derived cell line HaCaT keratinocytes were examined in vitro to explore the mechanisms relating to whether molecular hydrogen plays a role in wound-healing at the cellular level.

Methods

22 severely hospitalized elderly Japanese patients with pressure ulcer PU were recruited in the present study, and their ages ranged from 71.0 to 101.0 (86.7 ± 8.2) years old, 12 male and 10 female patients, all suffering from eating disorder and bedridden syndrome as the secondary results of various underlying diseases. All patients received routine care treatments for pressure ulcer PU in combination with molecular hydrogen water HW intake via TF for 600 mL per day, in place of partial moisture replenishment. On the other hand, HW was prepared with a hydrogen-bubbling apparatus which produces molecular hydrogen water HW with 0.8-1.3 ppm of dissolved hydrogen concentration (DH) and −602 mV to −583 mV of oxidation-reduction potential (ORP), in contrast to reversed osmotic ultra-pure water (RW), as the reference, with DH of < 0.018 ppm and ORP of +184 mV for use in the in vitro experimental research. In in vitro experiments, OUMS-36 fibroblasts and HaCaT keratinocytes were respectively cultured in medium prepared with molecular hydrogen water  HW and/or reversed osmotic ultra-pure water RW. Immunostain was used for detecting type-I collagen reconstruction in OUMS-36 cells. And intracellular reactive oxygen species (ROS) were quantified by NBT assay, and cell viability of HaCaT cells was examined by WST-1 assay, respectively.

Results

22 patients were retrospectively divided into an effective group (EG, n = 12) and a less effective group (LG, n = 10) according to the outcomes of endpoint evaluation and the healing criteria. Pressure Ulcers  hospitalized days in EffectiveGroup were significantly shorter than in LessseffectiveGroup (113.3 days vs. 155.4 days, p < 0.05), and the shortening rate was approximately 28.1%. Either in EG or in LG, the reducing changes (EG: 91.4%; LG: 48.6%) of wound size represented statistically significant difference versus before molecular hydrogen water HW intake (p < 0.05, p < 0.001). The in vitro data demonstrate that intracellular ROS as quantified by NBT assay was diminished by molecular hydrogen water HW, but not by reverse osmosys water ultraviolet-A (UVA)-irradiated HaCaT cells. Nuclear condensation and fragmentation had occurred for UVA-irradiated HaCaT cells in reverse osmosis water RW, but scarcely occurred in molecular hydrogen water HW as demonstrated by Hoechst 33342 staining. Besides, under UVA-irradiation, either the mitochondrial reducing ability of HaCaT cells or the type-I collagen construction in OUMS-36 cells deteriorated in reverse osmosis water  RW-prepared culture medium, but was retained in molecular hydrogen water HW-prepared culture medium as shown by WST-1 assay or immunostain, respectively.

Conclusions

molecular hydrogen water HW intake via TF was demonstrated, for severely hospitalized elderly patients with PressureUlcers, to execute wound size reduction and early recovery, which potently ensue from either type-I collagen construction in dermal fibroblasts or the promoted mitochondrial reducing ability and ROS repression in epidermal keratinocytes as shown by immunostain or NBT and WST-1 assays, respectively.

Introduction

PressureUlcer is common in the immobile elderly or other immobile patients suffering from diseases such as spinal cord injury, amyotrophic lateral sclerosis, multiple sclerosis, and muscular dystrophy, etc. Furthermore, aged and weak bedridden patients belong to a high risk population for Pressure Ulcers [1]. It is estimated that there are over one million elderly people who are suffering from the skin peculiarity and are facing the risk factors of Pressure Ulcers in USA [2]. Fundamentally, it is usually pointed out that social, psychological and financial expenses for Pressure Ulcers are immeasurable, patients and their families as well as health care providers are always receiving the mental strain [3].

For Pressure Ulcers , it is a primary research task to explore a cheap but effective preventive and curative method. Although various methods for prevention and treatment have been developed, they are far from sufficiently succeeding. While slightly delayed, basic studies are seen to steadily proceed in the same way as the clinical study. As the basic studies for wound healing, a lot of researchers are focusing on skin-constructing proteins such as collagen, elastin, laminin and fibronectin, and on metabolic activity and proliferating ability of dermal fibroblasts [45].

In relation to this matter, we had confirmed the fact that molecular hydrogen-dissolved in water HW, as an external use for skin, can promote the construction of the type-I collagen in fibroblastic cells of dermis [678]. We prepared molecular hydrogen-dissolved in water HW with a hydrogen-bubbling apparatus, exhibited a DH of 1.13 ppm and an ORP of −741 mV, in contrast a DH of < 0.01 ppm and an ORP of +150 mV for normal water [6]. Simultaneously, normal human dermal fibroblasts OUMS-36 and normal human epidermis-derived keratinocytes HaCaT were cultured using an immunostain, in addition, WST-8 and DAPI stains were conducted to examine the cytoprotective effects of molecular hydrogen-dissolved in water HW against UVA-ray irradiation. Six Japanese subjects were enrolled in a trial of molecular hydrogen water HW-bathing (DH, 0.2-0.4 ppm) every day for 3 months. The results obtained showed that molecular hydrogen water  HW-bathing significantly improved wrinkles on the back of the neck in four subjects on 90th day as compared to day 0. Thus the conclusion was achieved, in which molecular hydrogen water  HW can serve as a daily skin care routine to repress UVA-induced skin damages by ROS-scavenging and promotion of type-I collagen synthesis in dermis. On the other hand, many basic research studies demonstrated that molecular hydrogen water HW is widely applied to various diseases, as an oral intake for absorbing via the gastrointestinal tract [91011121314]. The researches obviously suggest that whether using a bathing type or oral intake type of treatment,molecular hydrogen water HW is still an effective method to repair the skin and scavenge the ROS [151617].

We theorized that a routine care treatment in combination with molecular hydrogen water  HW intake via TF for patients with PressureUlcers may improve wound healing and maintain a better health condition than before. The purpose of this study is to clarify the clinical effectiveness of wound healing for patients with PressureUlcers by means of an oral intake of molecular hydrogen water  HW via TF. Furthermore, OUMS-36 cells and HaCaT cells were examined to analyze the mechanisms relating to whether molecular hydrogen water  plays a role in wound healing at the cellular level, in vitro.

Methods

Clinical materials

Patients

Medical record data that were analyzed for this study were obtained from twenty-two elderly Japanese patients with Pressure Ulcers who were hospitalized and institutionalized in Kobayashi Hospital, Fukuyama City, Hiroshima Prefecture, Japan, which is a general hospital attached to a mixed long-term care facility. This study was approved by the Ethics Committee of Kobayashi Hospital.

The ages of PressureUlcers patients who we treated in this study ranged from 71.0 to 101.0 (86.7 ± 8.2) years old, and ten patients were women. On the time of admission, they had suffered from one or multiple diseases and complications, and almost all of them were bedridden elderly people at a high risk of PressureUlcers development, and all of them could not eat without other people’s aid. On the time of admission or during the hospitalization, all patients had been or were gradually appearing symptoms of PressureUlcers.

The types of diseases and complications in these patients, not only included eating disorder but 90% also showed the prevalence of being in the aged period, and 100% had impaired mobility. However, it must be emphasized that PressureUlcers incidence of new onset in Kobayashi Hospital remained approximately 2.10% in 2010–2011, persisted in low level. Because it was reported that average PressureUlcer incidence was 2.43% in a nationwide survey executed by Japanese Society of Pressure Ulcers [18].

Twenty-two patients were retrospectively grouped into EG (effective group, n = 12) and LG (less effective group, n = 10) according to the outcomes of endpoint evaluation and the healing criteria. Details with regard to the discharge from hospital for whether cure or not were analyzed, and baseline data were summarized (Table 1). In data processing, results of all patients were classified as stage I-IV according to the Guideline in 2009 of EPUAP (European Pressure Ulcer Advisory Panel) & NPUAP (National Pressure Ulcer Advisory Panel) that is used as assessment for the severity of PressureUlcers. Coincidentally, all patients in this study belonged to stage II or III.

Table 1

Characteristics of baseline data of PressureUlcers patients in two groups

Item

Effective group (EG)

Less effective group (LG)

Number of patients

12

10

Age (mean ± SD) at onset

87.9 ± 9.0

85.5 ± 7.3

  range

71.0-101.0

73.0-98.0

Gender (male/female)

4/8

8/2

Admission diagnosis

  PU

8

7

  Tumor

0

1

  Pneumonia

4

0

  COPD

0

1

  CIS

0

1

Hospitalized days (mean ± SD)

113.3 ± 89.6

155.4 ± 92.6

  range

32-379

63-335

DESIGN-Rating (mean ± SD) at onset

14.0 ± 5.4

12.7 ± 3.3

Wound size (mean ± SD) at onset

6.9 ± 0.9 cm2

6.3 ± 0.9 cm2

Locations*

  Total

16

12

  Back

3

0

  Sacrum

3

5

  Buttocks

3

2

  Ilium

1

3

  Greater trochanter

2

1

  Thigh

1

0

  Knee

1

0

  Heel

1

1

  Toes

1

0

Stages at onset (number of locations*)

  Stage II

6

4

  Stage III

10

8

Abbreviations: PU pressure ulcer, COPD chronic obstructive pulmonary disease, CIS cerebral infarction sequela, DESIGN-Ratingdepth, exudate, size, inflammation/infection, granulation, necrotic tissue.

*Some patients had multiple locations for pressure ulcers.

Clinical care treatments

Hospitalized routine care treatment

The treatment focused on preventing PressureUlcers from getting worse and on restoring healthy skin. According to the routine care treatments for all patients, nonsurgical therapies were selected, such as ointment, gauze dressing, wrapping, and bed-pad were used after washing by the acidic water disinfection. The skin care, pressure relief and nutritional support were aggressively used as a part of this care treatment [13]. The main care steps to treat PressureUlcers included:

  1. a.

    Managing the tissue load.

  2. b.

    Keeping the ulcer area clean and covered, and not letting it dry out.

  3. c.

    Body-position changes at least every 2 hours if the patient is confined to a bed, or as often as every 15 min if sitting in a wheelchair.

  4. d.

    To achieve positive nutritional nitrogen balance, patient consumed by TF approximately 30 to 35 calories per kg per day and 1.25 to 1.50 g of protein per kg per day.

Preparation for molecular hydrogen water HW

HW molecular hydrogen water was prepared with a molecular hydrogen-bubbling apparatus which consists mainly of a water supply section for manufacturing reverse osmosis water RW with less 0.018 ppm of DH and +184 mV of ORP, and molecular hydrogen water  HW with 0.8-1.3 ppm of DH and −602 mV to −583 mV of ORP. For comparing molecular hydrogen water  HW with reverse osmosys water RW, the water characteristic parameters were measured with the different dilution rates (Table 2, Figures 1 and 2). It must be emphasized that some stable characteristic indicators and the proprieties for innocuity and harmlessness of molecular hydrogen water were obtained from several separated in vivo and human experiments which we had reported [1920212223]. Meanwhile, via tube-feeding, Pressure Ulcers  patients were enforced to intake molecular hydrogen  water HW of 600 mL per day, in the morning and afternoon for approximately one hour, respectively, immediately after molecular hydrogen  water HW was manufactured everytime.

Table 2

Characteristic parameters obtained from hydrogen-dissolved water vs. reversed osmotic ultra-pure water

DH(ppm)

DO(ppm)

ORP (mV)

pH

Water temperature (°C)

Hydrogen-dissolved water (HW)

0.80-1.30

6.91

−602

7.40

24.1

Reversed osmotic ultra-pure water (RW)

< 0.018

8.26

+184

7.37

24.2

Abbreviations: DHdissolved hydrogen concentration, DOdissolved oxygen concentration, ORPoxidation-reduction potential.

Figure 1

Measurement results of diluting molecular hydrogen  water HW with reverse osmosys water RW. The dilution rates are showed as Figure 1. Figures 1a and –b show the ever-increasing tendencies on DO (dissolved oxygen concentration) and ORP (oxidation-reduction potential). Meanwhile, as shown by Figures 1c and –d, DH (dissolved hydrogen concentration) shows the ever-decreasing tendency which indicates the dissolved hydrogen in the hydrogen water was evaporated slowly by mixing with normal regular water. On the other hand, both molecular hydrogen  water HW with reverse osmosys water RW have been holding the temperature range of 23.2-24.1°C and pH 7.37-7.48 no matter from 1 to 11-fold dilution rate.

Clinical evaluations

The evaluative indices for clinical therapeutic effects on PRESSURE ULCERS consisted of the hospitalized days, wound size, classifications of PressureUlcers-stage and DESIGN- rating.

Hospitalized days

Because the increased length of hospitalized stay is an important index for a PressureUlcers patient of QOL (Quality of Life), the days from admission to discharge for twenty-two patients were counted.

Wound size

For obtaining precise objective information and monitoring the healing degree about wound, the medical-care staff measured the size, depth and area [24], utilized photography and diagrams for recording the shape and outline of the wound.

Classifications of PressureUlcers-stages

According to a well-known Panel Guideline established by EPUAP and NPUAP in 2009 [3], stage II includes the partial thickness for loss of skin involving epidermis, dermis or both. The ulcer is superficial and presents clinically as an abrasion or blister, but is not deeper than the dermis. On the other hand, stage III involves the full depth of the skin, and may extend into the subcutaneous tissue layer which has a relatively poor blood supply and can be difficult to heal [2526].

DESIGN-rating

DESIGN was an absolute evaluation tool and consumed as a clinical indicator to assess the quality of medical care. But, its score could not be compared the severity of PressureUlcers among different patients and their various ulcers. Because of this, the DESIGN-rating was invented to use as a simple and easy assessment of PressureUlcers [2728]. In our study, the DESIGN-rating score of every patient was recorded by the medical-care staff, at least once monthly.

In vitro experiments

Materials and methods

Normal human dermal fibroblastic cells OUMS-36

OUMS-36 cells were cultivated for 18 hours in molecular hydrogen  water HW or reverse osmosys water RW-prepared Dulbecco’s modified Eagle’s medium (DMEM; Nissui Pharmaceutical Co. Ltd., Tokyo) supplemented with 10% FCS (fetal calf serum) (GIBCO) in a CO2incubator to be kept at 37°C and pH 7.1-7.4 in a moistened atmosphere of 5% CO2. The spent medium was replaced by the fresh molecular hydrogen  water HW or reverse osmosys water RW-prepared culture medium, and was at once irradiated with UVA ray at doses of 12 or 18 J/cm2, corresponding to the normal dose range for the human daily life. The resultant cells were stained for the nuclei with 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI, Ultracruz Mounting Medium, sc-24941, Santa Cruz Biotechnology Inc., Santa Cruz, CA), and observed for type-I collagen reconstruction by immunostain using the first antibody directed against type-I collagen and the secondary antibody conjugated with FITC (fluorescein isothiocyanate), as observed with a fluorescence microscope (ECLIPSE E600, Nikon Corp., Tokyo) as previously described [6].

Normal human epidermis-derived keratinocytes HaCaT

HaCaT cells were similarly cultivated in molecular hydrogen  water HW or reverse osmosys water RW-prepared DMEM supplemented with 10% FCS (GIBCO), and similarly UVA-irradiated. The resultant cells were examined for cell viability by WST-1 methods using (phenyl)-5-(2-disulfophenyl)-2H-tetrazolium, monosodium salt as a redox indicator, and for ROS such as superoxide anion radicals by NBT (nitro blue tetrazorium) assay as previously described [6].

Statistical analysis

Either clinical study or in vitro research, the Student’s t-test was used to compare the difference in means ± SD between the control and treated groups using a Microsoft Office Excel 2010 software (Microsoft, Albuquerque, NM, USA) or a software package SPSS 11.0 (SPSS inc., Chicago, IL, USA) for Windows. A p-value that is below 0.05 was regarded to be statistically significant.

Results

The clinical results of routine care treatments in combination with molecular hydrogen  water HW via Tube for Feeding

The hospitalized days and the DESIGN-rating of PressureUlcers

For the PressureUlcer patients, the hospitalized days in EffectiveGroup were significantly shorter than in LesseffectiveGroup (113.3 days vs. 155.4 days, p < 0.05), and the PressureUlcers reduction rate was approximately 28.1% (Figure 3-a). Likewise, DESIGN-rating in EG was also decreased for comparing the onset with the endpoint (11.5 rates vs. 14.3 rates, p < 0.05) between pre-post evaluations including both in onset (evaluation in the initial time, at the day for the admission to hospital) and in endpoint (evaluation in the last time, at the day for the discharge from hospital or death day). In LG, no statistically significance was seen, in DESIGN-rating indicative of degree of severity for PU, between both of them (Figure 3-b).

Figure 3

Comparison of PU clinical effects for the hospitalized days and the DESIGN-rating in the effective group and in the less effective group. Figure 3a shows the period for the PU hospitalized days in EG was significantly shorter than in LG. Figure 3b indicates that the DESIGN-rating in EG was decreased for comparing the onset with the endpoint. Pre-post evaluations were performed, where the onset and the endpoint were included. All values are statistically compared. Statistical analysis was performed using Student’s t-test, and the significant differences are defined as p < 0.05. The data are presented as the means with the standard deviation (± SD, indicated by the vertical bar). * p < 0.05.

Results of wound size in two groups

Wound measurement is an important means to know the degrees of PU, and its measuring method was demonstrated in Figure 4-a (Figure 4-a). Either in EG or in LG, the reducing changes (EG: 91.4%; LG: 48.6%) of the wound sizes represent a statistically significant difference (p < 0.05, p < 0.001). Similarly, a significant difference is also seen between both EG and LG groups (p < 0.05) (Figure 4-b).

Figure 4

Measurement methods for wound size and results of wound size in the wound-size reductive change between both the groups. Figure 4a demonstrates the wound measurement method. As a protocol, initially, measure the greatest length along the axial direction (head to toe), and then the greatest width along the transverse direction (side to side) using a centimeter ruler. Finally multiply distances of length and width to obtain an estimate of surface area in square centimeters (cm2). Figure 4b indicates a statistically significant difference to the reducing change of wound size in two groups. Some patients had multiple locations for PU. Values are statistically compared. Student’s t-test, *p < 0.05, ***p < 0.001.

Expression of various PU-assessment indices forcing on both stage II and stage III

For observing the clinical effects in many respects, including the hospitalized days, DESIGN-rating and wound size, EG and LG were subdivided to four subgroups according to classifications of PU-stages (see Methods (3)-3). As a result, in stage II, a period for hospitalized days in EG showed significantly shorter than in LG (87.5 days vs. 387.0 days, p < 0.001). Contrary to this, in two group, there was no significance statistically for hospitalized days in stage III (Figure 5-a) owing to diseases other than PU. Moreover, in EG, the DESIGN-rating obtained from subgroups of stage II and stage III depicted a statistically significant difference (p < 0.05) (Figure 5-b). Meanwhile, the diminishment for wound size within subgroups of stage II and stage III presents any statistical differences (Figure 5-c). In a conclusion, stage II and stage III ulcers of EG healed faster and more effectively than those of LG.

Figure 5

Expression of various PU-assessment indices forcing on both stage II and stage III. Figures 5a to –c imply very significant differences among four subgroups based on stage II or stage III. P-values calculated from Student’s t-test, * p < 0.05, ** p < 0.01, *** p < 0.001.

Results of a typical case on time-dependent wound-healing progress: for an 85-year-old female patient with PressureUlcer

Figure 6 showed the time-dependent wound-healing progress for an 85-year-old female patient with PressureUlcer. She was admitted to the hospital for suffering from PressureUlcer. Wound findings at onset included: location: sacrum; wound size (cm2): 20.8; stage: II; DESIGN-rating: 16. Four months after routine care treatment plus a combination with molecular hydrogen water HW intake via TubeFeeding, the crater nearly disappeared. Wound findings at endpoint (vs. of onset) included: wound size (cm2): approximately 0 (disappearance); stage: I (improve); DESIGN-rating: 6 (decrease) (Figures 6-a to -d).

Figure 6

Results of a typical case on time-dependent wound-healing progress. An annual time-dependent wound healing progress for an 85-year-old female PressureUlcer patient is reported. She was admitted to the hospital seeking treatment to PressureUlcer. Figure 6a demonstrates photographs for the time-dependent wound-healing progress obtained from the same patient. Figures 6b to –d represent the decreased tendencies of wound size, DESIGN-rating, and stage, respectively.

Results of another typical case on time-dependent wound-healing progress: for an 80-year-old male patient with PressureUlcer

Figure 7 showed the time-dependent wound-healing progress for an 80-year-old male patient with PressureUlcer. His hospitalized period lasted 10 months and it could be divided into the two sub-periods. During the latter 5-month period, he received molecular  HydrogenWater treatment in the addition to the routine care. The outcome shows an improved result (Figures 7-a, -b).

Figure 7

Results of another typical case on time-dependent wound-healing progress. Similarly to Figure 6, Figure 7 also demonstrates a time-dependent wound healing progress, for an 80-year-old male PressureUlcer patient. Figure 7a shows the features photographed at the former period for routine care treatment alone. On the other hand, Figure 7bpresents ones photographed at the latter period for routine care treatment plus molecular Hydrogen Water intake. The latter period in using HydrogenWater intake shows a marked improved outcome.

In vitro experiments

Promotive effects on reconstruction of type-I collagen, as shown by immunostain, on normal human dermal fibroblasts OUMS-36 that were irradiated with UVA ray and then were administered with reverse osmosis water RW- or molecular hydrogen water HW-prepared culture medium, respectively

To study the reconstructive effect of molecular hydrogen water HW on type-I collagen, we used immunostain on OUMS-36 cells that were irradiated with UVA ray and then were administered with reverse osmosis water RW or molecular hydrogen water HW in vitro, respectively. Representative expressions and pixel values were plotted with a software ImageJ (http://rsb.info.nih.gov/ij/). Nuclear condensation (so-called pycnosis) and fragmentation (so-called karyorrhexis) were occurred for UVA-irradiated OUMS-36 cells in reverse osmosis water RW, but scarcely occurred in molecular hydrogen water HW (Figure 8). HW molecular hydrogen water group shows higher proliferation of cells with rounded morphology in fibroblasts and huge morphology, and more abundant in type-I collagen than ones of reverse osmosis water RW group.

Figure 8

Reconstructive effects of molecular hydrogen water HW in UVA-irradiated OUMS-36 cells. Figures 8a, –b: Distributional expressions of type-I collagen with immunostain (green) in OUMS-36 cells that were irradiated with UVA ray and were administered with reverse osmosis waterRW or molecular hydrogen water HW, respectively. Figure 8b: Each yellow dashed lines indicate type-I collagen-rich regions. Figure 8c: Relative fluorescence intensity plotted with the ImageJ to present the pixel number. Type-I collagen stain on OUMS-36 cells that were irradiated with UVA ray and were administered with reverse osmosis water RW or molecular hydrogen water HW, respectively, is showed. Figure 8d: The pseudocolor feature was plotted using ImageJ as an intensity which is corresponding to type-I collagen exhibition degree per one hundred cells (μm2/100 cells). Magnification: ×200; scale bars = 50 μm. Student’s t-test, *** p < 0.001.

Proliferative effects of nucleus-DAPI stain on UVA-irradiated normal human dermal fibroblasts OUMS-36 that were administered with reverse osmosis water RW- or molecular hydrogen water HW-prepared culture medium, respectively

With fluorescence microscopy, DAPI dye can be excited by UVA ray. To examine the reconstructive effect of molecular hydrogen water HW on type-I collagen by immunostain, we also counterstaind nuclei with a DAPI dye in UVA-irradiated OUMS-36 cells for observing the changes when OUMS-36 cells were administered with Reverse osmosis Water or molecular hydrogen water HW in vitro, respectively. Representative expression and relative fluorescence intensity were plotted with the ImageJ. The facilitative effect on nuclear condensation and fragmentation was observed for UVA-irradiated OUMS-36 cells in Reverse osmosis Water , but scarcely occurred in molecular hydrogen water HW as demonstrated by DAPI staining as like the result obtained from immunostain (Figure 9). Through Figure 9-c, the degrees of DAPI stain on HaCaT cells that were irradiated with UVA ray and were administered with  Reverse osmosis Water or molecular hydrogen water HW, respectively, were clarified.

Figure 9

Features of nucleus-DAPI stain on UVA-irradiated HaCaT cells. Figures 9a, –b: Distributional expressions of nucleus-DAPI stain (blue) in HaCaT cells that were irradiated with UVA ray and were administered with  Reverse osmosis Water or molecular Hydrogen Water, respectively. Figures 9c, –d: The relative fluorescence intensity and the pseudocolor feature for type-I collagen were plotted using ImageJ. Magnification: ×200; scale bars = 200 μm. Student’s t-test, *** p < 0.001.

ROS amounts in normal human epidermis-derived keratinocytes HaCaT as quantified by NBT assay

In HaCaT cells, the intracellular ROS amounts were increased in the Reverse osmosis Water -prepared culture medium with UVA-irradiation in different UVA ray doses, but were restored in the molecular hydrogen water HW-prepared culture medium as shown by NBT-stain for superoxide anion radicals. Cell morphology was observed to be more health and less harmful in molecular HydrogenWater than  Reverse osmosis Water (Figure 10). Figure 10-e showed that NBT-stain was denser in dark-blue color in Reverse osmosis Water -administered cells than in molecular HydrogenWater-administered cells, indicating the intracellular ROS repression in molecular Hydrogen Water-administered cells.

Figure 10

Intracellular ROS amounts in HaCaT cells as quantified by NBT assay. Figures 10a, –b: The retained cell morphology and the diminished ROS were shown in molecular hydrogen water HW-prepared culture medium for comparing with Reverse osmosis Water .Yellow dashed lines indicate abundant dark-blue dyes that were the reaction products where ROS such as superoxide anion radical was found to react with NBT-stain. Figures 10c, –d: The expressions of surface plotter by ImageJ. Figure 10e: The mean gray values obtained from ImageJ used to express the increase or decrease in superoxide anion radicals within normal human epidermis-derived keratinocytes HaCaT according to NBT-stain. In detail, the vertical axis shows the brightness presented as a mean gray value, which is considered as an index to show the cellular stained intensity and use to indicate ROS amounts. The cell morphologies of Reverse osmosis Water  RW and molecular hydrogen water HW were divided into the eight regions and then compared with their mean gray values by Student’s t-test (** p < 0.01). Magnification: ×200; scale bars = 100 μm.

Elevation of cell viability by pre-irradiational administration with molecular hydrogen-dissolved water to UVA-irradiated HaCaT cells as assessed by mitochondrial dehydrogenase-based WST-1 assay

In HaCaT cells, the cell viability was obviously increased in the molecular hydrogen water HW-prepared culture medium with UVA-irradiation, comparing with reverse osmosis water RW-prepared culture medium by WST-1 assay (Figure 11-d). Cell morphology was also observed to be less vulnerable in terms of diverse symptoms such as cell shrinkage, nuclear condensation and cell fragmentation for molecular hydrogen water HW than reverse osmosis water RW (Figures 11-b, -c). molecular hydrogen water HW group showed higher proliferation of cells with rounded morphology and huge morphology, in HaCaT cells than ones of Reverse osmosis Water group. All of these evidences predicted that molecular  hydrogen-dissolved water may exert cytoprotective effects against UVA ray on HaCaT cells.

Figure 11

Results of cell viability of HaCaT cells as assessed by WST-1 assay. Figure 11a: HaCaT cells are shown in the non-administered or non-UVA-irradiated status. Figures 11b, –c: The morphologic features of HaCaT cells are shown in reverse osmosis water RW or molecular hydrogen water HW, respectively, after irradiation with UVA ray. Figure 11d: The cell viability is shown for HaCaT cells after UVA-irradiation by WST-1 assay. Magnification: ×400; Scale bar = 100 μm. Student’s t-test, ** p < 0.01.

Discussion

The purpose of the present study was to examine the clinical effectiveness of wound healing for Pressure Ulcers using molecular hydrogen water HW intake via TubeFeeding. We have hypothesized that the routine care treatment in combination with molecular hydrogen water HW intake for PressureUlcer patients may improve wound healing, and maintain more healthy condition for them. Furthermore, normal human dermal fibroblasts OUMS-36 and normal human epidermis-derived keratinocytes HaCaT were examined to explore the mechanisms underlying to whether molecular hydrogen plays a role in wound-healing at aspect for cutis tissue, through in vitro experiments.

Our clinical results seem to suggest that molecular hydrogen water  HW oral intake via TubeFeeding is an effective means for wound healing of PressureUlcer patients, who suffered from eating disorder. Despite the limitations caused by practicing our clinical intervention for PressureUlcers, we were able to obtain the improving results in hospitalized days, wound size and other clinical indices by comparing EG with LG. Therefore, we estimated that molecular hydrogen water  HW absorbed by the gastrointestinal tract plays an important role in oxidative-stress reduction, extracellular matrix reconstitution, and anti-inflammatory effects. Several experiments have supported our considerations as follows.

At first, it was demonstrated that molecular hydrogen gas (H2) has a beneficial influence on the gastrointestinal tract [29]. Kajiya et al. established a mouse model of human inflammatory bowel disease (IBD) by supplying to mice drinking water containing a) 5% dextran sodium sulfate (DSS), b) 5% DSS and molecular hydrogen H2, or c) molecular hydrogen H2 only ad libitum up to 7 days. They found that on day-7, DSS-induced pathogenic outcomes including elevated levels of IL-12, TNF-α and IL-1- β in colon lesion, etc. were significantly suppressed by addition of molecular hydrogen H2 to DSS solution. Thereby, it was concluded that molecular hydrogen H2 can make an anti-inflammatory influence on gastrointestinal tract in vivo[30].

Secondly, Nakashima-Kamimura et al. examined whether drinking water containing the saturated dissolved molecular hydrogen (HW: 0.8 mM molecular hydrogen H2 in water) is applicable by examining the effects of oxidative stress, mortality, and body-weight loss as well as serum creatinine, and blood urea nitrogen (BUN) levels. In in vivo experiments, their results showed that molecular hydrogen was detected in the blood when molecular hydrogen water  HW was placed via gavage at a dose of 15 mL/kg in the stomach of a rat, and molecular hydrogen water  HW is applicable to alleviate nephrotoxic side-effects induced by an anti-cancer drug, such as cisplatin [31].

Thirdly, as molecular hydrogen gas can act as a scavenger of ROS, Cardinal et al. tested the effect of treatment with molecular hydrogen water HW in a rat model of kidney transplantation. In consequence, treatment with molecular hydrogen water  HW improved allograft function, slowed the progression of chronic allograft nephropathy (CAN), reduced oxidant injury and inflammatory mediator production, and improved overall survival. Their conclusion was that molecular hydrogen water HW is an effective antioxidant and anti-inflammatory agent in vivo[32].

It was previously shown that some free radicals inhibit the wound healing process [33]. molecular hydrogen H2 is a colorless, odorless, tasteless gas, and it possesses some peroxidant reducibility. molecular hydrogen H2 is possible to easily pass through the small intestine villi into the human body inside and blood stream [15], because its molecular weight is the smallest of all molecule species, and it has gaseous and electrically neutral properties, as well as it shows a strong diffusion capacity. Moreover, molecular hydrogen H2 maybe has its special channels for transporting into intracellular space, such as the aquaporins (AQPs) for water, especially molecular hydrogen-holding water, and the Rhesus (Rh) proteins [34].

Thus, coupled with the body itself and the enterogenous-H2 molecular hydrogen presence, due to specified intestinal bacteria, molecular hydrogen water HW intake via TubeFeeding can play an important role on improving the formation of wound granulates on disintegrated necrosis loci, and the ability to have an anti-inflammatory effect through an ROS-reduction mechanism.

Additionally, it should be pointed out that apoptotic cells can stimulate proliferation, wound healing, and tissue regeneration [35]. We are focusing on “the apoptosis-induced compensatory proliferation” which occurs in PressureUlcers [36]. Generally, necrosis has an effect of the secondary lethal damage to the wound-surrounding cells of PressureUlcers through cell swelling and burst. By contrast, cell debris that is caused by cell shrinkage and fragmentation in apoptosis in which karyorrhexis (i.e. nuclear fragmentation) and pycnosis (i.e. nuclear condensation) are revealed as an early event, is subjected to endocytosis by both the migratory professional phagocytes (e.g.macrophages and Langerhans cells in the epidermis) and the surrounding non-professional phagocytes. So, it is thought that “the compensatory proliferation” is induced for the reason that cell debris is peaceably handled to restrain the surrounding cells within a minimal deteriorating impact. On this occasion, ROS may be able to be suppressed by the molecular hydrogen water to evoke an apoptosis more gently, and subsequently, apoptosis that is caused in wound-surrounding cells of PressureUlcers stimulates the compensatory proliferation to lead to an early healing. Indeed, Cai JM et al. reported that 2% molecular hydrogen gas inhalation administered to a neonatal hypoxia-ischemia rat model could reduce apoptosis [37].

When molecular Hydrogen Water-intake via TubeFeeding was combined with routine care treatments, the wound healing process can be markedly accelerated. Hence, the effective mechanism of molecular Hydrogen Water possesses at least two possible pathways, firstly is an antioxidant effect and secondly is an anti-inflammatory effect. Moreover, we thought that molecular hydrogen water HW may have additional effects, i.e. reconstruction of collagen and cytoprotection for other dermal as well epidermal cells. Therefore, we carried out an in vitro experiment on normal human dermal fibroblasts OUMS-36 and normal human epidermis-derived keratinocytes HaCaT to examine their interaction. Therefore, either dermal or epidermal cells were respectively cultured in molecular hydrogen water HW or reverse osmosis water  RW-prepared medium. Immunostain was used for observing type-I collagen reconstruction in OUMS-36 cells and showed the promotive effect. And cell viability of HaCaT cells was examined in terms of cell morphological observation and WST-1 assay, and their generated ROS, especially superoxide onion radials, was measured by NBT assay, respectively, all of which showed the cell-death-repressive and ROS-scavenging effects.

We have attempted to draw the illustrations for assuming a cure mechanism from stage III to wound healing during Pressure Ulcers (Figure 12).

Figure 12

Mechanism for wound healing of pressure ulcer by molecular hydrogen-dissolved water. We are predicting that ROS can lead to a pressure ulcer, and the causative process is shown by the left illustration. First of all, such diverse factors as bedridden syndrome, mechanical pressure and local ischemia produce ROS which causes necrosis and apoptosis in combination with other pathologic factors, potently resulting in wounds and tissue defects of pressure ulcer. On the other hand, the right illustration shows the healing mechanism. Oral intake of nano-bubble molecular hydrogen water via drinking or tube-feeding passes by the mouth or esophagus, and it is absorbed by the epithelial cells of the small intestines. It is possible that molecular hydrogen gas transpires in past from molecular hydrogen water  HW and inhaled by the lung. Then, the absorbed nano-bubble molecular hydrogen migrates to cutis tissue through blood circulation and scavenges ROS abundantly generated in Pressure Ulcers. Finally, this process results in collagen reconstruction of fibroblasts in the dermis and the proliferation of keratinocytes in the epidermis, and causes angiogenesis and remodeling for repairs in the defected tissue.

Consequently, our in vitro data demonstrated that intracellular ROS was diminished by molecular hydrogen water  HW, but not by reverse osmosis water RW, in UVA-irradiated OUMS-36 fibroblasts. Nuclear condensation and fragmentation were occurred for UVA-irradiated OUMS-36 cells in reverse osmosis waterRW, but scarcely occurred in molecular hydrogen water  HW as demonstrated by DAPI staining. Besides, in HaCaT cells, the mitochondrial dehydrogenase, especially succinate dehydrogenase activity was diminished in reverse osmosis water  RW-prepared culture medium with UVA-irradiation, but was retained in molecular hydrogen water HW-prepared culture medium as shown by NBT and WST-1 assay. Thus, UVA-induced ROS, especially singlet oxygen and superoxide onion radicals were suggested to be scavenged by molecular hydrogen and result in cytoprotection against ROS-induced mitochondrial dysfunction.

Similar results have been reported from previous research works on reconstruction of collagen in other dermal or epidermal cells by molecular hydrogen water HW [3839].

As a mechanism for using molecular hydrogen water  HW to treat PressureUlcers at aspect of dermal and epidermal cells, we consider that there are three pathways as follows:

(1) the promotion of the formation of dermis structure as well as reconstruction to type-I collagen,

(2) the prevention of the formation of wound granules on disintegrated necrosis loci, and

(3) the repair and restoration of scar tissues.

Healing effects for PressureUlcers patients through molecular hydrogen water  HW oral intake via TubeFeeding as shown by our present study have been scarcely found in the past. Our experience in this study added further evidences to a possible role in medical therapies for Pressure Ulcers. Additionally, as well known, there are different methods to manufacture the hydrogen water by diverse research groups, so there are also different water-parameters about molecular hydrogen water HW. In order to show our data obtained from measurements with the different dilution ratios, we had specially set up Figures 1 and 2, as well as Table 2 to present these achievements. How to manufacture molecular hydrogen water  HW and reverse osmosis water RW is an important and essential matter in the field of hydrogen water medicine.

But, this study has some limitations that should be considered when interpreting the results. Firstly the study design could not be carried out as the randomized control trail (RCT), because generally PU-cure clinical intervention test cannot be executed as RCT owing to other diverse factors such as various diseases concurrence and complication. Clinical situation did not allow us to get clinical data prior to one as we designed. Secondly we could not design the trial into comparing the results both molecular hydrogen water HW oral intake and external washing of injurious sites with molecular hydrogen water  HW, respectively. These deserve the next-step study.

Conclusions

molecular hydrogen water  HW intake via Tube Feeding was demonstrated, for severely hospitalized elderly patients with Pressure Ulcers, to execute wound size reduction and early recovery, both of which potently ensue from either type-I collagen construction in dermal fibroblasts or the promoted mitochondrial reducing ability and ROS repression in epidermal keratinocytes as shown by immunostain, NBT and WST-1 assays, respectively.

https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-3-20

 

 

Consent

Written informed consents that were presented from the patients for the publication of this report and any accompanying images were obtained and confirmed as the ethical clearance by the Ethics Committee of Kobayashi Hospital, Fukuyama City, Hiroshima Prefecture, Japan.

Declarations

Acknowledgments

The authors are grateful to Kobayashi Hospital and the representative director Dr. Yoshizi Kobayashi, for their devoted support to part of clinical trial. This study was supported, in part, by grant-in-aid from JCAAMS (Japanese Center for Anti-aging MedSciences, Hiroshima).

Authors’ Affiliations

(1)

Department of Radiological Technology, Faculty of Health Sciences, Butsuryo College of Osaka

(2)

Life Science Research Center, Mie University

(3)

Hiroshima Kasei Co. Ltd

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Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro
  • Qiang Li,
  • Shinya Kato,
  • Daigo Matsuoka,
  • Hiroshi Tanaka and
  • Nobuhiko MiwaEmail author
Medical Gas Research20133:20

https://doi.org/10.1186/2045-9912-3-20

Received: 9 June 2013

Accepted: 5 September 2013

Published: 10 September 2013

Copyright

© Li et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

molecular hydrogen water periodontitis

Oxidative stress is involved in the pathogenesis of periodontitis. A reduction of oxidative stress by drinking molecular hydrogen-rich water (HW) might be beneficial to periodontal health.

In this pilot study, we compared the effects of non-surgical periodontal treatment with or without drinking molecular hydrogen-rich water HW on periodontitis.

13 patients (3 women, 10 men) with periodontitis were divided into two groups: The control group (n = 6) or the molecular hydrogen-rich water HW group (n = 7). In the molecular hydrogen-rich water HW group, participants consumed molecular hydrogen-rich water HW 4-5 times/day for eight weeks. At two to four weeks, all participants received non-surgical periodontal treatment. Oral examinations were performed at baseline, two, four and eight weeks, and serum was obtained at these time points to evaluate oxidative stress. At baseline, there were no significant differences in periodontal status between the control and molecular hydrogen-rich water HW groups. The molecular hydrogen-rich water HW group showed greater improvements in probing pocket depth and clinical attachment level than the control group at two, four and eight weeks (p < 0.05). The molecular hydrogen-rich water HW group also exhibited an increased serum level of total antioxidant capacity at four weeks, compared to baseline (p < 0.05). Drinking molecular hydrogen-rich water HW enhanced the effects of non-surgical periodontal treatment, thus improving periodontitis.

PMID:26783840
PMCID:PMC4665424
DOI:10.3390/antiox4030513

 

 

 2015 Jul 9;4(3):513-22. doi: 10.3390/antiox4030513.
Drinking Hydrogen-Rich Water Has Additive Effects on Non-Surgical Periodontal Treatment of Improving Periodontitis: A Pilot Study.

Author information

1
Departments of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. tetsuji@md.okayama-u.ac.jp.
2
Departments of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. de18053@s.okayama-u.ac.jp.
3
Departments of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. dekuni7@md.okayama-u.ac.jp.
4
Departments of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. de18019@s.okayama-u.ac.jp.
5
Departments of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. de18017@s.okayama-u.ac.jp.
6
Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. t-maru@md.okayama-u.ac.jp.
7
Departments of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. tomofu@md.okayama-u.ac.jp.
8
Departments of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan. mmorita@md.okayama-u.ac.jp.

molecular hydrogen water for vascular endotelial function

The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS), H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2) neutralizes detrimental ROS, especially the hydroxyl radical.

OBJECTIVES:

To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, molecular hydrogen H2, can be a useful modulator of blood vessel function.

METHODS:

The efficacy of water containing a high concentration of  molecular hydrogen H2 was tested by measuring flow-mediated dilation (FMD) of the brachial artery (BA). The subjects were randomly divided into two groups: the high- molecular hydrogen H2 group, who drank high- molecular hydrogen H2 water containing 7 ppm molecular hydrogen H2 (3.5 mg molecular hydrogen H2 in 500 mL water); and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high- molecular hydrogen H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline.

RESULTS:

FMD increased in the high- molecular hydrogen H2 water group (eight males; eight females) from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation) and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo group (ten males; eight females). The ratio to the baseline in the changes of FMD showed significant improvement (P<0.05) in the high- molecular hydrogen H2 water group compared to the placebo group.

CONCLUSION:

molecular hydrogen H2 may protect the vasculature from shear stress-derived detrimental ROS, such as the hydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response.

https://www.ncbi.nlm.nih.gov/pubmed/25378931

references:

PMID:25378931
PMCID:PMC4207582
DOI:10.2147/VHRM.S68844
 2014 Oct 17;10:591-7. doi: 10.2147/VHRM.S68844. eCollection 2014.
Consumption of water containing over 3.5 mg of dissolved molecular hydrogen could improve vascular endothelial function.

Author information

1
Department of Cardiology, Haradoi Hospital, Fukuoka, Japan.
2
MiZ Company Limited, Fujisawa, Kanagawa, Japan.
3
Department of Internal Medicine, Haradoi Hospital, Fukuoka, Japan.
4
Midorino Clinic, Aoba, Higashi-ku, Fukuoka, Japan.
5
Department of Rheumatology and Orthopedic Surgery, Haradoi Hospital, Fukuoka, Japan.

Molecular hydrogen(H2) treatment for acute erythymatous skin diseases

Molecular hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers

Background

We have treated 4 patients of acute erythematous skin diseases with fever and/or pain by molecular hydrogen H2 enriched intravenous fluid. We also added data from two volunteers for assessing the mode of molecular hydrogen  H2 delivery to the skin for evaluation of feasibility of molecular hydrogen  H2 treatment for this type of skin diseases.

Methods

All of the four patients received intravenous administration of 500 ml of molecular hydrogen  H2 enriched fluid in 30 min for more than 3 days except in one patient for only once. From two volunteers (one for intravenous molecular hydrogen  H2 administration and the other for molecular hydrogen  H2 inhalation), blood samples were withdrawn serially and air samples were collected from a heavy duty plastic bag covering a leg, before, during and after molecular hydrogen  H2 administration. These samples were checked for molecular hydrogen  H2 concentration immediately by gas chromatography. Multiple physiological parameters and blood chemistry data were collected also.

Results

Erythema of these 4 patients and associated symptoms improved significantly after the molecular hydrogen  H2 treatment and did not recur.

Administration of molecular hydrogen  H2 did not change physiological parameters and did not cause deterioration of the blood chemistry. The molecular hydrogen H2 concentration in the blood from the volunteers rapidly increased with molecular hydrogen  H2 inhalation and slowly decreased with cessation of molecular hydrogen H2 particularly in the venous blood, while molecular hydrogen  H2 concentration of the air from the surface of the leg showed much slower changes even after molecular hydrogen  H2 inhalation was discontinued, at least during the time of sample collection.

Conclusion

An improvement in acute erythemtous skin diseases followed the administration of molecular hydrogen H2 enriched fluid without compromising the safety. The molecular hydrogen H2 delivery study of two volunteers suggested initial direct delivery and additional prolonged delivery possibly from a slowly desaturating reservoir in the skin to the surface.

Introduction

Severe and acute erythematous skin diseases usually require immediate medical attention, particularly when the symptoms involve severe pain and/or fever. Treatment may have to be initiated before spending enough time and effort for investigating real causes of the rush or functional state of the other organs and the steroid agents tend to be the first choice of the treatment. However, the complications from the general use of steroid have been well known and therefore, non-dermatological clinics like ours frequently encounter difficulty in finding quick remedies with minimal side effects. Erythema is reddening of the skin due to inflammatory mechanisms either as primary culprits or secondary features and locally released inflammatory cytokines such as TNF-α, IL-1,8, GM-CSF etc., stimulate phagocytes and inflammatory cells and results in production of ROS (reactive oxygen species)[12]. The interaction between the ROS and nitric oxide leads to the formation of peroxynitrite radicals and also by the iron-mediated Fenton reaction, hydroxyl radicals, both of which are highly reactive and destructive to the cell membrane and mitochondria and polyunsaturated fatty acids(PUFAs) [3]. However, ROS dismutases, which are abundant in the skin and also currently available medications are ineffective to neutralize these most destructive radicals except Edaravone [4], of which use is strictly limited for the treatment of acute cerebral infarction patients with normal kidney and liver function.

molecular hydrogen  H2 may be useful in these situations because it immediately and simultaneously neutralizes both peroxynitrites and hydroxyl radicals [5] and also molecular hydrogen  H2 is known to cause no significant side effects since it is produced in the human intestine as a fermentation process, although not continuously[6].

We report four cases of acute erythematous skin disease patients who were suffering from skin rash and also from associated symptoms such as severe pain and/or fever. They were treated with regular medications first and when the conventional treatments failed, then, intravenous fluids which contained molecular hydrogen  H2 were added after a proper consent form was signed. However, molecular hydrogen  H2 administration may not be therapeutic unless enough concentration stays at the surface layer of the skin for a sufficient period and the concentration should be higher than that of internally produced molecular hydrogen  H2. Two volunteers participated in a molecular hydrogen  H2 delivery study where molecular hydrogen  H2 concentration in the blood and in the air at the surface of the skin was measured before, during and after molecular hydrogen  H2 administration by inhalation or by intravenous fluid infusion.

Methods

Patients and volunteers

Before recruiting the patients and volunteers to the current study, a complete PARQ conference was given to all of the patients and their family and to volunteers. Our specific consent form, which had been approved by the Nishijima Hospital Ethics Committee and the Nishijima Hospital Pharmacists Council, was signed before the study with clear understanding of the nature of the study.

Case history of 4 patients

Case 1

48 y.o. male who was in good health until 5 days prior to the admission to Nishijima Hospital when severe pain and skin rash involving his left side of the face made him to visit an emergency service where he was diagnosed as having herpes simplex infection and was treated with antivirus agents and pain medications. However, the pain increased and the left side of the face became numb. In addition, blisters in the erythematous area coalesced and formed ulcer-like appearance. The patient also noticed left ptosis and double vision and became unable to open the mouth, which made oral intake impossible. The patient was admitted to the hospital for deteriorated general condition with dehydration, severe pain and fever. On admission, the patient was found to have partial paralysis of the left 3 rd, 5th and 6th cranial nerves in addition to severe erythema with edema and small ulcers, covering the left side of the face and frontal region. The hydration treatment was initiated with 3 bags of 500 ml glucose and electrolyte solution and continued for 6 days with a decreasing dose during the hospitalization. Initially, two bags of these solutions (500 ml) had been enriched with molecular hydrogen H2. No antibiotic was given. Before the infusion therapy, the patient was unable to open his left eye and the mouth (Figure 1, upper left). The picture of Figure 1 upper right was taken after the patient was asked to open his left eye and the mouth. The patient was unable to do so, except for minimal opening of the mouth. However, 3 days after the admission and molecular hydrogen  H2 infusion, the patient’s condition remarkably improved, including erythema, ulcers, pain level, opening the eye and mouth (Figure 1, lower left) and the patient became afebrile. Since cranial nerve functions recovered also and he became able to take oral soft nutrients, intravenous hydration was decreased to 2 bags of molecular hydrogen  H2- enriched glucose-electrolyte solution (esuron B,200 ml/bag), daily. By the 6th hospital day, the patient was eating a regular food and his dehydration was corrected. He had no pain and the severe inflammation of the skin disappeared. The patient discharged home and no return of the skin erythema noted during a follow-up period (Figure 1, lower right).

Figure 1

Erythematous skin disease, Case 1. Before the molecular hydrogen  H2 treatment with severe erythema and edema (upper left), the patient was unable to open his left eye and the mouth except for a minimal degree with a maximal effort (upper right). Improved conditions, 3 days after the molecular hydrogen  H2 treatment (lower left) with opening eye and mouth. The severe inflammation of the skin almost disappeared in 6 days after molecular hydrogen  H2 treatment (lower right) and was discharged home and no return of the skin erythema noted during a follow-up period.

Case 2

67 y.o male lapsed into coma after a large basilar artery aneurysm rupture and subarachnoid hemorrhage. After the aneurysm was surgically clipped, the patient remained comatose and developed pneumonia and cystitis, with deterioration of the liver and kidney function. After multiple medications including antibiotic and anticonvulsant, his general condition had been stabilized until 2 months after the surgery when he became febrile and developed severe skin abnormality. The abnormality consisted of erythematous papules, severe skin edema, blisters and vesicles and shedding of the skin. The Stevens-Johnson syndrome was suspected and he was transported to a general hospital with dermatology department. However, the patient was sent back with several diagnosis such as drug erythema, thrombocytopenia, possible trichophyton infection etc. and use of steroid and antifungal cream were recommended but not systemic steroid. However, application of these creams further deteriorated the skin condition despite of discontinuation of suspected drugs and finally, it was decided to use molecular hydrogen  H2-enriched intravenous fluid. After a complete PARQ with the patient’s family who signed a consent,molecular hydrogen H2-enriched saline solution (500 ml) was given twice a day. Redness of the skin started fading and swelling and hardness of the skin from severe edema significantly improved in 3 days. His high fever subsided. After one week of the hydrogen treatment, the skin lesions almost disappeared (Figure 2, lower left) and general condition improved also. Although the patient remained comatose after the treatment and expired approximately 4 months after the surgery, the skin lesions did not recur.

Figure 2

Erythematous skin disease, Case 2, 3 and 4. Erythematous skin lesion of the case 3 in the entire face (upper left) started improving approximately 30 min after the molecular hydrogen  H2 infusion in the left side of the face first (upper-middle) and then in about one hour, the whole face improved (upper right). Severe swelling and erythema of case 2 subsided in 7 days after molecular hydrogen  H2 treatment (lower left). Finer papules of case 4 started coalescing (lower middle). In 3 days after molecular hydrogen H2 treatment (lower right), significant improvement was noted and the skin lesion did not recur.

Case 3

48 y.o female started feeling hot sensation in her face and developed erythema in the entire face (Figure 2, upper left) after a CT scan study with contrast enhancement for cerebral aneurysm. Drug eruption was suspected and a minophagenC solution (Minophagen Pharmaceutical Co.) which had been effective in these situations, was given intravenously. However, the erythema did not subside and the patient developed fever (38.5C), headaches and nausea. As an emergency measure, two bags of a 250 ml of saline solution (Terumo Co.), which had been enriched with molecular hydrogen  H2 was given. Approximately 30 min. after the infusion, the erythema started fading in the left side of the face first (Figure 2, upper middle) and then in about one hour, the whole face improved (Figure 2, upper right) and her body temperature started coming down in about one hour. At that point, the infusion stopped and the patient returned home. No recurrence of the skin rush nor fever was noted during a follow-up period.

Case 4

62 y.o. male had been intubated and mechanically ventilated with stable vital signs after severe subarachnoid hemorrhage from a ruptured cerebral aneurysm until 7 days after the ictus when the patient developed high fever and erythema which consisted of finer papules without fusing together. Initially, the patient was treated with local ointments with steroid but the erythema spread in the whole body and started coalescing (Figure 2, lower middle). In 3 days after molecular hydrogen  H2-enriched saline solution was given twice a day intravenously, the skin lesion started fading (Figure 2, lower right) and the elevated body temperature normalized.

Volunteers

Two volunteers who were already in Nishijima hospital with different medical conditions agreed to let the study to use molecular hydrogen H2 and their arterial access port and venous port which had been established for their medical treatment. The blood samples (1 ml at each time) were withdrawn from these ports, before, during and after molecular hydrogen  H2 administration by intravenous infusion of 500 cm3 of saline or by inhalation of 2% molecular hydrogen  H2 gas for 20 min followed by inhalation of 4% H2 gas. Both patients and their family understood perfectly that the study will not provide any benefit to them directly but possibly for the future of molecular hydrogen  H2 treatment research. All the proper PARQ and signing of the consent form had been done before the initiation of the study.

Results

Erythema of these 4 patients and associated symptoms, such as intensive pain in the face with neurological deficits and skin ulcers (case 1), fever and edematous hardening of the entire body, particularly in the extremities with skin ulcers (Case 2), rather mild but with acute fever and nausea and headache (case 3), mild but worsening and spreading skin lesions with fever (case 4), all improved significantly after the molecular hydrogen H2 treatment and did not recur.

The molecular hydrogen  H2 delivery study of two volunteers showed that the concentration of molecular hydrogen  H2 in the blood rapidly increased with molecular hydrogen H2 inhalation and slowly decreased with cessation of molecular hydrogen H2, particularly in the venous blood. However, molecular hydrogen  H2 concentration of the air samples in the plastic bag covering a leg showed much slower changes and continued to increase even after molecular hydrogen  H2 inhalation was discontinued, at least during the time of sample collection (Figure 5). The blood level of molecular hydrogen H2 was significantly higher when molecular hydrogen  H2 was given by inhalation as compared to via intravenous route.

Administration of molecular hydrogen  H2 did not change physiological parameters and did not cause significant deterioration of the blood chemistry, although some of these patients already had severe abnormalities before the molecular hydrogen  H2 treatment such as thrombocytopenia of case 2

The safety monitoring with physiological parameters and laboratory studies showed no ill effects on those multiple indices and organ function such as kidney and liver function, by this method of molecular hydrogen  H2 administration (Table 1). Even in the case 2 with thrombocytopenia, no other hematological worsening was noted. Clinical symptoms of the skin diseases of all four patients improved rather rapidly and significantly. Therefore, it may be reasonable to assume that molecular hydrogen H2 infusion in these situations was quite safe and effective.

In summary, erythema of these 4 patients and associated symptoms, such as intensive pain in the face with neurological deficits and skin ulcers, fever and edematous hardening of the entire body, rather mild but with acute fever and nausea and headache, mild but worsening and spreading skin lesions with red rush all improved significantly after the molecular hydrogen H2 treatment and did not recur.

The molecular hydrogen H2 delivery study of two volunteers showed that the concentration of molecular hydrogen H2 in the blood rapidly increased with molecular hydrogen H2 inhalation and slowly decreased with cessation of molecular hydrogen H2, particularly in the venous blood. However, molecular hydrogen H2 concentration of the air samples in the plastic bag covering a leg showed much slower changes and continued to increase even after molecular hydrogen  H2 inhalation was discontinued, at least during the time of sample collection.

The blood level of molecular hydrogen H2 was significantly higher when molecular hydrogen  H2 was given by inhalation as compared to via intravenous route.

complete article  https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-2-14

REMEMBER:

Molecular hydrogen-rich water generally shows a more prominent effect than molecular hydrogen gas, although the amount of hydrogen taken up by hydrogen water is ~100 times less than that given by hydrogen gas [11].

 

 

 

https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-2-14
Hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers
  • Hirohisa OnoEmail author,
  • Yoji Nishijima,
  • Naoto Adachi,
  • Masaki Sakamoto,
  • Yohei Kudo,
  • Jun Nakazawa,
  • Kumi Kaneko and
  • Atsunori Nakao
Contributed equally
Medical Gas Research20122:14

https://doi.org/10.1186/2045-9912-2-14

Received: 25 December 2011

Accepted: 20 May 2012

Published: 20 May 2012

Notes

Declarations

Acknowledgements

The authors would like to thank Miz Company for technical assistance for setting up the hydrogen water tank and initial measurement of H2 concentration in the intravenous fluid bag.

Authors’ Affiliations

(1)

Department of Neurosurgery, Nishijima Hospital

(2)

Department of Surgery, University of Pittsburgh

References

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Copyright

© Ono et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen

Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases.

Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-17. Effective treatments, including pathogenesis-based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS-targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether molecular hydrogen H2, a ROS scavenger, has a therapeutic effect on psoriasis-associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade.

Three methods were used to administer molecular hydrogen H2: Drop infusion of saline containing 1 ppm H2 ( molecular hydrogen H2-saline), inhalation of 3% molecular hydrogen H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 molecular hydrogen water).

Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C-reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each molecular hydrogen H2 treatment.

Furthermore, levels of TNFα, IL-6, and IL-17 were analyzed. The DAS28 and PASI score of the three patients decreased during molecular hydrogen H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment.

IL-6 levels decreased during molecular hydrogen H2 treatment in Case 1 and 2.

IL-17, whose concentration was high in Case 1, was reduced following  molecular hydrogen H2 treatment, and TNFα also decreased in Case 1.

In conclusion, molecular hydrogen H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.[1]

 

1.Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases.

1
Department of Rheumatology and Orthopaedic Surgery, Haradoi Hospital, Higashi‑ku, Fukuoka 813‑8588, Japan.
2
Department of Dermatology, Haradoi Hospital, Higashi‑ku, Fukuoka 813‑8588, Japan.
3
MiZ Company, Fujisawa, Kanagawa 251‑0871, Japan.
4
Department of Radiology, Haradoi Hospital, Higashi‑ku, Fukuoka 813‑8588, Japan.
5
Department of Internal Medicine, Haradoi Hospital, Higashi‑ku, Fukuoka 813‑8588, Japan.
6
Department of Orthopaedic Surgery, Kyushu University, Higashi‑Ku, Fukuoka 812‑8582, Japan.
7
Department of Cardiology, Haradoi Hospital, Higashi‑ku, Fukuoka 813‑8588, Japan.
8
Midorino Clinic, Higashi‑ku, Fukuoka 813‑0025, Japan
PMID:25936373
DOI:10.3892/mmr.2015.3707
https://www.ncbi.nlm.nih.gov/pubmed/25936373

 2015 Aug;12(2):2757-64. doi: 10.3892/mmr.2015.3707. Epub 2015 Apr 30.

molecular hydrogen water benefits for athletes, exercise, muscle fatigue

Muscle contraction during short intervals of intense exercise causes oxidative stress, which can play a role in the development of overtraining symptoms, including increased fatigue, resulting in muscle microinjury or inflammation. Recently it has been said that molecular hydrogen can function as antioxidant, so we investigated the effect of molecular hydrogen-rich water (HW) on oxidative stress and muscle fatigue in response to acute exercise.

Methods

Ten male soccer players aged 20.9 ± 1.3 years old were subjected to exercise tests and blood sampling. Each subject was examined twice in a crossover double-blind manner; they were given either molecular hydrogen-rich water HW or placebo water (PW) for one week intervals. Subjects were requested to use a cycle ergometer at a 75 % maximal oxygen uptake (VO2) for 30 min, followed by measurement of peak torque and muscle activity throughout 100 repetitions of maximal isokinetic knee extension. Oxidative stress markers and creatine kinase in the peripheral blood were sequentially measured.

Results

Although acute exercise resulted in an increase in blood lactate levels in the subjects given PW, oral intake of molecular hydrogen-rich water HW prevented an elevation of blood lactate during heavy exercise.

Peak torque of PW significantly decreased during maximal isokinetic knee extension, suggesting muscle fatigue, but peak torque of molecular hydrogen-rich water HW didn’t decrease at early phase.

There was no significant change in blood oxidative injury markers (d-ROMs and BAP) or creatine kinease after exercise.

Conclusion

Adequate hydration with molecular hydrogen-rich water pre-exercise reduced blood lactate levels and improved exercise-induced decline of muscle function. Although further studies to elucidate the exact mechanisms and the benefits are needed to be confirmed in larger series of studies, these preliminary results may suggest that molecular hydrogen-rich water HW may be suitable hydration for athletes.

Introduction

Since energy demands and oxygen consumption increase during supermaximal exercise, such as intermittent running, sprints, and jumps, production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) also increase, threatening to disturb redox balance and cause oxidative stress. During normal conditions, ROS and RNS are generated at a low rate and subsequently eliminated by the antioxidant systems. However, a greatly increased rate of ROS production may exceed the capacity of the cellular defense system. Consequently, substantial free radicals’ attack on cell membranes may lead to a loss of cell viability and to cell necrosis and could initiate the skeletal muscle damage and inflammation caused by exhaustive exercise [123]. Although well-trained athletes suffer from less oxidative stress reduction because their antioxidant systems adapt, accumulation of intense exercise can provoke an increase in oxidative stress [4]. To mitigate oxidative stress-induced adverse events during sports, antioxidant supplementation among athletes has been well documented. Although results of these studies are often contradictory depending on the antioxidant compounds and quantity, some studies demonstrate the beneficial effects of antioxidants on muscle fatigue or performance [56].

Recently, the beneficial effects of molecular hydrogen-rich water (HW) have been described in experimental and clinical disease conditions [78]. Although research on the health benefits of molecular hydrogen-rich water HW is limited and there is scant data on long-term effects, pilot studies on humans suggest that consuming molecular hydrogen-rich water HW may help prevent metabolic syndrome [9], diabetes mellitus [10], and cancer patientsside effects with radiotherapy [11]. Since molecular hydrogen is known to scavenge toxic ROS [12] and induce a number of antioxidant proteins [1314], we hypothesized that drinking molecular hydrogen water HW may be beneficial for athletes in reducing oxidative stress-induced muscle fatigue following acute exercise. In this study, we evaluated the efficacy of molecular hydrogen water on healthy subjects by measuring muscle fatigue and blood lactate levels after exercise. Although further studies are needed to elucidate the exact mechanisms and benefits, this report suggests that molecular hydrogen water  might be an appropriate hydration fluid for athletes.

Methods

Subjects

Ten male soccer players aged 20.9 ± 1.3 years old were subjected to exercise tests and blood sampling. None of the subjects were smokers or were taking any supplements/medicines. Each subject provided written informed consent before participation in accordance with the University of Tsukuba’s Human Research Ethics Committee. Physical characteristics of the subjects are shown in Table 1. All the players were involved in daily training sessions except the day of experiment.

Table 1

Subjects’ Physical Characteristics (n = 10)

Variable

Value

Age (year)

20.9 ± 1.3

Height (cm)

172.0 ± 3.8

Body weight (kg)

67.1 ± 5.2

BMI (kg/m2)

22.8 ± 1.4

VO2max (ml/kg/min)

53.2 ± 4.9

BMI: body mass index, VO2max: maximal oxygen uptake.

Dose and mode of administration of hydrogen-rich water

Participants were asked to drink one 500 ml bottle at 10:00 PM of the day before the test, one 500 ml bottle at 5:00 AM, and one 500 ml bottle at 6:20 AM on the day of examination. In summary, subjects consumed 1,500 ml of molecular hydrogen rich water HW or PW(final hydrogen concentrations of the placebo water (PW) and hydrogen-rich water (HW) were 0 and 0.92 ~ 1.02 mM, respectively [911]. Each subject was examined twice in a crossover double-blind manner, given either molecular hydrogen rich water HW or PW for one week intervals).

Protocol

The research protocol started at 6:00 AM. Subjects were given meals between 9:00 PM and 10:00 PM the day before experiments, and fasted overnight. No breakfast was given on the day of the experiments. The subjects were first required to rest in a sitting position for 30 minutes. The exercise test consisted of the following: 1) Maximal progressive exercise test to define maximal oxygen uptake (VO2max); 2) cycling an ergometer for 30 minutes at approximately 75 % VO2max (Exercise-1); and 3) Running 100 maximal isokinetic knee extensions at 90 ° sec-1 (Exercise-2). Blood samples were collected from an antecubital vein just before Exercise-1 (6:30 AM), immediately after Exercise-1 (7:15 AM), immediately after Exercise-2 (7:30 AM), 30 minutes after Exercise-2 (8:00 AM) and 60 minutes after Exercise-2 (8:30 AM).

Maximal progressive exercise test

First, to define maximal oxygen uptake (VO2max), the subjects were subjected to a maximal progressive exercise test on a bicycle ergometer (232CL, Conbiwellness, Tokyo). The test consisted of a continuous step test beginning at a 30 W load, and increasing by 20 W every minute until exhaustion. The subjects were instructed to ride at 50 rpm/min. Pulmonary gas exchange values were measured using an exhaled gas sensor (AE280S, Minato Medical®, Osaka, Japan) via a breath-by-breath system, and the mean values were calculated every 30 seconds for analysis. We determined that VO2max was reached when the oxygen consumption reached its plateau [15].

Fixed-load cycling at 75 % (high intensity) of VO2 max

Before the test started, the subjects rested for two minutes. After warming up at a load of 50 W for one minute, the subjects were instructed to ride at submaximal levels for 30 minutes. Pulmonary gas exchange values were monitored to maintain VO2max at approximately 75 %. During the experiments, the subjects were frequently verbally instructed to control the range of motion to maintain VO2max at approximately 75 %.

Maximal isokinetic knee extensions

A calibrated Biodex System 3 isokinetic device (Biodex Medical Systems, New York, USA) was used to measure peak torque (PT) and knee-joint position throughout 100 repetitions of maximal isokinetic knee extension. During testing, each subject was seated on the Biodex system 3 with 90° hip flexion, and restraining straps were placed across the waist and chest in addition to a rigid sternal stabilizer. The dynamometer was motor driven at a constant velocity of 90°/sec. Each subject performed a series of 100 isokinetic contractions using the knee extensors of the right leg from 90° of flexion to 0° (full extension). As the arm of the dynamometer moved up from 90° to 0°, subjects were encouraged to perform maximally for each contraction throughout the full range of motion. Subjects relaxed as the dynamometer arm moved back to 90°. Each contraction and relaxation period lasted one second and the total length of the contraction cycle was thus two seconds. All subjects were able to complete the full 100 contractions.

Measurement of muscle fatigue

To measure muscle fatigue, the widely used First Fourier transform technique (FFT) is utilized to analyze mean frequency of surface electromyogram (EMG) [16]. EMG signals were obtained from the rectus femoris muscle via electrodes connected to a 4-channel frequency-modulation transmitter (Nihon Kohden, Tokyo, Japan). All data were stored and analyzed using the FFT functions in Acknowledge 3.7.5 software (BIOPAC SYSTEM, Santa Barbara, USA). Mean power frequency (MPF) and median power frequency (MDF) were calculated as previously described [17]. MPF shift of the EMG signal toward lower frequencies has been extensively used in static contractions to indicate the development of peripheral fatigue.

Blood test

Blood lactate levels were determined using a commercially available Lactate Pro LT17170 kit (Arkray, Inc., Kyoto, Japan). The concentrations of derivatives of reactive oxidative metabolites (dROMs) and biological antioxidant power (BAP) in the peripheral blood were assessed using a Free Radical Analytical System (FRAS4; Wismerll, Tokyo, Japan). Laboratory tests for creatine kinase (CK) were conducted using standardized procedures at Kotobiken Medical Laboratory Services (Tokyo, Japan).

Statistical analysis

Repeated analysis of variance (ANOVA) tests were used to compare pre- and post-exercise measurements. The F-test with Bonferroni post hoc group comparisons was performed where appropriate. Probability values less than 0.05 were considered to be statistically significant. SPSS 18.0 was used to perform the statistical analysis. Since the experiment was planned to have a 90 % power of achieving significance at the 5 % level, the sample size in this model is calculated to be between 8.91 and 9.25 (90 % power and 5 % significance level) in blood lactate levels based on our previous experiences. Therefore, we assumed the sample size would be appropriate for accumulation of preliminary data.

Results

Blood analysis for lactic acid, d-ROMs, BAP and CK

As shown in Table 2, blood d-ROMs BAP and CK levels increased after exercise in subjects in both groups treated with PW and molecular hydrogen rich water HW. However, there was no statistical difference between the groups. Eventhough the blood lactate level were significantly increased in both molecular hydrogen rich water HW and PW at 45 and 60 min after exercise, these levels were comparably and significantly lower in the molecular hydrogen rich water HW than in the PW group (Figure 1).

Table 2

Changes in Blood Levels

0 min

45 min

60 min

90 min

120 min

d-ROMs (U.CARR)

PW

269.0 ± 50.8

285.7 ± 52.3*

287.0 ± 56.9*

274.2 ± 50.2

280.0 ± 47.6

HW

281.3 ± 61.8

303.5 ± 46.3*

308.6 ± 56.1*

296.1 ± 57.9

307.0 ± 45.8

BAP (μmol/L)

PW

2347.3 ± 155.8

2648.9 ± 96.5*

2632.8 ± 146.4*

2349.6 ± 152.0

2321.8 ± 196.9

HW

2336.7 ± 123.1

2659.1 ± 102.1*

2664.6 ± 201.0*

2299.8 ± 104.6

2356.4 ± 143.7

CK (IU/L)

PW

247.0 ± 105.1

296.5 ± 119.9*

300.9 ± 127.7*

264.7 ± 113.3*

256.3 ± 111.7

HW

407.4 ± 269.9

483.2 ± 314.0*

478.1 ± 314.5*

428.2 ± 282.0

353.7 ± 264.6

Data were shown as mean ± standard deviation (SD). *p < 0.05 vs 0 min.

Figure 1

Sequential changes of blood lactate levels during exercise. Blood lactate levels in the athletes given PW significantly increased immediately after exercise compared to the levels at pre-exercise. molecular hydrogen rich water HW significantly reduced blood lactate levels post exercise using bicycle ergometer. (*p < 0.05 vs. time 0. #p < 0.05 vs HW, N = 10).

Maximal knee extension exercise

At analysis for maximal knee extension exercise, we divided into five frames of 100-repetition knee extension at the peak torque of isokinetic knee extension exercise [18]. Each frame was corresponded to 20 repetitions; Frame 1 for the first 20 repetitions, Frame 2 for the following 21-40 repetitions, Frame 3 for 41-60 repetitions, Frame 4 for 61-80 repetitions and Frame 5 for the last 81-100 repetitions. Although the peak torque of subjects treated with PW significantly decreased during the first 40 repetitions (Frame 1-2), the reduction of peak torque in the subjects given molecular hydrogen rich water HW did not reach statistical difference, suggesting that molecular hydrogen rich water HW inhibited the early decrease of peak torque of the subjects (Figure 2 A).

MDF and MPF from EMG analysis

MDF and MPF in the subjects treated with PW or molecular hydrogen rich water HW significantly decreased with time during exercise. While these values significantly decreased at Frame 1-2, there was no statistical difference between the subjects receiving PW and those receiving HW (Figure 2 B, C).

Figure 2

(A) Changes in peak torque (PT) every 20 repetitions (rep = 1 frame) during 100 maximum isokinetic knee extensions. PT of the subjects treated with PW significantly decreased during the initial 40-60 contractions by approximately 20-25 % of the initial values, followed by a phase with little change. On the other hand, there was no statistical difference between Frame 1 and Frame 2 in HW, indicating that HW prevented the decreasing the peak torque during the first 2 Frames. HW, Hydrogen rich water; PW, Placebo water. (*p < 0.05 vs Frame 1, N = 10). (B) Changes in median frequency (MDF) every 20 repetitions (rep = 1 Frame) during 100 maximum isokinetic knee extensions. Although exercise significantly reduced MDF values during the first 2 Frames, there was no statistical difference between HW and PW in all Frames. HW, Hydrogen rich water; PW, Placebo water. (*p < 0.05 vs Frame 1, N = 10). (C) Changes in mean power frequency (MPF) every 20 repetitions (rep = 1 Frame) during 100 maximum isokinetic knee extensions. There was no statistical difference between HW and PW in all Frames. HW, Hydrogen rich water; PW, Placebo water. (*p < 0.05 vs Frame 1, N = 10).

Discussion

In this preliminary study, we showed that hydration with molecular hydrogen rich water HW attenuated increase of blood lactate levels and prevented post-exercise decrease of peak torque, an indicator of muscle fatigue. Muscle fatigue is caused by many different mechanisms, including the accumulation of metabolites within muscle fibers and the generation of an inadequate motor command in the motor cortex. The accumulations of potassium, lactate, and H+ have often been suggested as being responsible for the decrease in muscle contractility [19]. In addition, aerobic, anaerobic, or mixed exercise causes enhanced ROS production, resulting in inflammation and cellular damage [20]. Short bursts of heavy exercise may induce oxidative stress through various pathways such as electron leakage within mitochondria, auto-oxidation of the catecholamine, NADPH activity, or ischemia/reperfusion [21]. Although the mechanism involved in the efficacies of molecular hydrogen rich water HW remains unclear, our results show that hydration with molecular hydrogen rich water HW could be feasible for acute exercise. Proper and adequate hydration is helpful for elite athletes to achieve the best performance. molecular hydrogen rich water HW can easily replace regular drinking water on a routine basis and would potentially prevent adverse effects associated with heavy exercise.

Factors such as age, nutritional status, training level, and physical activity category can influence the results [2223]. Although we had anticipated that molecular hydrogen , a known antioxidant, would reduce oxidative stress following acute exercise, the effects of oral intake of molecular hydrogen rich water HW were marginal and did not affect the level of oxidative markers after exercise. This can be explained by the facts that the athletes in our study have routinely trained and their antioxidant defense systems may be more active. Previous studies reported that repeated aerobic training increases antioxidant enzyme activity and subsequently decreases oxidative stress [2242526]. Also, considering the short life-span of molecular hydrogen  in circulation [27], more frequent drinking of molecular hydrogen rich water HW during exercise might have additional effects. In a future study, the efficacy of molecular hydrogen rich water HW on untrained subjects or recreational exercisers, who may have poorly established antioxidant systems to combat exercise-induced oxidative stress, should be tested. Furthermore, different drinking protocols should be investigated.

We quantified muscle fatigue as a decline in the maximal force or power capacity of muscle, which means that submaximal contractions can be sustained after the onset of muscle fatigue. Similarly, blood lactate concentration is one of the most often measured parameters during clinical exercise testing, as well as during performance testing of athletes. Lactate has often been considered one of the major causes of both fatigue during exercise and post-exercise muscle soreness. Lactate generated from the anaerobic breakdown of glycogen in the muscle occurs only during short bouts of relatively high intensity exercise and it is usually related to fatigue and muscle soreness. Previous evidence has shown that inorganic phosphate from creatine phosphate was the main cause of muscle fatigue [28].

Dehydration in athletes may also lead to fatigue, poor performance, decreased coordination, and muscle cramping. Although further investigations will be warranted, drinking molecular hydrogen rich water HW may be an appropriate hydration strategy [29]. In this study, we administered molecular hydrogen rich water HW or PW to subjects prior to exercise. Further investigation is required to determine the best timing, dose, and hydrogen concentration of drinking water to optimize the effects of molecular hydrogen rich water HW.

In conclusion, our preliminary data demonstrated that consumption of molecular hydrogen rich water HW reduced blood lactate levels and improved muscle fatigue after acute exercise. Although further studies are absolutely warranted, drinking molecular hydrogen rich water HW would be a novel and effective fluid hydration strategy for athletes.

https://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-2-12

 

 

 

Declarations

Acknowledgements

This research was supported by a Daimaru Research Foundation grant awarded to SM.

Authors’ Affiliations

(1)

Doctoral Program in Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba
(2)

Department of Emergency and Critical Care Medicine, Hyogo College of Medicine

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  1. Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes
    • Kosuke Aoki,
    • Atsunori NakaoEmail author,
    • Takako Adachi,
    • Yasushi Matsui and
    • Shumpei Miyakawa
    Medical Gas Research20122:12

    https://doi.org/10.1186/2045-9912-2-12

    Received: 21 March 2012

    Accepted: 20 April 2012

    Published: 20 April 2012

Copyright

© Aoki et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

hydrogen-enriched water for mitochondrial and inflammatory myopathies

Molecular hydrogen has prominent effects on more than 30 animal models especially of oxidative stress-mediated diseases and inflammatory diseases. In addition, hydrogen effects on humans have been reported in diabetes mellitus type 2, hemodialysis, metabolic syndrome, radiotherapy for liver cancer, and brain stem infarction. Molecular hydrogen effects are ascribed to specific radical-scavenging activities that eliminate hydroxyl radical and peroxynitrite, and also to signal-modulating activities, but the detailed molecular mechanisms still remain elusive. Molecular hydrogen is a safe molecule that is largely produced by intestinal bacteria in rodents and humans, and no adverse effects have been documented.

Methods

We performed open-label trial of drinking 1.0 liter per day of molecular hydrogen-enriched water for 12 weeks in 5 patients with progressive muscular dystrophy (PMD), 4 patients with polymyositis/dermatomyositis (PM/DM), and 4 patients with mitochondrial myopathies (MM), and measured 18 serum parameters as well as urinary 8-isoprostane every 4 weeks.

We next conducted randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of hydrogen-enriched water or placebo water for 8 weeks in 10 patients with dermatomyositis  DM and 12 patients with mitochondrial myopathies MM, and measured 18 serum parameters every 4 weeks.

Results

In the open-label trial, no objective improvement or worsening of clinical symptoms was observed. We, however, observed significant effects in lactate-to-pyruvate ratios in progressive muscular dystrophy PMD and mitochondrial myopathies MM, fasting blood glucose in progressive muscular dystrophy PMD, serum matrix metalloproteinase-3 (MMP3) in polymyositis/dermatomyositis PM/DM, and serum triglycerides in polymyositis/dermatomyositis PM/DM.

In the double-blind trial, no objective clinical effects were observed, but a significant improvement was detected in lactate in mitochondrial myopathies  MM. Lactate-to-pyruvate ratios in  mitochondrial myopathies MM and MMP3 in dermatomyositis DM also exhibited favorable responses but without statistical significance.

No adverse effect was observed in either trial except for hypoglycemic episodes in an insulin-treated MELAS patient, which subsided by reducing the insulin dose.

Conclusions

Molecular hydrogen-enriched water improves mitochondrial dysfunction in mitochondrial myopathies  MM and inflammatory processes in polymyositis/dermatomyositis  PM/DM.

Less prominent effects with the double-blind trial compared to the open-label trial were likely due to a lower amount of administered molecular hydrogen and a shorter observation period, which implies a threshold effect or a dose-response effect of molecular hydrogen.

Background

Ohsawa and colleagues first reported an effect of molecular hydrogen gas on cerebral infarction in June 2007 []. Effects of molecular hydrogen administered in the forms of inhaled gas, drinking water, instillation, and intraperitoneal injection have been reported for 31, 4, and 5 diseases in animal models, cells, and humans, respectively [].

Molecular hydrogen exhibits prominent effects especially on oxidative stress-mediated diseases and inflammatory diseases in rodents. Molecular Hydrogen scavenges hydroxyl radicals and less efficiently peroxynitrite []. The radical-scavenging activities, however, are unlikely to be an exclusive mechanism, because the amount of radical oxygen species generated in rodents and humans is much more than the amount of molecular hydrogen molecules taken up by the body. Indeed, the amount of molecular hydrogen taken up by drinking molecular hydrogen-enriched water (HEW) is 100 or more times less than that by inhaling 2% molecular hydrogen gas, but drinking molecular hydrogen-enriched water HEW exhibits beneficial effects as good as or even better than inhaling 2% molecular hydrogen gas in rodents [], which suggests the lack of a simple dose-response effect.

Our previous study on type 1 allergy also indicates that molecular hydrogen suppresses type 1 allergy by acting as a gaseous signal modulator not as a free radical scavenger [].

Effects of molecular hydrogen in humans have been examined in five studies.

First, a randomized, double-blind, placebo-controlled crossover study of 900 ml/day of molecular hydrogen-enriched water HEW for 8 weeks in 30 patients with diabetes mellitus type 2 demonstrated significant decreases of electronegative charge-modified LDL cholesterol, small dense LDL, and urinary 8-isoprostanes [].

Second, an open-label trial of electrolyzed molecular hydrogen-enriched hemodialysis solution in 9 patients for 4 months [] and 21 patients for 6 months [] showed significant decreases of systolic blood pressure before and after dialysis, as well as of plasma monocyte chemoattractant protein 1 and myeloperoxidase.

see also alkaline ionized water / molecular hydrogen water and hemodialisys

Third, an open-label trial of 1.5-2.0 liters per day of moelcualr hydrogen enriched water HEW for 8 weeks in 20 subjects with metabolic syndrome exhibited a 39% increase of urinary superoxide dismutase (SOD), a 43% decrease of urinary thiobarbituric acid reactive substances (TBARS), an 8% increase of high density lipoprotein (HDL)-cholesterol, and a 13% decrease of total cholesterol/HDL-cholesterol ratio [].

Fourth, a randomized placebo-controlled study of 1.5-2.2 liters/day of molecular hydrogen enriched water HEW for 6 weeks in 49 patients receiving radiotherapy for malignant liver tumors showed marked improvements of QOL scores [].As the study was not blinded, subjective QOL scores tended to be overestimated by a placebo effect, but objective markers for oxidative stress were also significantly decreased.

Fifth, drip infusion of hydrogen-enriched saline in combination with Edaravone, a clinically approved radical scavenger for cerebral infarction, for 7 days in 8 patients with brain stem infarction was compared to 24 such patients receiving Edaravone alone []. Although the study was not randomized and not blinded, MRI markers of patients infused with molecular hydrogen showed significant improvements and accelerated normalization.

Being prompted by the prominent effects of molecular hydrogen on inflammatory diseases and oxidative stress-mediated diseases especially in rodents, we performed an open-label trial of drinking 1.0 liter per day of molecular hydrogen enriched water  HEW for 12 weeks in 14 patients with muscle diseases, and identified improvement in four parameters: (i) a decrease of the lactate-to-pyruvate ratio in mitochondrial myopathies (MM) and progressive muscular dystrophy (PMD); (ii) a decrease of serum matrix metalloproteinase-3 (MMP3) in polymyositis/dermatomyositis (PM/DM), (iii) a decrease of fasting glucose in PMD, and (iv) a decrease of serum triglycerides in polymyositis/dermatomyositis  PM/DM.

We then conducted a randomized, double-blind, placebo-controlled, crossover trial of 0.5 liter per day of molecular hydrogen enriched water HEW for 8 weeks in 12 mitochondrial myopathies MM and 10 dermatomyositis DM cases. We observed that molecular hydrogen enriched water HEW significantly improved serum lactate in mitochondrial myopathies MM. In both studies, some patients reported subjective improvement of fatigability, diarrhea, and myalgia, but others reported floating sensation and worsening of diarrhea.

We observed no objective improvement or worsening of clinical symptoms during each study.

Our studies imply that molecular hydrogen enriched water HEW improves clinical parameters in mitochondrial myopathies  MM and polymyositis/dermatomyositis  PM/DM, but 0.5 liter/day for 8 weeks is likely to be insufficient to demonstrate statistically significant effects.

Patients and methods

Patients

For the open-label trial, we recruited 5 patients with progressive muscular dystrophy PMD, 4 patients with polymyositis/dermatomyositis PM/DM, and 5 patients with mitochondrial myopathies MM.

The progressive muscular dystrophy PMD patients comprised 1 male with Miyoshi myopathy and 4 females with limb girdle muscular dystrophy type 2B with an average age and SD of 50.4 ± 15.9 years (range 25 – 66).

The polymyositis/dermatomyositis PM/DM patients comprised 2 males and 2polymyositis/dermatomyositis females with an average age of 53.8 ± 24.8 years (range 29 – 83). All the polymyositis/dermatomyositis PM/DM cases were taking 5 – 10 mg of prednisolone per day and were well controlled.

The mitochondrial myopathies MM patients comprised 4 cases with MELAS (2 males and 2 females with an average age of 45.8 ± 12.3 years, range 37 – 64) and a 54-year-old female with chronic progressive external ophthalmoplegia (CPEO).

For the randomized, double-blind, placebo-controlled, crossover trial, we recruited 12 patients with mitochondrial myopathies MM and 10 patients with dermatomyositis DM.

The mitochondrial myopathies  MM patients comprised 5 cases with MELAS (2 males and 3 females with an average age of 44.6 ± 17.6 years, range 20 – 65), as well as 7 cases with CPEO (3 males and 4 females with an average age of 49.1 ± 11.1 years, range 29 – 61).

The dermatomyositis DM patients comprised 3 males and 7 females with an average age of 49.6 ± 13.7 years (range 32 – 66). All thdermatomyositis e DM patients were well controlled with 5 – 10 mg prednisolone per day.

3 mitochondrial myopathies MM and 3 DM dermatomyositis patients participated in both trials. Both trials were approved by the Ethical Review Board of the Aichi Medical University. Informed consent was obtained from each patient.

Protocols

We purchased 500 ml molecular hydrogen enriched water HEW or placebo water in aluminum pouch from Blue Mercury Inc. (Tokyo, Japan). We measured molecular hydrogen concentrations using an H2-N molecular hydrogen needle sensor attached to a PA2000 2-Channel Picoammeter (Unisense Science, Aarhus, Denmark). The molecular hydrogen concentrations were ~0.5 ppm (~31% saturation). We also confirmed that molecular hydrogen in placebo water was undetectable with our system. For each trial, we instructed patients to evacuate the air from the pouch and to close a plastic cap tightly every time after they drink water to keep the molecular hydrogen concentration as high as possible.

For the open-label trial, patients took 1.0 liter per day of molecular hydrogen enriched water HEW in five to ten divided doses for 12 weeks. We measured 18 serum and one urinary parameters and recorded clinical symptoms at 0, 4, 8, 12, 16 weeks.

For the double-blind trial, patients took 0.5 liter per day of molecular hydrogen enriched water HEW or placebo water in two to five divided doses for 8 weeks. Between the 8-week trials with molecular hydrogen enriched water HEW and placebo, we placed a 4-week washout period. We measured 18 serum parameters and recorded clinical symptoms at 0, 4, 8, 12, 16, 20, 24 weeks. In the double-blind trial, we did not measure urinary 8-isoprostane levels.

The data were statistically analyzed using one-way repeated measures ANOVA for the open-label trial and two-way repeated measures ANOVA for the double-blind trial, both followed by the Bonferroni’s multiple comparison test using Prism version 4.0c (Graphpad Software, San Diego, CA).

Results

Open-label trial

Fourteen patients with PMD, PM/DM, and MM participated in the study and no patient dropped out of the study. Patients took 1.0 liter of molecular hydrogen enriched water HEW for 12 weeks and we measured 18 serum and one urinary parameters every 4 weeks (Table (Table1).1).

We observed no objective improvement or worsening of clinical symptoms during the study. All the patients reported increased micturition frequency. Two MELAS patients reported improvement of fatigability, and another MELAS patient complained mild occasional floating sensation. We estimated statistical significance using one-way repeated measures ANOVA analysis and detected five parameters (Figure (Figure1).1). Serum lactate-to-pyruvate (L/P) ratios of MM patients were high before the study, and were decreased during the study (Figure (Figure1A).1A). Serum L/P ratios and fasting glucose levels of PMD patients were elevated after the study, but the values were still within normal ranges (Figures (Figures1B1B and and1C).1C). Serum MMP3 levels of DM patients were decreased down to 72.9% of those before HEW, which were again increased after the study (Figure (Figure1D).1D). Serum triglyceride levels of DM patients were elevated after the study (Figure (Figure1E1E).

Table 1

Open-label trial of HEW in 14 myopathic patients

Figure 1

Temporal profiles of four parameters that demonstrate statistical significance by one-way repeated measures ANOVA in the open-label trial. Ratios of serum lactate/pyruvate (L/P) in 5 mitochondrial myopathies (MM) patients (A) and 4 progressive muscular 

Randomized, double-blind, placebo-controlled, crossover trial

Twelve MM and ten DM patients participated in the study and no patient dropped out of the study. Patients took 0.5 liter of molecular hydrogen enriched water HEW or placebo water for 8 weeks and we measured 18 serum parameters every 4 weeks (Table (Table2).2). An MM patient reported increased micturition frequency on HEW. A DM patient reported subjective improvement of fatigability and diarrhea on molecular hydrogen enriched water HEW, but an MM patient rather complained increased diarrhea at first on molecular hydrogen enriched water HEW. Another DM patient reported an improvement of myalgia on molecular hydrogen enriched water HEW. A MELAS patient had hypoglycemic episodes only on molecular hydrogen enriched water HEW, but the episodes subsided after the insulin dose was decreased. We observed no objective improvement or worsening of clinical symptoms during the study. Two-way repeated measures ANOVA analysis revealed that only serum lactate levels were significantly decreased in MM by molecular hydrogen enriched water HEW (Figure (Figure2A).2A). Temporal profiles of serum L/P ratios in MM (Figure (Figure2B)2B) and of serum MMP3 levels in DM (Figure (Figure2C)2C) also demonstrated favorable responses to molecular hydrogen enriched water HEW but without statistical significance.

Table 2

Randomized, double-blind, placebo-controlled, crossover trial of molecular hydrogen enriched water HEW in 10 DM and 12 MM patients

Figure 2

Temporal profiles of three parameters in the double-blind trial. Serum lactate (A) and L/P ratios (B) in 12 mitochondrial myopathies (MM) patients. (C) Serum MMP3 in 10 dermatomyositis (DM) patients. Patients took molecular hydrogen enriched water HEW or placebo for 8 weeks. Means and 

Discussion

We performed open-label and double-blind studies of molecular hydrogen enriched water HEW on myopathic patients. In the open-label study, we observed statistical significance of molecular hydrogen water effects in four parameters: L/P ratios in MM and PMD; fasting glucose in PMD; MMP3 in PM/DM; and triglycerides in PM/DM (Figure (Figure1).1).

In the double-blind study, serum lactate levels were significantly improved in MM. L/P ratios in MM and MMP3 in DM were also improved but without statistical significance (Figure (Figure2).2).

Small numbers of participants in both the open-label and double-blind studies might have failed to disclose statistically significant effects of molecular hydrogen enriched water HEW.

In MM, the mitochondrial electron transfer system (mETS) is compromised by mutations in mitochondrial DNA []. This results in a decreased influx of NADH into mETS and elevates NADH levels in the cytoplasm, which facilitates conversion of pyruvate to lactate by lactate dehydrogenase. Thus, lactate and L/P ratio are useful surrogate markers to estimate functions of mETS, and are usually abnormally elevated in MM []. Defective mETS also causes leakage of electrons from mitochondrial inner membranes and increases production of reactive oxygen species (ROS), which further damages mETS [,]. Reduction of the L/P ratios in the open-label and double-blind studies suggests that hydrogen alleviates mETS dysfunction in MM either by scavenging ROS or by yet unidentified signaling mechanisms.

MMP3 belongs to a family of calcium-dependent zinc proteinases induced by cytokines and secreted by inflammatory cells. MMPs enhance T-cell migration and adhesion, and also degrade the extracellular matrix proteins []. MMP3 is increased in a fraction of DM patients []. MMP3 may facilitate lymphocyte adhesion and enhance T-cell-mediated cytotoxicity by degrading extracellular matrix proteins in DM.

molecular hydrogen water improved serum MMP3 levels in the open-label and double-blind studies, which is expected to ameliorate pathogenic inflammatory processes that culminates in muscle fiber destruction.

We observed less prominent effects with the double-blind study compared to the open-label study. The lack of statistically significance in the double-blind study is possibly due to a lower amount of molecular hydrogen enriched water HEW (1.0 vs. 0.5 liter per day) and to a shorter observation period (12 vs. 8 weeks). In the open-label study, drinking 1.0 liter of molecular hydrogen enriched water HEW was not readily accommodated by most myopathic patients. molecular hydrogen does not show simple dose-response relationship in rodents [], and ad libitum administration of even 5%-saturated molecular hydrogen enriched water HEW markedly attenuates development of Parkinson’s disease in mice []. We thus reduced the amount of hydrogen to 0.5 liter in the double-blind trial, and also shortened the observation period to minimize the burden on the participants. This, however, might have masked effects of molecular hydrogen enriched water HEW. Indeed, when we compare studies of diabetes mellitus type 2 [], the current open-label trial, and metabolic syndrome [], the participants took 0.9, 1.0, and 1.5-2.0 liters of molecular hydrogen enriched water HEW, respectively. Ratios of total cholesterol/HDL-cholesterol are available at 8 weeks in all the studies, and are changed to 103.8%, 98.6%, and 95.8%, respectively, of those before molecular hydrogen administration, which is in accordance with a dose-response effect of molecular hydrogen enriched water HEW. Additionally, among the two previous studies [,] and the current open-label and double-blind studies, the most prominent effects are observed with 1.5-2.0 liters of molecular hydrogen enriched water HEW. As drinking a large amount of molecular hydrogen enriched water HEW is not easily accommodated by most patients especially in winter, a threshold effect and/or a dose-response effect should be further elaborated for each pathological state.

Conclusions

molecular hydrogen enriched water HEW is effective for mitochondrial dysfunction in MM and inflammatory processes in DM.

molecular hydrogen may have a threshold effect or a dose-response effect and 1.0 liter or more per day of molecular hydrogen enriched water HEW is likely to be required to exert beneficial effects.

 

Abbreviations

HEW: hydrogen-enriched water; PMD: progressive muscular dystrophy; PM: polymyositis; DM: dermatomyositis; MM: mitochondrial myopathies; CPEO: chronic progressive external ophthalmoplegia; MELAS: mitochondrial myopathy with lactic acidosis and stroke-like episodes; MMP3: matrix metalloproteinase-3.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

TI and KS examined patients and acquired data. MIand TI organized data and performed statistical analysis. MIand KO wrote the paper. MI4, MI5, and KO conceived the study. All authors read and approved the final manuscript.

Acknowledgements

We would like to thank the patients for their participation in these studies. We thank Fumiko Ozawa for her technical assistance. This work was supported by Grants-in-Aid from the Ministry of Health, Labor, and Welfare of Japan and the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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  • Kang K-M, Kang Y-N, Choi I-B, Gu Y, Kawamura T, Toyoda Y, Nakao A. Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Med Gas Res. 2011;1:11. doi: 10.1186/2045-9912-1-11. [PMC free article] [PubMed] [Cross Ref]
  • Ono H, Nishijima Y, Adachi1 N, Tachibana S, Chitoku S, Mukaihara S, Sakamoto M, Kudo Y, Nakazawa J, Kaneko K, Nawashiro H. Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study. Med Gas Res. 2011;1:12. doi: 10.1186/2045-9912-1-12.[PMC free article] [PubMed] [Cross Ref]
  • DiMauro S. Pathogenesis and treatment of mitochondrial myopathies: recent advances. Acta Myologica. 2010;29:333–338. [PMC free article] [PubMed]
  • Wei YH, Lu CY, Wei CY, Ma YS, Lee HC. Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin J Physiol. 2001;44:1–11. [PubMed]
  • McKenzie M, Liolitsa D, Hanna MG. Mitochondrial disease: mutations and mechanisms. Neurochem Res. 2004;29:589–600. [PubMed]
  • Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001;17:463–516. doi: 10.1146/annurev.cellbio.17.1.463. [PMC free article] [PubMed][Cross Ref]
  • Nishijima C, Hayakawa I, Matsushita T, Komura K, Hasegawa M, Takehara K, Sato S. Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis. Clin Exp Immunol. 2004;138:357–363. doi: 10.1111/j.1365-2249.2004.02615.x. [PMC free article] [PubMed][Cross Ref]
  • Fujita K, Seike T, Yutsudo N, Ohno M, Yamada H, Yamaguchi H, Sakumi K, Yamakawa Y, Kido MA, Takaki A, Katafuchi T, Nakabeppu Y, Noda M. Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. PLoS One. 2009;4:e7247. doi: 10.1371/journal.pone.0007247.[PMC free article] [PubMed] [Cross Ref]

Articles from Medical Gas Research are provided here courtesy of Wolters Kluwer — Medknow Publications
Logo of mgr
. 2011; 1: 24.
Published online 2011 Oct 3. doi:  10.1186/2045-9912-1-24
PMCID: PMC3231939
Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

Should molecular hydrogen therapy be included in a musculoskeletal medicine routine?

Molecular hydrogen (H 2) has recently been recognized as a potential novel therapeutic agent in biomedicine. Initially proposed to be a possible treatment for certain types of neuromuscular disorders, cardio-metabolic diseases and cancer,molecular hydrogen  H 2 improved clinical end-points and surrogate markers in several clinical trials, mainly acting as an anti-inflammatory agent and powerful antioxidant. In this paper, the medicinal properties of molecular hydrogen H 2 in musculoskeletal medicine are discussed with the aim to provide an updated and practical overview for health professionals working in this field.

Background

As the oldest and the most abundant molecule in the universe, molecular hydrogen (H 2) has been traditionally recognized as a biologically inert gas. However, several trials in the past 10 years reported beneficial effects of molecular hydrogen H 2 in the clinical environment, revealing its possible role as a novel therapeutic agent in medicine – . Usually administered orally or via inhalation, molecular hydrogen H 2 improves both patient- and clinician-reported outcomes, and biomarkers of different pathologies and disorders, from metabolic diseases to chronic systemic inflammatory disorders to cancer [for detailed review see Ref. ].

Its clinical relevance seems to be particularly notable in the musculoskeletal medicine, with several small-scale short-term studies –  reporting that molecular H 2 was able to restore the health and functional abilities of patients after acute injuries or chronic illnesses affecting the muscles and bones. Since musculoskeletal conditions account for a large proportion of a general practitioner’s workload , one might consider molecular hydrogen  H 2 as a promising medication or adjuvant that could alleviate these prevalent conditions. In this opinion paper, the medicinal properties of molecular hydrogen H 2 in musculoskeletal medicine are discussed to provide an updated and practical overview for health professionals working in this field.

Promising results from preliminary studies

Being prompted by the prominent effects of molecular hydrogen H 2 on disuse muscle atrophy, cartilage trauma, and osteopenia in animal studies – , a number of clinical investigators from 2010 onwards evaluated the effectiveness of molecular hydrogen H 2 in patients suffering from different muscle and bone ailments – from sprains and strains to chronic joint disorders to myopathies – . Typically, these studies were designed as single-blind pilot trials, with small sample sizes (< 40 participants) and of short duration (≤ 12 weeks). Although limited in size and scope, those studies can provide early support for specific therapeutic claims about molecular hydrogen H 2 in musculoskeletal medicine. In a first trial, a combination of oral and topical molecular hydrogen H 2 resulted in a faster return to normal joint flexibility in 36 young men who had suffered sports-related soft tissue injuries, when administered for 14 days as a complementary treatment to a traditional medical protocol for soft tissue injuries 7.molecular  hydrogen  H 2intervention (hydrogen-rich packs 6 times per day for 20 min and 2 g of oral molecular hydrogen H 2 daily) was found to augment plasma viscosity decrease after an injury, while other biomarkers of inflammation (C-reactive protein, interleukin-6) and clinical outcomes (pain scores at rest and at walking, degree of limb swelling) were not affected by the intervention 7.

Another study in Japan reported that drinking 530 ml of a liquid containing 4 to 5 ppm of molecular hydrogen H  (dissolved in water) every day for 4 weeks significantly reduced disease activity in 20 patients with rheumatoid arthritis, as evaluated by changes in the degree of tenderness and swelling in 28 joints and C-reactive protein levels 8.  Molecular hydrogen H 2 was administered as an adjuvant to regular disease-modifying anti-rheumatic drugs and biological drugs, with the efficacy of molecular hydrogen H 2 found to be not inferior comparing to abatacept, methotrexate or a combination of two. In total, 47.4% of patients went into remission, with anti-citrullinated protein antibody (ACPA)-positive patients (ACPA levels above 300 U/mL; patients with worse prognosis and higher rates of erosive damage) responding best to the treatment.

Finally, the consumption of water containing a high concentration of moleuculr hydrogen H 2 (31% saturation) for up to 12 weeks improved surrogate markers of muscle pain and fatigability in 22 patients with inherited and acquired myopathies treated with low-dose prednisone . Taken together, the above studies seem to pave the way for a future use of molecular hydrogen H 2 therapy in musculoskeletal medicine.

please note that although the article above adds  little salt regarding molecular hydrogen safety due to it’s novelty ,one of the best parts about molecular hydrogen water is that it has been shown to have a tremendous safety profile. This has been demonstrated in a few ways:

  • Out of 600-plus scientific studies, molecular hydrogen  H2 has shown no cytotoxic effects or cytotoxic by-products in the human body. 22
  • We have a basal level of molecular hydrogen  H2 in our blood stream at all times, around 1~5 micromolar or less. 23
  • Humans can produce up to 10 liters of molecular hydrogen  H2 a day with a good diet containing fruits, vegetables, and fiber-rich foods. This is due to the production of molecular hydrogen  H2 by our gut flora (gut bacteria). 24
  • Another reason we know molecular hydrogen H2 is safe is because it has been used to ameliorate decompression sickness in deep sea diving since 1945. 25 The molecular hydrogen H2 concentration has been as high 98.87 percent molecular hydrogen  H2 and 1.26 percent of O2, at 19.1 atm with minimal to no adverse or cytotoxic effects. 26 The United States military also has been using molecular hydrogen H2 for deep sea diving since the 60s. 27 Molecular hydrogen has been demonstrated to be extremely safe for the human body. 28

 

This information tells us that molecular hydrogen-rich water is safe for consumption in all age groups, from children to adults, as a preventive beverage that has the potential to reduce oxidative stress and so much more. Everyone, including children, is exposed to oxidative stress, which has been linked to the pathogenesis of nearly all disease conditions, including cancer. 29 Consuming water infused with molecular hydrogen is exactly what our society needs to aid in the battle against degenerative diseases.

Please note that most studies and research with molecular hydrogen gas were performed using molecular hydrogen rich water

References

1. Kajiyama S, Hasegawa G, Asano M, et al. : Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res.2008;28(3):137–43. 10.1016/j.nutres.2008.01.008 [PubMed] [Cross Ref]
2. Nakao A, Toyoda Y, Sharma P, et al. : Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study. J Clin Biochem Nutr.2010;46(2):140–9. 10.3164/jcbn.09-100 [PMC free article] [PubMed] [Cross Ref]
3. Nakayama M, Nakano H, Hamada H, et al. : A novel bioactive haemodialysis system using dissolved dihydrogen (H 2) produced by water electrolysis: a clinical trial. Nephrol Dial Transplant.2010;25(9):3026–33. 10.1093/ndt/gfq196 [PubMed] [Cross Ref]
4. Yoritaka A, Takanashi M, Hirayama M, et al. : Pilot study of H 2 therapy in Parkinson’s disease: a randomized double-blind placebo-controlled trial. Mov Disord. 2013;28(6):836–9. 10.1002/mds.25375[PubMed] [Cross Ref]
5. Xia C, Liu W, Zeng D, et al. : Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin Transl Sci. 2013;6(5):372–5. 10.1111/cts.12076[PMC free article] [PubMed] [Cross Ref]
6. Ostojic SM: Molecular hydrogen: An inert gas turns clinically effective. Ann Med. 2015;47(4):301–4. 10.3109/07853890.2015.1034765 [PubMed] [Cross Ref]
7. Ostojic SM, Vukomanovic B, Calleja-Gonzalez J, et al. : Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries. Postgrad Med. 2014;126(5):187–95. 10.3810/pgm.2014.09.2813[PubMed] [Cross Ref]
8. Ishibashi T, Sato B, Rikitake M, et al. : Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Med Gas Res. 2012;2(1):27. 10.1186/2045-9912-2-27 [PMC free article] [PubMed][Cross Ref]
9. Ito M, Ibi T, Sahashi K, et al. : Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med Gas Res.2011;1(1):24. 10.1186/2045-9912-1-24 [PMC free article] [PubMed] [Cross Ref]
10. Hunter DJ, Reddy KS: Noncommunicable diseases. N Engl J Med. 2013;369(14):1336–43. 10.1056/NEJMra1109345 [PubMed] [Cross Ref]
11. Fujita R, Tanaka Y, Saihara Y, et al. : Effect of molecular hydrogen saturated alkaline electrolyzed water on disuse muscle atrophy in gastrocnemius muscle. J Physiol Anthropol. 2011;30(5):195–201. 10.2114/jpa2.30.195 [PubMed] [Cross Ref]
12. Guo JD, Li L, Shi YM, et al. : Hydrogen water consumption prevents osteopenia in ovariectomized rats. Br J Pharmacol. 2013;168(6):1412–20. 10.1111/bph.12036 [PMC free article] [PubMed] [Cross Ref]
13. Hanaoka T, Kamimura N, Yokota T, et al. : Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide. Med Gas Res. 2011;1(1):18. 10.1186/2045-9912-1-18 [PMC free article] [PubMed] [Cross Ref]
14. Derry S, Wiffen P, Moore A: Topical Nonsteroidal Anti-inflammatory Drugs for Acute Musculoskeletal Pain. JAMA. 2016;315(8):813–4. 10.1001/jama.2016.0249 [PubMed] [Cross Ref]
15. Strehl C, Bijlsma JW, de Wit M, et al. : Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis. 2016;75(6):952–7. 10.1136/annrheumdis-2015-208916[PubMed] [Cross Ref]
16. The Food and Drug Administration (FDA): Agency Response Letter GRAS Notice No. 520. (Assessed at October 28, 2016). Reference Source
17. The Food and Drug Administration (FDA): Inspections, Compliance, Enforcement, and Criminal Investigations. (Assessed at October 28, 2016). Reference Source

Approved

1Department of Neurology and Psychiatry, Saint Louis University School of Medicine, Saint Louis, MO, USA
Competing interests: No competing interests were disclosed.
Review date: 2016 Dec 8. Status: Approved

The title is appropriate with reference to the content of the article.

The article is a review of the literature with reference to utilizing molecular hydrogen to enhance sports related injuries.

After a detailed review of the literature, the conclusion is there is not enough information to make any solid recommendation concerning utilizing molecular hydrogen to treat sports related injuries, so the implication is probably molecular hydrogen doesn’t improve recovery from sports related injuries enough to make any difference.

This appears to be a good review of the related literature.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

Approved

Xiaoli SunReferee1 and Ning ZhangCo-referee2
1Department of Diving Medicine, Second Military Medical University, Shanghai, China
2Department of Naval Aeromedicine, Second Military Medical University, Shanghai, China
Competing interests: No competing interests were disclosed.
Review date: 2016 Dec 8. Status: Approved

This opinion paper provides an undated and practical overview on the properties of molecular hydrogen in musculoskeletal medicine. The paper focuses on the preliminary studies of H2 on musculoskeletal medicine, and the concerns over the general use of products containing H2. I sympathize the author’s prudent attitudes, which toward the hydrogen should be regarded as an experimental agent and not recommended to general use provisionally. However, I think this paper should also mention the long-term diving practices which high pressure hydrogen inhalation involved to prove the possible safe use of H2 gas.

We have read this submission. We believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.


Articles from F1000Research are provided here courtesy of F1000 Research Ltd
Logo of f1000res
Version 1. . 2016; 5: 2659.
Published online 2016 Nov 10. doi:  10.12688/f1000research.9758.1
PMCID: PMC5147523
Should hydrogen therapy be included in a musculoskeletal medicine routine?
1Faculty of Sport and PE, University of Novi Sad, Novi Sad, Serbia
2University of Belgrade School of Medicine, Belgrade, Serbia
Competing interests: No competing interests were disclosed.

Effectiveness of oral and topical molecular hydrogen for sports-related soft tissue injuries

Because molecular hydrogen (water) therapy has been found beneficial for the treatment of inflammation, ischemia-reperfusion injury, and oxidative stress in humans, it seems useful to evaluate the effects of exogenously administered molecular hydrogen as an element in the immediate management of sports-related soft tissue injuries. The main aim of this pilot study was to examine the effects of 2-week administration of molecular hydrogen on the biochemical markers of inflammation and functional recovery in male professional athletes after acute soft tissue injury.

METHOD:

During the 2013 season (from March to May), 36 professional athletes were recruited as participants and examined by a certified sports medicine specialist in the first 24 hours after an injury was sustained. Subjects were allocated to 3 randomly assigned trials in a single-blind design. Those in the control group received a traditional treatment protocol for soft tissue injury. Subjects in the first experimental group followed the same procedures as the control group but with additional administration throughout the study of oral molecular hydrogen-rich tablets (2 g per day). Subjects in the second experimental group also followed the procedures of the control group, with additional administration throughout the study of both oral molecular hydrogen-rich tablets (2 g per day) and topical molecular hydrogen-rich packs (6 times per day for 20 minutes). Participants were evaluated at the time of the injury report and at 7 and 14 days after baseline testing.

RESULTS:

Oral and topical molecular hydrogen intervention was found to augment plasma viscosity decrease as compared with the control group (P = 0.04). Differences were found for range-of-motion recovery between the 3 groups; oral and topical molecular hydrogen intervention resulted in a faster return to normal joint range of motion for both flexion and extension of the injured limb as compared with the control intervention (P < 0.05).

CONCLUSION:

These preliminary results support the hypothesis that the addition of molecular hydrogen to traditional treatment protocols is potentially effective in the treatment of soft tissue injuries in male professional athletes.

 

 

Trial identification: Clinicaltrials.gov number NCT01759498.

PMID:25295663
DOI: 10.3810/pgm.2014.09.2813
 2014 Sep;126(5):187-95. doi: 10.3810/pgm.2014.09.2813.
Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries.

1Center for Health, Exercise, and Sport Sciences, Stari DIF, Belgrade, Serbia. sergej.ostojic@chess.edu.rs.

molecular hydrogen water for patients with rheumatoid arthritis: an open-label pilot study

Recently, molecular hydrogen (H2) was demonstrated to be a selective scavenger for the hydroxyl radical.

Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of Rheumatoid arthritis( a chronic inflammatory disease characterized by the destruction of bone and cartilage..).

We hypothesized that molecular hydrogen H2 in the water could complement conventional therapy by reducing the oxidative stress in Rheumatoid arthritis

The method to prepare water containing extremely high concentration of molecular hydrogen H2 has been developed.

20 patients with rheumatoid arthritis (RA) drank 530 ml of water containing 4 to 5 ppm molecular hydrogen (high H2) water every day for 4 weeks. After a 4-week wash-out period, the patients drank the high molecular hidrogen H2 water for another 4 weeks.

Urinary 8-hydroxydeoxyguanine (8-OHdG) and disease activity (DAS28, using C-reactive protein [CRP] levels) was estimated at the end of each 4-week period.

Results:

Drinking high molecular hydrogen H2 water seems to raise the concentration of molecular hydrogen H2 more than the H2 molecular hydrogen saturated (1.6 ppm) water in vivo.

Urinary 8-OHdG was significantly reduced by 14.3% (p < 0.01) on average. DAS28 also decreased from 3.83 to 3.02 (p < 0.01) during the same period.

After the wash-out period, both the urinary 8-OHdG and the mean
DAS28 decreased, compared to the end of the drinking period.

During the second drinking period, the mean DAS28 was reduced from 2.83 to 2.26 (p < 0.01). Urinary 8-OHdG was not further reduced but remained below the baseline value.

All the 5 patients with early rheumatoid arthritis (duration < 12 months) who did not show antibodies against cyclic citrullinated peptides (ACPAs) achieved remission, and 4 of them became symptom-free at the end of the study.

Conclusions: The results suggest that the hydroxyl radical scavenger -molecular hydrogen H2(dissolved in water) effectively reduces oxidative stress in patients with rheumatoid arthritis. The symptoms of rheumatoid arthritis were significantly improved with high molecular hidrogen H2 water.

 

 

 

 

Consumption of water containing a high
concentration of molecular hydrogen reduces
oxidative stress and disease activity in patients
with rheumatoid arthritis: an open-label pilot
study
Toru Ishibashi1*, Bunpei Sato2
, Mariko Rikitake1
, Tomoki Seo2
, Ryosuke Kurokawa2
, Yuichi Hara1
, Yuji Naritomi1
,
Hiroshi Hara1 and Tetsuhiko Nagao3

* Correspondence: toruishi@haradoi-hospital.com 1
Haradoi Hospital, Department of Rheumatology and Orthopaedic Surgery,
6-40-8 Aoba, Higashi-ku, Fukuoka 813-8588, Japan
Full list of author information is available at the end of the article
MEDICAL GAS
RESEARCH
© 2012 Ishibashi et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.

doi:10.1186/2045-9912-2-27
Cite this article as: Ishibashi et al.: Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Medical Gas Research 2012 2:27.

Molecular hydrogen (water) benefits/effects for metabolic syndrome

 

The objective of this study was to examine the effectiveness of molecular hydrogen rich water (1.5-2 L/day; molecular hydrogen concentration; 0.55-0.65 mM)) in an open label, 8-week study on 20 human subjects with potential metabolic syndrome.

Metabolic syndrome is characterized by cardiometabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome.

 

The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine.

Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4.

There was no change in fasting glucose levels during the 8 week study.

In conclusion, drinking molecular hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome.

 

 

 2010 Mar;46(2):140-9. doi: 10.3164/jcbn.09-100. Epub 2010 Feb 24.
Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study.

Heart, Lung and Esophageal Surgery Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 15213, USA.

PMID:20216947; https://www.ncbi.nlm.nih.gov/pubmed/20216947
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831093/
 
DOI:10.3164/jcbn.09-100

Alkaline Ionized Water/ Electrolyte Reduced Water treatment administration is effective in palliating hemodialysis 

Alkaline Ionized Water/ Electrolyte Reduced Water treatment administration is effective in palliating hemodialysis

Electrolyte Reduced Water treatment administration is effective in palliating hemodialysis -evoked oxidative stress as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in hemodialysis patients:

We explored whether alkaline ionized water/electrolyte-reduced water (ERW) could palliate chronic hemodialysis HD-evoked erythrocyte impairment and anemia.(Chronic hemodialysis (HD) patients increase erythrocyte susceptibility to hemolysis and impair cell survival).

43 patients undergoing chronic hemodialysis were enrolled and received alkaline ionized water/electrolyte-reduced water ERW administration for 6 month. We evaluated oxidative stress in blood and plasma, erythrocyte methemoglobin (metHb)/ferricyanide reductase activity, plasma metHb, and proinflammatory cytokines in the chronic hemodialysis  patients without treatment (n=15) or with vitamin C (VC)- (n=15), vitamin E (VE)-coated dialyzer (n=15), or alkaline ionized water/electrolyte-reduced water ERW treatment (n=15) during an  hemodialysis HD course.

The patients showed marked increases (15-fold) in blood reactive oxygen species, mostly H(2)O(2), after  hemodialysis without any treatment.  hemodialysis  resulted in decreased plasma Vitamin C, total antioxidant status, and erythrocyte metHb/ferricyanide reductase activity and increased erythrocyte levels of phosphatidylcholine hydroperoxide (PCOOH) and plasma metHb.

Antioxidants treatment significantly palliated single  hemodialysis course-induced oxidative stress, plasma and RBC PCOOH, and plasma metHb levels, and preserved erythrocyte metHb /ferricyanide reductase activity in an order Vitamin C>Electrolyte Reduced Water>Vitamin E-coated dialyzer.

However, Electrolyte Reduced Water had no side effects of oxalate accumulation easily induced by Vitamin C.

Six-month Electrolyte Reduced Water treatment increased hematocrit and attenuated proinflammatory cytokines profile in the hemodialysis patients.

In conclusion, Electrolyte Reduced Water treatment administration is effective in palliating hemodialysis-evoked oxidative stress, as indicated by lipid peroxidation, hemolysis, and overexpression of proinflammatory cytokines in hemodialysis patients.

PMID:16760903
DOI:10.1038/sj.ki.5001576
 2006 Jul;70(2):391-8. Epub 2006 Jun 7.

Electrolyzed-reduced water reduced hemodialysis-induced erythrocyte impairment in end-stage renal disease patients.

Author information

1
Department of Family Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.

Molecular  Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

Molecular  Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

We have found that molecular hydrogen (dihydrogen; H2) water has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters.

The objective of this study was to characterize the effects of molecular hydrogen H2-rich water (0.9-1.0 l/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome.

Serum analysis showed that consumption of molecular hydrogen H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels.

Western blot analysis revealed a marked decrease of apolipoprotein (apo)B100 and apoE in serum.

In addition, we found molecular hydrogen water H2 significantly improved HDL functionality assessed in four independent ways, namely:

i) protection against LDL oxidation,

ii) inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells,

iii) stimulation of cholesterol efflux from macrophage foam cells, and

iv) protection of endothelial cells from TNF-α-induced apoptosis.

Further, we found consumption of molecular hydrogen H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL.

In