Molecular hydrogen gas is usually given by inhaling 1–4 % hydrogen gas, which is below the explosion level (4 %). There is a single report, in which hydrogen gas was injected intraperitoneally .
Among the various routes of molecular hydrogen administration , the best method still remains uncertain. This is partly because only a few reports have addressed the difference of effects among molecular hydrogen administration methods.
A comparative review was conducted on the consumption of molecular hydrogen H2-rich water, i.p. or intravenous administration of molecular hydrogen H2-rich saline, and inhalation of molecular hydrogen H2 gas in regards to Molecular hydrogen (water) in the treatment of acute and chronic neurological conditions(Alzheimer’s, Parkinson’s,etc).
The results showed that although molecular hydrogen H2 concentrations in the brain tend to be high after either intravenous administration or inhalation, no significant differences have been observed in comparison with the concentrations after the consumption of molecular hydrogen H2-rich water and i.p. administration of molecular hydrogen H2-rich saline. Thus, although there have been variations based on the administration method, all methods have been found to result in the presence of molecular hydrogen H2 in the serum and brain tissue.
Liu et al.(39) measured molecular hydrogen H2 levels in the arteries, veins, and brain tissues after the inhalation of 2% molecular hydrogen H2 gas. They found that arterial molecular hydrogen H2 peaked at 30 min after administration, whereas venous and brain tissue molecular hydrogen H2 peaked at 45 min after administration. They reported that molecular hydrogen H2 levels were similar in arteries and brain tissues.
This demonstrated that molecular hydrogen H2 migrates to the brain tissue regardless of the method of administration(Thus, the studies might as well have been performed using molecular hydrogen water instead of molecular hydrogen gas or molecular hydrogen saline).
Furthermore, keep in mind that crossing the blood–brain barrier (BBB) is a very difficult task to achieve for many substances , thus the fact that molecular hydrogen H2 crosses the BBB and migrates to the brain tissue regardless of the method of administration (including by drinking molecular hydrogen water – which is the easiest method of administration molecular hydrogen ) is a strong indicator that one can benefit from drinking molecular hydrogen water just as much as from any other method of administration molecular hydrogen
However, when molecular hydrogen concentrations in drinking water and in inhaled gas are compared, there is no dose–response effect.
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 .
We have showed that drinking molecular hydrogen water, but not continuous molecular hydrogen gas exposure, prevented development of 6-hydorxydopamine-induced Parkinson’s disease in rats .
In addition, we recently showed that continuous exposure to molecular hydrogen gas and ad libitum per os administration of molecular hydrogen water modulated signaling pathways and gene expressions in different manners in mice .
We demonstrated that molecular hydrogen-responsive genes are divided into four groups: genes that respond favorably to molecular hydrogen gas, those that respond exclusively to molecular hydrogen water, those that respond to both molecular hydrogen gas and water, and those that respond only to the simultaneous administration of molecular hydrogen gas and water (Fig. 2).
As molecular hydrogen water and gas increase the molecular hydrogen concentrations in the rodent body to a similar level , the difference in the organs exposed to a high concentration of molecular hydrogen, the rise time of molecular hydrogen concentration, and/or the area under the curve of molecular hydrogen concentration may account for the difference in the modulated genes.
On the other hand, a collation of molecular hydrogen reports indicate that a similar degree of effects can be observed with different modalities of administration. For example, the marked effect of molecular hydrogen on a mouse model of LPS-induced acute lung injury has been reported by four different groups with three different modalities:molecular hydrogen gas [13, 14], molecular hydrogen water , and molecular hydrogen-rich saline [14, 16].
Similarly, the dramatic effect of molecular hydrogen on animal models of acute myocardial infarction has been reported by eight different groups with two different modalities: molecular hydrogen gas [17, 18, 19, 20] and molecular hydrogen-rich saline [21, 22, 23, 24].
To clarify the difference of molecular hydrogen’s effects with different modalities of administration, each research group should scrutinize the difference of the effects between molecular hydrogen gas, molecular hydrogen water, and molecular hydrogen-rich saline. This would uncover the best modality for each disease model, IF ANY, and also the optimal molecular hydrogen dose.
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