2016年9月，利用在山东泰安参加中国氢分子生物医学年会的机会，太田成男和我们共同发起成立了国际氢标准委员会，致力于制定氢气医学相关产品标准，以帮助国际氢气医学学术和产业领域。

   最新这一标准只针对氢水产品，这一标准是一个建议标准，没有强制性，是由国际氢标准委员会制定的，制定者是真正长期从事氢气医学学术研究的一线学者，这一标准会成为许多学术研究和产品的重要参照。

   这个标准也可以作为其他学术组织和政府机构制定相关标准的重要参考资料。这是英文原文，我们不久将推出中文版。

《氢思语》全权代表在中国的新媒体发布。

IHSA comments on the world-widecertification of drinkable hydrogen water; declared by “International HydrogenStandards Association”

起草发起人主要包括

Shigeo Ohta, Japan

GaeHo Lee, Korea

XueJun Sun, China

Shucun Qin, China

TylerW. LeBaron, USA

Introduction

Currentlythroughout the world, biomedical researchers and the general public arelearning about molecular hydrogen therapy, including hydrogen gas inhalation,hydrogen infused water (hydrogen water), etc. for the prevention of variousdiseases and overall health and wellness. The efficacy of molecular hydrogen isbased on published scientific research. However, there has currently been nodefinition or standard, by the scientist or the public, of what constitutes ahydrogen product for therapy in terms of concentration, dose, or otherrequirements.

Thissituation has led to confusion in the industry, media, government, andcommercial markets of hydrogen products. Since molecular hydrogen is acolorless, odorless, and tasteless gas, it is difficult for the consumer public to determine the concentration, or even the presence of molecularhydrogen in these products.

Therefore,expert scientists on hydrogen medicine from around the world have unitedtogether to discuss and define the international standards of molecularhydrogen. We established the International Hydrogen Standards Association(IHSA) in September 2016. These definitions and standards byIHSA will help advance the scientific research, guide and give responsibilityto the hydrogen industry, and provide protection/satisfaction to the publicconsumer.

Inthis document, IHSA specifically defines hydrogen water as water or liquidscontaining dissolved molecular hydrogen, which is termed by the chemical formula H2. Below is the recommendation on standardsof hydrogen water for the certification by IHSA, dated on September 15,2017.  

Methods to determine the hydrogenconcentration

Gas chromatography (GC) will be considered the primarymethod for measuring molecular hydrogen. GC should be the most reliable method for specialists in chemicalanalyses. In brief this method requires the transfer of H2 from theaqueous phase to the gas phase using a tightly closed vessel, where hydrogenconcentration can be measured by GC.  Thestandard operation procedure (SOP) for measurement by GC will soon bedetermined by IHSA to mitigate systematic errors.

IHSA will also adopt a secondary method using anelectrode that is specific to hydrogen. Several electrodes are currentlyavailable commercially; however, each has a merit and shortcoming. Thus, oneelectrode will be carefully selected for the measurement, and the standardoperation procedure (SOP) determined by IHSA. There may be other suitableoptions for general consumer use, but not for IHSA certification use, that IHSAmay recommend (e.g. different brands of electrodes, sensors, H2Blue,etc.).However, methods that depend on using the oxidation-reduction potential(ORP) to estimate hydrogen in water is not recommended. Although a negative ORPis one of the characteristics of hydrogen water, ORP itself does not show thehydrogen concentration. Thus, ORP should not be used as the method formeasurement of the hydrogen concentration.

The Unitindicating hydrogen concentration

IHSA will use the unit of mg/L when discussing theconcentration of hydrogen in water. This will help reduce the confusion fromusing other commonly units. For example, ppm (parts per million) has beenfamiliar for consumers and often used; however, ppm indicates two ways; one isweight per weight (wt/wt) and the other is weight per volume (wt/vol).  Since hydrogen is a gaseous molecule, thesetwo ways are often used, leading to some confusion. Thus, for this thisrecommendation and certification, milligram (mg) and milligram per litter(mg/L) are adopted as a dose and a concentration of hydrogen, respectively.

Concentration/dose

After much debate and consideration, we suggest thatthe minimal amount of hydrogen should be established as a dose per day in amaximal volume of solution. The standard has been determined to provide atleast 0.5 mg of H2 by ingesting a maximal volume of 1 L of productwater, or 500 mL of specialty beverages.

It is understood that more research is needed tofully know the minimum effective dose (MED) and the minimum effective concentration(MEC) of H2 at the cellular level. Ideally, the dose would be givenin mg/kg of body weight with an optimal time factor based on its half-life andpharmacokinetics/pharmacodynamics. However, this is more challenging with H2because unlike conventional pharmacological agents, H2 does not havesingle/specific receptor/target or organ function. The MED/MEC will likely varybased on age, body weight, disease, genetics, intestinal bacteria, diet, etc.The IHSA recommendation is simply a standard based on the current cell, animal,and human clinical studies. It is not perfect and is subject to change based onadditional biomedical research.

Justification

Animaland human studies generally provide between 0.5 mg to 1.6 mg or more per day.Unlike conventional drugs, it is logical that humans may require a similarequivalent dose of H2 as do rodents because there are no receptorsto bind H2 as there are for drugs. The IHSA standard of a minimum ofa 0.5 mg dose per liter of water is supported by the lower dose studies inanimals and humans. For example, in a mouse model of Parkinson’s disease, Fujita, K. et al (2009) reportedthat a concentration of 0.08 ppm, but not 0.04 ppm was effective in.Interestingly, 0.08 ppm would provide a dose of H2 per day that issimilar to a human ingesting about 0.5 mg of H2 per day (0.08 mg/L *0.005 L/0.05 kg * 60kg = 0.48 mg H2). Similarly, a 0.04 ppm wouldequate to about 0.25 mg per day in humans. These doses are in line with twohuman studies that suggest that 0.5 mg, but not 0.25 mg per day is effective.

Inone human study (Ito, M. et al. 2011), subjects ingested 0.25 mg/day bydrinking 0.5 L of 0.5 ppm H2 water. At this low dose, there were noobserved benefits. The researchers suggested that if they either a) consumedthe same amount of water at a higher concentration, or b) consumed a highervolume of water at a similar concentration, then they would have noticed abenefit. Indeed, the preliminary data (open-label trial) in the same article,used 1 L of water (0.5 mg H2 per day), and significant benefits wereobserved (*only 0.5 L were consumed in the placebo-controlled trial becausepatients struggled to consume 1 L per day). Another human study provided 0.5 mgH2 per day by ingestion 1 L of 0.5 ppm, and noted significantbenefits (Song G. et al. 2013).

Dose instead of concentration

Settinga specific concentration (e.g. 0.8 ppm) can be contested by companies who statethat people can get a higher dose of hydrogen by drinking 1 liter of 0.5 ppm,than they could by drinking a 250-mL can of 1 ppm H2 water (0.5 mgvs. 0.25 mg).

Volume

Althoughone can reach 0.5 mg of H2 by ingesting a large volume of lowconcentration H2-water (e.g. 5 L of 0.1 ppm), this is problematicbecause 1) some have difficulty drinking high volumes of water, and 2) it ispossible that ingesting H2 in this manner may not result inequivalent therapeutic effects as ingesting 0.5 mg at once. This is because thecellular concentration may not reach the “unknown” minimal requiredconcentration (e.g. 5-10 uM). Based on the above human studies, and currentguidelines for ingesting water, we have set the maximal volume as 1 L per dayfor water and 500 mL per day for specialty beverages (e.g. juice, carbonated drinks,teas, etc.).

Criteria

Packagedhydrogen water:

1)    provides at least 0.5mg per L serving

a.     minimum concentrationis 0.5 mg/L

b.    drinking 1 L of wateris practical for most people

2)    passes safety test fortoxins/heavy metals

3)    maintains minimumconcentration of 0.5 mg/L:

a.     until the statedexpiration date

b.    or for at least six (6)months if not stated

4)    pH must be in range 5to 9.5

5)    no false or damagingmarketing claims that could harm the credibility of the hydrogen research andindustry

Specialtybeverages:

1)    provides at least 0.5mg per 500 mL serving

a.     minimum concentrationis 1 mg/L

b.    drinking more than 500mL of a H2-rich beverage is not recommend for health

c.     however, each beveragewill be evaluated on a case-by-case basis.

                                              i.     If an H2 productcontains stimulants or other potentially harmful ingredients where even 500 mLis too high of a volume.

2)    passes safety test fortoxins/heavy metals

3)    maintains minimumconcentration of 0.5 mg/L:

a.     until the statedexpiration date

b.    or for at least six (6)months if not stated

4)    pH can range from 3 to10

5)    no false or damagingmarketing claims that could harm the credibility of the hydrogen research andindustry

Hydrogen-watergenerating devices:

1)    provides at least 0.5mg per liter serving regardless of source water composition being used in thedevice (e.g. RO water or mineral water with a pH range of 5.8 to 8.6)

2)    passes safety test fortoxins/heavy metals

3)    produces the minimumconcentration of 0.5 mg/L:

a.     for the duration of themanufacture warranty

b.    or for at least 1 yearif not stated (Maybe this should be given in “processing hours” not time.

4)    pH must be in range 5to 9.5 regardless of source water composition (e.g. RO water or mineral waterwith a pH range of 5.8 to 8.6)

5)    no false or damagingmarketing claims that could harm the credibility of the hydrogen research andindustry

—additional products that need IHSA standards

In these cases, IHSAshould, in principle, follow the standard of hydrogen water.

·      Hydrogen inhalationunits

·      Hydrogen cosmetics

·      Hydrogen IV

·      Hydrogen bath

·      Hydrogen shower

·      Hydrogen watergenerating additives (e.g. tablets)

·      Oral hydrogengenerating additives (e.g. pills)

·      Magnesium sticks

Examples

Aproduct can meet the standard of 0.5 mg per liter in many ways. For example,each product simply needs to provide a 0.5 mg dose by ingesting a maximum of 1L of said product. Any volume less than 0.5 L would require a minimumconcentration of 0.5 mg/L by the following reasons.

A250-mL can at 0.5 ppm would only provide 0.125 mg of H2 per can.However, by ingesting one liter (1 L) of the product (i.e. four cans), thetotal provided dose of H2 would reach 0.5 mg. Thus, the manufactureshould recommend drinking to 4 servings per day on the label. Similarly, a500-mL serving at a concentration of 0.5 ppm would only provide 0.25 mg of H2per serving. Ingesting 1 L of the product would provide the required 0.5 mg ofH2, and the manufacture would recommend at least two servings perday. Additionally, if a product provides a concentration of 0.8 ppm with avolume of 750 mL, the manufacture still needs to recommend drinking 1 L per day(e.g. 1.34 servings).

Alternatively,if a 250-mL package had a concentration of 2 ppm, then each serving wouldprovide the required 0.5 mg of H2, and only one can would need to berecommended. Similarly, a 500-mL serving at a concentration of 1 ppm, wouldrequire the customer to ingest 1 serving per day.

Lastly,products or hydrogen water devices whose concentration is less than 0.5 ppm,and thus cannot provide a dose of 0.5 mg of H2 per liter of product,cannot be certified.

Considerations:

WithH2 generating devices, perhaps we should also consider how long ittakes to generate 0.5 ppm. Some devices may be able to do it, but it may take over1 hour for a 250-mL portable device to reach 0.5 ppm, which would require 4hours to provide 0.5 mg.  Although, themanufacture would have to state how long it takes, perhaps it is better to onlycertify products that can make a total of 1 L of water at 0.5 ppm in less than20 min or something.  What your thoughts?

References

Fujita, K., Seike,T., Yutsudo, N., Ohno, M., Yamada, H., Yamaguchi, H., Sakumi, K., Yamakawa, Y.,Kido, M.A., Takaki, A. and Katafuchi, T., 2009. Hydrogen in drinking water reducesdopaminergic neuronal loss in the 1-methyl-4-phenyl-1, 2, 3,6-tetrahydropyridine mouse model of Parkinson's disease. PloS one, 4(9), p.e7247.

Ito, M., Ibi, T.,Sahashi, K., Ichihara, M., Ito, M. and Ohno, K., 2011. Open-label trial andrandomized, double-blind, placebo-controlled, crossover trial ofhydrogen-enriched water for mitochondrial and inflammatory myopathies. Medical gas research, 1(1), p.24.

Song, G., Li, M.,Sang, H., Zhang, L., Li, X., Yao, S., Yu, Y., Zong, C., Xue, Y. and Qin, S.,2013. Hydrogen-rich water decreases serum LDL-cholesterol levels and improvesHDL function in patients with potential metabolic syndrome. Journal of lipid research, 54(7), pp.1884-1893.

Implementations

There are many thingsto consider about the actual implementation of the IHSA standards. perhaps weshould be careful to not deviate to far from our field of expertise ofmolecular hydrogen. There are many issues that can arise that we will need todecide if it gets IHSA approval:

·     H2-infusedbeverages with stimulants (what volume of water)

·     H2-infusedbeverages with medically-active ingredients (what volume of water)

·     H2-infusedbeverages with legal ingredients in some areas, but illegal in others (e.g.marijuana). –may have legal repercussions for even testing it.

·     H2-generatingadditives that are not clearly toxic, but may not be legal (e.g. borohydride,magnesium, magnesium hydride, aluminum, etc.).

·     Variousforms of cosmetics, etc.

Also, establishingthe consistency/longevity of the product

·     Electrodedegradation and leaching of heavy metals

o  Maybefine with mild use, but harmful with heavy use

·     IfPEM/SPE devices get dry they many not perform adequately

·     Whatpercentage of machines need to be tested in order to provide certificate?