Friday, October 21, 2016

Hydrogen-Rich (H+) Water Helps Athletes Perform, Improves Our Health & Prolongs Our Lives, Really? - True or False

Is H+ rich water more effective than other 'snake oil versions' of water?
Recently, Raymond asked on the SuppVersity Facebook page whether I could "please do something on the subject of hydrogen supplementation via water or gas" - and that's what I plan to do today.

As Raymond rightly points out, the use of H+ water "seems to be a big deal in longevity circles, and perhaps it holds promise for 'our crowd' as well". The obvious question is: rightly so? Or, more specifically, is there credible evidence that H+ water has ergogenic and health-promoting effects in gymrats, athletes, and Mr. & Mrs. Average Joe.
If you want to make your water "ergogenic", use it to boil a fresh coffee ;-)

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Unfortunately, the best evidence in favor or H+ therapy comes from rodents, where hydrogen gas of less than 4 % was given by inhalation. If we follow Ichihara, et al. and summarize the results of pertinent studies, we would find a broad range of pathologies that includes 31 disease categories and 166 disease models, including human diseases, as well as treatment-associated pathologies with a predominance of oxidative stress-mediated diseases and inflammatory diseases.
Table 1: Overview of Clinical trials published as of June 2015 (from Ichihara, et al. 2015).
So, yes there's evidence that H+ treatments (specifically in gaseous form) can have health benefits - at least in common models of human disease. Evidence that guzzling expensive H+ water will have immediate or chronic performance enhancing effects are yet as scarce as RCTs that would confirm the practical relevance of the results of in vitro and animal studies in healthy or sick human beings.
In humans and with respect to the significantly more popular consumption of H+ water, however, we have almost only pilot studies like the one by Aoki et al. (2012):
  • Anti-fatigue effects in soccer players (Aoki, et al. 2012) --  In the study from the University of Tsukuba, each of the 10 soccer players who participated in the study was examined twice in a crossover double-blind manner; they were given either 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.
    Figure 1: Unimpressive - 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 (*p < 0.05 vs. time 0. #p 0.05 vs HW, N = 10 | Aoki. 2012).
    An analysis of the data shows that the oral intake of HW prevented an elevation of blood lactate during heavy exercise. That alone is not enough to impress anyone, but since HW also ameliorated the early peak torque decline during maximal isokinetic knee extension. On the other hand, significant changes in blood oxidative injury markers, such as d-ROMs and BAP, or creatine kinase after exercise were not observed.
Even though the lactate reduction is not half as relevant as the "lactate hypothesis of fatigue" would suggest (Taylor. 2016), it is still interesting to see that H+ has opposite effects to bicarbonate, which has been shown to allow for significant increases in lactate production by buffering the conversion of this alternative brain and muscle fuel to performance impairing lactic acid.
Don't confuse H+ water with deep sea water (DSW): If you want to learn more about the latter, I suggest you read the most recent review from Malaysia (Nani, et al. 2016) | download for free
Whether that's also why H+ has been found to inhibit the growth of colon cancer cells in vitro and if the results of Runtuwene, et al. have any real-world relevance, requires further research.
Figure 2: Schematic summary of molecular mechanisms of hydrogen (Ichihara. 2015).
Potential physiological mechanisms that could explain the anti-cancer effect, as they are illustrated graphically in Figure 2 from Ichihara, et al. (2015), have been identified years ago. The "master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated" (Ichihara. 2015), and as of now, it has not been identified.
Don't waste your money on oxygen-enriched (O-) water either! In the conclusion to his paper in the British Journal of Medicine a researcher from the Duke University rightly points out "oxygenated water fails both quantitative analysis and practical physiological tests of exercise performance and recovery". That's also because "[o]nly miniscule quantities of O2 can be dissolved in drinking water compared with that required for exercise, and significant intestinal absorption of O2 is unsubstantiated." In the absence of counter-evidence it is thus only logical for him to conclude that "[e]rgogenic claims for oxygenated water therefore cannot be taken seriously" (Piantadosi. 2006).
And yet, in view of the fact that a reduction in oxidative stress and inflammation appears to be an essential downstream effect of the effects of H+ on one or several unknown "master regulators", it can hardly surprise us that there are studies to suggest...
  • Figure 3: Plasma glucose and insulin concentrations in response to a 75-g OGTT before (○) and after (●) consumption of hydrogen-rich pure water for 8 weeks in 6 patients with IGT (Kajiyama. 2008).
    improvements in glucose management in type II diabetics (Kajiyama. 2008); the test water of which the subjects consumed 900ml/day for 8 weeks was produced by dissolving hydrogen gas directly into the pure water, yielding hydrogen-rich pure water with the following physical properties: pH 6.7 ± 0.1, low electric conductivity (0.9 ± 0.2 μS/cm), high dissolved hydrogen (1.2 ± 0.1 mg/L), low dissolved oxygen (0.8 ± 0.2 mg/L), and an extremely negative redox potential (−600 ± 20 mV)
  • increased antioxidant defenses & improved lipids in subjects with metabolic syndrome (Nakao. 2012; Song. 2013); 1.5–2 L/day and 0.8-1 L/day administered for 8 weeks and 10 weeks in Nakao et al. and Song et al., respectively 
  • improved oxidative status and quality of life in patients treated with radiotherapy for liver tumors (Kang. 2011); in the study hydrogen-rich water was produced by placing a metallic magnesium stick into drinking water (final hydrogen concentration; 0.55~0.65 mM)
Whether and to which extent this is related to or corollary with the increase in pH Ostojic and Stojanovic (2014) observed in exercised subjects in response to 14 days on 2l of hydrogen-rich water per day. In said study, the subjects', "52 presumably healthy physically active male volunteers" (Ostojic. 2014),
"[...i]ntake of HRW significantly increased fasting arterial blood pH by 0.04 (95% confidence interval; 0.01 - 0.08; p < 0.001), and postexercise pH by 0.07 (95% confidence interval; 0.01 - 0.10; p = 0.03) after 14 days of intervention. [In addition, f]asting bicarbonates were significantly higher in the HRW trial after the administration regimen as compared with the preadministration (30.5 ± 1.9 mEq/L vs. 28.3 ± 2.3 mEq/L; p < 0.0001)" (Ostojic. 2014).
If that was the mechanism, though, you'd yet be better off with bicarbonate supplementation which will lead to much more significant improvements in pre- and post-exercise pH. And as if the lack of an understanding of the mechanism was not yet enough, the fact that many have been conducted in thoroughbred horses is likewise not exactly adding to the persuasiveness of the few studies that focus on the purported ergogenic effects of H+ (Tsubone. 2013).
As scarce as the evidence of health benefits (Ohta. 2014) of H+ may be, it is much more convincing than the quasi-non-existent evidence for relevant ergogenic effects. 
So what? The evidence for health benefits of H+ water consumption or H+ inhalation, as scarce as it may be, is, almost extensive compared to the number of studies that investigated the often-advertised performance enhancing effects of H+ water - performance enhancing effect of which the only reliable human RCT shows that they are at best statistically, but hardly practically relevant.

Based on the currently available evidence, H+ water consumption / H+ gas inhalation can thus hardly be recommended  as an ergogenic practice in gymrats and/or pro-athletes | Comment on Facebook!
  • Aoki, Kosuke, et al. "Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes." Medical gas research 2.1 (2012): 1.
  • Ichihara, Masatoshi, et al. "Beneficial biological effects and the underlying mechanisms of molecular hydrogen-comprehensive review of 321 original articles." Medical gas research 5.1 (2015): 1.
  • Kajiyama, Sizuo, et al. "Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance." Nutrition Research 28.3 (2008): 137-143.
  • Kang, Ki-Mun, et al. "Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors." Medical gas research 1.1 (2011): 1.
  • Nani, Samihah Zura Mohd, et al. "Deep Sea Water: Beneficial Resource for Health." Evidence-Based Complementary and Alternative Medicine (2016).
  • Ohta, Shigeo. "Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine." Pharmacology & therapeutics 144.1 (2014): 1-11.
  • Ostojic, Sergej M., and Marko D. Stojanovic. "Hydrogen-rich water affected blood alkalinity in physically active men." Research in Sports Medicine 22.1 (2014): 49-60.
  • Nakao, Atsunori, et al. "Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study." Journal of clinical biochemistry and nutrition 46.2 (2010): 140-149.
  • Piantadosi, Claude A. "“Oxygenated” water and athletic performance." British journal of sports medicine 40.9 (2006): 740-741.
  • Runtuwene, Joshua, et al. "Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer." PeerJ 3 (2015): e859.
  • Song, Guohua, et al. "Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome." Journal of lipid research 54.7 (2013): 1884-1893.
  • Taylor, Janet L., et al. "Neural Contributions to Muscle Fatigue: From the Brain to the Muscle and Back Again." Medicine and science in sports and exercise (2016).
  • Tsubone, Hirokazu, et al. "Effect of treadmill exercise and hydrogen-rich water intake on serum oxidative and anti-oxidative metabolites in serum of thoroughbred horses." Journal of equine science 24.1 (2013): 1.