Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No. 7 • November 2012


APPETIZERS

He that falls in love with himself will have no rivals.
— Benjamin Franklin, 1758

Torture numbers, and they will confess to anything.
— Gregg Easterbrook

All men with power ought to be mistrusted.
— — James Madison (1751-1836)

Givers have to set limits because takers rarely do.
— Irma Kurtz

While there is no reason to panic, it is only prudent to make preparations to panic.
— cartoon caption by Robert Mankoff

The reason it takes a million sperm to find an egg is that none of them will stop to ask for directions.
— Adam Ferrara

I should have loved freedom, I believe, at all times, but in the time in which we live I am ready to worship it.
— A. de Tocqueville (quoted in
F. A. Hayek, The Road to Serfdom)

Today’s literature: prescriptions written by patients.
— Karl Kraus, Viennese dramatist,
critic, and satirist, b. 1874

Hydrogen Therapy

Here we continue our series on the emerging new field of medical therapy with hydrogen, where researchers have published studies (mostly so far in cell cultures and animal models of human disease) using hydrogen gas administered by breathing hydrogen or drinking hydrogen dissolved in water or saline solution. Excitingly, hydrogen gas is available as endogenous hydrogen gas produced by gut microbes living in your lower digestive tract and the consumption of select prebiotics can enhance this production. Hydrogen is known to be a very selective antioxidant that scavenges the highly toxic hydroxyl radical and also the potent oxidant peroxynitrite (created in the body by the chemical reaction of nitric oxide and superoxide radical). Hydrogen diffuses to reach all tissues, even including mitochondria, and it passes the blood-brain barrier. See our article “Hydrogen Therapy” for an introduction to this exciting new biomedical science, where the medicine (the hydrogen) can be conveniently produced by your own resident gut microbiota [see “Hydrogen Therapy” in the June issue of Life Enhancement]. NO prescription required!

Safety of Hydrogen Inhalation in Human Study

A new study1 focuses on safety issues in relation to the use of hydrogen therapy. As the authors explain. [i]n animal experiments, use of molecular hydrogen (H2) has been regarded as quite safe and effective, showing benefits in multiple pathological conditions such as ischemia-reperfusion injury of the brain, heart, kidney and transplanted tissues, traumatic and surgical injury of the brain and spinal cord, inflammation of intestine and lung, degenerative striatonigral tissue and also in many other situations. However, since cerebral ischemia patients are in old age group, the safety information needs to be confirmed.”1 The delivery of hydrogen by inhalation via a facemask was the focus of the safety test, with three patients as the subjects studied for the hydrogen concentration (HC) in arterial and venous blood before, during, after 4% (case 1) and 3% (case 2, 3) of hydrogen gas inhalation with simultaneous monitoring of physiological parameters. For a consistency study, HC in the venous blood of 10 other acute ischemic cerebral disease patients were obtained at the end of 30-minute hydrogen inhalation treatment.

What they found was that “the HC gradually reached a plateau level in 20 min after H2 inhalation in the blood, which was equivalent to the level reported by animal experiments. The HC rapidly decreased to 10% of the plateau level in about 6 min and 18 min in arterial and venous blood, respectively, after H2 inhalation was discontinued. Physiological parameters on these 3 patients were essentially unchanged by use of hydrogen.”

The only difficulties were in the consistency study. Consistency is important because of the need to achieve the same level of HC with each treatment. In this study, the researchers found considerable variability in HC in the 10 subjects studied and that this was due to the facial mask inhalation. “In unattended patients particularly with neurologically compromised condition, the facial mask was frequently not in the appropriate position when our staff returned to stop the inhalation at the end of 30-min treatment.” “Use of respiratory assistance and even a body position may have to be considered for the consistency of inhalation treatment.” There were other comments. However, these difficulties pertained to the administration of hydrogen by inhalation through a facemask. For those using prebiotics for enhancing endogenous hydrogen production by resident microbes, these issues are not relevant.

The important findings here were that there were “no significant change in the physiological parameters during and after H2 administration … except in some indices associated mainly with hyperventilation or breath holding.”1 (The latter were problems associated with the face mask.) As the author note, the number of subjects was small; hence, a larger study specifically for safety issues would be informative, especially if it could dissociate the safety of increased hydrogen from side issues such as face masks.

The most important data from our point of view was the kinetics—how fast the hydrogen concentration increased after administration began, how long it took to reach a steady state plateau, and how quickly it left both the arterial and venous blood.

The way that hydrogen reacts with hydroxyl radicals and the powerful promiscuous oxidant peroxynitrite is the same in mice and men. Because humans are far larger than mice, the blood and tissue hydrogen concentrations will change over time in a very different manner. This paper provides us with this very important data.

Hydrogen levels drop quickly after administration ceases. We believe that outside of a hospital, the best way to obtain benefits of hydrogen is from continuous 24/7/365 administration via colonic hydrogen producing bacteria. The use of carefully selected prebiotics can help assure a comfortable and beneficial rate of continous hydrogen production.

Reference

1. Ono H et al. A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level. Med Gas Res 2(1):2 (2012).

Researchers Report Hydrogen Protects Mice from Radiation-induced Thymic Lymphoma

A recent study1B on hydrogen as a possible radioprotectant in experiments with BALB/c mice begins by explaining that “… studies of mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that multi-steps and many factors, like Ras, PTEN, and Fas, were involved in radiation-induced carcinogenesis.” Earlier work by the authors of paper#1B also identified ERK1/2, STAT3 and SHP-2 as other factors involved in radiation-induced thymic lymphoma formation in BALB/c mice.

As the authors note, hydroxyl radicals are the main mediators of radiation injury and are able to react indiscriminately with nucleic acids, lipids, and proteins resulting in damage that can include DNA fragmentation, lipid peroxidation, and protein inactivation. In their earlier work, they showed experimentally that hydrogen treatment could protect cultured cells and mice from radiation damage using a single high dose model. “Importantly, these previous studies also showed that H2-rich saline/water is safe, easy to administer, and cost-effective.”

The experimental animals (but not the controls) were subject to whole body radiation to induce the development of lymphomas. The experimental group was given hydrogen-enriched saline by intraperitoneal injection five minutes prior to each dose of radiation. The control group received saline containing either hydrogen or no hydrogen via the same route as the irradiated mice. Results showed that the hydrogen significantly increased the survival rate of the mice 30 weeks after the radiation. Moreover, the radiation-induced thymic lymphoma rate in the hydrogen group was significantly lower than in the irradiated group that did not receive hydrogen and hydrogen also increased the latency period (the time to develop lymphoma) in the hydrogen-treated animals that developed lymphoma as compared to the irradiated group that didn’t receive hydrogen treatment.

The researchers evaluated the levels of intracellular ROS (reactive oxygen species) in peripheral blood mononuclear cells (PBMC) from the irradiated and control (nonirradiated) mice. ROS levels were much lower in the irradiated group that received hydrogen than in the irradiated control group. Extracellular serum ROS showed similar results. The levels of antioxidant enzymes SOD (superoxide dismutase) and GSH (glutathione) were at 4 hours after the last radiation treatment in the hydrogen treated group significantly higher than that of the control group, while MDA (malondialdehyde, a lipid peroxidation product) concentrations were significantly lower in the hydrogen group as compared to the controls.

Hence, as shown in this study,1B hydrogen therapy may reduce radiation-induced carcinogenesis.

Reference

1B. Zhao et al. Hydrogen protects mice from radiation induced thymic lymphoma in BALB/c mice. Int J Biol Sci 7(3):297-300 (2011).

Very Large Prospective Study Reports Protection Against Diverse Causes of Death by Dietary Fiber: Possible Role of Hydrogen Unmentioned

A huge prospective study of fiber intake and cause-specific mortality2 has reported impressive protection by dietary fiber in both men and women against total mortality and circulatory, digestive, respiratory, and inflammatory diseases (non-cardiovascular disease and noncancer types).

The study included 452,717 men and women from 23 centers in 10 countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom). Average age at recruitment was 50.8 ± 9.8 years, with women accounting for 71% of participants. Excluded were people who had cancer at baseline, or who reported a history of heart attack, angina, stroke, or diabetes. The dietary fiber was estimated largely by self-administered questionnaires.

Results showed that higher total dietary fiber intakes were associated with lower mortality. Those who ingested 28.5 g/day or more of fiber (the highest quintile) had a 24% lower mortality than those who ingested less than 16.4 g/day, with inverse associations between dietary fiber and mortality from smoking-related cancers, and circulatory, respiratory, digestive, and non-cardiovascular disease noncancer inflammatory diseases. The beneficial effects were derived mostly from cereal and vegetable fiber, with no effects from fruit fiber shown in men but an inverse relationship with mortality for respiratory diseases and non-cardiovascular/ noncancer inflammatory diseases in women consuming higher amounts of fruit fiber.

The models for analyzing the results were corrected for education, smoking status, alcohol consumption, BMI (body mass index), physical activity, total caloric intake, and ever use of menopausal hormone therapy in women.

Dietary fiber was found to reduce endotoxin concentration. Endotoxin (lipopolysaccharide) is released by bacteria and activates the immune system. Higher endotoxin levels in the circulation are generally associated with higher levels of inflammatory markers such as C-reactive protein, IL-6, and tumor necrosis factor-alpha. As the authors note (and we have reported in earlier newsletters), changes in gut microbiota as a result of a high fat meal may increase gut permeability, thereby increasing the endotoxin levels in the general circulation.

The authors briefly discussed the possible causes of the health benefits of dietary fiber. They mention SCFA (short chain fatty acids), produced by gut microbiota that consume dietary fiber (undigested carbohydrates that reach the lower digestive tract), as modulators of immunity. They also suggest that the reduction of systemic inflammation (via the decrease by dietary fiber of plasma endotoxin levels) may play a role. However, not mentioned was the release of hydrogen by gut bacteria that consume dietary fiber and the ability of hydrogen as a selective antioxidant (scavenging hydroxyl radicals and the oxidant peroxynitrite) to reduce inflammation and oxidative stress. In the case of those consuming large amounts of dietary fiber, considerable amounts of hydrogen could be produced and diffuse throughout the body, with most of it eventually being excreted via exhalation through the lungs.

There appears to be very little awareness at present of hydrogen as a likely source of at least a part of the health benefits derived from a diet high in dietary fiber, but the discovery of the major impact of the gut microbiota on health has attracted considerable interest. It cannot be long before the relationship between the gut bacteria and the hydrogen they produce from dietary fiber becomes a very hot research subject.

We couldn’t agree more with the author of the accompanying commentary piece3 on the dietary fiber study described above, when he titled his article, “Dietary fiber and mortality: convincing observations that call for mechanistic investigations.”

Finally, we note that it is not possible from the data2 to identify the numerous types of dietary fiber people get in a fiber-rich diet and to correlate those with the health benefits reported here. For example, different types of fiber consumed by the gut microbiota release different amounts of hydrogen and at a different rate. For more on this subject, see our article on “Hydrogen Therapy” in the June issue of Life Enhancement.

References

2. Chuang et al. Fiber intake and total and cause-specific mortality in the European Prospective Investigation into Cancer and Nutrition cohort. Am J Clin Nutr 96:164-74 (2012).
3. Landberg. Dietary fiber and mortality: convincing observations that call for mechanistic investigations. Am J Clin Nutr 96:3-4 (2012).

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