Hydrogen Sulfide: What a Gas For Body and Mind

Juvenon Health Journal 2011 volume 10 number 10

By Benjamin V. Treadwell, Ph.D.

Hydrogen Sulfide: What a Gas For Body and MindBlood gases have long been the subjects of scientific study. They act as messengers to help regulate biological pathways. Take nitric oxide (NO), for example. In 1998, the Nobel Prize was awarded to Louis Ignarro et al. for their work on NO’s importance to the brain, other organs and tissues, and the cardiovascular system.

Another gas, carbon monoxide (CO), is more than the toxic byproduct of fuel combustion in an automobile engine. Studies have shown it is also produced by our cells and may have positive biological pathway effects, similar to NO. In fact, research indicates NO, CO and a third gas, hydrogen sulfide (H2S), may have important functions in modulating brain activity related to memory and cognition.

Recent studies involving hydrogen sulfide have also produced exciting results connecting H2S and the metabolism of glucose, the primary source of energy for the brain. It seems, along with a potential role in improving memory formation and retention (See Juvenon Health Journal Volume 10, Number 6, “The Aging Brain: Why We Forget And What Might Help.”) H2S and its precursors, cysteine (LC) and N-acetylcysteine (NAC), may help prevent metabolic syndrome and type 2 diabetes.

What makes scientists think so? Read on.

Bad Smell, Good Gas
Researchers have recently demonstrated the presence of significant amounts of sulfur-containing hydrogen sulfide (H2S) in our tissues (10-160 uM in blood and brain). Where does this potentially beneficial substance come from?

Most of the H2S generated in our cells is from other sulfur-containing substances our body makes, such as the amino acid, cysteine. The cells of our tissues, including those of vital organs, like the liver, brain, heart and blood vessels, are capable of converting cysteine into H2S.

Running Low on H2S
Are low levels of cyseine (LC) and H2S a causative factor of impaired glucose metabolism?
Low levels of this metabolite and cysteine were reported in blood samples drawn from individuals that have blood sugar concerns in a recent clinical trial. This decrease correlated with an increase in markers of oxidative stress (inflammatory substances). Surprisingly, a subsequent study showed supplementing with cysteine produced a decrease in markers of oxidative stress in these individuals.

As a follow-up, researchers initiated another study to better understand these observed health benefits, specifically with respect to glucose metabolism. They hoped to determine the mechanism of action of cysteine and its putative metabolite, H2S.

Glucose Uptake Gridlock
The investigators set out to confirm whether low levels of cysteine and H2S were related to normal glucose metabolism. The experimental model they chose was the fat cell, the adipocyte, in vitro.

Fat tissue and these constituent cells play a key role in the body for the uptake of blood glucose and storage of its metabolites (lipids). In Individuals with blood sugar concerns, the insulin-directed metabolic pathways of glucose metabolism don’t function as well as they should. To test the capacity of cysteine or H2S to improve glucose metabolism, the cells were first put under stress by adding excess glucose to the culture.

Cells normally respond to high glucose levels by producing metabolic markers common to diabetes, which interfere with glucose transport through the cell membrane. As expected, the machinery for glucose uptake in the experimental adipocytes was suboptimal. Specifically, the glucose transporter molecule, GLUT4, responsible for carrying glucose from the blood (in this case, the cell culture medium) into the cell was inactive.

Activating Glucose Transport
The investigators repeated the experiment, adding either H2S or cysteine to the glucose-saturated growing cells. Remarkably, both sulfur compounds had the effect of activating the numerous regulators of glucose metabolism, culminating in triggering GLUT4 and the subsequent transport of glucose across the membrane into the cell.

The researchers speculate the reason for this positive outcome may be due to the antioxidant properties of both H2S and cysteine. (Studies have also demonstrated that the other precursor of H2S, N-acetylcysteine (NAC), promotes the synthesis of a key cellular antioxidant, glutathinone. It, too, could help neutralize the oxidants produced by cells exposed to high glucose.)

It appears, however, that the major effect of cysteine is actually due to the hydrogen sulfide gas (H2S) produced from it by specific enzymes. Exactly how this gas activates the insulin-directed pathway and improves insulin sensitivity is currently under investigation.

Supplementing with Cysteine
The study (mentioned earlier) that identified lower levels of H2S and cysteine in people with blood sugar concerns is revealing. It also seems to support the conclusion that adequate H2S/cysteine plays an important role in improving glucose metabolism and human health.

The major effect of cysteine is due to the hydrogen sulfide gas produced from it
Is supplementing with cysteine the answer? The experiments on cells in culture suggest it could be. Human research, in vivo, is ongoing and early studies have been encouraging. Treating people with supplemental cysteine lowered markers of oxidative stress, and improved insulin sensitivity and glucose metabolism.

Some foods, such as whey protein and garlic, contain high levels of cysteine. Red blood cells, according to recent experiments, have the capacity to convert the sulfur compounds contained in garlic to hydrogen sulfide.

Don’t like the taste of garlic (or the disagreeable odor associated with eating it)? Supplements containing cysteine, such as N-acetylcysteine (NAC), are another option to help maintain beneficial levels of the amino acid and the H2S it generates. NAC is also rapidly metabolized to glutathione. Glutathione, as mentioned earlier, acts as a powerful antioxidant in the body. It protects and energizes brain (supporting memory and cognition) as well as other tissue.

Ask Ben Dr. Treadwell
answers your questions.

question:  I was wondering whether there are any nutritional supplements one could take to maintain a healthy cardiovascular system, especially with regard to healthy blood pressure? — A

answer: Research suggests the nutrients ubiquinol (the more absorbable form of Coenzyme Q10) and N-acetylcysteine (NAC) may support cardiovascular health and, consequently, healthier blood pressure. Based on recent studies, the compound pterostilbene may also promote healthier cholesterol levels, help regulate blood pressure and combat atherosclerosis.

Coenzyme Q10 (CoQ10) acts as an antioxidant, protecting the heart muscle and supporting the high-energy requirements of heart-cell mitochondria. Although the body produces CoQ10, levels decline as we age. According to studies, supplementing with CoQ10 is effective for boosting CoQ10 levels.

N-acetylcysteine (NAC) is an amino acid that helps promote normal homocysteine levels in the blood. Maintaining normal levels of homocysteine is also important for maintaining heart health. NAC may also help support immune response, as well as help produce Glutathione (GSH), one of the most important antioxidants in the body.

Wild blueberries are a good source of pterostilbene. In addition to positive effects on cholesterol, blood pressure and arterial health, this polyphenol-rich fruit also has antioxidant and general anti-inflammatory properties.

Along with these nutrients, I’d recommend incorporating a program of regular exercise, as well as a healthy diet, low in processed sugars. Of course, it is always a good idea to consult with your health professional to be on the safe side.

Dr. Benjamin V. Treadwell is a former Harvard Medical School.

Research Update

Investigators from the Louisiana State University Health Sciences Center undertook a study to examine the potential relationship between blood levels of L-cysteine and its metabolite, hydrogen sulfide, and its effects on glucose metabolism. They published their results and conclusions in a recent issue of The Journal of Biological Chemistry.The title of their report is a paragraph in itself: “Hydrogen Sulfide and L-Cysteine increase Phosphatidylinositol 3,4,5-Trisphosphate (PIP3) and Glucose Utilization by Inhibiting Phosphatase and Tensin Homolog (PTEN) Protein and Activating Phosphoinositide 3-Kinase (PI3K)/Serine/Threonine Protein Kinase (AKT)/Protein Kinase Cζ/λ (PKCζ/λ) in 3T3l1 Adipocytes.”The team was aware that previous research had reported that individuals with blood sugar concerns tend to have low blood levels of the amino acid, L-cysteine (LC) and the hydrogen sulfide (H2S) gas produced from it. They hypothesized that reduced levels of these two sulfur-containing compounds actually caused sub-optimal glucose metabolism common to this diabetic condition.To test this new hypothesis, the authors chose fat cells, adipocytes, as their model. These cells are the body’s primary form of energy storage, providing a buffer against imbalances. Adipose tissue (composed of adipocytes) is also crucial in regulating how your body utilizes glucose. Certain individuals have trouble taking up glucose from the blood and metabolizing it in the body.

Briefly, there were two parts to the in vitro experiment. First, researchers established a baseline by incubating adipocytes in the presence of high glucose and examining the effect on the insulin-regulated glucose metabolic pathways. As expected, the high glucose-exposed cells produced elevated levels of oxidants and inflammatory components. Consequently, the capacity to transport glucose into the fat cells for metabolism was dramatically impacted.

The second part of the experiment involved repeating the incubation, but this time adding either H2S or its precursor, LC. The results? A decrease in markers of oxidative stress and inflammation, and an increase in the presence of the biological molecules necessary for transport of glucose across the cell membrane. In other words, this study provides evidence by which supplementing H2S or LC can up-regulate the insulin-signaling pathways.

The authors believe their work suggests the positive effect on glucose transport and metabolism is most likely due to the capacity of H2S to function as an antioxidant, neutralizing the stress of high-glucose exposure. They also mention the possibility that H2S /cysteine stimulates the production of the powerful endogenous antioxidant, glutathione. They note there may be similar benefits from consuming foods high in cysteine content, such as whey protein and garlic.

Read abstract here.
This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.