The ‘toxic gas’ that can boost your brain and heart health while putting the zing back into your love life

Men, what if the key to saving your brain, and your sex life, was simply eating more garlic?

As far back as ancient Egypt, garlic has been praised for its health-supporting abilities, from preventing colds to aiding digestion. In more recent times, it’s been associated with reducing erectile dysfunction, preventing heart disease, and improving memory. It’s reported to have antiviral, antifungal and antimicrobial properties. It was even used as an antibiotic during both World Wars.1 The reason garlic and other foods have these effects, however, has eluded researchers for many years.

Recent studies have found that behind garlic’s therapeutic benefits are sulphur-containing compounds and their ability to create hydrogen sulphide (H2S), long considered a toxic gas with only damaging effects on the body. For over 300 years, H2S was viewed as highly detrimental to living creatures for many reasons. For example, according to planetary scientists, approximately 251 million years ago (during the ‘Permian Triassic’ period of Earth’s history) high concentrations of H2S were responsible for the mass extinctions that occurred when large amounts of this gas were generated by the oceans.2

But it now appears that the degree to which H2S is harmful or helpful depends on its concentration.

Research reveals the real truth behind H2S

Hydrogen sulphide is the specific sulphur compound behind many health benefits. It’s now known to be an important and beneficial chemical-signalling molecule in our bodies.3 It’s the compound behind the strong odour of eggs, natural gas, garlic, and other organosulphur-containing foods. It’s known as a ‘gaso-transmitter’ because it moves freely like a gas through cell membranes to regulate cellular function while under the control of enzymes. Carbon monoxoide (CO) and nitric oxide (NO) are the other two compounds in the body that function similarly.

In the body, the enzymes cystathionine beta-synthase (CBS) and cystathionine gammalyase (CSE) form H2S from the sulphur-containing amino acids, L-cysteine and L-methionine. Of these, the enzyme CSE is considered to be the most important.4 Once formed, H2S circulates in the body through the bloodstream.

Cysteine and methionine are important amino acids in the synthesis of proteins, as well as in their overall structure and function. S-adenosyl methionine (SAMe) is made from (metabolised from) methionine and is an activator of the enzyme, CBS.5 However, in order to make methionine the body needs enough vitamin B12 (methylcobalamin), folate, riboflavin and pyridoxine. If there is a deficiency in any of these vitamins it leads to elevated homocysteine, a cardiovascular risk factor. Niacin, thiamine and pantothenic acid are also needed in methionine metabolism, making this a very B-vitamin intensive metabolic pathway.6

Understanding the role of H2S in the body and how it works has led to an abundance of research into ways to treat conditions in which it is low or abnormal, such as erectile dysfunction, heart failure, peripheral artery disease, inflammatory bowel disease, Alzheimer’s disease, diabetes and hypertension. Impaired sulphur detoxification pathways have even been hypothesised to play a role in the development of autism.7

Its role in protecting neurons and heart muscle from oxidative damage, regulation of the release of insulin, and its impact on longevity are just starting to be understood.8

In one recent study, researchers found that the more garlic a person ate, the lower their risk of cardiovascular disease.9 Red blood cells were collected from volunteers and then exposed to juice extracted from raw garlic. When the samples were checked for levels of dissolved H2S, researchers were able to verify garlic’s effects were related to the breakdown of allicin (diallyl thiosulphate) and other ‘polysulphides’ naturally occurring in garlic to H2S in red blood cells. The researchers determined that the amount of H2S produced affected the degree of vasodilation or relaxation of the blood vessels. (This process also involves support from glutathione and glucose present in cells.)

Better blood vessel dilation equals better erections

Erectile dysfunction (ED) is generally considered to be a vascular problem closely associated with cardiovascular disease and diabetes. The conventional approach usually involves treatment with patent medications which keep blood vessels dilated longer by inhibiting an enzyme technically termed phosphodiesterase type 5 (PDE5). PDE5-inhibitors include the patent medicines sildenafil (Viagra®) and tadalafil (Cialis®). (Icariin, a natural component of horny goat weed, is also a PDE5 inhibitor, although much weaker than the patent medicines.) While these do work for many men, they can become less effective over time, and for many others they don’t work at all.

Researchers looking for an additional approach have suggested that H2S might be useful in the treatment of erectile dysfunction. In both animal and human in-vitro studies, H2S has been shown to support erections.10 No one knows yet how it works exactly, but it has also been observed to increase blood vessel dilation and relaxation. [Although no one yet has published exactly how it does this, it appears to open up the potassium-adenosine triphosphate (K+-ATP) channels in the muscle of blood vessels.]

Others have studied the effects of H2S using electrical field stimulation of human corpus carvernosum, or erectile, tissue. For proper erectile function, balance needs to be maintained between blood vessel constriction and relaxation. Researchers have demonstrated that H2S is important in the processes leading to adequate blood pressure within erectile tissue.11,12,13 In fact, the CBS and CSE enzymes that form hydrogen sulphide are found on the very muscles involved in creating penile erections.

Other animal research studies have looked at the impact of H2S on erectile tissue and its concentration-related pro-erectile relaxing effects. One animal research study involved injecting sodium hydrogen sulphide into the corpus cavernosum of primates and showed that this could increase both cavernous pressure and penile length.14,15

It appears that H2S is an important component of erectile function in humans and that therapies based upon it show promise in the treatment of erectile dysfunction.16,17

The testosterone and H2S link

Testosterone appears to be an influence on how much H2S is produced. Some researchers write that testosterone may do this by promoting the conversion of the amino acid, L-cysteine, to H2S. This, in turn, activates ‘potassium channels’ in smooth muscle, resulting in testosterone-induced blood vessel dilation. It may also explain at least some of the mechanism behind testosterone’s cardiovascular benefits.18

Improve female sexual response naturally

While most studies of the effects of H2S have been conducted in males, at least one group of researchers investigated its possible role in smooth muscle relaxation in females. They found that H2S may play a part in female sexual response, as well.19

Hydrogen sulphide is found in lower concentrations in the female animal brain at any age, according to one animal study. When testosterone was administered to female mice just once, levels of both H2S and SAMe increased. The same researchers found that testosterone, SAMe and H2S decreased with castration in male mice.20

Brain health boosted without drugs

Research is starting to show that H2S may be a neurotransmitter in the central nervous system as well as in smooth muscle.21 Under normal conditions, the concentration of H2S in the brain is high compared to many other tissues, suggesting that it’s there for some physiologic purpose.22,23 Preliminary research shows that low H2S concentrations in the brain may contribute to abnormal brain ageing and pathological changes. Ischaemic stroke (stroke from lack of blood flow rather than a large excess of blood, which is termed ‘haemorrhagic stroke’), Alzheimer’s disease, Parkinson’s disease, and recurrent febrile (fever-induced) seizures may be influenced by abnormalities in the production of H2S.

Hydrogen sulphide levels have been found to be abnormally low in the brains of those with Alzheimer’s disease.24 In a relatively small study, the brains of 13 individuals with Alzheimer’s disease were autopsied and assessed for levels of H2S and then compared to others of a similar age with normal cognitive function.

The researchers found that one of the enzymes responsible for producing H2S, CBS, was reduced in the brains of those who died with Alzheimer’s disease, along with levels of hydrogen sulphide and S-adenosyl methionine. In contrast, homocysteine levels were increased. These results suggest that levels of H2S and its activators may play a role in some of the changes associated with Alzheimer’s disease.

We know that neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease may also be caused in part by increased levels of inflammation, oxidation from reactive oxygen species, and rates of cell death. Studies now show that H2S may have antioxidant and antiinflammatory effects in the brain as well as the rest of the body, and help to prevent cell death.25 Hydrogen sulphide `may be able to reduce the damage from amyloid beta accumulation in the brain because of these additional properties.26

The ability of H2S to protect neurons from oxidative damage caused by glutamate was demonstrated in cell culture using immature brain cells (neurons).27 Neurons were first treated with glutamate, which kills them within 24 hours because it inhibits the uptake of the amino acid cysteine, causing oxidative cell death (oxytosis). When similar neurons were simultaneously treated with glutamate and H2S, the cells didn’t die. Cells treated only with glutamate had reduced levels of glutathione, whereas those treated with H2S showed increased glutathione levels eight hours after treatment. Glutathione is protective to neurons under oxidative stress.

Hydrogen sulphide may be protective to the central nervous system in part through its regulation of pH in brain cells, in part by regulating the concentration of calcium inside of brain cells, and in part by mediating glutamate receptor (NMDA receptor) responses.28,29,30 Neuronal excitation stimulates its production and affects the long-term strength, or flexibility, of the hippocampus, related to memory.31

Regulating H2S may help regulate blood sugar

Hydrogen sulphide may play a role in the production of insulin by the pancreas. The physiologic range in which H2S is found in the body is typically between 45 and 300 uM. It is in this range that its beneficial properties of vasodilation and relaxation of blood vessels are noted.32 According to one animal study, however, pancreatic release of insulin is impaired in situations in which there’s an abnormally high level of H2S.33

In this complex study, a line of rats called Zucker diabetic fatty rats (ZDF) were studied for the impact of H2S inhibition on the release of insulin and other parameters. The diabetic fatty rats were compared to rats labelled as just ‘fatty’ and rats labelled as ‘lean’. What researchers found was that inhibiting H2S in the diabetic fatty rats decreased serum haemoglobin A1C, hyperglycaemia, and increased serum insulin levels to nearly normal ranges. In the other two rat populations, inhibition of H2S did not have an impact on blood sugar or insulin levels.

This study suggests that there may be a pathological mechanism related to production of H2S in the diabetic state and that focusing on inhibiting H2S may be a potential treatment for diabetes.

The produce-aisle solution to heart health

A diet rich in garlic, onions, leeks, mushrooms, beans and some fruits may be the best defence against cardiovascular disease, according to recent research.34 Hydrogen sulphide is produced from these foods by enzymatic processes in the smooth muscle of blood vessels and in many other organs, such as the liver.

Hydrogen sulphide’s relationship to nitrous oxide (NO) and blood pressure control is still somewhat controversial in research studies.35 Because H2S has significant cardioprotective benefits, finding a way to use the polysulphides derived from garlic, for example, may be good for cardiovascular health.

Even a small reduction in blood pressure can reduce the rate of heart disease as well as death from the condition, meaning that the ability of H2S to cause vasodilation and relaxation of smooth muscle is a potent tool in treatment. Some studies have compared the blood pressure reducing effects of garlic to those of commonly used blood pressure medicines.36,37

The benefit of the constituent in garlic oil, diallyl trisulphide (DATS), was recently demonstrated in an animal study of myocardial ischaemia (reduced blood flow to the heart) and reperfusion (restoring blood flow to the heart). All variables evaluated in the study were improved with its administration, including reduction in the size of the infarct (dead areas from the lack of blood flow) and improvement in heart muscle contraction capability. The data showed that using DATS as a donor for H2S provided cardiovascular protection.38

In other recent studies, H2S has been found to have a cell-protective effect. It can protect neurons from injury caused by variable blood flow (first cutting off the blood supply, then restoring it, technically called ‘ischaemia-reperfusion’) and cardiac muscle from oxidative stress. Hydrogen sulphide reduces inflammation, modulates the release of insulin, and reduces angiogenesis, all of which are beneficial to the cardiovascular system.39

Cancer prevention connection

Polysulphides, such as diallyl trisulphide (DATS) derived from garlic, are reported to have anticancer properties. In one study, DATS was found to kill prostate cancer cells leaving healthy prostate epithelial cells unaffected.40

Numerous other studies have linked these nutrients to reducing other types of malignancies. In addition to prostate, H2S reduces stomach, oesophageal and colon cancers.41,42,43 Hydrogen sulphide appears to promote apoptosis (cancer cell ‘suicide’) in many different cancer cells.44

Cruciferous vegetables contain organic sulphur-containing molecules (isothiocyanates), which are known to kill cancer cells. It’s thought that the ‘mechanism of action’ involves the physiologic production of, yes, you guessed it, H2S.45

Keep H2S under control for colon health

Hydrogen sulphide in the gastrointestinal tract is something most of us are familiar with, since the bacteria that produce it are often responsible for intestinal gas. It’s considered to be a gaseous signalling molecule in the rest of our body as well, but science is not clear in what ways it impacts the gastrointestinal tract.46

For some time, H2S has been viewed as a substance that creates problems for the epithelial cells of the colon.47 Studies in both animals and humans show it has a tendency to be pro-inflammatory, though some recent studies show it has anti-inflammatory properties as well.

‘Cellular respiration’ is a term used to describe the metabolic reactions that take place in cells to convert biochemical energy from nutrients into adenosine triphosphate (ATP), and then release waste products. Studies show that H2S, at non-toxic concentrations increases cellular respiration and promote cellular detoxification.48 Hydrogen sulphide has been associated with reducing NSAID (non-steroidal anti-inflammatory) damage to the stomach lining and may accelerate its repair of this damage.49

But too much H2S may be a problem. At higher concentrations, H2S toxicity may be a factor in the development of ulcerative colitis. Colon damage, characteristically associated with ulcerative colitis, has been thought to result from H2S inhibiting butyrate metabolism within colon lining cells.50 Butyrate (a ‘short chain fatty acid’) is produced right in the colon by many ‘friendly bacteria’, and is the number one source of energy for these particular cells.51

In ulcerative colitis, there are increased levels of H2S producing bacteria.52 As noted above, too much H2S means less butyrate and less energy for colon cells. Researchers looked at the role of sulphate-reducing bacteria in causing ulcerative colitis.53 They wanted to see what effect two substances would have on the activity of the sulphate-reducing (excess H2S causing) bacteria.

Study volunteers were divided into three groups, one group receiving metronidazole (an antibiotic and anti-protozoal formerly patented medicine), another group receiving the prebiotic oligofructose (‘prebiotics’ are substances which promote the growth of beneficial intestinal bacteria), and the third group received both.

Those taking metronidazole showed decreased activity of sulphate-reducing, H2S increasing bacteria, whether or not the research volunteers took oligofructose, too. As a consequence, there was a reduction in short-chain fatty acids including butyrate. That’s not so good for anyone with ulcerative colitis. In those taking only oligofructose, sulphate-reducing bacteria were not decreased, but levels of H2S itself were. With lower H2S inside the bowel, short-chain fatty acids increased, which would be good for those with ulcerative colitis.

The study suggests that there is some other mechanism related to the production of H2S in the colon and that using prebiotics, such as oligofructose, may have some beneficial effect.

Hope for treating eye diseases

Hydrogen sulphide’s benefits may even extend to the eyes. The gas may be a gaseous neuromodulator in the eye, too.54 It may offer hope in the treatment of glaucoma and other eye diseases through its ability to relax smooth muscle.

Eat more garlic and onions for better health!

Despite all the relatively complex biochemistry the practical implications are simple: Eat more garlic and onions for better health! Use garlic and onion in your cooking. Nearly everyone knows that these foods are an important part of the Mediterranean diet, which is associated with significantly less heart attack and stroke. And maybe it’s one reason that Italian, Greek and other (Mediterranean men have that sexy reputation that isn’t nearly as often attributed to men living further north in Europe!

In addition, more garlic and onions – and the consequent production of H2S – may help ward off Alzheimer’s disease and other types of cognitive decline, decrease risk of cardiovascular disease, and work against cancer. Modulating excess H2S may help in ulcerative colitis and type-2 diabetes. All of this is suggested by the very early innings of H2S research. Of the 54 research publications cited by this article, only two were published before the year 2000! Research into H2S is accelerating rapidly; there’s much more yet to be found!

Wishing you the best of health,

Dr. Jonathan V. Wright
Editor
Nutrition & Healing

Volume 7, Issue 5 – May 2013


Full references and citations for this article are available in the downloadable PDF version of the monthly Nutrition and Healing issue in which this article appears.

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