Dr. Sarah Myhill MD
August 4, 2009
We have good evidence that the fatigue in chronic fatigue syndrome is caused by poor mitochondrial function. We have a test to measure this - the Mitochondrial Function Profile blood test(1) - and we can see if this dysfunction occurs because of micronutrient deficiency, or something which is blocking mitochondria.
Hydrogen sulfide (H2S) fits into this picture because it inhibits mitochondrial function, and this provides a nice explanation as to why the abnormal gut flora can cause fatigue.
Work done by Professor Kenny De Meirleir(2) has shown that people with chronic fatigue syndrome consistently have higher levels of hydrogen sulfide in their urine compared to normal controls. Furthermore, this is associated with high levels of bacteria which are not normally found in the gut flora.
He has identified bacteria in the gut responsible for this. The idea is that an overgrowth of Streptococcus, Enterococcus and Prevotella bacteria results in foods being fermented to produce hydrogen sulfide, and it is this which causes the problems.
He further noted that overgrowth of these different bacteria correlated with symptoms.
In particular, Enterococcus is associated with:
- Arm pain
- Shoulder pain
- And sleep disturbance
Streptococcus correlated with:
- Post-exertional fatigue
- Mind going blank
- Cervical gland lymphodynia [swollen lymph nodes in the neck
- Palpitations, dizziness and faintness
All these associations were statistically highly significant.
The H2S Test
Increase in hydrogen sulfide levels can be measured by dint of a simple urine test that looks at hydrogen sulfide spilling over into the urine, and this test has been developed by Prof. De Meirleir in Belgium.
This is a simple "DIY at home" test, and the kit can be ordered directly from the Protea Biopharma website (in Belgium, www.proteabiopharma.com) or from my office (in the UK, www.drmyhill.co.uk) [and in North America now, for research purposes, via www.ProHealth.com].
Hydrogen Sulfide in Low Levels Has Important Actions
Hydrogen sulfide (H2S) is produced by normal cells and is an important gaseous signal molecule a little bit like carbon monoxide and nitrous oxide. It is involved in regulation of blood pressure, neuro-transmission, muscle relaxation and the regulation of inflammation.
- Endogenous hydrogen sulfide [produced in the body] plays a role in regulating blood pressure, body temperature, vascular smooth muscle, cardiac function, blood flow to the brain, and is an important modulator of the hypothalamus-pituitary-adrenal axis.
- At low dose levels exogenous H2S [from sources outside the body] produces a hibernation like state in mice with a decreasing core body temperature, apnea-like sleep, reduced heart and respiratory rates and a marked metabolic drop.
These symptoms are often experienced by CFS/ME sufferers.
Too Much Can Be Very Toxic
In excess, H2S acts as a mitochondrial poison inhibiting many enzymes involved in oxidative phosphorylation [manufacture by the mitochondria of energy in the form of ATP]. It also interferes with oxygen transport in red blood cells, a little bit like carbon monoxide. Almost always we see low levels of glutathione in CFS, which is a sulfur containing molecule.
From an evolutionary perspective, mitochondria are organelles descended from ancient eukaryotic sulfur-using microbes, and so it is not surprising that H2S targets mitochondria. H2S inhibits immune cells such as CD8, T cells, and Natural Killer cells, so contributing to the immune dysfunction. It also impacts on the hypothalamic-pituitary-adrenal axis. It regulates the use of oxygen by mitochondria.
The Gut Flora in CFS
The $64,000 question, which as yet nobody knows the answer to, is what to do about this problem? There are some strategies well worth trying, and one needs to understand the normal state of affairs to understand such strategies.
Normally, the stomach is extremely acid and this kills all bacteria that enter into it. This means digestion of foods, which requires hydrochloric acid, pancreatic enzymes and bile acids, takes place in a sterile environment, where foods are broken down into small polypeptides, fatty acids, simple sugars, etc., and most absorption takes place in the small intestine. Again, the small intestine should be sterile, although numbers of bacteria start to creep up in the last part of the small intestine.
The last part of the gut is the large intestine, and this is stuffed full of bacteria, namely Bifidobacteria, Lactobacilli and E-coli, and these bacteria are able to ferment foods to produce short chain fatty acids (a very desirable fuel for the body), help program the immune system, make some vitamins, and so on.
Problems can arise in any of these departments. So, for example, if the stomach and the small intestine are not sterile, then bacteria and yeasts can exist in the upper gut and ferment foods before they are properly digested. Inefficient digestion and absorption of food can result in more fermentation downstream. Eating a diet rich in refined carbohydrates encourages yeast overgrowth.
The gut should be inoculated at birth with immune-tagged mother’s friendly bacteria, so the immune system knows which are the good bugs and which are the bad bugs. When this is disrupted by lack of breast feeding, antibiotics, mercury from dental amalgam, vaccinations, and who knows what else, the immune system then does not know how to recognize good from bad.
Treatment of a Positive H2S Test Result
If one has the wrong bacteria in the upper gut, then H2S could be produced as a result of this fermentation process. So, improving gut function and restoring the normal gut flora will be centrally important to tackling gut fermentation producing hydrogen sulfide. The important issues that must be tackled are as follows:
Stoneage Diet - the evolutionarily correct diet which encourages growth of friendly bacteria;
Hypochlorhydria - acid is essential for sterilizing the stomach and upper gut;
Pancreatic function - essential for quick and efficient digestion of foods so they cannot be fermented downstream.
Gut dysbiosis - having the wrong bugs, possibly also in the wrong place;
Probiotics - essential to introduce the friendly bacteria to the gut. Kefir is an excellent cheap source of friendly bacteria.
However, problems will arise particularly where the immune system no longer recognizes good from bad. That is to say, undesirable bacteria have gained a foothold in the gut and the immune system does not evict them. The immune system seems to accept the status quo, so if these bacterial numbers could be kept low for as long as possible, the hope is that the immune system will eventually relearn good from bad.
What we need, of course, is an antibiotic which is not absorbed systemically and is specific to those hydrogen sulfide-producing bacteria.
This could be a prescription drug, or a herbal preparation. Initially, I would suggest rifaximin, which is a non-absorbable antibiotic [passes through stomach and into intestines without being absorbed into the blood stream], widely used for travelers' diarrhea with very few side effects and low risk of antibiotic resistance. It must be taken with high dose actively fermenting probiotics such as Kefir.
The joy of the urine test for hydrogen sulfide is that we have a way of checking as to whether or not we are making progress with the gut. My view at this stage therefore is to put in place as many of the above interventions as is reasonably possible to do, and take rifaximin 200mg three times daily for three days, then a maintenance dose of 200 mg daily and then re-check a urine test to see if we are making progress.
With time, new agents will doubtless become available that can be tried.
It may be that eating foods low in sulfur could be helpful, but sulfur is also essential for normal body biochemistry, and my view is that one should concentrate on gut function to ensure quick and efficient digestion into desirable end products rather than further food avoidance.
One could go on further to do more detailed analysis of gut flora to see which bacteria are present and, again, I will try to make this test available.** However, my guess is that this will not affect treatment, at least in the early stages when the aim is to restore gut function.
Professor De Meirleir's treatment regime includes all the above factors, but he believes that heavy metals may also be implicated here because they have a synergistic effect with H2S to make it more toxic.
Indeed, we know already that mercury vapor from dental amalgam can have a profound effect on gut flora. He suggests that H2S may combine with heavy metals, and the resultant compound distorts proteins to form prions. These prions then distort other normal proteins in what is known as the "rotten apple" effect. This magnifies the underlying poisoning by heavy metals and H2S.
So, heavy metal detoxification is likely to be an important part of the treatment program.
1. The Mitochondrial Function Profile blood test, developed by John McLaren Howard at Biolab in London, “combines several tests which together assess mitochondrial function and identify where the problem areas with energy production are,” Dr. Myhill explains. “It is exceptionally useful for chronic fatigue sufferers as it gives clear indications for a treatment regime.” To read more about the test - and, if you live in the UK - to order it through Dr. Myhill’s website, go to www.drmyhill.co.uk/test.cfm?id=85 (Note: unfortunately the test’s availability to non-UK residents has been suspended at least temporarily, because the volume of requests has exceeded the capacity of both the testing lab and Dr. Myhill’s practice.)
2. Protea Biopharma Press Conference (slides), London May 28, 2009. Prof K. De Meirleir, Chris Roelant, Marc Fremont. See also Lemle MD. "Hypothesis: Chronic fatigue syndrome is caused by dysregulation of hydrogen sulfide metabolism," Medical Hypotheses 2009;72(1):108-9. Epub 2008 Sep 16.