Hydrogen Sulfide and Chronic fatigue Syndrome: The Originator Speaks
Originator of H2S Theory Speaks
Dr. DeMeirleir made a big splash when he announced at a press conference that he had uncovered a new and important factor in chronic fatigue syndrome (ME/CFS) called hydrogen sulfide. What was lost in the flurry that followed was the fact that if it was not for an inquisitive mother of a daughter with chronic fatigue syndrome that press conference very well might never have happened.
Years before hydrogen sulfide had become even the smallest blip on the ME/CFS research community’s radar screen a rather remarkable woman named Marian Dix Lemle was developing a theory suggesting that it could lie at the heart of this disease.
I first met Marian Lemle two years ago at the IACFS/ME conference in 2007. She had written a paper proposing that the excessive production of hydrogen sulfide gas had put ME/CFS patients into a kind of hibernation like state. I was a little taken aback by it – I had never even heard of hydrogen sulfide before and certainly not the connection with chronic fatigue syndrome. I bumped into her several more times over the next couple of years and each time her interest in the subject remained undimmed.
She got a short paper published, a remarkable accomplishment, I thought, for someone without a medical background. Then the news flashed across the Internet – big breakthrough in ME/CFS! I eagerly scrolled through the news – it was hydrogen sulfide! You could’ve knocked me to the floor with a straw. But where was Marian? I saw no mention of Marian. (Marian was cited on the last slide of Dr. DeMeirleir’s presentation)
Marian Lemle had been in London. When she got back to the states I got a chance to talk with her. She just accomplished an amazing feat; opening a new field of inquiry in a disease doesn’t, after all, happen every day – especially if you’re a lay person .In truth if anyone was going to do something like this it was probably going to be someone like Marian Lemle. Previously a professional in the telecommunications field and a exhibited sculptor and painter, she is used to traversing and excelling in different fields. I asked her how this all came about.
“In Nov 2006 I attended a meeting in Washington where a prominent molecular biologist discussed an experiment where he gave H2S gas to mice and watched their metabolic and heart rates plummet as they entered a apneic-like low-level sleep state in which one part of their brain was always monitoring the environment.When he pumped oxygen back into the chamber the mice completely recovered. I started thinking about the kind of enervated torpor-like state that CFS patients experience and I asked him if this could be related to CFS. He thought it seemed possible.”
“From there I started turning over every clue I could. I prepared a short synopsis of my findings and asked the panel on ‘The Brain in Chronic Fatigue Syndrome” at the IACFS/ME Conference in Miami in 2007 what they thought of my idea. One of the Japanese researchers (Dr. Watanabe or Dr. Kuratsune) thought it was an interesting question. The rest of them (including Dr. De Meirleir) showed little interest.”
“A couple of months later Dr. Carl Peck, former Assistant Surgeon General and a friend of the family, approached me and asked to take a look at the paper.He aid it was groundbreaking and helped me formulate the hypothesis. We periodically met over the phone to discuss drafts of the paper.”
“I sent the paper to and talked to researchers at Johns Hopkins, the NIH and elsewhere.Eventually I talked to Dr. Suzanne Vernon, the Research Director at the CFID’s Association of America (CAA) and Kim McCleary, the President of the CAA. Dr. Vernon thought the theory “made biological sense” and directed me to Dr. Richard Deth, a prominent researcher working on mercury in autism. She encouraged me to publish the paper. All three were very supportive.”
“Dr. Deth told me that his work on thimerosal had lead him to think about sulfur metabolism in autism, but he’d missed a possible link with regard to H2S. He asked me for permission to share my ideas with his students and colleagues and I agreed. “
“I submitted the paper to the Journal of Medical Hypotheses early in 2008. The editor wrote back immediately and offered his help in getting a much shorter paper ready for publication. The abbreviated version of the original paper paper was e-published in September of 2008.”
In retrospect the doors opened for Marian Lemle quite quickly; Dr. Peck, Dr. Vernon and Dr. Deth all quickly realized that Marian was ontosomething and were happy to assist her. style=”padding-top: 0px; padding-right: 0px; padding-bottom: 0px; padding-left: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px; “> I noted, though, how difficult it can be for a lay person to get the research community’s attention.
While noting that that’s often true, Marian observed that “In scientific discovery, many new ideas come from people on the outside who haven’t been constrained by the thinking patterns that permeate the field.”In fact we don’t have to look far to find evidence of that in ME/CFS. Rich Van Konynenburg Ph.D. is in physics yet his ideas regarding glutathione and now methylation have sparked much interest in the field.
I mentioned Rich and Marian was quite emphatic that she felt that his work deserved more attention. She talked to Rich at the IACFS/ME conference and told me that he said “You’re right!” It turns out that the H2S theory fits in quite well with Rich’s methylation theory.
The Gut Connection - Dr. De Meirler and Dr. Chia have been focusing on the gut for several years now. Marian, however, does not have a singular focus on the gut, although she thinks the story could “begin there, within the context of our genetic boxes”. She notes the prevalence of gut dysbiosis (imbalance of intestinal flora) in CFS and is inclined to think of Lyme, salmonella and many other H2S-positive infections as a manifestation of this underlying dysbiosis. She takes it even further, saying that certain people may be particularly susceptible to the effects of H2S, having, “what, years ago was called “hyper-susceptibility” to Hydrogen sulfides”.
I noted that the gut is ‘consuming’ more interest all the time but it turns out that it’s only one organ of interest with regard to H2S. Marian noted that “if the gut connection doesn’t produce reliable results it may reduce interest in other areas…The story of H2S goes far beyond what happens in the gut. H2S is fundamental to life. Imagine, there is a parallel universe in the deep sea that relies on H2S to sustain some extraordinary life forms. H2S is to the deep sea world what oxygen and light are to life on earth. Who could have imagined this?”
“We may be fueled by oxygen and light, but it turns out that H2S is essential to our bodies as well. Hydrogen sulfide and oxygen may well turn out to be the yin and yang of homeostasis in our bodies”.
Marian noted that “our mitochondria are descended from ancient eukaryotic cells, which appear to have retained that deep sea capability to use H2S as an energy substrate.”
This is the third prong of her theory. She stated that “Drs. Myhill and Moore appear to have confirmed the first part of my hypothesis– that CFS is a mitochondrial disease. Dr. De Meirleir may prove the second; i.e., that H2S dsyregulation plays a key role. Now we must examine the role of H2S in the mitochondria.”
A Nitric oxide/mitochondrial connection? H2S’s ability to interfere with mitochondrial production has again brought the question of metabolic abnormalities to the fore in ME/CFS. The Pacific Fatigue Lab has documented that some chronic fatigue syndrome (ME/CFS) suffer a kind of metabolic implosion after exercise. At the last IACFS/ME conference a Spanish researcher presented preliminary findings of greatly increased levels of nitrates in ME/CFS patient’s blood following exercise. Nitrates are derived from nitric oxide. Could H2S dysfunction be the tie that binds with regard to nitric oxide and exercise metabolism?
Martin Pall believes nitric oxide plays a key role in a broad arena of disease (ME/CFS, FM, IBS, MCS). Italo Biaggoni is currently examining whether NO is causing the blood vessels to over dilate in ME/CFS patients. Some evidence suggests, however, that H2S may even be the puppet master controlling NO’s strings in our blood vessels.
H2S is produced in the brain, pancreas, liver, reproductive tissues and it affects smooth muscle functioning in our blood vessels. Dysregulated H2S production in any of them could cause dramatic effects.
The brain connection? The brain connection is particularly intriguing. ME/CFS patients often benefit from drugs (Klonopin) or practices (meditation, relaxation exercises) that slow down nervous system activity. In fact the whole class of CFS-like illnesses (Fibromyalgia, IBS, MCS, etc.) may be characterized by an over-active nervous system. Marian informed me that H2S is produced in the brain by cystathionine beta synthase and cystathionine gamma lyase and its release in the brain is triggered by neuronal excitation.
Increased levels of H2S in the brain may indicate that low blood flows in the brain have caused a free radical explosion in the blood vessels (resulting in cerebral ischemia). Interestingly, several studies have found evidence of ‘hypo-perfusion’ or low blood flows in the brains of the ME/CFS patients. Both Dr. Baraniuk’s and Dr. Shungu’s work suggests high rates of oxidative stress/mitochondrial problems occur in the brains of at least a subset of ME/CFS patients.
Marian also noted that the brain and gut share enough similarities that the gut is often referred to as the second nervous system or the ‘enteric nervous system’. Does the neuronal excitation presumably found in the central nervous systems of chronic fatigue syndrome patients extend to the gut as well? Could H2S play a role in the irritable bowel problems so often seen? She added “We already know that it has been tied to ulcerative colitis and colon cancer.”
A Protective Mechanism? H2S by itself is not ‘bad’; it’s a potent signaling molecule that triggers important reactions across the body. Interestingly in the case of cerebrial ischemia H2S is thought to have protective effects and this brings us back to the altered brain states in sleep, hibernation, torpor and all the states in between
Could H2S outside of the gut be protecting patients from the damaging effects of ‘high’ metabolic rates. Could that torpor like state the molecular biologist described which so caught Marian Lemle’s attention in 2006 be protective? Could H2S be stepping in to induce fatigue and thus shield patients from the effects of overexertion?
The Question As with all the intriguing theories in ME/CFS, the links abound. But will they stand up to rigorous scientific inquiry? (Will they get rigorous scientific inquiry might be a more applicable question.) Dr. De Meirleir has done something that Marian Lemle could never do on her own – capture the attention of the ME/CFS community. Before going public, he wrote her in an e-mail – “Your H2S hypothesis was confirmed by us“ and is working on extending it. He’s developed a test for H2S metabolites and has asserted that H2S producing bacteria are indeed present in high levels in ME/CFS patients’ guts.
Treatment Marian Lemle is not a physician but she is a mother with an ill daughter. Has she tried to apply her theory to her daughter’s health? She said “I’m quite cautious with regard to treatments for my daughter”. She noted that the standard treatments for H2S poisoning (usually from industrial accidents) include amyl nitrate (better known in the recreational drug community as ‘poppers’) and oxygen.(Injections of the sodium nitrite (used as a preservative in foods)are also used). Only the last is tenable for ME/CFS but she has concerns about providing oxygen to ME/CFS patients.
Another tack, which appears to be used by Dr. De Meirleir, is to isolate the bacteria in the gut and attack them with antibiotics while providing nutrients to heal the gut but she’s hesistant about using long-term antibiotics. Right now she’s watching and waiting to see how all this interest that she started resolves.1 comment