H2S Central Role in ME submission to csfac by marian dix lemle

Discussion in 'Fibromyalgia Main Forum' started by simpsons, May 30, 2009.

  1. simpsons

    simpsons Member

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    ProHealth Library

    Testimony to CFSAC on the hypothesis that
    dysregulated H2S metabolism plays central role
    in ME/CFS – Oct 28, 2008

    by Marian Dix Lemle

    May 29, 2009

    Note: Marian Dix Lemle is a remarkable lay
    researcher inspired by the desire to follow a lead she
    thinks might explain and generate a cure for her
    daughter's 'chronic fatigue syndrome' (ME/CFS).

    She has worked tirelessly for more than two years to
    interest the world's top experts in her hypothesis
    that hydrogen sulfide (H2S) plays a central role in

    And her efforts took on new meaning May
    28, 2009, the day Belgian researcher Dr.
    Kenny De Meirleir called a press conferen-
    ce in London to announce a theory of
    ME/CFS that centers around testing for
    dysregulated H2S metabolism:


    Good afternoon, Chairman Oleske, members of the
    Chronic Fatigue Syndrome Advisory Committee, and
    concerned members of the CFS community.

    My daughter's life - and by extension, our family's
    world - were turned upside down four and half years
    ago when our beautiful daughter, who had been
    President of her graduating class with a very bright
    future ahead of her, came down with what was then
    an unspecified virus, and was later diagnosed with
    the absurdly named disease "Chronic Fatigue

    For ten years prior to her getting sick, I had on the
    table in the living room this little artist's book called
    The Blind Men and the Elephant. In this well-known
    parable, one blind man touches the elephant's side
    and is certain he is touching a wall. The second
    blind man grabs a tusk and is certain he is holding a
    spear. The third touches a squirming trunk, and
    thinks it is a snake, and on it goes…

    I cherished this book because it so simply and
    elegantly illustrated how our conceptual framework,
    our view of a problem, can limit our ability to see
    the larger whole, particularly when combined with
    unwarranted certainty.

    It reminded me of the importance of thinking more
    broadly about a problem and maintaining an open
    mind, something that I, in turn, will ask of you here
    today, as I discuss a hypothesis I developed on

    I have been working in a very promising new area of
    research, akin to the discovery of nitric oxide in its
    importance, for which the Nobel Prize was awarded.
    Very few scientists or physicians are familiar with it.

    I should add that I am not looking for any research
    money, but instead, I am hoping to interest
    researchers in this idea.

    I could not have gotten to this point without the
    support of Dr. Carl Peck, a former Assistant Surgeon
    General, who, early on, felt that I had made a
    discovery and guided me through the process of
    writing the hypothesis, which was e-published ahead
    of print in September [2008] by the journal Medical

    [Note: Unfortunately the article "Hypothesis: Is
    ME/CFS caused by dysregulation of hydrogen sulfide
    metabolism?" had no abstract. Access to the text via
    the publisher requires subscription or payment -
    though Googling on the title will pull it up in several

    Almost two years ago to the day, I attended a
    lecture by a scientist who was able to induce a state
    of suspended animation in mice using the gas
    hydrogen sulfide, or H2S.

    As I listened to him, I was struck by the similarities
    between what happened to the mice, i.e., a
    decrease in core body temperature, an apnea-like
    sleep state, reduced heart and respiration rates, and
    a severe metabolic drop, and what happens to
    people with CFS/ME.

    Out of that idea grew my hypothesis that CFS/ME is
    caused by dysregulation of hydrogen sulfide
    metabolism. Further I postulate that the
    multi-system disturbances in the homeostasis of
    endogenous H2S result in mitochondrial dysfunction.

    Research on H2S – the gas that causes the
    characteristic smell of rotten eggs – dates to the
    1700's. At high concentrations, H2S is
    instantaneously deadly, on a par with cyanide.

    At low concentrations, some evidence suggests that
    H2S has beneficial effects and can act as an
    endogenous biological mediator. In fact, the brain,
    pancreas and the gastrointestinal tract produce H2S.

    Endogenous H2S plays a role in regulating blood
    pressure, body temperature, vascular smooth
    muscle, cardiac function, cerebral ischemia, and in
    modulating the hypothalamus/pituitary/adrenal
    axis. It even has been called a "master metabolic

    We refer to CFS/ME as a systemic disease, but no
    unifying thread has been found. H2S directly
    affects the neurologic, endocrine and immunologic
    systems - the very systems most involved in CFS.
    In persons with CFS/ME, one plausible etiology is
    an increase in the activity of endogenous H2S,
    thereby inhibiting mitochondrial oxygen utilization.

    In this view, fatigue and the other CFS/ME symptoms
    could be due to diminished physiological and cellular
    energy due to reduction in the capacity of
    mitochondria to utilize oxygen and synthesize ATP.

    Specifically, H2S binds to the mitochondrial enzyme
    cytochrome c oxidase, which is part of Complex IV of
    the electron transport chain, and attenuates
    oxidative phosphorylation and ATP production.

    Consistent with this finding, recent research on low
    level H2S toxicity points to increased formation of
    free radicals and depolarization of the mitochondrial
    membrane, a condition that would decrease ATP

    If poisoning renders mitochondria inefficient, one
    would expect cells to shift to anaerobic mechanisms,
    a shift that has been reported for CFS patients.

    Also consistent with this hypothesis is the fact that
    mitochondria are organelles descended from
    ancient eukaryotic sulfur-utilizing microbes. Thus,
    it is not surprising that they show a very high
    affinity for sulfide. In other words, they have
    retained the ancient capability of utilizing this gas.

    Given a predisposing genetic background, H2S may
    lead to genomic instability or cumulative mutations
    in the mitochondrial DNA. Alternatively, the effects
    of H2S could be initially mediated by changes in the
    redox potential of cells or changes in their sulfur

    Of importance, H2S plays a pivotal role in both
    aerobic and non-aerobic organisms as a signaling

    Bacteria in the gut both produce H2S and utilize it
    as a substrate alternative to oxygen. This is of
    particular relevance in the gastrointestinal tract,
    where unusually high levels of gram-negative
    bacteria, which increase intestinal permeability
    have been found in patients with CFS/ME.

    In addition to bacteria, many of the foods and
    substances people with CFS are sensitive or allergic
    to produce H2S under certain conditions, such as
    mold, milk, eggs, wine, corn syrup and the
    ever-ubiquitous yeast.

    CFS/ME is a model disease for multi-system
    disturbance. It is my hypothesis that the
    mitochondria in patients with CFS/ME, organelles
    required by every cell to sustain life, are unable to
    adequately utilize oxygen.

    This mitochondrial disturbance could be due to the
    combined effects of anaerobic conditions known
    to occur in CFS and associated low-level H2S
    toxicity. This increase in H2S alters fine signaling
    necessary for body homeostasis and, in my
    hypothesis, causes CFS/ME.

    New discoveries on H2S are being
    made every day.

    I would encourage you to go to PubMed or Google
    and type in your area of research and "H2S."

    * If you are interested in cardiac function, you will
    find last week's article in Science Daily about John
    Hopkins' Solomon Synder's finding that H2S controls
    blood pressure.

    * If you are interested in catecholamines, you can
    read about the inhibitory action of H2S donors on

    * If you are interested in immune function, you will
    find that exogenous hydrogen sulfide induces
    functional inhibition and cell death of cytotoxic
    lymphocyte subsets of CD8 (+) T cells and NK cells.

    • If you are prescribing vitamin B-12 to your
    patients, you will see evidence supporting
    hydroxocobalamin as an antidote against H2S
    poisoning, and so on.

    My hypothesis paper does not address the fact that
    H2S is increasing in the environment as a result of
    global warming, natural gas and crude oil refining,
    centralized animal feeding operations, and chemical

    It seems logical, though, that external levels could
    affect internal levels, just as oxygen does. Just
    yesterday I came across an article in last week's
    Science magazine about the role green sulfur
    bacteria played in the Permian-Triassic extinction, as
    H2S levels rose and oxygen decreased in the oceans.

    In summary, I ask you to keep an open mind and
    support this idea. A simple program could be
    undertaken. There are several genetic
    polymorphisms and enzyme deficiencies related to
    H2S and sulfur metabolism that should be
    investigated, after which H2S and associated
    chemicals such as thiols and glutathione levels in
    the body could be assessed.

    As H2S cuts across disciplines and appears to be
    implicated in several diseases, I think it would be an
    important focus for NIH. I feel confident that such a
    program would lead to discoveries.

    It may well provide a unifying lens through which
    to view the diverse manifestations of this complex
    disease. With determination and resources, we
    may discover that the disparate parts so many
    dedicated people have been researching for two
    decades can begin to add up to a new
    understanding of this very complex disease.

    Thank you.

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  2. cfsgeorge

    cfsgeorge New Member

    I'm very impressed with her CFS hypothesis. It's well written and really looks at the whole "elephant" as it pertains to CFS. This is exactly how the CFS/ME community should be looking at CFS.
  3. ulala

    ulala New Member

    I wonder if this is why when I got IV B12 that I felt 100% normal for 2-3 days.

    According to this article:

    "If you are prescribing vitamin B-12 to your
    patients, you will see evidence supporting
    hydroxocobalamin as an antidote against H2S
    poisoning, and so on".
    [This Message was Edited on 05/30/2009]
  4. karinaxx

    karinaxx New Member

    central nervous system, there for used successfully in all patients with some sort of brain, central nervous system issues.