Friday, May 29, 2009

More CFSAC Testimony - Science

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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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