RichVank,
"Hydrogen sulfide (H2S) has been getting more attention lately in connection with
CFS.
As I think many of you know, the methylation cycle and glutathione are both parts of the overall sulfur metabolism in the body, as is the production of H2S.
The various reactions that can produce H2S in the body include parts of the
human metabolism, and also the metabolism of certain bacteria in the gut.
The first place I heard about H2S in connection with CFS was from Dr. Amy Yasko, who
emphasizes that people who have genetic polymorphisms in their cystathionine beta synthase (CBS) enzyme, along with a methylation cycle block, will tend to generate more H2S.
I also heard about sulfur-related topics from Susan Owens, who runs the Yahoo
sulfurstories group and the group about trouble with Epsom salts. On the latter
topic, I have speculated that people who don't tolerate Epsom salts well may
have sulfate-reducing bacteria (SRBs) in their gut, which convert sulfate to
hydrogen sulfide. SRBs have been found in the gut in some people. As far as I
know, the human metabolism does not have a pathway for chemically reducing
sulfate, so I think the bacteria must be responsible for converting the sulfate to more chemically reduced species, such as H2S and eventually sulfite, and thus producing the sulfate intolerance in these people. Sulfate is the main form of sulfur normally excreted in the urine.
In the human metabolism, the two enzymes of the transsulfuration pathway, i.e.
cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL), aka
cystathionase, are capable of producing H2S from cysteine or homocysteine.
In my 2008 revision of the Glutathione Depletion--Methylation Cycle Block
hypothesis, described in the set of PowerPoint slides in the files section of
the cfs-yasko group's website, I proposed that cysteine becomes oxidized to cystine in
the oxidative stress condition present in CFS, and that CGL then catalyzes a pathway
starting with cystine that produces hydrogen sulfide and thiosulfate. I based
this on research summarized by Martha Stipanuk, who has worked a lot in this
area with rats.
Marian Lemle has proposed that hydrogen sulfide is involved in CFS. I had the privilege of meeting her at the
Reno conference in March, where we both presented poster papers. She is also a
friend of Prof. Dick Deth, who works primarily on autism, and who is very knowledgeable about the sulfur metabolism. Marian got
her paper published in the journal Medical Hypotheses, and she also presented
her hypothesis to the federal CFS Advisory Committee last October. Marian didn't
get into the biochemistry of how H2S is produced (she is a science writer, not a
scientist per se), but she noted that the symptoms of H2S poisoning are similar
to those of CFS, and that was the basis for her hypothesis that H2S is involved
in CFS. I thought this was interesting work, and I have interacted with her
concerning how her work and mine might be connected.
This past week, Dr. Kenny de Meirleir held a press conference and gave a talk at
the M.E. conference in London about what he reported to be a major breakthrough
in M.E. research. (By the way, Marian "hopped a plane to London" when she heard
that the press conference was to be held, and she was there for it, and for the
one-day M.E. conference that followed.)
Dr. de Meirleir and his group have found that hydrogen sulfide is elevated in
the urine in the most severely ill M.E. patients, and his company is now
offering a qualitative urine test for H2S. His view seems to be that the H2S is
being produced by bacteria in the gut in the severely ill patients, and I think
he is probably right about that.
I think that we will eventually be able to tie all of this together, but it will
take some careful lab work to nail it down.
Here are some speculations about what goes on: First, the sulfur in the human
body originates in the diet (and supplements, if they are used). It comes in as
sulfur-containing amino acids (methionine, cysteine, cystine, and taurine), and
also in the form of sulfate and a few other sulfur-containing species. The
sulfur in whatever amount of H2S is produced, by either the human metabolism or
the bacteria in the gut, must originate in the diet (and supplements) People who bathe in Epsom salts will absorb some sulfate through their skin.
In a normal, healthy person, a lot of the sulfur-containing substances are
digested in the gut and are absorbed into the blood, while some remain in the
gut. Also, some are transported into the gut via the bile, from the liver.
Bacteria in the gut therefore have access to some of it, and I think we are all
familiar with the rotten egg smell that can be associated with flatus, which
comes from hydrogen sulfide. So it is not unusual for bacteria in the gut to be
producing hydrogen sulfide.
It is quite common in CFS that there is dysfunction in the digestive system.
This can include low stomach acid, slow gastric motility, insufficient secretion
of pancreatic enzymes, insufficient secretion of bile, gluten or casein
sensitivity, fructose or lactose intolerance, candidiasis, dysbiotic bacteria,
intestinal permeability (leaky gut), a variety of other food sensitivities,
secretory IgA deficiency, protozoal or helminthic parasites, and others.
Under these circumstances, I think it is quite likely that less of the
sulfur-containing substances will be absorbed into the blood, and more will be
metabolized by bacteria in the gut. The results would likely be less methionine
available for the body's use (including for the methylation cycle), and more
hydrogen sulfide produced by bacteria in the gut, which can be absorbed into the blood, have
toxic effects on the cells of the body, and be excreted in the urine.
As I noted in a recent post, some of the people who have not responded to the
simplfied treatment approach for lifting the methylation cycle block appear to
be low in methionine. If there is not enough methionine available, the
methylation cycle will operate slowly, even if the partial block has been
lifted, because there is not enough "cargo" to be carried around this cycle or
to feed the transsulfuration pathway.
I think this fits in well with what Dr. de Meirleir has reported. If
sulfur-containing substances aren't being absorbed into the body, they would be
available to feed the bacteria in the gut.
So what does this mean for treatment? I think it means that if a person is
treated early enough in their illness, when their gut is still functioning
relatively well, the simplified treatment approach is likely to work. If their
methionine is low, they may also need to supplement it, or to increase their
protein intake in general, perhaps together with betaine HCl to augment stomach
acid and digestive enzymes to help break down the protein in the gut, so that
the amino acids can be absorbed.
If a person is severely ill, so that the digestive system is no longer able to
deliver much nutrition to their body, then I think it is likely that the
hydrogen sulfide level in their urine will be elevated, as Dr. de Meirleir has
reported, because the absorption of the sulfur-containing substances will be
lowered. In these cases, it seems reasonable to suspect that many of the
serious symptoms that are experienced are effects of hydrogen sulfide. Also in
these cases, there may need to be intravenous feeding until the gut is in better
condition, and the simplified treatment approach may not help until the gut is
in condition to absorb nutrients, and the methionine level is high enough that
the methylation cycle is being fed with it.
So how do we know where to draw the line between cases in which the simplified
treatment will work, and cases that will require additional efforts? I think
that measuring the methionine level in a urine amino acids test is one thing
that can be done, and perhaps the H2S test being offered by Dr. de Meirleir's
company would be another way to gauge this. This is all very new, so we don't
have experience to go on yet, but I do think all of this will fit together."
Best regards,
Rich
