Hi Ward,
Your demands for excellence are certainly apparent in your writing and in
the questions you are asking here. I will try for the same level of clarity
in my responses. :=)
>Specifically here are the words and concepts I am unclear on:
>
>>Neurological and auto-immune diseases, as well as malignancies, are
>>over-represented among celiacs (5), suggesting that glutens/gliadins may be
>>a major environmental contributor to such diseases.
>
>The word gliadins here seems to slip in without any definition--only some
>sort of unclear similarity (in my mind) to glutens due to the context. What
>exactly are gliadins
They are a sub-group of alcohol soluble proteins
> and why are they distinguished here from glutens
Due to my sloppy writing. I should have stuck with the term gluten.
>rather than simply lumped in together under the catchall term "gluten" that
>you are using as a catchall for many other proteins also found in cereal
>grains?
Yes, that is what I should have done.
>>There is abundant evidence connecting the advent of agriculture with
>>retardation of long bone growth, dental enamel hypoplasia, iron deficiency
>>anemia (indicated by porotic hyperostosis), juvenile osteoporosis, and joint
>>disease (18). Do these conditions sound familiar?
>
>All but two. I would like to know in plain terms what "dental enamel
>hypoplasia"
holes in dental enamel, usually horizontal, and usually due to a period or
periods of malnutrition
> is, as well as "porotic hyperostosis." I know from past study
>in the research that the latter is some kind of bone disease, but I can't
>remember exactly what kind. Please fill me in.
It is a condition where the outer layer of the bone becomes enlarged. It
indicates a condition of iron deficiency anemia.
>>We know, from palenotologists' study of human remains from the ancient past,
>>that when a culture begins to cultivate cereal grains they experience
>>substantial reductions in height, which is variously reported as 5" and
>>6"(2,4). Clearly, the reduction is substantial and significant. We know,
>>too, that these remains demonstrate weaker bone structure (through
>>reductions in peak bone-mass) and evidence of articular damage(3).
>
>I am not sure I know what "articular damage" refers to. Could you please
>explain? (Maybe just a technical term of good ole "arthritis"? :-\ )
Sorry, I don't agree with you here. Articular damage is joint damage. I'm
pretty convinced that it would be due to arthritis, but I think I would have
a fight on my hands trying to defend my position against some of the
practitioners who specialize in that area. You wouldn't believe how I've
been trashed on alt.support.arthritis on that very point. :=)
>>W.J.Lutz (4) has offered an alternative perspective on the "French Paradox."
>>(The "French Paradox" is the unusually low rate of death by myocardial
>>infarction among the French despite quite high per-capita rates of fat
>>consumption.)
>
>I know this may be being a bit picky about the languare here, but is there
>any reason "myocardial infarct" could not more simply be rendered as "heart
>attack" so it would be more clear to more people, or is there some reason
>"heart attack" is just not considered an accurate-enough term, and
>therefore it is mandatory to use "myocardial infarct" instead?
Nope, just sloppy writing. I tell my students to write what they mean, and
don't use specialized words unless they are necessary for clarity and
precision..... then I have to admit to the same error today. Don't tell my
students, okay?
>Further on...
>
>>This work is confirmed by Simmoon's observation that there is a negative
>>correlation between the frequency of antigen HLA-B8 and the length of time
>>wheat farming has been practised in various parts of Europe (19).
>
>What is "antigen HLA-B8," is this negative correlation good or bad, and
>what does it do in the body?
Sorry that presumes familiarity with celiac disease. It is a gene. It
indicates a predisposition for celiac disease. Although it is present in 20%
to 30% of the population, only a small fraction of those who have it develop
celiac disease.
A huge majority of celiacs have this gene.
It doesn't tell me a whole lot that there is a
>negative correlation when I don't even know what HLA-B8 is in the first
>place. I thought an antigen was a foreign protein the body reacted to by
>producing antibodies. The above statement--in my mind--seems to suggest
>that somehow a substance the body does not produce somehow varies with the
>consumption of wheat. That doesn't seem to make sense to me. Either that,
>or I am just not getting something here. Please explain.
I was saying (although not clearly) that the incidence of this gene is
reduced with an increased duration of wheat consumption. This suggests to me
that perhaps some of the other people with autoimmune diseases, and gluten
sensitivity, associated with HLA-B8 are suffering from gluten consumption.
It must have been serious enough, and the onset early enough (prior to
reproduction) to reduce this gene's representation in the gene pool.
>>Another interesting study done in China produced what the investigators
>>found to be rather surprising results(8). In this investigation, the
>>researchers plotted the diets of more than 3500 rural Chinese women, and
>>measured their levels of SHBG (sex-hormone binding globulins). They were
>>very surprised to find that wheat consumption, and perhaps reduced fish
>>consumption, were the strongest predictors of levels of SHBG, which would
>>indicate an increased risk of cardiovascular disease.
>
>I cannot figure out from the above whether the levels of SHBG went up or
>down in relation to wheat and fish consumption, only that there is some
>sort of correlation. Does SHBG go up when wheat and fish consumption go up,
>or is it the reverse?
It is the reverse, although I'm not clear about why. The SHBG correlate
positively with HDLs, which bespeaks a reduced risk of atherosclerosis.
That means that wheat consumption is associated with reductions in SHBG, and
therefore, with an increased risk.
> Furthermore, it is not clear to me from the above
>whether *higher* or *lower* levels of SHBG result in an increased or
>decreased risk of cardiovascular disease. It only seems to say that there
>is some sort of correlation, but what that correlation is is unclear to me
>here. Beyond this, what the heck do sex-hormone binding globulins (SHBG) do
>in the body in the first place, and why would it be good or bad if their
>levels went up or down?
As near as I can tell, they bind to sex hormones in the blood, presumably
for wasting, but I'm not at all sure of that. Why do you ask such difficult
questions?
>>Another study has connected gluten with neurological illness (9). This group
>>of researchers tested 53 patients with neurological illness of unknown
>>origin for antibodies against gliadin. More than half of them (30 people)
>>demonstrated these antibodies. Nine of those folks proved to have celiac
>>disease, but the other 21 only demonstrated an immune response to gluten, of
>>a type that is often dismissed as meaningless. This study has some
>>far-reaching implications for neurological research.
>
>This seems clear enough--that an immune response to gluten might still be
>problematic even if the person does not have classic hereditary markers for
>celiac disease.
Hey! That's one point for me!
>>Yet another indication that celiacs are not the only segment of the
>>population to suffer from the adverse effects of gluten is a study that was
>>carried out on a very small group of siblings of celiacs(10). When subjected
>>to rectal gluten challenge, half of the siblings showed an immune response
>>to gluten, but these results did not correlate with the hereditary
>>predictors of celiac disease.
>
>I am not sure I understand the underlying assumptions here you are basing
>your statements on. Are you saying that certain immune responses somehow
>are used as "markers" for certain hereditary characteristics (which perhaps
>cannot be directly determined except through these markers) that may
>predict for celiac disease? And that there are additional immune responses
>that you are postulating may also predict for it, but conventional
>scientific wisdom does not yet acknowledge them?
I'm saying that 1/2 of the siblings tested with a rectal gluten challenge
showed an immune response (either elevated levels of a specific type of
lymphocytes, or damage to the intestinal villi). This gluten sensitivity did
not correlate with the genetic markers we associate with gluten sensitivity
and celiac disease. That is, somehow another (probably genetic) factor also
seems to be at work in gluten sensitivity.
>>As for the connection between autoimmunity and cereal grains, it is clear
>>and compelling. The theoretical perspective of molecular mimicry suggests
>>that gliadin-derived peptides may activate the immune system against
>>collagenous tissues, and since intestinal permeability (not celiac disease)
>>is all that is required to allow the passage of these peptides into the
>>bloodstream, a significant number of many types of autoimmune diseases seem
>>likely to benefit from a gluten-free diet (11 ).
>
>This seems clear enough except for the part about collagen. According to my
>dictionary, collagen is a "fibrous protein constituent of bone, cartilage,
>tendon, and other connective tissue." So what? What is the point about
>collagen here? I would guess there is perhaps sp,e postulation being made
>here that the immune system's action against collagen could be the
>mechanism behind bone deterioration seen in Neolithic farming communities,
>but this is a leap I am simply guessing at.
No, my point is that in many autoimmune diseases, such as some types of
arthritis, celiac disease, some types of nephropathy, etc., there is
damage to the collagen.
> Is this is fact what is being
>suggested, or am I completely off base? I am unclear.
I think that gluten will eventually be revealed as one of the primary
causes of autoimmune diseases which are now thought to have multiple
interacting causes.
>>In total, then, there are several studies which demonstrate (often
>>coincidentally) that a much larger group than those with celiac disease are
>>mounting an immune response against gluten, and that this response is
>>causing or contributing to serious illness. Phytic acid in whole cereal
>>grains binds to minerals, including calcium. This chemical bond is not
>>broken in the GI tract. The net result is the binding and wasting of
>>much-needed dietary calcium, even among those whose immune systems can
>>tolerate gluten, and these grains may be implicated in osteoporosis (12).
>
>Okay, clear enough.
>
>>I would now like to draw your attention back to the issue of malignancy.
>>_Medical Hypotheses_ will soon publish a paper I have written which
>>suggests (among other things) that gluten may be implicated in a great many
>>cases of lymphoma (14). Gluten has been demonstrated to interfere with the
>>celiac patient's ability to mount an immune response to malignancies
>>(15,16,17). In my paper, I have postulated a dynamic whereby gluten may have
>>a similar effect in others who are simply sensitive to gluten, or who have a
>>sub-clinical form of this disease.
>
>This is clear language--thanks.
>
>>I would like to suggest that the evidence from antiquity, the pattern of the
>>spread of agriculture in Europe coinciding with the patterns of civilizatory
>>illnesses, the levels of SBHG associated with wheat consumption, the high
>>incidence of gliadin antibodies among those with neurological illnesses of
>>unknown origin, the sensitivity to gluten among siblings of celiacs in spite
>>of the absence of genetic indicators associated with celiac disease, and my
>>own investigation of the literature regarding lymphoma, all point to the
>>strong possibility that gluten is a dangerous substance to many more people
>>than just celiacs.
>
>Several questions here. Again, please explain what gliadin is and why
>antibodies against it would be something that might lead to neurological
>illness. What are the possible mechanisms you would postulate? And again,
>what do SBHGs do in the body, and are their correlated levels with
>increased wheat consumption ones of increase or decrease, and is more or
>less SBHG good or bad? I don't have the background in physiology or
>pathology to have a clue about any of this.
>
>Thanks, Ron. I know it may seem tedious to you to explain these things, but
>remember, not all of us have the background you do. I take Discover
>magazine, Science News, and read several issues of Scientific American a
>year, and I like to think I am science-literate for a layperson, but I am
>really struggling here with some of this.
Yes, this was written for a group of people who have celiac disease. Most of
us know that most celiacs have HLA-B8. We may not be too clear on what that
is, but we know it is in most celiacs, but only in a minority of the general
population. I guess I should have altered it for the list.
I was also under some time constraints. I had promised the organizer that I
would keep the talk under 15 minutes. (She knows me.) You might not believe
this, but I do get a little carried away, at times, and she didn't want me
going on and on for hours.
Thanks for your comments, Ward.
Best Wishes,
Ron
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