I had the pleasure of contributing a few suggestions and helping to edit
copy on the following speech, which was written by Ron Hoggan and presented
at the Annual General Meeting of the Calgary Chapter of the Canadian Celiac
Association on March 15, 1997.
Hoggan is a noted writer on celiac disease whose work has appeared in
numerous places, including at least one paper published in MEDICAL
HYPOTHESES.
Hoggan is also member of this mailing list, but agreed to let me post this
as the first official message for this list. Comments or questions on the
following speech are invited.
Dean Esmay
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Gluten is a Dubious Luxury of Non-Celiacs
by
Ron Hoggan
(Note: In this paper I use the term "gluten" generically, as we celiacs
use it, to refer to all proteins peculiar to cereal grains.)
One must wonder why, in spite of increasing lifespans in the advanced
industrialized nations, modern medicine has failed to clearly identify the
cause of many neurological, autoimmune and malignant diseases. The
gluten-free diet is only recommended where there is a clear indication of
advanced, gluten-induced disease, but is this the best advice?
We may sometimes feel disadvantaged by the strict gluten-free diet we have to
follow. It is costly and inconvenient. But perhaps it is those who continue
to consume glutinous foods who should be concerned. Gluten, while dangerous to
celiacs, has never been investigated for deleterious effects on the general
population. Yet we have studies that show that hunter-gatherers following
traditional life-ways do not develop the neurological, auto-immune and
malignant diseases that people living in the industrialized world
experience, and these people rarely eat gluten-rich foods (1,2). There is
already compelling evidence connecting the advent of agriculture to bone
and joint disease (3), and humankind has only been cultivating cereal
grains for approximately 10,000 years (2,4), which is but a brief moment in
evolutionary terms. Remember too, it is only a small population located in
the Near East, that has had that length of exposure to cereal grains (4);
most of the world has had agriculture for an even shorter period of time.
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. Yet this area of
investigation appears to have been avoided in research on these health
problems. One must wonder at the cause of this neglect of such an
important possibility.
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? Many are the commonest
signs of celiac disease, and they were apparently the rule, not the
exception, in cultures adapting to agriculture.
We know, from paleontologists' 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).
Additionally, ancient Egyptians, who consumed a diet that would be
considered very "heart-healthy" in our culture, have left behind mummies
which clearly demonstrate atherosclerosis (7). While the evidence from the
ancients is compelling, there can always be counter-arguments and debates
when we are reaching back as far as 10,000 years into the past. Yet a few
marginal pockets of scientific enquiry have explored a few elements of
modern implications of this issue.
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.) Dr. Lutz has studied the spread of agriculture through
Europe. He presents a picture whereby the spread of agriculture, and thus
the period of time a culture has been exposed to cereal grains, is
inversely related to the incidence of cardiovascular disease. The
underlying assumption, of course, is that the longer the exposure, the
greater the likelihood that those who were intolerant to these grains were
trimmed from the gene pool of such cultures; it seems that the less time a
culture has been exposed to gluten, the greater the portion of the
population that continues to develop cancers and cardiovascular disease.
(Lutz also provides similarly compelling data on the rates of breast cancer
mortality.)
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).
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.
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.
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.
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 ).
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).
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.
Ray Audette, a populist writer, has said that Stanislaw Tanchou "....gave
the first formula for predicting cancer risk. It was based on grain
consumption and was found to accurately calculate cancer rates in major
European cities. The more grain consumed, the greater the rate of cancer."
Tanchou's paper was delivered to the Paris Medical Society in 1843(20).
We hear all the time about pollution in the industrial world being the
source for modern man's high incidence of cancer. It is the chemical
additives, we are told, in the food we eat, that causes much of the
problem. Perhaps.
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.
Sources:
1. Eaton B, Konner M, Shostak M, " Stone Agers in the Fast Lane: Chronic
Degenerative Diseases in Evolutionary Perspective" _The American Journal of
Medicine_ 1988; 84:739-749
2. Eaton S, Konner M, "Paleolithic Nutrition" _NEJM_ 1985; 312(5): 283-289
3. Eaton S, Nelson D, "Calcium in evolutionary perspective" _Am. J. Clin.
Nutr._1991; 54: 281S - 287S
4. Lutz W J, "The Colonisation of Europe and Our Western Diseases" _Medical
Hypotheses_ 1995; 45: 115-120
5. Lindeberg S, et al. "Cardiovascular risk factors in a Melanesian
population apparently free from stroke and ischaemic heart disease:
the Kitava study" _J Intern Med_ 1994 Sep.
6. Lewin R, "A Revolution of Ideas in Agricultural Origins" _Science_ 1988;
240: 984-986
7. Zimmerman M, "The paleopathology of the cardiovascular system" _Tex Heart
Inst J_ 1993; 20(4): 252-257
8. Gates et. al. "Association of dietary factors and selected plasma
variables with sex hormone-binding globulin in rural Chinese women"
Am J Clin Nutr 1996; 63: 22-31.
9. Hadjivassiliou M, Gibson A, Davies-Jones G, Lobo A, Stephenson T,
Milford-Ward A, "Does cryptic gluten sensitivity play a part in neurological
illness?" _Lancet_ 1996; 347: 369-371
10. Troncone R, Greco L, Mayer M, Mazzarella G, Maiuri L, Congia M, Frau F,
deVirgilis S, Auricchio S, "In Siblings of Celiac Children, Rectal Gluten
Challenge Reveals Gluten Sensitization Not Restricted to Celiac HLA"
_Gastroenterology_ 1996; 111: 318-324
11. Ostenstad B, Dybwad A, Lea T, Forre O, Vinje O, Sioud M, "Evidence for
monoclonal expansion of synovial T cells bearing V Alpha 2.1/V beta 5.5
gene segments and recognizing a syntehtic peptide that shares homology with
a number of putative autoantigens"
12. Lindeberg, Staffan, personal correspondence Feb, 1997
14. Hoggan R, "Considering Wheat, Rye, and Barley Proteins as Aids to
Carcinogens" _Medical Hypotheses_ In Press 1997.
15. Maclaurin B, Cooke W, Ling N, "Impaired lymphocyte reactivity against
tumour cells in patients with coeliac disease" _Gut_ 1971; 12: 794-800
16. Egan L, Walsh S, Stevens F, Connolly C, Egan E, McCarthy C,
"Celiac-Associated Lymphoma" _Journal of Clinical Gastroenterology_ 1995;
21(2): 123-129
17. Swinson C, Slavin G, Coles E, Booth C, "Coeliac Disease and Malignancy"
_Lancet_ 1983; Jan 15: 111-115
18. Armelagos G, Van Gerven D, Martin D, Huss-Ashmore R, "Effects of
Nutritional Change on the Skeletal Biology of Northeast African (Sudanese
Nubian) Populations" _From Hunters to Farmers The Causes and Consequences of
Food Production in Africa_ Clark & Brandt (eds.) 1984; II: 37-146
19. Simoons F, "Celiac disease as a geographic problem" _Food, Nutrition
and Evolution_ 1981; eds. Walcher D, and Kretchmer N, Masson Publishing,
New York
20. Audette R, lowcarb listserv at: <[log in to unmask]>, March 11, 1997
from: Vilhjalmur Stefansson's book _Cancer Disease of
Civilization_ 1960; Hill and Wang, New York, NY.
Background Sources:
21. Davis D, "Paleolithic Diet, Evolution, and Carcinogens" _Science_ 1987;
238: 1633-1634
22. Carpenter K, "Protein requirements of adults from an evolutionary
perspective" _Am J Clin Nutr_1992; 55: 913-917
23. Eaton S, "Humans, Lipids and Evolution" _LIPIDS_ 1992; 27(10): 814-819
24. Troncone R, Greco L, Mayer M, Mazzarella G, Maiuri L, Congia M, Frau F,
deVirgilis S, Auricchio S, "In Siblings of Celiac Children, Rectal Gluten
Challenge Reveals Gluten Sensitization Not Restricted to Celiac HLA"
_Gastroenterology_ 1996; 111: 318-324
25. Marsh M, "Bone Disease and Gluten Sensitivity: Time to Act, to Treat,
and to Prevent" _The American Journal of Gastroenterology_ 1994; 89(12):
2105-2107
26. Young T, Hochman R, Scopelliti J, "Celiac Disease and Arthropathy: Case
Report and Literature Review" _The Guthrie Journal_ 1993; 62(3): 99-104
27. Lindh E, Ljunghall S, Larsson K, Lavo B, " Screening for antibodies
against gliadin in patients with osteoporosis" _Journal of Internal
Medicine_ 1992; 231: 403-406
28. de Boer W, Maas M, Tytgat G, "Disappearance of Mesenteric
Lymphadenopathy with Gluten-Free Diet in Celiac Sprue" _Journal of Clinical
Gastroenterology_ 1993; 16(4): 317-319
29. Mathus-Vliegen E, Halteren H, Tytgat G, "Malignant lymphoma in coeliac
disease: various manifestations with distinct symptomatology and prognosis?"
_Journal of Internal Medicine_ 1994; 236: 43-49
30. Rosenberg S, "The Low-Grade Non-Hodgkin's Lymphomas: Challenges and
Opportunities" _Journal of Clinical Oncology" 1985; 3(3): 299-310
28. Swinson C, Coles E, Slavin G, Booth C, "Coeliac Disease and Malignancy"
_Lancet_ 1983; Jan 15: 111-115
31. Wright D, Jones D, Clark H, Mead G, Hodges E, Howell W, "Is adult-onset
coeliac disease due to a low-grade lymphoma of intraepithelial T
lymphocytes?" _Lancet_ 1991; 337: 1373-1374
32. Gouldie R, Lee F, "Coeliac disease and lymphoma" _Lancet_ 1991; 338: 570
33. Freeman H, Weinstein W, Shnitka T, Piercey J, Wensel R, " Pirmary
abdominal Lymphoma" _The American Journal of Medicine_ 1977; 63: 585-594
34. Holmes G, Piror P, Lane M, Pope D, Allan R, "Malignancy in coeliac
disease-effect of a gluten free diet" _Gut_ 1989; 30: 333-338
35. Sturgess R, Ciclitira P, "Coeliac disease and lymphoma" _Lancet_ 1991;
338: 318-319
36. Egan L, Walsh S, Stevens F, Connolly C, Egan E, McCarthy C, _Journal of
Clinical Gastroenterology_ 1995; 21(20: 123-129
37. Lopes P, Morris D, Galbraith P, Lillicrap D, Pross H,
"Lymphoproliferative Disease of "Lak Cell" precursor Large Granular
Lymphocytes in Association with Celiac Disease" _American Journal of
Hematology_ 1993; 43: 116-122
38. Black, Paul "Psychoneuroimmunology: Brain and Immunology" _Scientific
American: SCIENCE & MEDICINE_ 1995; 2(6): 16-25
39. Kapur A, Isaacs P, Kelsey P, "Linear IgA dermatosis, coeliac disease,
and extralinear B cell lymphoma" _Gut_ 1995; 37: 731-733
40. Ilyas M, Niedobitek G, Agathanggelou A, Barry R, Read A, Tierney R,
Young L, Rooney N, "NON-HODGKIN'S LYMPHOMA, COELIAC DISEASE, AND
EPSTIEN-BARR VIRUS: A STUDY OF 13 CASES OF ENTEROPATHY-ASSOCIATED T- AND
B-CELL LYMPHOMA" _Journal of Pathology_ 1995; 177: 115-122
41. Cooke W, Holmes G, _Coeliac Disease_ 1984; Churchill Livingstone, NY
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