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    Willem-Karel Dicke: Pioneer in Gluten-free Diet in the Treatment of Celiac Disease


    Jefferson Adams
    Image Caption: Willem-Karel Dicke treats a patient Circa 1955.

    This article originally appeared in the Spring 2009 edition of Journal of Gluten Sensitivity.


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    Celiac.com 05/15/2010 - Willem-Karel Dicke was born in 1905, in Dordrecht, Holland, and died Utrecht in 1962.  Dicke was a Dutch pediatrician, the first clinician to develop the gluten-free diet, and to prove that certain types of flour cause relapses in celiac disease patients.

    From 1922 until 1929, Dicke studied medicine in Leiden.  He then specialized in pediatrics in Juliana Children’s Hospital in The Hague from 1929 until 1933.  In 1936, at just 31 years of age, he was named medical director of the hospital. 

    In the 1940s and 1950s he went on to formally establish the gluten-free diet, forever changing treatment methods and clinical outcomes of children suffering from celiac disease.  By 1952, Dicke recognized that the disease is caused by the ingestion of wheat proteins, not carbohydrates. 

    From the late 1880s into the 1920s and 30s, doctors like R. A. Gibbons, Sidney Haas and others pioneered the use of specialty diets to treat celiac disease.  Diets such as the banana diet, the fruit diet, the carbohydrate diet (fruit, puree of potatoes or tomatoes), the beefsteak diet, the milk diet had all been tried, with some success.

    In his now seminal 1950 thesis on celiac disease and wheat-free diet, Dicke lays out the results of the detailed dietary study he conducted over several years at the Juliana Children’s Hospital on a patient with celiac disease.

    The study likely had its earliest beginnings at the advent of Dicke’s promotion to medical director, if not slightly before.  From the testimony of Dicke’s wife in 1991, we know that Dicke was convinced of the beneficial effect of wheat free diet even before 1940.  She confirmed that between 1934 and 1936, Dicke began to conduct experiments with wheat free diets confirming Christopher Booth’s comments in The Lancet, Feb 25, 1989:

    “It was a young mother’s statement of her celiac child’s rash improving rapidly if she removed bread from the diet that alerted his interest,” when Dicke was a pediatrician in The Hague in 1936.

    Dicke published his first report on a wheat-free diet in Het Nederlands Tijdschrift voor Geneeskunde in 1941.  (W. K. Dicke: A simple diet for Gee-Herter’s Syndrome).  At the time, celiac was still called Gee-Herter’s syndrome.  It reads, in part:

    “In recent literature it is stated that the diet of Haas (Banana-diet) and Fanconi (fruit and vegetables) gives the best results in the treatment of patients suffering from coeliac disease.  At present (World War II) these items are not available.  Therefore, I give a simple diet, which is helping these children at this time of rationing.  The diet should not contain any bread or rusks.  A hot meal twice a day is also well tolerated.  The third meal can be sweet or sour porridge (without any wheat flour).”

    In the Netherlands, the last winter of World War II, the winter of 1944/45 became known as the ‘Winter of Hunger.’ 

    Delivery of regular food staples, such as bread, was largely disrupted, especially in the western part of the country.  This meant that people had to turn to uncommon foods, such as tulip bulbs, for sustenance.  It was during this time that Dicke became even more convinced that eating less grain, along with unusual foods, such as tulip bulbs, improved the clinical condition of his patients. 

    Dicke’s next major confirmation came when Allied planes started dropping bread in the Netherlands, and these same children began to deteriorate rapidly. 

    After World War II, Dicke conducted a series of experiments with standardized diets were performed on four children in the Wilhelmina Children’s Hospital in Utrecht and in one child in the Juliana Children’s Hospital in The Hague.  These experiments involved excluding or adding wheat or rye flour over long periods in the diets of these children with coeliac disease. 

    In Dicke’s post-war experiments, children were challenged with different cereals under a strict dietary protocol with measurement of total fecal output, fecal fat content, and the fat absorption coefficient was calculated.

    Dicke worked closely with biochemist J. H. van de Kamer of the Netherlands Central Institute for Nutritional Research TNO in Utrecht, who developed the first accurate and easily available method for measure fecal fat content in wet feces.  Dicke also worked closely with H. A. Weyers, a pediatrician from the Wilhelmina Children’s Hospital in Utrecht, who developed a method that used the coefficient of fat absorption to analyze fecal fat excretion in children with celiac disease.

    Based on these findings Dicke concluded in his 1950 thesis that wheat flour, but not well-purified wheat starch (amylum), and also rye flour, triggered the anorexia, the increased fecal output, and the streatorrhea common in celiac patients.  Dicke presented his doctoral thesis on the subject at the University of Utrecht in 1950.

    Dicke’s 1950 thesis refers to a celiac disease patient he treated in 1936.  The patient’s symptoms disappeared and he returned to normal weight and growth patterns after following a strict wheat free diet in the hospital.  However, each time the boy went home and was unable to maintain a wheat free diet, he suffered a decline in his growth curve. 

    Dicke charted these advances and reversals over four long-term admissions.  Each time the trend towards normal growth was restored.  In his thesis, Dicke presents several growth curves of children treated with a wheat free diet.  In long term studies over several years he shows that, with a wheat free diet, these children gain weight, reaching normal growth patterns when compared with age matched controls.  At the end of chapter 3 of his thesis he concludes that:

    “- if certain types of meal, such as wheat and rye are replaced in the daily diet, the patient improves;
    - acute attacks of diarrhea, do not occur, provided these types of meal are not given;
    - after a latent period which can vary in length, deterioration and acute attacks of diarrhea re-occur, if the objectionable types of meal are added to the diet too soon....”

    In 1953, together with van de Kamer and Weyers, he subsequently published Coeliac disease IV “An investigation into the injurious constituents of wheat in connection with their action on patients with coeliac disease.”

    They wrote that the alcohol soluble or the gliadin component of the water insoluble protein of wheat was responsible for the fat malabsorption in patients with celiac disease. 

    Although these findings were quickly confirmed by researchers in Britain, Scandinavia, and Germany, some researchers, especially in America, questioned the wisdom of a gluten free diet.

    After the establishment of the intestinal biopsy technique for the diagnosis of celiac disease, it became apparent that a wheat free diet should be maintained for long periods before an adequate response occurred, as Dicke had predicted. 

    In 1954, Dr. Dicke, Charlotte Anderson, and a number of their colleagues, confirmed these findings, and described the damage to the lining of the small intestine as being directly related to celiac disease.

    In 1957 he was appointed a professor of Utrecht University and became a medical director of Wilhelmina Children’s Hospital.

    To honor Willem Karel Dicke, Netherland’s Society of Gastroenterology established a gold medal in his name, to be presented to pioneering researchers in the field.  Willem Dicke himself was named as the recipient of the first gold Dicke Medal.

    Dr. Dicke died in 1962 of cerebrovascular disease.  He was just 57 years old.

    Jefferson Adams is a freelance writer living in San Francisco.  His poems, essays and photographs have appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden’s Ferry Review, Huffington Post, the Mississippi Review, and Slate among others.

    Sources:

    • Willem Dicke.  Brilliant Clinical Observer and Translational Investigator.  Discoverer of the Toxic Cause of Celiac Disease, by David Yan and Peter R.  Holt , M.D. DOI: 10.1111/j.1752-8062.2009.00167.x
    • GUT 1993; 34:1473-1475
    • Mulder, C.  “Pioneer in Glutenfree diet: Willem Karel Dicke 1905-1962 Over 50 Years of Gluten Free Diet.”  appended to: English translation by C.  Mulder June 1, 1993 of  Dicke, W.K.  “Coeliac Disease  Investigation of Harmful Effects of Certain Types of Cereal on Patients Suffering from Coeliac Disease.” Ph.  D.  Thesis, State University of Utrecht, 1950
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    Guest Hildegard Savage

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    Thank you, Jefferson Adams, for having done this valuable research, and for writing the article. All of us celiacs should know what Dr. Dicke did for us.

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    Guest Michelle

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    Very interesting about the history.

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    Thank you Mr. Adams, and a special thanks to Dr. Dicke for his extended efforts and studies. If it weren't for him, perhaps we still wouldn't know why we get sick like we do.

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    Guest isi keller

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    Surprised to read that porridge was offered as a food for celiac children. In my life as a glycemic index person I cannot tolerate oats in any way along with Millet. Sorghum is high on my list of no nos for glycemic index diets. The first time I ate it I did so in the belief it was gluten-free .After being layed low for a couple of days after eating it, I checked it out and was horrified to read its classified as a low gluten food.

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    Very interesting, a doctor who paid attention to the food supply and related effects...

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    Thank you, Jefferson Adams, for having done this valuable research, and for writing the article. All of us celiacs should know what Dr. Dicke did for us.

    His son now 75 is also a brilliant doctor on the edge and saving lives of cancer patients in Arlington Texas. I am a 23 year metastatic breast cancer survivor.

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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    Scott Adams
    We have recently reported on Lancet (1) a consistent cohort of patients affected by drug-resistant epilepsy with cerebral calcifications, half of which were cured by a gluten-free diet. All had an atrophic jejunal mucosa, which recovered on a gluten free diet. Gluten intolerance is now a recognized cause of brain calcifications and epilepsy, of dementia, of psychiatric disturbances: many researchers believe that, in genetically predisposed subjects, gluten is not healthy for the brain function (2).
    This is just too much.
    Having had over 25 years of variegated experience with gluten intolerance I find hard to imagine that the single most common food intolerance to the single most diffuse staple food in our environment might provoke such a complexity of severe adverse immune-mediated reactions in any part of the human body and function. The list is endless, but malignancies, adverse pregnancy outcome and impaired brain function are indeed complications above the tolerable threshold of this food intolerance.
    On the other end today we know very well that the majority (as many as 9 to 1) of gluten intolerant subjects, identified by familial or population screening, do not manifest any complaint, although they do have a flat intestinal mucosa (3).
    In conclusion a sizable proportion of our population (from 0.3 to 1%) is gluten intolerant and reacts with a wide spectrum of symptoms from no apparent reaction to severe life-threatening diseases.
    This intolerance is strongly linked to specific genetic markers which have indeed required thousands years to develop and be selected: the 'population genetic' time is of this dimension, while the changes in the environment and in the food we eat, require centuries or less.
    Where did they come from?
    Hunters, Fishers and Gatherers
    Human beings have been on Earth for over 3 millions year, but Homo Sapiens Sapiens, our nearest parent, is only 100,000 years old. For ninety thousand years he conducted a nomadic life getting food by hunting, fishing and collecting fruits, seeds, herbs and vegetables from nature. Only quite recently (about 10.000 years ago) did some nomadic tribes start to have stable settlements because they developed the ability to gather enough food to be stored. The cultivation of wild seeds begun.
    Ten thousand years ago the last glaciation came to an end: a Neo-thermal period ensued which marked the passage from the Paleolithic to the Neolithic age. Ices melted gradually from the equator to the poles over several thousands years when new fertile and humid lands were uncovered in South East Asia all of Europe was still covered with ice and Northern Countries had to wait up to 4000 years more to get out from a frozen environment.
    The Great Revolution: The First Farmers
    The discovery in the Neolithic age of ways to produce and store food has been the greatest revolution mankind ever experienced. Passage from collection to production originates the first system in which human labor is transferred onto activities which produced income for long periods of time. The principle of property was consolidated and fortifications to protect the land and food stores were developed.
    Archeological findings suggest that this revolution was not initiated by the man hunter and warrior, but by the intelligent observations made by the woman. The woman carried the daily burden of collecting seeds, herbs, roots and tubers. Most probably she used a stick to excavate roots and tubers: during this activity she observed the fall of grain seeds on the ground and their penetration into the soil with rain. She may have been surprised to find new plants in the places which she herself dug with a stick, and made the final connection between fallen seeds and new 'cultivated' plants.
    She was, for thousands years, the sole leader of the farming practices and provided a more and more consistent integration to the scanty products of the man hunter (6).
    To our actual knowledge, the origin of farming practices should be located in the 'Fertile Crescent': the wide belt of South East Asia which includes Southern Turkey, Palestine, Lebanon and North Iraq. In the highlands of this area abundant rainfall was caused by the neo-thermal switch. In all of this area existed, and still exists, a wide variety of wild cereals, sometimes in natural extended fields, induced by the rainfalls. Triticum Dicoccoides (wheat) and Hordeum Spontaneum (barley) were common and routinely collected by the local dwellers. The wild cereals had very few seeds (2-4) which fell easily on the ground on maturation.
    The people from the Uadi el-Natuf Tell of South East Asia (7800 B.C.) provided the first traces of the gradual shift from hunters to grain cultivators. Their economy was based on the hunt of the gazelle, but their diet also included collected grain seeds. These gradually came to form a substantial proportion of their energy input, as cultivation practices ensued. There were no grinding stones or mills and it was most probable that gathering prevailed on cultivation. But during the Proto-Neolithic superior a cuneiform mortar appeared. 1000-2000 years later (5000 B.C.) wild animals, more rare due to incoming drought, formed only 5% of the daily diet, while cereals and farmed animals become a sizable part of it (4).
    Stable settlements were founded: the village of Catal-Huyuk in Southern Turkey had a population of 5000 inhabitants 9000 years B.C. In that area a collection of sickles was found with inserted oxidian blades, smoothed by the routine contact with the siliceous stalk of cereals. The sickles indicate that it was possible to collect seeds not only by picking on the ground, but also by cutting stems of plants which were capable of retaining the seed in an ear (5). 'Mesopotamic' populations, originated in the first farmers, developed a great civilization with large cities and powerful armies to defend their land property and food stores. In Egypt a civilization based on farming practices developed in the 5th millennium: they became specialists in the cultivation of wheat, barley (to produce beer) and flax.
    The Expansion Of The Farmers
    While in South East Asia the progressive drought made hunting difficult and encouraged farming, in Europe the Paleolithic culture of hunters and gatherers persisted for 5000 years more, gradually transforming into the Mesolithic age.
    In the 'Fertile Crescent' the availability of food stores and the gradual development of animal farming stimulated an unprecedented demographic explosion. The nuclear family had had a small dimension for hundreds thousands of years: the birth rate had been limited by nomadic life. In transmigrations the mother had been able to carry one infant, while the others had been obliged to walk and move on their own. Small babies in between had less chances of surviving. Thus mankind remained of approximately the same size during entire ages.
    Farmers, on the contrary, were settlers, possessed food stores and most probably took advantages in the farming practices of more hands in the family. In this manner the family size exploded and, as a result, a progressive continuous need to gain more lands ensued.
    The farmer's expansion lasted from 9000 B.C. up to the 4000 B.C. when they reached Ireland, Denmark and Sweden covering most cultivable lands in Europe. The expansions followed the waterways of Mediterranean and of Danube across the time of Egyptians, Phoenicians, Greeks and Romans (7).
    The farmers' expansion was not limited to the diffusion of the agricultural practices, but was a 'demic' expansion: that is a substantial replacement of the local dwellers, the Mesolithic populations of Europe, by the Neolithic from South East Asia. More than 2/3 of our actual genetic inheritance originated in this new population, while the native genetic background has been progressively lost or confined to isolated geographical areas.
    The genetic replacement of the native European population is marked by the B8 specificity of the HLA system. Cavalli Sforza and coworkers showed that the migration of farmers is paralleled by the diffusion of B8. The frequency of B8 is inversely proportional to the time length of wheat cultivation. In practice B8 appears to be less frequent in populations which have lived on wheat for a longer time, as it is caused by a negative genetic selection in wheat cultivators (7). We are aware that in Ireland, where the wheat cultivation came only 3000 years B.C., a very high frequency of gluten intolerance has been reported.
    The Evolution Of Cereals
    The early wild cereals, of the Triticum (wheat) and Hordeum (barley) species were genetically diploid and carried few seeds, which usually fell on the ground at maturation, making any harvest very difficult. A chromosomes in single couples (diploidicity) allowed for a wide genetic and phenotypic heterogeneity with remarkable variations in the content of protein and starches. Poliploid plants occasionally originated in nature, but they had few chances to survive, without artificial (cultivation) practices and were usually lost (8).
    The beginning of farming, with the use of irrigation, allowed the survival, and the expansion, of poliploid grains. But the new poliploid grains had substantially reduced genetic variations (since each gene is represented in several copies) and more frequently autoimpollinate themselves, causing remarkable increase of the genetic uniformity.
    The first stable formation of poliploid grains is dated around 6000 years B.C.: the genetic uniformity caused a considerable rise in stability and yield, convincing the early farmer to induce a progressive and rapid replacement of the wild species.
    Genetic variability of grains was essential in order to adapt the plant to the very different environmental conditions of different areas, but the yield was generally low (9).
    Triticum Turgide Dicoccoides was crossed with Triticum Fanschii to originate the Triticum Aestivum, which is the progenitor of all our actual wheat. The Aestivum is an esaploid wheat with 42 chromosomes, versus the 14 of the T. Monococcum. Such powerful grain replaced all existing varieties to the point where genetic variability nowadays is lost: over the world we have 20,000 cultivated species of the same unique T. Aestivum wheat. The Triticum Turgidum Dicoccoides, progenitor of the actual 'durum' wheat with which pasta is made, had just few seeds encapsulated into a pointed and twilled kernel: at maturation the seeds fell on the soil and penetrated into it with rain, eased by the arrow-shaped structure of the kernel.
    Ten thousand years ago it was difficult to pick them up: hence the attempt, made by the Neolithics, to select varieties which could retain the seed longer, in order to allow for an harvest.
    Genetic variability was already substantially reduced in Roman times: 'farrum', i.e. spelt, (T. Dicoccoides) and 'Siligo' (T. Vulgaris) were the common grains. Siligo was used for bread making and contained a certain amount of gluten, while spelt, used mainly for soups, was poorer in gluten content (10).
    But cultivation of wheat and barley was not started or diffused in the whole world: only a small geographic area (South East Asia) developed gluten-containing cereals. In Asia rice was the cultivated species, while in America maize prevailed and in Africa sorghum and millet. All these plants were present in nature and were gradually cultivated in the places of origin (7).
    In our part of the world grains had for centuries been selected in order to improve their homogeneity and productivity, but soon (Roman times or before?) another desirable quality was preferred: the ability to stick, to glue up a dough to improve bread making. Early bread making activities pushed towards grains that contained greater amounts of a structural protein which greatly facilitated the bread making: the gluten. Gluten was not chosen because of its, at the time unknown, nutritional value (which is not absolutely special, since it is a protein with relatively low nutritional value), but for its commercial qualities.
    Rice, maize, sorghum, millet do not contain gluten: no leavened bread was prepared with them: the majority of mankind never lived on bread, as we do know it.
    Over the last 200 years of our modern age active genetic selection, and actual genetic manipulation, have changed the aspect of the original Triticacee enormously: from few grains and little gluten to great wheat harvests very enriched in gluten (50% of the protein content), well adapted to cultivation practices and ready to be handled by monstrous machinery.
    The Rise Of The Intolerance To Gluten
    Did everybody adapt to such profound changes in the basic nutrition over such a short period of time? South Eastern populations, presumably well adapted to the new foods, grossly replaced the existing Mesolithic European dwellers who still lived on hunting and gathering. But a proportion of the local populations (or, rather, of their inheritance ) persisted beside the invaders. The feeding changes were not well tolerated by everybody.
    The best similar example is lactose intolerance: populations that have more recently adapted to milk consumption, still lack the genetic ability to digest lactose over the infancy period. Environment has changed centuries before any change in the inheritance may have been possible.
    Similarly a considerable proportion of the hunters and gatherers of the pre-Neolithic ages have not fully adapted to the great feed changes induced by the cultivation of wheat. These people could not recognize gluten as a 'tolerable' protein available for digestion and absorption: they may have not have any problem or complaint for centuries, since the content of gluten in the grains was very low, but when 'industrial' quantities of gluten were induced by selection of wheat in order to improve bread making, they were exposed to unbearable quantities of an 'intolerable' protein or peptide.
    This population, genetically identifiable today by their specific HLA pattern, did not recognized, through their HLA system, the gluten peptide as a tolerable item, but, because of the similarity of some sequences of gliadin peptides with several pathogenic viruses, they generate a complex defense mechanism (an immune response) which does not eventually find the pathogen to destroy, and most probably activate an auto-immune response which ultimately is the origin of the damage to their intestine and other organs.
    These fierce descendants of hunters and fishers, exposed to this subtle enemy, could not develop the defense of tolerance and, in the attempt to fight the unknown, they ultimately develop a disease due to excess defense. For centuries they underwent a negative selective pressure, with less chances to survive, and then to be manifest (11).
    In the last millennium gluten-intolerant children mostly had a harsh time behind them: after weaning, malabsorption and malnutrition were the underlying causes of poor defense to infections during infancy and early childhood. Acute infectious diarrhea was the main killer of infants up to 50 years ago in Europe and up to 15 babies every thousand died for this condition. In the suburbs of Naples, only 25 years ago, infectious diarrhea was the main killer (25% on an infant mortality rate of 100 per thousands live births) (12).
    The vast majority of gluten intolerance occurred among these poor infants. In my own clinical experience 25 years ago I observed several fatal gastrointestinal infections in babies with the 'celiac crisis', which has now disappeared from our wards.
    Few chances to survive, few intolerant children that reached the reproductive age, and become capable of transmitting the intolerance, few adult cases. Then gluten intolerance may have become extinct, as was in fact the case with several other pathogenic conditions? Not at all.
    The intolerance most probably had some selective advantage which counterbalanced the gluten intolerance: it is possible to suggest that it was their very effective HLA Class II system that gave them a selective advantage against infections, which compensated the disadvantage due to gluten intolerance.
    When, in the last 50 years, infantile infections greatly diminished, the descendants of the hunters and gatherers with very active immune-defense, 'over reacted' more frequently to the gluten than to their ordinary enemy. Hence the rise of the cohort that now appears to manifest, in different manners, a gluten intolerance.
    However, not all populations of the world were ever exposed to such a nasty protein: the vast majority of mankind, after the development of agriculture, lived on maize, rice, sorghum and millet, tubers: all gluten free. All of them did not underwent the selective pressure of gluten intolerance and they may in fact have been the reservoir of wild genes.
    Finally, breast feeding most probably played a major role in preserving some children from the fatal infection of infancy (13). The capacities of breast milk to protect against viral and bacterial attack, the protection given by maternal antibodies and the delaying effect on the manifestation of symptoms of gluten intolerance (in the predisposed subjects) may all have protected the hunters and gatherers, who in this manner avoided to develop fatal symptoms and managed to survive and transmit their genes to our population.
    Hints On The Epidemiology Of Gluten Intolerance
    The epidemiology of gluten intolerance, as we know it today, is the complex result of the apparition of the population of hunters and gatherers in our modern world.
    As the cohort of those born before the World War II had few chances to survive infancy, we nowadays have few adult cases and few long term complications. Where the intolerance is still manifested mainly in the classical way (infants and small children, malabsorption, diarrhea, often switched on by an infection) we do not frequent encounter 'atypical' presentations and adult cases or long term complications. In this case the epidemiological calculations on observed cases made by gastroenterologist may be in great contrast with those made by pediatricians. On the contrary the rarity of 'classical' cases, which has been used as the proof of the 'disappearance' of gluten intolerance, is counterbalanced by the presence of atypical and late diagnosis, where actively searched for.
    Finally nutritional attitudes have played a major role with regard to the chances for hunters to manifest themselves in different age groups: the example of Sweden as compared to the nearest Denmark or Finland is paradigmatic (14).
    As shown by Maki et al, the ability to identify atypical cases may completely change the observed epidemiological pattern in a given region. Hence the reason for the 'iceberg': most cases still to be discovered (15). Similarly, population-based screening programs uncover more 'silent' than overt cases (3).
    Nevertheless, the 'cohort effect', regional differences and so on, have up to now failed to overcome the limits of numbers: when local incidence rates are compared with other regions' rates, the 95% Confidence Intervals of the rates are very often so wide to contain the all lot of observed rates. No clear-cut statistical difference has really been shown in the incidence of gluten intolerance in Europe (16).
    Wherever extensive studies on symptomatic cases have been run an incidence of 1 case per each 1000 live births has been reached, but very often the incidence has been much lower: up to 1 cases every 250 live births. Population screening studies invariably come to an incidence rate of 1 every 250. This is very close to the rate predicted by age-adjusted incidence density studies (17). Recent reports indicate an incidence close to 1 case per every 100 live births, but this finding needs confirmation.
    Gluten Sensitive Versus Gluten Intolerant
    But the epidemiology of gluten intolerance, which entails the tracing of a group of our ancestors, may completely change once we consider the increasing knowledge about the 'gluten-sensitive' individuals. 6 to 10% of first degree relatives of known cases themselves are gluten intolerant and have a flat intestinal mucosa (these are silent cases), but up to 30% of sibs of cases, when challenged with a dose of gluten (or its digest) activates a specific mucosal immune-response (with increase in intraepithelial infiltration and activation of T-Cells), without having any sign of mucosal damage (potential cases?) (18).
    We may, in the near future, have a substantial group of individuals who do not activate, in presence of gluten, a 'pathogenic' immune response (auto-immunity), but who recognize gluten as a 'suspect' protein in the same way as their peers really intolerant.
    Finally gluten intolerance is indeed linked to a specific genetic predisposition: most probably at least two genetic loci are involved in running the risk of intolerance.
    How many possess these specific genetic risk at a 'carrier' state? Certainly more than 5% of the actual population. In conclusion we have a wide population of 'gluten-reactants' in Europe (EC): at least 1 million cases of total intolerance to gluten - an estimated similar amount of 'gluten sensitive' people - 10-15 times more 'carriers' of the risk of becoming gluten intolerant.
    So we have found our ancestral hunters and gatherers: they are a substantial proportion of our actual community and do deserve a 'gluten-free' alternative not only as a therapeutic mean, but as an option of our daily life.
    References Gobbi G, Bouquet F, Greco L, Lambertini A, Tassinari CA, Ventura A, Zaniboni MG: "Coeliac Disease, epilepsy and cerebral calcifications" Lancet, 340, Nx 8817, 439-443, 1992 Epilepsy and other neurological disorders in Coeliac Disease. Republic of S. Marino Meeting, April 10-12 1995, G. Gobbi edt., Raven Press, in preparation. Catassi C, Ratsch IM, Fabiani E, Rossini M, Bordicchia F, Candela F, Coppa GV, Giorgi PL: Coeliac Disease in the year 2000: exploring the iceberg. Lancet, 1994, 343: 200-203. Furon R. Manuel de Prehistorie Generale., 1958, Payor, Paris. Cambel H, Braidwood RJ. An old farmer's village in Turkey. Le Scienze, 1970, 22: 96-103. Heichelheim F. An Ancient Economic History. A.W. Sijthoff edt., Leiden, 1970. Cavalli-Sforza L. Chi Siamo (Who are we). 1993 Mondadori, Milano. Raven PH, Evert RF, Eichorn S Biology of plants. 4th ed. Worth Publ. Inc, New York, 1986. Feldman M, Sears ER The wild gene resources of wheat. Scientific American, 1981: 98-109. Lucio Giunio Moderato Columella " Libri rei rusticae" Anni 60-65 dopo Cristo. Ed. Einaudi,1977. Simoons FJ: Coeliac Disease as a Geographic Problem. Food, Nutrition and Evolution, 1982, 179-199. Greco,L.: " Malnutrizione di classe a Napoli" Inchiesta, 24, 53-63, 1976. Greco,L., Mayer,M., Grimaldi,M., Follo,D., De Ritis,G., Auricchio,S.: "The effect of Early Feeding on the onset of Sympthoms in Coeliac Disease" J.Pediat. Gastroenterology Nutrition, 4:52-55, 1985. Maki M, Holm K, Ascher H, Greco L.: Factors affecting clinical presentation of coeliac disease: role of type and amount of gluten containing cereals in the diet. In "Common Food Intolerances 1: Epidemiology of Coeliac Disease", Auricchio S, Visakorpi JK, editors, Karger, Basel, 1992, pp 76-83. Maki M, Kallonen K, Landeaho ML, Visakorpi JK.:Changing pattern of childhood coeliac disease in Finland. Acta Paediatr Scand 1988; 77:408-412. Greco L, Maki M, Di Donato F, Visakorpi JK. Epidemiology of Coeliac Disease in Europe and the Mediterranean area. A summary report on the Multicentric study by the European Society of Paediatric Gastroenterology and Nutrition. In "Common Food Intolerances 1: Epidemiology of Coeliac Disease", Auricchio S, Visakorpi JK, editors, Karger, Basel, 1992, pp 14-24. Magazzu, Bottaro G, Cataldo F, Iacono G, Di Donato F, Patane R, Cavataio F, Maltese I, Romano C, Arco A, Totolo N, Bragion E, Traverso G, and Greco L: "Increasing Incidence of childhood celiac disease in Sicily: results of a multicentric study" Acta Paediatr, 83:1065-1069, 1994. Troncone R, Greco L, Mayer M, Mazzarella G, Maiuri L, Congia M, Frau F, De Virgiliis S, Auricchio S.: "In half of Siblings of Coeliac Children rectal gluten challenge reveals gluten sensitivity not restricted to coeliac HLA.

    Roy Jamron
    This article appeared in the Summer 2008 edition of Celiac.com's Scott-Free Newsletter.
    Celiac.com 06/16/2008 - Do vitamin D deficiency, gut bacteria, and timing of gluten introduction during infancy all combine to initiate the onset of celiac disease? Two recent papers raise the potential that this indeed may be the case. One paper finds that when transgenic mice expressing the human DQ8 heterodimer (a mouse model of celiac disease) are mucosally immunized with gluten co-administered with Lactobacillus casei bacteria, the mice exhibit an enhanced and increased immune response to gluten compared to the administration of gluten alone.[1] A second paper finds that vitamin D receptors expressed by intestinal epithelial cells are involved in the suppression of bacteria-induced intestinal inflammation in a study which involved use of germ-free mice and knockout mice lacking vitamin D receptors exposed to both friendly and pathogenic strains of gut bacteria.[2] Pathogenic bacteria caused increased expression of vitamin D receptors in epithelial cells. Friendly bacteria did not.
    If one considers these two papers together, one notices: (1) Certain species of gut bacteria may work in conjunction with gluten to cause an increased immune response which initiates celiac disease; (2) The presence of an adequate level of vitamin D may suppress the immune response to those same gut bacteria in such a way as to reduce or eliminate the enhanced immune response to gluten caused by those gut bacteria, thus preventing the onset of celiac disease.
    Vitamin D has recently been demonstrated to play a role in preserving the intestinal mucosal barrier. A Swedish study found children born in the summer, likely introduced to gluten during winter months with minimal sunlight, have a higher incidence of celiac disease strongly suggesting a relationship to vitamin D deficiency.[3] Recent studies found vitamin D supplementation in infancy and living in world regions with high ultraviolet B irradiance both result in a lower incidence of type 1 diabetes, an autoimmune disease closely linked to celiac disease.[4][5]
    Gut bacteria have long been suspected as having some role in the pathogenesis of celiac disease. In 2004, a study found rod-shaped bacteria attached to the small intestinal epithelium of some untreated and treated children with celiac disease, but not to the epithelium of healthy controls.[6][7] Prior to that, a paper published on Celiac.com[8] first proposed that celiac disease might be initiated by a T cell immune response to "undigested" gluten peptides found inside of pathogenic gut bacteria which have "ingested" short chains of gluten peptides resistant to breakdown. The immune system would have no way of determining that the "ingested" gluten peptides were not a part of the pathogenic bacteria and, thus, gluten would be treated as though it were a pathogenic bacteria. The new paper cited above[1] certainly gives credence to this theory.
    Celiac disease begins in infancy. Studies consistently find the incidence of celiac disease in children is the same (approximately 1%) as in adults. The incidence does not increase throughout life, meaning, celiac disease starts early in life. Further, in identical twins, one twin may get celiac disease, and the other twin may never experience celiac disease during an entire lifetime. Something other than genetics differs early on in the childhood development of the twins which initiates celiac disease. Differences in vitamin D levels and the makeup of gut bacteria in the twins offers a reasonable explanation as to why one twin gets celiac disease and the other does not. Early childhood illnesses and antibiotics could also affect vitamin D level and gut bacteria makeup. Pregnant and nursing mothers also need to maintain high levels of vitamin D for healthy babies.
    Sources:
    [1] Immunol Lett. 2008 May 22.
    Adjuvant effect of Lactobacillus casei in a mouse model of gluten sensitivity.
    D'Arienzo R, Maurano F, Luongo D, Mazzarella G, Stefanile R, Troncone R, Auricchio S, Ricca E, David C, Rossi M.
    http://dx.doi.org/10.1016/j.imlet.2008.04.006
    [2] The FASEB Journal. 2008;22:320.10. Meeting Abstracts - April 2008.
    Bacterial Regulation of Vitamin D Receptor in Intestinal Epithelial Inflammation
    Jun Sun, Anne P. Liao, Rick Y. Xia, Juan Kong, Yan Chun Li and Balfour Sartor
    http://www.fasebj.org/cgi/content/meeting_abstract/22/1_MeetingAbstracts/320.10
    [3] Vitamin D Preserves the Intestinal Mucosal Barrier
    Roy S. Jamron
    https://www.celiac.com/articles/21476/
    [4] Arch Dis Child. 2008 Jun;93(6):512-7. Epub 2008 Mar 13.
    Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis.
    Zipitis CS, Akobeng AK.
    http://adc.bmj.com/cgi/content/full/93/6/512
    [5] Diabetologia. 2008 Jun 12. [Epub ahead of print]
    The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide.
    Mohr SB, Garland CF, Gorham ED, Garland FC.
    http://www.springerlink.com/content/32jx3635884xt112/
    [6] Am J Gastroenterol. 2004 May;99(5):905-6.
    A role for bacteria in celiac disease?
    Sollid LM, Gray GM.
    http://dx.doi.org/10.1111/j.1572-0241.2004.04158.x
    [7] Am J Gastroenterol. 2004 May;99(5):894-904.
    Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease.
    Forsberg G, Fahlgren A, Hörstedt P, Hammarström S, Hernell O, Hammarström ML.
    http://dx.doi.org/10.1111/j.1572-0241.2004.04157.x
    [8] Are Commensal Bacteria with a Taste for Gluten the Missing Link in the Pathogenesis of Celiac Disease?
    Roy S. Jamron
    https://www.celiac.com/articles/779/


    Jefferson Adams
    Celiac.com 01/08/2014 - Push-back mounts against a controversial new report alleging that genetically engineered foods may trigger gluten sensitivity and celiac disease.
    In the first salvo, Celiac Disease Foundation CEO Marilyn Geller derided the report, published last week by the Institute for Responsible Technology (IRT), as merely "speculative."
    Then followed comments by leading plant geneticist, Dr. Wayne Parrott, professor of crop science at the University of Georgia, that the report relied on "a handful of deeply flawed"studies and ignored "more than 1,000 studies that have been published in refereed journals and which show that GM crops are as safe as their counterparts."
    According to Geller, no one has offered scientific evidence "for a GMO/celiac disease link that is supported by the CDF Medical Advisory Board.
    For their part, the authors of the IRT report admit that there is no data to prove that GMO consumption causes gluten sensitivity.
    However, they try to hedge slightly by claiming that more and more research shows that GMO consumption may worsen celiac symptoms or lead to gluten sensitivity. Here again, they offer no good data to support their claims.
    Source:
    FoodNavigator.com

    Jefferson Adams
    Celiac.com 05/12/2014 - Currently, researcher know almost nothing about the natural history and evolution of celiac disease in ancient populations.
    But, a set of recently unearthed bones from ancient Rome show signs of a struggle with celiac disease, and may help researchers to better understand the natural history and evolution of the condition.
    Researchers believe the bones are those of an 18 to 20-year old upper class Roman woman, who likely had celiac disease or gluten intolerance, as her skeleton reveals signs of malnutrition and osteoporosis and her attempts to manage it by changing her diet.
    DNA analysis has confirmed that the woman carried two copies of an immune system gene variant strongly associated with celiac disease. Although celiac disease can be influenced by numerous environmental factors, the gene variant is found in nearly all contemporary celiac populations.
    The combination of genetic risk factors and malnutrition in someone likely to have good access to nutritious food, make celiac disease a reasonable diagnosis, says Gabriele Scorrano, a biological anthropologist at the University of Rome Tor Vergata.
    An article about the study appears in Nature, and the study itself appears in the American Journal of Physical Anthropology.

  • Recent Articles

    Jefferson Adams
    Celiac.com 07/19/2018 - Maintaining a gluten-free diet can be an on-going challenge, especially when you factor in all the hidden or obscure gluten that can trip you up. In many cases, foods that are naturally gluten-free end up contain added gluten. Sometimes this can slip by us, and that when the suffering begins. To avoid suffering needlessly, be sure to keep a sharp eye on labels, and beware of added or hidden gluten, even in food labeled gluten-free.  Use Celiac.com's SAFE Gluten-Free Food List and UNSAFE Gluten-free Food List as a guide.
    Also, beware of these common mistakes that can ruin your gluten-free diet. Watch out for:
    Watch out for naturally gluten-free foods like rice and soy, that use gluten-based ingredients in processing. For example, many rice and soy beverages are made using barley enzymes, which can cause immune reactions in people with celiac disease. Be careful of bad advice from food store employees, who may be misinformed themselves. For example, many folks mistakenly believe that wheat-based grains like spelt or kamut are safe for celiacs. Be careful when taking advice. Beware of cross-contamination between food store bins selling raw flours and grains, often via the food scoops. Be careful to avoid wheat-bread crumbs in butter, jams, toaster, counter surface, etc. Watch out for hidden gluten in prescription drugs. Ask your pharmacist for help about anything you’re not sure about, or suspect might contain unwanted gluten. Watch out for hidden gluten in lotions, conditioners, shampoos, deodorants, creams and cosmetics, (primarily for those with dermatitis herpetaformis). Be mindful of stamps, envelopes or other gummed labels, as these can often contain wheat paste. Use a sponge to moisten such surfaces. Be careful about hidden gluten in toothpaste and mouthwash. Be careful about common cereal ingredients, such as malt flavoring, or other non-gluten-free ingredient. Be extra careful when considering packaged mixes and sauces, including soy sauce, fish sauce, catsup, mustard, mayonnaise, etc., as many of these can contain wheat or wheat by-product in their manufacture. Be especially careful about gravy mixes, packets & canned soups. Even some brands of rice paper can contain gluten, so be careful. Lastly, watch out for foods like ice cream and yogurt, which are often gluten-free, but can also often contain added ingredients that can make them unsuitable for anyone on a gluten-free diet. Eating Out? If you eat out, consider that many restaurants use a shared grill or shared cooking oil for regular and gluten-free foods, so be careful. Also, watch for flour in otherwise gluten-free spices, as per above. Ask questions, and stay vigilant.

    Jefferson Adams
    Celiac.com 07/18/2018 - Despite many studies on immune development in children, there still isn’t much good data on how a mother’s diet during pregnancy and infancy influences a child’s immune development.  A team of researchers recently set out to assess whether changes in maternal or infant diet might influence the risk of allergies or autoimmune disease.
    The team included Vanessa Garcia-Larsen, Despo Ierodiakonou, Katharine Jarrold, Sergio Cunha,  Jennifer Chivinge, Zoe Robinson, Natalie Geoghegan, Alisha Ruparelia, Pooja Devani, Marialena Trivella, Jo Leonardi-Bee, and Robert J. Boyle.
    They are variously associated with the Department of Undiagnosed Celiac Disease More Common in Women and Girls International Health, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America; the Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom; the Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom; the Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom; the Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom; the Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom; and Stanford University in the USA.
    Team members searched MEDLINE, Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) for observational studies conducted between January 1946 and July 2013, and interventional studies conducted through December 2017, that evaluated the relationship between diet during pregnancy, lactation, or the first year of life, and future risk of allergic or autoimmune disease. 
    They then selected studies, extracted data, and assessed bias risk. They evaluated data using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). They found 260 original studies, covering 964,143 participants, of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies, covering 542,672 participants, of other maternal or infant dietary exposures, including 80 trials of 26 maternal, 32 infant, or 22 combined interventions. 
    They found a high bias risk in nearly half of the more than 250 milk feeding studies and in about one-quarter of studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with probiotics during late pregnancy and lactation may reduce risk of eczema. 44 cases per 1,000; 95% CI 20–64), and 6 trials, suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitization to egg. GRADE certainty of these findings was moderate. 
    The team found less evidence, and low GRADE certainty, for claims that breastfeeding reduces eczema risk during infancy, that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus, and that probiotics reduce risk of infants developing allergies to cow’s milk. 
    They found no evidence that dietary exposure to other factors, including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake, influence risk of allergic or autoimmune disease. 
    Overall, the team’s findings support a connection between the mother’s diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitization to food, respectively.
    Stay tuned for more on diet during pregnancy and its role in celiac disease.
    Source:
    PLoS Med. 2018 Feb; 15(2): e1002507. doi:  10.1371/journal.pmed.1002507

    Jefferson Adams
    Celiac.com 07/17/2018 - What can fat soluble vitamin levels in newly diagnosed children tell us about celiac disease? A team of researchers recently assessed fat soluble vitamin levels in children diagnosed with newly celiac disease to determine whether vitamin levels needed to be assessed routinely in these patients during diagnosis.
    The researchers evaluated the symptoms of celiac patients in a newly diagnosed pediatric group and evaluated their fat soluble vitamin levels and intestinal biopsies, and then compared their vitamin levels with those of a healthy control group.
    The research team included Yavuz Tokgöz, Semiha Terlemez and Aslıhan Karul. They are variously affiliated with the Department of Pediatric Gastroenterology, Hepatology and Nutrition, the Department of Pediatrics, and the Department of Biochemistry at Adnan Menderes University Medical Faculty in Aydın, Turkey.
    The team evaluated 27 female, 25 male celiac patients, and an evenly divided group of 50 healthy control subjects. Patients averaged 9 years, and weighed 16.2 kg. The most common symptom in celiac patients was growth retardation, which was seen in 61.5%, with  abdominal pain next at 51.9%, and diarrhea, seen in 11.5%. Histological examination showed nearly half of the patients at grade Marsh 3B. 
    Vitamin A and vitamin D levels for celiac patients were significantly lower than the control group. Vitamin A and vitamin D deficiencies were significantly more common compared to healthy subjects. Nearly all of the celiac patients showed vitamin D insufficiency, while nearly 62% showed vitamin D deficiency. Nearly 33% of celiac patients showed vitamin A deficiency. 
    The team saw no deficiencies in vitamin E or vitamin K1 among celiac patients. In the healthy control group, vitamin D deficiency was seen in 2 (4%) patients, vitamin D insufficiency was determined in 9 (18%) patients. The team found normal levels of all other vitamins in the healthy group.
    Children with newly diagnosed celiac disease showed significantly reduced levels of vitamin D and A. The team recommends screening of vitamin A and D levels during diagnosis of these patients.
    Source:
    BMC Pediatrics

    Jefferson Adams
    Celiac.com 07/16/2018 - Did weak public oversight leave Arizonans ripe for Theranos’ faulty blood tests scam? Scandal-plagued blood-testing company Theranos deceived Arizona officials and patients by selling unproven, unreliable products that produced faulty medical results, according to a new book by Wall Street Journal reporter, whose in-depth, comprehensive investigation of the company uncovered deceit, abuse, and potential fraud.
    Moreover, Arizona government officials facilitated the deception by providing weak regulatory oversight that essentially left patients as guinea pigs, said the book’s author, investigative reporter John Carreyrou. 
    In the newly released "Bad Blood: Secrets and Lies in a Silicon Valley Startup," Carreyrou documents how Theranos and its upstart founder, Elizabeth Holmes, used overblown marketing claims and questionable sales tactics to push faulty products that resulted in consistently faulty blood tests results. Flawed results included tests for celiac disease and numerous other serious, and potentially life-threatening, conditions.
    According to Carreyrou, Theranos’ lies and deceit made Arizonans into guinea pigs in what amounted to a "big, unauthorized medical experiment.” Even though founder Elizabeth Holmes and Theranos duped numerous people, including seemingly savvy investors, Carreyrou points out that there were public facts available to elected officials back then, like a complete lack of clinical data on the company's testing and no approvals from the Food and Drug Administration for any of its tests.
    SEC recently charged the now disgraced Holmes with what it called a 'years-long fraud.’ The company’s value has plummeted, and it is now nearly worthless, and facing dozens, and possibly hundreds of lawsuits from angry investors. Meantime, Theranos will pay Arizona consumers $4.65 million under a consumer-fraud settlement Arizona Attorney General Mark Brnovich negotiated with the embattled blood-testing company.
    Both investors and Arizona officials, “could have picked up on those things or asked more questions or kicked the tires more," Carreyrou said. Unlike other states, such as New York, Arizona lacks robust laboratory oversight that would likely have prevented Theranos from operating in those places, he added.
    Stay tuned for more new on how the Theranos fraud story plays out.
    Read more at azcentral.com.

    Jefferson Adams
    Celiac.com 07/14/2018 - If you’re looking for a simple, nutritious and exciting alternative to standard spaghetti and tomato sauce, look no further than this delicious version that blends ripe plum tomatoes, garlic, olive oil, basil, and firm sliced ricotta to deliver a tasty, memorable dish.
    Ingredients:
    12 ounces gluten-free spaghetti 5 or 6 ripe plum tomatoes ¼ cup extra virgin olive oil 2 cloves garlic, crushed ¾ teaspoons crushed red pepper ¼ cup chopped fresh basil 2 tablespoons chopped fresh parsley Kosher salt and black pepper ⅓ cup pecorino Romano cheese, grated ½ cup firm ricotta, shaved with peeler Directions:
    Finely chop all but one of the tomatoes; transfer to large bowl with olive oil and ¼ teaspoon salt.
    Cook spaghetti until al dente or desired firmness, and drain, reserving ¼ cup cooking water. 
    Meanwhile, chop remaining tomato, and place in food processor along with garlic, red pepper, and ½ teaspoon salt; puree until smooth. 
    Gently stir mixture into the bowl of chopped tomatoes.
    Add cooked spaghetti, basil and parsley to a large bowl.
    Toss in tomato mixture, adding some reserved pasta water, if needed. 
    Spoon pasta into bowls and top with Romano cheese, as desired.