THE FIBER CONTROVERSY
A Critique of "Fiber Deficiency" ALBERT I. MENDELOFF, M.D.
Johns Hopkins School of Medicine, Baltimore, Maryland
The patterns of disease are constantly changing, both for the physician and the veterinarian. These changes have always posed challenges to scient i s t s - w h a t has happened to the people or the animals? What has altered in the air they breathe, in the water they drink, or the food they eat? Our current ecological awareness of the subtle and not-sosubtle changes in the milieu we inhabit makes us suspicious of the long-range implications of even the most minute changes in our way of life. By the same awareness, we realize that the changes wrought in that milieu over the past century, even the past generation, may have been of great magnitude and may be exerting deleterious or favorable effects on the generation now entrusted with the earth. Alas, we also realize that it is probably impossible to know what those alterations may have been, since we didn't know what to measure then, nor do we now. Still, the rational spirit is dauntless; the ecologically minded, perhaps antiintellectual, attitude now predominating in the Western world, especially among the young, engenders frequent conceptual formulations designed to explain our current human condition. The incredible improvement in life expectation, personal cleanliness, and freedom from infections and infestations our people enjoy have now been deprecated. A resentful reaction to the facts that a new set of diseases threatens our much longer life has begun to dominate current thinking. Surely we must be doing something wrong if we have to die of cancer, even long after age 65; our way of life must be at fault if at 80 we have serious problems with arteriosclerosis. Structural anomalies like hiatus hernia and diverticulosis now are found to have unequal distribution among the world's people, generally paralleling the standard of living and the increasing longevity of the group at highest risk. Into this field have moved various sciDigestive Diseases, Vol. 21, No. 2 (February 1976)
entists and anthropologists, and none has been more assiduous in providing sweeping answers to such problems than the British investigator Dr. Denis Burkitt. Fiber Deficiency and Disease Based on the remarkably infrequent prevalence among some black Africans living in their rural habitats of such disorders as colonic polyps, inflammatory bowel disease of chronic type, diverticular disease of the colon, hiatal hernia, appendicitis, and possibly peptic disease, Dr. Burkitt and his fellow English physicians working in Africa have sought to incriminate the Western diet as the source of most of our chronic diseases. Although it may be true that human health has advanced more in the past century than in all recorded time up to then, we are, they say, now reaping the sad rewards of such victories over disease by encouraging new disorders formerly only rarely encountered. By looking at the diet eaten by the black Africans especially, Dr. Burkitt has selected as the key item the fact that these people have a high dietary intake of vegetable fiber, resulting in a high fecal output, divided into 4-8 stools per day. By his reckoning, this is a very good thing, and alone is responsible for their relative freedom from the colonic disorders noted above, and perhaps also contributes to their infrequent experience with varicose veins and ischemic heart disease. As viewed by Dr. Burkitt, there is a basic dietary need for large amounts of indigestible food fiber, a striking characteristic of the African diet; this postulated need for dietary fiber is not met by Western food intakes; ergo, the Western world suffers from a new dietary disorder, "fiber deficiency." The clinical manifestation of fiber deficiency is first, constipation; by Dr. Burkitt's standards, the stool bulk of Westerners (85-150 g/day) and the frequency of defecation (3-21 stools/wk) to pass it are
109
BURKITT VS MENDELOFF both considerably less than the ideal, ie, African standards of 200-500 g/day passed in 30-60 movements per week. The postulation of dietary deficiency of indigestible food residues as a cause of a multitude of serious and not-so-serious human disorders has the merit of conciseness and of novelty. It has appealed to millions of people as a plausible explanation of chronic illness, one which can readily be cured by simply increasing the intake of foods high in dietary fiber or of preparations of fiber without food. Furthermore, and not least in its appeal, in an energyconscious world the idea that food has its greatest cost benefit when eaten directly as food, rather than as animal tissue expensively created by feeding the original grain to beasts, makes excellent sense. We then have presented to us a logical argument that we should increase our intake of natural grains and vegetables in order to provide more indigestible residues to the colon, where some is broken down by bacteria to other materials, absorbable or not, and some is left to increase the bulk of fecal residue reaching the left colon and ultimately the rectum. Attempts to support this argument from medical observations have included the indubitable fact that high-residue feeding does change the microbial flora of the colon in that the bacteria become more aerobic; this is thought to be desirable because anerobes have the ability to convert neutral steroids and other lipid-soluble materials into potential or actual carcinogens. A further postulate is that increased residues result, on average, in more frequent evacuations of larger volume stools, and that therefore the time of contact of these postulated carcinogens with the colonic mucosa is reduced by the increased colonic traffic per 24 hr; by inference, colonic neoplasms-polyps and carcinomas--are less likely to find favorable circumstances for growth; furthermore, the increased bulk in the left half of the colon favors lower intraluminal pressure, less contractile effort of the colonic musculature, and less diverticular disease. Obviously, if stools are larger, more frequent, and less productive of high intraluminal pressures, constipation will cease to exist, straining at stool will not be necessary, and varicose veins will not be produced. At the other end of the abdominal cavity, straining pressures will not push the stomach up through the diaphram, and hiatus hernia will cease to be a problem. Inside the lumen, the insoluble fibers will bind up a number of noxious materials, will reduce the reabsorption of bile acids, and thus decrease the lithogenicity of bile. 1 10
Analysis of Postulated Relations between Dietary Fiber and Physiology Basic Dietary Data. There is something terribly simplistic about all this, and life is just not simple. The last 100 years have featured the most dramatic changes in the living style of humans in all recorded time, and one would be unable to mention one single activity--eating, drinking, breathing, walking, love-making, fighting, to name a few--which has not undergone drastic alterations, both quantitative and qualitative. One wonders even whether the air he breathes on any Sunday is the same as on the day before or the day after. How, then, can one decide that diet alone, and only one element of that diet, is capable of accounting for major changes in the prevalence of human diseases over this period? The Burkitt thesis ignores the fact that because Africans eat more dietary fiber they eat less of other items, and these other items are quite variable. We get back to the old nutritional problem of whether dietaries are distinguished because they contain less of A or more of B plus C. There are precious few published analyses of the dietary intakes of more than one group of rural and urban African blacks, although a number of studies have been carried out on the colonic flora of African blacks versus whites on Western diets. The bacteriological changes noted to occur in the stools of persons eating highfiber and low-fiber diets, stressed by Burkitt, have been shown to relate to more consistently to the dietary content of beef protein and beef fat, neither of which is eaten by African rural natives, than to fiber (1). How then can we be sure that African diets differ from Western diets only in fiber? We cannot, and they obviously do not. Fiber and Human Pathophysiology. Elsewhere I have reviewed the specific arguments about the effects of various kinds of fiber on gastroenterologic function; other excellent reviews are available (2). They hardly support the Burkitt hypothesis. In the presence of so many other risk factors for arteriosclerotic disease, the argument for the importance of dietary fiber for that entity becomes rather trivial. For thrombophlebitis, varicose veins, and hemorrhoids, the argument rests on the relationship between fiber in the diet and the frequency of bowel movements. This relationship is capable of reproducible demonstration only in studies with patients who have infrequent stools; fed large amounts of wheat bran, they have larger and more frequent stools. However, persons who have normally 1-3 stools daily do not respond so readily to increased Digestive Diseases, Vol. 21, No. 2 (February 1976)
THE FIBER CONTROVERSY bran intake by increased bulk, frequently, or rapid transit times (3). It is of interest that persons who have total colectomy, on resumption of their former dietary programs, usually stabilize their bowel pattern at 1-3 movements per day, with a stool bulk very little different from that characterizing their performance before they developed the illness for which the colectomy was carried out. The concept of transit time has received much recent study, for which we can certainly thank the stimulus provided by Dr. Burkitt. The results, however, have been surprising. It has been almost invariably shown that transit times, no matter how measured, may show marked changes without any correlation with the total daily stool volume or weight (3). In an interesting study from Hawaii (4), transit times among the Issei, with a low incidence of colon cancer, were identical with those of the Nisei, a much more colon-cancer-prone group; Hawaiian-Japanese, with an even higher incidence of colon cancer, showed transit times comparable with those of rural Africans! Furthermore, the number of stools passed per day in these three groups were similar and did not correlate with the transit times. Fiber Intake and the Prevalence of Human Disease
It would thus appear that the basic assumptions made by Dr. Burkitt from his observations on rural African bowel habits cannot readily be translated even into simple predictions of colonic function among other peoples. If we look at the other side of the argument, that which rests on the correlation of fiber intake with the incidence and prevalence of various diseases of Western peoples, we encounter other difficulties. Although few would argue that most of these disorders are massively influenced by what we term changes in our environment, it is difficult to be sure that their prevalence is moving unidirectionally. Certainly in the United States (5, 6) and now also in England (7) there has been a very definite decrease in the incidence of acute appendicitis over the past three decades, the same period in which diverticular disease and ischemic heart disease have been increasing. H o w can we defend such divergent trends as due to the same causes? Diverticular disease, which the English work has tended to consider a single entity, consists of two entirely different clinical and pathological entities, one associated with the irritable colon syndrome, found in persons under the age of 45, and a much larger group which is closely age-dependent and in fact is found in a very high percentage of very old Digestive Diseases, Vol. 21, No. 2 (February 1976)
persons; when a disease is expressed, often asymptomatically, in a population s o o l d , one might conclude that it is evidence of a healthy way of life rather than the result of life-long diet deficiency of some dietary ingredient! As to colon cancer, the rapidly accumulating data from all over the world are not in accord with the fiber hypothesis. Epidemiologists concerned with colonic c a n c e r have decided, on the basis o f a number of studies, that this c o m m o n disease is more directly a s s o c i a t e d with increasing a m o u n t s of beef, and especially beef fat, than with variations in fiber intake. Indeed, the most recent reviews (8, 9) o f the e p i d e m i o l o g y o f colon c a n c e r do not even mention dietary fiber as a possible factor. Poiyposis of the colon, a difficult nosoiogic problem, seems, on the basis of meticulous necropsy studies in populations of Hawaiian Japanese and Colombian Indians, to increase in populations with high risk for colorectal carcinoma, although hyperplastic polyps are more closely associated with carcinoma than are adenomatous polyps or diverticulosis. All of these lesions show marked increases with increasing age of the population, and in some clinical and hospital series over 50% of the cases occur in persons over 70 years of age. As noted before, this would be compatible with extraordinarily good health during the three-score years and 15 now expected at birth. Is there a black African population with such a life expectancy? It may just as well be argued that the diet of rural black Africans is detrimental to a long and healthy life; and is fiber the basic noxious agent? I would certainly not say so, but then I would not arbitrarily select one of many dietary possibilities and tout it on the basis of so little evidence, in any case. How then should we look at this hypothesis? First of all, we have to develop better methods of assaying food for its content of "indigestible resid u e " ; currently our highly restricted assay for crude fiber bears a n uncertain relationship to total dietary fiber. The factor by which we multiply the former to obtain the latter must be different for each source of fiber--ie, wheat, oats, rye, v e g e t a b l e s - and we also are certain that those fiber-full materials we now feed to patients differ significantly according to the technology of the processing they receive. Secondly, we must act like scientists when we compare the dietaries of one people with those of a n o t h e r - - w e must look at the entire food intake of each people, not just one item which we have decided a priori to be the most important ingredient.
111
BURKITT
We also must realize that the intake of very large quantities of fibrous foods may well deprive the body of certain minerals and other nutrients by adsorption of the nutrients or by changing intestinal enzyme functions. Thus there may well be for food fiber the same range, from deficiency to surfeit, which characterizes all known types of food intake. We believe that patients with painful diverticular disease usually, but not always, are helped by increasing their dietary fiber intake, and that we have been wrong in the past to restrict it. In short, we are greatly indebted to Dr. Burkitt and his colleagues for stimulating research into a hitherto neglected area of animal nutrition, but we must be skeptical about his sweeping conclusions as to the effects of unspecified qualities of poorly defined nonnutrient materials in preventing and curing chronic disease affecting hundreds of millions of persons.
112
VS MENDELOFF
REFERENCES I. Hill MJ: Bacteria and the etiology of colonic cancer. Cancer 34:815-818, 1974 2. Cummings JH: Dietary fibre. But 14:69-81, 1973 3. Eastwood MA, Fisher N, Greenwood CT, Hutchison JB: Perspectives on the bran hypothesis. Lancet 1:1029-1033, 1974 4. Glober GA, Moore JO, Klein KL, Abra BC: Bowel transit times in two populations experiencing similar colon-cancer risks. Lancet 2:80-81, 1974 5. Mendeloff AI: Prevalence and significance of digestive diseases. Gastroenterology 68:1351-1363, 1975 6. Wylie CM, Holly TL: Is appendicitis decreasing in the U.S. population? PAS Rep 10(5):000, 1972 7. Cove-Smith JR, Langman MJS: Appendicitis and dietary fibre. Gut 16:409, 1975 8. Wynder EL, Reddy BS: Metabolic epidemiology of colorectal cancer. Cancer 34:801-806, 1974 9. Howell MA: Diet as an etiological factor in the development of cancer of the colon and rectum. J Chron Dis 28:67-80, 1975
Digestive Diseases, Vol. 21, No. 2 (February 1976)
A Critique of "Fiber Deficiency" ALBERT I. MENDELOFF, M.D.
Johns Hopkins School of Medicine, Baltimore, Maryland
The patterns of disease are constantly changing, both for the physician and the veterinarian. These changes have always posed challenges to scient i s t s - w h a t has happened to the people or the animals? What has altered in the air they breathe, in the water they drink, or the food they eat? Our current ecological awareness of the subtle and not-sosubtle changes in the milieu we inhabit makes us suspicious of the long-range implications of even the most minute changes in our way of life. By the same awareness, we realize that the changes wrought in that milieu over the past century, even the past generation, may have been of great magnitude and may be exerting deleterious or favorable effects on the generation now entrusted with the earth. Alas, we also realize that it is probably impossible to know what those alterations may have been, since we didn't know what to measure then, nor do we now. Still, the rational spirit is dauntless; the ecologically minded, perhaps antiintellectual, attitude now predominating in the Western world, especially among the young, engenders frequent conceptual formulations designed to explain our current human condition. The incredible improvement in life expectation, personal cleanliness, and freedom from infections and infestations our people enjoy have now been deprecated. A resentful reaction to the facts that a new set of diseases threatens our much longer life has begun to dominate current thinking. Surely we must be doing something wrong if we have to die of cancer, even long after age 65; our way of life must be at fault if at 80 we have serious problems with arteriosclerosis. Structural anomalies like hiatus hernia and diverticulosis now are found to have unequal distribution among the world's people, generally paralleling the standard of living and the increasing longevity of the group at highest risk. Into this field have moved various sciDigestive Diseases, Vol. 21, No. 2 (February 1976)
entists and anthropologists, and none has been more assiduous in providing sweeping answers to such problems than the British investigator Dr. Denis Burkitt. Fiber Deficiency and Disease Based on the remarkably infrequent prevalence among some black Africans living in their rural habitats of such disorders as colonic polyps, inflammatory bowel disease of chronic type, diverticular disease of the colon, hiatal hernia, appendicitis, and possibly peptic disease, Dr. Burkitt and his fellow English physicians working in Africa have sought to incriminate the Western diet as the source of most of our chronic diseases. Although it may be true that human health has advanced more in the past century than in all recorded time up to then, we are, they say, now reaping the sad rewards of such victories over disease by encouraging new disorders formerly only rarely encountered. By looking at the diet eaten by the black Africans especially, Dr. Burkitt has selected as the key item the fact that these people have a high dietary intake of vegetable fiber, resulting in a high fecal output, divided into 4-8 stools per day. By his reckoning, this is a very good thing, and alone is responsible for their relative freedom from the colonic disorders noted above, and perhaps also contributes to their infrequent experience with varicose veins and ischemic heart disease. As viewed by Dr. Burkitt, there is a basic dietary need for large amounts of indigestible food fiber, a striking characteristic of the African diet; this postulated need for dietary fiber is not met by Western food intakes; ergo, the Western world suffers from a new dietary disorder, "fiber deficiency." The clinical manifestation of fiber deficiency is first, constipation; by Dr. Burkitt's standards, the stool bulk of Westerners (85-150 g/day) and the frequency of defecation (3-21 stools/wk) to pass it are
109
BURKITT VS MENDELOFF both considerably less than the ideal, ie, African standards of 200-500 g/day passed in 30-60 movements per week. The postulation of dietary deficiency of indigestible food residues as a cause of a multitude of serious and not-so-serious human disorders has the merit of conciseness and of novelty. It has appealed to millions of people as a plausible explanation of chronic illness, one which can readily be cured by simply increasing the intake of foods high in dietary fiber or of preparations of fiber without food. Furthermore, and not least in its appeal, in an energyconscious world the idea that food has its greatest cost benefit when eaten directly as food, rather than as animal tissue expensively created by feeding the original grain to beasts, makes excellent sense. We then have presented to us a logical argument that we should increase our intake of natural grains and vegetables in order to provide more indigestible residues to the colon, where some is broken down by bacteria to other materials, absorbable or not, and some is left to increase the bulk of fecal residue reaching the left colon and ultimately the rectum. Attempts to support this argument from medical observations have included the indubitable fact that high-residue feeding does change the microbial flora of the colon in that the bacteria become more aerobic; this is thought to be desirable because anerobes have the ability to convert neutral steroids and other lipid-soluble materials into potential or actual carcinogens. A further postulate is that increased residues result, on average, in more frequent evacuations of larger volume stools, and that therefore the time of contact of these postulated carcinogens with the colonic mucosa is reduced by the increased colonic traffic per 24 hr; by inference, colonic neoplasms-polyps and carcinomas--are less likely to find favorable circumstances for growth; furthermore, the increased bulk in the left half of the colon favors lower intraluminal pressure, less contractile effort of the colonic musculature, and less diverticular disease. Obviously, if stools are larger, more frequent, and less productive of high intraluminal pressures, constipation will cease to exist, straining at stool will not be necessary, and varicose veins will not be produced. At the other end of the abdominal cavity, straining pressures will not push the stomach up through the diaphram, and hiatus hernia will cease to be a problem. Inside the lumen, the insoluble fibers will bind up a number of noxious materials, will reduce the reabsorption of bile acids, and thus decrease the lithogenicity of bile. 1 10
Analysis of Postulated Relations between Dietary Fiber and Physiology Basic Dietary Data. There is something terribly simplistic about all this, and life is just not simple. The last 100 years have featured the most dramatic changes in the living style of humans in all recorded time, and one would be unable to mention one single activity--eating, drinking, breathing, walking, love-making, fighting, to name a few--which has not undergone drastic alterations, both quantitative and qualitative. One wonders even whether the air he breathes on any Sunday is the same as on the day before or the day after. How, then, can one decide that diet alone, and only one element of that diet, is capable of accounting for major changes in the prevalence of human diseases over this period? The Burkitt thesis ignores the fact that because Africans eat more dietary fiber they eat less of other items, and these other items are quite variable. We get back to the old nutritional problem of whether dietaries are distinguished because they contain less of A or more of B plus C. There are precious few published analyses of the dietary intakes of more than one group of rural and urban African blacks, although a number of studies have been carried out on the colonic flora of African blacks versus whites on Western diets. The bacteriological changes noted to occur in the stools of persons eating highfiber and low-fiber diets, stressed by Burkitt, have been shown to relate to more consistently to the dietary content of beef protein and beef fat, neither of which is eaten by African rural natives, than to fiber (1). How then can we be sure that African diets differ from Western diets only in fiber? We cannot, and they obviously do not. Fiber and Human Pathophysiology. Elsewhere I have reviewed the specific arguments about the effects of various kinds of fiber on gastroenterologic function; other excellent reviews are available (2). They hardly support the Burkitt hypothesis. In the presence of so many other risk factors for arteriosclerotic disease, the argument for the importance of dietary fiber for that entity becomes rather trivial. For thrombophlebitis, varicose veins, and hemorrhoids, the argument rests on the relationship between fiber in the diet and the frequency of bowel movements. This relationship is capable of reproducible demonstration only in studies with patients who have infrequent stools; fed large amounts of wheat bran, they have larger and more frequent stools. However, persons who have normally 1-3 stools daily do not respond so readily to increased Digestive Diseases, Vol. 21, No. 2 (February 1976)
THE FIBER CONTROVERSY bran intake by increased bulk, frequently, or rapid transit times (3). It is of interest that persons who have total colectomy, on resumption of their former dietary programs, usually stabilize their bowel pattern at 1-3 movements per day, with a stool bulk very little different from that characterizing their performance before they developed the illness for which the colectomy was carried out. The concept of transit time has received much recent study, for which we can certainly thank the stimulus provided by Dr. Burkitt. The results, however, have been surprising. It has been almost invariably shown that transit times, no matter how measured, may show marked changes without any correlation with the total daily stool volume or weight (3). In an interesting study from Hawaii (4), transit times among the Issei, with a low incidence of colon cancer, were identical with those of the Nisei, a much more colon-cancer-prone group; Hawaiian-Japanese, with an even higher incidence of colon cancer, showed transit times comparable with those of rural Africans! Furthermore, the number of stools passed per day in these three groups were similar and did not correlate with the transit times. Fiber Intake and the Prevalence of Human Disease
It would thus appear that the basic assumptions made by Dr. Burkitt from his observations on rural African bowel habits cannot readily be translated even into simple predictions of colonic function among other peoples. If we look at the other side of the argument, that which rests on the correlation of fiber intake with the incidence and prevalence of various diseases of Western peoples, we encounter other difficulties. Although few would argue that most of these disorders are massively influenced by what we term changes in our environment, it is difficult to be sure that their prevalence is moving unidirectionally. Certainly in the United States (5, 6) and now also in England (7) there has been a very definite decrease in the incidence of acute appendicitis over the past three decades, the same period in which diverticular disease and ischemic heart disease have been increasing. H o w can we defend such divergent trends as due to the same causes? Diverticular disease, which the English work has tended to consider a single entity, consists of two entirely different clinical and pathological entities, one associated with the irritable colon syndrome, found in persons under the age of 45, and a much larger group which is closely age-dependent and in fact is found in a very high percentage of very old Digestive Diseases, Vol. 21, No. 2 (February 1976)
persons; when a disease is expressed, often asymptomatically, in a population s o o l d , one might conclude that it is evidence of a healthy way of life rather than the result of life-long diet deficiency of some dietary ingredient! As to colon cancer, the rapidly accumulating data from all over the world are not in accord with the fiber hypothesis. Epidemiologists concerned with colonic c a n c e r have decided, on the basis o f a number of studies, that this c o m m o n disease is more directly a s s o c i a t e d with increasing a m o u n t s of beef, and especially beef fat, than with variations in fiber intake. Indeed, the most recent reviews (8, 9) o f the e p i d e m i o l o g y o f colon c a n c e r do not even mention dietary fiber as a possible factor. Poiyposis of the colon, a difficult nosoiogic problem, seems, on the basis of meticulous necropsy studies in populations of Hawaiian Japanese and Colombian Indians, to increase in populations with high risk for colorectal carcinoma, although hyperplastic polyps are more closely associated with carcinoma than are adenomatous polyps or diverticulosis. All of these lesions show marked increases with increasing age of the population, and in some clinical and hospital series over 50% of the cases occur in persons over 70 years of age. As noted before, this would be compatible with extraordinarily good health during the three-score years and 15 now expected at birth. Is there a black African population with such a life expectancy? It may just as well be argued that the diet of rural black Africans is detrimental to a long and healthy life; and is fiber the basic noxious agent? I would certainly not say so, but then I would not arbitrarily select one of many dietary possibilities and tout it on the basis of so little evidence, in any case. How then should we look at this hypothesis? First of all, we have to develop better methods of assaying food for its content of "indigestible resid u e " ; currently our highly restricted assay for crude fiber bears a n uncertain relationship to total dietary fiber. The factor by which we multiply the former to obtain the latter must be different for each source of fiber--ie, wheat, oats, rye, v e g e t a b l e s - and we also are certain that those fiber-full materials we now feed to patients differ significantly according to the technology of the processing they receive. Secondly, we must act like scientists when we compare the dietaries of one people with those of a n o t h e r - - w e must look at the entire food intake of each people, not just one item which we have decided a priori to be the most important ingredient.
111
BURKITT
We also must realize that the intake of very large quantities of fibrous foods may well deprive the body of certain minerals and other nutrients by adsorption of the nutrients or by changing intestinal enzyme functions. Thus there may well be for food fiber the same range, from deficiency to surfeit, which characterizes all known types of food intake. We believe that patients with painful diverticular disease usually, but not always, are helped by increasing their dietary fiber intake, and that we have been wrong in the past to restrict it. In short, we are greatly indebted to Dr. Burkitt and his colleagues for stimulating research into a hitherto neglected area of animal nutrition, but we must be skeptical about his sweeping conclusions as to the effects of unspecified qualities of poorly defined nonnutrient materials in preventing and curing chronic disease affecting hundreds of millions of persons.
112
VS MENDELOFF
REFERENCES I. Hill MJ: Bacteria and the etiology of colonic cancer. Cancer 34:815-818, 1974 2. Cummings JH: Dietary fibre. But 14:69-81, 1973 3. Eastwood MA, Fisher N, Greenwood CT, Hutchison JB: Perspectives on the bran hypothesis. Lancet 1:1029-1033, 1974 4. Glober GA, Moore JO, Klein KL, Abra BC: Bowel transit times in two populations experiencing similar colon-cancer risks. Lancet 2:80-81, 1974 5. Mendeloff AI: Prevalence and significance of digestive diseases. Gastroenterology 68:1351-1363, 1975 6. Wylie CM, Holly TL: Is appendicitis decreasing in the U.S. population? PAS Rep 10(5):000, 1972 7. Cove-Smith JR, Langman MJS: Appendicitis and dietary fibre. Gut 16:409, 1975 8. Wynder EL, Reddy BS: Metabolic epidemiology of colorectal cancer. Cancer 34:801-806, 1974 9. Howell MA: Diet as an etiological factor in the development of cancer of the colon and rectum. J Chron Dis 28:67-80, 1975
Digestive Diseases, Vol. 21, No. 2 (February 1976)
