Fibre and colorectal cancer

THE LANCET

consumption may arise from the fact that they contain additional, not-yet-identified health-promoting constituents. “Health is not a priority for most people in the course of their daily lives, and only surfaces when health problems emerge. Studies have found little evidence that changes in health related behaviour were a response to formal health messages.”4 Compliance with the requirements, dietary and non-dietary, for lessening the risk for colon cancer seems a forlorn hope, as with breast cancer also.5 *A R P Walker, I Segal *Human Biochemistry Research Unit, Department of Tropical Diseases, School of Pathology of the University of the Witwatersrand, and the South African Institute for Medical Research, Johannesburg 2000, South Africa; and Gastroenterology Unit, Baragwanath Hospital and University of the Witwatersrand

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Wasan HS, Goodlad RA. Fibre-supplemented foods may damage your health. Lancet 1996; 348: 319–20. Boyle P, Kevi R, Lucchini F, La Vecchia C. Trends in diet-related cancers in Japan: a conundrum? Lancet 1993; 342: 752. Walker ARP, Walker BF. Nutrition-related diseases in Southern Africa: with special reference to urban populations in transition. Nutr Res 1995; 15: 1053–94. Austoker J. Diet and cancer. In: Cancer prevention in primary care. London: BMJ Publishing Group, 1995: 171. Walker ARP, Walker BF. Dietary fat and the risk of breast cancer. N Engl J Med 1996; 334: 1606–07.

SIR—Wasan and Goodlad1 correctly point out that there are problems with the definition of dietary fibre. They note epidemiological evidence that dietary fibre protects against colorectal cancer. One of us (MJH) has reviewed 58 publications and can confirm that conclusion. Wasan and Goodlad then discuss the mechanisms whereby dietary fibre might influence development of colorectal cancer, emphasising the importance of crypt-cell proliferation (CCPR) which can be stimulated by some types of “fermentable” fibre substances. There are indeed contradictions in evidence from animal models concerning the protective effects of fibre; the proper conclusion from these should be that studies in animals, where the effect of diet depends on the carcinogen initiator used, its route of administration, and on the sex and strain of animal (table), do not properly describe colorectal cancer in man. The discrepancies do not mean that fibre may promote colorectal carcinogenesis in man; only direct studies in human beings can do that, and the epidemiological evidence only shows protection. Similarly, the authors note that some vitamins which suppress CCPR in the human colon may increase the tumour rate when taken as supplements; this merely calls into question the value of the CCPR as a marker of colon cancer Type of fibre

Cellulose (20% or 40%) Cellulose Cellulose 15% Hemicellulose Hemicellulose Bran (20%) Bran (20%) Bran Bran (20%) Carrot (20%) Pectin (15%) Pectin (15%) Pectin

Rat model

Effect‡

Agent*

Route†

Sex

AOM DMH DMH DMH DMH DMH DMH DMH DMH DMH DNU AOM DMH

sc sc po sc po po sc sc po sc ir sc sc

m M M M M M M .. F M F F M

– ↓ – – ↓ ↓ – ↑ – ↑ – ↓ ↑

For references see Hill’s 1989 review.2 *Carcinogens: AOM=azoxymethane, DMH=dimethylhydrazine, DNU=dimethylnitrosourea. †sc=subcutaneous, po=oral, ir=intrarectal. ‡–=none, ↑=promote, ↓=protect.

Table: Effect of type of fibre, initiating carcinogen, and sex of rats on experimental colon carcinogenesis

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risk. It does not mean that fibre fractions which also suppress CCPR will increase the risk of colon cancer. An observed inverse relation between intake of dietary fibre and risk of human colon cancer remains—and it will do so until we have some substantiated evidence from studies in man that it is not true. In the meantime, what we still need is a good hypothesis to explain it. The hypothesised role of short-chain fatty acids may also be true. Our conclusion from the evidence given by Wasan and Goodlad is that CCPR may not be important and that the animal models must continue to be treated with caution. Your “talking point” on this paper did not emphasise that it was a “viewpoint” and ended with the sweeping statement: “Until we know more about the effects on our health of what we eat, it seems wise to treat with caution the claims made for high-fibre foodstuffs”. The potential claims made for dietary fibre fall under several headings (eg, hyperlipidaemia, cancer, obesity, and diabetes) and a generalised statement could be misleading, especially at a time when other claims are under intense scrutiny—for example, the US Food and Drug Administration is considering a food-specific health claim for oat products and prevention of coronary heart disease.3 Repeated in your press release and picked up by newspapers, television, and radio, this generalised statement was confusing and potentially damaging to the uphill process of achieving improved population dietary change. As longstanding readers of, and contributors to, The Lancet we cannot believe that you intended to do either. ARL has in 1995/96 academic year received funding from the Kellogg Company, and has in the past consulted for Quaker Oats UK Ltd and Ferrosan A/S Denmark.

Michael J Hill, *Anthony R Leeds European Cancer Prevention Organisation UK, Lady Sobell, Gastrointestinal Unit, Wesham Park Hospital, Slough; and *Department of Nutrition, Kings College London, London W8 7AH, UK

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Wasan HS, Goodlad RA. Fibre-supplemented foods may damage your health. Lancet 1996; 348: 319–20. Hill MJ. Experimental studies of fat, fibre and calories in carcinogenesis. In: Miller AB, ed. Diet and the aetiology of cancer. Berlin: Springer Verlag, 1989: 31–38. Food and Drug Administration. Food labeling: health claims; oats and coronary heart disease. Fed Reg 1996; 61: 296–313.

SIR—While the precise influence is difficult to quantify there is a consensus among scientists that diet does have a very significant role in the development of colon cancer and also in some other cancers, and in heart disease, stroke, obesity, diabetes, osteoarthritis, gallstones, varicose veins, haemorrhoids, and diverticulosis, all diseases that are rare in the Third World. Awareness that this epidemic of “diseases of affluence” is related to inappropriate dietary habits has led to the publication of guidelines, all of which recommend an increase in dietary fibre and a reduction in fat. In effect this means a return to a dietary balance that is predominantly plant-based. The current recommendation in the USA is for a doubling in fibre intake to 25–35 g daily. The lack of a universally accepted definition of fibre does not mean that the consumption of foods that contain added fibre by a population whose fibre consumption is low need be harmful. Within a diet that includes different plant-based foods, there will be a variety of types of fibre. Some forms of fibre may be present in greater quantities than others over the lifetime of any individual. Surely, evaluation of the risk of increasing the fibre content of foods should be judged in this context, and in the context of current dietary habits that increase the incidence of many diseases. In 1990, the diet of Americans was judged to be responsible for nearly 40% of deaths.2

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THE LANCET

The consumption of relatively high fibre diets has been associated epidemiologically with a lower risk of colon cancer.3 Animal studies with oat bran have been either neutral or negative but the preponderance of experiments with wheat bran (mostly insoluble fibre) and the azoxymethane/dimethylhydrazine rat model, including our own studies, have demonstrated an inverse relation with colon cancer. We have also demonstrated that colon cancer can be inhibited by psyllium, a cereal that contains 80% fibre, of which 75% is soluble. Synergism between wheat bran and psyllium doubled the colon cancer inhibitory effect.4 Recognising the limitations of chemically-induced colon cancer, we are now collaborating with Dr Makato M Taketo in Japan who has developed a “knockout mouse”, a model that relies on spontaneous genetic mutation not on chemical carcinogenesis.5 Initial results have demonstrated a 37% inhibition of intestinal polyps as a result of exposing these mice to a diet that contained 8% wheat bran fibre and 5% fat by weight. This inhibition is comparable with that observed with both wheat bran and psyllium in the azoxymethane model. Having chosen to concentrate on inconsistencies in experimental data that are as likely to result from methodological as from biological variances, Wasan and Goodlad attempt to justify their position by stating that studies in man have failed to demonstrate a reduced risk of colorectal cancer due to fibre itself. Since this could only be established by prospective studies, and since none have been done, this is hardly surprising. Alluding to problems with beta-carotene does little to clarify the issue; adding fibre to a diet that is deficient is very different from giving a large dose of a single nutrient to a high-risk population. The proposal that the individual constituents of dietary fibre must be evaluated in prospective human trials to establish safety sets a new standard for foods of all sorts. Should we now demand prospective data on the non-detrimental effect of meat and dairy products, or even fish and chips, before they can continue to be sold to the public? George Washington University Medical Center has received unconditional financial support from the Kellogg Company, some of which was allotted to the authors by the university.

*Oliver Alabaster, Narayan Shivapurkar Institute for Disease Prevention, George Washington University Medical Center, Washington, DC 20037, USA

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Wasan HS, Goodlad RA. Fibre-supplemented foods may damage your health. Lancet 1996; 348: 319–20. McGinnis JM, Foege WW. Causes of death in the United States. JAMA 1993; 270: 18. Greenwald P, Lanza P. Role of dietary fibre in the prevention of colon cancer. In: DeVita V, Hellman S, Rosenberg SA, eds. Important advances in oncology. Philadelphia: Lippincott, 1986: 37–54. Alabaster O, Tang ZC, Frost A, Shivapurkar N. Potential synergism between wheat bran and psyllium: enhanced inhibition of colon cancer. Cancer Lett 1993; 75: 53–58. Oshima M, Takahashi, M, Oshima H, et al. Effects of docosahexaenoic acid (DHA) on intestinal polyp development in APC∆716 knockout mice. Carcinogenesis 1996; 16: 2605–07.

SIR—Wasan and Goodlad’s viewpoint article1 is a disservice to public health. It jumbles types of dietary fibre and fibre supplementation, confuses a single putative marker for colon carcinogenesis with risk of developing the disease, and ignores the importance of fibre for normal intestinal function. “Fibre” is a collective term and the origin of types of fibre is important. Eastwood likened the labelling of total fibre in foods to that of giving the total vitamin content rather than individual components.2 Lumping of wheat bran with cellulose is not justified because animal studies with wheat

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bran show the most consistent reduction in colon carcinogenesis while cellulose studies are highly inconsistent.3 Likewise, guar, pectin, carrageenan, and alfalfa are different types of fibre and have given conflicting results. An important distinction ignored by Wasan and Goodlad is that most highly processed forms of fibre do not show protection in colon cancer assays but less processed, more slowly fermented sources such as wheat bran and psyllium show significant benefit. The authors conclude that there is conflicting evidence about whether cell proliferation is a risk factor but then spent more time discussing how fibre might stimulate cell proliferation. This issue is complex and there are many factors already identified that impinge upon fibre’s effects on colonic carcinogenesis.4 In the absence of conclusive evidence we should learn from human intervention trials rather than relying exclusively on animal and in-vitro studies. When patients with at least one colorectal adenoma that had been resected were fed a wheat-bran-supplemented, low-fat diet, no new large adenomas were seen after 48 months of follow-up.5 Addition of wheat bran to diets of patients has resulted in significantly reduced faecal bile-acid concentrations and cell proliferation rates. These studies do not directly address the issue of dietary fibre and colon carcinogenesis but a definitive study on that would be impossible. DMK has in the past received funding from the Kellogg Company and Proctor and Gamble.

David M Klurfeld Department of Nutrition and Food Science, Wayne State University, College of Science, Detroit, MI 48202, USA

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Wasan HS, Goodlad RA. Fibre-supplemented foods may damage your health. Lancet 1996; 348: 319–20. Eastwood MA. What does the measurement of dietary fibre mean? Lancet 1986; i: 1487. Klurfeld DM. Insoluble dietary fibre and experimental colon cancer: are we asking the proper questions? In: Kritchevsky D, Bonfield C, Anderson JW, eds. Dietary fibre: chemistry, physiology, and health effects. New York: Plenum, 1990: 403–15. Klurfeld DM. Dietary fibre-mediated mechanisms in carcinogenesis. Cancer Res 1991; 52: 2055s–59s. MacLennan R, Macrae F, Bain C, et al. Randomized trial of intake of fat, fiber, and beta-carotene to prevent colorectal adenomas: the Australian Polyp Prevention Project. J Natl Cancer Inst 1995; 87: 1760–66.

SIR—The viewpoint by Wasan and Goodlad1 was picked up by the media2 in a fashion that may make many people consume no more dietary fibre at all. The authors based their conclusions on evidence about fermentable (soluble?) fibre. They should have described the differences between different fibres (eg, fermentable and less or not fermentable, soluble and insoluble, ionic and nonionic).3,4 Some, especially insoluable and less fermentable ones, have shown mainly beneficial effects on health and they contribute to increased longevity, bind and excrete mutagens,2 inhibit invasion by highly metastatic B16–BL6 melanoma cells,3 and decrease numbers of lung tumour colonies.4 The discussion should have been widened to cover potentially carcinogenic or anticarcinogenic effects of fibres in the colon as a function of their matrix structure3 (and not fermentability only).5 The 1992 meta-analysis by Howe et al that found a lower risk with higher fibre intake in 13 studies seems to have been played down by Wasan and Goodlad. Howe et al found “a monotonic decreasing dose-response relationship” for fibre intake that could not have arisen by chance (p<10—10). The authors have not mentioned the relation of high fibre intake with longevity, an issue addressed in a comparison5 of

Vol 348 • October 5, 1996