- Email: [email protected]
Fibre and colorectal cancer
THE LANCET
nutrition patterns in high-longevity Abkhazia and Azerbaidjan and low-longevity Ukraine which pointed to a role for high fibre content in the diet in increased longevity. *B D Dimitrov Centre for Cancer Epidemiology, University of Manchester, Manchester, UK; and *Department of Social Medicine, Higher Medical Institute, Plovdiv 4002, Bulgaria
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Wasan HS, Goodlad RA. Fibre-supplemented foods may damage your health. Lancet 1996; 348: 319–20. Reynolds L. Cancer warning over high fibre. Daily Express (London), Aug 2, 1996: 25. Ryden P, Robertson JA. The effect of fibre source and fermentation on the apparent hydrophobic binding properties of wheat bran preparations for the mutagen 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx). Carcinogenesis 1995; 16: 209–16. Saiki I, Murata J, Nakajima M, Tokura S, Azuma I. Inhibition by sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells. Cancer Res 1990; 50: 3631–37. Grigorov IuG, Kozlovskaia SG, Medovar Bla, Semes’ko TM, Sineok LL. Bases of rational nutrition in old age. Vestn Acad Med Nauk SSSR 1990; 1: 58–61.
have subsequently shown potential harmful effects. These trials also demonstrate that adequate studies in man are possible. We would also point out that to our knowledge no one has ever published beneficial effects of “fish and chips”. We felt that the media response to our report was generally responsible, and presented a balanced view, contrary to that in the scientific press, which we feel has exaggerated the benefits of fibre. The implication that we should let such supplementation go unchallenged merely to avoid possible misrepresentation by the press is disturbing. Several specific fibres and one combination are advocated by your correspondents in cancer prevention. The worrying implication is that the food and drug companies with superior marketing would be able to promote the so-called best fibre. Why is there a belief that it is easier to promote specific fibre supplementation as opposed to giving the public the facts and choices? We reiterate that we encourage the use of specific fibre supplements only within a scientific context of controlled prospective trials. *Harpreet S Wasan, Robert A Goodlad Imperial Cancer Research Fund, Lincoln’s Inn Fields, London WC2A 3PX , UK
Authors’ reply SIR—Although we entirely share Walker and Segal’s sentiments, our article was intended to redress the gross imbalance in the assumption that increasing fibre intake reduces the risk of colon cancer, rather than the equally important issues of implementation of dietary change. It was not our intention to discuss issues outside cancer prevention and we agree that in any risk assessment that all health benefits have to be taken into account. Furthermore, omission of speculative hypothesis on possible mechanisms of fibre chemoprevention was necessarily obviated by our sceptical stance. The epidemiological data now seem to have been conveniently interpreted to imply that there are benefits to increasing consumption of specific fibres. We are concerned that specific fibres could be promoted as chemopreventative, especially since fibre supplements in laboratory animals can augment carcinogenesis, as corroborated by Hill and Leeds in their table. On the basis of such animal studies, pharmaceuticals often have to carry carcinogenic risk warnings and such data have delayed drug development (for example, proton-pump inhibitors). Furthermore, studies attributing benefits to specific fibres often have confounding variables in their design, such as a concomitant decrease in fat consumption, as highlighted in Alabaster’s data. The fact that non-interventional epidemiological evidence does not support cancer promotion by fibre does not imply that the unbalanced introduction of high-fibre supplements will have the same outcome. Hill and Leeds have also confused various estimates of cell proliferation with the definitive crypt-cell production rate. We are dismayed at the negative reception to our conclusion that more prospective trials be undertaken before any recommendations can be reached. Klurfield’s statement that “definitive studies are impossible” is particularly puzzling, since while citing human data that even the original authors suggest should be treated with caution, he omits to add that wheat bran alone had no benefit. Is he then implying that reverting back to biomarkers, such as faecal bile-acids, for which the relevance is even more contentious, is sufficient? We are surprised at the stance on -carotene taken by Alabaster and Shivapurkar, especially because they have shown that both -carotene and bran are chemoprotective, with identical methods. -carotene remains an excellent example of how one should remain cautious in interpreting “highly beneficial” biomarker data. Several intervention trials
Vol 348 • October 5, 1996
Shocking safety concerns SIR—Pascual-Leone and colleagues (July 27, p 233)1 take advantage of recent technological developments that enable repetitive transcranial stimulation of the brain at frequencies up to 30 Hz. Safety studies have largely allayed fears of secondary epilepsy with this technique, and guidelines have been formulated to protect against this complication. However, there is growing epidemiological evidence that low frequency, low intensity electromagnetic fields are associated with cancer. Indeed, this association is now acknowledged by the National Radiological Protection Board.2 The effect of pulsed electromagnetic fields is unclear, but some studies suggest that magnetic field strengths in the millitesla range may have a promoter or copromoter effect in carcinogenesis, as well as increasing growth in cancer cell lines.3–5 Hitherto, in studies with repetitive transcranial magnetic stimulation of the brain, the possibility of delayed malignant disease has not been considered. Such investigations use magnetic field strengths around 1000 times greater than those commonly used in experiments on carcinogenesis. Nor is the duration of exposure inconsequential. Pascual-Leone and colleagues’ study involved a total of 50 000 shocks to each patient, delivered in 10 Hz trains over the course of 5 months. Long-term follow up of such patients would be prudent, especially if repetitive transcranial brain stimulation is to be accepted as a treatment for depression. P Brown National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK
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Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet 1996; 348: 233–37. Boulton A. Sparks fly over electromagnetic link with cancer. BMJ 1996; 312: 463. Holmberg B. Magnetic fields and cancer: animal and cellular evidence, an overview. Environ Health Perspect 1995; 103: 63–67. Cridland NA, Sienkiewicz ZJ, Kowalczuk CI, Saunders RD. Recent biological studies relevant to carcinogenesis. In: Ueno S, ed. Biological effects of magnetic and electromagnetic fields. New York: Plenum Press, 1996: 221–38. Hannan CJ, Liang Y, Allison JD, Searle JR. In vitro cytotoxicity against human cancer cell lines during pulsed magnetic field exposure. Anticancer Res 1994; 14: 1517–20.
959
nutrition patterns in high-longevity Abkhazia and Azerbaidjan and low-longevity Ukraine which pointed to a role for high fibre content in the diet in increased longevity. *B D Dimitrov Centre for Cancer Epidemiology, University of Manchester, Manchester, UK; and *Department of Social Medicine, Higher Medical Institute, Plovdiv 4002, Bulgaria
1 2 3
4
5
Wasan HS, Goodlad RA. Fibre-supplemented foods may damage your health. Lancet 1996; 348: 319–20. Reynolds L. Cancer warning over high fibre. Daily Express (London), Aug 2, 1996: 25. Ryden P, Robertson JA. The effect of fibre source and fermentation on the apparent hydrophobic binding properties of wheat bran preparations for the mutagen 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline (MeIQx). Carcinogenesis 1995; 16: 209–16. Saiki I, Murata J, Nakajima M, Tokura S, Azuma I. Inhibition by sulfated chitin derivatives of invasion through extracellular matrix and enzymatic degradation by metastatic melanoma cells. Cancer Res 1990; 50: 3631–37. Grigorov IuG, Kozlovskaia SG, Medovar Bla, Semes’ko TM, Sineok LL. Bases of rational nutrition in old age. Vestn Acad Med Nauk SSSR 1990; 1: 58–61.
have subsequently shown potential harmful effects. These trials also demonstrate that adequate studies in man are possible. We would also point out that to our knowledge no one has ever published beneficial effects of “fish and chips”. We felt that the media response to our report was generally responsible, and presented a balanced view, contrary to that in the scientific press, which we feel has exaggerated the benefits of fibre. The implication that we should let such supplementation go unchallenged merely to avoid possible misrepresentation by the press is disturbing. Several specific fibres and one combination are advocated by your correspondents in cancer prevention. The worrying implication is that the food and drug companies with superior marketing would be able to promote the so-called best fibre. Why is there a belief that it is easier to promote specific fibre supplementation as opposed to giving the public the facts and choices? We reiterate that we encourage the use of specific fibre supplements only within a scientific context of controlled prospective trials. *Harpreet S Wasan, Robert A Goodlad Imperial Cancer Research Fund, Lincoln’s Inn Fields, London WC2A 3PX , UK
Authors’ reply SIR—Although we entirely share Walker and Segal’s sentiments, our article was intended to redress the gross imbalance in the assumption that increasing fibre intake reduces the risk of colon cancer, rather than the equally important issues of implementation of dietary change. It was not our intention to discuss issues outside cancer prevention and we agree that in any risk assessment that all health benefits have to be taken into account. Furthermore, omission of speculative hypothesis on possible mechanisms of fibre chemoprevention was necessarily obviated by our sceptical stance. The epidemiological data now seem to have been conveniently interpreted to imply that there are benefits to increasing consumption of specific fibres. We are concerned that specific fibres could be promoted as chemopreventative, especially since fibre supplements in laboratory animals can augment carcinogenesis, as corroborated by Hill and Leeds in their table. On the basis of such animal studies, pharmaceuticals often have to carry carcinogenic risk warnings and such data have delayed drug development (for example, proton-pump inhibitors). Furthermore, studies attributing benefits to specific fibres often have confounding variables in their design, such as a concomitant decrease in fat consumption, as highlighted in Alabaster’s data. The fact that non-interventional epidemiological evidence does not support cancer promotion by fibre does not imply that the unbalanced introduction of high-fibre supplements will have the same outcome. Hill and Leeds have also confused various estimates of cell proliferation with the definitive crypt-cell production rate. We are dismayed at the negative reception to our conclusion that more prospective trials be undertaken before any recommendations can be reached. Klurfield’s statement that “definitive studies are impossible” is particularly puzzling, since while citing human data that even the original authors suggest should be treated with caution, he omits to add that wheat bran alone had no benefit. Is he then implying that reverting back to biomarkers, such as faecal bile-acids, for which the relevance is even more contentious, is sufficient? We are surprised at the stance on -carotene taken by Alabaster and Shivapurkar, especially because they have shown that both -carotene and bran are chemoprotective, with identical methods. -carotene remains an excellent example of how one should remain cautious in interpreting “highly beneficial” biomarker data. Several intervention trials
Vol 348 • October 5, 1996
Shocking safety concerns SIR—Pascual-Leone and colleagues (July 27, p 233)1 take advantage of recent technological developments that enable repetitive transcranial stimulation of the brain at frequencies up to 30 Hz. Safety studies have largely allayed fears of secondary epilepsy with this technique, and guidelines have been formulated to protect against this complication. However, there is growing epidemiological evidence that low frequency, low intensity electromagnetic fields are associated with cancer. Indeed, this association is now acknowledged by the National Radiological Protection Board.2 The effect of pulsed electromagnetic fields is unclear, but some studies suggest that magnetic field strengths in the millitesla range may have a promoter or copromoter effect in carcinogenesis, as well as increasing growth in cancer cell lines.3–5 Hitherto, in studies with repetitive transcranial magnetic stimulation of the brain, the possibility of delayed malignant disease has not been considered. Such investigations use magnetic field strengths around 1000 times greater than those commonly used in experiments on carcinogenesis. Nor is the duration of exposure inconsequential. Pascual-Leone and colleagues’ study involved a total of 50 000 shocks to each patient, delivered in 10 Hz trains over the course of 5 months. Long-term follow up of such patients would be prudent, especially if repetitive transcranial brain stimulation is to be accepted as a treatment for depression. P Brown National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK
1
2 3 4
5
Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet 1996; 348: 233–37. Boulton A. Sparks fly over electromagnetic link with cancer. BMJ 1996; 312: 463. Holmberg B. Magnetic fields and cancer: animal and cellular evidence, an overview. Environ Health Perspect 1995; 103: 63–67. Cridland NA, Sienkiewicz ZJ, Kowalczuk CI, Saunders RD. Recent biological studies relevant to carcinogenesis. In: Ueno S, ed. Biological effects of magnetic and electromagnetic fields. New York: Plenum Press, 1996: 221–38. Hannan CJ, Liang Y, Allison JD, Searle JR. In vitro cytotoxicity against human cancer cell lines during pulsed magnetic field exposure. Anticancer Res 1994; 14: 1517–20.
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