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Resistant Starch Attentuates Colonic DNA Damage Induced by Higher Dietary Protein in Rats

Shusuke Toden, Anthony R. Bird, David L. Topping, and Michael A. Conlon

From CSIRO Health Sciences and Nutrition, Adelaide, South Australia (ST, ARB, DLT, MAC) and Discipline of Physiology, School of Molecular and Biomedical Science, University of Adelaide, South Australia (ST)


Epidemiologic studies suggest that dietary complex carbohydrates are protective against colorectal cancer but dietary protein may increase risk. However, experimental data to support these relationships are scant. We have shown in rats that consumption of a high-protein (25% casein) diet for 4 wk resulted in a twofold increase in damage to colonocyte DNA compared with a low-protein (15% casein) diet. This was associated with thinning of the colonic mucous barrier and increased levels of fecal p-cresol. Addition of resistant starch as a high-amylose maize starch to the diet increased cecal short-chain fatty acid pools and attenuated DNA damage, suggesting protection against genotoxic agents. In humans, this could translate to altered risk of colonic cancer.

Nutr Cancer 2005;51(1):45-51.

Commentary on this paper

Across the community, there has been considerable interest in recent times in the use of high protein diets as an approach to weight loss. Unfortunately, the possible downsides to such a dietary approach has not necessarily been considered.

A high protein diet is a consistent feature across the Western diets that are associated with a high risk for colorectal cancer and several epidemiological studies have specifically targeted protein as being a contributory factor to risk. The mechanism is as yet unclear but one of the postulates is that protein is fermented in the colon to agents that are potentially damaging to DNA. Cresols are one of those fermentation products that might generate mutations in DNA and so increase risk for progression to cancer.

To date however, there has been little work done to link changes in levels of protein fermentation products with damage to DNA. The study reported in this publication indicates that when rats are fed a high protein diet, protein fermentation products are increased in the faeces and there is a concomitant increase in damage to DNA of colonocytes (the cells lining the colon).
Of particular interest is whether other dietary factors can decrease protein fermentation products and perhaps decrease the degree of DNA damage. In this study, they reported that feeding of resistant starch increased carbohydrate fermentation products (certain short chain fatty acids) and that this was directly associated with a reduction in damage to DNA and in faecal cresol levels.

While more direct work needs to be done in humans, these studies suggest a mechanistic link between high protein intakes and risk for colorectal cancer. It might be wise to caution people who maintain a high protein diet over a prolonged period that this is a possibility.

On the positive side, consumption of fermentable carbohydrates in the diet might well help to counteract this effect. It is unclear whether resistant starch is the only fermentable carbohydrate that has this beneficial effect and further studies will be needed to clarify this.

Professor Graeme Young, Flinders Medical Centre, Adelaide, Australia

   



 

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