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Revisiting Fiber and Colorectal Cancer

By Kevin Klatt

Colorectal cancers are the third most common worldwide, and represent one of the major areas of prevention research. Rates of these cancers increase with industrialization, and are uncommon in Africa and much of Asia. A number of potential nutritional targets have been posited, based on preclinical and epidemiological data; however, these remain controversial. The American Institute of Cancer Research’s 2011 report (1) on Colorectal Cancer states that there is convincing evidence that foods high in fiber decrease risk and red and processed meats increase risk of colon cancer. However, there are few controlled feeding studies in humans have corroborated these associations; indeed, a large body of literature (2-7) focusing on dietary fiber supplementation back in the late 90’s and early 2000’s did not show any support for any positive effects of high fiber/low-fat diets on recurrent adenomas . However, these studies can/have been criticized for: 1. not being long enough 2. fail to capture of a window of true prevention (as subjects already had adenomas) 3. The dose/type of fiber. Since these trials, considerable experimental data (8,9) has been generated to suggest that the type of fiber, its dose, and the type/amount of short chain fatty acid fermentation products likely add some complexity to the inconsistent epidemiological associations between fiber intake and colorectal cancer risk.

A recent study published in Nature Communications (10) provides a novel perspective on this contentious topic of high-fiber diets and colon. The study employed a food-based dietary intervention in 2 populations: African Americans and rural South Africans (a sensible population to study given Burkitt’s original observations that rural Africans are nearly free of large bowel diseases). Twenty healthy, middle-aged African Americans and 20 rural Africans were first examine in their home environments for 2 weeks, to examine their normal food intake, before being housed in their respective research facilities for the 2 weeks of the dietary intervention (to ensure compliance). African Americans were given the ‘African style’ diet that was low in fat (16% kcals) and high in fiber (55g/day). Participants from Africa were given a western style diet that was higher in fat (52% kcals) and lower in fiber (12g/day). Notably, the high fiber diet was achieved using HiMaize, a purified resistant starch product. The authors look at outcomes related to mucosal epithelial cell proliferation (Ki67 staining) and markers of inflammation (CD3+ intraepithelial lymphocyte and CD68+ lamina propria macrophage staining), to examine the effect of diet on predicted neoplastic change and increased risk of colon cancer. They further look at alterations in microbial composition, highlighting changes in microbes with the baiCD gene, responsible for the deconjugation of bile acids and production of their carcinogenic, secondary metabolites. Their results quite nicely show that the high fiber intervention alters biomarkers in directions that suggest a protective effect against colorectal cancer, while also finding some interesting nuances related to amino acid and choline metabolism.

While providing encouraging results for the role of nutrition in colorectal cancer development, the study leaves us with more hypotheses to test, and a renewed interest in the way in which fiber and its fermentative products might act to buffer against colorectal cancer. Without hard clinical outcomes, it’s difficult to get too excited about the results in light of the multiple fiber interventions that have failed in the past. The biomarkers chosen are not without their scrutiny, as it has been noted that decreases in apoptosis rather than increased cell proliferation better predict tumorigenesis in animal models of colorectal cancer (11). Regardless of one’s enthusiasm about biomarker changes over 2 weeks, it does force us to critically think about previous study designs that have cast doubt on fiber’s role in colon cancer. The authors in this current study employ highly butyrogenic starches, at doses not tested in the trials that have failed before. There is consistent molecular evidence that butyrate works in a paradoxical manner, both stimulating cell proliferation at low concentrations and inhibiting it at high (12), leaving open the possibility that the previous doses of fiber were too low to see a beneficial effect.

Given the Western diets low concentrations of dietary fiber, particularly resistant starches (13), as well as the increased enthusiasm to fortify the food supply with added fibers, further research examining the role of particular fibers, their appropriate doses, and their relationship to clinical outcomes appear warranted. The type 2 resistant starch utilized in this study is uncommon in the food supply, coming largely from raw potatoes, unripe bananas, and some legumes and represents a potential area for food technologists to significantly alter the food supply for better health (14).

References
1. http://www.aicr.org/continuous-update-project/colorectal-cancer.html
2. http://www.ncbi.nlm.nih.gov/pubmed/11073017
3. http://www.ncbi.nlm.nih.gov/pubmed/10770979
4. http://www.ncbi.nlm.nih.gov/pubmed/10770980
5. http://www.ncbi.nlm.nih.gov/pubmed/7730878
6. http://www.ncbi.nlm.nih.gov/pubmed/7473832
7. http://www.nejm.org/doi/pdf/10.1056/NEJM199901213400301
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926973/
9. http://www.ncbi.nlm.nih.gov/pubmed/20937167
10. http://www.nature.com/ncomms/2015/150428/ncomms7342/full/ncomms7342.html
11. http://carcin.oxfordjournals.org/content/18/4/721.abstract
12. http://jn.nutrition.org/content/134/2/479.full
13. http://linkinghub.elsevier.com/retrieve/pii/S0002-8223(07)01932-3
14. http://advances.nutrition.org/content/4/3/351S.full