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Clinical Review: Milly Ryan-Harshman and Walid Aldoori Diet and colorectal cancer: Review of the evidence Can Fam Physician 2007; 53: 1913-1920 [Abstract] [Full text] [PDF]

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Re: safety of folic acid for patients who have had colon cancer

Harold Pupko   (30 December 2007)

Author's Reply to Dr. Pupko

Walid Aldoori   (12 December 2007)

Warning: Folic Acid May Promote Colorectal Cancer

Harold Pupko   (3 December 2007)

Re: safety of folic acid for patients who have had colon cancer 30 December 2007
Harold Pupko, M.D. Send letter to journal: Re: Re: safety of folic acid for patients who have had colon cancer Drhappi{at}aol.com Harold Pupko	I thank Dr Aldoori for his response to my letter, but based on my reading of the literature, I would be reluctant to suggest to patients who have had colon cancer, with the possibility of undiagnosed metastases, that they can continue to safely take folic acid supplementation, even at dosages acceptable to Health Canada.
Author's Reply to Dr. Pupko 12 December 2007
Walid Aldoori, Medical Director Wyeth Consumer Healthcare Inc. Send letter to journal: Re: Author's Reply to Dr. Pupko aldoorwa{at}wyeth.com Walid Aldoori	I would like to take this opportunity to thank Dr. Pupko for his letter as it highlighted the main reason why, along with Dr. Ryan- Harshman, I frequently author nutrition review articles for practicing physicians. We are aware about recent articles suggesting that “high” dose folic acid might accelerate the growth of an already existent colorectal neoplasm. It is worth mentioning that the authors of these studies acknowledge the overwhelming evidence that folic acid at an “appropriate dose” when taken at an “ appropriate time” is beneficial in reducing the risk of colorectal adenoma as well as other conditions. Although the exact preventative dose as well as the timing and the temporal relationship are not delineated, one of the first seminal papers on the subject provided as yet the best answers to the beneficial dose and duration of use. In an analysis of a large cohort study of nearly 90,000 women, Giovannucci el al. provided strong evidence that the use of multivitamin preparations containing folic acid for 15 years or more was associated with a substantial reduction in the risk of colon cancer (1). In this study the benefit was particularly strong in the highest category of folic acid intake which had a median intake of 676 mcg. This study provided strong evidence that it is the long term intake (15+ y) which was relevant for colon cancer prevention as well as the beneficial dose range. This study was instrumental as to why Centrum® Select contains 600 mcg along with a generous amount of B12 at 25 mcg. It is worth mentioning that the current Recommended Dietary allowance (RDA) for folic acid is 400 mcg and the Tolerable Upper Intake level (UL) is 1 mg/ day. I think that Dr. Pupko is not trying to imply that 600 mcg is a “supraphysiologic dose”. In November 2007, the Natural Health Product Directorate (NHPD) of Health Canada released their multivitamin monograph which included all the required warnings for multivitamin/multimineral preparations well after the publication of the 2007 literature that Dr. Pupko is citing. NHPD correctly recognizes that the levels of folic acid which are allowed in Canada in nonprescription products (up to 1 mg /day) are safe and efficacious. We will continue to follow the scientific literature as well as monitor dietary intakes of Canadians so as to adjust the levels of nutrients in nutritional products to provide total intakes of these nutrients which are safe and efficacious in health and disease. (1) Multivitamin use, folate, and colon cancer in women in the Nurses’ Health Study. Giovannucci E, et al. Ann Intern Med 1998;129:517- 524. Walid Aldoori, MB. B.Ch., MPA, ScD Medical Director, Wyeth Consumer Healthcare Canada.
Warning: Folic Acid May Promote Colorectal Cancer 3 December 2007
Harold Pupko, M.D. Private Practice Send letter to journal: Re: Warning: Folic Acid May Promote Colorectal Cancer Drhappi{at}aol.com Harold Pupko	The article on the evidence connecting diet and colorectal cancer attempts to present an up to date review on the subject by including literature to December 2006. Unfortunately, it is incomplete, as the literature of 2007 presents us with a startling new concept that has importance in treating patients today. Evidence is accumulating that folate possesses dual modulatory effects on colorectal carcinogenesis, depending on the timing and dose of folate intervention. As Kim points out in his excellent review of the subject, folate deficiency has an inhibitory effect, whereas folate supplementation has a promoting effect on the progression of established colorectal neoplasms. On the other hand, folate deficiency in normal colorectal mucosa appears to predispose it to neoplastic transformation, while modest levels of folic acid supplementation suppress such transformation. Supraphysiologic supplemental doses enhance the development of cancer in normal colorectal mucosa (1). I doubt that multivitamin manufacturers will ever post warnings about this new thinking on the bottle, and it is up to us as physicians to share this knowledge with our patients. We would never treat patients with folic acid without first checking for B12 deficiency for fear of unmasking this. Perhaps we should routinely order colonoscopies before encouraging our patients to take a multivitamin with folic acid in the 50 plus population. I note that one of the authors is an employee of Wyeth, a company that manufactures a multivitamin for adults over 50 (Centrum Select) with 0.6 mg of folic acid per tablet. I invite Dr.Aldoori’s comments on why this dosage was selected, especially in light of this new evidence. (1) Kim, YI Folate and colorectal cancer: an evidence based critical review Mol Nutr Food Res 2007 Mar;51(3):267-92