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Too much of a good thing: folic acid and vitamin B12 supplementation and cancer risk in the elderly

When researchers looked at how B12 and folic acid affect osteoporosis in the elderly, they didn't find a strong positive effect. They did, however, notice an uptick in cancer rate. This study took a deeper look at the matter.

Study under review: Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial

Introduction

Plenty of people use supplements nowadays[1]. In elderly populations, almost half in the U.S.[2], about one-third in the U.K.[4], and about one-fourth in the Netherlands[4] use dietary supplements. Although[5] daily low-dose multivitamin supplements have been linked to reductions in incidence of cancer, supplements may not[1] always be good, and context (e.g., baseline nutrition, diet, disease) is important to consider. In fact, excess supplementation of antioxidants has demonstrated higher cancer incidence before[6].

Folic acid is one particular vitamin that has controversy[7] surrounding its use in fortification of foods. Some countries, such as the U.S and Canada, mandate fortification[8] of wheat flour for prevention of neural tube defects, while other countries, such as Norway, refrain from fortification because of the uncertainty of cancer risk and epigenetic changes. While vitamin B12 is generally abundant in the average diet, vitamin B12 and folic acid both play a key role[9] in DNA methylation and synthesis, as well as amino acid metabolism. Changes in DNA methylation[10] are associated with a higher risk of various cancers and folic acid supplementation[11] may play a role in chemoprevention. Interestingly, experimental evidence[12] suggest that folate deficiency may help initiate cancer and is associated with higher homocysteine[13] levels and cancer risk, but large doses of folic acid could also potentiate cancer.

Some recent studies[14] and models[15] suggest that folic acid supplementation may actually increase the risk of cancer by promoting[16] the progression of pre-neoplastic and undiagnosed neoplastic tissue (“neoplasm” is an abnormal tissue growth that can be non-cancerous or cancerous). A meta-analysis of 10 RCTs reported a borderline significant[17] (but not significant) greater risk of cancer incidence following folic acid supplementation. Whether and to which extent this risk is related to specific genetic polymorphisms relating to folate metabolism, such as the TT variant of MTHFR 677C>T[18] (rate limiting enzyme in folate metabolism) which may hold greater[14] cancer mortality risk than the CC or TC variants, still needs to be established.

Previous exploratory results from the B-vitamins for the PRevention of Osteoporotic Fractures (B-PROOF)[19] study reported a higher incidence of self-reported cancer in the intervention group relative to the control group after a two to three year follow up. This study, designed to evaluate the protective potential of B vitamins on osteoporotic fracture, determined that there was no effect of B vitamin supplementation of osteoporotic fracture in elderly people (at least 65 years old). The goal of the study under review was to validate the cancer findings from the B-PROOF study with data on confirmed cancer diagnoses from the participants of the study in order to evaluate the long-term effects of folic acid and vitamin B12 supplementation on the risk of overall cancer incidence.

A good amount of the elderly population uses dietary supplements, but whether they provide the desired health effects or in what context they are best taken is still uncertain. Folic acid and vitamin B12 are of particular interest in the context of supplementation because of their role in DNA methylation and synthesis. Some studies suggest a reduction in cancer risk, while other studies report increases in cancer risk. The study under review aimed to evaluate the long-term effects of folic acid and vitamin B12 supplementation on the risk of cancer.

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Other Articles in Issue #50 (December 2018)