Intake and Biomarkers of Folate and Risk of Cancer Morbidity in Older Adults, NHANES 1999-2002 with Medicare Linkage

Abstract

BackgroundAfter the 1998 mandatory folic acid fortification of enriched cereal-grain products in the U.S., safety concerns were raised that excess consumption of folic acid and high blood folate biomarkers detected in adults may increase the risk of certain types of cancer.MethodsBaseline data from about 1400 participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2002, aged ≥ 57 years were linked to Medicare and mortality files through December 31, 2007. Using cox proportional hazards regression models, we assessed associations between dietary folate equivalents, folate biomarkers, the presence of unmetabolized folic acid and, overall cancer incidence.ResultsWith 8,114 person-years of follow-up (median follow-up, 6.3 years), about 125 cancer cases were identified. After adjusting for confounders, the hazard ratios of the highest quartile versus the second quartile of RBC folate and dietary folate equivalents were 0.54 (95% CI: 0.31–0.93) and 0.54 (95% CI: 0.30–0.95), respectively. Additionally, serum and RBC folate as continuous variables were inversely and significantly associated with cancer incidence (p<0.01). No significant associations were observed between the presence of unmetabolized folic acid, intake of naturally-occurring food folate or folic acid separately, and cancer incidence.ConclusionsHigh total folate intake and biomarkers in older adults appear to be protective against cancer in post-folic acid fortification years. This study does not show a negative impact of current level of folic acid fortification on cancer risk. As this is one of the few studies to examine the association between unmetabolized folic acid and cancer outcome, a study including a larger nationwide representative sample of the U.S. population is needed.

Elevated Total Homocysteine in All Participants and Plasma Vitamin B12 Concentrations in Women Are Associated With All-Cause and Cardiovascular Mortality in the Very Old: The Newcastle 85+ Study

“…Although it is still debatable whether homocysteine is a causal factor or a marker of CVD and mortality ( 25 ), others have shown that supplementation with folic acid decreased the risk of CVD, especially stroke ( 3 ). There was no significant association between RBC folate concentration and all-cause and cardiovascular mortality—a finding, similar to some studies ( 26–31 ) but not others ( 3 , 32–34 ). To the best of our knowledge, the effect of folate on all-cause and cardiovascular mortality has not been investigated in a very old population and the possibility of an age group-specific effect cannot be discounted.…”

Serum folate concentrations and all-cause, cardiovascular disease and cancer mortality: A cohort study based on 1999–2010 National Health and Nutrition Examination Survey (NHANES)

“…Although our results differ from several studies [8,14], they are largely in agreement with a number of reports [9,[15][16][17]. Although the underlying mechanisms by which lower folate status contributes to mortality remain unclear, some possible explanations could be considered.…”

High levels of circulating folate concentrations are associated with DNA methylation of tumor suppressor and repair genes p16, MLH1, and MGMT in elderly Chileans

“…Those authors did not find significant associations between the presence of non-metabolized FA, intake of naturally-occurring food folate or FA separately, and cancer incidence [50]. …”

“…On the contrary, a recent study with more than 1400 older adults (≥57 years) with a median follow-up of 6.3 years showed that high total folate intake appear to be protective against cancer in post-FA fortification years. Those authors did not find significant associations between the presence of non-metabolized FA, intake of naturally-occurring food folate or FA separately, and cancer incidence [ 50 ].…”