High folic acid or folate combined with low vitamin B-12 status: potential but inconsistent association with cognitive function in a nationally representative cross-sectional sample of US older adults participating in the NHANES. Issue 6 (29th August 2020)

• Record Type: Journal Article
• Authors: Bailey, Regan L; Jun, Shinyoung; Murphy, Lisa; Green, Ralph; Gahche, Jaime J; Dwyer, Johanna T; Potischman, Nancy; McCabe, George P; Miller, Joshua W
• Is Part Of: American journal of clinical nutrition. Volume 112:Issue 6(2020)
• Page Start: 1547
• Page End: 1557
• Publication Date: 2020-08-29
• Subjects: folate -- unmetabolized folic acid -- vitamin B-12 -- interaction -- cognitive function -- older adults -- NHANES; Diet therapy -- Periodicals; Nutrition -- Periodicals; Dietetics -- Periodicals; 613.205
• DOI: 10.1093/ajcn/nqaa239
• Languages: English
• ISSNs: 0002-9165

Abstract

ABSTRACT: Background: Potential safety concerns relative to impaired cognitive function may exist when high folic acid exposures are combined with low vitamin B-12 status. Objectives: We aimed to examine the relation of the coexistence of high folate and low vitamin B-12 status with cognitive function, utilizing various definitions of "high" folate status. Methods: Cross-sectional data from older adults (≥60 y; n = 2420) from the 2011–2014 NHANES were analyzed. High folate status was defined as unmetabolized serum folic acid (UMFA) > 1 nmol/L or serum total folate > 74.1 nmol/L, and low vitamin B-12 status as methylmalonic acid > 271 nmol/L or serum vitamin B-12 < 150 pmol/L. Logistic regression models estimated ORs of scoring low on 1 of 4 cognitive tests: the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR) and Word Learning tests, and the Animal Fluency test (AF). Results: A significant interaction was observed relative to scoring low on the DSST (<34; UMFA; P -interaction = 0.0071) and AF (serum folate; P -interaction = 0.0078) for low vitamin B-12 and high folate status. Among those with low vitamin B-12, high UMFA or high serum total folate was associated with higher risk of scoring low on the DSST (OR: 2.16; 95% CI: 1.05, 4.47) and the AF (OR: 1.93; 95% CI: 1.08, 3.45). Among those with "normal" vitamin B-12, higher UMFA or serum total folate was protective on the CERAD-DR. In noninteraction models, when high folate and normal vitamin B-12 status was the reference group, low vitamin B-12 combined with high UMFA was associated with greater risk based on the DSST (<34, OR: 2.87; 95% CI: 1.85, 4.45; <40, OR: 2.22; 95% CI: 1.31, 3.75) and AF (OR: 1.97; 95% CI: 1.30, 2.97); but low vitamin B-12 and lower UMFA (OR: 1.69; 95% CI: 1.16, 2.47) was also significantly associated for DSST < 40 risk. Conclusions: Low vitamin B-12 was associated with cognitive impairment both independently and in an interactive manner with high folate for certain cognitive performance tests among older adults.