Among Vitamin B12 Deficient Older People, High Folate Levels are Associated with Worse Cognitive Function: Combined Data from Three Cohorts

Moore, Eileen M.; Ames, David; Mander, Alastair; Carne, Ross; Brodaty, Henry; Woodward, Michael; Boundy, Karyn; Ellis, Kathryn A.; Bush, Ashley I.; Faux, Noel; Martins, Ralph N.; Masters, Colin L.; Rowe, Christopher C.; Szoeke, Cassandra; Watters, David

doi:10.3233/jad-131265

Cited by 81 publications

(57 citation statements)

References 25 publications

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“…Evidence from the National Health and Nutrition Examination Survey reported that although higher folate was generally associated with better cognitive health, a combination of high plasma folate (>59 nmol/l) with low plasma B 12 (<148 pmol) and elevated methylmalonic acid (a B 12 -specific functional biomarker), was actually associated with poorer cognitive performance compared with individuals with normal concentrations of these biomarkers (57) . Furthermore, Moore et al (58) showed participants with high red cell folate and low serum B 12 were three times more likely to have impaired cognitive performance. In contrast, however, analysis from the Hordaland Health study failed to confirm this association in their analysis (59) .…”

Section: Evidence Linking B-vitamins With Brain Health In Ageingmentioning

confidence: 99%

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

et al. 2014

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Nutrition plays a fundamental role in supporting the structural and functional development of the human brain from conception, throughout early infancy and extending into later life. A growing body of evidence suggests that folate and the metabolically related B-vitamins are essential for brain health across all age groups, owing to their specific roles in C 1 metabolism and particularly in the production of S-adenosylmethionine, a universal methyl donor essential for the production of neurotransmitters. Emerging, though not entirely consistent, evidence suggests that maternal folate status throughout pregnancy may influence neurodevelopment and behaviour of the offspring. Furthermore optimal B-vitamin status is associated with better cognitive health in ageing. Of note, a recent clinical trial provided evidence that supplementation with folic acid and related B-vitamins over a 2-year-period reduced global and regional brain atrophy, as measured by MRI scan in older adults. In terms of potential mechanisms, the effects of these B-vitamins on cognitive health may be independent or may be mediated by nutrient-nutrient and/or relevant gene-nutrient interactions. Furthermore, a new area of research suggests that the in utero environment influences health in later life. Folate, an important cofactor in C 1 metabolism, is indirectly involved in DNA methylation, which in turn is considered to be one of the epigenetic mechanisms that may underlie fetal programming and brain development. The present review will explore the evidence that supports a role for folate and the related B-vitamins in brain health across the lifecycle, and potential mechanisms to explain such effects.

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Section: Evidence Linking B-vitamins With Brain Health In Ageingmentioning

confidence: 99%

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

et al. 2014

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“…Although none of the researchers from studies cited above have reported adverse effects from Bvitamin supplementation caution should be taken when recommending B-vitamins without awareness of current nutrient status due to the finding of Moore et al (2014) and Malouf et al (2008). These researchers showed that B-vitamin supplementation may be detrimental to cognition in those that have optimal levels of B12 prior to supplementation.…”

Section: B-vitaminsmentioning

confidence: 95%

A healthy diet to reduce the risk of dementia in people with a learning disability

Harper

2017

Learning Disability Practice

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“…Early reports on folic acid supplementation of vitamin B-12-deficient patients have shown that folic acid ameliorates the megaloblastic anemia and hematologic abnormalities seen in severe vitamin B-12 deficiency but has no effect on the neurologic conditions that are associated with the deficiency (14). Current evidence has suggested that excess folate intake worsens the clinical and metabolic manifestations of vitamin B-12 insufficiency as indicated by increases in the prevalences of anemia and cognitive dysfunction and the concentrations of homocysteine and methylmalonic acid in plasma (15)(16)(17)(18)(19). Hence, we hypothesized that high folate intake can modify the association between the TCN2 polymorphism and peripheral neuropathy.…”

Section: Introductionmentioning

confidence: 99%

Transcobalamin 776C→G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake

Sawaengsri

Bergethon

Qiu

et al. 2016

The American Journal of Clinical Nutrition

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Background: The 776C/G polymorphism of the vitamin B-12 transport protein transcobalamin gene (TCN2) (rs1801198; Pro259Arg) is associated with a lower holotranscobalamin concentration in plasma. This effect may reduce the availability of vitamin B-12 to tissues even when vitamin B-12 intake is adequate. Clinical outcomes associated with vitamin B-12 insufficiency could potentially be worsened by high folate intake. Objective: We determined the association of the TCN2 776C/G polymorphism and folate intake with peripheral neuropathy in elders with normal plasma concentrations of vitamin B-12. Design: Participants in this cross-sectional study (n = 171) were from a cohort of community-based, home-bound elderly individuals aged $60 y who underwent an evaluation by physicians including an assessment for peripheral neuropathy. Participants were administered food-frequency and general health status questionnaires, anthropometric measurements were taken, and a fasting blood sample from each subject was collected. Results: Odds of neuropathy were 3-fold higher for GG genotypes than for CC genotypes (OR: 3.33; 95% CI: 1.15, 9.64). When folate intake was .2 times the Recommended Dietary Allowance (800 mg), GG genotypes had 6.9-fold higher odds of neuropathy than CC genotypes (OR: 6.9; 95% CI: 1.31, 36.36). There was no difference between the genotypes in the odds of peripheral neuropathy when folate intake was #800 mg (OR: 1.5; 95% CI: 0.18, 12.33). Conclusion: The TCN2 776C/G polymorphism is associated with increased odds of peripheral neuropathy in the elderly, even with a normal vitamin B-12 status, especially if their folate intake is .2 times the Recommended Dietary Allowance.Am J Clin Nutr 2016;104:1665-70.

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Among Vitamin B12 Deficient Older People, High Folate Levels are Associated with Worse Cognitive Function: Combined Data from Three Cohorts

Abstract: High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

Cited by 81 publications

References 25 publications

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

Emerging roles for folate and related B-vitamins in brain health across the lifecycle

A healthy diet to reduce the risk of dementia in people with a learning disability

Transcobalamin 776C→G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake

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