The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low B12 status is primarily associated with food-bound malabsorption, while sub-optimal vitamin B6 status is attributed to increased requirements in ageing. Observational evidence links low status of folate and the related B-vitamins (and/or elevated concentrations of homocysteine) with a higher risk of degenerative diseases including cardiovascular disease (CVD), cognitive dysfunction and osteoporosis. Deficient or low status of these B-vitamins alone or in combination with genetic polymorphisms, including the common MTHFR 677 C → T polymorphism, could contribute to greater disease risk in ageing by causing perturbations in one carbon metabolism. Moreover, interventions with the relevant B-vitamins to optimise status may have beneficial effects in preventing degenerative diseases. The precise mechanisms are unknown but many have been proposed involving the role of folate and the related B-vitamins as co-factors for one-carbon transfer reactions, which are fundamental for DNA and RNA biosynthesis and the maintenance of methylation reactions. This review will examine the evidence linking folate and related B-vitamins with health and disease in ageing, associated mechanisms and public health implications.

Background: Mandatory folic acid fortification of food is effective in reducing neural tube defects and may even reduce stroke-related mortality, but it remains controversial because of concerns about potential adverse effects. Thus, it is virtually nonexistent in Europe, albeit many countries allow food fortification on a voluntary basis. Objective: The objective of the study was to examine the effect of a voluntary but liberal food fortification policy on dietary intake and biomarker status of folate and other homocysteine-related B vitamins in a healthy population. Design: The study was a cross-sectional study. From a convenience sample of 662 adults in Northern Ireland, those who provided a fasting blood sample and dietary intake data were examined (n = 441, aged 18–92 y). Intakes of both natural food folate and folic acid from fortified foods were estimated; we used the latter to categorize participants by fortified food intake. Results: Fortified foods were associated with significantly higher dietary intakes and biomarker status of folate, vitamin B-12, vitamin B-6, and riboflavin than were unfortified foods. There was no difference in natural food folate intake (range: 179–197 μg/d) between the fortified food categories. Red blood cell folate concentrations were 387 nmol/L higher and plasma total homocysteine concentrations were 2 μmol/L lower in the group with the highest fortified food intake (median intake: 208 μg/d folic acid) than in the nonconsumers of fortified foods (0 μg/d folic acid). Conclusions: These results show that voluntary food fortification is associated with a substantial increase in dietary intake and biomarker status of folate and metabolically related B vitamins with potential beneficial effects on health. However, those who do not consume fortified foods regularly may have insufficient B vitamin status to achieve the known and potential health benefits.

Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing.

Background: National survey data of erythrocyte glutathione reductase activation coefficient (EGRac) indicate that suboptimal riboflavin status may be a problem in all population age groups, but the cutoff for deficiency is controversial. In addition, the effectiveness of different biomarkers of riboflavin status has not been critically evaluated.

Context Emerging evidence suggests that deficiencies of folate-related B-vitamins can arise with metformin treatment and are independently linked with cognitive dysfunction, a co-morbidity of diabetes. Objective To determine the impact of hyperglycemia and metformin use on relevant B-vitamin biomarkers and cognitive outcomes in older adults. Setting and Participants Community-dwelling older people (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the TUDA cohort study in 2008-2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on glycosylated hemoglobin (HbA₁c) ≥ 5.7% (39 mmol/mol), either with (n = 318) or without (n = 1986) metformin treatment. Main Outcome Measures Biomarkers of folate, vitamin B12, vitamin B6 and riboflavin were measured. Cognitive assessments included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB). Results Metformin use was associated with higher risk of deficiency of vitamin B12 (combined B12 index ≤ -1; odds ratio (95% CI): 1.45 (1.03-2.02)) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; 1.48 (1.02-2.15)). Fortified foods when eaten regularly had a positive impact on all relevant B-vitamin biomarkers, even with hyperglycaemia. After adjustment for relevant co-variates, metformin use was associated with an increased risk of cognitive dysfunction as assessed using the RBANS (1.36 (1.03-1.80) and FAB (1.34 (1.03-1.74). Conclusions Use of metformin in older adults is associated with poorer cognitive performance; B-vitamin deficiency may be implicated. Fortified foods can optimize B-vitamin status and may be beneficial for maintaining better cognitive health in older people with or at risk of diabetes.

Background: Mild vitamin B-12 deficiency is common among older adults, but evidence for setting dietary recommendations is limited because most studies have administered vitamin B-12 via nonoral routes or at doses several hundred times higher than current recommendations. Furthermore, different biomarkers of vitamin B-12 status have not been systematically reviewed.