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.

A compromised vitamin B ₁₂ status is common in older people despite dietary intakes that typically far exceed current recommendations. The maintenance of an optimal status of vitamin B ₁₂ is not only dependent on adequate dietary intake but more critically on effective absorption which diminishes with age. The measurement of vitamin B ₁₂ is complicated by the lack of a gold standard assay. There are a number of direct and functional indicators of vitamin B ₁₂ status; however, none of these are without limitations and should be used in combination. Vitamin B ₁₂ is of public health importance, not only because deficiency leads to megaloblastic anaemia and irreversible nerve damage, but also because emerging evidence links low B ₁₂ to an increased risk of a number of age-related diseases, including cardiovascular disease, cognitive dysfunction, dementia and osteoporosis. Furthermore, there are concerns relating to potential adverse effects for older adults with low vitamin B ₁₂ status of over-exposure to folic acid in countries where there is mandatory fortification of food with folic acid. The aim of this review is to examine the known and emerging issues related to vitamin B ₁₂ in ageing, its assessment and inter-relationship with folate.

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.

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.