A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study

Abstract

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12–50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0–12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95 % CI 0.9–1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95 % CI 1.1–1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies.

Vitamin B12 deficiency and impaired expression of amnionless during aging

“…One study evaluating the effect of a combination of vitamin B12 and folate on endpoints of physical function failed to detect significant improvements in parameters linked to frailty. 58 Our results have demonstrated that the patho-physiological decline of intestinal and renal function of vitamin B12 transport during aging directly contributes to poor vitamin B12 status. It is therefore likely that a proportion of individuals in the elderly population are poorly responsive to vitamin B12 supplementation.…”

“…There is only limited evidence for the efficacy of vitamin B12 on frailty parameters, and studies evaluating vitamin B12 in the elderly are often performed in combination with other micronutrients. One study evaluating the effect of a combination of vitamin B12 and folate on endpoints of physical function failed to detect significant improvements in parameters linked to frailty . Our results have demonstrated that the patho‐physiological decline of intestinal and renal function of vitamin B12 transport during aging directly contributes to poor vitamin B12 status.…”

Influence of B Vitamins on Proliferation and Differentiation of Osteoblastic Bovine Cell Cultures: An In Vitro Study

“…This study mainly focuses on the elucidation of the metabolic pathways during biomineralization to get an idea of these processes in vivo and in vitro. Previous experiments with seven different B vitamins in different concentrations revealed a positive effect on cell proliferation with increasing concentrations caused by three B vitamins pyridoxal (B 6 ), folic acid (B 9 ), and cobalamine (B 12 ) (Dhonukshe-Rutten et al 2003;Swart et al 2016).…”

Vitamin B12 and homocysteine associations with gait speed in older adults: The Baltimore Longitudinal Study of Aging

“…vitamin B12 and folate supplementation, have not consistently shown reductions in cognitive decline (40, 41). physical function decline (42), nor reduced risk of cardiovascular disease (43, 44). Alternatively, homocysteine might be a marker of disease severity rather than a causal agent of disease.…”