title: 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.
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. k.swart@vumc.nl.
authors.forename: Karin M A
authors.initials: KM
authors.lastname: Swart
authors.affiliation: Department of Internal Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Annelies C
authors.initials: AC
authors.lastname: Ham
authors.affiliation: Department of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.affiliation: Department of Internal Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Anke W
authors.initials: AW
authors.lastname: Enneman
authors.affiliation: Department of Internal Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Dijk
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Evelien
authors.initials: E
authors.lastname: Sohl
authors.affiliation: Department of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Elske M
authors.initials: EM
authors.lastname: Brouwer-Brolsma
authors.affiliation: Department of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Nikita L
authors.initials: NL
authors.lastname: van der Zwaluw
authors.affiliation: Department of Internal Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.affiliation: Department of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.affiliation: Department of Internal Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Nathalie
authors.initials: N
authors.lastname: van der Velde
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brug
authors.affiliation: Department of Internal Medicine, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
authors.affiliation: Department of Internal Medicine, Endocrine Section and the EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
mesh_terms: D000058:Accidental Falls / Q000517:prevention & control / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects / Q000502:physiology; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D018737:Hand Strength / Q000502:physiology*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D058866:Osteoporotic Fractures / Q000453:epidemiology; D010809:Physical Fitness; D014805:Vitamin B 12 / Q000008:administration & dosage*
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Aging; Falling; Folic acid; Homocysteine; Physical function; Vitamin B12