title: Effects of Two-Year Vitamin B12and Folic Acid Supplementation on Depressive Symptoms and Quality of Life in Older Adults with Elevated Homocysteine Concentrations: Additional Results from the B-PROOF Study, an RCT.
abstract: Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N= 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B12and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D₃. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. -0.02,p= 0.004). In conclusion, two-year supplementation with vitamin B12and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL.
authors.affiliation: EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. ej.dekoning@vumc.nl.|Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. ej.dekoning@vumc.nl.
authors.forename: Elisa J
authors.initials: EJ
authors.lastname: de Koning
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. nikitavanderzwaluw@gmail.com.
authors.forename: Nikita L
authors.initials: NL
authors.lastname: van der Zwaluw
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. janneke.vanwijngaarden@gmail.com.
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.affiliation: EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. e.sohl@vumc.nl.|Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. e.sohl@vumc.nl.
authors.forename: Evelien
authors.initials: E
authors.lastname: Sohl
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. elkse.brouwer-brolsma@wur.nl.
authors.forename: Elske M
authors.initials: EM
authors.lastname: Brouwer-Brolsma
authors.affiliation: EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. harm.vanmarwijk@manchester.ac.uk.|Department of General Practice and Elderly Care Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. harm.vanmarwijk@manchester.ac.uk.|Primary Care Research Center, Institute of Population Health, University of Manchester, Oxford Road, M13 9PL Manchester, UK. harm.vanmarwijk@manchester.ac.uk.
authors.forename: Harm W J
authors.initials: HW
authors.lastname: van Marwijk
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. a.enneman@erasmusmc.nl.
authors.forename: Anke W
authors.initials: AW
authors.lastname: Enneman
authors.affiliation: EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. k.swart@vumc.nl.|Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB 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 University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. s.c.vandijk@erasmusmc.nl.
authors.forename: Suzanne C
authors.initials: SC
authors.lastname: van Dijk
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. a.ham@erasmusmc.nl.
authors.forename: Annelies C
authors.initials: AC
authors.lastname: Ham
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. n.vandervelde@erasmusmc.nl.
authors.forename: Nathalie
authors.initials: N
authors.lastname: van der Velde
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. a.g.uitterlinden@erasmusmc.nl.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. b.penninx@vumc.nl.|Department of Psychiatry, VU University Medical Center/GGZ inGeest, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. b.penninx@vumc.nl.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of General Practice and Elderly Care Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. p.elders@vumc.nl.
authors.forename: Petra J M
authors.initials: PJ
authors.lastname: Elders
authors.affiliation: EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. p.lips@vumc.nl.|Department of Internal Medicine/Endocrinology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. p.lips@vumc.nl.
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. rosalie-dhonukshe-rutten@wur.nl.
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.affiliation: EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. nm.vanschoor@vumc.nl.|Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. nm.vanschoor@vumc.nl.
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.affiliation: Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. lisette.degroot@wur.nl.
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
mesh_terms: D000339:Affect; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003863:Depression / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D019587:Dietary Supplements; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D009426:Netherlands; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014805:Vitamin B 12 / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: depressive symptoms; folic acid; homocysteine; hyperhomocysteinemia; older adults; quality of life; randomized controlled trial; vitamin B12