Effects of Two-Year Vitamin B12 and 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

Elisa J de Koning; Nikita L van der Zwaluw; Janneke P van Wijngaarden; Evelien Sohl; Elske M Brouwer-Brolsma; Harm W J van Marwijk; Anke W Enneman; Karin M A Swart; Suzanne C van Dijk; Annelies C Ham; Nathalie van der Velde; André G Uitterlinden; Brenda W J H Penninx; Petra J M Elders; Paul Lips; Rosalie A M Dhonukshe-Rutten; Natasja M van Schoor; Lisette C P G M de Groot

doi:10.3390/nu8110748

Effects of Two-Year Vitamin B₁₂ and 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

Nutrients. 2016 Nov 23;8(11):748. doi: 10.3390/nu8110748.

Authors

Elisa J de Koning^{1

2}, Nikita L van der Zwaluw³, Janneke P van Wijngaarden⁴, Evelien Sohl^{5

6}, Elske M Brouwer-Brolsma⁷, Harm W J van Marwijk^{8

9

10}, Anke W Enneman¹¹, Karin M A Swart^{12

13}, Suzanne C van Dijk¹⁴, Annelies C Ham¹⁵, Nathalie van der Velde¹⁶, André G Uitterlinden¹⁷, Brenda W J H Penninx^{18

19}, Petra J M Elders²⁰, Paul Lips^{21

22}, Rosalie A M Dhonukshe-Rutten²³, Natasja M van Schoor^{24

25}, Lisette C P G M de Groot²⁶

Affiliations

¹ EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
² Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
³ Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. [email protected].
⁴ Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. [email protected].
⁵ EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
⁶ Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
⁷ Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. [email protected].
⁸ EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
⁹ Department of General Practice and Elderly Care Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
¹⁰ Primary Care Research Center, Institute of Population Health, University of Manchester, Oxford Road, M13 9PL Manchester, UK. [email protected].
¹¹ Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. [email protected].
¹² EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
¹³ Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
¹⁴ Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. [email protected].
¹⁵ Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. [email protected].
¹⁶ Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. [email protected].
¹⁷ Department of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. [email protected].
¹⁸ EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
¹⁹ Department of Psychiatry, VU University Medical Center/GGZ inGeest, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
²⁰ Department of General Practice and Elderly Care Medicine, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
²¹ EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
²² Department of Internal Medicine/Endocrinology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
²³ Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. [email protected].
²⁴ EMGO Institute for Health and Care Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
²⁵ Department of Epidemiology and Biostatistics, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. [email protected].
²⁶ Division of Human Nutrition, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. [email protected].

Abstract

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B₁₂ and 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 B₁₂ and 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 B₁₂ and 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.

Keywords: depressive symptoms; folic acid; homocysteine; hyperhomocysteinemia; older adults; quality of life; randomized controlled trial; vitamin B12.

Publication types

Multicenter Study
Randomized Controlled Trial

MeSH terms

Affect*
Age Factors
Aged
Biomarkers / blood
Depression / diagnosis
Depression / etiology
Depression / prevention & control*
Depression / psychology
Dietary Supplements*
Double-Blind Method
Drug Combinations
Female
Folic Acid / administration & dosage*
Homocysteine / blood*
Humans
Hyperhomocysteinemia / blood
Hyperhomocysteinemia / diagnosis
Hyperhomocysteinemia / drug therapy*
Male
Netherlands
Psychiatric Status Rating Scales
Quality of Life*
Risk Factors
Time Factors
Treatment Outcome
Up-Regulation
Vitamin B 12 / administration & dosage*

Substances

Biomarkers
Drug Combinations
Homocysteine
Folic Acid
Vitamin B 12