title: Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia.
abstract: B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514.
authors.affiliation: Department of Internal Medicine, Erasmus MC, 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 MC, Rotterdam, The Netherlands.
authors.forename: Anke W
authors.initials: AW
authors.lastname: Enneman
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Karin M A
authors.initials: KM
authors.lastname: Swart
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Janneke P
authors.initials: JP
authors.lastname: van Wijngaarden
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Annelies C
authors.initials: AC
authors.lastname: Ham
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Jonge
authors.affiliation: Department of Clinical Chemistry, Metabolic Unit, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Edith J
authors.initials: EJ
authors.lastname: Feskens
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Johanna Marianne
authors.initials: JM
authors.lastname: Geleijnse
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Natasja M
authors.initials: NM
authors.lastname: van Schoor
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Rosalie A M
authors.initials: RA
authors.lastname: Dhonukshe-Rutten
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Renate T
authors.initials: RT
authors.lastname: de Jongh
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Lips
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Lisette C P G M
authors.initials: LC
authors.lastname: de Groot
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands Netherlands Consortium for Healthy Ageing, Rotterdam, Leiden, The Netherlands.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ton H
authors.initials: TH
authors.lastname: van den Meiracker
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Francesco U S
authors.initials: FU
authors.lastname: Mattace-Raso
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands Department of Internal Medicine, Section of Geriatrics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Nathalie
authors.initials: N
authors.lastname: van der Velde
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands Department of Internal Medicine and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D019587:Dietary Supplements; D004311:Double-Blind Method; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D009426:Netherlands; D013997:Time Factors; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D004338:Drug Combinations; D018836:Inflammation Mediators; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: B-PROOF; B-vitamins; Biomarkers; endothelial function; folic acid; homocysteine; inflammation