Skip to main content
Top
Published in: European Journal of Nutrition 3/2015

01-04-2015 | Original Contribution

Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly

Authors: Linlin Wang, Hongtian Li, Yuan Zhou, Lei Jin, Jianmeng Liu

Published in: European Journal of Nutrition | Issue 3/2015

Login to get access

Abstract

Purpose

We investigated whether daily supplementation with low-dose B vitamins in the healthy elderly population improves the Framingham risk score (FRS), a predictor of cardiovascular disease risk.

Methods

Between 2007 and 2012, a double-blind randomized controlled trial was conducted in a rural area of North China. In all, 390 healthy participants aged 60–74 were randomly allocated to receive daily vitamin C (50 mg; control group) or vitamin C plus B vitamins (400 µg folic acid, 2 mg B6, and 10 µg B12; treatment group) for 12 months. FRSs were calculated for all 390 subjects.

Results

Folate and vitamin B12 plasma concentrations in the treatment group increased by 253 and 80 %, respectively, after 6 months, stopped increasing with continued supplementation after 12 months and returned to baseline levels 6 months after supplementation cessation. Compared with the control group, there was no significant effect of B vitamin supplementation on FRSs after 6 months (mean difference −0.38; 95 % CI −1.06, 0.31; p = 0.279), whereas a significant effect of supplementation was evident after 12 months (reduced magnitude 7.6 %; −0.77; 95 % CI −1.47, −0.06; p = 0.033). However, this reduction disappeared 6 months after supplementation stopped (−0.07; 95 % CI −0.80, 0.66; p = 0.855). The reduction in FRS 12 months after supplementation was more pronounced in individuals with a folate deficiency (10.4 %; −1.30; 95 % CI −2.54, −0.07; p = 0.039) than in those without (4.1 %; −0.38; 95 % CI −1.12, 0.36; p = 0.313). B vitamins increased high-density lipoprotein cholesterol by 3.4 % after 6 months (0.04; 95 % CI −0.02, 0.10; p = 0.155) and by 9.2 % after 12 months (0.11; 95 % CI 0.04, 0.18; p = 0.003). Compared with the control group, this change in magnitude decreased to 3.3 % (0.04; 95 % CI −0.02, 0.10; p = 0.194) 6 months after supplementation cessation.

Conclusions

Daily supplementation with a low-dose of B vitamins for 12 months reduced FRS, particularly in healthy elderly subjects with a folate deficiency. These reduced effects declined after supplementation cessation, indicating a need for persistent supplementation to maintain the associated benefits.
Literature
1.
go back to reference Ueland PM, Loscalzo J (2012) Homocysteine and cardiovascular risk: the perils of reductionism in a complex system. Clin Chem 58:1623–1625CrossRef Ueland PM, Loscalzo J (2012) Homocysteine and cardiovascular risk: the perils of reductionism in a complex system. Clin Chem 58:1623–1625CrossRef
2.
go back to reference McCully KS (2007) Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr 86:1563S–1568S McCully KS (2007) Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr 86:1563S–1568S
3.
go back to reference Hustad S, Midttun O, Schneede J, Vollset SE, Grotmol T, Ueland PM (2007) The methylenetetrahydrofolate reductase 677C→T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. Am J Hum Genet 80:846–855CrossRef Hustad S, Midttun O, Schneede J, Vollset SE, Grotmol T, Ueland PM (2007) The methylenetetrahydrofolate reductase 677C→T polymorphism as a modulator of a B vitamin network with major effects on homocysteine metabolism. Am J Hum Genet 80:846–855CrossRef
4.
go back to reference Robinson K (2004) Renal disease, homocysteine, and cardiovascular complications. Circulation 109:294–295CrossRef Robinson K (2004) Renal disease, homocysteine, and cardiovascular complications. Circulation 109:294–295CrossRef
5.
go back to reference Durga J, Bots ML, Schouten EG, Grobbee DE, Kok FJ, Verhoef P (2011) Effect of 3 y of folic acid supplementation on the progression of carotid intima-media thickness and carotid arterial stiffness in older adults. Am J Clin Nutr 93:941–949CrossRef Durga J, Bots ML, Schouten EG, Grobbee DE, Kok FJ, Verhoef P (2011) Effect of 3 y of folic acid supplementation on the progression of carotid intima-media thickness and carotid arterial stiffness in older adults. Am J Clin Nutr 93:941–949CrossRef
6.
go back to reference Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Sleight P, Peto R, Collins R (2010) Effects of homocysteine-lowering with folic acid plus vitamin B12 vs. placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA 303:2486–2494CrossRef Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Sleight P, Peto R, Collins R (2010) Effects of homocysteine-lowering with folic acid plus vitamin B12 vs. placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA 303:2486–2494CrossRef
7.
go back to reference Clarke R, Halsey J, Bennett D, Lewington S (2011) Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials. J Inherit Metab Dis 34:83–91CrossRef Clarke R, Halsey J, Bennett D, Lewington S (2011) Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials. J Inherit Metab Dis 34:83–91CrossRef
8.
go back to reference Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354:1578–1588CrossRef Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354:1578–1588CrossRef
9.
go back to reference Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354:1567–1577CrossRef Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354:1567–1577CrossRef
10.
go back to reference The VITATOPS Trial Study Group (2010) B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol 9:855–865CrossRef The VITATOPS Trial Study Group (2010) B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol 9:855–865CrossRef
11.
go back to reference Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ (1998) Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 279:359–364CrossRef Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ (1998) Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 279:359–364CrossRef
12.
go back to reference Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT (2001) Low dietary folate intake is associated with an excess incidence of acute coronary events: the Kuopio Ischemic Heart Disease Risk Factor Study. Circulation 103:2674–2680CrossRef Voutilainen S, Rissanen TH, Virtanen J, Lakka TA, Salonen JT (2001) Low dietary folate intake is associated with an excess incidence of acute coronary events: the Kuopio Ischemic Heart Disease Risk Factor Study. Circulation 103:2674–2680CrossRef
13.
go back to reference Lee M, Hong KS, Chang SC, Saver JL (2010) Efficacy of homocysteine-lowering therapy with folic acid in stroke prevention: a meta-analysis. Stroke 41:1205–1212CrossRef Lee M, Hong KS, Chang SC, Saver JL (2010) Efficacy of homocysteine-lowering therapy with folic acid in stroke prevention: a meta-analysis. Stroke 41:1205–1212CrossRef
14.
go back to reference Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X (2007) Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 369:1876–1882CrossRef Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X (2007) Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 369:1876–1882CrossRef
17.
go back to reference Elshorbagy AK, Oulhaj A, Konstantinova S, Nurk E, Ueland PM, Tell GS, Nygard O, Vollset SE, Refsum H (2007) Plasma creatinine as a determinant of plasma total homocysteine concentrations in the Hordaland Homocysteine Study: use of statistical modeling to determine reference limits. Clin Biochem 40:1209–1218CrossRef Elshorbagy AK, Oulhaj A, Konstantinova S, Nurk E, Ueland PM, Tell GS, Nygard O, Vollset SE, Refsum H (2007) Plasma creatinine as a determinant of plasma total homocysteine concentrations in the Hordaland Homocysteine Study: use of statistical modeling to determine reference limits. Clin Biochem 40:1209–1218CrossRef
18.
go back to reference Gale CR, Ashurst H, Phillips NJ, Moat SJ, Bonham JR, Martyn CN (2001) Renal function, plasma homocysteine and carotid atherosclerosis in elderly people. Atherosclerosis 154:141–146CrossRef Gale CR, Ashurst H, Phillips NJ, Moat SJ, Bonham JR, Martyn CN (2001) Renal function, plasma homocysteine and carotid atherosclerosis in elderly people. Atherosclerosis 154:141–146CrossRef
19.
go back to reference National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third report of the National Cholesterol Education Program (NCEP) expert panel on detection E, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421 National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third report of the National Cholesterol Education Program (NCEP) expert panel on detection E, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421
20.
go back to reference House AA, Eliasziw M, Cattran DC, Churchill DN, Oliver MJ, Fine A, Dresser GK, Spence JD (2010) Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA 303:1603–1609CrossRef House AA, Eliasziw M, Cattran DC, Churchill DN, Oliver MJ, Fine A, Dresser GK, Spence JD (2010) Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA 303:1603–1609CrossRef
21.
go back to reference Tighe P, Ward M, McNulty H, Finnegan O, Dunne A, Strain J, Molloy AM, Duffy M, Pentieva K, Scott JM (2011) A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy. Am J Clin Nutr 93:11–18CrossRef Tighe P, Ward M, McNulty H, Finnegan O, Dunne A, Strain J, Molloy AM, Duffy M, Pentieva K, Scott JM (2011) A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy. Am J Clin Nutr 93:11–18CrossRef
22.
go back to reference O’Broin S, Kelleher B (1992) Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol 45:344–347CrossRef O’Broin S, Kelleher B (1992) Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol 45:344–347CrossRef
23.
go back to reference Petrie JC, O’Brien ET, Littler WA, de Swiet M (1986) Recommendations on blood pressure measurement. Br Med J (Clin Res Ed) 293:611–615CrossRef Petrie JC, O’Brien ET, Littler WA, de Swiet M (1986) Recommendations on blood pressure measurement. Br Med J (Clin Res Ed) 293:611–615CrossRef
24.
go back to reference Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847CrossRef Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847CrossRef
25.
go back to reference Collaboration Homocysteine Lowering Trialists’ (2005) Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 82:806–812 Collaboration Homocysteine Lowering Trialists’ (2005) Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 82:806–812
26.
go back to reference Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH (1993) Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 39:1764–1779 Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH (1993) Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 39:1764–1779
27.
go back to reference Federation of American Societies for Experimental Biology (1984) Assessment of the folate nutritional status of the U.S. population based on data collected in the second National Health and Nutrition Examination Survey, 1976–1980. Federation of American Societies for Experimental Biology, Bethesda, MD Federation of American Societies for Experimental Biology (1984) Assessment of the folate nutritional status of the U.S. population based on data collected in the second National Health and Nutrition Examination Survey, 1976–1980. Federation of American Societies for Experimental Biology, Bethesda, MD
28.
go back to reference Izzo R, de Simone G, Giudice R, Chinali M, Trimarco V, De Luca N, Trimarco B (2010) Effects of nutraceuticals on prevalence of metabolic syndrome and on calculated Framingham Risk Score in individuals with dyslipidemia. J Hypertens 28:1482–1487CrossRef Izzo R, de Simone G, Giudice R, Chinali M, Trimarco V, De Luca N, Trimarco B (2010) Effects of nutraceuticals on prevalence of metabolic syndrome and on calculated Framingham Risk Score in individuals with dyslipidemia. J Hypertens 28:1482–1487CrossRef
29.
go back to reference Bhupathiraju SN, Tucker KL (2011) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults. Am J Clin Nutr 93:37–46CrossRef Bhupathiraju SN, Tucker KL (2011) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults. Am J Clin Nutr 93:37–46CrossRef
30.
go back to reference Vermeulen EG, Stehouwer CD, Twisk JW, van den Berg M, de Jong SC, Mackaay AJ, van Campen CM, Visser FC, Jakobs CA, Bulterjis EJ, Rauwerda JA (2000) Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. Lancet 355:517–522CrossRef Vermeulen EG, Stehouwer CD, Twisk JW, van den Berg M, de Jong SC, Mackaay AJ, van Campen CM, Visser FC, Jakobs CA, Bulterjis EJ, Rauwerda JA (2000) Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. Lancet 355:517–522CrossRef
31.
go back to reference Morrison KM, Atkinson SA, Yusuf S, Bourgeois J, McDonald S, McQueen MJ, Persadie R, Hunter B, Pogue J, Teo K (2009) The Family Atherosclerosis Monitoring In early life (FAMILY) study: rationale, design, and baseline data of a study examining the early determinants of atherosclerosis. Am Heart J 158:533–539CrossRef Morrison KM, Atkinson SA, Yusuf S, Bourgeois J, McDonald S, McQueen MJ, Persadie R, Hunter B, Pogue J, Teo K (2009) The Family Atherosclerosis Monitoring In early life (FAMILY) study: rationale, design, and baseline data of a study examining the early determinants of atherosclerosis. Am Heart J 158:533–539CrossRef
32.
go back to reference Wilcken DE, Dudman NP, Tyrrell PA, Robertson MR (1988) Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: possible implications for prevention of vascular disease. Metabolism 37:697–701CrossRef Wilcken DE, Dudman NP, Tyrrell PA, Robertson MR (1988) Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: possible implications for prevention of vascular disease. Metabolism 37:697–701CrossRef
33.
go back to reference Verhaar MC, Stroes E, Rabelink TJ (2002) Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 22:6–13CrossRef Verhaar MC, Stroes E, Rabelink TJ (2002) Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 22:6–13CrossRef
34.
go back to reference Villa P, Perri C, Suriano R, Cucinelli F, Panunzi S, Ranieri M, Mele C, Lanzone A (2005) L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism. J Clin Endocrinol Metab 90:4622–4629CrossRef Villa P, Perri C, Suriano R, Cucinelli F, Panunzi S, Ranieri M, Mele C, Lanzone A (2005) L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism. J Clin Endocrinol Metab 90:4622–4629CrossRef
35.
go back to reference Paradisi G, Cucinelli F, Mele MC, Barini A, Lanzone A, Caruso A (2004) Endothelial function in post-menopausal women: effect of folic acid supplementation. Hum Reprod 19:1031–1035CrossRef Paradisi G, Cucinelli F, Mele MC, Barini A, Lanzone A, Caruso A (2004) Endothelial function in post-menopausal women: effect of folic acid supplementation. Hum Reprod 19:1031–1035CrossRef
36.
go back to reference Imamura A, Murakami R, Takahashi R, Cheng XW, Numaguchi Y, Murohara T, Okumura K (2010) Low folate levels may be an atherogenic factor regardless of homocysteine levels in young healthy nonsmokers. Metabolism 59:728–733CrossRef Imamura A, Murakami R, Takahashi R, Cheng XW, Numaguchi Y, Murohara T, Okumura K (2010) Low folate levels may be an atherogenic factor regardless of homocysteine levels in young healthy nonsmokers. Metabolism 59:728–733CrossRef
37.
go back to reference Tran-Dinh A, Diallo D, Delbosc S, Varela-Perez LM, Dang QB, Lapergue B, Burillo E, Michel JB, Levoye A, Martin-Ventura JL, Meilhac O (2013) HDL and endothelial protection. Br J Pharmacol 169:493–511CrossRef Tran-Dinh A, Diallo D, Delbosc S, Varela-Perez LM, Dang QB, Lapergue B, Burillo E, Michel JB, Levoye A, Martin-Ventura JL, Meilhac O (2013) HDL and endothelial protection. Br J Pharmacol 169:493–511CrossRef
38.
go back to reference Crider KS, Zhu JH, Hao L, Yang QH, Yang TP, Gindler J, Maneval DR, Quinlivan EP, Li Z, Bailey LB, Berry RJ (2011) MTHFR 677C→T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. Am J Clin Nutr 93:1365–1372CrossRef Crider KS, Zhu JH, Hao L, Yang QH, Yang TP, Gindler J, Maneval DR, Quinlivan EP, Li Z, Bailey LB, Berry RJ (2011) MTHFR 677C→T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. Am J Clin Nutr 93:1365–1372CrossRef
40.
go back to reference Antoniades C, Antonopoulos AS, Tousoulis D, Marinou K, Stefanadis C (2009) Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials. Eur Heart J 30:6–15CrossRef Antoniades C, Antonopoulos AS, Tousoulis D, Marinou K, Stefanadis C (2009) Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials. Eur Heart J 30:6–15CrossRef
41.
go back to reference Loscalzo J (2006) Homocysteine trials—clear outcomes for complex reasons. N Engl J Med 354:1629–1632CrossRef Loscalzo J (2006) Homocysteine trials—clear outcomes for complex reasons. N Engl J Med 354:1629–1632CrossRef
Metadata
Title
Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly
Authors
Linlin Wang
Hongtian Li
Yuan Zhou
Lei Jin
Jianmeng Liu
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 3/2015
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-014-0729-5

Other articles of this Issue 3/2015

European Journal of Nutrition 3/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.