Skip to main content

Advertisement

Log in

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

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

FRS:

Framingham risk score

RDA:

Recommended dietary allowance

References

  1. Ueland PM, Loscalzo J (2012) Homocysteine and cardiovascular risk: the perils of reductionism in a complex system. Clin Chem 58:1623–1625

    Article  CAS  Google Scholar 

  2. McCully KS (2007) Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr 86:1563S–1568S

    CAS  Google Scholar 

  3. 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 80:846–855

    Article  CAS  Google Scholar 

  4. Robinson K (2004) Renal disease, homocysteine, and cardiovascular complications. Circulation 109:294–295

    Article  Google Scholar 

  5. 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 93:941–949

    Article  CAS  Google Scholar 

  6. 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 303:2486–2494

    Article  CAS  Google Scholar 

  7. 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 34:83–91

    Article  CAS  Google Scholar 

  8. 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 354:1578–1588

    Article  CAS  Google Scholar 

  9. 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 354:1567–1577

    Article  CAS  Google Scholar 

  10. 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 9:855–865

    Article  Google Scholar 

  11. 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 279:359–364

    Article  CAS  Google Scholar 

  12. 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 103:2674–2680

    Article  CAS  Google Scholar 

  13. Lee M, Hong KS, Chang SC, Saver JL (2010) Efficacy of homocysteine-lowering therapy with folic acid in stroke prevention: a meta-analysis. Stroke 41:1205–1212

    Article  CAS  Google Scholar 

  14. 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 369:1876–1882

    Article  CAS  Google Scholar 

  15. US Food and Drug Administration (2000) Letter regarding dietary supplement health claim for folic acid, vitamin B6, and vitamin B12 and vascular disease (Docket No. 99P-3029). http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm072865.htm#tab

  16. US Food and Drug Administration (2001) Settlement reached for health claim relating B vitamins and vascular disease. http://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm072855.htm

  17. 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 40:1209–1218

    Article  CAS  Google Scholar 

  18. Gale CR, Ashurst H, Phillips NJ, Moat SJ, Bonham JR, Martyn CN (2001) Renal function, plasma homocysteine and carotid atherosclerosis in elderly people. Atherosclerosis 154:141–146

    Article  CAS  Google Scholar 

  19. 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. 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 303:1603–1609

    Article  CAS  Google Scholar 

  21. 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 93:11–18

    Article  CAS  Google Scholar 

  22. O’Broin S, Kelleher B (1992) Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol 45:344–347

    Article  Google Scholar 

  23. Petrie JC, O’Brien ET, Littler WA, de Swiet M (1986) Recommendations on blood pressure measurement. Br Med J (Clin Res Ed) 293:611–615

    Article  CAS  Google Scholar 

  24. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847

    Article  CAS  Google Scholar 

  25. 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

    Google Scholar 

  26. 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

    CAS  Google Scholar 

  27. 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. 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 28:1482–1487

    Article  CAS  Google Scholar 

  29. 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 93:37–46

    Article  CAS  Google Scholar 

  30. 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 355:517–522

    Article  CAS  Google Scholar 

  31. 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 158:533–539

    Article  Google Scholar 

  32. 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 37:697–701

    Article  CAS  Google Scholar 

  33. Verhaar MC, Stroes E, Rabelink TJ (2002) Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 22:6–13

    Article  CAS  Google Scholar 

  34. 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 90:4622–4629

    Article  CAS  Google Scholar 

  35. 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 19:1031–1035

    Article  CAS  Google Scholar 

  36. 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 59:728–733

    Article  CAS  Google Scholar 

  37. 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 169:493–511

    Article  CAS  Google Scholar 

  38. 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 93:1365–1372

    Article  CAS  Google Scholar 

  39. Office of Dietary Supplements National Institutes of Health (2013) Dietary supplement fact sheet. http://ods.od.nih.gov/factsheets/list-all/

  40. 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 30:6–15

    Article  CAS  Google Scholar 

  41. Loscalzo J (2006) Homocysteine trials—clear outcomes for complex reasons. N Engl J Med 354:1629–1632

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by two grants from the National Natural Science Foundation of China (Grant Nos. 30572071; 30471486). We thank Dr. Zuguo Mei (U.S. Centers for Disease Control and Prevention) and Dr. Shufeng Zhou (University of South Florida) for their thoughtful review and editing of this manuscript. We thank all participants for their dedication and the local health workers for their assistance with subject recruitment and data collection.

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jianmeng Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Li, H., Zhou, Y. et al. Low-dose B vitamins supplementation ameliorates cardiovascular risk: a double-blind randomized controlled trial in healthy Chinese elderly. Eur J Nutr 54, 455–464 (2015). https://doi.org/10.1007/s00394-014-0729-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-014-0729-5

Keywords

Navigation