Skip to main content

Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status



Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians.


Double-blind, placebo controlled, randomised crossover study.


Community dwelling vegetarians.


Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. Intervention: Vitamin B-12 (500µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41).


How-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound.


The mean age of the subjects was 45+9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028).


Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention.

This is a preview of subscription content, access via your institution.


  1. 1.

    Key TJ, Appleby PN, Davey GK, Allen NE, Specncer EA, Travis RC. Mortality in British vegetarians: review and preliminary results from EPIC-Oxford. Am J Clin Nutr. 2003;78(suppl):533S–538S.

    PubMed  CAS  Google Scholar 

  2. 2.

    Woo J, Kwok T, Ho SC, Sham A, Lau E. Nutritional status of elderly Chinese vegetarians. Age Ageing 1998;27:455–461.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Hung CJ, Huang PC, Lu SC, Li YH, Huang HB, Lin BF, Chang, SJ, Chou HF. Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores. J Nutr 2002;132:152–158.

    PubMed  CAS  Google Scholar 

  4. 4.

    Kwok T, Chook P, Tam L, Qiao M, Woo JLF, Celermajer DS, Woo KS. Vascular dysfunction in vegetarians: An apparent paradox? J Am Coll Cardiol. 2005;46:1957–1958.

    PubMed  Article  Google Scholar 

  5. 5.

    Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–1115.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999;340:14–22.

    PubMed  Article  Google Scholar 

  7. 7.

    Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997;96:1432–1437.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000;101:948–954.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899–1906.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Woo J, Leung SSF, Ho SC, Sham A, Lam TH, Janus ED. A food frequency questionnaire for use in the Chinese population in Hong Kong: description and examination of validity. Nutrition Research 1997;17:1633–1641.

    Article  CAS  Google Scholar 

  11. 11.

    Woo KS, Chook P, Lolin YI, Cheung ASP, Chan LT, Sun YY, Sanderson JE, Metreweli C, Celermajer DS. Hyperhomocysteinaemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 1997;96:2542–2544.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Woo KS, Chook P, Lolin YI, Sanderson JE, Metreweli C, Celermajer DS. Folic acid improves arterial endothelial function in adults with hyperhomocysteinaemia. J Am Coll Cardiol. 1999;34:2002–2006.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Shipchandler MT, Moorre EG. Rapid, fully automated measurement of plasma homocysteine with Abbott IMX analyzer. Clin Chem. 1995;41:991–994.

    PubMed  CAS  Google Scholar 

  14. 14.

    Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995;91:1314–1319.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC. Close relationship of endothelial cell function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235–1241.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Schroeder S, Enderle MD, Ossen R, Meisner C, Baumbach A, Pfohl M, Herdeg C, Oberhoff M, Haering HU, Karsch KR. Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. Am Heart J. 1999;138:731–739.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O, Deanfield JE. Noninvasive measurement of human endothelium-dependent arterial responses: Accuracy and reproducibility. Br Heart J. 1995;74:247–253.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Woo KS, Chook P, Chan LLT, Cheung ASP, Fung WH, Qiao M, Lolin YI, Thomas GN, Sanderson JE, Metreweli C, Celermajer DS. Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation. Am J Med. 2002;112:535–539.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Salonen R, Salonen JT. Determinants of carotid intima-media thickness: a population-based ultrasonography study in eastern Finnish men. J Intem Med. 1991;299:225–231.

    Article  Google Scholar 

  20. 20.

    Blankenhom DH, Hodis HN. George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal. Arterioscler Thromb Vase Biol. 1994;14:177–192.

    Article  Google Scholar 

  21. 21.

    Woo KS, Chook P, Raitakari OT, McQuillan B, Feng JZ, Celermajer DS. Westernization of Chinese adults and increased subclinical atherosclerosis. Arterioscl Throm Vasc Biol. 1999;19:2487–2493.

    Article  CAS  Google Scholar 

  22. 22.

    Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988;75:800–802.

    Article  Google Scholar 

  23. 23.

    Barnard ND. The lipid-lowering effect of lean meat diets falls far short of that of vegetarian diets. Arch Litern Med. 2000;160:395–396.

    Article  CAS  Google Scholar 

  24. 24.

    Clarke R, Daly LE, Robinson K, Naughten E, Cahalane S, Fowler B, Graham I. Hyperhomocysteinemia: An independent risk factor for vascular disease. N Engl J Med. 1991;324:1149–1155.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Lindenbaum J, Rosenberg IR, Wilson PWF, Stabler SP, Allen RH. Prevalence of vitamin B12 deficiency in the Framingham elderly population. Am J Clin Nutr. 1994;60:2–11.

    PubMed  CAS  Google Scholar 

  26. 26.

    Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH, Nordrehaug JE. Serum total homocysteine and coronary heart disease. Int J Epidemiol. 1995;254:704–709.

    Article  Google Scholar 

  27. 27.

    Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565–575.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Kaul S, Zadeh AA, Shah PK. Homocysteine hypothesis for atherothrombotic cardiovascular disease: not validated. J Am Coll Cardiol. 2006;48:914–923.

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578–1588.

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Lonne E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr, Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–1577.

    Article  Google Scholar 

  31. 31.

    Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, Buring JE, Manson JE. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease. JAMA 2008;299:2027–2036.

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Heinz J., Kropf S., Luley C, Dierkes J. Homocysteine as a Risk Factor for Cardiovascular Disease in Patients Treated by Dialysis: A Meta-analysis. Am J Kidney Dis 2009;54:478–489.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    The Vitatops Trial Study Group. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, paralled, placebo-controlled trial. Lancet Neurol 2010;9:855–65

    Article  Google Scholar 

  34. 34.

    Antoniades C, Shirodaria C, Warrick N, Cai S, de Bono J, Lee J, Leeson P, Neubauer S, Ratnatunga C, Pillai R, Refsum H, Channon KM. 5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation. 2006;114:1193–1201.

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Spijkerman AM, Smulders YM, Kostense PJ, Henry RM, Becker A, Teerlink T, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study. Arterioscl Thromb Vasc Biol. 2005;25:778–784.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Krajcovicova-Kudlackova M, Blazicek P, Babinska K, Kopcova J, Klvanova J, Bederova A, Magalova T. Traditional and alternative nutrition-levels of homocysteine and lipid parameters in adults. Scandinavian Clin Lab Invest. 2006;60:657–664.

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to K. S. Woo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kwok, T., Chook, P., Qiao, M. et al. Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. J Nutr Health Aging 16, 569–573 (2012).

Download citation

Key words

  • Vegetarians
  • vitamin B-12
  • endothelial function
  • intima-media thickening