The journal of nutrition, health & aging

, Volume 16, Issue 6, pp 569–573 | Cite as

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

  • T. Kwok
  • P. Chook
  • M. Qiao
  • L. Tam
  • Y. K. P. Poon
  • A. T. Ahuja
  • J. Woo
  • D. S. Celermajer
  • K. S. Woo
Article

Abstract

Objective

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.

Design

Double-blind, placebo controlled, randomised crossover study.

Setting

Community dwelling vegetarians.

Participants

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).

Measurement

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

Results

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).

Conclusions

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

Key words

Vegetarians vitamin B-12 endothelial function intima-media thickening 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  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.PubMedGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Shipchandler MT, Moorre EG. Rapid, fully automated measurement of plasma homocysteine with Abbott IMX analyzer. Clin Chem. 1995;41:991–994.PubMedGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefGoogle Scholar
  22. 22.
    Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988;75:800–802.CrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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.CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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;9:855–65CrossRefGoogle 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.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle 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

Copyright information

© Serdi and Springer Verlag France 2012

Authors and Affiliations

  • T. Kwok
    • 1
  • P. Chook
    • 1
    • 2
  • M. Qiao
    • 1
  • L. Tam
    • 1
  • Y. K. P. Poon
    • 1
  • A. T. Ahuja
    • 3
  • J. Woo
    • 1
  • D. S. Celermajer
    • 4
  • K. S. Woo
    • 1
    • 2
    • 5
  1. 1.Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongChina
  2. 2.School of Life SciencesThe Chinese University of Hong KongHong KongChina
  3. 3.Department of Diagnostic Radiology and Organ ImagingThe Chinese University of Hong KongHong KongChina
  4. 4.Department of CardiologyThe University of SydneySydneyAustralia
  5. 5.Room 191, Science Centre South Block, Biochemistry Programme, School of Life SciencesThe Chinese University of Hong KongShatin NT, Hong Kong SARChina

Personalised recommendations