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.
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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.
Woo J, Kwok T, Ho SC, Sham A, Lau E. Nutritional status of elderly Chinese vegetarians. Age Ageing 1998;27:455–461.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Shipchandler MT, Moorre EG. Rapid, fully automated measurement of plasma homocysteine with Abbott IMX analyzer. Clin Chem. 1995;41:991–994.
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.
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.
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.
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.
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.
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.
Blankenhom DH, Hodis HN. George Lyman Duff Memorial Lecture. Arterial imaging and atherosclerosis reversal. Arterioscler Thromb Vase Biol. 1994;14:177–192.
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.
Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988;75:800–802.
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.
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.
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.
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.
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.
Kaul S, Zadeh AA, Shah PK. Homocysteine hypothesis for atherothrombotic cardiovascular disease: not validated. J Am Coll Cardiol. 2006;48:914–923.
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.
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.
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.
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.
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
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.
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.
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.
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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). https://doi.org/10.1007/s12603-012-0036-x
- vitamin B-12
- endothelial function
- intima-media thickening