Skip to main content Accessibility help

Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis

  • Derek Obersby (a1), David C. Chappell (a1), Andrew Dunnett (a2) and Amalia A. Tsiami (a1)


There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B12 can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B12 deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B12 levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B12 of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B12 did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B12, from which it can be concluded that the usual dietary source of vitamin B12 is animal products and those who choose to omit or restrict these products are destined to become vitamin B12 deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis
      Available formats


Corresponding author

*Corresponding author: Dr A. Tsiami, E-mail:


Hide All
1 European Vegetarian Union (2011) How many vegetarians?
2 Foods Standards Agency (2011) Public attitude to food issues.
3 The Economic and Social Research Institute (2011) World population of vegetarians.
4 Foods Standards Agency (2011) Vegetarian and vegan diets.
5Ravaglia, G, Forti, P, Maioli, F, et al. (2006) Apolipoprotein E e4 allele affects risk of hyperhomocysteinemia in the elderly. Am J Clin Nutr 84, 14731480.
6Ueland, PM, Refsum, H, Beresford, M, et al. (2000) The controversy over homocysteine and cardiovascular risk. Am J Clin Nut 72, 324332.
7Humphrey, LL, Fu, R, Rogers, K, et al. (2008) Homocysteine level and coronary heart disease: a systematic review and meta-analysis. Mayo Clin Proc 83, 12031212.
8Malinow, MR, Bostom, AG & Krauss, RM (1999) Homocysteine, diet, and cardiovascular disease: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99, 178182.
9Ubbink, JB (2001) What is a desirable homocysteine level? In Homocysteine in Health and Disease, pp. 485490 [Carmel, R and Jacobsen, DW, editors]. Cambridge: Cambridge University Press.
10Kluijtmans, LA, Boers, GH, Tribels, FJ, et al. (1997) Common 844INS68 insertion variant in the cystathionine beta-synthase gene. Biochem Mol Med 62, 2327.
11Selhub, J (1999) Homocysteine metabolism. Ann Rev Nutr 19, 217246.
12Dudman, NPB, Guo, X, Gordon, RB, et al. (1996) Human homocysteine catabolism: 3 major pathways and their relevance to the development of arterial occlusive disease. J Nutr 126, 4 Suppl., 1295S1300S.
13Herrmann, W, Obeid, R, Schorr, H, et al. (2005) The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings. Curr Drug Meta 6, 4753.
14Herbert, V & Zalusky, R (1962) Interrelationship of vitamin B12 and folic acid metabolism: folic acid clearance studies. J Clin Invest 41, 12631276.
15Noronha, JM & Silverman, M (1962) On folic acid, vitamin B12, methionine and formiminoglutamic acid. In Vitamin B12 and Intrinsic Factor 2. Europasches Symposion, p. 728 [Heinrich, HC, editor. Hamburg:, Enke.
16Scott, JM & Weir, DG (1981) The methyl folate trap. A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia. Lancet ii, 337340.
17Chanarin, I, Deacon, R, Lumb, M, et al. (1985) Cobalamin–folate interrelations: a critical review. Blood 66, 478489.
18Butensky, E, Harmatz, P & Lubin, B (2008) Nutritional Anemias. Nutrition in Paediatrics, 4th ed.,chapter 62. Hamilton, ON: BC Decker, Inc.
19European Commission (2008). Commission Directive 2008/100/EC of 28 October 2008 amending Council Directive 90/496/EEC on nutrition labelling for foodstuffs as regards recommended daily allowances, energy conversion factors and definitions. J Eur Union, 285/9–285/12.
20Herbert, V (1994) Staging vitamin B12 (cobalamin) status in vegetarians. Am J Clin Nutr 59, Suppl. 1213S1222S.
21Herbert, V & Das, KC (1994) Folic Acid and Vitamin B12 Nutrition in Health and Disease, 8th ed., pp. 402425. Philadelphia, PA: Lea and Febiger.
22Carmel, R, Rosenberg, AH, Lau, KS, et al. (1969) Vitamin B12 uptake by human small bowel homogenate and its enhancement by intrinsic factor. Gastroenterology 56, 548555.
23Herzlich, B & Herbert, V (1984) The role of pancreas in cobalamin (vitamin B12) absorption. Am J Gastroenterol 79, 489493.
24Herzlich, B, Schiano, T, Moussa Zimbalist, E, et al. (1986) Decreased intrinsic factor secretion in AIDS: relation to parietal cell acid secretory capacity and vitamin B12 malabsorption. Am J Gastroenterol 87, 1781117818.
25Herbert, V, Subak-sharpe, GJ & Hammock, D (1990) The Mount Sinai School of Medicine Complete Book of Nutrition. New York: St Martin's Press.
26Herbert, V (1992) Everyone should be tested for iron disorders. J Am Diet Assoc 92, 15021509.
27Simopoulos, A, Herbert, V & Jacobson, B (1993) Genetic Nutrition: Designing a Diet Based on Your Family Medical History. New York: Macmillan Press.
28Herbert, V (1994) Staging vitamin B12 status in vegetarians. Am J Clin Nutr 59, 1213s1222s.
29Jourdain JR (2005) Evaluation of the use of pectin in children living in the regions contaminated by caesium. Radiological Protection and Human Health Division. Report IRSN/DRPH/2005-008.
30Li, D (2011) Chemistry behind vegetarianism. J Agric Food Chem 59, 777784.
31JBI000308 (2011) Qualitative, meta analysis of statistics assessments and review instruments. Joanna Briggs Inst 9, 104–121.
32Spiegel, MR (1991) Statistics, pp. 88189. New York: McGraw Hill.
33Cappuccio, FP, Bell, R, Perry, IJ, Gilg, J, et al. (2002) Homocysteine levels in men and women of different ethnic and cultural background living in England. Atherosclerosis 164, 95102.
34Haddad, EH, Berk, LS, Kettering, JD, et al. (1999) Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Am J Clin Nutr 70, 586S593S.
35Bissoli, L, Di Francesco, V, Ballarin, A, et al. (2002) Effect of vegetarian diet on homocysteine levels. Ann Nutr Metab 46, 7379.
36Herrmann, W, Schorr, H, Obeid, R, et al. (2003) Vitamin B-12 status, particularly holotranscobalamin “II” and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr 78, 131136.
37Koebnick, C, Garcia, AL & Dagnelie, PC (2005) Long-term consumption of a raw food diet is associated with favourable serum LDL cholesterol and triglycerides but also with elevated plasma homocysteine and low serum HDL cholesterol in humans. J Nutr 135, 23722378.
38Yen, CE, Yen, CH, Cheng, CH, et al. (2010) Vitamin B12 status is not associated with plasma homocysteine in parents and their preschool children: lacto–ovo, lacto, ovo vegetarians & omnivores. J Am Coll Nutr 29, 713.
39Mann, NJ, Li, D, Sinclair, AJ, et al. (1999) The effects of diet on plasma homocysteine in healthy male subjects. Eur J Clin Nutr 53, 895899.
40Krajcovicova-Kudlackova, M, Blazicek, P, Kopvova, J, et al. (2000) Homocysteine levels in vegetarians versus omnivores. Ann Nutr Metab 44, 135138.
41Herrmann, W, Schorr, H, Purschwitz, K, et al. (2001) Total homocysteine, vitamin B12 and total antioxidant status in vegetarians. Clin Chem 47, 10941101.
42Majchrzak, D, Singer, I & Manner, M (2006) B-Vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans. Ann Nutr Metab 50, 485491.
43Huang, YC, Chang, SJ, Chiu, YT, et al. (2003) The status of plasma homocysteine and related to B-vitamins in healthy young vegetarians and non-vegetarians. Eur J Nutr 42, 8490.
44Antony, AC (2001) Prevalence of cobalamin and folate deficiency in India. Am J Clin Nutr 74, 157159.
45Refsum, H, Yajnik, CS, Gadkari, M, et al. (2001) Hyperhomocysteinemia and elevated methylmalonic acid indicate a high prevalence of cobalamin deficiency in Asian Indians. Am J Clin Nutr 74, 233241.
46Waldmann, A, Koschizke, JW, Leitzmann, C, et al. (2003) Homocysteine and cobalamin status in German vegans. Public Health Nutr 74, 6772.
47Su, TC, Jeng, JS, Wang, JD, et al. (2006) Homocysteine, circulating vascular cell adhesion molecule and carotid atherosclerosis in postmenopausal vegetarian women and omnivores. Atherosclerosis 184, 356362.
48Karabudak, E, Kiziltan, G & Cigerim, NA (2008) A comparison of some of the cardiovascular risk factors in vegetarian and omnivorous Turkish females. J Hum Nutr Diet 21, 1322.
49Krivosikova, Z, Krajcovicova-Kudlackova, M, Spustova, V, et al. (2010) The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet. Eur J Nutr 49, 147153.
50Hung, CJ, Huang, PC, Lu, SC, et al. (2002) Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores. J Nutr 132, 152158.
51Joosten, E, van dem Berg, A, Riezler, R, et al. (1993) Metabolic evidence that deficiencies of vitamin B12 (cobalamin), folate, and vitamin B6 occur commonly in elderly people. Am J Clin Nutr 58, 468476.
52Herrmann, W, Schorr, H, Bodis, M, et al. (2000) Role of homocysteine, cystathionine and methylmalonic acid measurement for diagnosis of vitamin B12 deficiency in high-aged subjects. Eur J Clin Invest 30, 10831089.
53Dong, A & Scott, SC (1982) Serum vitamin B12 and blood cell values in vegetarians. Ann Nut Met 26, 209216.
54Herbert, V (1985) Biology of disease: megaloblastic anemia. Lab Invest 52, 319.
55Mathan, VI (1988) Tropical sprue in Southern India. Trans R Soc Trop Med Hyg 82, 1014.
56Balaji, LN & Dustagheer, A (2000) Nutrition scenario in India – implications of clinical practice. J Indian Med Assoc 98, 536538, 542.
57Gilsing, AMJ, Crowe, FL, Sanders, TAB, et al. (2010) Serum concentrations of vitamin B12 and folate in British male omnivores, vegetarians and vegans: results from a cross-sectional analysis of the EPIC-Oxford cohort study. Eur J Clin Nutr 64, 933939.
58The Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. J Am Med Ass 288, 20152022.
59Wald, DS, Law, M & Morris, JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325, 1202.
60Ward, M, McNulty, H, McPartlin, J, et al. (1997) Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. Q J Med 90, 519528.
61The Heart Outcomes Prevention Evaluation (HOPE2) Investigators (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. New Eng J Med 354, 15671577.
62Cooper, BA & Rosenblatt, DS (1987) Inherited defects of vitamin B12 metabolism. An Rev Nut 7, 291320.
63Pezacka, E, Green, R & Jacobsen, DW (1990) Glutathionylcobalamin as a intermediate in the formation of cobalamin coenzymes. Biochem Biophys Res Commun 169, 443450.
64Kelly, G (1997) The coenzyme forms of vitamin B12: towards an understanding of their therapeutic potential. Alt Med Rev 2, 459471.
65Crane, MG (1994) Vitamin B12 studies in total vegetarians. J Nutr Med 4, 114.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed