Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians

Am J Clin Nutr. 2003 Jul;78(1):131-6. doi: 10.1093/ajcn/78.1.131.


Background: Vegetarians have a lower intake of vitamin B-12 than do omnivores. Early and reliable diagnosis of vitamin B-12 deficiency is very important.

Objective: The objective was to investigate vitamin B-12 status in vegetarians and nonvegetarians.

Design: The study cohort included 66 lactovegetarians or lactoovovegetarians (LV-LOV group), 29 vegans, and 79 omnivores. Total vitamin B-12, methylmalonic acid, holotranscobalamin II, and total homocysteine concentrations were assayed in serum.

Results: Of the 3 groups, the vegans had the lowest vitamin B-12 status. In subjects who did not consume vitamins, low holotranscobalamin II (< 35 pmol/L) was found in 11% of the omnivores, 77% of the LV-LOV group, and 92% of the vegans. Elevated methylmalonic acid (> 271 nmol/L) was found in 5% of the omnivores, 68% of the LV-LOV group, and 83% of the vegans. Hyperhomocysteinemia (> 12 micromol/L) was present in 16% of the omnivores, 38% of the LV-LOV group, and 67% of the vegans. The correlation between holotranscobalamin II and vitamin B-12 was weak in the low serum vitamin B-12 range (r = 0.403) and strong in the high serum vitamin B-12 range (r = 0.769). Holotranscobalamin II concentration was the main determinant of total homocysteine concentration in the vegetarians (beta = -0.237, P < 0.001). Vitamin B-12 deficiency led to hyperhomocysteinemia that was not probable in the upper folate range (> 42.0 nmol/L).

Conclusions: Vegan subjects and, to a lesser degree, subjects in the LV-LOV group had metabolic features indicating vitamin B-12 deficiency that led to a substantial increase in total homocysteine concentrations. Vitamin B-12 status should be monitored in vegetarians. Health aspects of vegetarianism should be considered in the light of possible damaging effects arising from vitamin B-12 deficiency and hyperhomocysteinemia.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Diet, Vegetarian*
  • Female
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / etiology*
  • Male
  • Methylmalonic Acid / blood*
  • Middle Aged
  • Osmolar Concentration
  • Transcobalamins / analysis*
  • Vitamin B 12 / blood*


  • Biomarkers
  • Transcobalamins
  • Homocysteine
  • Methylmalonic Acid
  • Folic Acid
  • Vitamin B 12