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 B 12 can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B 12 deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B 12 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 B 12 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 B 12 did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B 12 , from which it can be concluded that the usual dietary source of vitamin B 12 is animal products and those who choose to omit or restrict these products are destined to become vitamin B 12 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.

Vegetarians are known to be deficient in vitamin B12, due to a lack of dietary animal products, which can elevate plasma total homocysteine (tHcy). Elevated total tHcy can render vegetarians susceptible to cardiovascular disease (CVD). There are a limited number of published studies in relation to the efficacy of methylcobalamin to normalise plasma tHcy of vitamin B12 deficient vegetarians. The primary objective of the present study was to explore the relationship between supplementary oral methylcobalamin and levels of tHcy of vitamin B12 deficient vegetarians; to reduce the risk of developing primary CVD. A randomised double blind placebo controlled pilot study was conducted to monitor and analyse baseline and post treatment levels of plasma tHcy, 49 volunteer vegetarians were recruited to participate in this study. Statistical analysis employing SPSS software indicated that methylcobalamin reduced mean baseline plasma tHcy of 15.5 µmolL-1 (n=39) to a mean plasma tHcy level of 8.4 µmolL-1 (P < 0.001). In a second group that contained details of ten withdrawn participants, which was conducted on an ‘Intention to Treat’ (ITT) basis, indicated that methylcobalamin was shown to be reduced from a mean baseline plasma tHcy of 14.7 µmolL-1(n=49) to a mean plasma tHcy level of 9.1 µmolL-1 (P < 0.001). The findings of the study have the potential to alert vegetarians of the possible risk of becoming vitamin B12 deficient, and to help avoid the risk of developing homocysteine related CVD. The quality data obtained in the study will allow an accurate sample size to be calculated for a future definite clinical study.

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Homocysteine can be remethylated through the major folic cycle path. It is recycled to methionine in a reaction catalyzed by the enzyme methionine synthase and is absolutely dependent on the essential vitamin B12 methylcobalamin (MeCbl). All other forms of vitamin B12 must be converted to MeCbl prior to their usage (1) . This can prove to be problematic, particularly for the aged (2,3) . Vegetarians are known to be susceptible to vitamin B12 deficiency, due to a lack of dietary animal produce, which can elevate plasma total homocysteine (tHcy). There is positive evidence that links elevated plasma (tHcy) with cardiovascular disease (CVD) (4) .The specific objective of the present study was to establish if supplementary MeCbl will optimise elevated levels of plasma tHcy of vitamin B12 deficient vegetarians.The design of the study was a parallel double blind randomised placebo controlled trial. The treatment regimes were either a 1 mg MeCbl lozenge (the intervention group) taken every second day for 16 weeks or identical placebo. Successful participants firstly completed a confidential questionnaire/application form and met the study criteria, which included having a baseline plasma tHcy level > 10 μmolL −1 and who had been practicing vegetarianism for ⩾ 3 years, age 18 to 65 years old were recruited via the Vegetarian and Vegan Societies. The subjects comprised lactovegetarians/ lactoovovegetarians (n = 25) and vegans (n = 14). During the study participant diets were closely supervised by the compilation of diet diaries. Homocysteine assay was conducted by the accredited and validated self-test kit supplied and tested by Yorktest Laboratories Ltd. The study was approved by the University Ethics Committee and conducted in accordance with the WMA declaration of Helsinki. The protocol for the study was registered with ClinicalTrials.gov Protocol Registration System. A paired samples t test on baseline and post intervention levels of plasma t Hcy was performed employing SPSS software, with the null hypothesis (H0) being defined as 'there will be no reduction in plasma tHcy following treatment' H0 was rejected if the change in plasma tHcy was not zero, but accepted if it was zero. The results are summarised below:The results indicates that H0 can be rejected for the MeCbl group since P < 0·05 and CI 95 % does not pass through zero whereas the placebo group H0 is accepted, since P > 0·05 and CI 95 % passes through zero. The paired samples t test also demonstrated that MeCbl effectively optimised homocysteine levels of baseline mean value of 15·5μmolL −1 to post intervention mean level of 8·4μmolL −1 (not shown).Examination of participant food diaries confirmed that strict vegetarian diets were maintained throughout the period of the study and that all other bio-regulation of homocysteine nutrients met RDA and AI values. Overall, it is therefore reasonable to deduce that the results of the study indicate that MeCbl optimises elevated levels of homocysteine (to <10μmolL −1 ) of vitamin B12 deficient vegetarians and will ...

There is strong evidence indicating that elevated plasma homocysteine levels are a major independent biomarker and/or a contributor to chronic conditions, such as cardiovascular disease (CVD) (1,2) . It has been shown that a deficiency of vitamin B12 can elevate homocysteine (3) . Vegetarians are a group of the population who are potentially at greater risk of vitamin B12 deficiency than omnivores, brought about by a dietary inadequacy or absence of animal produce, the only normal source of vitamin B12. There is no vitamin B12 synthesized by any plant, nor does any plant use or store vitamin B12 (4) .The object of the present study is to stratify a range of acceptable cohort studies that compare the homocysteine and vitamin B12 status of vegetarians and omnivores and to compile a systematic review and meta-analysis of which to-date there is no record of any publication. A further object is to investigate the relationship between levels of plasma tHcy and the associated risk of developing CVD.Search methods employed in the present study have identified 244 entries from which by screening, using set inclusion and exclusion criteria revealed sixteen eligible cohort case study publications from 1999 to 2010 that compared concentrations of plasma total homocysteine (tHcy) and serum vitamin B12 of omnivores, lactovegetarians or lactoovovegetarians (LV-LOV's) and vegans.Of the sixteen studies (2958 participants) which were identified; only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B12 did not differ from omnivores, which appears to be due to confounding circumstances. The meta-analysis confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B12. Values are mean, standard deviation, and significant difference value P of LV-LOV's and vegans from omnivores for plasma tHcy and serum vitamin B12 calculated levels, of the selected cohort studies.The Table above summarises the results from the calculated values of the selected cohort case studies indicating that vegans have the highest plasma tHcy and the lowest serum vitamin B12 concentrations. LV-LOV's were second highest plasma tHcy and second lowest plasma vitamin B12, from which it is reasonable to conclude that the usual dietary source of vitamin B12 is from animal products and those who choose to omit or restrict these products are destined to become vitamin B12 deficient, which can consequently result in elevated plasma tHcy and a potential increased risk of developing CVD.