Functional hyperhomocysteinemia in healthy vegetarians: no association with advanced glycation end products, markers of protein oxidation, or lipid peroxidation after correction with vitamin B(12).

Vegetarians are at risk of developing hyperhomocysteinemia (HHcy). The predominant or selective consumption of proteins of plant origin shifts homocysteine (Hcy) metabolism to the remethylation pathway (1), which requires vitamin B12 as a cofactor and methyltetrahydrofolate as a substrate. In the vegetarian diet, the intake of folic acid exceeds the recommended dietary allowance (RDA), whereas intake of vitamin B12 is inadequate or even absent (2). HHcy represents an independent risk factor for cardiovascular disease (3). Autooxidation of Hcy produces reactive oxygen species (ROS) (4), which may stimulate lipid peroxidation and formation of advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs). Interaction of AGEs with their specific receptor, RAGE, induces formation of ROS (5). In mice, HHcy was shown to enhance the expression of RAGE (6). AGEs, AOPPs, and lipid peroxidation products are implicated in the pathogenesis of degenerative and inflammatory diseases, including atherosclerosis (7). In vegetarians, plasma concentrations of AGEs are mildly but significantly increased compared with populations on a Western mixed diet (8). We therefore investigated ( a ) whether there is an association between Hcy and plasma AGE concentrations or markers of protein oxidation and lipid peroxidation, and ( b ) whether supplementation of vitamin B12 affects the mentioned analytes in vegetarians with HHcy produced by a potential vitamin B12 deficit. The study was approved by the Institutional Ethics Board and was conducted according to the Declaration of Helsinki. All participants gave written consent to participate. We investigated 63 healthy vegetarians in whom HHcy had been revealed previously. The normohomocysteinemic (NHcy; Hcy 12.0 μmol/L) attributable to vitamin B12 deficiency (plasma B12 <220 pmol/L) who had plasma …

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