Ability of dietary factors to affect homocysteine levels in mice: a review

Abstract Homocysteine is associated with several diseases, and a series of dietary factors are known to modulate homocysteine levels. As mice are often used as model organisms to study the effects of dietary hyperhomocysteinemia, we collected data about concentrations of vitamin B12, vitamin B6, folate, methionine, cystine, and choline in mouse diets and the associated plasma/serum homocysteine levels. In addition, we more closely examined the composition of the control diet, the impact of the mouse strain, sex and age, and the duration of the dietary intervention on homocysteine levels. In total, 113 out of 1103 reviewed articles met the inclusion criteria. In the experimental and control diets, homocysteine levels varied from 0.1 to 280 µmol/l. We found negative correlations between dietary vitamin B12 (rho = − 0.125; p < 0.05), vitamin B6 (rho = − 0.191; p < 0.01) and folate (rho = − 0.395; p < 0.001) and circulating levels of homocysteine. In contrast, a positive correlation was observed between dietary methionine and homocysteine (methionine: rho = 0.146; p < 0.05). No significant correlations were found for cystine or choline and homocysteine levels. In addition, there was no correlation between the duration of the experimental diets and homocysteine levels. More importantly, the data showed that homocysteine levels varied widely in mice fed control diets as well. When comparing control diets with similar nutrient concentrations (AIN-based), there were significant differences in homocysteine levels caused by the strain (ANOVA, p < 0.05) and age of the mice at baseline (r = 0.47; p < 0.05). When comparing homocysteine levels and sex, female mice tended to have higher homocysteine levels than male mice (9.3 ± 5.9 µmol/l vs. 5.8 ± 4.5 µmol/l; p = 0.069). To conclude, diets low in vitamin B12, vitamin B6, or folate and rich in methionine are similarly effective in increasing homocysteine levels. AIN recommendations for control diets are adequate with respect to the amounts of homocysteine-modulating dietary parameters. In addition, the mouse strain and the age of mice can affect the homocysteine level.