Atherosclerosis Prevention by Nutritional Factors: a Meta-analysis in Small Animal Models

Background And Aims: Atherosclerosis prevention in small laboratory models has been used as a preclinical stage in the development of functional foods with claimed antiatherogenic properties. However, a high heterogeneity of experimental atherosclerosis models as well as species-specific differences in lipoprotein metabolism could limit the usefulness of these developments. To solve this, we have performed a meta-analysis on the effects of nutritional complements (i.e. less than 2% of diet) with potential antiatherogenic properties in mice, rabbits and hamsters, and compared the outcomes with those obtained in humans.

Methods And Results: A meta-analysis comprising works dealing with dietary prevention of experimental atherosclerosis (i.e. macroscopic and/or pathological evidences of atheromatosis in aorta) has been performed (n = 110 works). Quality criteria were applied resulting in selection of 16 works comprising 511 animals. Despite high heterogeneity, there is a significant effect of nutritional interventions reducing atheroma globally (mean effect 24.38% (95% CI: 13.24-35.51%) of prevention). In mouse studies (20.64% (95% CI: 8.38-32.90%)) and in rabbits (40.48% (95% CI: 6.73-74.23%)) this effect was significant, in contrast with hamster-based works (95% CI: 13.66-49.48%). Meta-regression showed that reduction of atheroma plaque formation was not linked to changes either in total circulating cholesterol or LDL cholesterol levels.

Conclusion: Nutritional addition of selected compounds significantly prevents experimental atheromatosis, but the reproduction of positive effects observed in humans was very limited. These analyses reinforce the need for adequate standardization of atherosclerosis studies in preclinical models and for human intervention trials.