Aims: More than two billion people worldwide are deficient in key micronutrients. Single micronutrients have been used athigh doses to prevent and treat dietary insufficiencies. Yet the impact of combinations of micronutrients in smalldoses aiming to improve lipid disorders and the corresponding metabolic pathways remains incompletely understood.Thus, we investigated whether a combination of micronutrients would reduce fat accumulation and atherosclerosisin mice. Methods and results: Lipoprotein receptor-null mice fed with an original combination of micronutrients incorporated into the daily chowshowed reduced weight gain, body fat, plasma triglycerides, and increased oxygen consumption. These effects wereachieved through enhanced lipid utilization and reduced lipid accumulation in metabolic organs and were mediated, inpart, by the nuclear receptor PPARa. Moreover, the micronutrients partially prevented atherogenesis when administeredearly in life to apolipoprotein E-null mice. When the micronutrient treatment was started before conception,the anti-atherosclerotic effect was stronger in the progeny. This finding correlated with decreased post-prandial triglyceridaemiaand vascular inflammation, two major atherogenic factors. Conclusion: Our data indicate beneficial effects of a combination of micronutritients on body weight gain, hypertriglyceridaemia,liver steatosis, and atherosclerosis in mice, and thus our findings suggest a novel cost-effective combinatorial micronutrient-based strategy worthy of being tested in humans.