Background/Aims: Increased ingestion of tomato, containing lycopene, has been associated with a decreased risk for atherosclerosis, although the exact molecular mechanism is still unknown. Here we review the available evidence for a direct regulation of tomato lycopene on cholesterol metabolism using results from experimental and human studies. Results: In human macrophages lycopene dose dependently reduced intracellular total cholesterol. Such an effect was associated with a decrease in cholesterol synthesis through a reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and expression, a modulation of low- density lipoprotein (LDL) receptor and acyl-coenzyme A:cholesterol acyltransferase activity. An increase in cholesterol efflux through an enhancement of ABCA1 and caveolin-1 expression was also observed. In animal models of atherosclerosis, lycopene and tomato products decreased plasma total cholesterol, LDL cholesterol and increased high-density lipoprotein cholesterol. In agreement with the experimental results, most human intervention trials analyzed show that dietary supplementation with lycopene and/or tomato products reduced plasma LDL cholesterol dependently on the dose and the time of administration. Conclusions: Although lycopene and tomato products seem to possess direct hypocholesterolemic properties, more experimental studies are needed to better understand the mechanisms involved. There is also a need for more well-designed human dietary intervention studies to better clarify the role of lycopene as a hypocholesterolemic agent.

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