Comparative and Combined Effects of Epigallocatechin-3-gallate and Caffeine in Reducing Lipid Accumulation in Caenorhabditis elegans

Epigallocatechin-3-gallate (EGCG) and caffeine, two phytochemicals found in a wide range of natural dietary sources, have been reported to have protective effects against hyperlipidemia, a major risk factor for cardiovascular disease. However, their relative efficacy and synergy in lowering lipid level are unclear. This study intended to compare lipid-lowering activity of EGCG and caffeine and to elucidate their joint action using Caenorhabditis elegans ( C. elegans ) as a model organism. The worms were exposed to EGCG, caffeine or both agents, and lipid accumulation determined by levels of total lipids, triglycerides and cholesterol was monitored. A 3 × 3 factorial design combined with response surface methodology was used to characterize the nature of interactive effects. Total lipids, triglycerides and cholesterol in C. elegans were reduced by either EGCG or caffeine in a dose-dependent manner, with EGCG displaying a stronger lipid-lowering efficacy than caffeine. Overall, the EGCG/caffeine combination for lowering lipids was more effective than either substance alone. Factorial regression models revealed that the combination was antagonistic for total lipid reduction, perhaps due to a “ceiling” effect, and was synergistic for triglyceride-lowering and additive for cholesterol-lowering. Taken together, our work proposes the use of a combination of EGCG and caffeine as an alternative dietary intervention for the prevention of hyperlipidemia, and additionally highlights the suitability of C. elegans model for evaluating lipid-lowering capacity of natural products.