TOTUM-070 is a botanical complex with demonstrated efficacy to reduce LDL-cholesterol in several preclinical models. This clinical trial aims to assess, for the first time in humans, the efficacy of TOTUM-070 on plasma lipids concentration in subjects with moderate hypercholesterolemia. Our hypothesis is that Totum-070 taken daily for 24weeks will decrease fasting blood LDL-cholesterol compared to placebo.

This multicentric randomized, double-blind, placebo-controlled trial included 120 subjects (men and women, aged 18–70years), with moderate hypercholesterolemia (between 130 and 190mg/dL), who were not receiving cholesterol-lowering medication. Subjects were randomly assigned to consume TOTUM-070 or placebo for 24weeks. The primary outcome was the fasting blood LDL-cholesterol concentration after 24weeks (V3). Secondary outcomes included other plasma lipid parameters such as triglycerides, total cholesterol, non-HDL-cholesterol, and apolipoproteins. Intermediate analysis was scheduled after 12weeks of supplementation (V2). Atherogenic index was calculated using the log10 (TG/HDL-chol) equation. Safety markers were also measured. Analysis was performed by intention to treat. The HEART study is registered at ClinicalTrials.gov: NCT04760951.

Blood LDL-cholesterol concentration was reduced by −13% and −9% compared to placebo after 12 and 24weeks of supplementation, respectively (from 146±26mg/dL at baseline to 127±18mg/dL after 12weeks, P<0.001; and 133±21mg/dL after 24weeks, P<0.01). In addition, TOTUM-070 consumption reduced blood levels of total cholesterol (−15% at 12weeks P<0.05; −16% at 24weeks, P<0.01), non-HDL-cholesterol (−14% at 12weeks, P<0.01; and −17% at 24weeks, P<0.0001), triglycerides (−5% vs. placebo at both 12 and 14weeks, P<0.05), apolipoprotein B (−7% at V2 and V3, P<0.01) and apolipoprotein B/apolipoprotein A1 ratio (−3% after 12weeks, P=0.06; −4% after 24weeks, P<0.05) when compared to placebo. Moreover, the atherogenic index decreased −6% after 12 and 24weeks when compared to placebo (P<0.05). In addition, safety markers showed that TOTUM-070 was well tolerated.

In conclusion, this Phase II clinical trial showed that daily intake of TOTUM-070 lowers LDL-cholesterol in subjects with moderate hypercholesterolemia. TOTUM-070 is safe, well tolerated, and has additional favorable effects on other lipid parameters. TOTUM-070 might be a promising candidate for cardiac risk prevention.