Purpose: Increasing evidence reinforces the benefits of reduction of low-density lipoprotein (LDL-C) levels on cardiovascular outcomes. Different targets are suggested based on cardiovascular risk (CVR). According to the current European guidelines, a goal of LDL-C≤ 115mg/dL is desirable for patients with low-moderate CVR. However, a high percentage of these patients are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. In this retrospective analysis, we evaluate the effects of dietary supplementation with a novel monacolin/berberine/bergamot nutraceutical formulation on plasma lipid levels of subjects with low-moderate hypercholesterolemia who are not treated with conventional drug or other dietary supplements. Patients and Methods:526 adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners according to prespecified criteria. All selected patients had a baseline and 30-day value of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, and transaminases and have started a dietary supplementation with this novel nutraceutical. Similarly, 104 subjects with comparable clinical features but not treated with any supplements were also selected. Results:At 30-day, the administration of nutraceuticals was associated with a significant reduction of LDL-C (124 ± 14 vs. 100 ± 13 mg/dL, Δ 24.5mg, p-value <0.0001) and TC levels (210 ± 56 vs. 187 ± 60, p-value < 0.0001), in the absence of a significant change of transaminase levels. No side effects were reported in the database during the observation period. Conclusion: This novel nutraceutical is an effective dietary supplement to achieve a significant and early LDL-C reduction in patients with hypercholesterolemia at low-moderate CVR.Keywords:Cardiovascular Risk; Hypercholesterolemia; Nutraceuticals