Bergamot Has Positive Quantitative and Qualitative Effects of Plasma Lipids, Decreases Oxidative Stress, and Improves Control of Plasma Glucose Levels

Dyslipidemia is often treated with statins, which inhibit 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase. Some patients with dyslipidemia have adverse reactions to prescription statins or do not reach target plasma lipid levels with statins alone. Herbal treatments may help patients reduce total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Citrus (Citrus spp., Rutaceae) fruits have been found to benefit lipid metabolism and may help reduce the risk of developing cardiovascular disease. The fruit of bergamot (Citrus bergamia) is high in flavonoids and has been shown to be antimicrobial, analgesic, and anti-inflammatory, and to alter plasma glucose and lipid concentrations. The goal of this review was to summarize research on the effect of bergamot on plasma lipid concentrations and lipid metabolism.

PubMed and Scopus were searched up to September 2015 for preclinical and clinical studies with any of the following keywords: bergamot, cardiovascular risk, dyslipidemia, lipids, lipoproteins, high-density lipoprotein, low-density lipoprotein, lipid-lowering drugs, nutraceuticals, natural compounds, and the statin.

Eleven preclinical studies were found. These studies were conducted in animal models and in isolated cell lines. Bergamot contains the flavonoids neoeriocitrin, neohesperidin, naringin, rutin, neodesmin, poncirin, brutieridin, melitidin, and rhoifolin. In rats with hypercholesterolemia, brutieridin, melitidin, and neoeriocitrin have statin-like qualities and reduce TC, TGs, LDL-C, and very-low-density lipoprotein cholesterol (VLDL-C). Similar results were found in rats with hyperlipidemia. In addition, oxidation levels of LDL-C and malondialdehyde levels were lower in rats fed bergamot. These findings are consistent with a decrease in oxidative stress with bergamot consumption. Bergamot juice was also found to scavenge free radicals in vitro. Studies have also investigated the mechanisms by which bergamot acts on plasma lipid levels. A study in rats found increased excretion of sterols in a fecal material with consumption of bergamot. Bergamot flavanones from the peel (brutieridin, melitidin, and HMG-neoeriocitrin) also have been found to bind to the active site of HMG-CoA reductase, causing inhibition of the enzyme in a manner similar to statins. In human hepatoma cells (HepG2), the bergamot constituents naringenin and hesperetin decreased synthesis of apolipoprotein B-containing lipoproteins.

Three clinical studies were found. In one study, bergamot alone was compared to placebo, two dosages of rosuvastatin (10 or 20 mg per day), and bergamot plus the lower dose of rosuvastatin. Bergamot decreased TC and LDL-C to a similar extent as 10 mg per day of rosuvastatin. Bergamot also significantly reduced the ratio of LDL-C to high-density lipoprotein cholesterol (HDL-C) and markers of oxidative stress. Additionally, bergamot significantly enhanced the effect of rosuvastatin in patients with mixed hyperlipidemia. In a second study, the effect of bergamot versus placebo was compared in patients with metabolic syndrome and fatty liver disease. Bergamot significantly reduced fasting glucose levels, LDL-C, TGs, and small, dense LDL levels, and increased HDL-C compared to placebo. In a final study, the effect of bergamot was assessed in patients who had to discontinue use of statins due to adverse effects. Patients were divided into four groups. One group had hypercholesterolemia, a second group had hyperlipidemia, the third group had hyperlipidemia plus metabolic syndrome, and the last group had discontinued statins due to muscle cramps and a significant increase in serum creatine kinase levels. In the first three groups, bergamot decreased plasma TC and LDL-C and increased HDL-C. In the group with metabolic syndrome, control of plasma glucose levels increased with bergamot consumption, and in the fourth group, TC and LDL-C decreased with bergamot consumption.

The results of these studies suggest that bergamot has positive quantitative and qualitative effects on plasma lipids, decreases oxidative stress, and improves control of plasma glucose levels. The dosages of bergamot used in human studies range between 500 mg and 1300 mg per day. It is unknown if these dosages are appropriate or if drug interactions could occur with bergamot consumption. In addition, the flavonoids are the most studied component of bergamot, but other active compounds are known to exist within bergamot. Studies of these compounds would be useful. The authors suggest that further studies should be conducted to determine appropriate dosage, drug interactions, and the mechanism of action of bergamot.

Giglio RV, Patti AM, Nikolic D, et al. The effect of bergamot on dyslipidemia. Phytomedicine. October 2016;23(11):1175-1181.

  • Bergamot Orange (Citrus bergamia, Rutaceae)
  • Dyslipidemia