Cholesterol Control: Bergamot, Berberine, and Amla May Help

  • Like statins, amla, or Indian gooseberry, inhibits HMG-CoA enzyme activity.

Imbalanced blood fat levels—including elevated total and LDL cholesterol—continue to plague westernized civilizations as well as those increasingly adopting western dietary practices. As we know, these are significant risk factors for coronary heart disease, heart attack, and stroke.

High LDL cholesterol levels are a major risk factor for atherosclerosis because LDL cholesterol molecules are highly prone to oxidation. Oxidation causes molecules to structurally modify and become more likely to stick to the walls of blood vessels, particularly those of the heart and brain, contributing to the formation of plaque. This plaque can cause the narrowing of arteries, while also making them less flexible. In this event, circulating clots are more likely to get stuck in these narrowed blood vessels, leading to heart attack and stroke.

According to 2011 Centers for Disease Control and Prevention (CDC) estimates, more than one in three American adults has elevated LDL cholesterol, while nearly 14% of Americans have high total cholesterol, putting them at a doubled risk of heart disease compared with those individuals with optimal cholesterol levels.

Primary treatment with statin medications has served to effectively address elevated total cholesterol and LDL levels in many individuals; however, statin therapy is not without its risks. Recent studies point to factors such as increased blood sugar levels and possibly type 2 diabetes, particularly in women using statin drugs (Journal of the American College of Cardiology, 2012). Moreover, there are a number of treated patients who are statin intolerant for various reasons, including because of risks associated with nutritional deficiencies caused by or aggravated by statin drugs (Journal of Postgraduate Medicine, 2011). Beyond this, individuals with metabolic syndrome often are unable to achieve their lipid reduction goals with statins alone (The American Journal of Cardiology, 2008).

With the continued prevalence of cholesterol imbalances and the problems associated with statin use in many individuals, it’s fortunate that there are viable alternatives in the realm of therapeutic nutrition that are effective and inherently have a high level of safety. Recent studies in this area have shown promising results with a number of novel botanical extracts that have long been used in traditional systems of medicine. This research shows impressive benefits for lowering total cholesterol and LDL cholesterol levels, along with significantly improving several other heart health parameters.

Bergamot Polyphenols

The Bergamot orange (Citrus bergamia) is a yellow-colored citrus fruit the size of a lemon mainly grown in the southern Calabria region of Italy. It is distinct from other citrus fruits based on its unique profile and high concentration of flavonoids and flavonoid glycosides. Preliminary cell-based and animal research studies have shown several of these flavonoids to possess anti-atherosclerotic properties, including the ability to inhibit LDL oxidation. Some also have structural similarity to the natural substrate of the HMG-CoA reductase enzyme, which is the major target of statin drugs. Inhibiting this enzyme’s function serves to decrease cholesterol synthesis.

A recent study by Vincenzo Mollace and colleagues in Italy (Fitoterapia, 2011) investigated the effect of bergamot extract high in polyphenols, in both rats and humans. In rats with diet-induced hyperlipidemia, 10 and 20 mg/kg of bergamot polyphenols orally administered daily for 30 days led to significant reductions in total cholesterol, LDL, and triglycerides, with moderate elevations in HDL cholesterol levels seen compared to rats fed the hypercholesterolemic diet alone.

The human study was conducted as a randomized, double-blind, placebo-controlled trial consisting of 237 patients with high cholesterol levels (104 patients with isolated hypercholesterolemia/LDL levels greater than 130 mg/dL) (Group A); 42 patients with elevated cholesterol and triglycerides (Group B); 59 patients with high cholesterol, triglycerides, and blood sugar (Group C); and a final group of 32 patients classified as post–statin therapy who had stopped simvastatin due to musculoskeletal and liver adverse effects (Group D). Each of the above groups was divided into three subgroups. One subgroup received 500 mg of bergamot polyphenols per day; the second received 1000 mg/day; the third group received placebo. The post–statin therapy group received 1500 mg of bergamot polyphenols per day after a 60-day statin washout period. All patients were treated for 30 days.

In aggregate, groups A, B, and C showed an average reduction in total cholesterol of 21.8% and LDL cholesterol of 24.1% and an increase in HDL levels of 22.3% with 500 mg/day. The group taking 1000 mg/day of bergamot polyphenols saw reductions of 29.4% and 36.0% in total cholesterol and LDL, respectively, while achieving an increase in HDL levels of 40.1%. All parameters in the placebo group were essentially unchanged from baseline. In the post-statin group, there was a 25.0% reduction in total cholesterol, 27.6% decrease in LDL levels, and a 23.8% increase in HDL—with none of the side effects seen earlier with statin therapy in this group. Based on these results, the bergamot polyphenols proved to be an effective therapeutic intervention for elevated cholesterol levels as well as a safe and beneficial alternative for individuals intolerant to statin drugs.

Berberine

Berberine is an alkaloid native to several plants and is an active component of a number of herbs used in traditional Chinese medicine. It is thought to reduce blood lipid levels through a mechanism distinct from that of statin drugs, which work by inhibiting the HMG-CoA reductase enzyme, thus decreasing cholesterol synthesis. Berberine has been shown to work by improving the function of liver LDL receptors, independent of any effect on the activity of HMG-CoA reductase (Nature Medicine, 2004).

Given a mechanism of action distinct from that of statins, it is possible that berberine may be used in combination with statin medications in cases necessitating this. However, berberine has shown significant effects on blood lipid control when used on its own. In addition to benefits on cholesterol levels, berberine has been studied for its ability to significantly lower elevated blood sugar levels.

Hui Dong and colleagues from Huazhong University of Science and Technology in Hubei, China, conducted a meta-analysis published this year (Planta Medica, 2013) reviewing the effect of berberine supplementation on blood lipids. The researchers analyzed results from 11 randomized controlled trials comprising a total of 874 participants with elevated blood lipids and/or type 2 diabetes using daily doses of berberine ranging from 600 mg/day to 1500 mg/day. The pooled results indicated that berberine led to significant decreases in total cholesterol (average reduction of 24 mg/dL), triglycerides (average reduction of 44 mg/dL), and LDL cholesterol (average reduction of 25 mg/dL). They also noted that berberine supplementation caused a small but significant increase in beneficial HDL cholesterol levels.

Amla

Amla (Emblica officinalis) is an herb commonly used in traditional Ayurvedic and Unani medical practice for its tonifying and balancing effects. Also known as Indian gooseberry, it is widely renowned for its multiple therapeutic effects. Studies in animals and humans have confirmed its benefits in reducing cholesterol levels and supporting heart health. The fruit extract has been found to have potent antioxidant effects, including reducing oxidative stress that occurs with the aging process. Additionally, compounds in amla fruit have been shown to inhibit liver HMG-CoA reductase enzyme activity in animals, similar to statin-like effects.

Dr. Benny Antony and colleagues in Angamaly, India, conducted a controlled human trial (Indian Journal of Pharmaceutical Sciences, 2008) to evaluate the effect of a special trademarked amla extract, Amlamax, in individuals with elevated cholesterol levels. Amlamax is an amla fruit extract standardized to 30% galloellagitannins. Of the 30 patients that were selected for the four-month study, 15 were designated as control subjects (serum total cholesterol 200–240 mg/dL) while the remaining subjects were placed in the intervention group (serum total cholesterol greater than 240 mg/dL). The intervention group received 500 mg of Amlamax twice daily, while the control subjects were placed on a restrictive diet and exercise program. Subjects taking Amlamax showed significant reductions from baseline in total cholesterol (17%), LDL cholesterol (21%), and triglycerides (24%), while levels of HDL cholesterol increased (14%). No significant changes from baseline were observed in the control group.

Biswas Gopa and colleagues from the Department of Pharmacology at Baroda Medical College (Vadodara, Gujarat, India) undertook a comparative human trial (Indian Journal of Pharmacology, 2012) to evaluate the effect of amla fruit juice powder administration (500 mg/day) versus simvastatin (20 mg/day) in 60 patients with type II hypercholesterolemia (total cholesterol levels greater than 240 mg/dL and LDL cholesterol greater than 130 mg/dL). Forty patients were treated with amla, while 20 were treated with simvastatin, for six weeks. Treatment with amla resulted in a near 10% decrease in total cholesterol levels and a near 15% decrease in LDL cholesterol from baseline, and an approximate 15% increase in HDL levels. These results were on par with the effects noted with 20 mg simvastatin daily for six weeks.

High Cholesterol? Go Natural First

Elevated levels of cholesterol and, in particular, LDL cholesterol continue to be important factors in overall heart risk in westernized societies. Physicians often prescribe statin medications as first-line therapies to lower blood lipid levels; however, these drugs are not without risk. Moreover, many people are unable to tolerate long-term statin therapy for a variety of reasons. Certain populations, including those with metabolic syndrome, may often be unable to achieve recommended blood lipid targets with statin therapy alone.

Given these concerns, it’s important to know that several natural therapeutics—including herbal extracts such as bergamot, berberine, and amla—offer significant promise for addressing healthy cholesterol and blood lipid levels. Research has found that these extracts can bring about real and meaningful changes in lipid levels, bringing them into a healthier range. Used as potentially safer first-line alternatives or in conjunction with other cholesterol-lowering therapies, these natural options are worthy of consideration for those looking for help in meeting their heart-healthy targets.