BERBERINE – Therapeutic Applications*
Berberine has long been used in traditional Ayurveda and Chinese medicine to treat many health conditions, including intestinal problems, bacterial infections and inflammation.
Berberine is present in many plants, including the European barberry, goldenseal, Oregon grape, yellow root, phellodendron and tree turmeric. It is found in roots, rhizomes, stems and the bark of the plants.
It is a quaternary ammonium salt from the protoberberine group of isoquinolone alkaloids. Alkaloids are nitrogenous organic molecules or compounds, of plant origin, which have pronounced physiological actions or pharmacological effects in humans and animals. They include many drugs and poisons, for example, morphine, quinine, atropine and strychnine.
Berberine is strongly yellow coloured which is why, in earlier times, Berberis species were used to dye wool, leather and wood.
As a traditional medicine or dietary supplement, berberine has shown some activity against fungal infections, Candida, parasites and bacterial/viral infections. It is considered an antibiotic. It has been used to treat trachoma and leishmaniasis.
Berberine prevents and suppresses pro-inflammatory cytokines, acting as an anti-inflammatory agent which partly explains its versatile health effects.
Metabolic Effects of Berberine
Over a third of the approximately 2,800 studies on berberine listed on PubMed were published in the last five or so years, reflecting recent interest in this isoquinolone alkaloid and its therapeutic applications.
The fundamental mechanism of action underlying berberine's impact on human health is probably its action on the adenosine monophosphate-activated protein kinase (AMPK). To understand what berberine does, one must first understand AMPK.
AMP-activated protein kinase (AMPK)
AMPK is an enzyme (-ase means enzyme) that plays a role in cellular energy homeostasis. AMPK can be regarded as a metabolic master switch, regulating several intracellular (inside the cell) systems including the cellular uptake of glucose, the beta-oxidation of fatty acids and the biosynthesis of glucose transporter 4 (GLUT4) and mitochondria.
Mitochondria are spherical or rod shaped organelles found in large numbers in the cytoplasm of most cells in which the biochemical processes of respiration and energy production occur. They are referred to as the "powerhouse of the cell since they act as the site for the production of high-energy compounds, such as AMP and ATP, which are vital energy sources for several cellular processes." They use glucose and oxygen to produce energy, releasing carbon dioxide in the process.
The AMPK enzyme acts as the central energy regulatory control switch regulating how energy is produced and used in the body. AMPK induces a cascade of events within cells that are all involved in maintaining energy homeostasis. It is via AMPK that low energy status switches cellular metabolism from ATP-consuming anabolic pathways to ATP-producing catabolic pathways. AMPK regulates an array of biological activities that normalise lipid, glucose, and energy imbalances.
Metabolic syndrome occurs when these AMPK-regulated pathways are turned off, triggering a syndrome that includes hyperglycaemia, diabetes, lipid abnormalities, energy imbalances and their complications.
The net effect of AMPK activation is "stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells."
AMPK is activated by energy depletion and inhibited by energy excess. High glucose and glycogen levels inhibit AMPK. This inhibition leads to many of the long-term consequences of diabetes. Exercise and caloric restriction activate AMPK, which explains their benefit in treating diabetes. High fat intake also inhibits AMPK.
One way to appreciate AMPK activation potential is to think of it as having the same effect on a patient as increasing exercise, while at the same time restricting caloric intake. Think of the effects of AMPK suppression as similar to those of eating a high-energy diet while leading a very sedentary lifestyle.
Only few chemicals are known to activate AMPK. Berberine is one of them.
Health Benefits of Berberine
The article Berberine in the Treatment of Type 2 Diabetes Mellitus. A systematic Review and Meta-Analysis was published in the journal Evidence -Based Complimentary and Alternate Medicine, volume 2012, Article ID 591654. This meta-analysis, by Hui Dong et al, combined data from 14 randomised trials involving 1,068 patients. Treatment with both berberine and lifestyle modification showed significant hypoglycaemic and antidyslipidaemic benefits. The authors state: "Berberine has beneficial effects on blood glucose control in the treatment of type 2 diabetic patients and exhibits efficacy comparable with that of conventional oral hypoglycaemics [metformin, glipizide and rosiglitazone].... It has no serious adverse effects except for mild to moderate gastrointestinal discomfort."
· Polycystic Ovary Syndrome
Metformin is also used as treatment for polycystic ovary syndrome. Berberine has been shown to compare favourably with metformin in the treatment of this condition.
· Metabolic Syndrome
Details of the metabolic syndrome are set out in my September 2008 newsletter Metabolic Syndrome. The importance of weight loss (caloric restriction) and exercise in therapy were emphasised.
As set out above, berberine is useful in the treatment of metabolic syndrome, because it has the same effect as exercise and restricting caloric intake. It reduces insulin resistance and normalises the lipid profiles characteristic of this condition.
· Weight Gain Triggered by Antipsychotic medications
Metformin has been shown to reduce the effect of weight gain triggered by antipsychotic medication, especially in females. Berberine has similar beneficial effects.
An article published by W. Kong et al (Nat. Med. 2004: 10) described berberine as "a novel cholesterol-lowering drug" that worked through a "unique mechanism unique from statins". In the clinical study on 32 hypercholesterolaemic patients for 3 months, the treatment with berberine reduced serum cholesterol by 29%, triglycerides by 35%, and LDL-cholesterol by 25%.
Berberine has been shown to work synergistically with statin drugs.
In another study, by X. Xie and colleagues, a randomised controlled trial of 60 patients with fatty liver disease, in which numerous biomarkers were measured, showed that 3 months of berberine treatment (500 mg twice per day) gave 70% improvement in the liver ultrasounds, and a significant decrease in cholesterol and triglycerides.
Other studies, both animal and human, show similar results.
· Cardiovascular Disease
While improving lipids (cholesterol and triglycerides) may improve cardiovascular disease (CVD) or risk, berberine has other beneficial actions that lower CVD risk. It improves arterial endothelial function and suppresses pro-inflammatory cytokines, actions that should improve heart health.
Many studies have shown that berberine has significant antimicrobial activity against bacteria, viruses, protozoas, helminths, and chlamydia.
· Mental and Brain Health
A recent study conducted at the Shandong University of Technology in China, by Jia Liyun et al, published in the Journal of Pharmacy and Pharmacology (volume 64, 2012), found that "berberine helps prevent oxidation damage to biomolecules in the brain, inhibits enzymes which breakdown important memory molecules, reduces peptides that interfere with proper memory function, and lowers lipids that interfere with cerebral blood flow." Its interaction with brain and mental health shows that berberine may also be able to ward off Alzheimer's disease.
· Other Possible Applications
Other studies have shown that berberine improves bone density and preserves cartilage, protects against acute brain damage, reduces inflammation, and may reduce cancer cells spreading.
Thorne Research produces Berberine-500 Veggie Capsules. These contain 500 mg Berberine hydrochloride per capsule. The suggested dose is 1-2 capsules two times daily.
Another way of obtaining berberine is to use one of the plant sources. For example, Eclectic Institute produces Goldenseal Root, 400 mg Veggie Capsules. These contain "Fresh Raw Freeze-Dried ... Rhizome and Root". They are said to contain 7.5 - 9.5% berberine and hydrasline. They recommend 1 to 3 capsules per day. (Both available from )
While the known clinical applications for berberine are diverse, there are a few generalisations that can allow us to understand its potential. Berberine activates AMPK in a manner similar to how exercise stimulates increased strength and weight loss. Thus, any condition that would be favourably impacted by a patient losing weight and/or exercising more may be impacted favourably by oral berberine supplementation. It is therefore appropriate to consider using berberine in patients with insulin resistance, pre-diabetes, diabetes, metabolic syndrome, heart disease and hypertension, dyslipidaemia, cancer, depression and other neuropsychiatric diseases.
*Copyright 2014: The Huntly Centre.
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