Berberine: Research, Absorption, and Genetics

Berberine is a supplement that I've written about as a 'Lifehack' in a number of different articles. It is a natural compound with some amazing research on it in animal and cell studies, and it seems to be almost unbelievable. The drawback seems to be poor absorption in the intestines decreasing its effectiveness.

There is fascination research on berberine, so I'm going in-depth on:

  • what berberine is
  • how it works
  • who might benefit from it
  • how to increase absorption

What is berberine?

Berberine, a natural compound, is found in plants such as Oregon grape, barberry, and goldenseal. Plants containing berberine have traditionally been used for gastrointestinal infections. For thousands of years it has been used as part of Traditional Chinese Medicine, and different plants containing berberine have been used by various cultures around the world.

When isolated as a supplement, berberine is a very bitter, yellow powder.

What do studies show about berberine?

There are literally thousands of studies on berberine addressing a bunch of different aspects of health. I'm just going to hit the highlights here...

Decreased blood glucose and increased insulin sensitivity:

One way that berberine improves blood glucose levels is through activating AMPK (adenosine monophosphate-activated protein kinase). AMPK is an enzyme involved in regulating energy production in the body.  When energy is low, AMPK causes glucose or fatty acids to be brought into the cell and used for energy. Activating AMPK also decreases the production of cholesterol and triglycerides. AMPK activation also modulates insulin release from the pancreas and causes lipolysis (using fat for energy).

Berberine activates AMPK in a dose-dependent manner (meaning that more berberine causes more AMPK).[ref]  In addition to moderating the release of insulin, berberine also up-regulates the expression of the insulin receptors. This should increase insulin sensitivity.[ref]

A clinical trial found berberine to lower fasting blood glucose levels, postprandial blood glucose levels, and decrease insulin resistance after a month. There was also a decrease in IL-6 and TNF-alpha (inflammatory cytokines). This trial included a comparison group using standard drug therapy (blood pressure medicine and diabetes drugs). Both groups were told to exercise for a half-hour a day. Both groups had about the same reduction in treatment parameters - in other words, berberine was as effective as diabetes drugs plus blood pressure meds.[ref]

A meta-analysis combining the data from 14 trials of berberine found that berberine to be about as effective as prescription diabetes medications (metformin, glipizide, or rosiglitazone). No serious adverse effects reported.[ref]

Improving cholesterol levels:

Berberine has shown in studies to reduce both LDL and triglyceride levels. Average LDL reductions ranged from 20 to 50 mg/dL.[ref] One study found that berberine upregulates the LDL receptor, which causes a decrease in serum LDL levels. For the 32 patients in the study who had high cholesterol, three months of berberine reduced LDL by 25% and also reduced triglycerides by 35%.[ref]

Combining berberine with a statin, simvastatin, has shown to be much more effective than either berberine or the statin alone.[ref]

Berberine may be most effective, though, for people who have high cholesterol due to a PCSK9 genetic variant. 

Fatty Liver Disease:

A clinical trial showed that berberine reduced non-alcoholic fatty liver disease. Berberine has shown to be more effective even than the diabetes medication pioglitazone (Actos) for weight loss and improving lipids. The study participants took 500 mg of berberine 30 minutes before each meal (3x per day). Participants were also told to reduce calorie intake and exercise in the control, berberine, and Actos groups. So the good results were due to a combo of exercise, decreased calories, and berberine.[ref]

Animal studies show that berberine is working to reduce fatty liver disease at least partly through increasing SIRT1. SIRT1 is a gene associated with longevity and a healthy lifespan. A deficiency of SIRT1 causes fatty liver. On the other hand, in mice bred to be fat and diabetic increasing SIRT1 slowed insulin resistance.[ref]

Weight loss - perhaps:

Since berberine activates AMPK, it should cause either reduced fat accumulation or weight loss.[ref] But a lot of things cause weight loss in theory - and animal studies.[ref]

One clinical trial of 500 mg of berberine, 3X daily, found an average weight loss of 5 lbs occurred after 12 weeks.[ref]

Improves intestinal barrier:

An intestinal barrier lines the intestines to keep out microbes. The epithelial cells making up the intestinal cell wall adhere together in a 'tight-junction'. Basically, the tight junctions prevent anything from slipping in between the cells. Inflammatory cytokines such as TNF-alpha and interferon-gamma can damage the tight junctions, leading to a 'leaky gut'.  Berberine has shown in cell studies to prevent inflammatory cytokines from causing leaky gut.[ref] In a mouse model of inflammatory bowel diseases, berberine reduces the damage and prevents the decrease of the tight junction protein (zonulin).[ref]

While it is generally a good idea to prevent the 'leaky gut', some medications actually include substances that decrease tight junctions for better medication absorption. So, you may want to be careful of stacking berberine with certain prescription drugs.


Studies show one cause of DNA mutations that cause cancer is chronic inflammation. Researchers estimate that about 20% of cancers are related to inflammation - either through infection (e.g. HPV for cervical cancer), exposure to toxins and irritants (e.g. lung cancers), or inflammation due to autoimmune diseases.  Inflammatory cytokines are a double-edged sword, though, with cancer. On the one hand, they can exacerbate or promote cancerous growth; on the other hand, they can also attack and destroy cancerous cells.[ref]

Berberine has shown to promote the apoptosis (cell death) of cancer cells and also suppress metastasis. In humans, the effects of berberine on cancerous cells are most likely to be seen in the intestinal cells because of poor absorption.  Within the intestines, it acts as an anti-inflammatory and helps to protect the intestinal wall.  It does this by activating AMPK and inhibiting NF-κB.[ref]

In mouse models of colon cancer, berberine cuts the number of tumors in half. It does this through activating AMPK, inhibiting mTOR, and inhibiting NF-κB.[ref]


Traditionally, plants containing berberine have been used to combat viral and bacterial pathogens.

In a randomized control trial from the '80s, patients with 'acute diarrhea' due to E. coli were given either 400 mg of berberine or nothing (I think...).  Twice as many in the berberine group stopped having diarrhea compared to the control group with E. coli (42% vs 20%). The study also looked at cholera and found that berberine reduced stool volume (measured in liters - ugh!) when stacked with tetracycline.[ref]  My take away -- don't get cholera.

In mice, berberine prevents the recurrence of C. difficile infections. (Note that the C. diff was initially treated with vancomycin - this was just looking at the recurrence rate)[ref]

Cell studies show berberine to have some efficacy against Candida.[ref][ref]  A lot of studies show that berberine can augment specific antibiotics.  This may not be a stand-alone treatment option, but rather something to consider alongside other antibiotics.

Irritable Bowel Syndrome:

A placebo-controlled clinical trial found that berberine was better than a placebo for reducing the symptoms of IBS-D. The patients receiving berberine had decreased diarrhea frequency and less abdominal pain.[ref]

Acetylcholinesterase inhibition:

Berberine can act as an inhibitor of acetylcholinesterase. Acetylcholine is the main neurotransmitter in the peripheral and central nervous system, and acetylcholinesterase is basically the off switch for stopping the neuron after firing. Inhibiting acetylcholinesterase turns off the 'off switch'.  This potentially would be good for Alzheimer's patients.[ref][ref] (I'm not sure at what doses, though, you would need to take to really impact acetylcholinesterase... if normal doses acted as an acetylcholinesterase inhibitor, it seems like it would be noticeable in healthy people.)

Circadian Rhythm:

An interesting study came out recently that showed that berberine interacts with BMAL1, a core circadian clock gene. The study found berberine increased FGF21 (important for weight loss) through modulating BMAL1 in brown fat. The study concludes that berberine may be good for people with obesity if related to circadian rhythm dysfunction.[ref]  (Read more about circadian dysfunction and weight gain.)


PCOS (polycystic ovarian syndrome) is a condition that can involve altered hormone levels, insulin resistance, and ovarian cysts.

A study in China found 400 mg of berberine, 3 times per day, improved menstruation and ovulation in women with PCOS.[ref]  Trials show berberine to be more effective than metformin (diabetes medication) in some parameters for women with PCOS.[ref]


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