Dry berberis heap on the desk

Berberine. A Supplement Worth Considering?

Barberry dried - Berberine. A Supplement Worth Considering?

Dried barberry (berberis) – a source of berberine


There are thousands of supplements (a.k.a. “natural health products“) on the market today.


Many of them lack the evidence needed to back up their claims. On the other hand, there’s heaps of supplements that do have robust data to support their use.


Anyone who categorically dismisses supplements as “a waste of time”, “expensive urine” or automatically “dangerous” hasn’t done their due diligence, e.g. homework. Or worse; is practicing unsubstantiated authoritarianism.


A supplement of interest is berberine. It’s one of the few supplements shown to be as effective as several commonly prescribed medications.

What is berberine?

Berberine refers to a bioactive compound. Unlike cinnamon, which refers to a specific species of plant for example, berberine can be extracted from several botanical sources (1).  Berberine therefore is a chemical, not a plant.


Berberine belongs to a class of compounds of plant origin called alkaloids which have pronounced physiological effects in humans (2).


FUN FACT: like curcumin, berberine is intensely yellow-coloured and it was once used to dye wool, leather and wood.


Berberine has been part of traditional Chinese medicine for over 5000 years where it’s been used for various ailments. The best source of berberine is goldenseal but is also found in Oregon grape and barberry.

What are the benefits of berberine?

Berberine benefits insulin metabolism. It helps to reduce insulin resistance (improve insulin sensitivity) and therefore all of insulin’s associated metabolic functions.


It may also work by protecting the beta cells of the pancreas; the cells that are responsible for producing insulin. Having beta cells that function well, and throughout life, will ensure insulin is around to do it’s job.


Berberine may also reduce “hepatic gluconeogenesis“. This is something everyone’s liver does. It has the ability to take non carbohydrate based molecules such as protein and fat, and turn it into glucose for fuel.


This glucose is different from the glucose you get from the digestion of carbohydrate (sugars and starches), but is used by your cells in the same way.


By reducing the rate of gluconeogenesis, berberine can help to keep blood sugar levels lower and balanced.


Berberine also reduces inflammation  which has been shown to improve the action of insulin, and therefore blood sugar control independent of the action of insulin.


Berberine also has anti-fungal and antimicrobial properties (3, 4, 5, 6). This is why it’s sometimes used to treat gut issues such as small intestinal bacterial overgrowth or SIBO (7).

Berberine molecule - Berberine. A Supplement Worth Considering?How does berberine work?

Berberine is a well-researched compound which has been shown to exert potent effects on many different systems in the body (8).


The precise mechanisms is beyond the scope of this post and are really technical and complicated but once inside your cells, berberine gets to work.


It attaches itself to various targets where it influences how cells function, including how cells use and produces energy (9).


Berberine does this specifically by activating an enzyme (a specialized protein that enables biochemical reactions) called AMP-activated protein kinase or AMPK for short (10).


AMPK can be seen as the metabolic master switch where if influences various metabolic pathways and activities. It’s so important, that it can be found in various cells and organs including the brain, kidney, heart, liver, and muscles. (11, 12, 13)


This enzyme plays a huge role in overall energy metabolism which involves hormones such as insulin and therefore glucose and fatty acid metabolism. By activating AMPK, berberine therefore influences and benefits metabolic/insulin resistance syndrome disorders.

It lowers blood sugar

Bar none, berberine is best known and researched for it’s ability to lower blood sugar (14).


Studies have shown that taking 500 mg, three times per day (1500 mg total) improves blood sugar and glucose control, and other markers of type 2 diabetes just as well as the diabetes drug Metformin (Glucophage) (14, 15).


It’s so effective that it’s one of few supplements that have been shown to work as well as a medication.


Berberine lowers blood sugar via many mechanisms (16):

  • It improves insulin sensitivity and so glucose (sugar in the blood), moves into muscle cells, the brain, spinal chord and liver easier.
    • This is because insulin is more effective at its job
  • It tells the liver to make less sugar (glucose creation from amino acids and glycerol)
  • Helps to slow the digestion of carbohydrate in the gut so carbohydrate is absorbed slowly
  • It increases the number of beneficial bacteria in the digestive tract which also positively influences blood sugar levels
  • It decreases the conversion of excess blood sugar into triglycerides (the hallmark of insulin resistance syndrome/metabolic syndrome and type 2 diabetes).
    • Higher triglycerides levels promote insulin resistance which, in turn, further increases blood sugar


And the results are impressive. One gram  (1 g) of berberine per day lowered fasting blood sugar by 20% (7.0 to 5.6 mmol or 126 to 101 mg/dL) in a study of 116 diabetics (the equivalent of moving blood sugar from the diabetic range to normal levels) (17).


Not only that, but it also lowered A1C by 12% (A1C is a marker of longer term blood sugar control; it roughly represents the average blood sugar during the previous 3 months). Because berberine influences insulin metabolism, improvements in cholesterol and triglycerides were also seen (17).


A review of 14 studies found that berberine is as effective as traditionally used oral diabetes medications including rosiglitazone, glipizide and metformin (18).

It balances blood lipids

Cardiovascular disease is a disorder of inflammation and is not a “disease” of LDL cholesterol. This topic goes beyond the scope of this post but suffice it to say that cardiovascular disease risk involves blood sugar levels, insulin levels and response to carbohydrate intake and the balance/ratio of serum lipids such as LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides.


Having said that, many of the traditional laboratory indices that are used to assess cardiovascular disease risk are positively modified by berberine (19):

  • Lowers triglycerides by 0.50 mmol (44 mg/dL)
  • Lowers LDL cholesterol by 0.65 mmol (25 mg/dL)
  • Raises HDL cholesterol by 0.05 mmol (2 mg/dL)
  • Lowers total cholesterol by 0.61 mmol (24 mg/dL)

Berberine helps to lower LDL cholesterol by blocking the actions of an enzyme called PCSK9. This results in more LDL being cleared from the blood by the liver and other cells (20, 21).


More importantly though, berberine has been shown to lower something called apoB by 13-15% (22, 23). ApoB is a marker of how many LDL molecules you have in your blood. This is also referred to as the LDL “particle number”. The more LDL particles (LDL-P) you have in your blood, the greater (much greater) your risk for cardiovascular disease.


LDL-P is far more predictive of heart disease risk than LDL-C and it’s much more problematic (24, 25, 26). LDL-P is not routinely tested in Canada but a proxy is to look that the ratios of triglycerides and HDL.


If triglycerides are high (> 1.70 mmol) and HDL is low (< 1.0-1.30 mmol), you’ll have what’s called “Pattern B” which typically tracks with elevated background insulin levels (hyerpinsulinemia). The LDL particles will be small in size and there will be more of them circulating in your blood stream – no beuno.

Glucometer - Berberine. A Supplement Worth Considering?

Might help with weight management

Before you get too excited or default to automatic rejection, it’s important to consider the big picture. This isn’t about quick fixes but berberine may support weight management and weight loss.


Two studies have looked at berberine’s impact on weight (27). One study looked at 37 men and women with metabolic syndrome (more aptly called insulin resistance syndrome). It was a 12 week study where subjects took 300 mg of berberine, 3 times a day. All variables considered and controlled for, the subjects’ average BMI decreased from 31.5 to 27.4. They also lost central adiposity (belly fat) (28).


It’s believed that berberine’s positive impact on energy and fat regulating hormones, such as insulin, adiponectin and leptin, was responsible for this observation (29).


Chronic elevated insulin levels are known to reduce the breakdown of body fat (lipolysis) and increase the production of triglycerides (from dietary carbohydrate) which get deposited into the liver, muscles and fat cells. This is both a result of, and leads to more, insulin resistance which berberine improves.

Anti-inflammatory and antioxidant

The onset of many chronic diseases are thought to be initiated by increased inflammation, and, in turn, chronic disease drives inflammation. This sets the stage for a viscous circle of insult and injury. One such disease is diabetes. Oxidative stress and inflammation are proved to be critical for diabetes’ pathogeneis.


Berberine has been shown to have potent antioxidant and anti-inflammatory properties (30, 31, 32). Recent studies have shown that berberine’s antioxidant and anti-inflammatory activities contributed in part it its efficacy against diabetes (33) and potentially obesity induced insulin resistance (34).


Berberine has also been shown to reduce inflammation of the airways caused by inhalation of cigarette smoke and from dust mite allergens by reducing inflammation promoting proteins (cytokines) TNF-alpha, IL-1B, and MCP-1 (35, 36).

Berberine helps with fatty liver

Non-alcohol fatty liver disease (NAFLD) is a very common liver disorder. It refers to a group of conditions where there is accumulation of excess fat in the liver in people who drink little to no alcohol (37).


Over time, an excess of fat in the liver can lead to liver inflammation (hepatic steatosis) and subsequent scarring of the liver tissue a.k.a. cirrhosis.


While the exact cause(s) of NAFLD is unknown, what is known is that the disease is tightly linked to insulin. Specifically high blood levels of insulin which drive fat accumulation in the liver.


Through many mechanisms such as improving how insulin ‘works’ in the liver, by activating AMPK, improving the gut environment, and improving fat transportation in the liver, berberine has been shown to reduce fat build-up in the liver cells (38, 39, 40, 41, 42).


Liver schematic - Berberine. A Supplement Worth Considering?


Are there any side-effects or concerns?

Most studies on berberine used 1500 mg per day; 500 mg with each meal. Some have gone as high as 2000 mg per day. Berberine seems to have a ceiling when it comes to its therapeutic effect.


The largest complaint with berberine supplementation is mild gastrointestinal distress, especially if a larger dose is taken at once. Other digestive issues include cramping, diarrhea, flatulence, and constipation (43). Otherwise, it appears to have few side effects.


As an active alkaloid, berberine has been known to interact with other liver enzymes which used for pharmaceutical drug metabolism. Translation? It can interfere with the metabolism (breakdown and excretion) of prescription medications.


But to put it in perspective, most drugs have the potential to interact with each other. To be safe, always check with your doctor or a pharmacist before supplementing with berberine.


You may have heard that berberine can cause low blood sugar (hypoglycemia) in high doses, but this is reportedly very uncommon.

Is berberine safe?

In a word, yes, but it’s always best to consider it’s use with a doctor’s guidance. It does have a lot of good quality data behind it but the long term safety and adverse events haven’t been sufficiently evaluated.


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Bottom line

Berberine is one of very few supplements that are as effective as a prescription medication. It has powerful effects on various aspects of health, especially blood sugar control.


If you want to try a berberine supplement, be sure to get a high-quality supplement. You can buy them (here, here, here, and here).


The people who stand to benefit the most are individuals with type 2 diabetes and metabolic syndrome (a better name is insulin resistance syndrome). However, it may also be useful as a general supplement to support healthy insulin levels.


As with any supplement, it’s best not to ‘self medicate’. Be sure to check with your doctor before starting berberine or any supplement. If you want to safely incorporate supplements into your health regimen, be sure to also get the advice of a licensed and regulate nutrition professional or other regulated practitioner who’s educated on the role of natural health products and nutraceuticals.


Doug Cook RDN is a Toronto based integrative and functional nutritionist and dietitian with a focus on digestive, gut, mental health.  Follow me on FacebookInstagram and Twitter.