What is berberine?

Berberine is an active compound extracted from herbal plants such as Goldenseal, Chinese goldenthread, Rhizoma coptidis, Phellodendron, barberry and Indian barberry.

The majority of Berberine is extracted into a salt form known as Berberine Hydrochloride. Purity is standardized to be 97% and up or higher.

Berberine is famously known for its cholesterol-lowering and hypoglycemic effects.

Numerous studies have conducted to analyze Berberine’s effect on cardiovascular diseases, metabolic syndromes and weight loss. Along this article we’ll go over everything you need to know about Berberine.

History

Berberine is an ancient Chinese medicinal herb dated back to 3000BC. Berberine can be extracted from various types of plant species such as Goldenseal, Chinese goldenthread, Rhizoma Coptidis, Oregon grape, Phellodendron, Indian barberry and various shrubs found across the Himalayas.

Originally used for diarrhea, inflammation, stomach and liver issues.

But now, today’s health issues such as diabetes and cardiovascular diseases are debilitating our society.

Published medical journals are revealing potential findings of drugs and supplements tackling today’s health complications.

One supplement in particular, Berberine, has shown to be a promising treatment for cardiovascular and metabolic diseases.

Blood sugar

Berberine may greatly support lowering high blood sugar levels. It activates key signals to process glucose in our system. Hypoglycemic effects can occur through various mechanisms such as glucose uptake, activation of AMPK, insulin secretion, and alleviate insulin resistance.

Human studies were conducted with 36 patients with type 2 diabetes. One group was treated with Berberine and the other with Metformin. Berberine shared similar reductions in their hbA1c, fasting glucose, and triglycerides. This study suggests that Berberine is as comparative to Metformin. After a 3 month period, notable decreases in hbA1c dropped from 9.5% to 7.5%. (1)

“In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (0.5 g 3 times a day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (from 9.5%+/-0.5% to 7.5%+/-0.4%, P<.01), fasting blood glucose (from 10.6+/-0.9 mmol/L to 6.9+/-0.5 mmol/L, P<.01), postprandial blood glucose (from 19.8+/-1.7 to 11.1+/-0.9 mmol/L, P<.01), and plasma triglycerides (from 1.13+/-0.13 to 0.89+/-0.03 mmol/L, P<.05) were observed in the berberine group.”

Glucose production

Berberine may hinder gluconeogenesis which halts the production of glucose in our liver. Berberine downregulates HNF-4a, a protein gene responsible for glucose proliferation, which slows the creation of more glucose in the liver.

A rat experiment was observed in which they were fed a high fat diet. After administering Berberine, results indicated improvements in rats' fasting blood glucose. Berberine metabolizes PEPCK1, which are gluconeogenesis enzymes that inhibits glucagon function, resulting in slowing the production of glucose. (2, 3, 4)

“In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly… The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR.”

Glucose uptake

Berberine may increase glucose uptake. When cells reach low energy levels in various regions of our body it activates AMPK. This process pulls glucose from our blood and transports it to our cells for energy. (5)

This ensures cells in our muscles, tissues, and organs receive glucose while maintaining their cellular function. This is one of the key processes in lowering blood glucose. (6)

“Glucose uptake was increased by berberine in 3T3-L1 preadipocytes as well. Berberine-stimulated glucose uptake was additive to that of insulin in 3T3-L1 adipocytes, even at the maximal effective concentrations of both components.” “In isolated rat muscles, activation of AMPK is associated with increases in glucose uptake through an insulin-independent mechanism. Studies done in rodents have shown that the activation of AMPK by AICAR is accompanied by decreases in blood glucose concentrations, in part due to enhanced muscle glucose uptake.”

Insulin secretion/sensitivity

Berberine may or may not helps insulin secrete into our system by signaling GLP-1. This hormone helps the pancreas to secret insulin throughout our body. This improves beta cell production and insulin sensitivity. (7)

Other conflicting studies revealed Berberine may have a reverse effect on insulin secretion. Instead of producing insulin it may inhibit secretion. Findings suggested the effects of AMPK and cAMP signaling from Berberine decrease the secretion of insulin. Berberine may have a potential to benefit patients with high insulin production but may have a possibility of inhibiting it. Berberine may not be a reliable treatment of insulin secretion since it was shown to secrete and inhibit insulin in different studies. (8)

Insulin resistance

Berberine's hypoglycemic effect improves overall impact on lowering insulin resistance. Berberine's primary effect, activation of AMPK, utilizes stored glucose and transports it to energy deprived cells allow the body to utilize insulin more efficiently.

A study of of type 2 diabetic patients were examined, it consisted of 2 groups: obese and non-obese. The results were measured by insulin resistance and body mass index. BBR displayed significant improvements in IR and BMI in all groups but BMI was notably improved in the obese group than the non-obese group. This suggests that Berberine may have a positive effect on both IR and obesity. (9)

“Wu and Wei [88] observed efficacy of BBR in treating T2DM. Seventy-two cases were assigned to obese group and nonobese group, and BBR (0.02 mg/kg) was administrated orally for 8 to 10 weeks. Results showed that insulin resistance and body mass index (BMI) of all cases improved after treatment, compared with before treatment (P < 0.01). BMI of obese group reduced more significantly than that of nonobese group (P < 0.01), indicating that BBR was more applicable to prediabetes and the early stage of T2DM characterized by insulin resistance and obesity.”

Gut bacteria

Berberine may induce antimicrobial activity. It helps process short chain fatty acids to reduce gastrointestinal inflammation. It also inhibit key enzymes that suppress the absorption of carbohydrates in the intestines.

Berberine was able to decrease a diverse set of microbiota ones that are linked to obesity. (9)

It was shown to lower lipopolysaccharides, which are known to damage intestinal walls. The potential to decrease weight gain and modulate gut microbiome has shown to maintain intestinal integrity by alleviating bacterial flora linked to obesity and diabetes. (10)

Mice induced with high fat diets were observed to study the effects of Berberine in their gut. Results displayed Berberine to decrease polysaccharides and inhibit growth of lactobacillus which led to a reduction in visceral adipose tissues. (11)

KEY TAKEAWAY:

Berberine’s main attribute is its hypoglycemic factor. It strongly supports high blood sugar, lower insulin resistance, regulate glucose production, increase glucose uptake and modulate bacterial inflammation. Berberine has participated in decades of studies and research on alleviating diabetes and metabolic syndrome in humans.

Total cholesterol

Total cholesterol is a congregate summary of cholesterol throughout the body. This includes LDL, blood fat, triglycerides, and other lipid measurements.

Berberine may support lowering total cholesterol by decreasing overall lipid levels from our liver, bloodstream, and visceral fat tissue.

LDL receptors

Low-density Lipoprotein is considered the "bad" cholesterol that builds up plaque in our arteries. Berberine helps stimulate LDL receptors usually found in the liver. Overstimulation of these receptors helps pull LDL out of the blood and eliminate them from the body. (12)

One study of 32 patients received 500mg of Berberine which was administered two times a day. After three months, the results indicated reductions in overall cholesterol specifically 25% reduction in LDL. Metabolites of Berberine were able to upregulate LDL receptors showing potent hypolipidemia effects.(13)

“In one study, 32 patients who were not receiving other lipid-lowering therapies were given Berberine 500 mg twice daily for three months. In these patients, significant reductions in LDL, triglycerides, and total cholesterol were seen from baseline (25% reduction in LDL, 35% reduction in triglycerides, and 29% reduction in total cholesterol”

Triglycerides

Triglycerides are produced from a surplus of consumed calories which are later stored into fat cells. This also increases fatty tissue around our bodies.

Berberine activates a key mechanism called AMPK which regulates cellular energy in our tissues. (14)

It helps breakdown sugar and fats to restore energy. This process oxidizes fatty acids in the liver which assists in metabolizing lipids. A study of T2D Chinese patients with dyslipidemia were treated with 1g of Berberine everyday for three months and showed a reduction in blood triglycerides by 36%. Activation of AMPK can support liver weight, cholesterol, and triglyceride reductions. (15)

“In Chinese patients with type 2 diabetes and dyslipidemia, 1 g/d of BBR twice a day for 3 months lowered blood TAG 36% [43]. Again, in type 2 diabetic Chinese patients, BBR at 1 g/d twice daily for 2 months or 1.5 g/d thrice daily for 13 weeks lowered TAG by 18% and 21%, respectively”

Plaque build up

Berberine may lower the risk of atherosclerosis which is the build-up of plaque on the arteries. Decreasing LDL collaterally alleviates endothelial inflammation. Berberine can help ameliorate LDL adhesion which prevents lipids from attaching to the artery walls. (16)

It signals complex pathways to improve vascular receptors, inhibits thickening of artery walls, and provides anti-inflammatory effects. Inflammatory markers such as IL-6 and TNF -α which increase due to high cholesterol and blood pressure were shown to be reduced by Berberine in rat models. (17)

This potentiates Berberine’s anti-atherosclerosis function and protecting artery walls.

“Expression levels of TLR4, Myd88 and NF-κB were increased in spontaneous hypertension group. However, their expression levels were significantly reduced in Berberine group than those in spontaneous hypertension group (P < 0.05). Similarly, levels of IL-6 and TNF-α were increased in spontaneous hypertension group and decreased in Berberine group”

Statins

Berberine appeared to work synergistically with statins and other cholesterol lowering medications to further enhance duo effects.

Berberine combined with Simvastatin, Atorvastatin, and Ezetimibe showed significant reduction in LDL, triglycerides and overall total cholesterol.

Various studies were comparing efficacies between a combination of Berberine with statins versus statins alone.

One study revealed the combination of Berberine and Simvastin had greater reduction in LDL cholesterol in 63 patients with high cholesterol than Berberine and Simvastin separately. (18)

Another similar study with a combination of Berberine and Atorvastatin was more effective than Atorvastatin alone in suppressing cell formation, fat and cholesterol congregation. (19)

A study revealed Berberine co-administered with other herbal ingredients had a greater reduction in LDL and triglycerides than Ezetimbe alone. (20)

Please consult with your doctor if you are already taking medication before supplementing Berberine.

“Combination of BBR with SIMVA up-regulated the LDLR messenger RNA in rat livers to a level about 1.6-fold higher than the monotherapies did. Significant reduction of liver fat storage and improved liver histology were found after the combination therapy. The therapeutic efficacy of the combination was then evaluated in 63 hypercholesterolemic patients. As compared with monotherapies, the combination showed an improved lipid-lowering effect with 31.8% reduction of serum LDL cholesterol (P < .05 vs BBR alone, P < .01 vs SIMVA alone).”

“The results from Oil Red O staining and HPLC revealed that BBR effectively suppressed foam cell formation and lipid and cholesterol accumulation . . . The results obtained in the present study demonstrate that the combination of atorvastatin and BBR is more effective in inhibiting foam cell formation than using atorvastatin alone.”

“Combined treatment with these drugs was as effective as STs in moderate doses (LDL cholesterol -37%, triglycerides -23%). In HeFH patients the addition of BBR resulted in LDL cholesterol reductions inversely related to those induced by the stable therapy (r = -0.617, P <0.0001), with mean 10.5% further decrease.”

Cardiac rhythm

Berberine was found to decreased in abnormal ventricular contractions.

Berberine treated patients with chronic heart failure. A clinical study included 100 patients with ventricular tachyarrhythmia. After treatment of Berberine, results showed that it caused 50% or greater reduction in ventricular premature contractions. This suggests Berberine may provide a modest potential in normalizing cardiac palpitations. More studies are needed. (21, 22, 23)

KEY TAKEAWAY:

Berberine’s other main attribute is its regulation of cholesterol. Its potent functions includes lowering total cholesterol, removing LDL, decreasing triglycerides, anti-inflammation in artery walls, normalize heart palpitations and synergisms with other cholesterol lowering drugs. Research and studies have published promising evidence in alleviating high cholesterol and other lipid measurements.

Anti-Inflammation

What’s inflamed?

On the scope of diabetes, it is also considered an inflammatory disease in which mechanisms and functions of insulin are inflamed.

How does Berberine work?

Measuring reduction in pro-inflammatory cytokines helps determine Berberine’s effect. Cytokines are groups of proteins and sub-proteins that signal cells to tackle immunity, inflammation and fostering growth of new blood cells.

Some cytokines are pro-inflammatory (aggravate the disease) and some are anti-inflammatory (ameliorate the disease). Berberine reduces pro-inflammatory cytokines such as TNF-α, IL-6, IL-1β, MMP9, COX2, iNOS, MCP-1, CRP, HP. These complex cytokines could be reduced by activation of AMPK and other key signaling pathways. Inflammation can occur through the heart, arteries, and liver.

TNF-α is responsible for cell inflammation more specifically, cellular death. This cytokine increases the risk of atherosclerosis by building up of plaque and dead tissue cells on the artery walls.

Berberine’s AMPK activation can inhibit production of pro-inflammatory cytokines such as iNOS and TNF-α. iNOS is an overproduction of nitric oxide heavily linked to insulin resistance. (24)

NF-α along with IL-6, and IL-1β, can cause inflammation in the liver. High fat diet is a common occurrence that leads to an inflammation on the liver. AMPK mediates this by decreasing hepatic steatosis (build-up of fat in the liver).

Overall inflammation activity of Berberine targets complex enzymes and markers that help sensitize insulin secretion, reduction in insulin resistance and improving cardiovascular function. (25)

Berberine was shown to downregulate NF-κB which controls many cellular behaviors such as DNA transcription, cytokine production, and cell death/growth. This inhibition of this pathway helps reduce the development of inflammation in insulin resistance and improve metabolic issues. (26)

KEY TAKEAWAY:

Berberine’s anti-inflammatory response aids in reducing pro-inflammtory cytokines in fatty liver, artery walls, and decrease insulin resistance through the activation of AMPK.

Antimicrobial

What are microbes?

Gut microbiota are microorganisms that live in our stomach. Our gut contains trillions of microorganisms with up to 1000 or more verified bacteria. There have been documented associations between gut microbiota and diseases. Some bacterial organisms may influence obesity, diabetes and cancer. While other bacteria will carry endotoxins such as lipopolysaccharides.

Lipopolysaccharides (LPS-antigen) consist of lipid, polysaccharide (carb molecule), and O-antigen that surrounds the walls of the bacteria. LPS stimulates pro-inflammatory cytokine IL-8 which aggravates stomach, gut bacteria, and gut hormones. Berberine supports reduction of LPS thus decreasing leakage into the bloodstream.

How does Berberine work?

High fat diets can lead to a production of proinflammatory cytokines as we discussed above. LPS can induce cytokines to increase oxidative stress and visceral fat buildup.

In a study of high-fat diet fed rats, Berberine descended inflammatory levels of LPS. Reduction of intestinal bacterial such as LPS can decrease gastro-inflammation and leakage into the bloodstream. (27)

Ameliorating bacterial inflammation can lessen lipid circulation and lower the risk of atherosclerosis, fatty liver disease, and visceral fat tissue. (28)

After Berberine was treated in rats, gut microbiota profile was analyzed and discovered alterations in the gastrointestinal bacteria. A study of Berberine reported a decrease in glautia and allobaculum bacteria which is linked to obesity. (29)

Berberine displayed modulation in a variety of bacteria species. One of which is combating the growth and secretion of cholera and E. coli. (30) We can see why the first uses of Berberine pertained to its gastrointestinal amelioration. As for connection of modulating gut microbiota to anti-diabetic properties is still ongoing.

Berberine is able to fend off harmful bacteria and serves as a treatment for diarrhea.

"LPS levels in portal plasma were significantly higher in HFD-fed rats compared with control rats (Fig. 3A). Following treatment with Berberine for 6 weeks, LPS plasma levels in HFD-fed rats were significantly reduced when compared with the untreated HFD-fed rats; however, LPS levels in Berberine-treated rats remained higher than in control rats."

KEY TAKEAWAY:

Berberine’s anti-inflammatory response aids in prohibiting proinflammtory cytokines in fatty liver, artery walls, and decrease insulin resistance through the activation of AMPK.

Depression

How does berberine work?

Berberine has the potential to treat withdrawal and relapse symptoms in drug-dependent rats.

A study involved morphine induced rats that showed signs of withdrawals for three days after discontinuation. Withdrawals displayed depression and anxiety-like symptoms. After administering Berberine, it prevented the increase of corticotropin releasing factor which regulates fear and anxiety signals in the brain. (31)

Berberine was also able to prevent the decrease of brain-derived neurotrophic factor which produces proteins in the brain cells to maintain growth and function. Stopping the decrease of BDNF can prevent depression and anxiety-like behaviors. These results may play a beneficial factor in withdrawal and relapse issues. (32)

Another study was conducted to experiment the effects of Berberine on PTSD of rats. It was aimed to see if Berberine can reverse dopamine dysfunction. After treatment, the results appeared to have restored neurochemical imbalances. (33)

It was discovered that behavior stresses began to decrease and exhibited signs of reduced anxiety. (34)

In comparison of the Berberine group and non-Berberine group, their findings concluded a significant increase in dopamine concentrations. Berberine and Fluoxetine (antidepressant) had similar levels of dopamine tissues in the hippocampus and amygdala. (35)

More research and evidence are needed to verify these findings since no human clinical studies were performed. For now, Berberine appeared to have alleviating treatments in anxiety-like behavior and dopamine rehabilitation associated with PTSD.

KEY TAKEAWAY:

Berberine was able to show anti-depressant like functions. It was only observed to treat withdrawal and relapse symptoms in mice. It may show mild ailment in drug-related addiction but not a strong indicator for overall depression due to limited studies.

Anti-tumor

How does Berberine work?

The effects of Berberine on ovarian cancer cells were examined. Ovarian cancer is the proliferation of tumor cells in the ovaries.

When Berberine was applied on ovarian cancer cells it induced pro-apoptotic behavior, which encourages the death of cells and inhibits the growth of cancer cells. It was also noted to have a synergistic effect with an anti-tumor drug, cisplatin. Berberine may have a potential in serving anti-tumor effects in various cancers. (36)

Berberine’s anti-tumor effects was also tested on a wide array of cancers. Researchers examined the effects of Berberine on the animals’ (rats, mice and hamsters) cancer cells. Breast, liver, colorectal, gastric and sarcoma cancers were tested.

During the study, results revealed breast, esophageal and lung cancers had the most positive benefits when administered with Berberine. (37)

Berberine’s key mechanisms include inhibition of cell proliferation, induced apoptosis, slow cell migration and decreased amounts of new blood vessels. Berberine does display a great potential in mitigating certain types of cancers in animals. (38)

Other studies have discovered anti-tumor effects of Berberine in the digestive system. Several mechanisms of Berberine can stimulate certain enzymes, pathways, and inhibit inflammatory cytokines.

Berberine induced inhibition of new blood vessel growth, which includes tumor invasion, proliferation and metastasis. It may also contain synergistic effects when combined with d-limonene to further increase anti-cancer effectiveness. (39)

“Berberine reduces the level of IL-8, which is related to its inhibition of PI3K signaling pathways54,55. A synergistic anti-gastric cancer effect was also observed when Berberine was used in combination in vivo and in vitro models, such as the combination of Berberine and d-limonene.”

Berberine was shown to produce significant tumor suppressing effects by signaling AMPK and down-regulation of CD147. (40)

Berberine may possess cell cycle arrest and induce apoptosis in colorectal cancer. Cells are designed to undergo cell division and duplication by multiplying and ensure proper replication of DNA. When tumor cells begin to grow, Berberine can act as an inhibitor to stop the cells from duplicating. (41)

“It has been reported that Berberine can inhibit colorectal adenocarcinoma growth by inducing G₂/M phase arrest and down-regulating the expression of related cyclins, such as cyclins B1, cdc2 and cdc25c.”

When Berberine was combined with irinotecan, it appeared to stop activation of NF-κB, which are proteins that help maintain cell function such as cell growth and survival. This inhibitory effect may be beneficial in increasing cell destruction and metastasis in colon cancer cells. (42)

“Berberine is combined with irinotecan to potentiate the cytotoxicity of colon cancer cells, which might be attributed to an increased rate of apoptosis, possibly mediated by the inhibition of NF-κB activation.”

Berberine’s anti-tumor effect may play a significant role in alleviating various cancers throughout the body.

It has a promising possibility of stopping the growth of tumors, inducing cell cycle arrest, and halting cancer cell migration. Studies have also combine Berberine with other cancer fighting medications to potentiate anti-tumor properties and provide a greater insight in Berberine’s anti-tumor mechanisms.

KEY TAKEAWAY:

Berberine may provide significant evidence in anti-cancer treatments. Berberine may induce cellular death, suppress cell growth and slow cell migration on targeted cancer cells.

Antioxidants

Free radicals are unstable atoms, specifically electrons, seeking to pair with other electrons. These free flowing electrons can cause oxidative damages in the body. They can also be in high chemical reactivity which can cause damage to cells such as proteins, lipids, and DNA. (43)

One of the most concerning radicals are reactive oxygen species. Oxygen derived radicals can be essential and also damaging to the human body. (44)

Depending on the chemical balance of these atoms, it can provide necessary gears for various enzymes. But too much oxidative radicals can cause damage to cells.

Lipid peroxidation is the process of free radicals stealing electrons from cell membranes, which can disrupt cell signaling, proteins, and induce DNA damage.

Refrain from confusing this process with fat oxidation, which is simply burning fat into energy. This process involves the transportation of fatty acids into the mitochondria to produce ATP (energy).

“An experimental study demonstrated the effect of Berberine on lipid peroxidation after inducing chemical carcinogenesis in small animals (rats). An increase in LPO (lipid peroxidation) was observed after carcinogenesis induction, but also its significant reversal after Berberine administration (30 mg/kg). Berberine shows therefore at least partial antioxidant properties, due to its effect on lipid peroxidation”

In this case with Berberine on lipid peroxidation, it was able to reverse the effects in carcinogenic induced rats. More research is needed to investigate the properties of Berberine on lipid peroxidation since this was only tested on rats. (45)

Berberine was also noted to scavenge free radicals. A therapeutic property that protects harm or neutralizes oxidants. Some studies found Berberine to have a comparable antioxidant effect of vitamin C. (46)

Berberine may prove as a potential antioxidant treatment. Through various research, it can support cell signaling, reverse lipid peroxidation, and protect against oxidative stress. Berberine’s antioxidant properties may possess therapeutic potential.

Increases in blood sugar can weaken antioxidant actions. Key antioxidant enzymes that protect oxidative stress on cells such as superoxide dismutase and glutathione peroxidase. Both are beneficial against oxidative damage in cells. Berberine was shown to increase SOD activity and providing greater antioxidant protection in diabetic rats. (47,48)

“ Administration of Berberine to rats with diabetes mellitus increased the SOD (superoxide dismutase) activity and decreased the MDA (malondialdehyde) level (marker of lipid peroxidation).”

KEY TAKEAWAY:

Berberine also has antioxidant effects such as protection against cellular oxidation and it promotes healthy cell function. More studies are needed to confirm its antioxidant effectiveness.

Polycystic Ovary Syndrome (PCOS)

PCOS is a hormonal imbalance in female’s reproductive organs. Women with PCOS have a higher risk of developing metabolic syndrome, cardiovascular disease, and weight gain. Obesity is a common occurrence amongst women with PCOS.

Berberine was investigated for the treatment on PCOS. A randomized controlled trial was conducted with 102 Chinese women with PCOS. Random selection was performed which split the sample size of two groups: one group received 500mg three times a day and the other was given a placebo as the control group. (49)

Results after a 4 month treatment concluded a decrease in insulin resistance, cholesterol, triglycerides, and LDL for majority of patients treated with Berberine. Menstral balances and ovulation rates were restored in a small number a patients. This study suggests Berberine's potential for alleviating PCOS symptoms but more research is needed to reaffirm the results due to a small sample size and limited studies. (50)

“A total of 98 of 102 subjects (96.1%) completed the four month treatment, including 69 (70.4%, 69/98) normal weight and 29 (29.6%, 29/98) overweight/obese. Fourteen women (14.3%, 14/98) had regained regular menses after Berberine treatment and there was no significant difference between normal weight and overweight/obese groups. The ovulation rate was 25.0% over four months in the whole group, 22.5% in the normal weight group and 31.0% in the overweight/obese group. Sex hormone binding globulin, insulin resistance, total cholesterol, total triglyceride and low-density lipoprotein cholesterol decreased after Berberine treatment in the normal weight group only.”

KEY TAKEAWAY:

Berberine may have a modest potential in relieving symptoms of PCOS. Weight and diabetes seems more applicable for Berberine in PCOS related issues but only has a subtle support for ovarian and menstrual problems.

What is AMPK?

AMPK (adenosine monophosphate-activated protein kinase) activator is a health promoting enzyme that signals cells and tissue to maintain energy balance. It's a complex process with overwhelming benefits. AMPK detects depletion of cellular energy and begins to promote production of ATP. This occurs from exercising or caloric restriction. During this event, AMPK regulates metabolic processes in the liver, heart, skeletal, muscle, pancreas and fat. When activated in the liver, it inhibits lipogenesis (fat production) lowering total cholesterol and oxidizes fatty acids. Activation in the hypothalamus helps break down glucose for energy, prevent glucose storage and increase uptake into the muscle for energy. It simulates various cells and tissues to restore fuel and energy into the cells by breaking down glucose and lipids. This improves overall health issues such as diabetes, heart disease and weight loss. (51,52)

What happens when Berberine activates AMPK?

AMPK on diabetes includes an increase in glucose uptake, induces insulin secretion, decreases insulin resistance and prevents apoptosis. Once cellular energy has reached low levels it signals the body to generate energy that has been stored in sugar and fat. It also affects other internal mechanisms that leads to antioxidants and inflammation. AMPK on cholesterol has a tremendous study on lowering TAG, decrease atherosclerosis, and cardiac health. (53,54)

“BBR (5 mg/kg/d, p.o., 3wk) improved fatty liver in obese mice by regulating neural signaling from the central nervous system and peripheral AMPK signaling”

“In obese db/db and ob/ob mice, BBR treatment reduced liver weight, hepatic and plasma triglyceride, and cholesterol contents. In the liver and muscle of db/db mice, BBR promoted AMPK activity and fatty acid oxidation and changed expression of genes involved in lipid metabolism.”

KEY TAKEAWAY:

Berberine can activate AMPK, which is a powerful mechanism in supporting cellular processes in maintaining sufficient energy throughout the body by using up the body’s glucose and lipid profiles. A powerful mechanism in improving diabetes and cardiovascular health.

Does Berberine help muscle growth?

Unfortunately Berberine does not help muscle growth or stimulate protein synthesis. It actually upregulates Atrogin-1, a protein expression that increases muscle degradation and inhibits protein synthesis. This process can cause muscle atrophy. If you are trying to build muscle this is not the ideal supplement you should take. Although depending on if your fitness goals are to slim down, then taking Berberine may accelerate the process by stimulating AMPK which we know helps metabolize glucose and cholesterol.  (55)

“The inhibition of mTOR/rpS6 signaling is one of the key effects of AMPK activation [91, 101, 102]. AMPK mimics the impact of growth factor down-regulation associated with calorie restriction by inhibiting activity of the mammalian target of rapamycin complex 1 (mTORC1)”

KEY TAKEAWAY:

Berberine is not an optimal supplement for muscle growth.

Supplement Interactions

Various studies of Berberine have combined the supplement with other nutraceutical ingredients such as:

• Sodium caprate
• Cinnamon
• Milk thistle
• Astaxanthin
• Red yeast rice
• Chitosan
• CoQ10
• Quercetin
• Gymnema sylvestre

All of these combinations were studied to examine the effectiveness on absorption, glucose, and cholesterol. So far most studies have shown positive results, some combinations performing better than Berberine alone. (56, 57, 58, 59, 60)

KEY TAKEAWAY:

Berberine’s effectiveness was shown to increase glucose and cholesterol's lowering effect by co-administering with other herbal supplements with similar function.

DNA damaging

Yes most, if not all, herbal supplements have pros and cons. We’ll go over the cons of Berberine.

One study reported DNA damaging induced by goldenseal. Alkaloid constituents of goldenseal extracts that aggravated DNA structure were Berberine and palmatine. (61)

Berberine was seen to suppress DNA building enzymes known as topoisomerase. Inhibiting these enzymes may produce gene toxicity and increase tumor growth. (62)

A rat study was conducted and found an increase of liver cancer. While other studies of Berberine have tested to find DNA damaging mechanism, other studies were abundant in the anti-tumor like properties.

This suggests that Berberine may provide a positive ailment in anti-cancer treatments. Although it may sound alarming, keep in mind that this is just coming from one study. Berberine may have a potential in damaging DNA structure. (63)

KEY TAKEAWAY:

Berberine was noted to induce DNA damage and increase liver cancer in rats. Conflicting studies have published Berberine to have anti-tumor like effects instead. But at the moment more studies are needed to confirm this finding.

Low bioavailability

Although Berberine promotes alleviating benefits it may seem lackluster due to its low bioavailability.

In animal studies, Berberine was administered orally and intravenously (injection into the veins), absorption revealed to be about .68%, less than 1%. Berberine's poor absorption is also due in fact it is a substrate for P-glycoprotein. When Berberine reaches our intestines it first has to go through a protective barrier that prevents chemicals and molecules from being absorbed through the intestinal tract. (64)

In short, P-glycoprotein latches onto Berberine, discontinuing its passage which causes low permeability in the gut.

To increase absorption you must co-administer Berberine with a P-glycoprotein inhibitor. Researchers increased Berberine’s bioavailability by using pharmaceutical P-glycoprotein inhibitors such as Cyclosporine A, Verapamil, and the monoclonal antibody C219. (65)

In comparison with Metformin, Metformin is better absorbed than Berberine. Metformin does not bind to P-glycoprotein therefore it permeates through the intestines better than Berberine. (66)

A study to improve Berberine’s absorption, researchers coadministered both Berberine and metformin as a synergistic mechanism to allow Berberine enter the bloodstream through metformin while simultaneously increase the effectiveness of both drugs. (67)

Permeation enhancers were also tagged along with Berberine to significantly increase gut absorption. These enhancers were a few nutraceutical supplements such as cassia cinnamon, milk thistle (another P-glycoprotein inhibitor), and chitosan. These herbal additives improved Berberine’s permeation. Lipid transporters such as sodium caprate and sodium deoxycholate were also shown to greatly increase bioavailability. (68)

Derivatives of Berberine, usually synthesize in labs, such as Dihydroberberine and Dimethyldihydroberberine were studied to have greater stability, bioavailability, and efficacy than Berberine alone. Both derivatives displayed superior function over Berberine. (69,70)

Berberine absorption can be improved in a multitude of fashion. Whether through pharmaceutical administration, herbal additives, lipid transporters, or derivatives all studies verified increased bioavailability to some degree. Some applications may seem impractical but realistic methods are to combine Berberine with nutraceutical supplementation. All other treatments were done via lab experiments and modifying the structure of Berberine.

“One of attributable factors is BBR's poor oral bioavailability [128] that has been reported to be less than 1%”

“Pharmacokinetic studies have indicated that BBR has poor oral bioavailability”

KEY TAKEAWAY:

Berberine and many other supplement have inherently poor absorption rates. Many compounds, supplements and synthetic alterations have been used to combine and increase Berberine’s absorption.

Side effects/toxicity

Most Berberine supplements in the market are dosed from 1000mg-1200mg a day. These high dosages will not only provide you its potent benefits but may also experience gastrointestinal discomfort. Common side effects include diarrhea, constipation, flatulence, and upset stomach. No severe incidents were reported. Berberine’s toxicity profile observed in clinical trials resulted in patients reporting mild gastrointestinal irritation. (71,72)

KEY TAKEAWAY:

Berberine has a low toxicity profile which only mild symptoms were reported during clinical studies. Usually high dosages of Berberine may lead to abdominal discomfort.

Dosage

Most daily dosage comes 600mg-1500mg. Milligrams per capsule can range from 450mg-600mg. (73)

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