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Berberine For Diabetes – Is Berberine Natural Metformin Alternative?

Barberry is a natural source of berberine

Incidences of insulin resistance, obesity, and other metabolic disorders have reached massive proportions in industrialized nations. The current popular glucose-lowering drug available by prescription is called metformin. This drug comes with potential side effects, some of which are very serious (1).

Berberine is a plant compound that developed a reputation as a natural metformin alternative. This is because it can help the body reduce blood sugar in multiple ways with relatively few side effects.

Here, we’ll examine a number of berberine’s benefits and see where it stacks up in terms of its ability to lower blood sugar, improve metabolism, and perform its other duties in various systems of the body. We dug through mountains of scientific studies so you don’t have to.

What is Berberine & Where Does it Come From?

Berberine is a phytonutrient and alkaloid found in several different plants, including goldenseal, European barberry, phellodendron, coptis, Oregon grape, and tree turmeric (2).

The Chinese Medicine and Ayurveda communities have been aware of the benefits of berberine since ancient times, including its ability to lower blood sugar. Traditionally, it has been used for treating inflammation, infections, parasites, wounds, skin and stomach ulcers, indigestion, hemorrhoids, and diarrhea in many parts of the world. Widespread diabetes is relatively new in history, so they didn’t pay much attention to it in ancient times. (3)(4)

What are the Benefits of Berberine?


Lowers Blood Sugar & Improves Insulin Sensitivity

Berberine lowers blood glucose as much as common drugs used for that purpose. It does this in several different ways.

Supports Insulin Production in the Pancreas

A 2012 study noted berberine’s ability to decrease glucose and insulin in the blood of humans and animals and strengthen insulin sensitivity. (4)

The researchers explained one of the mechanisms behind these benefits: the regulation and repair of pancreas islets. Islets are groups of cells in the pancreas that make hormones. One of the hormones is insulin, which allows your cells to absorb glucose and use it for energy.

“These results indicate berberine may have a two-way regulation in pancreas islets. In typical type 2 diabetes with notable insulin resistance, berberine lowered blood insulin levels through increasing insulin sensitivity. However, in type 1 diabetes or the late stage of type 2 diabetes characterized by poor β-cell function, berberine was able to increase insulin secretion via repairing destructed or exhausted islets, which may be related to its antioxidant and anti-lipid peroxidation properties.”

Activates the “Metabolic Master Switch” Enzyme

One glucose-lowering talent of berberine is the ability to activate the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. AMPK is an enzyme produced in the brain. It has earned the nickname of “metabolic master switch” because it plays an important role in energy metabolism. Defects of this enzyme’s signaling pathway can result in obesity and other metabolism problems. Berberine helps to activate AMPK. This helps the body regulate the metabolism of glucose and fats. (5)

Stimulates Enzymes that Break Down Glucose

A 2014 study sought to determine whether AMPK activation was the only mechanism by which berberine could lower blood sugar and found that it is not. They did this by chemically blocking AMPK activation. The results showed that even when AMPK was blocked, berberine still lowered blood sugar. So did metformin. The authors concluded that berberine and metformin not only activate AMPK. They also promote glucose metabolism through the stimulation of glycolysis, which is the breakdown of glucose by enzymes in the body. (6)

Reduces Breakdown of Certain Carbs & Starches

Berberine is also able to work against diabetes because it works in the same way as alpha-glucosidase inhibitor and alpha-amylase inhibitor drugs (e.g. miglitol and acarbose). These are medications that prevent the digestion of carbohydrates and reduce the impact of eating carbs on blood sugar (7)(8). Specifically, they inhibit enzymes that break down sugars and starches. Natural forms of these exist in plants and include curcumin and berberine. (9)

They also decrease glucose transportation across the intestinal epithelium layer, (the layer of cells between the intestines and the stomach where food is absorbed into the body).

Prevents the Liver from Creating Too Much Glucose

Berberine has also been found to inhibit gluconeogenesis, or the production of glucose that takes place in the liver. (10)

Supports Metabolism

The same mechanisms that allow berberine to control blood sugar levels and insulin sensitivity also make it good for the overall metabolism of carbs and fats.

If you’ve read this article from the beginning, you know that it inhibits glucose production in the liver and glucose digestion in the belly. It activates the enzyme, AMPK, which regulates fat and sugar metabolism. It also repairs and supports islets, the clusters of cells in the pancreas that produce insulin.

May Promote Weight-Loss

In one study, obese human subjects took 500mg of berberine three times daily for 12 weeks. They lost an average of five pounds (2.3kg). They also lost more cholesterol and triglyceride than they would have through other weight loss methods. (11)

Another study of humans with metabolic syndrome led to greater weight loss in the same amount of time. In three months, their body mass indices (BMI) dropped from an average of 31.5 to 27.4, taking them from obese to overweight status. They took 300mg, three times daily. Insulin resistance likely played a role in the amount of weight lost. (12)

A 6-month study of metformin and weight loss monitored 154 patients who took up to 500mg twice per day. They lost a considerable amount of weight, especially those with high insulin resistance. Untreated participants gained weight. (13)

Berberine has multiple mechanisms that help regulate metabolism and cause weight loss.

AMPK triggers the production of new mitochondriaAMPK triggers the production of new mitochondria (pictured)

Reduces Inflammation

A 2014 review of studies examined berberine’s anti-inflammatory effects in those with metabolic disorders like diabetes, which is also an inflammation disorder. In the analysis, they noted a large number of antioxidant and anti-inflammatory activities in humans and animals. (14)

Kills Bacteria, Viruses & Fungi

A lot of scientific studies reveal berberine’s ability to kill bacteria, viruses, fungi, and parasites. There are too many to mention here. However, here are some notable ones.

A 2014 study noted its ability to fight candida overgrowth, a fungal infection that begins in the digestive system and can spread to all body systems. (15)

A 2011 rodent study reduced influenza virus mortality from 90% to 55%. (21)

Researchers in 2005 found that berberine helped certain antibiotics fight the deadly methicillin-resistant staphylococcus aureus (MRSA) bacteria in a synergistic relationship compared to controls. (16)

Quickens Wound Healing

Berberine’s anti-bacterial and anti-inflammatory effects can help wounds heal more quickly.

Promotes Heart Health & Lowers Cholesterol

High blood sugar, triglycerides, and unhealthy cholesterol increase the risk of heart disease. Berberine reduces all three and elevates the level of healthy cholesterol. (17)

In a long-term study published in 2003, berberine significantly improved the survival rate of people who previously suffered from heart failure. (18)

Lowers Fat Build-Up in the Liver

In a 2013 analysis of scientific studies examined berberine’s ability to reduce fat storage in the liver. Researchers confirmed this ability and recommended more studies to determine how berberine accomplishes this. (19)

May Improve Mood

A 2008 study increased levels of serotonin (19%), dopamine (52%), and norepinephrine (29%) in the brains of rats within 15 days using berberine. (20)

Researchers examined existing studies in 2019 and noted numerous ways in which berberine improves moods, especially in patients with mood disorders. (22)

Encourages Good Gut Bacteria Balance


gut bacteria3D Image of Intestinal Bacteria

A 2010 study of adult men of all ages, shapes, and sizes linked excesses of certain types of “bad bacteria” in the gut with type 2 diabetes. (23)

In a 2018 analysis of existing studies, researchers pointed out several connections between metabolic disorders like diabetes and the gut bacteria ecosystem. They blame the current high levels of diabetes on a modern diet rich in carbohydrate-rich and fat-rich processed foods and a lack of fiber. Healthy gut bacteria feed on the fiber and create short-chain fatty acids (SCFA’s) that reduce inflammation. People with diabetes have lower levels of gut bacteria that create SCFA’s. All of these factors, combined with the overuse of antibiotic drugs, lead to more diabetes cases than in previous periods of history. (24)

The same researchers also noted other chemicals produced by healthy gut bacteria that help prevent metabolic disorders and support the immune system and organs in all systems of the body.

According to a Chinese study in 2011, berberine that does not get absorbed and used by the body may suppress “bad” gut bacteria and inhibit their reproduction. Some of these bacteria strains help create the conditions for diabetes. Berberine that does get absorbed may help suppress these strains, too, but the scientists were mainly looking at the berberine that stayed in the digestive system.  (25)

The researchers cited a study showing that berberine does not suppress healthy probiotic strains in the lactobacillus and bifidobacterium groups. These groups include most of the healthy strains you will find in probiotic supplements, yogurt, and other probiotic-rich foods. They also pointed out another study of a probiotic milk beverage slowing down a number of diabetic symptoms in rats consuming high amounts of fructose. By suppressing bad bacteria, berberine supports the growth of probiotics.

Reduces the Severity of Acne

A 2012 Iranian study of adolescents with moderate to severe acne lowered their Michaelson’s acne severity scores by an average of 45% in four weeks compared to a placebo. They used 600mg of oral barberry extract daily. (33)

Berberine vs. Metformin: Is Berberine the Natural Substitute?

First of all, let us remind you that this article is not intended to be a substitute for diagnosis and sound medical advice from your doctor. Second of all, below is some great news for berberine.

A 2008 study followed 36 adults, who were newly diagnosed with type 2 diabetes, for three months. Subjects were randomly assigned berberine or metformin. Both showed similar effectiveness at lowering blood sugar. Berberine worked better than metformin for fat metabolism. (26)

In part B of the study, they looked at 48 adults with “poorly controlled” type 2 diabetes. Berberine improved blood sugar and cholesterol levels as well as fat metabolism. The only side effects reported were temporary gastrointestinal symptoms: farting, gas pains, diarrhea, and constipation. There was no damage to liver or kidney functions. (26)

The medical scientists concluded that berberine “may serve as a new drug candidate in the treatment of type 2 diabetes.” They noted its low cost and relative safety compared to established drugs with similar effects. They also recommended new studies embracing a larger share of the diabetes patient population. (26)

A 2015 analysis of scientific studies published in the Journal of Ethnopharmacology compared the effects of berberine on those with type 2 diabetes. Researchers looked at 27 randomized controlled clinical trials with a total of 2,569 patients participating. These were placebo studies. Some also compared results of berberine to placebos with and without exercise programs and other “lifestyle interventions.” Others compared berberine with oral drugs that lower blood sugar. (27)

The researchers concluded that berberine with lifestyle intervention was more effective at lowering blood glucose compared to lifestyle intervention alone with placebo. Berberine showed additional positive effects on blood sugar when combined with similar pharmaceutical drugs. They concluded that berberine’s ability to lower blood sugar is as effective as conventional treatments. They also recommended berberine for those who can’t afford pharmaceuticals while calling for more studies to settle unanswered questions. (27)

Verdict: Berberine does appear to act as a natural alternative to glucose-lowering drugs like metformin, but remember: Always consult with your healthcare provider before treating any diseases with nutrients. They have the resources to perform proper diagnoses and tests. If you have a complex health condition or multiple illnesses, they are also better equipped to detect these things.

Berberine vs Metformin Side Effects

side effects medicine pillsMetformin Side Effects

Common Side Effects

From (1)

“Commonly reported side effects of metformin include: lactic acidosis, diarrhea, nausea, nausea and vomiting, vomiting, and flatulence. Other side effects include: asthenia, and decreased vitamin b12 serum concentrate.”

The same website recommends telling your doctor if you experience the above problems after taking metformin. Other common side effects to watch for include muscle cramps, painful urination, stomach pain or discomfort, fever, chills, sleepiness, and appetite loss.

Less Common Side Effects

Less common effects of metformin include cold sweats, anxiety, dizziness, blurry vision, fast or irregular heartbeat, headache, confusion, slurred speech, difficulty breathing, weakness, and a few others.

Recall that metformin can cause lactic acidosis. Extreme cases of lactic acidosis caused by metformin have caused dangerously low blood pressure, hypothermia, and death. Some extreme cases began with minor symptoms like “malaise, myalgia, respiratory distress, somnolence, and abdominal distress.” (1)

Metformin may be a bad idea if you have advanced cirrhosis of the liver because it can increase the risk of lactic acidosis. Both metformin and berberine may be OK, or even beneficial if you have other liver conditions, but you need to ask your doctor about this. (29)(30)

A 13-year study of the effects of long-term metformin use compared to a placebo, published in 2016, revealed vitamin B12 deficiency and anemia as common side effects. Those low in B12 had a higher likelihood of developing peripheral neuropathy. The dose was 850mg twice per day. Patients were enrolled in a diabetes program. (28)

In a 2015 study, medical scientists performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment on stroke patients with impaired glucose intolerance. About side effects, the researchers noted:

“19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3–10 weeks.” (31)

Berberine Side Effects

Berberine is widely revered as an alkaloid that lowers blood glucose significantly with relatively few side effects.

You may recall from the 2008 study mentioned above that some berberine patients taking 500mg three times per day experienced farting (19%), abdominal pains (3.4%), diarrhea (10.3%), and constipation (6.9%). The effects were temporary. (26)

Another negative side effect of berberine is that if you are currently taking other substances that lower blood sugar, like metformin, the combination may cause your blood sugar to go too low. Make sure to consult your doctor if you think you might be in this category.

On the other hand, some medical scientists note that berberine can work synergistically with other substances that lower blood sugar, at least at specific dosages. However, don’t turn yourself into a human drug lab without medical supervision.

You also want to be cautious when taking berberine with blood-thinning herbs or drugs, or if you have a history of overly low blood pressure. (32)

If you want to use berberine to treat a disease like diabetes, then you definitely want to talk to your doctor first. Do this regardless of whether you currently use drugs, herbs, or extracts of any kind.

Please also consult your doctor if you are pregnant or breastfeeding and wish to supplement with berberine. There is a possible link to brain damage in fetuses and other health risks in newborn babies. (32)

Berberine Dosage – How Much Should I Take?

Berberine is well absorbed by the body. However, it is also metabolized in the liver very quickly. This means that it’s absorbed and used by the body very quickly. After a few hours, blood tests can only measure very small levels of it.

This means that you need to take berberine after every meal to have a constant supply in your body. It is why studies involving people with diabetes often take a dosage of 500mg three times per day. Don’t take more than 500mg at one time, as this can sometimes produce gastrointestinal side effects.

Make sure to choose a pure berberine supplement as well, as many brands sell weaker complexes that will not be as effective.

How Long Does Berberine Take To Work?

You might notice lower blood sugar levels after about one week of use, but this effect may not become apparent for three or four weeks.

The length of time required for berberine to show benefits may vary according to the benefit you are seeking and conditions within your body.

Where To Buy Berberine?

At Intelligent Labs we have produced an ultra-pure berberine supplement in capsules that deliver it in the clinically recognized 500mg dosage. Third-party lab testing ensures the purity of the product and accurate labeling.

Final Thoughts

Berberine is good at reducing blood sugar and increasing insulin sensitivity with relatively few side effects. It has demonstrated a high number of positive health benefits outside of its anti-diabetic and cholesterol-lowering benefits. This plant-based phytonutrient is touted in multiple scientific studies as a natural alternative to metformin and other drugs that decrease blood sugar.

If you are interested in its other health benefits, please read our other article on berberine benefits.

This article is for educational purposes only and is not intended to be a substitute for sound medical advice from your doctor or results from your medical lab. Diagnosis and treatment can be very nuanced, especially if you have multiple medical conditions or any medical condition that affects more than one system in the body. We cannot promise that berberine, or any other supplement, can treat or cure any disease.

Scientific References

1. Metformin Side Effects. (Medically Reviewed November 20, 2018).

2. Berberine. Reference page. WebMD. (No date).

3. Neag MA, Mocan A, Echeverría J, et al. Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacol. 2018; 9: 557.

4. Yin J, Ye J, Jia W. Effects and mechanisms of berberine in diabetes treatment Acta Pharmaceutica Sinica B. 2012; 2(4): 327-334.

5. Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master switch:  possible roles in Type 2 diabetes American Journal of Physiology-Endocrinology and Metabolism. 1999; 277(1): E1-E10.

6. Xu M, Xiao Y, Yin J, et al. Berberine promotes glucose consumption independently of AMP-activated protein kinase activation. PLoS ONE. 2014; 9(7): e103702.

7. Alpha-Glucosidase Inhibitors for Diabetes. Reference page. WebMD. (No date).

8. Amylase Inhibitors. Health Information Library. PeaceHealth. (Reviewed June 8, 2015).

.9 Jhong CH, Riyaphan J, Lin SH, Chia YC, Weng CF. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico. Biofactors. 2015; 41(4): 242-51.

10. Li A, Liu Q, Li Q, Liu B, Yang Y, Zhang N. Berberine Reduces Pyruvate-driven Hepatic Glucose Production by Limiting Mitochondrial Import of Pyruvate through Mitochondrial Pyruvate Carrier 1. EBioMedicine. 2018; 34: 243-55.

11. Hu, Yueshan, et al. “Lipid-lowering effect of berberine in human subjects and rats.” Phytomedicine: International Journal of Phytotherapy & Phytopharmacology. 2012; 19(10): 861+.

12. Yang J, Yin J, Gao H, et al. Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evid Based Complement Alternat Med. 2012; 2012: 363845.

13. Seifarth C, Schehler B, Schneider HJ. Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes. 2013; 121(1): 27-31.

14. Li Z, Geng Y, Jiang J, Kong W. Antioxidant and Anti-Inflammatory Activities of Berberine in the Treatment of Diabetes Mellitus Evidence-Based Complementary and Alternative Medicine. 2014; 2014: 1-12.

15. Dhamgaye S, Devaux F, Vandeputte P, et al. Molecular Mechanisms of Action of Herbal Antifungal Alkaloid Berberine, in Candida albicans PLoS ONE. 2014; 9(8): e104554-.

16. Yu HH, Kim KJ, Cha JD, et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J Med Food. 2005; 8(4): 454-61.

17. Dong H, Zhao Y, Zhao L, Lu F. The Effects of Berberine on Blood Lipids: A Systemic Review and Meta-Analysis of Randomized Controlled Trials Planta Med. 2013; 79(06): 437-446.

18. Zeng XH, Zeng XJ, Li YY. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2003;92(2):173-6.

19. Liu Y, Zhang L, Song H, Ji G. Update on Berberine in Nonalcoholic Fatty Liver Disease Evidence-Based Complementary and Alternative Medicine. 2013; 2013: 1-8.

20. Kulkarni SK, Dhir A. On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol. 2008; 589(1-3): 163-72.

21. Wu Y, Li JQ, Kim YJ, Wu J, Wang Q, Hao Y. In vivo and in vitro antiviral effects of berberine on influenza virus. Chin J Integr Med. 2011; 17(6): 444-52.

22. Fan J, Zhang K, Jin Y, et al. Pharmacological effects of berberine on mood disorders. J Cell Mol Med. 2019; 23(1): 21-8.

23. Larsen N, Vogensen FK, van den Berg FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE. 2010; 5(2): e9085.

24. Aw W, Fukuda S. Understanding the role of the gut ecosystem in diabetes mellitus. J Diabetes Investig. 2018; 9(1): 5-12.

25. Han J, Lin H, Huang W. Modulating gut microbiota as an anti-diabetic mechanism of berberine. Med Sci Monit. 2011; 17(7): RA164-7.

26. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metab Clin Exp. 2008; 57(5): 712-7.

27. Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015; 161: 69-81.

28. Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016; 101(4): 1754-61.

29. Miralles-Linares F, Puerta-Fernandez S, Bernal-Lopez MR, Tinahones FJ, Andrade RJ, Gomez-Huelgas