Berberine, a powerful antioxidant: Benefits, side effects and research

Berberine is a bitter, yellow-coloured compound commonly found in tree turmeric, Oregon grape, European barberry, goldthread, goldenseal and Phellodendron.

Berberine-containing plants are abundant in different parts of the world and could treat skin diseases, inflammatory disorders, fevers, wounds, digestive and respiratory diseases, tumours and microbial infections.

What is Berberine?

Berberine is a natural alkaloid used to synthesise and design new and powerful drugs [1].

Knowledge of the effectiveness of Berberine in treating these diseases has been available for millennia. In modern times, the investigation into the safety and efficacy of Berberine in treating different conditions has been underway, and the results of these studies give individuals options for taking medicines or complementary and natural products containing the compound.

In ancient times, Berberine was used to treat diseases and purify the blood; according to in old historical records found in 650 BC in Ashurbanipal’s library in Assyria [2], Barberry fruit (Berberis vulgaris) is reported to purify the blood.

Ayurvedic or Chinese medicine consisting of Berberis sp. plants’ roots, bark, and leaves treated a wide range of mouth, eye and ear infections, including haemorrhoids and treatment of vaginal and uterine disorders, and indigestion and dysentery for more than 3000 years [3].

A recent review [4] has demonstrated the safety and efficacy of Berberine in managing metabolic disorders. Notably, the study showed that Berberine is well-tolerated with few reported adverse reactions. Further, Berberine has no negative effects on the participants’ diet.

While studies strongly support the safety and efficacy of Berberine, it is still crucial to consult a doctor before taking berberine supplements.

Berberine is a natural alkaloid used to synthesise and design new and powerful drugs [1].

Benefits of berberine

Studies examined Berberine’s effectiveness, safety, and efficacy in treating or managing different health conditions. The following are some of the studies in recent years.

Studies examined Berberine's effectiveness, safety, and efficacy in treating or managing different health conditions. The following are some of the studies in recent years.

Type 2 diabetes

Type 2 diabetes remains a significant health issue across the world since this can lead to complications such as diabetic foot, diabetic retinopathy, cardiovascular diseases, and stroke.

A pilot study [5] examined Berberine’s efficacy and safety in treating patients with type 2 diabetes. Although the study was small, it showed the following results:

·  The hypoglycaemic effect of Berberine is similar to metformin.

·  Patients taking Berberine demonstrated significant reductions in the following:

  • Fasting blood glucose
  • Haemoglobin A1c (HbA1c)
  • Postprandial blood glucose
  • Plasma triglycerides

Patients with poorly controlled type 2 diabetes participated in the pilot study.

  • The HbA1c decreased to 7.3% from 8.1%
  • Fasting plasma insulin decreased by 28.1%
  • Total cholesterol and LDL-C or low-density lipoprotein cholesterol also decreased.

The study showed that Berberine is not only a potent oral hypoglycaemic agent but can also be helpful in the metabolism of lipids in the body. 

Although the pilot study reported significant improvements in the participants’ blood glucose and insulin levels, considering potential side effects would help individuals decide whether to take Berberine.

A third (34.5%) of the participants reported transient gastrointestinal effects. These effects disappeared when participants stopped taking Berberine.

In animal studies, Berberine demonstrated several anti-inflammatory and antioxidant properties [6]. Results of these animal model studies indicated that:

  • Berberine has antioxidant properties, as demonstrated in changes in antioxidant enzyme levels and oxidative stress markers [7,8].
  • Antioxidants are compounds abundantly found in the human body that inhibit oxidation.
  • When oxidation occurs, cells produce free radicals that, in turn, damage other cell organisms. Intake of Berberine can reduce cell damage and promote better health outcomes.

These studies also increased an antioxidant enzyme, suggesting that Berberine could inhibit oxidative stress.

When an imbalance between antioxidants and free radicals occurs, this results in oxidative stress. The body cannot readily detoxify these radicals or repair damages caused by the free radicals.

  • Malondialdehyde (MDA), an oxidative stress marker, is reduced in the presence of Berberine.
  • Glutathione, which helps clear peroxides, is increased in animals treated with Berberine.


Published studies show that obesity is a significant risk factor for type 2 diabetes mellitus, stroke, hypertension, and cardiovascular diseases. Berberine has been shown in animal and human studies to treat obesity. Here are some examples of clinical trials or animal model studies supporting the effects of Berberine on obesity:

  • A meta-analysis [9] of 15 trials that enrolled 1,297 patients reported that triglycerides reduced significantly following the intake of Berberine.
  • The same meta-analysis reported a significant increase in high-density lipoprotein, which shows the efficacy of berberine treatment on high-density lipoprotein. High-density lipoprotein (HDL) increases the risk of stroke and heart disease.
  • In animal studies [10], Berberine reduces the ability of the liver to produce glucose by decreasing enzymes responsible for glucose production. o
  • Preclinical data [11] suggested that Berberine has a beneficial effect on regulating the gene responsible for cholesterol absorption.
Published studies show that obesity is a significant risk factor for type 2 diabetes mellitus, stroke, hypertension, and cardiovascular diseases.

Gut Flora and Gut Health

The gut flora (microorganisms present in the gut) are shown to regulate the health of individuals and may affect the development of diabetes mellitus, obesity, cardiovascular diseases, inflammation, and other diseases [12].

Berberine benefits the intestinal immune system and immune cells. It can reduce log-grade inflammation by inhibiting expressions of inflammatory cells such as interleukin and tumour necrosis factor.

Berberine reduces glucose levels and lipids by increasing the gut bacterial population, producing a compound that reduces lipids and glucose.


Colon cancer remains the fifth leading cause of cancer death and the fourth leading cause of cancer worldwide [13].

Berberine increases the population of bacteria that produce short-chain fatty acids in the gut microbiota. These bacteria are essential in improving the integrity of the gut, thereby reducing the risk of colon cancer.

Berberine inhibits the proliferation of cancer cells in the colon. Berberine is known to mediate the degradation of ß-catenin, a biomarker responsible for the development of colon cancer.


Dementia is commonly seen in older adults and is an umbrella term used to describe conditions that affect individuals’ cognition. As the disease progresses, individuals can experience moderate to severe cognitive impairment. Many patients can lose their memory, while others would require assistance from family members or caregivers in assisting them during mealtime, bathing, grocery shopping and other daily activities.

Preclinical studies suggest that Berberine has beneficial effects on dementia [14]. However, it is not yet known if individuals with more advanced stages of dementia exhibit similar findings. The preclinical studies only recruited patients with mild to moderate dementia. Despite this observation, current studies suggest the following:

Dementia is commonly seen in older adults and is an umbrella term used to describe conditions that affect individuals' cognition
  • Berberine affects neurotransmitters, influences anti-oxidative stress and directly affects multi-target pathways.
  • Since neurotransmitters in patients with dementia are affected, intake of Berberine might delay cognitive impairment by increasing the production of neurotransmitters.
  • Berberine can delay the development of dementia through multiple mechanisms [15]:
  • Enhancing cognition in the brain and preventing brain damage
  • Alleviating risk factors of dementia such as cardiovascular disease, metabolic dysfunction and kidney or liver diseases.

Diabetes-related cognitive impairment

A review and meta-analysis of several animal model studies [16] indicated that Berberine could improve memory and learning in diabetes-related cognitive impairment (DCI) animal models. However, animal model studies have small sample sizes. Hence, more studies are needed to verify the findings of the meta-analysis. Despite the small sample sizes of the reviewed studies, the results are promising and show the potential of Berberine in managing diabetes-related cognitive impairment.

Lipid metabolism plays a vital role in maintaining the function and structure of the neurons in the brain. Increased total cholesterol in the brain can significantly increase the risk of cognitive impairment [17].

Since the brain is rich in lipids, any increase in lipids can impact the brain’s memory, cognition or thinking, decision-making, problem-solving and communication. Increased lipid level in the brain is associated with an increased risk of cognitive impairment. Berberine can reduce the production of lipids, which can result in the protection of the brain and reduce the risk of cognitive impairment.

Antimicrobial property

The antimicrobial property of Berberine has been well-studied in the past. Berberine has antimicrobial activity against viruses, worms, parasites, fungi, and bacteria [18]. Berberine has significant antimicrobial activity against the following:

  • Cryptococcus species, Vibrio, Shigella, Proteus, Pseudomonas, Clostridium, Klebsiella, Salmonella, Streptococcus, Staphylococcus [19].
  • Enterotoxigenic Escherichia coli can cause diarrhoea [20].
  • Berberine inhibited the overgrowth of coliforms and staphylococci organisms without affecting indigenous bifidobacteria and lactobacilli [21].

Hypertension/high blood pressure

Hypertension is one of the significant risk factors for stroke and other diseases across the world. Some individuals might prefer alternative therapies instead of pharmacologic therapies due to the potential adverse effects of the latter.

A study [22] has found that when compared to a placebo, Berberine reduces blood pressure effectively. There was an 11.80 mmHg decrease in systolic blood pressure and an 11.10 mmHg decrease in diastolic blood pressure.

These findings are crucial since a ten mmHg reduction in blood pressure significantly improves health outcomes. The extent of reduction of blood pressure during intake of Berberine is promising since this rivals the majority of hypertension drugs in the market.

Many patients are often concerned with synthetic medications’ adverse side effects and prefer to receive natural products such as Berberine supplements. Hence, considering the preferences of the patients when seeking treatment for their hypertension will help increase patient satisfaction with their care.

To date, Berberine is a safe alternative to treating hypertension. While there may be safety concerns, no studies suggest that Berberine can damage the liver or kidneys during treatment.

Further, Berberine does not lead to adverse events when taken in appropriate dosages. An animal study [23] discovered that Berberine lowered blood pressure in diabetic rats through improved vasodilation.

Inflammation and anti-tumour activity

Berberine has anti-tumour activity [24]. These include:

  • Promoting tumour cell apoptosis (cell death)
  • Inhibiting the growth of tumour cells
  • Inducing the differentiation of tumour cells
  • Inhibiting the metastasis (spread) and expression of tumour cells

Berberine has anti-inflammatory effects, which include the following:

  • Reduction of proinflammatory cytokines. Cytokines are proteins that affect the immune system.
  • Down-regulating several proinflammatory genes

Side effects

Despite the effectiveness of Berberine in treating several diseases and potentially preventing or treating cancer, intake of this supplement may lead to side effects. Although most studies showed that Berberine was well-tolerated, there is evidence from an animal study [25] that Berberine might negatively affect the heart. Heart cells from neonatal rats were harvested and cultured to examine the effects of Berberine and other alkaloids in the plant Rhizoma coptis. Results revealed that:

  • Berberine resulted in cardiac arrest/heart attack and arrhythmia (irregular heartbeats) in the heart cells of neonatal rats.
  • The arrhythmia or cardiac arrest depended on the dose and duration of use of Berberine.

However, these results were observed in animal and preclinical studies but not in human studies. It is also unclear which dose could be considered cardiotoxic in humans. Since investigations are still needed to examine the potential heart effects of Berberine on humans, current safety data on Berberine may inform individuals on whether this supplement is safe. Current safety data showed that berberine supplements are generally well tolerated by patients with different diseases.

A study [26] that examined the lethal dose 50 (LD50) values of different laboratory animals:

  • Cats administered with Berberine at 100 mg/kg dosages orally vomited for 6-8 hours. However, when cats ingested the exact dosage for 8-10 days, this caused the death of all animals.
  • Cats administered with 50 to 100 mg/kg of berberine sulfate for ten days resulted in haemorrhagic inflammatory (bleeding) problems not only in the small intestine but also in the large intestine.
  • In dogs, poisoning with low amounts of Berberine resulted in vomiting, diarrhoea, nausea, increased saliva, muscular tremor, and in some cases, even paralysis.

Drug interactions

Before taking Berberine, it is imperative to examine whether this supplement can interact with the current medications. Here are some examples of drug interactions when Berberine is co-administered with certain medications:

Macrolides and berberine

Berberine can treat infections caused by microorganisms and has been used for thousands of years. However, it is unclear if taking Berberine with antimicrobials is safe. Recent evidence from the literature suggests that patients taking macrolides (antimicrobial) should be cautious when taking Berberine.

One study [27] found that intake of Berberine with antimicrobials such as clarithromycin increased the risk of drug toxicities, including adverse effects on the heart. Although the study reviewed preclinical studies, there are still no human studies examining the toxic effects of Berberine. Hence, consult your doctor when taking Berberine with macrolides or antimicrobials.

Berberine and drugs metabolised in the liver

Berberine inhibits cytochrome 450, enzymes necessary in the production of steroids, and cholesterol and detoxifying foreign chemicals [28]. The liver metabolises medications that are substrates of cytochrome 450. Hence, Berberine can affect the effectiveness of drugs that act as substrates to cytochrome 450. Since Berberine can change how the liver quickly metabolises these drugs, it can also change their side effects and effects.

Berberine and simvastatin and fenofibrate

When administered with lipid-lowering drugs, there were no drug-drug interactions between Berberine and these drugs [29]. Animal model studies showed that Berberine could affect the metabolism of midazolam. Midazolam is a short-acting hypnotic-sedative drug, and when taken together with Berberine, this might lead to increased sedation or sleepiness and breathing problems [30]. Individuals who take midazolam to make them sleep should not take Berberine supplements.

Berberine and metformin

Berberine also interacts with metformin [31]. Since Berberine has hypoglycaemic effects, co-administration with metformin can result in increased metformin concentrations in the plasma of the patients. Patients may experience dangerously low blood glucose levels or hypoglycaemia. When hypoglycemia happens, individuals who are taking Berberine and metformin will experience dizziness, anxiety, fast heartbeat, and confusion.

Berberine and losartan

Berberine can potentially interact with losartan, a medication used to treat high blood pressure. An animal study [32] showed that co-administration of Berberine from Gingko leaf tablets (GLT) with losartan resulted in an increased concentration of losartan in the blood. GLT can inhibit losartan metabolism, leading individuals to experience dangerously low blood pressure. Hence, individuals must consult a healthcare practitioner when planning to take Berberine with losartan.

Berberine and antiplatelet drugs

Thrombotic diseases, associated with stroke and cardiovascular diseases, are the leading causes of mortality and morbidity worldwide [33]. Inhibition of thrombus formation (blood clot) prevents cardiovascular or cerebrovascular diseases. Both anticoagulants and antiplatelet drugs currently treat blood clot formation. 

Natural products isolated from medicinal plants can have antiplatelet activity and good safety pharmacological profile. One of these natural products includes Berberine. A recent study [34] examined how Berberine can inhibit the aggregation of platelets.

The study showed that the primary metabolite of Berberine is metabolite berberrubine (M2). In vitro, both M2 and Berberine inhibited activation of ADP-induced integrin αIIbß3, suppressed the binding of fibrinogen to the platelets, and reduced the level of P-selection on the membranes of the platelets. This pathway demonstrates how both Berberine and M2 inhibit the formation of blood clots or thrombi.

In addition, the study’s results indicate that Berberine may also have anticoagulant activity. Berberine exerts its effects on thrombus formation through multiple pathways. Considering the excellent safety profile of Berberine when treating blood clots could help ease any patient concerns.

Taking Berberine: appropriate dosage

Taking an appropriate dosage of Berberine is essential to prevent adverse events or effects of the supplement. The proper dosage of Berberine would be dependent on the following:

Age: When taking medications or supplements, consider the individual’s age since very young populations, the older adults or elderly metabolise medications differently than, the younger adult population. The elderly may have compromised renal and liver function, while the young patients have underdeveloped metabolic processes. The liver and kidney are common sites of metabolism and excretion of drugs or supplements.

Gender: There are gender differences in the pharmacokinetics and pharmacology of specific medications and supplements. Considering how men and women metabolise, Berberine may provide information on the appropriate dosage for men and women. For example, there is evidence [35] that medications may stay longer in female bodies than males.

Diet: The diet of individuals planning to take Berberine should be considered as food, like medications, can interact with supplements. This food-supplement interaction can influence the amount of Berberine absorbed in the body.

Medications: Current medications can interact with Berberine. Hence, patients must be aware of the potential interactions of Berberine with other medicines. Currently, there are limited human studies on the interaction of Berberine with other medications. Some of these studies only include interactions of Berberine with anti-hypertensive drugs and drugs used to manage Type 2 diabetes mellitus.

Based on the studies conducted on Berberine, the following dosages were considered safe or well-tolerated:

A study reported that patients tolerated Berberine well, given at 300 mg three times a day in combination therapy. The same study showed that none of the patients suffered from severe gastrointestinal effects or adverse events when Berberine was used alone or in combination with another medication.

The same study reported that side effects such as flatulence, constipation, diarrhoea, and abdominal pain were only recorded in the first four weeks of berberine intake taken alone or in combination therapy. Notably, more than a third or 34.5%, of the patients experienced these side effects. The study also monitored the participants’ livers and kidneys and found no damage to these organs during the investigation and follow-up period.

Clinical data from a systematic review [36] showed that the usual intake of Berberine ranged from 600 mg to 2700 mg per day for individuals with hypertension. Importantly, none of the patients receiving this dosage range exhibited severe adverse effects when treated for hypertension with Berberine. In addition, Berberine appeared to have a renal protective function in patients with hypertension.

Generally, dosages ranging from 600 to 2700 mg/day for hypertensive patients and 1200 mg/day for those with type 2 diabetes were well tolerated, with no reported serious adverse events. Studies did not report any liver or renal damage.

Individuals must know that Berberine does not cause severe damage to the liver and kidneys. Most medicines used to treat hypertension and diabetes mellitus can lead to adverse events in high-risk populations such as old patients. Finding an alternative medication to current pharmacotherapy can help patients choose the most appropriate medicine for their health.


Photograph: Amtiko/ShutterStock
The information included in this article is for informational purposes only. The purpose of this webpage is to promote broad consumer understanding and knowledge of various health topics. It is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.