Berberine - Health Benefits, Dosage and Side Effects

Berberine is a plant alkaloid that can be formulated as a dietary supplement in two formulations, berberine hydrochloride or berberine sulfate. Supplementation with berberine helps with weight loss and lowering high blood pressure, levels of "bad" cholesterol, and blood sugar. 

Keep reading and find out what are the health benefits of berberine, the right dosage, and possible side effects of supplementation. 

Berberine - what is it?

Berberine is an isoquinoline alkaloid compound isolated from the berberine plant and used in traditional Chinese medicine. Early writings suggest that different parts of the berberine plant were used even in 650 BC. 

Berberine can be found in plants of several plant families, such as the following:

• Annonaceae,
• Berberidaceae,
• Menispermaceae,
• Papaveraceae,
• Ranunculaceae
• Rutaceae.

However, the highest amount of berberine can be found in the plants of the Berberis genus, especially in the bark, stem, and roots. These plants are geographically very widespread and used in Chinese, Indian, South African, and other traditional medicine practices, with a long list of uses, ranging from eye infections to stomach issues. 

Berberine is usually extracted from plant preparations with conventional organic-solvent methods at high temperatures. However, newer extraction methods, such as ultrasound-assisted solvent extraction and supercritical fluid extractions can be used with the same efficiency, while being better for the environment (1). 

Best berberine supplement

Once extracted, berberine is prepared as a supplement into two main formulations: berberine HCl (or berberine hydrochloride) and berberine sulfate/chloride/bromide.

The hydrochloride salt of berberine is less soluble in water, while sulfate, chloride, or bromide salts are more water soluble and usually more bitter. In that case, the supplement is often formed with the addition of sugar (1). All formulations are fine, but the berberine chloride salt is the one most often administered in clinical trials.

Berberine - benefits

According to scientific research on animal models, berberine acts on the AMP-activated protein kinase (AMPK) (2). AMPK is a protein responsible for regulating energy levels and activating different metabolic pathways in the cell.

Berberine helps with weight loss

Berberine has a lot of potential to be a weight-loss supplement.

How long does it take for berberine to work for weight loss? One study has shown that it took 3 weeks for obese participants to lose around 2.5 kilograms of body mass and 3.6% of body fat (3). They took 1.5 g of berberine daily. 

This was confirmed by some other studies as well, where berberine was given as a supplement, and participants lost a significant amount of body mass and fat, without changing any other condition (e.g. diet or exercise) (4). 

However, there is no data on berberine's effect on aiding weight loss in healthy individuals or a consensus on how long it should be given to obese ones. More clinical trials are needed. 

Berberine lowers blood sugar levels

Berberine is effective in lowering blood sugar levels in individuals with type II diabetes, which was shown in multiple studies. Berberine (usually 1-1.5 g) had a glucose-lowering effect and could lower diabetic markers and fasting sugar levels by 20% (5). 

So far, data shows that berberine could be as potent as some approved anti-diabetic drugs (e.g. metformin). However, there is little evidence on if and how berberine helps healthy individuals. 

Berberine lowers total cholesterol levels and high blood pressure

One of the major advantages of berberine is its proven effect in the fight against heart diseases, mainly by lowering total blood cholesterol.

It means that berberine does not only lower the levels of sugars but also decreases "bad" LDL cholesterol and total blood triglycerides. This was proven in several human studies as well (for review, see reference 6). 

From studies done to investigate the molecular mechanism of berberine, it became clear that berberine could act on the protein named "proprotein convertase subtilisin/kexin type 9", which is a major regulator of LDL cholesterol metabolism (7). 

Berberine could help with the polycystic ovarian syndrome (PCOS)

Even though it's thought that berberine can help with PCOS and improve fertility, there is not enough evidence on that front, at least not until now. 

One study did show that berberine improves menstrual patterns in PCOS infertile women up to the point of regaining regular menstrual patterns and ovulation (8). Participants took 400 mg of berberine 3 times a day for four months. Another study showed berberine might be useful in IVF treatments and improving fertility (9). Participants took berberine for three months. 

However, when berberine's effect is compared to other conventional fertility or PCOS treatments (e.g. letrozole), berberine is much less effective (10). 

Berberine - dosage per day

Even though there is no clear consensus on the right daily dosage of berberine, most studies have used the daily dose of 1500 milligrams, or 1.5 grams. This would usually be divided into thirds, meaning one would take 500 milligrams of berberine 3 times a day. 

Read more about the appropriate dosage and form of berberine in our articles: 

• Finding the Right Dose: How Much Berberine Do I Need?
• Taking Berberine: Best Times, Forms, and Other Considerations

Berberine supplement - side effects

Berberine has been used for thousands of years and has a clean record of safety. Daily doses of about 1.5 grams did not cause major side effects. Minor reported side effects were:

• diarrhea,
• constipation,
• gas and bloating,
• nausea (11). 

Is berberine bad for kidneys? No, on the contrary, there has been some evidence that berberine protects the liver and kidneys against toxicity caused by ferrous sulfate, and has an overall protective role on those organs (12). 

However, berberine can react to some medicines (13), such as:

• cyclosporine,
• dextromethorphan,
• losartan,
• medicines for diabetes,
• medicines for high blood pressure,
• medicines for the liver,
• metformin,
• midazolam,
• pentobarbital,
• tacrolimus,
• sedative medications. 

In addition, there is no evidence that berberine is safe when pregnant or breastfeeding, so it's better not to take it in those cases. Make sure to discuss taking berberine or any new dietary supplement with your health care provider, especially if you take any medication. Start with lower doses and gradually increase your intake if necessary. 

Literature:

1. Juan Manuel Germán-Acacio, David Eduardo Meza-Sánchez, David Morales-Morales, Chapter 3 - Therapeutically relevant natural products as AMPK activators in the treatment of diabetes, Editor(s): Atta-ur-Rahman,
   Studies in Natural Products Chemistry, Elsevier, Volume 66, 2020, Pages 57-90, ISSN 1572-5995, ISBN 9780128179079, https://doi.org/10.1016/B978-0-12-817907-9.00003-9.
2. Neag MA, Mocan A, Echeverría J, Pop RM, Bocsan CI, Crişan G, Buzoianu AD. Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front Pharmacol. 2018 Aug 21;9:557. doi: 10.3389/fphar.2018.00557.
3. Hu Y, Ehli EA, Kittelsrud J, Ronan PJ, Munger K, Downey T, Bohlen K, Callahan L, Munson V, Jahnke M, Marshall LL, Nelson K, Huizenga P, Hansen R, Soundy TJ, Davies GE. Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine. 2012 Jul 15;19(10):861-7. doi: 10.1016/j.phymed.2012.05.009.
4. Asbaghi O, Ghanbari N, Shekari M, Reiner Ž, Amirani E, Hallajzadeh J, Mirsafaei L, Asemi Z. The effect of berberine supplementation on obesity parameters, inflammation and liver function enzymes: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN. 2020 Aug;38:43-49. doi: 10.1016/j.clnesp.2020.04.010.
5. Xie W, Su F, Wang G, Peng Z, Xu Y, Zhang Y, Xu N, Hou K, Hu Z, Chen Y, Chen R. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022 Nov 16;13:1015045. doi: 10.3389/fphar.2022.1015045.
6. Ju J, Li J, Lin Q, Xu H. Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials. Phytomedicine. 2018 Nov 15;50:25-34. doi: 10.1016/j.phymed.2018.09.212.
7. Ataei S, Kesharwani P, Sahebkar A. Berberine: Ins and outs of a nature-made PCSK9 inhibitor. EXCLI J. 2022 Aug 17;21:1099-1110. doi: 10.17179/excli2022-5234.
8. Li L, Li C, Pan P, Chen X, Wu X, Ng EH, Yang D. A Single Arm Pilot Study of Effects of Berberine on the Menstrual Pattern, Ovulation Rate, Hormonal and Metabolic Profiles in Anovulatory Chinese Women with Polycystic Ovary Syndrome. PLoS One. 2015 Dec 8;10(12):e0144072. doi: 10.1371/journal.pone.0144072.
9. An Y, Sun Z, Zhang Y, Liu B, Guan Y, Lu M. The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clin Endocrinol (Oxf). 2014 Mar;80(3):425-31. doi: 10.1111/cen.12294.
10. Ionescu OM, Frincu F, Mehedintu A, Plotogea M, Cirstoiu M, Petca A, Varlas V, Mehedintu C. Berberine-A Promising Therapeutic Approach to Polycystic Ovary Syndrome in Infertile/Pregnant Women. Life (Basel). 2023 Jan 2;13(1):125. doi: 10.3390/life13010125.
11. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Berberine. [Updated 2020 Oct 6]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564659/
12. Gholampour F, Keikha S. Berberine protects the liver and kidney against functional disorders and histological damages induced by ferrous sulfate. Iran J Basic Med Sci. 2018 May;21(5):476-482. doi: 10.22038/IJBMS.2018.25199.6241.
13. Berberine. Medline Plus. National Library of Medicine.