Berberine for Overall Health: Benefits, Side Effects and Dosage

Berberine, an alkaloid compound naturally found in plant roots and bark, offers exceptional blood-sugar and lipid regulating, antibiotic, cardioprotective, anti-inflammatory, anti-cancer, anti-obesity, and neuroprotective properties. Unlike pharmaceutical compounds offering these berberine is sold over-the-counter and at a fraction of the cost.

Berberine is an active compound found in Rhizoma coptidis, Coptis chinensis (Chinese goldthread), Berberis amurense Rupr., and Phellodendron amurense Rupr., Hydrastis Canadensis (goldenseal), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), and Berberis aristata (tree turmeric). ^[1][2][3]

Related: The Importance of Green Tea Extract for Overall Health

Berberine has been used in ancient Chinese and Indian medicine since 200 A.D. ^[1] it's commonly prescribed in a medical setting as an antibiotic for bacterial diarrhea, intestinal parasite infections, and certain eye infections. ^[3] it's also may be prescribed to manage diabetes, high blood sugar, or lipid levels. ^[4]

This article will discuss berberine recommended dose, use, benefits, and frequently asked questions.

Berberine Recommended Dosage & Use

Berberine hydrochloride is the most common form of berberine used in both supplements and over-the-counter medications. ^[2] You can also find and consume berberine in sulfate, citrate, and phosphate forms. ^[1]

Consume 900 to 2,000mg of berberine daily with or immediately after a meal, split into 3 or 4 doses to maximize the benefits and minimize the side effects. ^[5] A dose of 900 to 1,200mg is used to treat diarrhea and a dose of 500mg taken three times per day is used to manage diabetes in adults. ^[6][5]

To assess tolerance begin with the lowest recommended dose and adjust up or down depending on your body's response. While berberine is generally well tolerated in healthy individuals, consult with your physician or health care professional if you're using daily prescription medications affecting the brain, heart, liver, or blood.

A Deeper Look at Berberine Benefits

Berberine has glucose and lipid metabolism regulating properties that rival prescription medications. Metformin is a well-known prescription drug used in diabetics to control blood sugar. When 36 type-2 diabetic adults consumed either 500mg of berberine or metformin three times per day for 3 months, both groups experienced similar statistically significant decreases in hemoglobin A1c, fasting blood glucose, post-meal blood glucose, and triglyceride blood levels. ^[2]

These findings are extremely promising for those looking to use natural compounds to control blood sugar. A second study dosed 48 type-2 diabetic adults with berberine for three months and found it significantly lowered fasting blood glucose, post-meal blood glucose, hemoglobin A1c, total cholesterol, and LDL (bad) cholesterol. ^[2]

When 12 patients with metabolic syndrome consumed 500mg of berberine three per day for three months, 36% of patients no longer had metabolic syndrome while all lowered their systolic blood pressure, triglycerides, glucose levels, insulin levels, and insulinogenic index. ^[7] A fourth study of 58 type 2 diabetic patients dosing berberine at 1,000mg per day further the supported the beneficial impact discussed above as well as found berberine to be effective at increasing glucose disposal rate. ^[4] Berberine might just be the best natural compound for managing Type-2 Diabetes.

Berberine is also effective in treating non-alcoholic fatty liver disease (NAFLD), a condition arising from the extended excessive consumption of high-calorie foods. As a result, normal lipid metabolism is impaired or altered. ^[8] Combined with lifestyle intervention berberine reduced liver fat content by over 50% and is more effective than pioglitazone, a popular drug prescribed to Type 2 diabetics, in decreasing body weight and improving lipid profile. ^[9]

Berberine decreases liver fat by counteracting the impaired function of MTTP, a gene used to make microsomal triglyceride transfer protein. ^[8][10] A study of 144 adults consuming 500mg of berberine twice per day significantly decreased body weight, BMI, cholesterol, and triglycerides over placebo. ^[11] These findings further support the use of berberine in diabetic and obese individuals.

Berberine has a strong positive effect on the brain and may protect against Alzheimer's, cerebral ischemia, mental depression, schizophrenia and anxiety. ^[12] Daily berberine administration of 5mg/kg of bodyweight in mice for 15 days increased norepinephrine by 29%, serotonin by 19%, and dopamine by 52%. ^[13]

Norepinephrine, is the neurotransmitter responsible for the fight-or-flight while serotonin and dopamine are neurotransmitters commonly classified as "feel-good" hormones. When researchers doubled the dose of berberine to 10mg/kg serotonin and dopamine significantly increased but norepinephrine did not. ^[13] These findings offer promise for may greatly alleviate or reverse the effects of certain psychological disorders.

Berberine's anti-cancer effects are profound. Berberine inhibits and decreases activator protein 1 (AP-1) binding in cancer cells. ^[14] AP-1 plays a significant role in increasing the size and number of cancer cells in the body. Berberine also stops the cell cycle and promotes programmed cell death in cancerous liver cells. ^[15]

Berberine even appears to directly target cancerous cells up to 24 hours after post-consumption. ^[16] The compound also works synergistically with chemotherapeutic drugs to increase the body sensitivity during treatment. ^[17] While berberine may not be the cure for cancer it does appear to slow or stop cancer cell growth.

Berberine exhibits powerful anti-inflammatory and cardioprotective benefits. The compound prevents pro-inflammatory cytokines, proteins used for cell signaling. ^[18] Keeping inflammatory proteins low minimizes your risk for infection and many diseases.

When 14 healthy individuals consumed 1,200mg of berberine per day for 30 days they experienced a significant decline in circulating endothelial microparticles (EMPs). ^[19] Excessively high EMPs suggest a higher likelihood of vascular disease development as well as issues related to the inner lining of blood vessels.

Berberine accomplishes this by activating the 5' AMP-activated protein kinase (AMPK) signaling cascade. ^[20] A study of 79 patients with chronic congestive heart failure received 1,200mg to 2,000mg of berberine per day experienced greater left ventricular ejection fraction and exercise capacity as well as fewer and less intense ventricular premature complexes compared to placebo. ^[21]

Those with high inflammation and heart conditions may benefit greatly from berberine when used in conjunction with diet, exercise, and prescription medications.

Berberine FAQs

Does Berberine have any side effects?

Unlike other natural compounds with pharmaceutical-grade effects, Berberine and its sources have low toxicity and no reports of serious side effects. ^[22][23] One study on 48 type-2 diabetic adults found that 35% of the patients experienced momentary and short-lived gastrointestinal issues. ^[2]

Spread your berberine dose out in to 3 or 4 smaller doses throughout the day to minimize the likelihood of cramps or diarrhea. A second study reported that 5 of 58 type-2 diabetic patients experienced mild or moderate constipation. ^[4]

Short-term (<1 year) berberine consumption has no negative impact on kidney or liver function. ^[2] While data related to long-term (>1 year) berberine use is limited, experts don't advise against taking this compound long-term.

Is Berberine safe to stack with other supplements?

Berberine is safe to stack with staple supplements like fish oil, whey protein, multivitamins, creatine, BCAAs, and caffeine. Stack berberine with sodium caprate or p-glycoprotein inhibitors like milk thistle to increase absorption.5 Milk thistle also has strong liver-protective properties. ^[5]

Do NOT combine berberine with phosphodiesterase (PDE) inhibitors as their fat-burning properties will be reduced. Berberine has a high interaction-potential with certain medication.

Do NOT combine berberine with macrolide antibiotics like azithromycin, compounds interacting with enzymes CYP2D6, CYP2C9, and CYP3A4, organic anion transporter proteins. ^[5] Do NOT stack berberine with Type-2 Diabetes prescription drugs like metformin. A healthy individual regularly using moderate doses of berberine should experience numerous benefits with little to no side effects.

References

1) Yin, Jun, Hanjie Zhang, and Jianping Ye. "Traditional Chinese Medicine in Treatment of Metabolic Syndrome." Endocrine, metabolic & immune disorders drug targets 8.2 (2008): 99-111. Print.
2) Yin, Jun, Huili Xing, and Jianping Ye. "Efficacy of Berberine in Patients with Type 2 Diabetes." Metabolism: clinical and experimental 57.5 (2008): 712-717. PMC. Web.
3) Berberine. National Center for Biotechnology Information. Altern Med Rev, Apr. 2000. Web.
4) Zhang, Y. "Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine." National Center for Biotechnology Information. J Clin Endocrinol Metab, July 2008. Web.
5) Frank, Kurtis, et al. "Berberine." Examine.com. N.p., n.d. Web.
6) Yan, Fang et al. "Berberine Promotes Recovery of Colitis and Inhibits Inflammatory Responses in Colonic Macrophages and Epithelial Cells in DSS-Treated Mice." American Journal of Physiology - Gastrointestinal and Liver Physiology 302.5 (2012): G504-G514. PMC. Web.
7) Pérez-Rubio, K. G., et al. "Effect of Berberine Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion." National Center for Biotechnology Information. Metab Syndr Relat Disord, Oct. 2013. Web.
8) Chang, X., et al. "Berberine Reduces Methylation of the MTTP Promoter and Alleviates Fatty Liver Induced by a High-fat Diet in Rats." National Center for Biotechnology Information. J Lipid Res, Sept. 2010. Web.
9) Yan, H. M., et al. "Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease." National Center for Biotechnology Information. PLoS One, Aug. 2015. Web.
10) MTTP - Microsomal Triglyceride Transfer Protein. Genetics Home Reference. U.S. National Library of Medicine, 8 Feb. 2016. Web.
11) Derosa, G., et al. "Effects of Berberine on Lipid Profile in Subjects with Low Cardiovascular Risk." National Center for Biotechnology Information. Expert Opin Biol Ther, Apr. 2013. Web.
12) Kulkarni, S. K., and A. Dhir. "Berberine: a Plant Alkaloid with Therapeutic Potential for Central Nervous System Disorders." National Center for Biotechnology Information. Phytother Res, Mar. 2010. Web.
13) Kulkarni, S. K., and A. Dhir. "On the Mechanism of Antidepressant-like Action of Berberine Chloride." National Center for Biotechnology Information. Eur J Pharmacol, June 2008. Web.
14) Kuo, C. L., C. W. Ciu, and T. Y. Liu. "The Anti-inflammatory Potential of Berberine in Vitro and in Vivo." National Center for Biotechnology Information. Cancer Lett, 20 Jan. 2004. Web.
15) Auyeung, K. K., and J. K. Ko. "Coptis Chinensis Inhibits Hepatocellular Carcinoma Cell Growth Through Nonsteroidal Anti-inflammatory Drug-activated Gene Activation." National Center for Biotechnology Information. Int J Mol Med, Oct. 2009. Web.
16) Pinto-Garcia, L., et al. "Berberine Inhibits Cell Growth and Mediates Caspase-independent Cell Death in Human Pancreatic Cancer Cells." National Center for Biotechnology Information. Planta Med, Aug. 2010. Web.
17) Tan, Wen et al. "Berberine Hydrochloride: Anticancer Activity and Nanoparticulate Delivery System." International Journal of Nanomedicine 6 (2011): 1773-1777. PMC. Web.
18) Li, N., et al. "Berberine Attenuates Pro-inflammatory Cytokine-induced Tight Junction Disruption in an in Vitro Model of Intestinal Epithelial Cells." National Center for Biotechnology Information. Eur J Pharm Sci, Apr. 2010. Web.
19) Wang, J. M. "Berberine-induced Decline in Circulating CD31+/CD42- Microparticles is Associated with Improvement of Endothelial Function in Humans." National Center for Biotechnology Information. Eur J Pharmacol, July 2009. Web.
20) Wang, Y., et al. "Berberine Prevents Hyperglycemia-induced Endothelial Injury and Enhances Vasodilatation Via Adenosine Monophosphate-activated Protein Kinase and En..." National Center for Biotechnology Information. Cardiovasc Res, June 2009. Web.
21) Zeng, X. H. "Efficacy and Safety of Berberine for Congestive Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy." National Center for Biotechnology Information. Am J Cardiol, n.d. Web.
22) Tang, J., et al. "Berberine and Coptidis Rhizoma As Novel Antineoplastic Agents: a Review of Traditional Use and Biomedical Investigations." National Center for Biotechnology Information. J Ethnopharmacol, Oct. 2009. Web.
23) Dong, Hui et al. "Berberine in the Treatment of Type 2 Diabetes Mellitus: A Systemic Review and Meta-Analysis." Evidence-based Complementary and Alternative Medicine: eCAM 2012 (2012): 591654. PMC. Web.