Berberine: Its Potential for a Metabolic Makeover

By Ashley Reaver, MS, RD, CSSD May 22, 2015

Berberine_InsideTracker

I have spent the last few months combing through massive amounts of research to find supplement recommendations that improve the biomarkers monitored by InsideTracker. Our recommendations come from peer-reviewed, scientific studies that produce significant results. Some of my findings were expected, like zinc increases zinc—not very exciting, but others were incredibly interesting. I found dozens of these recommendations, which are provided to InsideTracker users only when they are right for optimizing their unique biomarker profile. One of these was garlic, which I wrote about in a post last month. Simple, ordinary garlic actually has some pretty legitimate health benefits. Another one was something that no one at InsideTracker had ever heard of before: berberine.

Berberine is an alkaloid compound, meaning that it contains mainly basic nitrogen compounds. (1) Plants containing alkaloids have been used as medicinal, recreational and lethal drugs for centuries. Some common alkaloid compounds you may be familiar with are caffeine, codeine, morphine, and nicotine. Berberine is usually found in the roots, stems and bark of plants of the Berberis family, among others.

Long used as an antibiotic in traditional medicine, berberine’s effect on modern day chronic disease is gaining momentum. A 2012 meta-analysis including over 1000 type 2 diabetics found that berberine was as effective as conventional oral hypoglycemic treatment for reducing fasting blood glucose.(2) Also, when added to oral hypoglycemics, berberine further reduced fasting blood glucose and hemoglobin A1C, a longer term measure of glucose metabolism. One of the studies included in the meta-analysis found that supplementation with 1.0g of berberine daily for 3 months significantly reduced mean fasting blood glucose by 21% from 126 mg/dL to 100 mg/dL. (3)

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One theory is that berberine activates an enzyme involved in many aspects of energy metabolism called AMPK.(4) AMPK increases insulin sensitivity by stimulating glucose uptake by muscles interfering with insulin secretion. Decreased insulin sensitivity is a hallmark of type 2 diabetes. It results in decreased glucose removal from circulation and, therefore, high fasting blood glucose. AMPK also improves cardiovascular health by encouraging healthy lining of the blood vessels, (5) reducing pro-inflammatory agents, (6) and activating beneficial pathways in lipid metabolism. (7)

In the same meta-analysis, berberine decreased total cholesterol, LDL cholesterol and triglycerides, and increased HDL cholesterol for diabetics. (2) Another study found similar effects in obese individuals without diabetes. In this study, obese men were given 1.5g berberine for twelve weeks, taken in three 500mg doses throughout the day. Total cholesterol decreased by 12% and triglycerides fell by 23%. (8) The most prescribed conventional medications for lowering cholesterol are statins. Statins work by inhibiting cholesterol synthesis via HMG-CoA reductase, an essential enzyme in the formation of cholesterol from fatty acids in the liver. Statins may also have some negative side effects such as high liver function labs, increased risk of diabetes, and muscle pain. (9)

Some individuals should not take statins, such as those with liver disease. Berberine may be an alternative treatment for them and for anyone else avoiding statin medication because it decreases cholesterol through a completely different pathway. It increases the amount of LDL, “bad cholesterol”, receptors on the liver. (7) This allows more LDL to be taken out of circulation. Similar to the effects of garlic, HDL cholesterol increases as a result because it remains in circulation longer with less LDL to remove in the body.

Rounding out berberine’s “jab-jab-cross” on metabolic syndrome is it’s potential to spur weight loss. One of the studies in humans found that treatment with berberine also resulted in mild weight loss, about 5 pounds, for those treated compared to placebo. (8) It is thought to interfere with adipocyte differentiation, (10) which is essentially the development of new fat storage cells. Humans can create new fat cells through adulthood.(11) Berberine’s effect on the outcome of new fat cells not only has implications for weight gain, but for hormonal and metabolic processes, too.

In addition to these conditions, there are currently 14 clinical trials being conducted on berberine’s potential effects on conditions ranging from colon cancer and ulcerative colitis to polycystic ovary syndrome. (12) Its potential as an anticancer agent appears promising. It has anti-proliferative effects that block not only tumor growth, but also its ability to spread to other cells when tested on cancerous cells in vitro. (13)

As previously mentioned, berberine has historically been used as an antibiotic and to treat a range of ailments from diarrhea to eye infections, and possibly even MRSA. (14) Berberine accumulates in bacterial cells and damages its DNA, stopping cell growth and ultimately leading to its death. Perhaps, in this time of growing concern over antibiotic resistance, berberine may be the next wave of defense for infections, as well.

The clinical trials are continuing to gather information about safety and effectiveness as well as dosage recommendations of berberine as a prescription drug. (12) Currently, berberine is available only as a supplement. Supplements are not regulated by the Food and Drug Administration, which means their manufacturing procedures are not monitored. When choosing a berberine supplement, look for companies that have Current Good Manufacturing Processes (CGMP) and are certified by the United States Pharmacopeia (USP), if possible. Pregnant or lactating women and women that may become pregnant should not use berberine. Research has not been conducted on its safety for these populations.

So, is berberine the knock out punch for metabolic syndrome when diet and exercise aren’t enough? For those with less than optimal metabolism biomarker levels, perhaps berberine will provide the shot of adrenaline needed to optimize them. InsideTracker scours scientific research to find nutrition, exercise and supplement interventions that directly impact your biomarkers. Berberine is just one of the many research-backed recommendations that we will specifically tailor to your individual biochemistry. Could berberine work for you?

 

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References:

1.Huang ZJ, Zeng Y, Lan P, Sun PH, Chen WM. Advances in structural modifications and biological activities of berberine: an active compound in traditional Chinese medicine. Mini-Reviews in Medicinal Chemistry. 2011 Nov;11(13):1122-9.

2.Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evidence Based Complementary and Alternative Medicine. 2012:591654.

3.Zhang Y, Li X, Lui W, Yang J, Zhu N, Huo L, Wang M, Hong J, Wu P, Guoguang R, Ning G. Treatment of Type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. Journal of Clincal Endocrinology and Metabolism. 2008 Jul;93(7):2559-65.

4.Winder WW and Hardie DG. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. American Journal of Physiology. 1999 Jul; 277(1): E1-10.

5.Wang Y, Huang Y, Lam KS, Li Y, Wong WT, Ye H et al. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovascular Research. June 2009;82 (3): 484–92

6.Jeong HW1, Hsu KC, Lee JW, Ham M, Huh JY, Shin HJ, Kim WS, Kim JB. Berberine suppresses proinflammatory responses through AMPK activation in macrophages. American Journal of Physiology Endocrinology and Metabolism. 2009 Apr;296(4):E955-64.

7.Abidi P, Zhou Y, Jiang JD, Liu J. Extracellular signal-regulated kinase-dependent stabilization of hepatic low-density lipoprotein receptor mRNA by herbal medicine berberine. Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (10): 2170–6.

8.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.

9.Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circulation: Cardiovascular Quality and Outcomes. 2013 Jul;6(4):390-9.

10.Hu Y and Davies GE. Berberine increases expression of GATA-2 and GATA-3 during inhibition of adipocyte differentiation. Phytomedicine. 2009(16): 864-873.

11.Gregoire FM1, Smas CM, Sul HS. Understanding adipocyte differentiation. Physiological Reviews. 1998 Jul;78(3):783-809.

12.www.clinicaltrials.gov

13.Tillhon M, Guaman Ortiz LM, ombardi P, Scovassi Al. Berberine: new perspectives for old remedies. Biochemical Pharmacology. 2012 Nov 15;84(10):1260-7.

14.Yu HH, Kim KJ, Cha JD, Kim HK, Lee YE, Choi NY et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. Journal of Medicinal Food 2005; 8 (4): 454–61.

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