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Since I saw my first patient in 1989, I’ve refined my approach to health and healing. Probably the biggest needle mover is my growing respect for plant medicine and its role in healing. My enthusiasm for berberine is in lockstep with my personal and professional experience prescribing herbs, but also as the evidence continues to mount about their relative safety and benefits. In this series, I will feature my favorite herbal therapies that you may want to consider, depending on your issues, and discuss with your integrative clinician. Our first herb is the herbal superstar known as berberine. When it comes to re-balancing your hormones, I believe in starting first with targeted lifestyle changes, such as upgrading the way you eat, move, and think. Fill the likely nutritional gaps. If that doesn’t work, try herbal therapies, and if you still are suffering, consider bioidentical hormone therapy. In my book, The Hormone Reset Diet, I recommend berberine as you finish the 21-day protocol, when you liberalize your eating. Berberine is insulin-sensitizing, anti-inflammatory, and anti-oxidant activity will help you stay out of harm’s way, if it’s used strategically and wisely.
What is berberine?Berberine is a naturally-occurring yellow plant extract with a long history of medicinal use in Ayurvedic and Chinese medicine. Found in the roots, rhizomes, stems, and bark of various plants including goldenseal (Hydrastis Canadensis), barberry (Berberis vulgaris), goldenthread (Coptis chinensis), Oregon grape (Berberis aquifolium), phellodendron (Phellodendron amurense, and not to be confused with the unrelated household plant, philodendron), and tree turmeric (Berberis aristata). Historically, berberine’s rich yellow color made it valuable as a natural dye.
What does berberine do?Berberine is a mixed nutraceutical, meaning that it has several effects that we can divide into the broad categories of lowering blood sugar, lipids, and body weight. ((Pang, B., et al. "Application of Berberine on Treating Type 2 Diabetes Mellitus." International Journal of Endocrinology (2015). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377488/)) Here are some of the proven applications of berberine: 1. Anti-diabetes. Berberine reduces blood glucose in people with diabetes by several mechanisms, including reducing production in the liver. Berberine lowers fasting glucose, fasting insulin, post-prandial glucose, and HbA1c by growing new insulin receptors ((Cicero, A. F., et al. "Antidiabetic properties of berberine: from cellular pharmacology to clinical effects." Hospital Practice (1995) 40, no. 2 (2012): 56-63; Zhang, Y., et al. "Treatment of type 2 diabetes and dyslipidemia with thenatural plant alkaloid berberine." The Journal of Clinical Endocrinology & Metabolism 93, no. 7 (2008): 2559-2565; Yin, J., et al. "Efficacy of berberine in patients with type 2 diabetes mellitus." Metabolism 57, no. 5 (2008): 712-717; Zhang, H., et al. "Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression." Metabolism 59, no. 2 (2010): 285-292; Wei, W., et al. "A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome." European Journal of Endocrinology 166, no. 1 (2012): 99-105; Dong, H., et al. "Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis." Evidence-Based Complementary and Alternative Medicine (2012); Pang, B., et al. "Application of Berberine on Treating Type 2 Diabetes Mellitus." International Journal of Endocrinology (2015).)) In fact, berberine boosts insulin receptor expression four-fold. That’s impressive for a plant! ((Zhang, H., et al. "Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression." Metabolism 59, no. 2 (2010): 285-292. 2. Anti-PCOS. Several studies show a benefit of berberine in resetting PCOS. Taking berberine 500 mg three times daily for 3 months can reduce fasting plasma glucose, markers of insulin resistance, total cholesterol, low-density lipoprotein cholesterol, triglycerides, testosterone levels, and waist-to-hip ratios. Furthermore, berberine can increase high-density lipoprotein cholesterol and sex hormone binding globulin in women compared with placebo. In addition, berberine is superior to metformin, a common prescription for PCOS, at improving lipid parameters, reducing waist-to-hip ratio, and increasing SHBG in PCOS patients. ((Wei, W., et al. "A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome." European Journal of Endocrinology 166, no. 1 (2012): 99-105.)) Additionally, in women with PCOS undergoing in vitro fertilization, berberine is superior to metformin at achieving more live births with fewer side effects. ((An, Y., et al. "The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment." Clinical Endocrinology 80, no. 3 (2014): 425-431.))
3. Anti-obesity. In a small pilot study, obese patients given 500 mg three times per day lost 5 pounds and dropped triglycerides 23 percent compared to pretreatment but the study lacks a control group or randomization. ((Hu, Y., et al. "Lipid-lowering effect of berberine in human subjects and rats." Phytomedicine 19, no. 10 (2012): 861-867.)
4. Anti-microbial. Berberine helps treat or prevent fungal, parasitic, and bacterial infections. On gut flora or microbiota, berberine has a favorable effect on gut flora or microbiota, which may be one
mechanism of its glucose-lowering and anti-inflammatory results. ((Han, J., et al. "Modulating gut microbiota as an anti-diabetic mechanism of berberine." Medical Science and Technology 17, no. 7 (2011): RA164-RA167.))
5. Anti-lipid. In a meta-analysis, 11 randomized trials of 847 participants—all of relatively low quality—showed that berberine significantly reduces total cholesterol, triglycerides, low-density lipoprotein (LDL, or “bad” cholesterol), and is associated with an impressive increase in high-density lipoprotein. ((Dong, H., et al. "The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials." Planta Med 79, no. 6 (2013): 437-446.))
Additionally, in women with PCOS undergoing in vitro fertilization, berberine is superior to metformin at achieving more live births with fewer side effects. ((Li-Weber, M. "Targeting apoptosis pathways in cancer by Chinese medicine." Cancer letters 332, no. 2 (2013): 304-312; Caliceti, C., et al. " Potential Benefits of Berberine in the Management of Perimenopausal Syndrome." Oxidative Medicine and Cellular Longevity 2015 (2015).))
Berberine is able to activate an enzyme called Adenosine Monophosphate-Activated Protein Kinase (AMPK) while inhibiting Protein-Tyrosine Phosphatase 1B (PTP1B). Activating AMPK is important to health, and appears to play a key role in reversing insulin resistance, promoting glycolysis, and reducing oxidative stress. One result of activating AMPK is suppression of hepatic glucose output,so that insulin and IGF-1 levels are lower. Both berberine and metformin, (as mentioned previously, the drug commonly used for diabetes and PCOS), activate AMPK. ((Yin, J., et al. "Berberine improves glucose metabolism through induction of glycolysis." American Journal of Physiology-Endocrinology and Metabolism 294, no. 1 (2008): E148-E156; Hwang, J., et al. "AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols." New Biotechnology 26, no. 1 (2009): 17-22.))
Here’s a cool fact: Owing to AMPK inhibition, berberine is normoglycemic, which means it reduces blood sugar only if elevated. Berberine has another action that metformin does not: it blocks proprotein convertase subtilisin kexin 9 (PCSK9), which plays a key role in metabolism of lipoprotein. Some people overexpress PCSK9 because of a genetic variant, and berberine helps lower their LDL particles by 10 to 32 percent. ((Cameron, J., et al. "Berberine decreases PCSK9 expression in HepG2 cells." Atherosclerosis 201, no. 2 (2008): 266-273; Li, H., et al. "Hepatocyte nuclear
factor 1α plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine." Journal of Biological Chemistry 284, no. 42 (2009): 28885-28895; Pisciotta, L., et al. "Nutraceutical pill containing berberine versus ezetimibe on plasma lipid pattern in hypercholesterolemic subjects and its additive effect in patients with familial hypercholesterolemia on stable cholesterol-lowering treatment." Lipids in Health and Disease 11 (2012): 123.))
What’s the best dose of berberine?
The best dose depends on your goals.
- For diabetes, 500 mg twice daily for three months is effective. Other studies show a benefit at three times daily.
- You can’t take berberine all at once because of poor intestinal uptake. As with most herbs, it’s better to take berberine in multiple doses throughout the day.
- The best dose is what works for you – there’s no such thing as one size fits all. Yet the dose used in many women in the clinical trials that show benefit to blood sugar, microbiome, hot flashes, and cholesterol panels is 500 mg three times per day.
- Please be sure to see the caution below about not taking berberine for longer than 8 weeks.
Can I take berberine in pregnancy?
According to the Natural Medicine database, berberine is rated LIKELY UNSAFE because it crosses the placenta and may harm the baby. In one study, newborn infants exposed to berberine had elevated bilirubin and kernicterus. ((Chan E. Displacement of bilirubin from albumin by berberine. Biology of the Neonate 63 (1993): 201-8.)) Furthermore, there are limited data that berberine may cause preterm
contractions. Similarly, berberine is considered LIKELY UNSAFE in nursing women as it can be transferred to your baby in breast milk.
How long can I take berberine?
It’s recommended that you take berberine for only 8 weeks at a time and then take a holiday owing to the effect of the herb on cytochromes P450 (CYPs) in the liver. ((Guo Y, et al. Repeated administration of berberine inhibits cytochromes P450 in humans. European Journal of Clinical Pharmacology 68, no. 2 (2012) : 213-7.))
When you see an effect of berberine on cytochromes P450, it may lead to drug-drug interactions, which should be reviewed with a knowledgeable clinician and/or pharmacist. Many supplements should be used in this way—pulsed in an 8-week cycle, and then off for some length of time such as two to four weeks, then restarted if symptoms aren’t resolved.
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