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What is Berberine and Should You Take It?

Yellow Oregon grape flowers (berberine).As the number of people living with cardiovascular disease, metabolic syndrome, diabetes, cancer, and other health scourges continues to skyrocket, so too does the demand for safe, effective treatments. People don’t just want to pop pills that mask symptoms and make it possible to “live with” a disease. And as much as we know that diet and lifestyle changes—being less sedentary, sleeping more, reducing stress—are needed to make real, sweeping public health impacts, implementation is a huge challenge. In the meantime, people need remedies that get to the root causes of their chronic health woes—ideally without a laundry list of possible side effects

Enter berberine, an alkaloid compound found in various plants. This is a textbook example of modern science confirming ancient wisdom. Chinese and ayurvedic medicine have valued berberine-containing plants like barberry, goldenseal, and tree turmeric for hundreds of years, using them to treat everything from gout to indigestion to hemorrhoids to skin infections to cancer. Now, research is uncovering exactly how berberine works—and it turns out to be quite a remarkable little substance. 

To date, there is pretty good evidence that berberine is useful for two applications in particular, and there are hints that it might serve other purposes as well. Let’s dive in.

Likely Benefits of Berberine

For Managing Blood Sugar, Insulin, and Type 2 Diabetes

In type 2 diabetics, berberine seems to lower fasting blood sugar and fasting insulin, decrease HbA1c (a three-month blood glucose average), and improve insulin sensitivity. 

Some studies even suggest that berberine can be as effective as the drugs that are currently considered standard of care, notably metformin. There is also an additive benefit: administering metformin with berberine seems to be more effective than metformin alone. However, as the authors of one review pointed out, studies comparing the two tend to be of less-than-ideal quality. Shockingly, drug companies aren’t exactly falling all over themselves to fund research to see if an herb can replace one of their lucrative products. 

Nevertheless, this is a big deal. Insulin resistance, hyperglycemia, and the resulting inflammation are the common threads connecting numerous chronic diseases. It’s possible, even likely, that berberine could be used as a primary or adjunct therapy for many diseases that run rampant today. Take PCOS as an example. Insulin resistance is a hallmark of PCOS, and metformin is often prescribed to manage symptoms and encourage ovulation. In one study, 150 women received berberine, metformin, or a placebo before undergoing IVF. Women in both treatment groups showed similar improvements in metabolic health (lower BMI, less insulin resistance, lower fasting glucose and insulin), but 18 of those who took berberine had a successful pregnancy, compared to 14 in the metformin group and 7 in the placebo group. 

For Blood Lipids

Studies in rodents and humans with high cholesterol and type 2 diabetes pretty consistently find that berberine lowers LDL-C and triglycerides, usually while boosting HDL. It may also lower ApoB. ApoB is a lipoprotein that many cardiovascular disease experts now recognize is a more accurate marker of atherosclerotic disease risk than LDL or total cholesterol. In animal studies, berberine has been shown to decrease the severity of the plaques that characterize atherosclerosis.

Setting aside questions about the value of lowering LDL across the board, berberine could be a viable option for people who don’t want to or are unable to take statins. For example, researchers conducted a study on type 2 diabetics with high cholesterol who were “statin intolerant,” meaning they experienced unsafe side effects when taking a statin. Participants were either still taking low-dose statins, a different a non-statin drug used to lower LDL, or nothing. Everyone took around 500 mg of berberine a day—either alone or alongside the drug they were already taking—combined with silymarin (aka milk thistle), which boosts berberine’s bioavailability. After one year, all three groups had lower LDL and total cholesterol, with nonsignificant changes in HDL and triglycerides. They also had lower fasting glucose and HbA1c. Of note, berberine alone was as effective as berberine plus one of the drugs. The berberine-alone group also experienced fewer side effects.

For folks who are already taking statins, adding berberine can increase the drugs’ lipid-lowering effects. Anecdotally, some folks use berberine to taper off of statins altogether. 

Other Possible Benefits of Berberine

As is often the case with more niche supplements, the available research on berberine tends to be somewhat limited in terms of volume and quality, especially when we’re talking about studies done in humans. Given what we currently know, the following applications are worth noting but far from definitive:

Cancer. A large number of in vitro (cell) studies have found that berberine has anti-cancer properties, but this has yet to be shown in actual cancer patients.  

Depression: Berberine supplementation may be useful in alleviating depression. However, so far this finding has only been demonstrated in rodents (yes, rats can be depressed).

Memory: Berberine may enhance memory, especially counteracting memory deficits associated with diabetes and inflammation in the brain. 

Non-alcoholic fatty liver disease: The progression of NAFLD is strongly related to insulin resistance, and some studies have already shown that berberine can improve glycemic control and insulin sensitivity in folks with NAFLD. More generally, berberine may support liver health. 

Microbiome: Researchers postulate that one of the ways berberine is able to exert its many effects is by improving gut health and function by modulating the microbiome. Berberine is also used to treat H. pylori infections.

Longevity: Berberine delays cellular senescence—the loss of the ability to replicate, which is one of the things that defines the aging process—in isolated cells, fruit flies, and mice. Direct anti-aging effects have yet to be demonstrated in humans, though, and one study in yeast actually found that it shortened lifespan.

How Does Berberine Do All This?

First and foremost, berberine activates AMPK. AMPK, you may remember, is an enzyme that is central to metabolic regulation at the cellular level. Its basic function is to ensure that cells have enough energy. AMPK has all sorts of health- and longevity-promoting effects, including activating insulin pathways, increasing glucose uptake, regulating blood lipids, inhibiting tumor growth, reducing inflammation and oxidative stress, and stimulating mitochondrial biogenesis and autophagy. Many of the behaviors we consider “healthy”—exercise, fasting, heat stress—are beneficial in large part because they affect AMPK signaling.

Aside from its impact on AMPK, researchers are discovering that berberine has an extensive array of actions throughout the body. Here are a handful of note:

  • Berberine metabolites increase the expression of LDL receptors in liver cells, which helps pull LDL from the bloodstream, accounting for some of the lipid lowering effects.
  • Promotes the expression of genes that decrease lipogenesis (fat formation) and increase mitochondrial uncoupling. The latter causes cells to burn more energy for heat, increasing metabolic rate and possibly promoting fat loss. Mitochondrial uncoupling is why brown fat is more metabolically active than white fat.
  • Inhibits PCSK9, a protein that binds with LDL receptors and prevents LDL from being removed from the bloodstream. PCSK9-inhibiting drugs are sometimes prescribed to patients with high LDL, especially folks with familial hypercholesterolemia.
  • GLP-1 is a peptide that plays an important role in insulin secretion. GLP-1 response is impaired in diabetics. Berberine apparently binds with an enzyme called DPP IV that normally breaks down GLP-1. Basically, berberine prevents DPP IV from doing its job, allowing more GLP-1 to stay in the system.
  • Can cross the blood brain barrier and influence the action of neurotransmitters like noradrenaline and serotonin.
  • Has antibacterial and antiprotozoal effects.

Finally, some of the metabolic benefits might be chalked up to weight loss as some, but not all, studies find that taking berberine leads to lower waist circumference and BMI. I tend to see these as concomitant effects—metabolic health and body composition improving in concert with one another, creating a positive feedback loop. 

Any Downsides?

There’s no such thing as a free lunch, even with “natural” remedies. Overall, berberine has a pretty good reputation for safety, and studies consistently note that berberine is better tolerated and leads to fewer adverse events than the drugs it might replace (or complement). However, you should not take berberine if you are pregnant or breastfeeding, as it’s unsafe for newborns and infants. Kids shouldn’t start it without medical supervision.

Since berberine affects liver metabolism, it can affect how certain medications are broken down and absorbed, so do your due diligence here if you’re on any prescription meds. 

Berberine – Yes or No?

Here’s where it stands for now: berberine looks quite promising for many aspects of metabolic health, but there’s still more research to be done, especially in humans. If you’re already taking metformin, a PCSK9 inhibitor, or a statin, or your doctor is pressuring you to do so, it is worth looking into. For blood sugar control, insulin sensitivity, lowering triglycerides, improving your TG:HDL ratio, your frontline strategies should always be diet and lifestyle, but there is certainly a case for exploring berberine in addition to these other strategies, especially when your best efforts still aren’t delivering the desired results. A dose of 1000-1500 mg per day is pretty standard. It’s not clear if this is optimal for every use case, but this is an active area of research, so stay tuned. 

Have you experimented with berberine? If so, why, and what were your results? Let me know in the comments.


About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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