Evidence: Very High Possible Benefits: High Safety: Reasonable
TABLE OF CONTENTS
What is berberine?
Berberine is a compound that can be extracted from many plants, such as the Oregon grape, goldenseal, Coptis, berberry, and tree turmeric. It is comparable in the mechanisms of action and effects on the body to a medication called metformin. This article is about the main benefits of berberine, its potential side effects, the best time to take it, and more.
Possible benefits
All of the potential benefits mentioned below are dose-dependent. As with other adaptogenic herbs, there is a sweet-spot dose that allows you to get most of the benefits without causing meaningful side effects or tolerance buildup in the body. We will discuss the best dosing protocol later in this article.
Major benefits
Reduced blood glucose – Berberine is one of the if not the most effective supplements for lowering blood glucose levels. It is comparable in potency to hypoglycemic drugs Metformin or Glibenclamide. Berberine (at doses of 1000-1500 mg daily) is also the most effective supplement we know of for reducing HbA1c, a biomarker of glucose metabolism. The supplement can also improve insulin sensitivity and reduce fasting insulin but only by a small amount.
Increased lifespan – Berberine has the potential to increase lifespan due to inducing AMPK, inhibiting telomerase, and other important mechanisms. While much more evidence is needed, the research so far seems promising in this regard.
Minor benefits
Improved cholesterol levels – While not very potent, berberine can slightly increase HDL and lower LDL cholesterol levels. Berberine may be synergistic in this regard with statins as it reduces cholesterol levels through PCSK9 inhibition.
Improved exercise capacity in people with heart problems – This benefit is mild and doesn’t apply to healthy individuals. In healthy people, high doses of berberine may actually worsen exercise performance in the long term.
Reduced blood pressure – One study showed a slight decrease in systolic blood pressure in people with metabolic syndrome taking 1.5 grams of berberine for 3 months.
Anti-depressive effects – The supplement may increase dopamine and serotonin levels in the brain. Low doses have been shown to reduce symptoms of depression in mice. Interestingly, high doses do not seem to have this effect. When converted into human doses, 1.6 mg/kg may have anti-depressive effects but doses of 8 mg/kg likely don’t. However, human studies are needed to confirm or disprove this benefit.
Possible side effects
The side effects below are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.
Hypoglycemia – Because berberine has a huge effect on blood sugar levels, high doses can cause blood sugar to drop too low.
Skeletal muscle atrophy – This side effect was shown in mice studies but it likely applies to humans as well, though to a small extent.
Allergic reaction – Some people are allergic to this compound or to herbs berberine is extracted from and may experience an allergic reaction after they start taking it.
Nausea – This side effect is most common when people take the supplement on an empty stomach.
Diarrhea – You can usually prevent diarrhea or stomach discomfort by taking this supplement with a meal.
Toxicity – As an adaptogen, berberine acts as a mild stressor on the body. That is usually a great thing as it allows your body to adapt to specific forms of stress and become more resilient. However, stressing the body too much can be counter-productive and cause multiple side effects, including toxicity. While acute toxicity is extremely rare, taking very high amounts of this compound could lead to chronic toxicity and cause health problems over time. To prevent chronic toxicity or the buildup of tolerance, staying below 1500 mg in a day is best unless you have a great reason to take more.
Contamination – If growing or storing conditions are not adequately controlled, herbs containing berberine can be contaminated with bacteria, molds, and other potentially harmful microorganisms. Some growers also use pesticides and herbicides that can be unsafe. Another issue is that herbal extracts and supplements can get contaminated with other supplements and chemicals during the manufacturing process. Choose the brand you get herbs and herbal supplements from wisely. It is often best to use websites like Amazon, where thousands of users have reviewed and rated the products. You are less likely to buy something of lower quality there.
Who should not take berberine?
You should probably avoid taking berberine if you:
are allergic to this compound or to herbs that berberine is extracted from
exercise a lot
have healthy blood glucose levels
experience a severe adverse reaction after taking the supplement (though a mild adverse reaction is usually a great thing as it is a sign that the supplement is working and causing a hormetic response that allows the body to adapt and become more resilient)
are pregnant or breastfeeding (berberine and plants containing berberine should not be used in this regard as they may put some unnecessary risk to the child)
Who will benefit the most?
You should consider taking the supplement if you:
have high blood glucose levels
have a high budget for supplements and are willing to experiment with a variety of them (assuming you don’t fall into any of the categories that should avoid this supplement, berberine appears safe and is unlikely to do more harm than good for most people)
How much berberine should you take?
Because berberine can be considered an adaptogen, it acts as a mild hormetic stressor on the body, which allows your body to adapt and become more resilient to certain kinds of stressors in the long term.
A higher dose does not necessarily lead to more pronounced benefits. Instead, there appears to be an inverted U-shaped dose-response pattern. In other words, you want to find a sweet-spot dose that allows you to get the benefits of berberine without putting too much pressure on the body or quickly causing the body to develop tolerance to the compound.
If you purchase an extract standardized for berberine, the sweet spot dose of berberine is about 1000-1500 mg, spread into at least 2-3 doses.
The higher end of this range usually provides slightly more benefits in the short term. If you plan to take this herb for a longer time (multiple months or years), the lower end is probably a better way to go since you would develop tolerance faster if you were to take higher doses.
While higher doses are generally safe, taking more than the sweet-spot dose daily would be counter-productive as your body would quickly develop tolerance.
Additionally, very high doses can put too much pressure on your system and cause health problems if you take the supplement for a prolonged period.
While this herb could theoretically cause acute toxicity, you’d need to take an extremely high dose that would be way beyond what even the most potent supplements contain.
Like most other adaptogens, it is best to cycle berberine and take about two days off weekly to reset your tolerance. That will allow you to keep getting the benefits in the long term.
Keep in mind that the effects of this herb are cumulative. Therefore, you must take it for at least 2-4 weeks to notice most of the benefits. But again, cycling the herb and not taking it at least twice a week is necessary to prevent tolerance in the long term.
Best time to take berberine
It is best to take this supplement with food or right after you finish eating. This will help reduce the blood sugar spike following a meal.
You also want to spread the daily dose into at least 2-3 smaller doses and take each of them with a different meal. If you practice OMAD (one meal a day), you may not need to take berberine more than once.
Whether you take this supplement in the morning or the evening typically does not make much difference. Both options are fine so just focus on taking it with a meal.
Interactions
Metformin Berberine and metformin have almost identical mechanisms of action and effects on the body. When taken together, they can be either additive or synergistic.
Statins Berberine may be synergistic with statins as it reduces cholesterol levels through PCSK9 inhibition.
Sodium caprate Sodium caprate may significantly increase the absorption of berberine.
Macrolide antibiotics Berberine should never be used with macrolide antibiotics, such as azithromycin.
Cyclosporine Berberine might decrease how quickly the body breaks down cyclosporine, which can increase the effects of cyclosporine.
Where to buy berberine?
In most countries, Amazon is the best option for ordering berberine and other herbal extracts. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.
Some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.
FAQ
As with most other adaptogenic supplements, it is best to cycle berberine and take a break from it for about two days per week to reset your tolerance back to baseline. That will keep your body sensitive to the compound and allow you to keep getting the benefits in the long term.
All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, you may need a highly accurate scale to dose them correctly (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes time which can add up over months or years. The disadvantage of capsules is that they are often made of bovine gelatine, which rarely comes from ethical sources.
Yes, you can. This compound should not impact your sleep in any negative way. Whether you take it in the morning or the evening typically doesn’t make much difference. Just make sure to take this supplement with or right after a meal.
This supplement should not become harmful once it exceeds the expiration date, but it can lose potency over time. Keep this herbal supplement in a cold, dark, and dry place and it should remain just as potent for many months or even years.
As an adaptogen, berberine acts as a mild stressor on the body. That is usually a great thing as it allows your body to adapt to specific forms of stress and become more resilient. However, putting too much pressure on the body can be counter-productive and cause multiple side effects, including toxicity. While acute toxicity is extremely rare, taking very high amounts of this compound could lead to chronic toxicity and cause health problems over time. High doses can also make you develop tolerance much faster than lower doses so they may be less effective in the long term.
While you could safely take higher doses, there is usually no point in taking more than 1500 mg of berberine daily. This amount should give you most of the benefits without meaningful side effects. Paradoxically, taking a higher dose would likely lead to fewer benefits as the body would quickly become accustomed to the supplement.
The half-life of berberine in the body depends on multiple factors but generally, it has a half-life of a few hours.
The effects of this supplement are cumulative. Therefore, you must take it for at least 2-4 weeks to notice most of the benefits. But again, cycling the supplement and not taking it at least twice a week is necessary to prevent tolerance in the long term.
Yes, berberine is vegan-friendly. If you buy this herbal extract in a capsulated form, beware that the capsules often contain animal-based gelatin. Instead, find a brand that puts its products into cellulose capsules.
No, it does not. The supplement does not interfere with fasting in any significant way.
References
Most of the information in this guide is based on scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything you read in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.
