Berberine

Dr. Andrew Huberman Mentions but Personally Avoids

Huberman discusses berberine across 4 videos, primarily in the context of blood glucose management and fasting. In his hunger and satiety episode, he notes that berberine and metformin can potently lower blood glucose but warns about hypoglycemia risks. In his fasting episodes, he describes berberine as a glucose disposal agent that can accelerate the transition to a fasted state and mimic fasting effects, though he advises caution. However, in his dedicated longevity supplements AMA, he explicitly states he avoids metformin, berberine, and rapamycin, citing lack of sufficient human data for longevity and the presence of significant side effects.

I'll just be very direct and say I do not take metformin. And I also don't take what some people call the poor man's version of metformin, which is berberine. Berberine gives me brutal headaches. Berberine lowers blood glucose. That's why I think it's giving me brutal headaches. A lot of people have explored or are thinking about exploring taking metformin or berberine for sake of lowering blood glucose and lowering a particular cellular, let's just say, pathway or a set of molecules, mTOR being the most common of them. mTOR, mammalian Target of Rapamycin, is abundant in developing cells. It's responsible for the growth of individual cells.

▶ 18:56 · AMA #12: Thoughts on Longevity Supplements (Resveratrol, NR, NMN, Etc.) & How to Improve Memory

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Dr. Peter Attia Uses Clinically for LDL

Attia provides the most clinically detailed berberine coverage across 4 videos. He has two dedicated clips on berberine where he explains its dual mechanisms: as a weak AMPK activator (similar to metformin, decreasing hepatic glucose output) and as a weak PCSK9 inhibitor (improving LDL receptor recycling). He uses berberine empirically in patients with elevated LDL who lack other clear markers of poor clearance, noting it can occasionally produce significant improvements in lipid profiles. He explicitly prefers pharmaceutical-grade metformin over berberine for glucose management due to better regulation and consistency. For brand quality, he recommends Thorne for berberine due to its pharmaceutical-grade scrutiny.

…insights about berberine so berberine is a plant derived extract that has two properties one of which it gets a lot of attention for one of which it might not be as well known the first is that it is a weak am p kinase activator and for those of you that have you know shown an interest in what metformin does that's sort of the the that's probably the secret sauce of metformin is its AMPK activation so berberine when taken at you know sort of recommended OTC doses which I remember the doses anymore I think it's like a it might be actually a comparable dose to metformin it might be…

▶ 00:03 · Insights about berberine (AMA #3)

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• 02:24 · Insights about berberine (Qualy #52)
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Dr. Mark Hyman Recommends as AMPK Activator

Hyman discusses berberine across 4 videos in two distinct contexts: as an AMPK-activating longevity compound and as an herbal antimicrobial for gut health. In his anti-aging mechanisms video, he highlights berberine alongside quercetin, resveratrol, and lipoic acid as compounds that activate AMPK and downstream pathways like FOXO and PGC1 to combat inflammation and oxidative stress. A guest on his show (Michael Murray) discusses berberine specifically for mitochondrial health and cellular protection as part of a longevity supplement protocol alongside PQQ and ergothionine. In his gut health videos, Hyman recommends berberine as an herbal antimicrobial for treating yeast overgrowth and restoring gut flora, typically combined with oregano.

…you actually activate this and you can also do it through various compounds that are found in food like quercetin which is in onions from herbs like ginseng resveratrol green tea berberine which comes from certain plants and of course lipoic acid which is a nutrient you can get through supplements all these things will activate this ampk and drive these metabolic pathways that activate all these other pathways that are regulating aging like the foxo and the daf2 and the pcg1 which is a master metabolic switch that drives all these incredible pathways that essentially do everything we're talking about they work primarily by reversing the things that we know…

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How much berberine should you take per day?

The 5 experts have no dosage consensus. The typical range is 500-1500mg per day, split into 2-3 doses (commonly 500mg per dose). Attia uses it empirically and adjusts based on patient response. Start low at 500mg and assess tolerance before increasing, ideally under medical supervision if on diabetes medications.

Is berberine nature's metformin?

Not exactly. Attia calls berberine a weak AMPK activator similar to metformin that decreases hepatic glucose output, but he prefers pharmaceutical-grade metformin for glucose management. His primary use for berberine is actually LDL cholesterol via PCSK9 inhibition, not blood sugar — which differs from the popular 'nature's metformin' framing.

What are berberine's side effects?

Berberine can potently lower blood glucose, risking hypoglycemia — especially with diabetes medications or on an empty stomach (Huberman). GI side effects like diarrhea, constipation, cramping, and nausea are common, particularly at higher doses. It may interact with CYP3A4 and CYP2D6 medications like statins and blood thinners, and should be avoided in pregnancy.

When should you take berberine?

Take berberine with meals to reduce GI side effects and align with its glucose-lowering mechanism. When used as a glucose disposal agent, take it shortly before or with a carbohydrate-containing meal (Huberman context). Start at a low 500mg dose and assess tolerance before increasing.

Does berberine lower cholesterol?

Yes, for some patients. Attia identifies berberine as a weak PCSK9 inhibitor — it can significantly improve LDL clearance in patients who overexpress the PCSK9 enzyme. He uses it empirically for elevated LDL and recommends the Thorne brand for pharmaceutical-grade quality. This LDL use, not blood sugar, is his primary reason for prescribing it.