I think it is. Let’s revisit this in five years when berberine data catches up to Metformin.
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I thought we decided Imeglimin was the better metformin. Should I cancel my order and hit amazon? LOL
I don’t think anything is better for lowering glucose levels than metformin. My system just does not tolerate metformin. I take Imeglimin; it is second-best.
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The main problem w/berberine IMO is its numerous drug interactions based on potent effects on multiple liver enzyme pathways, including but not limited to CYP3A4. For instance, it can completely screw up a once weekly rapamycin regimen by lengthening the effective half-life of the rapa and keeping one from ever reaching a trough in serum levels. I bled for hours from a simple tiny shaving cut due to its interaction with Plavix.
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It’s better at everything except that it has fewer studies and human data, arguably lacking what’s most important.
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This never gets old. The reason so many OTC supplements have such positive reception and reputation amongst consumers is exactly because we don’t have the kind of rigorous studies of them that pharmaceutical drugs are obliged to undergo.
I’ve said it before and I’ll say it again, a million times: I much prefer pharma drugs in my stack than any supplement for this very reason. Not only are extensive studies performed before regulatory approval, but you then have tons of clinical studies and an obligation to report any side effects over decades. None of this applies to supplements in the US. Not to mention when you buy a pharma drug, you are assured at least a minimum standard of quality and manufacturing - you know what you’re getting… you absolutely do not when buying supplements.
And that’s just the start of it. When researching a pharma drug, I can look at numerous studies and really follow possible interactions with other drugs and everything is well characterized with dosages specified. You have the information to make an informed choice (insofar as possible). But what do I do with some botanical extract that has a single dodgy small study somewhere claiming some benefit or other and zero other studies? There is no comparison. And if you mention a pharma drug, a botanical fan can always send you studies about side effects (because at least such studies exist), and then says “no side effects reported from the botanical”. Go figure.
The other day I had dinner with some friends. There was a guest and the discussion erupted over statins - I never participate, because it’s pointless. The guest was opposed to statins - instead they used “red yeast rice”… facepalm. There’s no sense in having such arguments. The discussion all focused on the evils of statins. I stayed out of it.
The berberine vs metformin discussion often has features of such. At least berberine has more studies behind it, but it’s still too woefully understudied to be making confident assertions about.
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In some countries RYR has the statin removed.
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Though, 1,000 to.1,500 mg are probably far less potent in terms of its effects on CYP3A4 than half a cup of grapefruit juice. And grapefruit juice’s effects will hang around for a while, taking several days to clear from the body from just one dose.
And a few grams (a teaspoon or two) of black pepper probably alao has a more potent effect than berberine.
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I don’t think this is true. From memory, a single serving of grapefruit inhibits cyp3a4 in the intestine and therefore increases rapa absorption, but has little or no effect on liver 3a4 (and thus no effect on elimination/metabolism of rapa).
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Google Gemini 3-thinking:
https://gemini.google.com/share/9a422f042c94
My question:
which has a more potent effect on CYP3A4, a half cup of grapefruit juice of 1,000 mg of berberine?
Its response:
When comparing the two, grapefruit juice generally has a more potent and clinically significant effect on CYP3A4 activity than 1,000 mg of berberine.
While both substances inhibit this enzyme, their mechanisms and the “depth” of that inhibition differ substantially.
…
The Bottom Line: If you are looking at which one will more drastically change how your body processes medication, grapefruit juice is the more powerful disruptor. It effectively “shuts down” the metabolic pathway in the small intestine for several days, whereas berberine’s effect is more transient and less absolute.
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Please read what I said above in the previous post. You are completely missing the point, which is intestinal vs liver inhibition of cyp 3a4. Your comparison above would only be valid for someone guzzling grapefruit juice multiple times per day every day. People who use grapefruit with rapa only take it once with each weekly dose (in which case it only affects intestinal 3a4). Berberine is taken 2 or 3 times daily continuously and absolutely does affect both intestinal and liver 3a4.
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I agree with your whole post but as for this last part, remember I used the term “I think berberine is better than Metformin” and not “berberine is definitely better than Metformin”, leaving open the possibility of being wrong. I am very careful not to make definitive claims unless it’s obvious. My personal educated guess is if Berberine did have as much research at Metformin, it would be shown to be better overall. We don’t have that yet so that’s why I am limiting my statement to “I think.”
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Berberine is primarily a competitive reversible inhibitor of CYP3A4. While it is present, it
competes with other substrates for the enzyme’s active site and when its concentration is lower, then it dissociates from the enzyme which can be active again.
Grapefruit contains furanocoumarins which are mechanism-based (suicide) inhibitors of CYP3A4. They work by binding to the active site and becoming metabolized into a reactive intermediate and by that they permanently inactivate the enzyme and new enzyme has to be synthesised before CYP3A4 activity can be restored.
For me the question is, how to compare the knock out effect of grapefruit juice with a daily dose of 1000 mg beberine.
I am glad you brought that up because it doesn’t get discussed enough. That is a big reason I don’t take berberine anymore, along with the fact my insulin sensitivity is as good as it gets (my fasted insulin was 1.8) as I’m on Reta, Empagliflozin, and Acarbose.
That being said, I still have a feeling berberine would do very well in the ITP. I believe it was the second best performer in the Ora worm testing if I’m not mistaken
Ironically for those that don’t know RYR contains a statin, namely lovastatin. That’s Mevacor, an FDA approved drug.
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Unless you drink grapefruit juice every day, who cares? Drinking it once per week or once every two weeks has no effect on liver cyp 3a4 and only affects intestinal 3a4.
Taking berberine daily does in fact inhibit multiple liver enzyme pathways in humans:
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And what about black pepper and piperine? (E.g. in black pepper Chinese dishes which can have 250 to 300 mg of piperine.)
Since metformin no longer agrees with me. Taking metformin now is like taking a strong laxative that lasts for more than one day. Berberine is among many things that I tried as a replacement for metformin. For me it simply did not work as well. Some studies equate the two in fasting glucose-lowering capabilities and found that they were basically equivalent.
But at least one " Meta-Analysis of Randomized Clinical Trials" showed:
Conclusions: The hypoglycemic effect of berberine alone is not better than metformin. But berberine combined with metformin has good efficacy and safety in the treatment of T2DM.
What is the science behind ‘science-backed’ supplements?
Yes, easier to forget daily creatine doses. I know I forget especially on days I’m not working out. Otherwise just add to protein drink for after workout. Good idea to add to Keurig coffee in morning. Been attempting to do that on non-workout days. Thanks for the suggestion. 
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