Berberine Promotes Fat Loss and Activates Autophagy

Berberine powder

Berberine is an OTC plant product that’s been used in traditional Chinese medicine for centuries, if not millennia. It is anti-diabetic (lowers blood sugar), anti-microbial (has been used to treat diarrhea), and promotes autophagy, the cellular self-cleansing process that is crucial for ridding cells of accumulated junk, and which declines with age. Berberine promotes fat loss and activates autophagy.

Berberine lowers blood sugar as effectively as metformin

In a study done on diabetics, berberine lowered blood sugar as effectively as metformin.(1)

Metformin is a cheap, un-patented, prescription drug that is the first-line choice in diabetes. Its mechanisms are many, but lowering blood sugar appears to be due to lowering gluconeogenesis in the liver. That’s the process by which the liver makes glucose from fats and protein when no carbohydrate sources, whether from the diet or glycogen stores, are available.

Berberine also lowers blood sugar by the same mechanism.(2) As such, it mimics a low-carbohydrate diet.

The extent to which berberine lowered blood sugar, along with HbA1c (a measure of long-term blood glucose levels), insulin, and insulin resistance was not small either, especially considering that no other interventions (diet, exercise) were undertaken. Fasting insulin was lowered by 28%, for example.

Berberine activates autophagy

Autophagy, the junk-removal process used by cells, declines with age, and is causal in the accumulation of damaged molecules and cellular organelles with aging.(3)

Anything that increases autophagy in general is anti-aging. Intermittent fasting is the best known way to increase autophagy, which makes it a potent anti-aging intervention.

Berberine induces and/or boosts autophagy, by upregulating AMPK and downregulating mTOR.(4)

Thus, berberine can be added to a fasting program to increase its effects, making it a potent anti-aging combination.

Through autophagy activation, berberine also alleviates inflammation from oxidized LDL, making it potentially useful in preventing heart disease. (See previous link.)

Berberine suppresses DNA damage and mTOR signaling

Berberine also suppresses DNA damage; it lowers the level of constitutive mTOR signaling, the growth-signaling mechanism that leads to aging cells and cellular senescence.(5) It shares this ability with rapamycin, metformin, resveratrol, vitamin D, and aspirin.

As mTOR leads to muscle growth when activated, and weightlifting activates mTOR, should one be concerned about how berberine will affect muscle growth?

I doubt it, mainly because berberine affects the level of constitutive,  i.e. basal mTOR activity. A weightlifting workout should be plenty to override this and lead to muscle growth. But you don’t want mTOR to be overly active at other times, as it leads to cellular senescence, a bad thing.

Berberine leads to fat loss

Metformin is known to cause fat loss, and berberine does this also.

In patients with metabolic syndrome, berberine dropped body mass index (BMI) from 31.5 to 27.4. That’s yuuge. Waist circumference dropped 5 centimeters.

Bodybuilders often use metformin for cutting fat; there seems to be no reason that berberine wouldn’t be equally effective.

Berberine is over-the-counter

I’m on record as saying that metformin seemed a little underwhelming to me. My reasoning was that it showed great results in diabetics, but if you already are lean and have your diet and exercise geared in, the results might not be so impressive. Presumably most of my readers are already on top of their diet and exercise.

But one reason I didn’t want to bother with metformin is that it requires a prescription, which of course entails a doctor visit and a trip to the drugstore. The fact that I can get berberine OTC makes a big difference to my motivation in taking it.



A typical dosage of berberine for diabetics is 500 mg, three times daily, with meals. This is the same as for metformin.

Since I’m not a diabetic, I’m only taking twice a day. [Update: currently, once a day.] The half-life is short, a few hours, so it needs to be dosed more than once daily for full effect. However, if you’re in good shape already, a once-daily dose could be both effective and a good thing to add to your regimen.

I’ve been taking berberine for a couple of weeks now, and based on what I know about it, it seems a good idea. Especially if you’re overweight and/or have some way to go in your health and fitness program. I’ve also added it to my supplements buying guide.

PS: Check out my Supplements Buying Guide for Men.

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  1. neven says:

    I remember looking at berberine some time ago, but eventually decided not to take it because possible interference with hypertrophy:
    …The increase in AMPK will inherently suppress muscle hypertrophy in muscle cells…[]
    Can you comment on this?

  2. neven says:

    Ha, I need some vision supplements too 🙂

  3. Cloudswrest says:

    Do you have one of those cheap glucose meters you can buy at Walmart and any drugstore? Be interesting to see a morning fasting sugar level both on and off Berberine.

    • P. D. Mangan says:

      Cheap glucose meters? They sell you the meter, then you have to buy the expensive test strips! But, no, unfortunately I don’t have one.

      • Cloudswrest says:

        They’re not THAT expensive. 50 for $15. They can be expensive for a real diabetic who has to test multiple times a day. But for spot checking a few times a week as part of a fitness regimen it’s trivial. I have one. I’ll give it a test once I come up to speed on Berberine.

        • P. D. Mangan says:

          Then I should get one. I’ll be interested to hear your results.

          • Allan Folz says:

            I have to second the BG meter. A single test strip is cheaper than a single dose of most supplements.

            If you can use BG as a proxy for insulin (I’m not sure if it necessarily always is — for example, protein causes an insulin response, but does it increase BG?) and if your primary goal is lowering insulin, then a meter is going to give you invaluable feedback on how different things that you do effect that goal. It would also allow you to compare the relative efficacy of various supplements, which could end up saving more money that the meter even cost.

    • Nicholas the Jovian says:

      I was wondering about this, too. The reply to markb’s comment answered all of my other questions in one go.

      Quick note regarding the Amazon link: it goes to an offer for 900mg capsules. Diabetics and Mangan alike take 500mg. The price/capsule is lower than most of the 500mg offers, though.

  4. markb says:

    Hi, PD

    In your opinion, should this be taken fed or fasted?

    • P. D. Mangan says:

      Mark, most people take berberine with meals for the blood sugar lowering effect. However, other than for someone who potentially has or could become hypoglycemic, there doesn’t seem to be any reason not take it fasting. I spoke to someone who’s been taking it awhile, no ill effects either way, so that’s what I’ve been doing: one in AM with coffee, one in evening with dinner, or sometimes before bed. I also had concerns about taking it with my habitual low-carb diet – again, blood glucose lowering effects – I’ve had zero no ill effects.

      • markb says:

        I posted my question the day before going on a four-week trip, and then forgot all about it! Thanks for answering my question, PD.

  5. JP says:

    Slightly OT. I just started taking Nutrabio creatine. I mixed it with my whey protein drink and it made the drink taste really gross. How do you take your creatine?

    • P. D. Mangan says:

      Hmmm, that’s exactly how i take creatine, by adding it to my whey shake. I don’t notice any difference in taste.

    • Tuba says:

      On my lift days (M,W,F) I take creatine with 33 grams of dry whey powder in 3/4 cup of homemade (goat milk) yogurt. At the same time I take L-Citrulline, B6 and Ursolic Acid. After lifting I have a protein breakfast (such as eggs) and avoid anti-oxidants until after lunch or so.

  6. Don says:

    Berberine impairs muscle metabolism by two novel mechanisms. It impairs mitochonidrial function stimulating the expression of atrogin-1 without affecting phosphorylation of forkhead transcription factors. The increase in atrogin-1 not only stimulated protein degradation but also suppressed protein synthesis, causing muscle atrophy.

    • P. D. Mangan says:

      As far as I can tell, anything that activates AMPK also increases atrogin expression. So, fasting phytochemicals, metformin, etc., and all these things enhance health.

    • Rob H says:

      Hi Don,

      You are absolutely right – but this is a good thing: it seems that activation of AMP-K, fasting, muscle breakdown and autophagy are all part of the same process – what Dr Valter Longo would describe as ‘hitting the off switch’ in order to activate the repair processes.. BUT, as Dr Longo also explains, what we need is a good balance between this ‘AMP-K’ repair pathway and the opposing ‘M-TOR’ pathway: which is the polar opposite: ie anabolism etc.. In fact the writer of the above article you quote recognised this in his follow-up article:

      My only beef with the article in the link above though is that the writer seems to suggest hitting BOTH pathways at the same time, which appears to me to be analagous to pressing both the brake and the accelerator pedals at the same time! The way I choose to tackle this myself is to activate the AMP-K pathway at night, ie going into the fasted overnight phase. I take resveratrol and a baby aspirin at 10pm to kick things off. Then take a green tea extract capsule and grapeseed extract capsule the following morning, and 3 days per week fast through to midday (ie 16-18 hours fast in total, 3 days per week). I then usually work-out fasted (after taking BCAAs/ leucine immediately beforehand) and then try to activate the opposing M-TOR pathway hard, ie by ingesting 30g whey protein right after my workout and making sure I have 30g of good quality animal protein for lunch and dinner, and some aged hard cheese at about 9pm, before switching over to the AMP-K pathway again with resveratrol & aspirin at 10pm before bed..

      I am just about to add in some berberine to my routine: taking 1 x 400mg capsule before bed each night to amplify the AMP-K cycle at night. I really believe the path to good health lies in strongly and intermittently activating AMP-K and then M-TOR – but NOT at the same time. I feel that nutrient timing is a very overlooked factor, especially when it comes to activating AMP-K vs M-TOR. Dennis – does your research support this point of view?

      • Rob H says:

        Oh, and one other thing Dennis: the reason I am considering Berberine (and to be honest the reason I got into this whole healthy eating business in the first place) is that my mother was diagnosed with metastatic breast cancer 3 years ago – a recent MRI scan revealed this has now spread to her spine and skeleton, but despite this fact she is fine in herself, albeit much more frail now through her 2 weeks on, 2 weeks off use of the chemotherapy drug Capeciteabine. I’m looking for ideas on what other supplements she can take and berberine seemed like one of the strongest options. Would you consider writing a future blog post on what you would recommend to someone who is trying to fight metastatic cancer? For example, you mentioned Alpha Lipoic Acid in a recent article, and I do take this myself every other day. However, I recently came across this article on pubmed which is very negative towards ALA: Many thanks! Rob.

        • P. D. Mangan says:

          Hi Rob. Funny thing about mTOR and AMPK is that exercise, particularly weightlifting, could be expected to activate both. I do think nutrient timing is important; it’s almost the centerpiece of my book Stop the Clock, activating autophagy/AMPK and mTOR in turn, avoiding both damage buildup in aging and frailty. I don’t have a strong opinion of ALA, but I don’t take it myself and the antioxidant aspect of it has always made me somewhat wary, although it’s done well in aging experiments. I believe very little of it is needed, so the link you point to may be not entirely relevant, but I don’t know.

          Something like metastatic cancer is so serious that I generally avoid giving my own opinion on it. One thing that’s intrigued me lately is the effect of aspirin on metastasis.

          • Rob H says:

            That’s very interesting Dennis, and thanks for the link to the article re aspirin – I am very interested to find anything that can help with metastatic cancer. I have had my mother taking baby aspirin each night for the past couple of months (largely based on your recommendations).The ‘Metabloc’ (ALA & hydroxycitrate) you mentioned in your post ‘The End of Cancer’ sounds like it could be worth a try if I can find some hydroxycitrate. And yes, I think I will revisit your book ‘Stop the Clock’ which probably warrants a 2nd read now (excellent book by the way!)

        • Elaine says:

          Hi Rob, Berberine is a very important one for your mom. Additionally, consider mega dose Vitamin C administered by IV – many naturopathic Drs offer this. The megadose Vitamin C allows the body’s own immune system to become strong enough to fight the cancer. Berberine actually inhibits the growth of cancer cells and causes cancer cell death, and causes Chemo to be more effective. Together, I think Berberine + mega dose Vitamin C would be great. Google megadose vitamin c + cancer treatment to see some results of those who’ve used it. Also check out the site called Doctor Yourself and click on cancer. Lots of great info. I hope your mother has a good outcome. -Elaine

          • Rob H says:

            Many thanks for your kind and helpful comments Elaine, that has spurred me to look into the Vitamin C IV further. I initially heard about that a few years ago from a British nutritionist called Patrick Holford, but to be honest I initially dismissed that approach as a bit ‘OTT’ but have seen more recent reports (including of course some useful points on this site) explaining the mechanism behind it which is very convincing. It appears that very high dose IV Vit C is very different to Vit C supplements: it appears to transform it into a pro-oxidant which then destroys cancer cells.. Just need to convince my mother now! (at least she doesn’t have a needle phobia like I do!)

            My Mum also takes ‘Salvestrols’ (see link here to an article about them from Patrick Holford:

            The theory is that they offer an improved sirtuin effect compared to resveratrol, but I just take plain old resveratrol myself each evening. In addition to the Berberine each evening I now have her taking a baby aspirin and magnesium. She takes vitamin D, grapeseed extract, glucosamine and a probiotic in the mornings. The cancer seems to be stable at the moment, but she is becoming very frail and losing her short term memory, maybe because of the capecitabine (Chemotherapy tablets) which she takes 2 weeks on, 2 weeks off. I am considering giving her whey protein each morning to try to prevent further caxexia (sarcopenia) but not sure if that will spur further cancer growth, so have held off so far.

            But thank you so much for your kind advice – it is much appreciated!

            All the best, Rob.

          • P. D. Mangan says:

            Rob, you’ll probably like my next post, coming soon.

      • neven says:

        Article about concurrent activation of amp-k and m-tor

  7. Dr. Phil May says:

    I also take Berberine along with some of the other supplements you mention, and am in full agreement with your views. Berberine can also be used to lower cholesterol.

    I have to be a little careful with berberine because of its pharmacokinetics, it interacts with my hypertension medication Losartan.

    As a matter of interest, berberine has a very poor adsorption. I take milk thistle to try to overcome this difficulty.

    Kind regards


    • P. D. Mangan says:

      Thanks for that, Phil. It’s possible that one way, maybe even a major way, that berberine works is through modification of the gut flora, although this is speculative. Berberine does modify it, as can be seen in its traditional use as an anti-diarrheal, but the speculative part is how this affects its other targets such as blood sugar. Metformin does this also which may account for the side effects of gut discomfort. I mention this only becuase, if this is the case, absorption could be less important than thought. As I say, speculative.

  8. Lobo says:

    What’s your take on supplement timing for berberine?

    • P. D. Mangan says:

      It can be taken either fed or fasted. I’ve been taking 1 in the morning and (sometimes) 1 at dinner.

  9. Jer says:

    Hi Pd.
    Thanks for the information as usual.

    As an Fyi, the link at the end of your article is dead :”supplements buying guide”.

    “I’ve been taking berberine for a couple of weeks now, and based on what I know about it, it seems a good idea. Especially if you’re overweight and/or have some way to go in your health and fitness program. I’ve also added it to my supplements buying guide.”

    I presume you are still on Berberine once a day. Have you noticed any mental/physical effects? (e.g. more energy, clarity of thought, weightloss). I ask because sometimes I notice nothing when I take these things! is it still your go-to anti-ageing supplement?


    • P. D. Mangan says:

      Hi Jer – I do still take berberine, once a day. I agree about not noticing anything, because I don’t think I do. Generally, I feel very good and have lots of energy, do a high intensity lifting workout every 3 days, so hopefully everything is working as it should. I haven’t tested my blood glucose lately and berberine should decrease it. (Thanks for the fyi)

  10. Jer says:


  11. Serge says:

    Many health-sites articles on berberine advise to take it for no longer than several weeks. I presume that’s because it has anti-microbial effect. Whether that arised from practical experience or they just feel like adding as many warnings as they can invent I do not know. So…. what is the gut feeling? That is, – asking those who did try to take berberine for extended periods of time – what does practical experience tell? Does any one feel that there ought to be pauses in berberine consumption?

    • P. D. Mangan says:

      Hi Serge – I take berberine, but not daily, using it as an occasional AMPK booster/hormetic. In China, they use it as an anti-diabetic, taking it 3 times daily. Whether the latter dosing schedule is totally safe, I couldn’t say. My feeling is that if one needs blood glucose control, one would be better fixing what made it wrong, i.e. diet, exercise, obesity, than taking a lot of berberine or anything else like metformin.

  12. Myra says:

    Can berberine be taken while water or dry fasting or is it recommended to always have it with food? Please advise.

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