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Berberine Dosage: Is Berberine Better Than Metformin?

Berberine, long a staple in Traditional Chinese Medicine, is a supplement derived from golden seal and other plant compounds, that is used for a wide variety of purposes, from gut repair to lowering markers of cardiovascular risk like LDL-C, and even as tool for keeping blood sugar in check. 1 Often mentioned in the same conversation as berberine because of their similar metabolic targets, Metformin, is a popular diabetes drug that lowers blood sugar and blood cholesterol, and that has also shown promise in reducing the risk for certain types of cancers. 2 3 4

Why are biohackers using Metformin?

According to Tim Ferriss, Silicon Valley executives have been taking metformin as a prophylactic measure for cancer prevention and as a longevity strategy. I know a friend or two who takes Metformin in NYC as well. Metformin has been shown to inhibit the mTOR pathway, which “plays a pivotal role in metabolism, growth and proliferation of cancer cells.” Although it isn’t proven, biohackers largely use metformin as an anti0cancer drug. Ironically, there have been several Metformin recalls due to unacceptably high levels of NDMA in many drug samples. For more on the quality control issues with Metformin doses, see the FDA’s page.

Side effects of Metformin

Biohacker and professional trainer, Ben Greenfield believes Metformin harms athletic performance and mitochondrial function over the long term. WebMD lists many side effects of metformin, such as:
  • B12 deficiency
  • Physical weakness
  • Muscle pain
  • Upper respiratory tract infection
So, if the rub in Metformin is that it controls blood sugar swings and aids glucose disposal, but also causes weakness and a general lack of performance, maybe it’s wise to hunt for natural alternatives, especially in light of all the metformin recalls?

Is berberine better than metformin?

Berberine is a natural alkaloid compound long used in Traditional Chinese and Aryuvedic medicine. When taken orally, berberine has a hypoglycemic effect in that it lowers blood sugar.[ footnote id=”5″] In fact, studies show that supplementing with berberine is just as effective at treating type 2 diabetes as metformin and that it also inhibits the mTOR pathway as metformin does. 6 7 Why then wouldn’t berberine act as a buffer against the spiking insulin levels that increase circulating levels of IGF-1 and eventually mTOR? Why isn’t everyone taking a little berberine everyday, especially with high glycemic meals? There are five answers:
  1. As far as cancer is concerned, berberine may behave differently depending on the dose administered
  2. Most people haven’t heard of berberine
  3. Berberine carries with it some unpleasant side effects
  4. Berberine is actually more expensive than metformin which costs only a few dollars a pill

Dosing berberine

When micro dosed, at very small levels, this peer reviewed study published in the Journal PLOS One, found that berberine actually encouraged the growth of cancer cells and interfered with cancer drug therapies:
Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM) inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX).
These findings are known as hormesis, the situation where a low dose can cause adaptation, where a higher dose is destructive. The question becomes: what does a dose that has anti-cancer effect look like in milligrams? 1.25 – 5μM is between 0.42 – 1.68mg of berberine, which is a very very low dose. Even a “micro-dose” regimen at 200mg is far higher than the amount shown to encourage cancer growth and diminish activity of cancer medications. Many supplements offer berberine in 1,000 mg doses.

Side effects and cycling use

When I took berberine, I saw side effects from higher doses at 500 -1,000mg a day. For some people, lower doses may be the way to go, although the studies on diabetes dosed at 500mg a few times a day. Berberine is a plant, but acts like a drug. It will lower blood sugar and can cause dizziness. Another common berberine complaint with higher doses of berberine is upset stomach, which is part of the reason I was taking smaller doses.

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Although the anticancer effect is unclear, it appears that occasional 6-8 week courses of berberine between 100-1,000mg a day are safe. In addition to preventing spikes in blood sugar, using berberine in this way could also prove beneficial to heart health and digestive health for many people. I plan to use berberine for maintaining gut health and occasionally as a hedge against very high glycemic meals.

Dr. Aaron Gardner, BSc, MRes, PhD

Dr. Aaron Gardner, BSc, MRes, PhD is a life-scientist with a strong background in genetics and medical research, and the developing fields of personalized medicine and nutrition. Read his full bio here.

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  1. Tom says:

    How/where did you get the conversion of μM to mg? According to your calculation, the anticancer of Berberine is at 3.36mg to 26.88mg high doses but then the supplements out there which sell each capsule at 500mg is more than enough. Then why do I see articles recommend Berberine for cancer treatment at 500mg, three times per day?

  2. Theresa Gadoury says:

    I take 1000 grams of metformin twice a day. I just got Berberine in the mail because I remember taking it last year and it made me feel fabulous. That was before I found out I am a diabetic. Also, I take Isosorbide Monotnit ER and I have been trying to see if there is any danger in interactions between the Berbine and either of these. Also, whether it’s OK to take both Metformin and Berberine at the same time.

  3. Patricia says:

    I use Andrew Lessman procaps vitamins. Love them. Made in USA. I’ve been on two routines of berberine over about 6 months. A1 c and cholesterol are both in normal range. Have noticed some skin lesions that itched and would bleed when I scratched them are mostly gone. I had some increased intestinal activity at first but now am back to normal. I take 6 pills a day, 250 mg each, with meals. Also had sore,somewhat lumpy breasts for years. Now they are totally smooth, not sore or lumpy. I was a letter carrier for 32 yrs. My skin looks much better except for crepeiness. Could have been cancerous and now my skin hasn’t looked so good in years.the only thing I did different was taking the berberine.Was taking 5 pills because of cost. Didn’t get these results until I took 6. The recommended dose.

  4. Jaidev says:

    Sent me more details of benefits of berberine .
    How to reduce cholestral , LDL

  5. omnivore says:

    I’m suspicious of the credentials of self-help gurus who make distinctions between “natural” remedies and “drugs.” Many drugs are derived from plants. For instance, metformin is derived from French lilac, which has been used for centuries to treat diabetes–just as berberine has. Recent research shows the two work together synergistically.

    • Kirk Yager says:

      Synergistic of what pathway magnitude?

      Berberine functions as a blockade of OCT1,in which metformin is highly dependent on.

  6. Coco says:

    I’m taking 3, 400mg caps a day, with 75mg Banaba extract, usually all at one time. I wonder if I take 400mg 3 times a day would be better and get the same results? My last A1C was my highest ever, so I started Berberine, taking 1200 mg all at once, my numbers have dropped significantly, without exercising. Yes some intestinal issues, but not to any point of being concerned.

  7. Sacha says:

    I believe you have not interpreted the review correctly, its high doses of berberine need for cancer treatment not low doses. Please check. I quote:
    ” In the present study, we firstly demonstrated that the effects of berberine on cell growth exhibited typical hormetic dose response in several cancer cell lines, i.e. relative low doses of berberine stimulated the growth of cancer cells, while high doses of berberine inhibited cell growth. LATER IT SAYS.Moreover, low dose berberine remarkably attenuated the in vitro anticancer activity of chemotherapeutic” BUT THIS IS IN THE CONTEXT OF DRUGS, BUT AGAIN ITS LOW DOSES

    • As I say in the post, my micro dose is a high dose compared to the defined “low dose” in the studies I cite. I was taking 200mg, or 200 times the defined low dose, which means my micro dose is a high dose, just not a high dose relative to the usual 500mg dose of most supplements.

      Rather than focus on low or high dose, look to the milligram dose.

      • Ralph says:

        Is the dose based on our weight? I am 53 year old, 228 pounds 6.1 feet tall. Can be 500 mg once daily low enough to cause cancer? Do we have calculated dosage for berberine like mg/kg body weight?

    • Hey Kev, I think the idea behind the liver issue with berberine is the fact that it’s a nitrogenous compound and therefore must be broken down by the liver as part of the urea cycle. An excess of nitrogen can equal an excess of ammonia over time which, depending on the individual, can tax the liver.

  8. ILene says:

    I’m taking Berberine 500mg twice a day for 2 months to lower my cholesterol….my total number dropped 60 points and my LDL went from 147 to 98!!! I initially had some stomach upset, but now it seems much better. Question: Do I need to stop taking Berberine for 2-3 weeks??? or longer???…and if so would it be as if I’m starting up again (ie. stomach upset)?
    My friend has been taking Berberine for 4 years without stopping and her Integrative Doc says it’s ok. Very Confused on dosing….have any answers? Thank you so much…..

  9. Kathart says:

    I was taking Berberine glucose mgmt HCI 400mg 1x daily and had subsequent intestinal distress so bad I couldn’t leave my house. It did reduce my blood glucose levels quite well. But I had to stop. I still need to take it to help with elevated glucose but need to take as you describe. I also could not take metformin for same reason, only more intense and longer lasting.

    So are you saying you would take only intermittent when you had a “cheat” meal or only for a couple of weeks at a time? What does that do to your blood glucose overall when start and stop is used? Also I’ve been unable to find it at lower than 400mg dose

    • Well, I see berberine as a supplement to “cycle” every so often, not for everyday use for months, years. Yes, I will go on a berberine cycle for a few weeks and empty 1/3 – 1/2 of a 500mg pill and take that, usually when I eat a higher glycemic meal (oatmeal with banana for example). My concern is that my blood sugar is normal and I don’t want to crash it. I haven’t measured my blood glucose levels while taking berberine. Anytime I have played around with a blood glucose monitor, it’s been such a pain in the ass I inevitably stop.

      As far as dosing is concerned, I feel most supplement dosing is arbitrary at best, we all have to figure out what works best for each of us. Based on my research, even a dose of 200mg would put you well above the hormesis levels described in the study I cite, but it’s obviously something to discuss with your doctor. Thanks for reading and thanks for the comment.

    • Jaley Moss says:

      You can get andrew lessman at procap laboratory. He is has it at 250mg. I love all of his vitamins. They are very pure and also very good. From fish oil, to Coq10 to healthy skin and hair which is a b complex with a lot of biotin in it. I take over 10 of his supplements. I have been taking them for around 9 years. I just started the berberine as my a1c was in the prediabetic stage. I go to the dr. in a couple of days to get my lab work to see how I am doing. Further more being on his supplements I am the only one who doesn’t have high cholesterol in my family who is older. the only reason my sugar got high was because I had plantar fascisis and bone spurs when not warming up before exercise. Now I can exercise like i used to. Getting old sucks. I have been on the berberine for maybe almost 2 months planning to stop soon for a two week break.Hope this helps


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