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Micro-dosing berberine: good idea? bad idea?

Berberine Supplement

Relevant podcast: Dissenting opinions on popular supplements, peptides, collagen, metformin, omega-3 and more with our industry insider.

Does taking small doses of berberine, even below the 500 mg dose offered by most supplement manufacturers confer benefit? Is berberine a viable alternative to metformin, the diabetes drug some biohackers take as part of an anticancer regimen?

Berberine is a supplement used for a wide variety of purposes, from gut repair to lowering LDL-C, and even as anticancer product because it regulates blood sugar.1

One area of interest for those of us trying to stave off cancer is blood sugar. You’ve probably heard the common refrain – sugar feeds cancer. And it is true that both insulin spikes as well as certain amino acids like the BCAAs can turn on the cancer pathways.2

Glucose, Insulin, IGF-1, then mTOR

Glucose, and of course sucrose as well, causes inflammatory spikes in insulin and also act to feed cancer cells.

Both normal cells, and cancer cells feed at the same trough, or so the thinking goes. The Mayo Clinic claims to have debunked this theory as a “cancer myth,” but it seems to be at the heart of the ketogenic philosophy. From where I am sitting, the jury seems to still be out.

Enter Metformin, 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.3 4 5

To quote an article in the Annals of Translational Medicine, discussing Metformin’s use in Cancer Therapy:

It is believed that systemic effect of metformin manifested by the reduction of circulating level of insulin and insulin-like growth factor 1 (IGF-1) might be associated with anticancer action. Insulin/IGF-1 is involved not only in regulation of glucose uptake but also in carcinogenesis through up-regulation of insulin/IGF receptor signaling pathway. The excessive food consumption (insulin) leads to increased liver production of IGF-1 that binds to IGF-1 receptor and insulin receptor. Then, through insulin receptor substrate (IRS) the signal is transmitted to phosphoinositide 3-kinase (PI3K), and Akt/protein kinase B (PKB) that indirectly activates (not phosphorylates) mTORC1.

Prophylactic use of 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 here in NYC as well.

As we establish above, Metformin has been shown to inhibit the mTOR pathway, which “plays a pivotal role in metabolism, growth and proliferation of cancer cell.” I refer you back to the quote above from the Annals of Translational Medicine, and ask whether metformin’s reduction in cancer risk is evidence that glucose levels do indeed play a role in cancer growth? Idea being that limiting large spikes of insulin limits IGF-1 and then mTOR. There seems to be a case to be made that this is the case.

Side effects of Metformin

Ben Greenfield believes Metformin harms athletic performance and mitochondrial function over the long term, and you needn’t look much further than WebMD for a long list of side effects 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?

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.6

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.7 8

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 behaves very 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 use must be cycled or it taxes the liver
  5. Berberine is a lot more expensive than metformin which costs only a few dollars a pill

Dosing berberine

I will get to the liver and side effects in a moment, but the behavior of berberine at different doses is of interest here because we’re discussing micro-dosing and I decided to take smaller than recommended doses in the first place to get around those side effects.

When truly micro dosed, at very small levels, this peer reviewed study 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. I believe this is the same concept associated with antibiotics, and why people are encouraged to finish all of a prescription. The bugs not killed by the lower dose will now become resistant to the therapy.

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.

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 compound, and alkaloid. What is the definition of an alkaloid?

According to Google an alkaloid is:

any of a class of nitrogenous organic compounds of plant origin that have pronounced physiological actions on humans. They include many drugs (morphine, quinine) and poisons (atropine, strychnine).

Pronounced physiological actions.

Berberine is a plant, but acts like a drug. It will lower blood sugar and can cause dizziness. Some commentators online have said that berberine will only lower blood sugar if elevated, making it a normoglycemic, but I haven’t seen evidence for this in my research – please share in the comments if you have a good source.

Another common berberine complaint with higher doses of berberine is upset stomach, which is part of the reason I was taking smaller doses.

Berberine should not be taken indefinitely

Berberine is not a supplement you should buy on subscription as long term use could harm the liver.9 It’s better used in cycles of 6-8 weeks, with nice long break periods in between.


Although the anticancer efficacy 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.

I plan to use berberine for maintaining gut health and occasionally as a hedge against very high glycemic meals.

John O'Connor

John O'Connor is the founder of Gene Food, host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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