Should Biohackers use Metformin?

This pharmaceutical is an insulin hack and the most studied diabetes drug, yet remains highly controversial as an anti-aging and longevity tool for biohackers.

Originally Published on LimitlessMindset.com

Guys and gals, I have as a researcher, Metformin. I pride myself on being able to discern the difference between information and misinformation, between science and marketing hype and I’m not sure if I’ve ascertained the truth about Metformin. I’ve tried to wrap my head around the vast amount of research and commentary on Metformin and honestly, I’m not sure if Metformin is a game changing anti-aging drug or a really problematic product.

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This article is mostly going to focus on decoding what the human studies are saying about Metformin and how this squares up with the anecdotal experiences of Biohackers online. For more of my own personal experiences, thoughts and comparisons please see the written and video reviews in the sidebar.

Scientific Research

Impressively you can find +17,000 scientific papers referencing Metformin and a number of human clinical trials. The most notable meta analysis of Metformin analyzed more than a dozen randomised controlled trials totalling over 13,000 patients was published in 2012 and concluded:

And they had some indication that sulphonylurea bitherapy caused an increase in mortality. That’s concerning.

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History

French lilac has been used for centuries in folk medicine of which Metformin’s properties are derived. French lilac was a remedy for frequent irritation which is now known to be symptom of diabetes.

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From a 2012 paper out of Korea University College of Medicine.

It’s now an extremely popular drug with +80 million prescriptions written annually in the United States alone.

Metformin makes an appearance in one of my favorite books, by Tim Ferriss

Mechanism of Action

A Metabolism Hack

Biohackers may find it helpful who have indulged for years in a rich in carbohydrates and sugars and are switching to a keto or paleo style diet. Imagine a heroin or methamphetamine addict, they need their narcotics to feel normal because their neurotransmitter receptors have been desensitized by years of abusing drugs. They can no longer take real pleasure in a succulent meal, a conversation with a friend or having sex with their partner because their neurobiology has grown numb to serotonin and dopamine. They need to restore the sensitive of those receptors to have a normal life. That’s sort of what Metformin does by stimulating the GLUT4 receptors.

An Insulin Hack

Insulin is a crucial hormonal regulator of our internal homeostasis. From a 2012 paper detailing its mechanism:

  • Metformin increases the body’s sensitivity to insulin.
  • Reduces liver — the production of glucose. The liver converts a lot of the protein that we consume into glucose (sugar). Metformin prevents this which is beneficial to (like me) who are consuming a lot of protein. If you’re spending your hard earned money on fancy whey protein powder or steak dinners you want as much of that protein as possible to contribute to muscle growth.

An AMPK Hack

Metformin activates the AMPK energy system — the endurance energy system — which switches the body over to more of a fat burning energy mode. Naturally the body prefers to burn glucose, the body to burn sugars, Metformin this which is obviously beneficial for those who need to lose weight.

The 2012 paper explains…

A mTOR Hack

From a detailed Longecity article:

Does this mean that Rapamycin is a metformin alternative? Possible, although it’s prohibitively expensive.

Vs Type 2 Diabetes

The notable study on Metformin was The UK Prospective Diabetes Study, over 5000 people struggling with diabetes participated making it the largest diabetes study ever. It begins with an interesting tidbit of history

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Being such a substantial study, a 10 year follow up was conducted.

And a 2008 French paper added:

It would be smart to get your personal genotyping done to determine if you carry many of the 48 risk factor genes for diabetes. If you do there’s some evidence backed preventative measures you would want to make a part of your lifestyle. Doctors will often prescribe Metformin to people who are prediabetic but there’s a lot better options for averting diabetes than hacking your metabolism with this contentious pharmaceutical.

Diabetes Risk Factor Genes Spreadsheet

For Body Building

That’s the premise of a very thorough 2016 article published in EMBO Reports:

It goes on to explain…

Experiential

An effect that caught my attention was that it maybe a shortcut to a more -esque body. According to Dan the , it has a notable effect on your physique and musculature.

Glucose aversion was reported by Dr. Edward Omron, it makes consumption of carbs and sugary food a distinctly unpleasant experience. Thus, it conditions you to avoid unhealthy food. Which sounds great for those struggling with obesity or diabetes or failing to find the self control to change their diets. He also reported…

  • Improved his long term memory recall.
  • It made him look less old, it made his face less round and fat and more angular and defined.

Expect a bit of diarrhea and discomfort the first week on Metformin, after one month the gastrointestinal discomfort will go away.

Apparently it makes your poop and pee smell worse. So keep the damn window open in your bathroom!

A Will Power Diet Hack

If you’ve ever had friends or family that tried to quit smoking cigarettes, they may have tried this drug Chantix® that makes smoking a really awful experience. Conditioning them to overcome their self destructive addiction. Metformin, for many has a similar effect on their urge to eat sugary, carbohydrate rich foods. It’s an appetite suppressant for many, on Longecity it was reported

Vs Cancer

Lewis Cantley of the Cancer Center at Weill Cornell Medicine asserted…

Why black people should take metformin…

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From Dr. Lee Know’s recent book

Cofactors

Ipragliflozin — A recent Russian phase 3 randomized placebo-controlled trial totalling 165 patients noted that Ipragliflozin was safe and enhanced Metformin’s positive effect in reducing HbA1c and body weight after 12 weeks.

Vitamin B-12 — Metformin is especially problematic for those who are B12 deficient. It’s a really smart idea to supplement methylated B-12 with Metformin.

Niacinamide — There’s an interesting presentation on a self experimenter’s 23 month trial the two.

Usage & Dosage

1000 milligrams daily is a typical dosage. With Metformin you want to start with a smaller dosage and work up to a larger dose (or whatever your physician has prescribed)

For example, start with 500 milligrams, taken with your largest meal of the day and incrementally increase the dose. Add another 500 milligrams with your other meals. Increase the dose gradually by 500 milligrams weekly.

  • 1–2 grams total daily is a typical dosage for treating or preventing diabetes.
  • Bodybuilders may want to take up 2000 milligrams to maximize muscle gains.

Price

It’s an off patent and very affordable drug, costing $5 — $25 monthly for regular users, depending upon the source. A month’s supply from RUPharma.com is just about $8.

Side Effects

Increasing Metformin dosage too fast often results in some unpleasant side effects; diarrhea, nausea, heartburn, stomach cramps, etc. This can be avoided by starting with a low dose and working your way up slowly.

Lactic acidosisJames McCormack makes the case at the BCCFP Family Medicine Conference that Lactic acidosis is really not a concern unless you’re taking Metformin in ridiculous dosages. You really don’t need to worry about it if you’re taking a reasonable 500 milligrams or 1 gram daily dose. Can be reversed by taking Vitamin B1.

Mcmanis, a very thorough biohacker on Longecity reported that when starting with Metformin…

Metformin might lower testosterone, from Tim Ferriss’s interview with Dominic D’agostino

Conflicts: In combination with beta-blockers (Acebutolol, Atenolol, Bisoprolol, etc) it may lower blood sugar. Quinolones (antibiotics) may increase blood sugar. Cimetidine, a heartburn drug has been implicated in one of the rare cases of Lactic acidosis.

Apparently Metformin has a very distinctive scent that often makes your poop and pee smell awful and according to some biohackers this smell persists as long as you are taking Metformin. It doesn’t make your skin or breath stink, but your family, roommates or coworkers may hate you if they have to use the bathroom after you! I polled the members of a Metformin Facebook group about this very unappealing potential side effect and the majority of users responded that it had no effect on their bathroom smells.

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Risk Grade: B-

  • It is heavily studied worldwide which is encouraging. However, the most authoritative meta analysis of clinical trials couldn’t conclude that it was useful and helpful.
  • It has undergone a massive clinical trial giving Metformin to over 5000 people and a 10 year follow up study was conducted. If it produced serious negative side effects in a statistically significant proportion of its users this giant study would have noted that.
  • The major thing that scares people about Metformin is the Lactic acidosis which can actually kill you. However, unless you have liver or renal issues or you’re drastically deficient in B-Vitamins you really don’t need to worry much about this.
  • There’s some concern about its effect on kidney function, from a 2017 study of 600 Taiwanese

It’s a somewhat contentious drug amongst the biohacking gurus; Dr. Mercola called it a Dave Asprey agreed: Ben Greenfield disagreed saying: Biohacking body builder extraordinaire Jay Campbell has used it for 17 years and contends that

The Metformin Alternative: Berberine

At this point you may be saying to yourself

I’ll direct your attention to the nutraceutical Berberine; It simulates the effects of diet, exercise and weight loss. T-Nation.com advises a dosage of 500 milligrams three times a day, you can take it as a capsuled supplement or as an herbal tea steeped in boiling water.

There are four clinical studies totalling +1300 diabetics evaluating Berberine’s effect on Insulin.

A 2003 Chinese study evaluated its effect on exercise capacity

Although, I’ve heard from a credible source that Berberine as a supplement is problematic; that many vendors of the stuff are not selling pure Berberine. Thus I’d urge you to only order or consume it after you see COA verifying the quality.

The evidence for Berberine as an insulin hack for diabetics and as an AMPK “exercise in a bottle” hack for gym bros is not as strong as with Metformin. It seems to me that there’s a lot of better lifestyle options to turn to before using this pharmaceutical.

Conclusion…

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I think I’m going to pass on Metformin. The main upside for a healthy guy like me in my mid 30’s would be muscle gains in the gym. I don’t really care about body building, I don’t care about having huge muscles. I go to the gym several times a week to stay lean and maintain health. The first week on Metformin is supposed to be pretty unpleasant and it makes your business in the bathroom a very supposedly, I don’t see being worth the potential muscle gains. The potential side effects make it very unappealing to an otherwise healthy, happy non-diabetic biohacker like myself.

Originally Published on LimitlessMindset.com

Written by

Adventuring philosopher, Pompous pontificator, Writer, K-Selected Biohacker, Tantric husband, Raconteur & Smart Drug Dealer 🇺🇸

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