Metformin has a bunch of undesirable side effects. I don't see an easy way to quantify the importance of those side effects, so I try to evaluate how likely it is that the benefits of metformin will apply to me.

The obvious way in which metformin might cure or prevent age-related diseases is by curing insulin resistance. Some educated-sounding people have been saying that insulin resistance contributes significantly to Western disease (aka diseases of civilization, including cardiovascular disease, diabetes, dementia, and some subset of cancer). Doctors have arguably been undertreating insulin resistance, because it doesn't produce immediate disease-like symptoms. Maybe if metformin were still patented, the patentholder would be pushing the FDA to get insulin resistance classified as a disease.

Insulin resistance seems to be non-existent in cultures that most resemble our pre-farming ancestors, so it sure looks like it's avoidable via lifestyle changes (the best guesses are diet (high fiber, whole foods), exercise, and sleep). That suggests it's possible, although maybe hard, to get the benefits attributed to metformin without the side effects.

I pay close attention to my insulin resistance, via blood tests, and have avoided metformin for now because it looks like my lifestyle is good enough that I have few insulin-related risks so far. If my A1C gets above 5.6, I'll think pretty carefully about getting metformin.

[ Question ]

What supplements do you use?

by ioannes_shade 1 min read28th Jul 201921 comments


Cross-posted to my personal blog.

There's a rationalist tradition of thinking carefully about supplements & nootropics: 1, 2, 3

However, I haven't seen a record of what supplement regimens people end up using in practice.

I've been fooling around with supplement stacks for a few years now and feel pretty good about my current regimen (outlined below), but want to see if there's any low-hanging fruit I've missed.

So I'm curious... what supplements do you use? (Reply below, or shoot me an email)

Also curious to hear about obvious mistakes and/or oddities in my current stack.

My supplement regimen

Disclaimer: I'm not a doctor, this isn't medical advice, etc. etc.

Background: 27 years old, biological male, ~200 lbs, BMI of 25, pescatarian

Supplements I take:

Supplements I'm considering:

  • Apparently Tyrosine boosts cognitive performance during stress. There are noticeable subjective effects when I take 1.0 - 2.0 g on an empty stomach. I tried some recently and enjoyed it. It's safe, cheap, and legal so I may start using it regularly to complement my caffeine use.
  • Following this post, I may start taking Vitamin K2 in the morning to complement my Vitamin D3 supplementation.
  • Romeo has told me that Choline is a good daily supplement (apparently many people are deficient & deficiency is associated with depression). I haven't poked the literature on this yet.

Supplements I don't take any more:

  • I used to take fish oil daily. Gwern likes it, but I didn't notice any effect & was scared off by the potential negative effects. Also I eat sushi sometimes which probably does some of the work fish oil would do.
  • I used to take a small aspirin daily but stopped after a large RCT found that the downside risk probably negates the benefit.
  • For a while I took lithium to boost mood, but stopped after my replication of Gwern's RCT failed to show an effect.


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7 Answers

I'm curious why you mentioned the health risks of fish oil while linking to a page saying fish oil doesn't contain Mercury. Is that not the health risk you were thinking of?

I take creatine, D3 and fish oil. (Only five days a week because I take them at work. When I keep them at home I forget.) I don't remember exactly why those. When I stopped taking them all for a while I thought I felt a bit worse in ways I no longer remember, so I started again, and possibly I then started to feel better.

I take anti inflammatories though I haven't blinded subjective effects. Berberine (similar in action and effect size to metformin), ginger, curcumin phytozome. Rest is the same. D3+k2. Theanine + ashwaghanda if I'm having a stimulant. Melatonin if sleep is disrupted. If one gets a subjective effect from a supplement one should investigate why this might be the case and try to solve the root cause. ie for me I had above normal inflammation from foods I didn't know I was allergic to (mild).

Daily supplements:

  • 10mg pregnenolone: sometimes a bit more, aiming for blood levels around 60-80 ng/dL. Seems to increase my mental energy.
  • 25mg dhea: I'm uncertain about the dose, and I'm experimenting a bit to see if I can detect effects.
  • ~3000 IU vitamin D: aiming for blood levels just over 50 ng/mL.
  • 100mcg vitamin K2 mk7
  • 1mg folate: I'm homozygous for MTHFR C677T; it seems to improve my mood.
  • 1mg B12: it's keeping my blood levels around 800 pg/mL, compared to < 500 before supplementing.
  • 1g omega-3 (currently in the form of Bulletproof Omega Krill Complex).
  • Stem Cell 100, once per day
  • 500mg N-Acetyl-L-Cysteine: possibly helps lower my homocysteine, but my results are pretty noisy.
  • ashwagandha: I had very interesting thyroid effects when I was getting too much iodine from kelp, but now that I've fixed my iodine levels, I don't detect any effects.
  • ResveraCel (Thorne), contains Nicotinamide Riboside, Quercetin Phytosome, Trans-Resveratrol, Trimethylglycine.
  • curcumin (Life Extension Bio-curcumin): I suspect I have inflammation due to a temporary problem, and will likely go back to taking this less regularly in a few months.
  • caffeine: from tea, green tea extract pills, or occasionally a 100mg pill.

Supplements taken less than once per day:

  • creatine, 1 or 2 grams (no clear effects).
  • melatonin, typically 300mcg, timed release version.
  • liver, and organ meat pills, from Ancestral Supplements.
  • green mussel
  • kratom: typically 0.25 teaspoon of Maeng Da, mildly stimulating with reduced anxiety?
  • phenibut: taken about once a month, for the anti-anxiety effect, with a bit of stimulation.

A majority of these choices are influenced by Bredesen's book The End of Alzheimers, or by a prior source with similar advice.

You might be interested in Testa's omega-3 supplements. They contain both DHA and EPA but come from farmed algae, so they don't have the mercury issues that fish oil does.

I take two per day based on some advice from someone on the LessWrong Slack.

I take Creatine (as a vegetarian), Tyrosine (because I notice increased cognitive energy -- may be placebo), and 5HTP (seems to promote a sense of calm, may be placebo).

I recommend everyone take a full amino acid supplement, and see if it seems to make a difference subjectively. If it does, you might be deficient in one or more particular aminos, and you can further experiment.

  • Omega3 from algae, 750 mg a day
  • Vitamin D, ~2000 IU a day
  • B12, 2.5 mg per week
  • Melatonin 0.4 mg as needed for sleep
  • Creatine, 4–5 g a day
  • Planning to get Ashwaganda
  • Coffee, but that's more of a drug than supplement

I, too, take Metformin but then again I have diabetes and it's prescribed for me.

I also take COQ10 300mg. I was having bad leg and foot cramps at night, probably from the statins I take. I read that COQ10 would help and indeed it does seem to have done the trick.