I took metformin 500mg/day for a year and it didn’t do jack for me, zero impact on A1c, BG levels etc., though I tolerated it no problem. Since then, I’ve read enough about metformin, that I decided it’s not for me (impact on exercise, time of conversion from pre- to full DMT2, compared to lifestyle intervention studies etc.). I’d sooner try pioglitazone - my insulin production is elevated, so maybe increased sensitivity can take care of BG.
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“time of conversion from pre- to full DMT2”
what does this refer to? does metformin accelerate conversion?
Vida
#59
I measured taurine in blood an urine on the same day. My blood levels were a little below reference range and my urine levels were very high. I was “wasting” taurine because a high uriribe beta alanine level (of unknown cause) was apparently outcompeting it for reabsorption at the renal tubules
So i have beensupplementinng for several years but just recently have stopped and will reassess . after one month. While it has raised my taurine blood levels a little, i seem to have adapted after tge first year and initial big improvements in urinr levels of taurinre, beta alanine and anserine vanished. Then from the taurine, i have started losing cysteine in my urine and levels have gotten too low in my blood- cant be a good thing i don’t think. And then do not know if the taurinrme is cause but i am not conjugating taurine with bile acids- not a good thing.
Taurine had no effectvon my blood pressure or glucose level.
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No, the issue rather is that the conversion is not much delayed compared to lifestyle interventions. Diet + exercise did much better in head to head comparison to metformin. D+E had lower A1c outcomes and took longer to get to DMT2 compared to metformin.
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well, yes, of course, I mean, why would anybody opt against good diet and exercise? Surely nobody here, when comparing drugs like empa versus metformin, needs to be reminded to exercise.
Anyways, your example is interesting, as metformin did not help you although it looks like, as you wrote yourself, that it is your liver that is the main factor. BTW, I clearly feel the impact of metformin on exercise, but go along with the research results on that the outcome is actually equal strength with more efficient muscles.
Yes, but I think the idea is that those two interventions are not necessarily additive. Because say you are doing D+E, and now you add MET. Well, the if addition of MET suddenly degrades the effectiveness of exercise, then you are now no longer having effective D+E. Also, even if the muscles are not worse off with MET (which is highly speculative), certainly aerobic benefits are degraded and the insulin sensitivity benefits of exercise are similarly degraded. At which point, you would like in preference want first D+E as the most effective, and use MET only as a monotherapy, i.e. without exercise (which to be fair, most people would default to).
The observations of efficient muscles with Ex+Met are not “highly speculative”, however, regarding insuline sensitivity, I am not so sure. If it is similar to the issue of less muscle build, I will continue with 250mg before meals (max 2/d), because I am clearly building sufficient muscle on it.
“use MET only as a monotherapy, i.e. without exercise (which to be fair, most people would default to)”
??? Clearly, exercise does no harm when taking metformin. Metformin makes resistance training more difficult, but so is putting on more weight on the barbells! We do not tell people to reduce the weight they lift because it makes the exercise easier. And that is how I see the added difficulty by metformin, namely increasing the resistance (like more weight) but with the additional benifit of more efficient rather than merely bigger muscles.
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Sorry to jump into the middle of your conversation but this “metformin is bad for exercise adaptation” has gotten accepted as a fundamental truth a bit prematurely. The guy who got metformin approved by the FDA says that metformin only has effects on the liver. He said, “no molecule of metformin ever got into a muscle”. (He was a recent guest on Attia’s podcast).
Now, I don’t know about you but to me that makes me think, “then how can metformin have detrimental effects on exercise adaptation?” I no longer worry about it. I take metformin a few days every 2 weeks around my rapa dose.
Any ideas?
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ChatGPT does not agree
Metformin is a widely used drug for type 2 diabetes, and it distributes into various tissues in the body, but not all equally. Here’s a breakdown of where metformin can go:
Tissues Metformin Can Get Into:
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Liver: Major target tissue – metformin suppresses glucose production here.
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Intestines: High concentrations accumulate in the gut; may play a role in its glucose-lowering effects.
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Kidneys: Metformin is excreted unchanged through the kidneys, so it accumulates here too.
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Muscle: Enters skeletal muscle where it increases glucose uptake.
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Adipose (fat) tissue: Can enter, though effects here are less well understood.
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Heart: Some evidence it reaches cardiac tissue.
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Mitochondria (within cells): Especially in the liver and muscle cells; it inhibits mitochondrial complex I, affecting energy metabolism.
Tissues Metformin Doesn’t Penetrate Well:
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Brain/Central Nervous System: Very limited penetration due to the blood-brain barrier.
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Fatty tissues: While it can enter, the uptake is relatively lower compared to more perfused tissues like the liver or kidney.
Its uptake into cells often depends on organic cation transporters (OCTs) – proteins that actively move metformin into tissues.
Metformin itself does not need to get into muscle or any other tissue to have an effect. Metformin most certainly impacts muscle and other tissues.
Metformin induces muscle atrophy by transcriptional regulation of myostatin via HDAC6 and FoxO3a
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Also, just to make clear, I am not urging anyone to not use metformin for any reason. Metformin has been cleared by the FDA, and if your physician prescribes it, you should follow your physician’s advice. I am not a doctor and I don’t offer medical advice.
I am explaining why I personally don’t take metformin at this time, and have no plans to do so, unless compelling research comes out that changes my mind.
As I understand it, the evidence is that metformin negatively affects exercise adaptations, and this is one of the reasons why I don’t want to take it. However if you see benefits, I am very happy for you. YMMV.
Thanks. I cannot understand what they did in your referenced study. It looks like only a portion was done in a live animal (vs. in a dish). And the part they did “in vivo” is hard to understand how the metformin got into the tissues that were tested.
This could all be true but if Ralph DeFronzo PhD, the guy who got metformin approved by the FDA is correct, metformin does not get into muscle of human beings. Any effects are occurring in liver (and maybe kidney, I can’t remember exactly)
That said I don’t know that means metformin doesn’t affect exercise adaptation, it just means it isn’t happening in the muscle. Perhaps the higher lactate (from the liver) is causing a stress signal that is too much…or some such indirect effect. Or, in my experience, metformin made hard exercise feel harder, which lowered how hard I could go, which no doubt lowered my adaptation to exercise because I didn’t exercise as hard.
But don’t worry. I’m not seeking your approval to take metformin. I’m just sharing potentially useful information for people to consider in their calculus.
Here’s the podcast in case you are interested.
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I am puzzled (and should be given I am not a scientist), but does it matter that metformin doesn’t get into the muscle to explain metformin’s impact on exercise adaptation?
According to the following: Reczek, Colleen R., et al. "Metformin targets mitochondrial complex I to lower blood glucose levels." Science Advances 10.51 (2024): eads5466.
Metformin is a cost-effective oral medication generally administered twice daily to humans to reduce blood glucose levels. The molecular mechanisms by which acute metformin administration lowers blood glucose are not fully understood
Our data illustrate the necessity of mitochondrial complex I inhibition for the blood glucose–lowering effects of metformin
Any other glucose inhibitor discussed in the video such as SGLT1 or SGLT2, or not discussed like acabose would seem superior given the drawbacks to the holistic mitochondria inhibition. This same researcher in the video has published papers on acabose so I am puzzled (again) why he even mentions metformin other that for all practical purposes it is free. Too many drawbacks to it use, at least for active people.
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TAURINE DIURETIC AND RENAL-REVITALIZING EFFECTS IN NONAGENARIANS
https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/j.1532-5415.2010.03207.x
"Long-term oral taurine (OT 3 g/d) ameliorates CHF,1 so it was desired to determine whether OT (1.0 g three times per day) relieves edema without causing hypotension in nonagenarians. Forty-nine residents of an extended-care nursing home (20 taking antihypertensive therapy) who developed edema (score ≥2, Appendix A) despite hospital-prescribed diuretics or excessive hypotension precluding effective diuretic usage were enrolled from March 1, 2007, to March 31, 2010.
The remarkable effects of OT on edema were apparent within the first month of treatment (Figure 1A); decreases in body weight occurred with some delay. Required doses of diuretics decreased after institution of OT in the majority of residents. Serum albumin levels increased in 32 hypoalbuminemic residents"
“Taurine is one of the major organic osmolytes that cells use to compensate for changes in extracellular osmolality to maintain cell volume. In the supraoptic nucleus of the hypothalamus, taurine is highly concentrated in astrocytes, and released in an osmo-dependent manner under hypoosmotic conditions.4 OT will increase interstitial fluid [taurine] that, acting through its agonist action on neuronal glycine receptors, will amplify the inhibition of the release of vasopressin and oxytocin that occurs physiologically only when hypoosmotic,4promoting diuresis independent from osmolality. The findings of the current study suggest that inadequate antidiuretic hormone secretion plays a major role in older adults. The improved hypoalbuminemia (Figure 1B) and OT-induced inhibition of vasopressin and oxytocin allowed greater diuresis with minimal Na+ involvement, thus not causing hypotension.”
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Owen, thanks for your helpful post. Now that you have upped dosage to 5.5g, do you take that in divided doses? When during the day do you take Taurine? Do you take it with food or empty stomach?
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RapaW
#72
A downside of taurine: It drives leukemia growth
Just saw this, not directly related to longevity but worth noting.
A downside of taurine: It drives leukemia growth | ScienceDaily
Original paper: 1. Sonali Sharma, Benjamin J. Rodems, Cameron D. Baker, Christina M. Kaszuba, Edgardo I. Franco, Bradley R. Smith, Takashi Ito, Kyle Swovick, Kevin Welle, Yi Zhang, Philip Rock, Francisco A. Chaves, Sina Ghaemmaghami, Laura M. Calvi, Archan Ganguly, W. Richard Burack, Michael W. Becker, Jane L. Liesveld, Paul S. Brookes, Joshua C. Munger, Craig T. Jordan, John M. Ashton, Jeevisha Bajaj. Taurine from tumour niche drives glycolysis to promote leukaemogenesis. Nature, 2025; DOI: 10.1038/s41586-025-09018-7
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New research in Nature (14 May 2025) shows that acute myeloid leukaemia and blast-crisis CML stem cells over-express the taurine transporter SLC6A6 (TAUT), siphon taurine from the bone-marrow niche, activate mTOR-driven glycolysis, and accelerate disease; deleting taurine synthesis or blocking TAUT slows these cancers and lengthens survival in mouse and patient-derived models.
Taurine itself is still FDA-GRAS and non-mutagenic, so it probably doesn’t initiate cancer - but for TAUT-positive clones it functions as high-octane fuel. This explains why taurine extended lifespan in healthy mice without increasing their usual lymphomas: those tumours don’t depend on TAUT. For us, ordinary dietary doses remain low-risk, yet gram-level self-experiments deserve caution, particularly if you carry clonal haematopoiesis, odd blood counts, or a past marrow malignancy.
Taurine’s longevity promise survives, but context now matters - make sure you know which engine you’re fueling.
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jnorm
#74
Worth mentioning that taurine levels in the bone marrow/BM interstitial fluid were 5,000ng/mL (rising 1.7-fold in leukemia), which is much lower than serum levels in mice. For example, in Taurine deficiency as a driver of aging they were shown to peak at 100-150ng/mL in early life, falling to ~50ng/mL by 55 weeks old.
We know that a causatively significant portion of taurine in the BM niche/microenvironment is paracrine-derived, since cysteine dioxygenase type 1/CDO1-inhibition in osteolineage cells could attenuate leukemia growth. Additionally, the 100-fold concentration gradient (using a serum value of 50 since most acute myeloid leukemias/AMLs arise in late life) suggests that supplementation wouldn’t significantly affect niche levels.
One study in humans showed 1.5g taurine/day for 2 weeks could increase serum levels by 50%, but this wouldn’t be expected to raise niche levels much, as the concentration gradient opposing net diffusion into the BME would still be massive. It’s also unclear how taurine would enter the BME, if at all. ChatGPT suggests non-specific anion channels (e.g pannexins) and facilitated diffusion via a hypothetical taurine uniporter as possibilities, but both of these would promote taurine efflux from the BME due to the concentration gradient. TauT wouldn’t reverse at these concentrations either, so even if it was expressed on the basolateral endothelium, it would also promote taurine efflux from the BME.
Overall, I think it’s unlikely taurine supplementation would significantly impact BME levels, at least not directly. Also, taurine’s sulfur is in the fully oxidized sulfonic acid (-SO3H) state, and this oxidation is irreversible in humans, so taurine won’t directly increase cysteine levels either.
One thing this paper does do is provide further support for diets low in sulfur-containing amino acids like cysteine and methionine. AML is rare enough that the lifespan increase from methionine restriction probably isn’t mediated via a reduction in AML risk, but a potential reduction in AML risk would be a nice secondary benefit nonetheless.
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Thiago
#76
Hi everyone,
I’m a healthy 40-ish-year-old experimenting with taurine for general cardiometabolic and longevity benefits. I’m trying to decide between:
Split dosing: 2 g with breakfast, 2 g with lunch, 2 g before bed (total = 6 g/day)
Single bolus: taking the full dose at once to hit a high plasma peak
From what I’ve read, oral taurine peaks ~1–2 h after ingestion, the half-life is ~1 h, and levels drop back to baseline in ~6 h. That makes me wonder whether a steadier exposure (higher AUC) is more useful than chasing a short-lived spike.
Questions
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Has anyone here compared split vs single-dose taurine in practice or seen data on which gives better real-world benefits (BP, exercise performance, sleep, etc.)?
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Does a higher peak confer any unique advantage, or is it mostly wasted because the kidneys dump the excess?
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Any side-effects you noticed when moving from 3–4 g/day up to 6 g/day?
All insights, anecdotes, and links to papers are welcome—thanks!
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