How long does the supplemented creatine take to break down?
Reading the article I would have imagined it only last those 10 seconds before it gets used up, but that cannot be true since supplementation would be practically challenging.
Does it get stashed away somewhere outside of the cells?
During those 10 seconds, creatine isn't used up; it's just that a phosphate group is removed from it (converting phosphocreatine to regular creatine). I think it's generally understood that you lose a small percentage of your total creatine per day, though the pharmacokinetics are still an issue of some debate AFAICT.
Banger of a post, although I echo the others in that I'm surprised you didn't look at impacts when sleep deprived. Which alone is a pretty strong argument for keeping it around, on top of the significant strength and workout gains.
My favorite go-to's for "thinking hard does not make you burn calories" are:
They have studied chess masters in the middle of competitive matches, and the incremental calorie burn is only ~4 calories more per hour:
N. Troubat et al, "The stress of chess players as a model to study the effects of psychological stimuli on physiological responses" (2009)
Also, high IQ may actually point you the other direction in terms of calorie burn - this one looked at people doing memory problems, and found that poor performers spent 4.5x more calories than people who perform well on mental problems! (if you proxy by VO2, VO2 in low performers went up 22 ml/min vs 5 in high performers, both of these are tiny btw, over an hour it would be 6.6 cals and 1.5 cals respectively)
R.W. Blacks and K.A. Seljos, Metabolic and cardiorespiratory measures of mental effort... (1994)
Is there any evidence for increased creatine causing increased rates of musculoskeletal injury? All else being equal, being able to do 5-15% more work seems like it would put extra strain on ligaments, tendons, and the muscle cells you already have.
Not that this would make a huge difference to the average person that does max exertion once in a blue moon.
Thank you for all this research! Have you seen anything about a link between creatine and prostate cancer? I’ve had some FUD about this, and wonder if it’s related to the (dubious?) testosterone linkage?
I didn't stumble across anything like that. To the best of my knowledge, creatine is almost universally considered safe (or at least to have ~zero known downsides)
I really enjoyed this essay and feel I have something to add since you mentioned the "trouble" of taking daily creatine: based on everything I have been able to find, there's minimal downside to putting your creatine in the hot beverage you probably drink every morning. I've been putting a scoop into my first hot drink of the day for a while now and haven't noticed a difference in taste or texture.
Creatine is a protein, and the temperature of a hot drink and the amount of time the creatine is in it for before being consumed (<15 minutes) mean there is minimal protein breakdown (since, after all, people don't lose their mind about protein/creatine loss for braising, grilling, pressure cooking, smoking, or otherwise cooking meat for a long time or at a high temperature).
and https://www.nature.com/articles/s41598-024-54249-9, showing that single-dose creatine significantly improves cognitive performance in subjects exposed to 21 hours sleep deprivation compared to placebo (n = 15)
"Say you think there’s a 50% chance creatine increases IQ by 1 point and a 50% chance it’s useless. Is it actually worth the trouble of taking 5 grams of creatine every day for an expected increase of 0.5 IQ points? I’m not sure."
But don't the clear strength benefits justify basically anyone taking creatine, and if there are marginal cognitive benefits on top, then great?
That's a totally reasonable view. I just don't want to make any assumptions about anyone else's values! (I'd imagine that only a minority of the population regularly do any activities where creatine would make much difference?)
I was writing this comment with the median reader of your blog in mind, who, presumably, engages in some form of strength training if they’re interested in health optimization enough to read essays like this one
Just to weigh in: after creatine supplementation my ability to concentrate greatly increases. 5 g provides a small boost; at around 20 g I feel much more energetic. The effect is noticeable around 30 minutes after a single 5 g dose. On days when I don't supplement creatine, I have noticeable brain fog.
This doesn't rule out a placebo. And I don't have any evidence that creatine improves my cognitive performance other than my reported internal states. Still, I think the effect is real. Creatine makes me feel better.
As a side note, I'm likely not neurotypical. My ability to focus has always been very poor. I wonder if creatine improves attentiveness in those with ADHD?
Very interesting. There are several theories of dementia that have to do with energy failing to reach neurons. Here's hoping someone tries to inject creatine past the BBB.
Just sharing a mechanistic hypothesis for you to consider as to why some report cognitive benefits, I don't have any interesting data beyond what you already shared.
Have you evaluated the use of large single doses of Creatine in cases of sleep deprivation? Even if modest continued supplementation doesn’t yield extra cognitive benefits— being able to mega-dose away some of the cognitive loss from lack of sleep seems hugely valuable (especially given that creatine is far easier to get than Modafinil).
Anecdotally, the megadoses have helped me when sleep deprived.
Also— anectdotally, ~10-15g per day continued supplementation I notice no particular increases in my processing abilities, but i do seem to have more sustained cognitive energy. I can work on hard-ish things seemingly far longer before my brain burns out.
Either way, it also makes working out easier and more intensive— so that probably also has an indirect advantage to boosting cognitive benefits if you can do better HIIT.
Or or or, it is simply that I remember to supplement creatine only when I am in a hypomanic and already energized state, which with me atleast, is the very likely cause.
I'm not aware of any experiments that tested anything like that, so I can only speculate. Mechanistically, you could argue that a large one-off dose might work better for the brain because it won't have time to downregulate cerebral production of creatine. On the other hand, transport between the body and brain seems quite limited. Regarding if it gives you the ability to work longer, I suppose it's possible, but the problem is that thinking hard just doesn't change energy usage to any significant degree. (And that the analogy to exercise isn't promising; creatine doesn't help (much) with endurance exercise.)
I suspect there's just not much we can say with confidence, just because we don't understand the mechanisms to say much with confidence and because (AFAIK) there are no long-term RCTs: There actually *are* a bunch of creatine RCTs that ran for 1-2 years, but they all seem to be in older adults from the general population, not weight lifters.
I've been running some self-experiments that use my own reaction time as a proxy for cognitive function, following a protocol developed by the late psychologist Seth Roberts. As a long-time vegan, I take in very little dietary creatine, so I expected creatine monohydrate to give me a noticeable boost in processing speed. It didn't. Supplementing had no measurable effect on my speed.
The graph below captures the result. Lower values are better, since they represent faster reaction times:
The same graph shows an earlier finding that surprised me: metformin made me faster. I don't have a full write-up of the creatine experiment yet, but I wanted to share the data here.
If anyone is interested in collaborating on this kind of work, I'd be glad to hear from you. There's a contact email on the site. These projects tend to be more fun and productive with more than one person involved.
Great article, thanks!
How long does the supplemented creatine take to break down?
Reading the article I would have imagined it only last those 10 seconds before it gets used up, but that cannot be true since supplementation would be practically challenging.
Does it get stashed away somewhere outside of the cells?
During those 10 seconds, creatine isn't used up; it's just that a phosphate group is removed from it (converting phosphocreatine to regular creatine). I think it's generally understood that you lose a small percentage of your total creatine per day, though the pharmacokinetics are still an issue of some debate AFAICT.
Banger of a post, although I echo the others in that I'm surprised you didn't look at impacts when sleep deprived. Which alone is a pretty strong argument for keeping it around, on top of the significant strength and workout gains.
My favorite go-to's for "thinking hard does not make you burn calories" are:
They have studied chess masters in the middle of competitive matches, and the incremental calorie burn is only ~4 calories more per hour:
N. Troubat et al, "The stress of chess players as a model to study the effects of psychological stimuli on physiological responses" (2009)
https://www.researchgate.net/publication/23455094_The_stress_of_chess_players_as_a_model_to_study_the_effects_of_psychological_stimuli_on_physiological_responses_An_example_of_substrate_oxidation_and_heart_rate_variability_in_man
Also, high IQ may actually point you the other direction in terms of calorie burn - this one looked at people doing memory problems, and found that poor performers spent 4.5x more calories than people who perform well on mental problems! (if you proxy by VO2, VO2 in low performers went up 22 ml/min vs 5 in high performers, both of these are tiny btw, over an hour it would be 6.6 cals and 1.5 cals respectively)
R.W. Blacks and K.A. Seljos, Metabolic and cardiorespiratory measures of mental effort... (1994)
https://psycnet.apa.org/record/1994-36481-001
Is there any evidence for increased creatine causing increased rates of musculoskeletal injury? All else being equal, being able to do 5-15% more work seems like it would put extra strain on ligaments, tendons, and the muscle cells you already have.
Not that this would make a huge difference to the average person that does max exertion once in a blue moon.
The (57) Does creatine make angle is underrated. Most commentary only sees the surface version.
Thank you for all this research! Have you seen anything about a link between creatine and prostate cancer? I’ve had some FUD about this, and wonder if it’s related to the (dubious?) testosterone linkage?
I didn't stumble across anything like that. To the best of my knowledge, creatine is almost universally considered safe (or at least to have ~zero known downsides)
The best! Thanks for the write-up :)
I really enjoyed this essay and feel I have something to add since you mentioned the "trouble" of taking daily creatine: based on everything I have been able to find, there's minimal downside to putting your creatine in the hot beverage you probably drink every morning. I've been putting a scoop into my first hot drink of the day for a while now and haven't noticed a difference in taste or texture.
Creatine is a protein, and the temperature of a hot drink and the amount of time the creatine is in it for before being consumed (<15 minutes) mean there is minimal protein breakdown (since, after all, people don't lose their mind about protein/creatine loss for braising, grilling, pressure cooking, smoking, or otherwise cooking meat for a long time or at a high temperature).
Its fine to put in hot stuff and this helps it dissolve nicely, but creatine is not a protein
You’ve got me here at 11pm bolting upright so I can drink some creatine and then reading further and lying back down then rinse and repeat…
Perhaps the purported effect is secondary to improved psychiatric health?
https://www.psychiatrypodcast.com/psychiatry-psychotherapy-podcast/episode-238-creatine-mental-health-benefits
Two studies to highlight:
https://doi.org/10.1523/JNEUROSCI.3113-14.2015, showing that ~20g/day creatine preserves cognitive performance after artificial hypoxia compared to placebo (n = 15)
and https://www.nature.com/articles/s41598-024-54249-9, showing that single-dose creatine significantly improves cognitive performance in subjects exposed to 21 hours sleep deprivation compared to placebo (n = 15)
"Say you think there’s a 50% chance creatine increases IQ by 1 point and a 50% chance it’s useless. Is it actually worth the trouble of taking 5 grams of creatine every day for an expected increase of 0.5 IQ points? I’m not sure."
But don't the clear strength benefits justify basically anyone taking creatine, and if there are marginal cognitive benefits on top, then great?
That's a totally reasonable view. I just don't want to make any assumptions about anyone else's values! (I'd imagine that only a minority of the population regularly do any activities where creatine would make much difference?)
I was writing this comment with the median reader of your blog in mind, who, presumably, engages in some form of strength training if they’re interested in health optimization enough to read essays like this one
Just to weigh in: after creatine supplementation my ability to concentrate greatly increases. 5 g provides a small boost; at around 20 g I feel much more energetic. The effect is noticeable around 30 minutes after a single 5 g dose. On days when I don't supplement creatine, I have noticeable brain fog.
This doesn't rule out a placebo. And I don't have any evidence that creatine improves my cognitive performance other than my reported internal states. Still, I think the effect is real. Creatine makes me feel better.
As a side note, I'm likely not neurotypical. My ability to focus has always been very poor. I wonder if creatine improves attentiveness in those with ADHD?
Very interesting. There are several theories of dementia that have to do with energy failing to reach neurons. Here's hoping someone tries to inject creatine past the BBB.
https://splittinginfinity.substack.com/p/links-33
Supplementing creatine spares under-methylated people 50% of their daily SAMe that would normally be spent on endogenous creatine synthesis.
Which is why it works so well to improve energy/cognitive performance on the elderly and sleep deprived (both groups are methyl constrained).
And on me!
I have MTHFR T/T homozygous genes which makes me methylfolate production run at 30% of that of a normal person.
Fwiw when reading about mtfhr on reddit this opinion seems fairly common. So at least it's an N=4 echo chamber situation.
(5mg doesn't seem to make a big difference for my G/G variant. Didn't try 30mg.
What's your evidence that it works well on the elderly, sleep deprived, or yourself?
Just sharing a mechanistic hypothesis for you to consider as to why some report cognitive benefits, I don't have any interesting data beyond what you already shared.
OK, fair enough!
Have you evaluated the use of large single doses of Creatine in cases of sleep deprivation? Even if modest continued supplementation doesn’t yield extra cognitive benefits— being able to mega-dose away some of the cognitive loss from lack of sleep seems hugely valuable (especially given that creatine is far easier to get than Modafinil).
Anecdotally, the megadoses have helped me when sleep deprived.
Also— anectdotally, ~10-15g per day continued supplementation I notice no particular increases in my processing abilities, but i do seem to have more sustained cognitive energy. I can work on hard-ish things seemingly far longer before my brain burns out.
Either way, it also makes working out easier and more intensive— so that probably also has an indirect advantage to boosting cognitive benefits if you can do better HIIT.
Or or or, it is simply that I remember to supplement creatine only when I am in a hypomanic and already energized state, which with me atleast, is the very likely cause.
I'm not aware of any experiments that tested anything like that, so I can only speculate. Mechanistically, you could argue that a large one-off dose might work better for the brain because it won't have time to downregulate cerebral production of creatine. On the other hand, transport between the body and brain seems quite limited. Regarding if it gives you the ability to work longer, I suppose it's possible, but the problem is that thinking hard just doesn't change energy usage to any significant degree. (And that the analogy to exercise isn't promising; creatine doesn't help (much) with endurance exercise.)
https://www.nature.com/articles/s41598-024-54249-9
Study i read. Was convincing enough to me…
Interesting, thank you! I'd be interested too in differences between people that take creatine and people that don't, in the long term, for lifting.
I suspect there's just not much we can say with confidence, just because we don't understand the mechanisms to say much with confidence and because (AFAIK) there are no long-term RCTs: There actually *are* a bunch of creatine RCTs that ran for 1-2 years, but they all seem to be in older adults from the general population, not weight lifters.
I've been running some self-experiments that use my own reaction time as a proxy for cognitive function, following a protocol developed by the late psychologist Seth Roberts. As a long-time vegan, I take in very little dietary creatine, so I expected creatine monohydrate to give me a noticeable boost in processing speed. It didn't. Supplementing had no measurable effect on my speed.
The graph below captures the result. Lower values are better, since they represent faster reaction times:
https://www.self-experiments.org/wp-content/uploads/2026/07/metformin-creatine-graph-1.png
The same graph shows an earlier finding that surprised me: metformin made me faster. I don't have a full write-up of the creatine experiment yet, but I wanted to share the data here.
I love it when people run personal experiments like this. I aspire to be this type of person some day.
Ack, several times when writing this post I thought to myself that I should mention your results. My apologies for forgetting!
You can find my other self-experiments here: https://www.self-experiments.org/
If anyone is interested in collaborating on this kind of work, I'd be glad to hear from you. There's a contact email on the site. These projects tend to be more fun and productive with more than one person involved.