Creatine is doing quieter work than the muscle it is famous for

Metabolic series, part two. Part one showed that the fate of a carbohydrate is decided by the state of the body receiving it; this one looks at a molecule whose job is to buy time inside the cell, before part three asks why energy can be missing while the labs read normal.

“Should I take creatine?” is the question I get more than any other, and I’ve stopped answering it straight.

Not out of caution. The honest answer turns on a number nobody in the conversation has, me included.

Here is how it looks like. Creatine adds no fuel like the way a carbohydrate adds fuel, and it doesn’t make fibres pull harder. What it does is hold your ATP concentration steady across the short window where you’re spending ATP faster than you can remake it. That window opens early in any hard exertion. It’s why the fourth heavy set feels like a different exercise from the first.

So, the narrow claim: the effect you can rely on lands on repeatable work rather than on peak output. That’s not a claim about potency. Plenty of people take it and notice nothing at all, and they aren’t doing it wrong.

This is an educational and strategic perspective, not personal medical advice. The views are the author’s own and not statements by Atlas Cove Lda.

Your muscle carries almost none of the molecule it spends.

Cytosolic ATP sits at around three to six millimolar depending on the cell type. The phosphocreatine pool beside it runs as high as thirty. That imbalance is deliberate (Wallimann et al., 2011).

Creatine kinase works the exchange both ways. Wherever ATP is being burned it strips a phosphate off phosphocreatine and hands it to spent ADP, and near the mitochondria, where ATP gets made, it runs the same reaction backwards. Wallimann and colleagues describe the result as a buffer doing two jobs at once, holding the ATP concentration steady across seconds and also shuttling high-energy phosphate between the places it’s produced and the places it’s needed.

Phosphocreatine gets spent so ATP doesn’t have to fall. That’s how a muscle goes straight into near-maximal output without every enzyme that assumes stable ATP falling over in the first second.

What the arrangement can’t do is last. The pool drains fast under real load, and once it’s low you’re running on slower machinery that brings its own costs. That’s the part of a set which stops feeling like the start of it.

If the buffer is what empties, the interesting question is how quickly it refills.

Greenhaff and colleagues went at that directly in 1994. Eight men, twenty grams of creatine a day for five days, then biopsies of the vastus lateralis at rest and at twenty, sixty and a hundred and twenty seconds into recovery from a single intense electrically evoked isometric contraction (Greenhaff et al., 1994).

Five of the eight raised total muscle creatine by about a quarter. In those five, and only in those five, phosphocreatine refilling across the second minute improved by roughly thirty-five percent. The other three gained five to seven percent and got nothing measurable.

Three things about that study should travel with the number. The effect sat in the second minute rather than the first, which points at the slower phase of refilling. The contraction was evoked electrically, so this is cleaner physiology than it is sport. And there was no placebo arm, with the supplemented trial always run second, which is the sort of detail that should make you hold the figure loosely and the mechanism firmly.

A molecule working on the gap between efforts isn’t working on the effort. Nearly everything else follows from that. It won’t add weight to your one-rep max in any way you’d notice. It might bring your fifth set closer to your first.

Muscle creatine gets measured in millimoles per kilogram of dry muscle, and untrained men sit somewhere near a hundred and twenty.

Hultman and colleagues ran thirty-one men through four intake schedules, with results tidier than nutrition research usually manages (Hultman et al., 1996). Six days at twenty grams a day lifted total creatine by about twenty percent, roughly twenty-three millimoles per kilo of dry mass. Two grams a day after that held the level flat for four more weeks. The group that stopped was back at baseline by day thirty-five. A separate group took three grams a day with no loading phase at all and landed in the same place by day twenty-eight.

So the loading week is optional. It buys you three weeks.

Read all of that as a record of what a trial gave people, never as a prescription. The shape matters more than the schedule: there’s a ceiling, most of us start fairly close to it, and the gap that’s left decides whether anything happens.

Which is where diet walks in, since you get creatine out of meat and fish as well as making your own. Burke and colleagues found vegetarians at roughly 117 millimoles per kilo of dry mass where non-vegetarians sat at 130, and the vegetarians on creatine gained more muscle creatine than any other arm of the trial (Burke et al., 2003). Across the whole sample, the size of the gain ran inversely to where people started, at r equals minus 0.77.

Put that beside Greenhaff’s five and three and the inconsistency stops being mysterious. I eat meat most days and I lift three times a week, so my own headroom was probably small. No complaint there. It’s the molecule doing precisely what the papers say it does.

What connects a fuller phosphocreatine pool to a bigger, stronger muscle is disappointingly ordinary, and it’s worth stating plainly, because the flashier explanations get more airtime than they’ve earned.

More buffer lets you tolerate slightly more training volume. More volume is more mechanical stimulus, and more stimulus is more adaptation. The compound builds nothing itself. It makes the building cheaper.

Chilibeck and colleagues pooled twenty-two trials covering seven hundred and twenty-one participants, all of them drawn out of studies with a mean age of fifty or above, resistance training two or three times a week for anywhere between seven and fifty-two weeks. Creatine alongside training gave a mean difference of 1.37 kg of lean tissue over training alone, confidence interval 0.97 to 1.76, with standardised mean differences of 0.35 for chest press and 0.24 for leg press (Chilibeck et al., 2017).

Now the figure that should actually shape what you expect. Ten of those twenty-two trials found no creatine effect at all. A pooled estimate describes a population. You’re one person carrying an unknown amount of room.

There’s a second explanation in circulation that I treat more carefully than most people seem to. Creatine is osmotically active, it pulls water into the cell, and cell swelling has been put forward as an anabolic signal in its own right. Reasonable idea. Awkward measurement problem, though: intracellular water counts toward lean tissue mass on a DXA scan, so a trial reporting extra lean tissue can’t cleanly separate contractile protein out of fluid. Burke’s correlation of 0.61 between the creatine gain and the lean tissue gain, plus 2.4 kg against 1.9 kg in the two supplemented arms, fits real hypertrophy and fits hydration equally well. I’d call it unsettled, and I’d be glad to be shown otherwise.

Neurons run the same creatine kinase system and meet demand spikes that outrun oxidative supply for the reasons muscle does. Getting the creatine in there is the problem.

Roschel and colleagues put the brain rise at roughly five to ten percent under supplementation, about half what muscle manages, with the protocol that would reliably move it still undetermined, and at least one study measuring both tissues found muscle up and brain unchanged (Roschel et al., 2021).

What that rise does splits along one line, and the line is strain.

McMorris and colleagues gave nineteen people creatine or placebo for seven days, then kept them awake for twenty-four hours with light exercise scattered through it. The creatine group fell off less on random movement generation, choice reaction time, static balance and mood. Verbal and spatial recall showed nothing. Neither did plasma catecholamines or cortisol (McMorris et al., 2006).

That’s a smaller loss under load, and it isn’t a gain in a rested person. The difference matters more than the marketing lets on, because trials in rested, well-slept adults come back inconsistent, and Roschel’s review declines to conclude anything firm about them.

One appealing bridge collapses when you look at it properly. The best-known cognitive trial recruited only vegetarians and vegans, chosen precisely because their baseline sits low, and Roschel’s review notes both that a comparable trial in meat eaters found nothing and that brain creatine looks similar in vegetarians and omnivores anyway. The diet argument that works downstairs doesn’t obviously work upstairs. I’d rather say so than let two findings lend each other weight neither has earned.

This one shows up in a doctor’s office instead of a gym, and it’s the part I’d most want you to have read.

Creatinine, the marker routine panels use to stand in for kidney function, is what creatine breaks down into. So its concentration reports on your muscle mass and on your dinner as well as on your filtration. Antonio and colleagues note that supplementation and a meat-heavy diet can both raise blood and urinary creatinine, and that rises arriving that way are unlikely to mean your kidneys are failing (Antonio et al., 2021).

The pattern across the studies they gather isn’t uniform. Twelve found no rise at all. Eight found a rise that stayed inside the reference range. Two went past the normal limit.

A number that moves for a non-pathological reason still needs explaining rather than dismissing. If a panel comes back with a raised creatinine or a dropped eGFR, tell the clinician what you’re taking and how much meat you eat, so the value gets read properly instead of argued about. None of that replaces a clinical judgement about your own kidneys, and anyone with existing renal disease is in a different conversation entirely.

Almost nothing in a supplement cupboard can be tested by the person who bought it. Creatine can, because the mechanism predicts something specific enough to watch for.

What it predicts is a smaller gap between your first set and your last.

So write down the reps you get at a fixed load across three or four sets. Do it this week, then do it again in twelve. If the drop-off hasn’t narrowed and nothing else in your training changed, whatever room you had was small, and this particular lever belongs to somebody else.

Here’s my confession. I took creatine for years and never once ran that test. I stopped during one Ironman build because nothing in the endurance log had moved, which was a daft reason, since an endurance log records pace and heart rate and volume and none of those are quantities a phosphocreatine buffer touches. The one thing it plausibly affected was the quality of my last set in the gym. That was the session I’d already decided was optional.

There’s an order to this, though, and it comes before any purchase. The benefit travels through training volume you can tolerate, so buffering a stimulus you aren’t applying buffers nothing. The strength work that part two of the applied physiology series called the highest-return hour in a crowded week comes first. A compound that makes it marginally more repeatable comes after. Get the order wrong and the supplement question turns unanswerable, which is roughly why it never gets answered.

Supplements are worth something at the margins and worth nothing underneath. That’s my position, and creatine hasn’t shifted it. What creatine does have going for it is that it’s cheap, heavily studied, and unusually honest about its own limits once you read past the label.

An Atlas Cove week starts by measuring the things a later decision has to rest on, rather than handing anyone a list of what to take. Whether a molecule like this does anything for you turns on your headroom, your diet, your training and what your bloods already say. A shelf category answers none of that.

The Atlas Cove Method

The loudest version of a supplement’s story almost never matches the version the physiology will carry. Here the supported version is small: a buffer that shortens the refill between hard efforts, in the people who had room for it, which shows up as slightly more tolerable volume and eventually as slightly more muscle and slightly more strength, with a brain case that’s real under strain and unresolved at rest.

Small, and better evidenced than most of what sits beside it on that shelf. Whether any of it is true for you is a question your own notebook answers in twelve weeks, and nobody selling it to you can answer that at all.

This is an educational and strategic perspective, not personal medical advice. The views are the author's own and not statements by Atlas Cove Lda.

1. Wallimann, T., Tokarska-Schlattner, M., & Schlattner, U. (2011). The creatine kinase system and pleiotropic effects of creatine. Amino Acids, 40(5), 1271-1296. DOI: 10.1007/s00726-011-0877-3

2. Greenhaff, P. L., Bodin, K., Söderlund, K., & Hultman, E. (1994). Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. American Journal of Physiology, 266(5 Pt 1), E725-E730. DOI: 10.1152/ajpendo.1994.266.5.E725

3. Hultman, E., Söderlund, K., Timmons, J. A., Cederblad, G., & Greenhaff, P. L. (1996). Muscle creatine loading in men. Journal of Applied Physiology, 81(1), 232-237. DOI: 10.1152/jappl.1996.81.1.232

4. Burke, D. G., Chilibeck, P. D., Parise, G., Candow, D. G., Mahoney, D., & Tarnopolsky, M. (2003). Effect of creatine and weight training on muscle creatine and performance in vegetarians. Medicine & Science in Sports & Exercise, 35(11), 1946-1955. DOI: 10.1249/01.MSS.0000093614.17517.79

5. Chilibeck, P. D., Kaviani, M., Candow, D. G., & Zello, G. A. (2017). Effect of creatine supplementation during resistance training on lean tissue mass and muscular strength in older adults: a meta-analysis. Open Access Journal of Sports Medicine, 8, 213-226. DOI: 10.2147/OAJSM.S123529

6. Roschel, H., Gualano, B., Ostojic, S. M., & Rawson, E. S. (2021). Creatine supplementation and brain health. Nutrients, 13(2), 586. DOI: 10.3390/nu13020586

7. McMorris, T., Harris, R. C., Swain, J., Corbett, J., Collard, K., Dyson, R. J., Dye, L., Hodgson, C., & Draper, N. (2006). Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology, 185(1), 93-103. DOI: 10.1007/s00213-005-0269-z

8. Antonio, J., Candow, D. G., Forbes, S. C., Gualano, B., Jagim, A. R., Kreider, R. B., Rawson, E. S., Smith-Ryan, A. E., VanDusseldorp, T. A., Willoughby, D. S., & Ziegenfuss, T. N. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? Journal of the International Society of Sports Nutrition, 18(1), 13. DOI: 10.1186/s12970-021-00412-w