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Creatine monohydrate
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In one pass Creatine is one of the best-evidenced gym supplements.
Educational content, not medical advice — consult a clinician.
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Chapter 1
What creatine is
Creatine is one of the best-evidenced gym supplements. The body already has it, stored mostly in muscle, where it supplies fast energy for short bursts of effort.
Creatine (methylguanidinoacetic acid) is a small molecule derived from three amino acids; the liver, kidneys, and pancreas make it from arginine, glycine, and methionine.
It is not an essential nutrient, since you can live without eating it. But what the body makes covers only basic turnover (about 1 g a day), and the rest comes from red meat and fish (1-2 g a day).
The body holds about 120–140 g of creatine in total, 95% of it in skeletal muscle. About 2/3 of that is stored as phosphocreatine (PCr) and 1/3 is free creatine.
Creatine (methylguanidinoacetic acid) is a small molecule derived from three amino acids; the liver, kidneys, and pancreas make it from arginine, glycine, and methionine.
It is not an essential nutrient, since you can live without eating it. But what the body makes covers only basic turnover (about 1 g a day), and the rest comes from red meat and fish (1-2 g a day).
The body holds about 120–140 g of creatine in total, 95% of it in skeletal muscle. About 2/3 of that is stored as phosphocreatine (PCr) and 1/3 is free creatine.
Mechanism · Why extra creatine can still be stored
The key is an asymmetry: a normal diet (1–2 g a day) fills muscle stores only to 60–80% of saturation, leaving 20–40% of room.That is the physical reason supplementation works. It is not that the body lacks something; the tank can hold more, so you top it up.
A few common situations:
5 g a day for 4 weeks raises muscle PCr by about 20–30%, close to the saturation ceilingVegetarians start with PCr about 10–15% lower, so the change after supplementing is more obviousBeyond 5 g a day, the extra is excreted in urine and does not keep accumulating
This saturation model decides every aspect of how creatine is used: you are filling a tank, not taking an everyday nutritional supplement. Once it is full, 3–5 g a day keeps it there.
Chapter 2
How it recharges muscle energy
Creatine is muscle's fast backup battery. It stays charged at rest, and the moment you exert yourself it discharges, handing energy back to , the currency cells actually spend.
ATP is the energy cells spend directly, but the ATP stored in muscle lasts only about 2 seconds of maximal effort before it runs low. That is when phosphocreatine (PCr) steps in; its phosphate bond carries slightly more energy than ATP's. When ATP gives up a phosphate and becomes ADP, PCr immediately passes its own phosphate across, rebuilding ATP from ADP and turning back into plain creatine. The enzyme that catalyzes this step is (CK), and the whole transfer takes milliseconds.
PCr holds enough charge for about 8–12 seconds of maximal effort. This is the fastest of the body's three energy systems, the phosphagen system; the other two are glycolysis (about 30 seconds to 2 minutes) and aerobic oxidation (which can keep going).
ATP is the energy cells spend directly, but the ATP stored in muscle lasts only about 2 seconds of maximal effort before it runs low. That is when phosphocreatine (PCr) steps in; its phosphate bond carries slightly more energy than ATP's. When ATP gives up a phosphate and becomes ADP, PCr immediately passes its own phosphate across, rebuilding ATP from ADP and turning back into plain creatine. The enzyme that catalyzes this step is (CK), and the whole transfer takes milliseconds.
PCr holds enough charge for about 8–12 seconds of maximal effort. This is the fastest of the body's three energy systems, the phosphagen system; the other two are glycolysis (about 30 seconds to 2 minutes) and aerobic oxidation (which can keep going).
Mechanism · What a fuller store changes
Once muscle PCr rises by about 20%, several things improve at the same time:1. High-intensity output lasts longer: short bursts such as lifting, sprinting, and jumping hold their pace better through seconds 6–12. Branch 2003 pooled about 100 placebo-controlled trials and found effects that were small but significant, clearest in repeated laboratory strength tasks lasting 30 seconds or less and in upper-body movements; no benefit was seen for events like running or swimming
2. Faster recovery between sets: during the rest between sets, PCr is rebuilt by aerobic metabolism, and a bigger store refills more fully, so the next set holds up
3. Indirect muscle growth: creatine itself does not build protein, but the extra 1–2 reps or extra weight per set add up to a larger training stimulus, which shows after 8–12 weeks
4. Water drawn into cells: creatine carries water with it into muscle cells, total body water rises by 1–2 kg, and the cells swell; part of this is water inside the cells, but studies also see real growth in muscle-fiber cross-section
5. Antioxidant and anti-inflammatory effects: a few studies see slightly lower inflammation markers after hard training; the signal is weak
6. PCr in the brain rises too: this is the molecular starting point for the chapter on the brain (the brain also uses PCr to buffer )
Chapter 3
Which uses have the best evidence
Creatine is one of the few supplements whose main uses all have large numbers of , but the strength of evidence differs widely between uses, so they need to be looked at separately.
High certainty (several , plus the position stand of the International Society of Sports Nutrition, ISSN): performance in short, high-intensity bursts, muscle gain during strength training, and recovery between setsModerate (one meta-analysis or several randomized trials): older adults who add creatine to strength training gain somewhat more lean mass and strengthLow (small trials or mechanism only): long mental tasks, add-on treatment for depression, recovery after concussion, postpartum fatigue, muscular dystrophy, ALSAlmost no evidence: fat loss, anti-wrinkle, longevity
High certainty (several , plus the position stand of the International Society of Sports Nutrition, ISSN): performance in short, high-intensity bursts, muscle gain during strength training, and recovery between setsModerate (one meta-analysis or several randomized trials): older adults who add creatine to strength training gain somewhat more lean mass and strengthLow (small trials or mechanism only): long mental tasks, add-on treatment for depression, recovery after concussion, postpartum fatigue, muscular dystrophy, ALSAlmost no evidence: fat loss, anti-wrinkle, longevity
Evidence · What the ISSN position stand says
The International Society of Sports Nutrition (ISSN) 2017 position stand (Kreider and colleagues, JISSN) is the most widely cited current review of creatine.Its core position can be summarized in a few points (paraphrased):
> 1. Creatine monohydrate is the most effective nutritional supplement currently available to athletes for increasing high-intensity exercise capacity and lean body mass during training
> 2. Creatine monohydrate is not only safe but has been reported to have some therapeutic benefits in healthy and diseased populations from infants to the elderly; there is no compelling scientific evidence that short- or long-term use (up to 30 g a day for 5 years) harms healthy people or patients who may benefit
> 3. With proper precautions and supervision, creatine monohydrate is acceptable for child and adolescent athletes and may offer a safer nutritional alternative to dangerous anabolic steroids; but it is recommended only for young athletes in serious, supervised training who eat a balanced diet, understand correct use, and do not exceed recommended doses
> 4. Creatine monohydrate is the most studied and most clinically effective form of creatine
> 5. The fastest way to load is about 0.3 g/kg a day for 5–7 days, followed by 3–5 g a day to maintain; starting at 3–5 g a day also raises stores within 3–4 weeks
The text also notes that creatine is found in large amounts in ordinary food and that no sports organization currently bans it.
Few supplements receive such explicit backing from a major society. Two things to keep in mind, though. First, the position confirms only one or two quite specific uses; it is not a green light for all kinds of health claims. Second, know the interests involved when you read it: the ISSN takes sponsorship from supplement companies, and several authors of this stand and of the 2021 question-and-answer review have run industry-funded creatine research or advise creatine manufacturers. That does not overturn the conclusions of the many independent trials, but it is background a reader should have.
Chapter 4
Creatine and the brain
The idea that creatine only matters for muscle is out of date; for the past 20 years research has been looking at what it does in the brain. So far, though, the effects seen are mostly small and confined to a few situations.
Why it makes chemical sense:
Brain tissue also uses PCr to buffer , with the same enzyme as muscle (), though the energy demand curve differsThe 5% of creatine outside skeletal muscle is spread across tissues such as the brain and heart, and both neurons and astrocytes use itThe brain is energy-hungry: it is only 2% of body weight but uses 20% of the body's energy, so an ATP shortfall can show up as weaker attention and slower reactions
The situations in which the brain's energy reserve may run low are where supplementing has the best chance of showing an effect: sleep loss, a vegetarian diet, older age, and short bursts of intense mental work. This is not a miracle brain pill; it is an extra reserve tank for when the brain's stores are squeezed, the same logic as in muscle.
Why it makes chemical sense:
Brain tissue also uses PCr to buffer , with the same enzyme as muscle (), though the energy demand curve differsThe 5% of creatine outside skeletal muscle is spread across tissues such as the brain and heart, and both neurons and astrocytes use itThe brain is energy-hungry: it is only 2% of body weight but uses 20% of the body's energy, so an ATP shortfall can show up as weaker attention and slower reactions
The situations in which the brain's energy reserve may run low are where supplementing has the best chance of showing an effect: sleep loss, a vegetarian diet, older age, and short bursts of intense mental work. This is not a miracle brain pill; it is an extra reserve tank for when the brain's stores are squeezed, the same logic as in muscle.
Evidence · How strong the brain evidence is
The two most cited pieces of research on creatine and the brain do not reach quite the same conclusion, so they need to be read together.Avgerinos 2018 (Exp Gerontol) is a systematic review of 6 randomized trials in 281 healthy people. It concluded that creatine may improve short-term memory and reasoning (intelligence tests); results for long-term memory, attention, executive function, reaction time, mental fatigue, and other domains conflicted; cognitive scores in young people did not change; and in memory tasks, vegetarians responded better than meat-eaters.
Sandkühler 2023 (BMC Medicine) is the largest of creatine and cognition so far: 123 people, about half vegetarian and half omnivore, 5 g a day for 6 weeks per phase, in a preregistered crossover design. Bayesian analysis supported a small positive effect: backward digit span (working memory) came close to statistical significance, the Raven reasoning test showed no significant difference, and the other exploratory tests showed no improvement. Vegetarians did not benefit more than omnivores, and side effects were reported clearly more often on creatine than on placebo.
By group, the individual studies look like this:
Vegetarians: Rae 2003 (Proc R Soc B) gave 45 young vegetarians 5 g a day for 6 weeks in a double-blind crossover design, and both working memory (backward digit span) and the Raven reasoning test improved clearly. It is the most cited brain-creatine trial, but it was small, and the larger Sandkühler 2023 did not reproduce a vegetarian advantageSleep deprivation: McMorris 2006 (Psychopharmacology) gave 19 people 20 g a day (4 × 5 g) for 7 days, then kept them awake for 24 hours with light exercise in between. At 24 hours, the creatine group declined less in random movement generation, choice reaction time, balance, and mood. The sample was very small; Cook 2011 saw partly similar results in sleep-deprived rugby playersAcute mental load: in the double-blind crossover trial by Watanabe 2002, 8 g a day for 5 days reduced mental fatigue during repeated mental arithmeticOlder adults: the review by Roschel 2021 considers that a few small studies suggest better memory in older adults, more so when combined with strength training, but large trials have not confirmed itRecovery from concussion and traumatic brain injury: small pediatric studies such as Sakellaris 2006 suggest faster recovery; the evidence is thinAdd-on treatment for depression: only one randomized trial, Lyoo 2012, in which women with major depressive disorder added 5 g of creatine a day to an antidepressant (an ), and their depression scores improved faster and further
Young, healthy people who eat meat and sleep well: the effect is very weak and may be close to zero. The honest conclusion: if you eat enough meat and fish, sleep 7–8 hours a night, and do not train, taking creatine purely for your brain is poor value.
mcmorris-2006-sleeplyoo-2012-creatine-ssri-depression
In practice · Should students and desk workers take it?
This is the question many people care about most, and the answer depends on which group you are in.Worth considering (5 g a day):
Vegetarians, flexitarians, and people who eat almost no red meat or fish: their diet contains almost no creatine. Rae 2003 saw memory and reasoning scores improve in vegetarians, but a larger trial did not reproduce any extra advantage for vegetarians, so keep expectations modestPeople who are chronically short of sleep (< 6 hours, 4 or more days a week): small trials suggest it softens part of the decline from sleep loss, but it cannot replace sleep; it is only a small bufferPeople over 40 with heavy mental workloads who also do strength training: you already gain muscle benefits from the training, and the brain may get a small extra bonusPeople with long-term fatigue during pregnancy or breastfeeding: the evidence is thin and safety data in pregnancy are limited, so a doctor must agree firstPeople being treated for major depression with an antidepressant (an ): only one trial, Lyoo 2012, supports it, so talk to your psychiatrist first and do not add it on your own
Fine to take, but the brain benefit is weak (you are buying it for your muscles, and the brain is a side effect): young, healthy people who eat meat and do strength or power training. The main gain is in muscle; at most the brain gets a barely noticeable improvement in working memory.
Really not necessary (save your money):
Young, healthy people who eat plenty of meat and fish, sleep 7–8 hours a night, and have no training plan: the brain's reserve is already close to full, and nothing in their day would bring out an effect. At 5 g a day, you will most likely notice no difference, and objective test effects are close to zeroCramming it the week before a university entrance exam: that is not how it works. Creatine takes about 4 weeks to fill the stores, so a week of it before an exam is pointless, and it does not make you alert (that is caffeine's job)
A practical plan for learners:
1. Get the basics right first: sleep at least 7 hours a night, do 30 minutes of moderate exercise a day, eat at least 0.8 g of protein per kg of body weight a day, and have 5 servings of fruit and vegetables a day. These pay back far more than any supplement
2. If you already do all of that and still want to try: 5 g a day for 4 weeks, keeping a diary of your subjective focus and reaction speed before and after
3. Do not pay extra for brain creatine or nootropic versions: the ingredient is exactly the same as plain creatine monohydrate; only the marketing differs
4. Feeling no buzz is normal: creatine is not a stimulant, and the I feel smarter sensation you may expect will basically not happen. The real improvement, if any, is quiet: slightly faster reactions and fewer test errors
Chapter 5
Who benefits
With creatine, who should use it is a more useful question than does it work.
The clearest beneficiaries:
People doing strength and power training: weightlifting, sprinting, soccer, basketball, climbing, CrossFitVegetarians: their baseline PCr is low, so the change after supplementing is especially clearOlder adults doing strength training: creatine alone does little, but creatine plus strength training at least 2 times a week is one of the few combinations for sarcopenia supported by a (Chilibeck 2017)
May benefit, but the evidence is weak:
Thinking under sleep loss; memory and reasoning in vegetarians (Rae 2003 saw improvement, but a larger trial did not reproduce a vegetarian advantage)Recovery after concussion or traumatic brain injuryPostpartum fatigue and postpartum depression
No need to bother:
People focused on endurance (marathon, distance running, long-distance cycling): creatine mainly helps short bursts, is neutral for endurance, and may be a slight drawback because of the added weightPeople trying to lose fat: creatine does not burn fat directly, and at first body weight actually rises 1–2 kg from waterHealthy people with no training plan: without training to trigger it, creatine alone does close to nothing
The clearest beneficiaries:
People doing strength and power training: weightlifting, sprinting, soccer, basketball, climbing, CrossFitVegetarians: their baseline PCr is low, so the change after supplementing is especially clearOlder adults doing strength training: creatine alone does little, but creatine plus strength training at least 2 times a week is one of the few combinations for sarcopenia supported by a (Chilibeck 2017)
May benefit, but the evidence is weak:
Thinking under sleep loss; memory and reasoning in vegetarians (Rae 2003 saw improvement, but a larger trial did not reproduce a vegetarian advantage)Recovery after concussion or traumatic brain injuryPostpartum fatigue and postpartum depression
No need to bother:
People focused on endurance (marathon, distance running, long-distance cycling): creatine mainly helps short bursts, is neutral for endurance, and may be a slight drawback because of the added weightPeople trying to lose fat: creatine does not burn fat directly, and at first body weight actually rises 1–2 kg from waterHealthy people with no training plan: without training to trigger it, creatine alone does close to nothing
In practice · Women, older adults, special cases
Do women benefit as much as men? Yes: with matched training, the gains are similar (Antonio 2021). Creatine is only for men is a marketing myth.Older adults (65 and over) take the same dose as younger adults, and their relative benefit may be larger, because their baseline PCr is lower and the combination with strength training works better. The by Chilibeck 2017 pooled 22 randomized trials with 721 people (mean ages 57–70) doing strength training 2–3 times a week for 7–52 weeks. The groups given creatine gained about 1.37 kg more lean mass than those who trained without it, and their chest-press and leg-press strength rose more as well (standardized effect sizes of 0.35 and 0.24, small to moderate).
Children and adolescents: the ISSN position considers supervised use acceptable, but recommends it only for adolescent athletes in structured training, not for healthy children. Parents should not treat it as a growth supplement; there is no evidence it increases height.
People with diabetes: at standard doses, studies have not seen it worsen blood-sugar control; anyone on glucose-lowering medicine should still tell their doctor.
Kidney disease and chronic kidney failure: not recommended. Research shows creatine does not damage healthy kidneys, but people who already have chronic kidney disease are hard to monitor. Blood creatinine is a breakdown product of creatine, so supplementing raises it and makes the estimated glomerular filtration rate () look lower, which confuses the doctor's judgment. Anyone having their kidney function tested should tell the doctor they take creatine.
Pregnancy and breastfeeding: data are limited, so use with caution. It is not contraindicated, but there are no randomized safety trials.
People taking several medicines: there is little research on creatine combined with other drugs, so be cautious at high doses and ask your doctor first.
Chapter 6
How much and when to take it
Creatine is one of the few supplements whose dosing is clear to the point of being boring.
Form: choose creatine monohydrate. The ISSN states plainly that it is the most studied and most clinically effective form; the next-generation creatines (hydrochloride, ethyl ester, Kre-Alkalyn, buffered) are mostly marketing, not progress.
Two ways to fill up:
Fast loading: to fill the stores within 7–10 days, take 20 g a day on days 1–5, split into 4 doses (5 g × 4), then 3–5 g a day from day 6 to maintainSlow filling: if you are in no hurry, take 5 g a day from day one, and the stores fill in about 28 days
After 4 weeks, both routes leave the same level of creatine in muscle. Fast loading can cause mild stomach upset (bloating, diarrhea) and slow filling does not, so most people choose the slow route.
Timing: absorption is best with a meal that contains carbohydrate and protein, because insulin helps muscle take up creatine. Taking it after training may be slightly better in theory, but the difference is tiny; keeping the stores saturated over time is what matters.
Form: choose creatine monohydrate. The ISSN states plainly that it is the most studied and most clinically effective form; the next-generation creatines (hydrochloride, ethyl ester, Kre-Alkalyn, buffered) are mostly marketing, not progress.
Two ways to fill up:
Fast loading: to fill the stores within 7–10 days, take 20 g a day on days 1–5, split into 4 doses (5 g × 4), then 3–5 g a day from day 6 to maintainSlow filling: if you are in no hurry, take 5 g a day from day one, and the stores fill in about 28 days
After 4 weeks, both routes leave the same level of creatine in muscle. Fast loading can cause mild stomach upset (bloating, diarrhea) and slow filling does not, so most people choose the slow route.
Timing: absorption is best with a meal that contains carbohydrate and protein, because insulin helps muscle take up creatine. Taking it after training may be slightly better in theory, but the difference is tiny; keeping the stores saturated over time is what matters.
Myth · Do you need to cycle off?
Creatine should be cycled, 4 weeks on and 4 weeks off is a 1990s gym saying with no scientific basis:After you stop, muscle PCr stores drift back to baseline over 4–6 weeksThere is no risk that the body stops making its own (internal synthesis is not suppressed)Cycling brings no health benefit at all; it just wastes 4 weeks of saturation
The right approach is to take 3–5 g every day without breaks. The ISSN position stand states that there is no compelling evidence that use of up to 30 g a day for as long as 5 years harms health.
Some common claims, set one by one against the data (based mainly on the question-and-answer review by Antonio 2021):
Creatine damages the kidneys: at standard doses, decades of research have not found kidney damage in healthy people. It is not recommended for people who already have chronic kidney disease, because it interferes with monitoring, not because it harms the kidneys directlyHair loss and baldness: this worry comes from a small 2009 study of rugby players, in which blood dihydrotestosterone (DHT) rose 56% after 7 days of loading and stayed 40% above baseline during maintenance. It remained within the normal range throughout, later studies did not reproduce it, and there is no evidence at the level of hair follicles. Current evidence does not show that creatine raises testosterone or DHT or causes hair loss; if you are still worried, you can simply not take itWater retention and puffiness: the water that rises is inside the cells (drawn into muscle), not under the skin. A short-term gain of 1–2 kg of water weight is expectedIt causes dehydration and cramps: experimental and clinical studies have not seen such an increase. In a season-long follow-up of a college football team (players chose for themselves whether to take it), those taking creatine actually had fewer cramps, heat illnesses, and episodes of dehydrationMuscles shrink the moment you stop: half right. The 1–2 kg of water inside cells that creatine brings disappears after you stop; the real muscle growth from training does not vanish when you stop
Chapter 7
Why it's unlike most supplements
Creatine holds an unusual place among supplements: it does not really behave like one.
Where it resembles a drug:
A single, clearly defined molecule (not a mixed extract)A mechanism clear enough to be in biochemistry textbooksDosing studied over and over to the point of boredomNot on the World Anti-Doping Agency (WADA) prohibited list, and banned by no sports organizationIn human studies, use of up to 30 g a day for as long as 5 years has shown no safety problems
Where it does not:
No prescription needed, and it is cheapAlready present in ordinary food (red meat, fish)A modest effect, not a dramatic one
That is why creatine is often called a cheap drug or the least supplement-like supplement. It also casts light on the rest of the supplement market: most other supplements have far weaker evidence than creatine, yet sell for more and are marketed more aggressively.
Where it resembles a drug:
A single, clearly defined molecule (not a mixed extract)A mechanism clear enough to be in biochemistry textbooksDosing studied over and over to the point of boredomNot on the World Anti-Doping Agency (WADA) prohibited list, and banned by no sports organizationIn human studies, use of up to 30 g a day for as long as 5 years has shown no safety problems
Where it does not:
No prescription needed, and it is cheapAlready present in ordinary food (red meat, fish)A modest effect, not a dramatic one
That is why creatine is often called a cheap drug or the least supplement-like supplement. It also casts light on the rest of the supplement market: most other supplements have far weaker evidence than creatine, yet sell for more and are marketed more aggressively.
In practice · How to buy and store it
Only buy products like this:Creatine monohydrate: the ingredient list shows only this, or this plus a small amount of carbohydrate or flavoringReputable brands: Optimum Nutrition (ON Gold Standard), MyProtein, Bulk, BulkSupplements; in China, large brands such as MuscleTech and Combit are also fineCreapure® is a creatine raw-material trademark of the German company AlzChem, marketed on its high purity. Whether it is worth paying more is your call (several authors of the review by Antonio 2021 serve as scientific advisers to that company)
Do not buy products like this:
Micronized creatine: a marketing word; ordinary monohydrate powder is already fine enoughKre-Alkalyn, buffered, hydrochloride, ethyl ester, nitrate: several times the price and no better than monohydrate (several head-to-head randomized trials)Pre-workout powders with creatine plus a long list of other ingredients: you cannot tell the dose of each, and the ingredient lists are padded
Price guide: creatine monohydrate is among the cheapest supplements. At 5 g a day, 1 kg lasts 200 days, so a year's supply costs far less than any brain or anti-aging supplement, while the evidence is the strongest.
Storage: keep it dry and away from light, and use it within 6 months of opening. Do not mix it with hot water: above 60°C, creatine slowly turns into creatinine over time (harmless, but wasted). Cold water, warm water, milk, and juice are all fine.
References · 11
- Kreider, R. B., et al. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 18. Position stand: short- and long-term creatine supplementation, up to 30 g/day for 5 years, is safe and well tolerated in healthy individuals and in a number of patient populations from infants to the elderly; the stand adds that significant health benefits may come from ensuring a habitual low-dose creatine intake (e.g., 3 g/day) throughout the lifespan (abstract, PMID 28615996). 10.1186/s12970-017-0173-z
- Antonio, J., et al. (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? Journal of the International Society of Sports Nutrition, 18, 13. 10.1186/s12970-021-00412-w
- Branch, J. D. (2003). Effect of creatine supplementation on body composition and performance: a meta-analysis. International Journal of Sport Nutrition and Exercise Metabolism, 13(2), 198–226. 96 papers (100 studies) of randomized, placebo-controlled, blinded human trials: small but significant effect sizes for body composition (0.17) and for exercise tasks of 30 s or less (0.24), 30-150 s (0.19) and over 150 s (0.20); larger effects after loading-only regimens and for repetitive-bout, upper-body and laboratory tasks; field tasks smaller (0.14), and creatine does not appear to improve running or swimming performance; no difference by sex or training status (abstract, PMID 12945830). 10.1123/ijsnem.13.2.198
- Sandkühler, J. F., Kersting, X., Faust, A., et al. (2023). The effects of creatine supplementation on cognitive performance — a randomised controlled study. BMC Medicine, 21, 440. One preregistered, randomized, double-blind, placebo-controlled crossover trial in 123 people (about half vegetarian, half omnivore): creatine 5 g/day for 6 weeks vs placebo. Backward Digit Span effect bordered on significance (p = 0.064), Raven's matrices did not (p = 0.327), and none of eight exploratory tests improved; Bayesian evidence supported a small beneficial effect; vegetarians did not benefit more; side effects were reported more often on creatine (RR 4.25). It pools no other trials; the 16-RCT description this record once gave was wrong (abstract, PMID 37968687). 10.1186/s12916-023-03146-5
- Avgerinos, K. I., Spyrou, N., Bougioukas, K. I., & Kapogiannis, D. (2018). Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental Gerontology, 108, 166-173. 10.1016/j.exger.2018.04.013
- Rae, C., et al. (2003). Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proceedings of the Royal Society B, 270(1529), 2147–2150. 10.1098/rspb.2003.2492
- Roschel, H., Gualano, B., Ostojic, S. M., & Rawson, E. S. (2021). Creatine supplementation and brain health. Nutrients, 13(2), 586. 10.3390/nu13020586
- Forbes, S. C., Cordingley, D. M., Cornish, S. M., et al. (2022). Effects of creatine supplementation on brain function and health. Nutrients, 14(5), 921. 10.3390/nu14050921
- Watanabe, A., Kato, N., & Kato, T. (2002). Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neuroscience Research, 42(4), 279-285. Double-blind placebo-controlled crossover: 8 g/day of creatine for 5 days reduced mental fatigue during repeated mental arithmetic, and altered the task-evoked cerebral oxygenation response measured by near-infrared spectroscopy. 10.1016/S0168-0102(02)00007-X
- Chilibeck, P. D., et al. (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. 22 randomized trials, 721 older adults (mean age 57-70 across studies), creatine or placebo during resistance training 2-3 days/week for 7-52 weeks: lean tissue mass +1.37 kg (95% CI 0.97-1.76) more with creatine; chest press SMD 0.35, leg press SMD 0.24 (abstract, PMID 29138605). 10.2147/OAJSM.S123529
- Candow, D. G., et al. (2019). Effectiveness of creatine supplementation on aging muscle and bone: focus on falls prevention and inflammation. Journal of Clinical Medicine, 8(4), 488. 10.3390/jcm8040488