A Creatine Trial in Middle Age, and the Age Gap in the Memory Evidence
A study described as covering middle-aged and older adults enrolled people aged 45 to 65, with an average age of 54. The difference between the label and the sample turns out to be the most useful thing about this trial, seeing as the creatine evidence differs considerably at different ages.
The study, published in August in the Journal of the International Society of Sports Nutrition, tested whether or not creatine monohydrate changes body composition, cognitive function, and markers of health in adults who were not already training [1].
What the creatine trial found
Seventy-three healthy sedentary adults enrolled, and 64 completed the twelve-week protocol [1]. Forty were women and 24 were men. Participants chose for themselves whether to join a non-exercise group or an exercise-and-diet group. Within whichever group they chose, they were then randomly assigned, double-blind, to either creatine monohydrate at 2 × 5 g per day or a matching maltodextrin placebo. I am describing the protocol that was tested, which is not a dose recommendation.
Body composition was measured by DXA scan, a low-dose X-ray that measures fat and lean tissue separately. Participants also gave fasting blood samples and completed a battery of cognitive tests at the start, at six weeks, and at twelve weeks.
In the group that did not exercise, creatine increased lean tissue mass, strength, and muscular endurance, with favorable changes in selected blood lipids, HbA1c (a measure of average blood sugar over the previous few months), and selected measures of cognition and memory. In the exercise-and-diet group, creatine increased lean tissue mass, produced a greater reduction in body fat percentage, and improved strength, endurance, and selected measures of cognition and memory. Supplementation was well tolerated.
There are two limits to that reporting. The authors state directly that the individual cognitive and biomarker findings should be interpreted as exploratory, which is their caution rather than mine. And the published abstract gives the direction of each change without the magnitudes, so there is no way to tell you how much lean mass changed or how much any cognitive score changed. Direction without magnitude is less to base a decision on than it first appears.
The design has one feature that limits what the comparison between groups can show. Participants selected their own exercise arm. Randomization applied only to creatine versus placebo within each arm, which means the supplement comparison is randomized while any comparison between exercisers and non-exercisers is not. People who choose to join an exercise and weight-loss program differ from people who choose not to, in ways no statistical adjustment fully captures.
What larger creatine studies have found
The muscle claim is where I would set expectations lowest, which may be the reverse of what you would expect.
A meta-analysis examined creatine combined with resistance training using direct imaging of muscle, meaning MRI, CT, or ultrasound rather than whole-body estimates, across 10 studies and 44 outcomes [2]. The pooled estimate was 0.11, with a 95% credible interval running from -0.02 to 0.25. The authors describe that as a very small effect, and the interval includes zero. Their moderator analysis found a somewhat larger benefit in younger adults than in older ones.
So the most precisely measured research on muscle produces a small effect that is largest in the young. That is a reasonable expectation to carry into any single twelve-week trial.
The memory results are different, and the age pattern is the most useful part. A meta-analysis of randomized trials of creatine and memory in healthy people found an overall improvement over placebo (standardized mean difference 0.29, 95% CI 0.04 to 0.53) [3]. Broken down by age, the benefit was concentrated in adults aged 66 to 76 (SMD 0.88) and essentially absent in participants aged 11 to 31 (SMD 0.03). Heterogeneity was high in the overall analysis and higher still in the older subgroup, which means the individual studies disagreed considerably with one another.
Now set the new trial's participants against that. At 45 to 65 years old, their ages are between the two age bands where memory has actually been measured. They are older than the group that showed nothing and younger than the group that showed the largest effect. Whether or not the memory benefit extends to people in their fifties is unsettled, and this trial's cognitive findings are exploratory by the authors' own designation.
One further detail on the protocol. An expert review from the same society journal describes creatine as relatively well tolerated at recommended dosages, which it gives as 3 to 5 g per day or 0.1 g per kilogram of body mass [4]. This trial used 10 g per day, roughly double that maintenance range. That is a legitimate research choice and it is not the amount most guidance describes.
Where creatine fits as we age
What I would resist is creatine as a longevity supplement. What I find more defensible is creatine as one input into a specific problem that does arrive with age.
That problem is sarcopenia, the progressive loss of muscle mass and strength across the decades. It is a major contributor to frailty, falls, and lost independence, and unlike much of what worries people about aging, it responds to effort. The interventions with the strongest evidence are resistance training and adequate protein.
Creatine is a smaller addition to that. If someone is already training, already eating enough protein, and looking for something modest to add, creatine is among the better-studied and better-tolerated options available. It is also inexpensive. If someone is not training at all, then adding creatine addresses the smaller factor and leaves the larger one, the training itself, unaddressed.
The finding here that most deserves follow-up is the one in the non-exercising group, where creatine alone increased lean mass and strength in sedentary people. If larger studies confirm it, it would be most useful for people who cannot exercise. That includes many of the patients I see with post-viral fatigue, dysautonomia, and mast cell activation, for whom exertion can cause a flare. I am cautious about extending the finding that far. This trial studied healthy sedentary volunteers, not people with exertion intolerance. Extending the finding from one group to the other is a hypothesis, and I am naming it as a hypothesis rather than offering it as a result.
Weighing creatine in your fifties
Resistance training and adequate protein have the strongest evidence for preserving muscle as you age. Creatine is an addition to those two, and it does not replace either of them.
The memory evidence is strongest in adults in their late sixties and seventies, absent in young adults, and poorly characterized in between. If you are in your fifties, your age group has not been studied well, and this trial does not settle the question.
The trial's 10 g per day is roughly double the 3 to 5 g per day that the expert review describes as the recommended range [4]. More is not automatically better, and the studied amounts are not a prescription.
If you have kidney disease, or you take medication that affects your kidneys, talk it over with your provider before you start rather than after. And whenever you have bloodwork drawn, put every supplement you take on the list you hand the person who ordered it.
References
Primary research located and verified via PubMed.
Chun J, Liu Y, Kibler GL, Lee H, Babakhani K, Rhoades N, Bivins I, Ko J, Dickerson B, Gonzalez DE, Sowinski RJ, Rasmussen CJ, Kreider RB. Effects of creatine supplementation with and without exercise and diet intervention on body composition, cognitive function, and markers of health in middle-aged and older adults. J Int Soc Sports Nutr. 2026;23(sup1):2716273. PMID 42578920. https://doi.org/10.1080/15502783.2026.2716273 (digest source article; ISRCTN83081058)
Burke R, Piñero A, Coleman M, Mohan A, Sapuppo M, Augustin F, Aragon AA, Candow DG, Forbes SC, Swinton P, Schoenfeld BJ. The Effects of Creatine Supplementation Combined with Resistance Training on Regional Measures of Muscle Hypertrophy: A Systematic Review with Meta-Analysis. Nutrients. 2023;15(9):2116. PMID 37432300. https://doi.org/10.3390/nu15092116
Prokopidis K, Giannos P, Triantafyllidis KK, Kechagias KS, Forbes SC, Candow DG. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(4):416-427. PMID 35984306. https://doi.org/10.1093/nutrit/nuac064
Antonio J, Candow DG, Forbes SC, Gualano B, Jagim AR, Kreider RB, Rawson ES, Smith-Ryan AE, VanDusseldorp TA, Willoughby DS, Ziegenfuss TN. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? J Int Soc Sports Nutr. 2021;18(1):13. PMID 33557850. https://doi.org/10.1186/s12970-021-00412-w
A note before you go
This article is educational and is not medical advice. It describes what researchers tested and what they found, and none of it is a recommendation to start, stop, or change a supplement. Creatine can affect some lab results, and it is not the right choice for everyone, particularly if your kidneys are part of your medical history. Please bring the question to the provider who knows that history. If muscle and memory as you age are what brought you here, the least glamorous parts of the answer, which are training and protein and sleep, are also the best evidenced.
If this resonates with what you're experiencing and you'd like to explore a naturopathic approach, book a consultation with our clinic.
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