Does one dose of creatine supplementation fit all?

Since the late 1990s, there has been substantial research investigating the beneficial effects of creatine supplementation on measures of muscle accretion and performance, bone structure, and brain function across a variety of populations. However, the optimal dose of creatine needed to achieve these benefits is unclear. Further, whether a 'tissue-creatine dose relationship' exists is unknown. In general, a creatine-loading phase (20 grams/day for ≤ 7 days), with and without a creatine maintenance phase (i.e., 3-5 grams/day) appears sufficient to produce skeletal muscle benefits. Alternatively, a relative dosing strategy of 0.10-0.14 grams of creatine/kg/day appears to be a viable option, especially for healthy older adults. Beyond skeletal muscle, a small body of research shows that creatine supplementation can have favourable effects on measures of bone biology and structure in both disease state populations and healthy older adults. The relative dosing strategy of 0.10-0.14 grams of creatine/kg/day and exercise training produces the most consistent bone benefits. From a brain perspective, both absolute and relative creatine dosing strategies are effective for increasing brain creatine levels but the optimal dosage and/or duration of ingestion to enhance brain function is unclear. Overall, there is evidence that ≥ 20 grams/day or 0.3 grams/kg/day for ≤ 7 days or ≥ 4 grams/day for several months is likely required to increase total brain creatine concentrations. Confounding variables such as baseline (pre-supplementation) tissue creatine levels, muscle fiber morphology, bone remodelling/repair processes, brain bioenergetics, habitual dietary intake of creatine, biological sex, age, and physical activity likely dictate the dose of creatine required to produce a meaningful tissue response. The purpose of this narrative review is to (1) summarize the effects of different creatine supplementation protocols on tissue accumulation in skeletal muscle, bone, and brain, (2) discuss variables that likely influence the tissue's responsiveness to creatine supplementation, and (3) determine whether creatine supplementation improves measures of muscle, bone or brain health and performance.