Does one dose of creatine supplementation fit all?

In a review published in the journal Advanced Exercise and Health Science, the team summarizes what is known about the effects of different creatine supplementation protocols in the body and discusses the variables that likely influence tissue responsiveness.

“Based on the current body of research, the dosages of creatine which appear to have beneficial effects on each tissue may vary,” Darren Candow, PhD, professor at the University of Regina in Canada and co-author on the review, told NutraIngredients-USA.

“A small dosage of creatine (i.e., 3-5 g/day), while being effective for improving measures of muscle mass and performance, has not been shown to improve measures of bone or brain structure/function in healthy adults. Whether a higher daily dose (i.e., 10 g/day) would achieve these benefits across tissues remains to be determined. Thus, at the present time, one dose of creatine likely does not fit all.”

Sergei Ostojic of the University of Agder, (Norway), Scott Forbes of Brandon University (Canada) and Jose Antonio of Nova Southeastern University (United States) also contributed to the review.

The knowns of creatine supplementation

First isolated and extracted from animal skeletal muscle by French philosopher and chemist Michel Eugène Chevreul in 1832, creatine is an organic acid derived from reactions involving amino acids arginine, glycine and methionine in the kidneys, liver and brain.

Since the late 1990s, an extensive body of science has focused on substantiating its benefits as supplement for muscle accretion and performance.

“It is well established that creatine supplementation (i.e. loading phase, with and without maintenance phase; 0.1-0.14 g/kg/day), primarily when combined with resistance training, improves measures of lean tissue mass, regional muscle growth and muscle performance (i.e., strength, endurance, power) in young and older adults,” Dr. Candow said.

More recently, studies have begun to explore the less known effects on bone structure and brain function across a variety of populations.

Supplementation with 8 g of creatine or more a day and resistance training has been shown to reduce markers of bone resorption and bone mineral density loss and increase bone geometry (i.e., strength) in healthy older adults—a population at risk of osteopenia, osteoporosis and frailty.

“The majority of studies showing bone benefits from creatine used a relative dosing strategy (≥ 0.1 g/kg/day) and all included an exercise stimulus,” the researchers wrote. “However, the direct effects of creatine on cells involved in the bone remodeling process (i.e., osteoblasts, osteocytes, osteoclasts) are unknown. Further, whether creatine supplementation increases creatine accumulation in human bone remains to be determined.”

The review also pointed to a few well-designed studies showing that high-dose creatine supplementation (20 g a day or 0.3 g/kg a day for at least 7 days) or lower-dose creatine (4–5 g/day for several months) can increase total brain creatine levels in young and older adults. In addition, a recent study indicated that short-term, high-dose creatine can reverse cerebral metabolic alterations and fatigue-related cognitive decline due to sleep deprivation.

Confounding variables and future directions

Besides the remaining unknowns surrounding effects of supplementation on different body tissues, there is the known that not all individuals respond to creatine in the same way for a host of reasons.

“Confounding variables such as baseline (pre-supplementation) tissue creatine levels, muscle fiber morphology, bone remodeling/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 researchers wrote, noting that timing of supplementation relative to exercise and nutrient co-ingestion may also influence creatine uptake and retention.

The review called for further multidisciplinary and collaborative research to investigate these confounding factors to differentiate between responders and non-responders and ascertain whether and why different tissues may require different dosages of creatine supplementation from a whole-body perspective.

“We are currently determining whether there is an optimal timing of ingestion for creatine; whether a bolus ingestion protocol is different than an intermittent ingestion protocol, how creatine influences female health across the lifespan,” Dr. Candow said. “I do think that the vast majority of future creatine research will focus on the brain and perhaps female health.”