The Science of Creatine Supplements

More recent studies have investigated its usefulness in improving memory, and there’s even intriguing, though preliminary, research that creatine may play a role in supporting mental health in people with depression.

Many sports and nutrition groups have endorsed the safety and utility of the supplement, but Dr. David Dodick, professor emeritus at the Mayo Clinic and Chief Science and Medical Officer of the Atria Health Institute, still advises checking with your doctor before starting any new supplement. (Once you’ve done that, look for reputable brands with certifications from NSF Certified for Sport and USP Verified, both of which are third-party testers that ensure you’re taking what the label says you’re taking.)

Who it’s right for

Creatine is a widely studied supplement with strong evidence for safety and usefulness across many groups, including healthy adults, older adults, pre- and post-menopausal women, athletes, and more.

Who should be careful

According to the literature, people with kidney disease or with risk factors for kidney disease should avoid high-dose creatine supplementation (more than 3-5 g/day).

Dr. Dodick notes that numerous studies over the past two decades have consistently shown that long-term creatine supplementation (3–5g/day) does not impair kidney function in healthy people, however. A note for doctors: Creatine is metabolized to creatinine, a marker used in estimating kidney function on blood work. Since supplementation raises creatinine levels, this can create a false signal of kidney impairment on labs. This means clinicians must interpret this in context or use cystatin C or direct glomerular filtration rate (GFR) measurements for accuracy.

Additionally, there is limited safety research on the use of creatine supplements during pregnancy and breastfeeding, so it’s generally advised women avoid it during these times.

Creatine and lean muscle mass

A widely cited review published in 2022 in the journal Nutrition did a rigorous analysis of the evidence for creatine supplementation and increased muscle (also called lean body mass). Researchers analyzed 35 different papers that included a total of 1,200 people to find clear—or at least clearer—answers about who it’s right for. Notably, they found:

• Creatine supplements did, indeed, meaningfully improve muscle mass, but only in men
• When compared with people who did not exercise, those who did exercise saw an increase in muscle, especially among those who lifted weights
• Taking creatine without exercising conferred no additional muscle mass
• Age didn't appear to affect results—both younger and older people benefited similarly when lifting weights

Creatine and women

Another study looked with more granularity at the connection between creatine and muscle mass in women across the lifespan. They found that pre-menopausal women can experience improvements in strength and exercise performance with creatine supplementation. For post-menopausal women, benefits for muscle size and function appear when using higher doses—about twice what’s typically recommended for men.

Beyond muscle, creatine appears to offer women additional benefits when combined with resistance training, including bone health. This suggests that while the muscle-building effects may be less dramatic for women than men, creatine still provides benefits for women's physiology at different stages of life.

Creatine and brain health

Another paper looked at the effect of creatine supplementation on memory performance and found that there were no significant differences in results between men and women. The benefits of creatine supplementation for memory were similar—and positive—regardless of sex.

The main factor influencing results was age, with older adults (66-76 years) showing much more significant memory improvements than younger people (11-31 years), who showed minimal effects.

Why is this so? The brain uses a ton of energy—about 20% of the body’s energy reserves despite being just about 2% of body weight. Since we know creatine crosses the blood-brain barrier and increases brain energy stores, scientists suspect that the cells in the brain can use this additional energy in stressed states or when performing cognitively demanding tasks, such as memory recall.

Creatine and mental health

Creatine shows growing promise as an adjunctive treatment for depression, especially in women. In one study, women treated with creatine at a dose of 5 grams per day in addition to an SSRI had faster and greater reduction in depression scores and significantly higher rates of remission compared to a placebo two months after treatment was started. In a more recent study, creatine monohydrate in combination with cognitive behavioral therapy (CBT) exhibited a significantly greater reduction in depressive symptoms compared to those receiving CBT with a placebo.

The ideal form of creatine

Creatine monohydrate has been studied in hundreds of clinical trials over the past 30 years. It is highly absorbed, and is the most effective, safest, and affordable form of creatine, backed by the largest body of clinical evidence. It is also endorsed by expert consensus including the International Society of Sports Nutrition and the American College of Sports Medicine.

The bottom line

Research paints a nuanced picture of creatine's benefits, and the evidence is overwhelmingly positive. Whether you're looking to support muscle maintenance, cognitive function, mood, or overall health, creatine offers evidence-backed benefits. As with any supplement, consider your individual health needs, consult with your doctor, and choose a high-quality product to maximize potential benefits and minimize risks.

This article is part of Atria’s Future of Health newsletter. Subscribe here.