This May Be A Helpful Add-On Treatment For Women With Depression

Creatine has a well-earned reputation as a muscle supplement. And it's increasingly gaining recognition as a brain health supplement, fueling mental energy and supporting memory. It may also have an impact on mood.

A new systematic review published in Brain Medicine looked at clinical trials examining creatine monohydrate as an add-on to existing depression treatments. The findings were mixed, but two of the studies showed meaningful benefits, particularly in women using creatine alongside antidepressants or therapy. Here's what the research found and what it might mean for you.

Creatine & depression in women

One randomized controlled trial in women with major depressive disorder. Participants were already taking the antidepressant escitalopram and were given either creatine monohydrate or a placebo for 8 weeks. The creatine group showed significantly greater reductions in depressive symptoms and higher remission rates compared to the placebo group.

The second study combined creatine with cognitive behavioral therapy (CBT). Again, the creatine group showed greater symptom reduction compared to the placebo group, this time measured using the PHQ-9. Both studies involved women, which may not be a coincidence.

Where results are mixed

Not all the studies pointed in the same direction. Two found no significant effect of creatine (one testing 5 grams per day and another testing 10 grams per day) in patients who hadn't responded to prior antidepressant treatment. Another study tested a range of doses (2, 4, and 10 grams per day) in adolescent females and found no significant differences in depressive symptoms.

One study also examined creatine in patients with bipolar disorder and found no significant benefit. The review also flagged that creatine may carry a risk of triggering hypomania or mania in people with bipolar disorder, a meaningful safety consideration for that population.

Creatine's impact on mood & the brain

The brain is one of the most energy-demanding organs in the body1. It relies heavily on ATP (the molecule cells use for fuel), and creatine plays a role in replenishing this energy source. Some researchers believe that impaired brain energy metabolism may be one factor underlying depression, which is part of why creatine has become an area of interest.

Beyond energy, creatine may also influence dopamine and serotonin pathways, two neurotransmitters closely tied to mood regulation. Preclincial animal studies have suggested that creatine's effects on the brain may be sex-dependent (female animals appear to respond differently than males), which could help explain why the human trials showing benefit were conducted in women.

How to supplement to see a benefit

The studies that found a positive effect used 5 grams of creatine monohydrate per day. Higher doses in the review didn't produce better outcomes, so more isn't necessarily better here (although 10 grams a day may be helpful for some people). Creatine monohydrate is the most researched form and is generally well-tolerated, and the most commonly reported side effects are mild GI symptoms.

Consistency matters, too. Creatine works best when taken daily, not just on workout days. For even more brain health benefits, consider taking a creatine powder that also includes Cognizin® citicoline (like this one). Citicoline is a neuronutrient, and Cognizin® is a clincially studied form of it that has been shown to support long-term brain health, mental energy, and memory.

If you have bipolar disorder, it's a good idea to check in with your doctor before adding creatine, since the review noted a possible risk of hypomania or mania in that group.

The takeaway

The research on creatine for depression is genuinely exciting, and it's still early, so this systematic helps pull together what we currently known about the relationship between creatine and depression in the context of randomized controlled trials. Taking creatine for brain health is a smart move, and it may also have a positive impact on your mood.