Creatine is an organic compound best-known for aiding muscle growth and recovery. Two decades of creatine research on brain function now links creatine to better cognitive performance, memory, and reasoning, as well as protecting against certain neurological diseases.

The latest research indicates that supplementing with creatine monohydrate may also alleviate symptoms of depression.

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Creatine Sources and Roles

The human body produces its own creatine (1-2 grams daily) in the pancreas, liver, and kidneys using a combination of three amino acids:

• arginine

• glycine

• methionine

It can also utilize the creatine it gets from protein-rich foods such as red meat, seafood, and cow’s milk.

Most of the body’s creatine goes into the muscles, which then use it to create adenosine triphosphate (ATP), an energy source vital to muscular and cellular function. About 5 percent of creatine goes to the heart, brain and other tissues.

The brain needs enormous amounts of energy, and it uses creatine as one of its energy sources.

Risks of Low Creatine

Growing evidence indicates that disruptions in brain energy production and storage, particularly in the prefrontal cortex, can lead to depressive symptoms.

The prefrontal cortex handles cognitive functions and mood regulation. Research links lower levels of creatine in this area with higher levels of depression.

Who is at Risk?

Certain populations, like vegans, vegetarians, and those with certain diseases including liver disease, may have low levels of creatine in the body.

Females are also at risk. They have about 70 to 80 percent lower endogenous creatine stores, and they also obtain less creatine through their food than males.

Women experience higher rates of depression and cognitive decline than men, especially post-menopause. Therefore, females may experience more significant mood benefits from creatine supplementation than men.

Effects of Creatine Supplementation

• With Therapy

  In one recent double-blind, randomized, placebo-control trial, 100 people with major depressive disorder (half of whom were female) were given cognitive behavioral therapy (CBT) and took either creatine monohydrate or a placebo for eight weeks.

  While the CBT helped both groups, those who also took the creatine experienced significant improvements in their depressive symptoms compared to those on the placebo.

• With Medication

  Scientists believe supplemental creatine may also activate dopamine and serotonin receptors, which could provide even more mood-boosting benefits.

  In one randomized, double-blind, placebo-controlled trial, 52 women with major depressive disorder received a selective serotonin reuptake inhibitor (SSRI) and either 5 grams of creatine a day or a placebo.

  Those who received creatine augmentation showed significantly greater improvements as early as week two of treatment. SSRIs typically take several weeks to kick in.

Precautions

An adult dose of 3 to 5 grams of creatine daily is considered safe.

People who should consut with their healthcare practitioner before taking creatine include:

• pregnant or breastfeeding women

• people with bipolar disorder

• those with diabetes, liver, or kidney disease

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Selected Sources:

“Creatine for the treatment of depression” by B.M. Kious et al., Biomolecules, 8/23/19

“Effects of creatine supplementation on brain function and health” by S.C. Forbes et al., Nutrients, 2/22

“Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression . . .” by N.N. Sherpa et al, European Neuropsychopharmacology, 1/25

“An emerging role for creatine supplementation in the treatment of depression” by T. Yeater, K. Birkenbach, and P. Attia, https://peterattiamd.com

“A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder” by I.K. Lyoo et al., American Journal of Psychiatry

“Lower creatinine levels are associated with an increased risk of depression . . .” by F. Liu et al., Frontiers in Psychiatry, 2/24/25

“Relationship between depression, prefrontal creatine and grey matter volume,” by P. Faulkner et al., Journal of Psychopharmacology, 12/21