Creatine for Mental Health: What the Research Shows

May 30

Introduction to Creatine for Mental Health

Creatine monohydrate is well-known as a supplement for increasing strength and athletic performance, but emerging research suggests it may also play a significant role in mental health treatment, particularly for depression. Recent studies indicate that creatine, a naturally occurring compound that helps supply energy to cells, could be a promising adjunctive treatment for various mental health conditions. When taking a holistic approach to mental health it’s important to factor in supplements that may improve symptoms of mental illness such as creatine. This article goes over the current state of what we know about creatine in relation to mental health.

What Is Creatine and How Does It Work?

Creatine is a compound naturally produced in the body and found in foods like meat, fish, and poultry. In the body, creatine plays a crucial role in energy metabolism:

Creatine donates a phosphate group to ADP to regenerate ATP in times of high energy demand
In muscles, this provides energy for short bursts of intense activity (like strength training)
In the brain, creatine helps neurons maintain energy levels during periods of high demand

The brain uses energy differently than muscles do. Neurons primarily rely on oxidative phosphorylation for energy, getting lactate from supporting cells called astrocytes. During high energy demands—like during depression or sleep deprivation—phosphocreatine can provide a rapid energy source when other pathways are insufficient.

Research on Creatine for Depression

Several studies have examined creatine's effects on depression with promising results:

Creatine Combined with Psychotherapy

A 2025 study in India tested 5 grams of creatine daily as an add-on to cognitive behavioral therapy (CBT) for depression. After eight weeks, the creatine group showed significantly greater reductions in depression scores (PHQ-9) compared to placebo. The creatine plus CBT group's scores dropped from 17.8 to 5.8 (almost no symptoms), while the placebo plus CBT group only dropped to 11.9.

Creatine with Antidepressants

A 2012 study of 52 women with major depressive disorder found that adding creatine (3g for one week, then 5g for weeks 2-7) to escitalopram treatment led to faster and greater improvements in depression scores, with significant effects appearing by week two.

Creatine for Bipolar Depression

A 2018 study examined creatine (6g daily) as an adjunctive treatment for bipolar depression. Over six weeks, the creatine group showed significant reductions in depression scores and improvements in functioning without triggering manic symptoms in most participants. The remission rate was significantly higher in the creatine group (52.9%) versus placebo (11.1%). However, it's worth noting that in this study and another, a small number of bipolar patients converted to hypomania or mania, suggesting caution may be needed when using creatine in bipolar disorder.

Creatine for Treatment-Resistant Depression

A 2011 open-label study of female adolescents with SSRI-resistant depression found that creatine supplementation led to significant improvements, with depression scores dropping from 69 to 30. Importantly, brain scans showed increased brain phosphocreatine levels, confirming that oral creatine can affect brain bioenergetics.

The Relationship Between Dietary Creatine and Depression

A large 2020 observational study found that people with the highest dietary creatine intake had 31% lower odds of having depression compared to those with the lowest intake. This association persisted even after controlling for factors like age, sex, education, race, ethnicity, healthcare access, BMI, antidepressant use, physical activity, and fish consumption.

Brain Imaging Studies

Research has found that lower creatine concentrations in the prefrontal cortex correlate with higher depression scores. One study found that creatine levels were positively correlated with gray matter volume, suggesting a connection to brain energy metabolism and structural integrity.Another study found that a 10-gram daily dose of creatine led to greater increases in brain phosphocreatine levels compared to lower doses (2g or 4g), with corresponding greater improvements in depression symptoms.

Optimal Dosing for Mental Health

While most studies have used 5 grams daily (the standard fitness dose), research suggests that higher doses may provide additional benefits for brain health:

10 grams daily has been shown to increase frontal lobe creatine by 9.1%, compared to only 4% with lower doses
Some studies have used 20 grams daily for a week as a "loading phase" before reducing to a maintenance dose
For acute situations like sleep deprivation, higher doses (20g/day) appear to provide cognitive protection

A "loading" approach (higher initial dose followed by maintenance dose) may be beneficial when starting creatine supplementation for mental health purposes.

Safety and Side Effects

Creatine has been extensively studied and shows an excellent safety profile:

Long-term studies (up to 5 years) show no harmful effects on kidney function in healthy individuals
No serious adverse events were reported in the mental health studies
Some participants may experience mild gastrointestinal discomfort
Creatine causes water retention in muscles, which may result in 2-5 pounds of weight gain (water weight)
Creatine may cause a false elevation in serum creatinine (a kidney function marker) without actual kidney impairment

People with pre-existing kidney disease should consult with their nephrologist before taking creatine.

Creatine for Cognitive Performance Under Stress

Research shows creatine may be particularly beneficial during times of stress or metabolic demand:

Studies of sleep-deprived individuals found that those taking creatine (20g/day for a week) maintained better executive function after 24-36 hours without sleep
During oxygen deprivation, creatine supplementation helped maintain cognitive performance despite low oxygen levels
These findings suggest creatine provides an energy buffer that helps the brain maintain function during periods of stress

Practical Considerations for Taking Creatine

Standard dose: 5-10 grams daily
Consider taking with food and plenty of water to minimize GI discomfort
Creatine is tasteless but has a slightly gritty texture when mixed with water
Increase water intake when taking creatine due to its water-retaining properties
Creatine can be found in powder or capsule form

Conclusion

Emerging research suggests creatine monohydrate may be a promising, low-cost, and generally safe option for enhancing mental health treatment. When considering a holistic approach to mental health- it’s important to factor in useful supplements like creatine. While more research is needed—particularly larger, multi-site studies—the current evidence is encouraging. Creatine appears to work by supporting brain energy metabolism, providing a buffer during times of metabolic stress. This mechanism may explain why it shows benefits not only for depression but also for cognitive performance during sleep deprivation and other stressful conditions. For those considering creatine for mental health, it's important to discuss this option with a healthcare provider who can evaluate individual circumstances and help monitor results. As with any approach to mental health, creatine should be considered as part of a comprehensive treatment plan that may include therapy, exercise, proper nutrition, and in some cases, medication.

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David Puder