Key takeaways:

1. Low brain creatine levels have been found in the brains of individuals with major depressive disorder and bipolar disorder. 

2. Small scale trials have found that creatine may enhance the effects of antidepressants, alleviate depression symptoms, improve mental fatigue, and enhance cognitive processing. 

3. The body creates about half the creatine we need. The other half must come from dietary sources. Fish and meat are rich sources of creatine. 

4. Pumpkin seeds, sesame seeds, and watermelon seeds do not contain creatine, but they are rich sources of methionine, arginine, and glycine (amino acids that the body can use to synthesize creatine).

Mental Health and Creatine:

The link between supplemental creatine intake and muscular strength, speed, stamina, performance, and muscular recovery has been well documented and noted in virtually all populations. New research is emerging that shows how supplemental creatine can have a direct and measurable impact on mental health conditions such as depression, bipolar disorder, and neurodegenerative diseases like Parkinsons.

Creatine is a non-protein amino acid found in the skeletal muscles (95%) and the brain and testes (5%).3 Creatine plays a crucial role in creating ATP, or adenosine triphosphate, the main source of energy for every cell in your body. As well as maintaining energy availability, creatine is an antioxidant. Antioxidants reduce cell damage by reducing oxidative stress caused by the formation and destructive properties of ROS (reactive oxygen species).3  

Researchers initially theorized that creatine played a role in mental health because creatine is found and produced in the brain. Creatine transporters are found at the blood-brain barrier, indicating that the brain uses dietary creatine as well as endogenous creatine (creatine that the body creates).4  Transporters can be thought of as shuttles that only let specific compounds into the brain, in this case creatine. Within the brain, creatine is found in the hippocampus, cerebellum, and prefrontal cortex.2 The hippocampus is involved in memory and learning, the cerebellum is involved in balance and posture, and the prefrontal cortex is involved in cognitive processing, decision making, and emotional expression. 

Major depressive disorder (MDD) and bipolar disorder (BP) involve alterations of brain bioenergetics, the production, consumption, and storage of energy. Reduced creatinine levels have been found in the brains of individuals with MDD and BP. Severity of BP has been found to be inversely related to brain creatine levels. Researchers theorized that if it is possible to increase brain creatine levels, it may help alleviate symptoms. It was found that 20g/ day of creatine monohydrate for a month increased levels by 4.7% in gray matter and 11.5% in white matter.2 Gray matter is where most of the processing in the brain occurs and white matter connects the different gray matter regions, allowing communication between them.

The Evidence for Creatine:

The National Health and Nutrition Examination Survey (NHANES) is a large program administered by the CDC. It examines a large sample (about 5,000 people per year) and collects health, dietary, demographic, lifestyle, and socioeconomic data. Researchers recently used NHANES data to examine the relationship between dietary creatine intake and depression.1

Data was used from over 19,000 people. The individuals were divided into 4 groups based on average daily creatine intake. In the lowest intake group (0-0.26g/day), the prevalence of depression was 10.23/100 people. In the highest intake group (0.7-3.16g/day), the prevalence of depression was 5.98/100 people. Daily creatine intake of 0.46g-3.16g/day was found to be protective against depression, especially in women. After controlling for other variables (such as socioeconomic status, other health concerns, and demographics), depression prevalence was 31% lower in the highest intake group than in the lowest intake group.

Parkinson's disease results from decreased levels of the neurotransmitter dopamine. A two year study of Parkinson patients found that patients taking creatine showed a significant improvement in mood and behavior compared to the placebo group. Other studies have found that creatine as an additive treatment to antidepressants help enhance and accelerate the effects of the medication.1  Creatine supplementation at a dose of 8g/day for 5 days reduced mental fatigue compared to a placebo on a standardized mental stress test. Multiple studies have shown that creatine has a positive impact on cognitive processing in sleep deprived individuals at sleep deprivation of up to 36 hours. It also improves cognitive function and processing in elderly persons who are not sleep deprived. Over 5 trials have found that supplemental creatine intake improves symptoms of depression, but larger trials are needed to confirm those results.2

Dietary & Supplemental Creatine:

The body needs 1-3g of creatine per day. The liver, kidneys, and brain can synthesize about half of the creatine needed daily from the amino acids methionine, arginine and glycine. The other half must be obtained through the diet or supplements.3  Creatine is found in protein rich foods such as meat and seafood. While plant foods do not contain creatine, pumpkin seeds, sesame seeds, and watermelon seeds all contain high amounts of methionine, arginine, and glycine that can be used to create creatine. 

It is worth noting that rich sources of dietary creatine are generally also rich sources of nutrients like omega-3 fatty acids, vitamin B12, and tryptophan that are known to have a positive effect on mental health. Tuna, salmon, cod, pork, and beef have about 0.2g of creatine per cooked 3oz serving. Herring can have up to double the amount of creatine than other fish or meats. 

Fitness and Creatine:

Creatine is one of the most studied and most effective supplements for increasing strength and enhancing muscular recovery, and has been studied in virtually all populations. Regular exercise, especially strength training and HIIT, alleviates symptoms of depression and anxiety. Exercise promotes BDNF, increases serotonin availability, and enhances neuroplasticity. 

If you’re looking to improve your mental health and physical fitness, creatine is a well-studied, safe supplement to add to your routine. Supplemental creatine intake of 20g/day (in 4 divided doses) for 5-7 days and then 5g/day after for at least 28 days has been shown to increase muscle strength and enhance muscular recovery following exercise sessions. There are many forms of creatine available, but 100% pure creatine monohydrate is the most studied and most effective form (it is also more affordable than other forms of creatine). While creatine is safe for the majority of individuals, people with renal disease or renal failure should not supplement with creatine before seeking the advice of their doctor or registered dietitian. 

What next?

It’s easy to feel overwhelmed when searching for reputable mental health information and care options. At Modyfi, we take a holistic approach to care. Our providers look at all aspects of your life, including fitness, nutrition, community, and more to collaboratively create treatment plans so you live life to the fullest. Book your first appointment today. 

References:

1. Bakian, A. V., Huber, R. S., Scholl, L., Renshaw, P. F., & Kondo, D. (2020). Dietary creatine intake and depression risk among U.S. adults. Translational psychiatry, 10(1), 52. https://doi.org/10.1038/s41398-020-0741-x

2. Kious, B. M., Kondo, D. G., & Renshaw, P. F. (2019). Creatine for the Treatment of Depression. Biomolecules, 9(9), 406. https://doi.org/10.3390/biom9090406

3. Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 18. https://doi.org/10.1186/s12970-017-0173-z

4. Roschel, H., Gualano, B., Ostojic, S. M., & Rawson, E. S. (2021). Creatine Supplementation and Brain Health. Nutrients, 13(2), 586. https://doi.org/10.3390/nu13020586