Does Creatine Improve Mental Health?

When you think of creatine, you probably picture bodybuilders and athletes chugging shakes to bulk up and boost their performance. But this supplement isn't just for gym-goers. An increasing number of studies suggest that creatine can also have powerful effects on mental health, particularly in alleviating depression and anxiety symptoms.

Depression is a complex disorder, but researchers believe mitochondrial dysfunction may play a key role [1]. The mitochondria are like the batteries of our cells, producing the energy currency ATP that powers all cellular functions. Brain imaging reveals that people with depression often have alterations in mitochondrial activity and energy metabolism in multiple brain regions compared to healthy individuals [2]. This energy deficit may contribute to the pathology of depression.

How Does Creatine Work?

Creatine is a reserve energy source that quickly replenishes ATP [3]. The creatine kinase/phosphocreatine system is a critical backup generator for the brain, buffering ATP levels in energy-hungry neurons [4]. Oral creatine supplementation has increased brain creatine content by as much as 13.3% in humans [5], providing extra fuel for depleted brain cells.

But the mental health benefits of creatine go beyond just providing an energy boost. Animal studies demonstrate that creatine has antidepressant-like effects comparable to ketamine and Prozac [6, 12]. Creatine also increases the formation of new synapses and the expression of proteins involved in neuroplasticity, the brain's ability to adapt and change [7]. This is crucial because depression and chronic stress can cause neurons to wither and retract their connections. By promoting the birth and growth of neurons and synapses, creatine may help reverse the brain atrophy seen in depression.

Human trials further support creatine's mood-lifting properties. Multiple studies have found that 2-10 grams of creatine daily can reduce depressive symptoms in both unipolar and bipolar depression when added to standard antidepressants [8, 9, 10]. These effects can manifest rapidly, with improvements seen in at least 2 weeks [9]. Creatine also shows promise as an augmentation strategy for patients who haven't responded to antidepressants alone. For example, in one trial, half of treatment-resistant patients who added creatine to their medication regimen experienced improvement in their depressive symptoms [11].

Creatine Versus Traditional Medicines

How does creatine compare to the mechanisms of traditional antidepressants? Interestingly, creatine shares many downstream effects with the fast-acting experimental drug ketamine. Both compounds increase activation of the mTOR signaling pathway, which is critical for synapse formation and plasticity [12]. Creatine also modulates multiple neurotransmitter systems implicated in depression, including activating dopamine receptors and enhancing serotonin release [13].

In addition to fighting depression, creatine may help buffer the brain against stress and anxiety. Acute stress rapidly depletes phosphocreatine levels in the brain [14], and this depletion correlates with the development of anxiety and PTSD-like behavior in animal models [15]. Creatine supplementation prevents this breakdown of phosphocreatine and reduces anxiety in chronically stressed rats [15]. In healthy humans, creatine improves mood and reduces mental fatigue induced by stressors like sleep deprivation [16, 17]. It also shows promise for treating PTSD symptoms in people with comorbid depression [18].

The most common supplemental form is creatine monohydrate, which has been extensively studied for physical and mental benefits. Typical antidepressant doses range from 2 to 10 grams per day, with 3 to 5 grams being the average effective dose [8, 9, 10]. Creatine is well-tolerated, with studies finding no adverse effects of long-term supplementation at recommended doses [19]. Best of all, creatine is widely available over the counter and costs pennies daily compared to some brand-name prescription medications. 

In conclusion, science indicates that creatine may benefit a holistic mental health treatment plan. When used responsibly with a balanced diet, lifestyle modifications, therapy, and/or medication, creatine may help light the way to brighter moods and calmer days.

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References:

1. Allen PJ. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value? Neurosci Biobehav Rev. 2012;36(5):1442-1462.
2. Kious BM, Kondo DG, Renshaw PF. Living High and Feeling Low: Altitude, Suicide, and Depression. Harv Rev Psychiatry. 2018;26(2):43-56.
3. Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids. 2011;40(5):1271-1296.
4. Andres RH, Ducray AD, Schlattner U, Wallimann T, Widmer HR. Functions and effects of creatine in the central nervous system. Brain Res Bull. 2008;76(4):329-343.
5. Dechent P, Pouwels PJ, Wilken B, Hanefeld F, Frahm J. Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol. 1999;277(3):R698-704.
6. Allen PJ, D'Anci KE, Kanarek RB, Renshaw PF. Chronic creatine supplementation alters depression-like behavior in rodents in a sex-dependent manner. Neuropsychopharmacology. 2010;35(2):534-546.
7. Cunha MP, Budni J, Pazini FL, et al. Involvement of PKA, PKC, CAMK-II and MEK1/2 in the acute antidepressant-like effect of creatine in mice. Pharmacol Rep. 2014;66(4):653-659.
8. Lyoo IK, Yoon S, Kim TS, et al. 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. Am J Psychiatry. 2012;169(9):937-945.
9. Roitman S, Green T, Osher Y, Karni N, Levine J. Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord. 2007;9(7):754-758.
10. Nemets B, Levine J. A pilot dose-finding clinical trial of creatine monohydrate augmentation to SSRIs/SNRIs/NASA antidepressant treatment in major depression. Int Clin Psychopharmacol. 2013;28(3):127-133.
11. Toniolo RA, Silva M, Fernandes FB, et al. A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression. J Neural Transm (Vienna). 2018;125(2):247-257.
12. Cunha MP, Pazini FL, Rosa JM, et al. Creatine, Similar to Ketamine, Counteracts Depressive-Like Behavior Induced by Corticosterone via PI3K/Akt/mTOR Pathway. Mol Neurobiol. 2017;54(9):6818-6834.
13. Cunha MP, Pazini FL, Oliveira Á, et al. Evidence for the involvement of 5-HT1A receptor in the acute antidepressant-like effect of creatine in mice. Brain Res Bull. 2013;95:61-69.
14. Kim SY, Lee YJ, Kim H, et al. Desipramine attenuates forced swim test-induced behavioral and neurochemical alterations in mice: an in vivo (1)H-MRS study at 9.4T. Brain Res. 2010;1348:105-113.
15. Kious BM, Sabic H, Sung YH, Kondo DG, Renshaw P. An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women. J Clin Psychopharmacol. 2017;37(5):578-583.
16. Watanabe A, Kato N, Kato T. Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res. 2002;42(4):279-285.
17. McMorris T, Harris RC, Swain J, et al. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology (Berl). 2006;185(1):93-103.
18. Amital D, Vishne T, Roitman S, Kotler M, Levine J. Open study of creatine monohydrate in treatment-resistant posttraumatic stress disorder. J Clin Psychiatry. 2006;67(5):836-837.
19. Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008;28(3):172-178.

 

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Always consult with your healthcare provider.