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Peter Bongiorno ND, LAc
Peter Bongiorno ND, LAc

Creatine for Muscle and Mood

Creatine supplements are shown to help antidepressants work better.

Key points

  • One study of depressed women taking an antidepressant found that those who also took creatine had a better effect from the antidepressant.
  • Creatine may help increase the production of the energy molecule ATP in the brain, decreasing the likelihood of the brain making one depressed.
  • It is best to talk to one's doctor first before using creatine with medication.

Creatine is a nitrogen-based compound that helps the body with energy. Typically used as a pure white powder mixed in a beverage, it is well-known as a muscle enhancer with athletes, especially those who like to pump iron. But there may be a new and exciting use for this common supplement.

Why We Need a New Approach

A large 2010 meta-analysis in the New England Journal of Medicine concluded that antidepressant medications work no better than placebo in mild to moderate cases of depression (1). Meta-analyses are basically studies that look at all the studies to date, to help decide if there really is an effect of the particular substance being studied. This meta-analysis was pretty clear that antidepressants don’t work any better than a sugar pill in all but the most severe cases of depression.

Generally, when medications do work, they typically take a minimum of 6 weeks to gain a noticeable helpful benefit, and can still take up to 12 weeks to reveal full benefit (2). This is where creatine fits in: It may help people who are not finding benefit from their antidepressant drugs.

Creatine + Antidepressant = Good Effect?

A new Korean study looked at 52 women diagnosed with major depression. Every woman received Lexapro (escitalopram), a common antidepressant medication. Then, the researchers gave about half the women 5 grams of creatine, and the other half the women received a placebo pill. By the second week, the women taking the creatine had a much better effect, and their scores showed they were not clinically depressed, whereas the placebo group had some improvement, but still scored in the depressed zone. These improvements continued by the end of the testing period, which was 8 weeks. Problem side effects like nausea, insomnia, and agitation were ascribed to the medication (3).

How Does Creatine Help?

Creatine is a popular exercise supplement known for its benefit in helping athletic performance. It also may have value for neurological conditions like muscular dystrophy (4). Creatine supplementation reduces the damage on our genetic material (which can increase cancer risk) as well as stops the fats from oxidizing in our blood (a problem that contributes to heart disease)(5), and protects our nerve cells from toxins (6). As far as creatine’s role for depression, it seems creatine may help increase the production of the energy molecule ATP in the brain, which may make the brain less likely to make us feel depressed.

Practical Use

In my practice, most first-time patients with depression are already on at least one anti-depressant. Many are on more than one, and in round-robin style, have already tried a number of antidepressant medications. From a naturopathic perspective, any natural supplement that we can offer to help medication work faster and better is welcome as a first step.

Once patients feel better, they can hopefully begin to work on the underlying causes of their mood challenges. These underlying issues often include nutrient deficiencies, poor food intake, lack of exercise, poor sleep, stressors, and environmental toxic load.

Creatine Caution With Bipolar Disorder

Right now, we do not know if creatine will have the same beneficial effect on men for one study with rats suggest only females may benefit (7).

Creatine is known to be pretty safe. As a caution, those with kidney issues or high blood pressure are recommended to be careful, although no negative effects have been shown. Please note though that one 10-person study showed 2 men with bipolar taking medication actually got worse with creatine (8), so it is prudent to talk to your doctor first before using creatine with medication, and it is best to avoid creatine if you have bipolar disorder until we understand more about how it works with brain chemistry.


1. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis.JAMA. 2010 Jan 6;303(1):47-53.

2. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163:1905–1917

3. Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, Bae S, Renshaw PF. 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 Sep 1;169(9):937-45. (

4. Banerjee B, Sharma U, Balasubramanian K, Kalaivani M, Kalra V, Jagannathan NR. Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized, placebo-controlled 31P MRS study.Magn Reson Imaging. 2010 Jun;28(5):698-707. Epub 2010 Apr 15.

5. Rahimi R.J Creatine supplementation decreases oxidative DNA damage and lipid peroxidation induced by a single bout of resistance exercise. Strength Cond Res. 2011 Dec;25(12):3448-55.

6. Roy BD, Bourgeois JM, Mahoney DJ, Tarnopolsky MA. Dietary supplementation with creatine monohydrate prevents corticosteroid-induced attenuation of growth in young rats. Can J Physiol Pharmacol. 2002 Oct;80(10):1008-14.

7. 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 Jan;35(2):534-46.

8. Roitman S, Green T, Osher Y, Karni N, Levine J. Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord. 2007 Nov;9(7):754-8.

About the Author
Peter Bongiorno ND, LAc

Peter Bongiorno is a naturopathic doctor and the author of Healing Depression: Integrated Naturopathic and Conventional Treatments.

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