Creatine and depression: why brain energy also matters in mental health

Creatine is usually associated with the gym, physical performance and improved muscle strength. It is one of the best-known supplements in sport, but recently it has started to gain attention in a very different field: mental health. More specifically, in research on depression.

The question has gained relevance following a review published in Brain Medicine and reported by SINC on 30 June 2026. The study analyses whether creatine could help relieve depressive symptoms when added to standard treatments, such as antidepressant medication or psychological therapy. The results open an interesting line of research, although they are still far from a definitive conclusion.

The interest starts from a simple idea: the brain also needs energy. Although we tend to think of creatine as something that supports muscle function, its main role is linked to the energy availability of cells. It participates in the regeneration of ATP, a key molecule that allows cells to carry out their work. And the brain, although it represents only a small part of body weight, maintains constant activity and a very high energy demand.

This relationship has led some researchers to ask whether improving certain brain energy mechanisms could influence symptoms such as fatigue, lack of motivation, cognitive slowing or difficulty sustaining attention. All of these can appear in depressive episodes, although they do not explain the condition by themselves.

We know that depression is a complex disorder. It does not respond to a single cause and cannot be reduced to one biological explanation. Psychological, social, genetic, hormonal and neurochemical factors are involved. For this reason, the World Health Organization reminds us that effective treatments exist, including psychotherapy and, in certain cases, pharmacological treatments. Within that framework, creatine is being studied as a possible complementary pathway for specific profiles, not as a general answer for everyone with depressive symptoms.

The review published in Brain Medicine analysed five randomised clinical trials carried out in South Korea, the United States, Brazil, Israel and India. In total, they included 238 participants at baseline: 126 received creatine and 112 received placebo. The average age was 36, and most participants were women.

The results were uneven. Two trials observed benefits in women with major depressive disorder when five grams of creatine per day were added to treatment with escitalopram for eight weeks. Another study found a greater reduction in symptoms when creatine was combined with cognitive behavioural therapy compared with therapy plus placebo.

By contrast, other studies did not obtain the same result. One trial found no improvement in people who had previously not responded to medication. Another, carried out in adolescents, also showed no differences compared with placebo. And the study focused on people with bipolar disorder during a depressive episode found no improvement; in addition, it reported episodes of hypomania or mania in two patients taking creatine.

This difference between studies is one of the key points of the research. In mental health, not all diagnoses, ages or clinical histories can be analysed as if they were equivalent. Major depression, treatment-resistant depression, adolescence and bipolar disorder all present different scenarios.

The biological basis of this line of research makes sense. If creatine participates in the energy availability of cells, it is reasonable to study its role in an organ as demanding as the brain. In addition, some studies have suggested a possible relationship between energy metabolism, neurotransmitters and depressive symptoms. But a plausible hypothesis needs broad and consistent trials before being transferred to clinical practice.

This is where one of the major challenges of science communication appears: communicating a possibility without turning it into a false promise. In topics related to mental health, nutrition and supplements, the risk of oversimplification is very high. A preliminary study can easily become an overly blunt and dangerous idea: “creatine cures depression”. And that is where part of what matters most is lost: the context and the nuances.

In fact, a review and meta-analysis published in the British Journal of Nutrition helps to better define the scope of the evidence. This study analysed eleven trials with 1,093 participants and found a possible small to moderate reduction in depressive symptoms, but with very low-quality evidence. In addition, the average effect did not reach a clinically important difference, and the authors noted that the real effect could be trivial or even null.

The most useful reading lies somewhere in the middle. Creatine should not be presented as a solution for depression, but the interest of this line of research should not be dismissed either. Current data suggest that it deserves further research, especially in well-defined patient groups and with study designs capable of answering specific questions: in which cases it might make sense, for how long, at what dose and alongside which interventions.

Beyond the supplement itself, this line of research is interesting because it broadens the way we talk about mental health. Depression does not only affect mood. It can alter sleep, appetite, concentration, energy, memory and the ability to maintain routines. In the same way, the body influences the brain: rest, diet, stress, hormones or certain physical illnesses can change how we feel and function.

Looking at depression through the lens of brain energy adds another layer to a phenomenon that is already complex in itself. Mental health needs approaches capable of connecting biology, context and environment. That is why studies like this are valuable even when they do not offer closed answers: they help formulate better questions.

The scientific question, therefore, is not whether anyone with depressive symptoms should take creatine. The real question is much more complex: which patients could benefit, with what diagnosis, at what point in treatment, with what follow-up and with what safety guarantees.

Answering those questions will be essential before bringing this line of research into clinical practice. In the meantime, its interest lies elsewhere: in reminding us that depression requires broad perspectives, capable of connecting symptoms, treatments, metabolism, habits and context without reducing the problem to a single explanation.