Does creatine supplementation reduce brain fog?

Creatine supplementation raises creatine concentrations in the brain, which can be measured using a technique that maps brain metabolites (MRS). Whether that increase actually relieves brain fog is a separate question: the cognitive effects depend on who you are and what situation you are in.

In healthy young people the effect is small and inconsistent. A systematic review of six randomised trials (281 participants) found a modest improvement in short-term memory and reasoning, but the studies contradicted one another on other cognitive domains such as attention, reaction time and long-term memory. A double-blind crossover study in fourteen healthy athletes showed that creatine improved accuracy on one memory task, but did not prevent the decline caused by mental fatigue on other tasks. Motivation and vitality were even lower with creatine than with placebo in that study.

The most consistent benefit is seen in situations of metabolic stress. Two reviews report that creatine supplementation helps with sleep deprivation, mental exhaustion after exertion, and oxygen deficiency at high altitude. For the everyday brain fog that people experience without a clear stressor, this effect has not been demonstrated.

In ME/CFS patients, a group for whom brain fog is a core symptom, there is one small feasibility study (11 completers, no placebo group) that found improved brain creatine levels, reduced fatigue and a shorter reaction time after six weeks of supplementation at 16 grams per day. Because of the absence of a control group and the small sample size, these are preliminary findings that do not permit conclusions.

The group for whom creatine supplementation appears most promising is vegetarians and vegans. They obtain very little creatine through diet and therefore have lower stores in muscles and brain. Multiple studies and reviews confirm that they respond better to supplementation than meat-eaters do, with measurable improvements in neuropsychological performance. This suggests that the cognitive effect of creatine is strongly linked to baseline levels: those who already have enough notice little benefit.

Regarding safety: multiple reviews confirm that creatine supplementation is safe at up to 20 grams per day for the general population. An exception applies to people with kidney disease, because the kidneys process creatine and those with kidney conditions have a reduced excretion capacity. Caution is warranted for this group.