In the most comprehensive investigation of the ketogenic diet’s mental health effects yet, researchers pooled 50 studies spanning six decades to see what we actually know about its influence on mood. The results are a mix of promising and “too early to say.”
Researchers from St Michael’s Hospital in Toronto were particularly interested in finding consistent evidence on whether eating keto could relieve symptoms of depression and anxiety. Overall, 50 studies made the cut, featuring 41,718 participants aged 18-70 years from 15 countries. Nearly half (23) of the studies had been conducted by US scientists, and most had been done in the last decade.
To break it down further, this systematic review and meta-analysis looked at 14 randomized controlled trials (RCTs), 17 quasi-experimental studies, five cross-sectional analyses, six clinical series – a group of case reports involving patients given similar treatment – and eight case reports. All studies were published between 1965 and 2025, with 41 focused on depression and 29 on anxiety, with some crossover. In 22 studies, participants had a clinical psychiatric diagnosis, while in others the mental health outcomes were secondary endpoints.
“Ketogenic diets (KDs) have been hypothesized to influence mental health through pathways involving mitochondrial function, inflammation, and neurotransmitters, but their therapeutic value in psychiatric populations remains uncertain,” the researchers noted.
The studies covered a wide range of groups: people with major depressive disorder, (MDD) bipolar disorder, schizophrenia, PTSD and generalized anxiety disorder (GAD), as well as non-psychiatric groups where mental health was measured alongside obesity or metabolism. Importantly, all studies made use of validated mental health scales such as the Patient Health Questionnaire-9 (PHQ-9) for depression and the Generalized Anxiety Disorder (GAD-7) scale.
The issue with many such large-scale studies is that due to the nature of individual research projects, a review can be like comparing apples and oranges. In an effort to represent the huge amount of data involved – gathered from different kinds of studies, with varying methods, populations and avenues of investigation – the researchers slotted them into subgroups to see if any patterns emerged.
Across 10 RCTs, participants on keto diets experienced greater improvements in depression scores than those in comparison groups (high-carbohydrate, for example). Statistically, this was described as having a “small-to-medium effect,” which essentially means most people in the trials didn’t experience dramatic changes, but the improvement was consistently greater than chance.
In studies that monitored participants’ ketone levels, to confirm metabolic ketosis, the improvement in depressive symptoms appeared more substantial. In studies that didn’t, the benefit compared with control groups was small and even disappeared in some. This suggests that the keto diet may only have a real influence in relieving depression when ketosis is reached – where the body switches to burning fat due to the absence of carbohydrates for fuel. Diets that allowed very few carbohydrates (around 10% of daily energy) were linked to greater mood improvements than more moderate low-carb diets (11%-20%).
The researchers also found that body size appeared to play a role in how effective keto was on depression. There were no meaningful mental health benefits found when participants were clinically obese, but the modest improvements were statistically significant in non-obese cohorts.
In the quasi-experimental studies – where everyone was on a keto diet, and there was no control group – the researchers found a moderate, but not dramatic, overall improvement in depressive symptoms overall. While there was a small difference in the results from the ketone-monitored studies and those that didn’t measure, it wasn’t a statistically significant one. In other words, the researchers found no robust evidence that ketone monitoring changed the outcome when it came to quasi-experimental study design.
What’s more, because participants in these studies aren’t randomly assigned or compared to a control group, the results can’t actually prove the diet caused any reported mental health improvements.
When it came to anxiety, the data was even less convincing. In nine RCTs that measured anxiety almost no difference between keto and other diets was found. However, less rigorous studies – where participants weren’t randomized – often showed improvement over time. The researchers, however, caution that this may be due to a number of variables –including the placebo effect, lifestyle changes or adherence – and not actually true diet-driven relief.
In six quasi-experimental studies that investigated anxiety, the statistics suggested a medium level of anxiety relief over time during the keto trial, but when these groups were split further into those that measured ketone levels versus those that didn’t, or those involving people with neurological disorders versus those without, there were no meaningful differences. Essentially, any change in anxiety symptoms were the same across all groups, so no specific factor could be credited with being beneficial.
“In this systematic review and meta-analysis of 50 studies, [keto diets] were associated with small to moderate improvements in depressive symptoms in randomized clinical trials and with larger improvements in quasi-experimental studies,” the researchers noted. “No significant associations were found for anxiety in randomized clinical trials.”
Meanwhile, the researchers found that in the clinical series and case reports, a decrease in psychotic symptoms and better mood regulation was observed in patients with schizophrenia and bipolar spectrum disorder. An additional PTSD study also found the diet was linked to positive outcomes, but more work is needed.
Overall, the team found that keto diets (KDs) may help reduce depressive symptoms, especially under well-supported, ketone-monitored conditions – but there’s not enough evidence to make clinical recommendations. And study into anxiety relief is still preliminary.
“In this systematic review and meta-analysis, KDs were associated with modest improvements in depressive symptoms, particularly with biochemical ketosis verification, while anxiety evidence was inconclusive,” they wrote. “Given heterogeneity, comparators, and short follow-up, well-powered trials with standardized, verified protocols, structured support, and pre-specified outcomes are needed to confirm efficacy and durability.”
Much like mental health treatment, there’s unlikely to be a one-size-fits-all fix found in diet. However, there’s a growing body of work investigating metabolic psychiatry. In previous studies, there have been interesting results when it comes to keto diets and bipolar disorder, cognitive functioning and epilepsy. The diet – which is categorized by its high-fat and low-carbohydrate content – was originally used to treat pediatric epilepsy, more than a century ago, in 1921. Now, it’s most often associated with type 2 diabetes and obesity management.
The review was published in JAMA Psychiatry.
Source: St Michael’s Hospital via MedicalXpress
