In February, Robert F. Kennedy Jr., the US secretary of health, made a characteristically bold claim. A doctor at Harvard University, he proclaimed, “has cured schizophrenia using keto diets”.
If you happened to be passing Harvard University that day, you might have heard the sound of that doctor’s palm hitting his forehead. “For the record, I have never ever once used the word ‘cure’ in any of my work,” says Christopher Palmer, a psychiatrist at Harvard Medical School. “Nonetheless, I have used the word ‘remission’…”
The idea that a diet best known as a fat-busting fad could treat serious mental illness might sound like the latest offering from the wild west of online wellness: something destined to be filed alongside raw water and coffee enemas in the annals of terrible suggestions.
But there are a number of reasons why the idea of using the diet for conditions affecting the brain deserves closer inspection. For one thing, over 100 years’ worth of research has shown that ketogenic diets have real, measurable effects on the body in general, as well as on the organ between your ears. For another, many of these changes – some at the cellular level, others throughout the whole body – are known treatment targets in mental illness.
With evidence from small trials and case studies indicating that ketogenic diets can dramatically improve symptoms in some people with mental health conditions, a growing number of scientists are wondering if what is called metabolic psychiatry could lead to much-needed new treatments for conditions affecting the brain and the mind-body connection.
“We’ve wasted 30 years thinking about dopamine and serotonin as the sole targets for psychiatric medications,” says Daniel Smith, a psychiatrist at the University of Edinburgh, UK. “This is a new paradigm. It’s exciting.”
Fuelling the brain
Nowadays, ketogenic diets are mainly associated with efforts to lose weight, but they were first developed more than a century ago to treat problems with the brain. At that time, few drugs were available for epilepsy. One thing that did seem to work was fasting for several days at a time, which significantly reduced seizures and sometimes stopped them altogether. The problem was, it wasn’t sustainable. Sooner or later, people would need to eat and when they did, their seizures would return.
Researchers set out to find a solution, and in the 1920s, Russell Wilder, a physician and epilepsy researcher at the Mayo Clinic in Minnesota, cracked it. He developed a high-fat, moderate-protein and very-low-carb diet to mimic fasting, while still providing enough energy to live on. He called it the ketogenic diet because it was designed to trigger the metabolic shift that happens when the body cannot get hold of carbohydrates from food and so has to switch to burning fats, generating small molecules called ketone bodies in the process.
As we are a species that mostly eats plants, carbohydrates are our default fuel. Carbs are quickly broken down into glucose during digestion, which can be burned in our cells for energy. This process takes place in the mitochondria, cellular organelles where food is converted into adenosine triphosphate (ATP), the body’s energy currency. What isn’t used straight away is stored as glycogen in the liver and muscles, to be called on between meals. When those stores are full, any spare calories are deposited as fat.
If food is short, and carbohydrates aren’t so easy to come by, the body reverses the process. First it releases stored glycogen, which can keep us ticking over for up to a day. When that runs out, the body begins to break into its fat reserves for energy.
Some of the fatty acids released are sent to be burned in the mitochondria, while others are passed to the liver, where they are converted into ketone bodies. Ketone bodies are smaller than fatty acids and, because they are water-soluble, are easier to transport in the blood to where they are needed. They also have the advantage of being small enough to cross the blood-brain barrier, allowing them to be used in place of glucose as fuel for the brain.
The keto diet is high-fat, moderate-protein and low-carb – making foods like eggs, meat, avocado and leafy greens typical fare
Addictive Stock/StockFood
It is an ingenious system, and the switch back and forth between fuel types probably came into play pretty regularly for our hunter-gatherer ancestors. For most modern humans, though, carbs are so easy to come by that the metabolic switch happens rarely, if at all.
Wilder’s idea was for a diet designed to flick the switch to fat burning, while providing enough fat in the diet so the body didn’t need to break down its own fat reserves. If this state of “nutritional ketosis” worked, it could be used as a more sustainable alternative to fasting.
In 1921, Wilder published a paper showing that it did indeed work. In three people with epilepsy, the ketogenic diet reduced seizures as effectively as fasting, and could be maintained for longer. Later research backed him up and the keto diet became an epilepsy treatment. When new anticonvulsant medications came along in the 1930s, though, Wilder’s diet fell out of favour, only to be used in young children and those who don’t respond to any available medications.
Nevertheless, the fact that it worked suggested that there’s something about “going keto” that corrects problems with brain function. Several decades of research later, we have a better idea of what’s happening under the lid when our bodies switch to back-up-fuel mode.
The short answer is: lots of things. The simplest and most obvious is that it involves eating far less sugar. While glucose is our body’s default energy source, having too much of it is known to be disastrous for the health of the body and brain. Long-term overindulging in carbs contributes to inflammation, insulin resistance, diabetes and obesity, while the evidence suggests that high-sugar diets are more likely to lead to low mood in people both with and without depression.
It is possible, then, that some of the keto diet’s effects come down to bringing us closer to the diet our bodies evolved to expect. “We are wired to like sugar, but in nature, sugar wasn’t around that much,” says Guido Frank, a psychiatrist at the University of California, San Diego. “It’s not that sugar is [always] bad for us, it’s about the quantity.”
One upshot of reducing carbs is a change in the microbiome. Ketogenic diets have been shown to inhibit the growth of carb-loving, pro-inflammatory bacteria in the gut, which may reduce inflammation throughout the body and brain. The well-known link between the microbiome and mental health, and the role of the gut-brain axis in regulating brain function, may also play a role in improving symptoms.
Some of these effects may be possible without going full keto. The classic ketogenic diet involves reducing carbohydrates from 45 per cent of total calories to just 1 to 5 per cent. Reducing carbs less dramatically, or following a low-glycaemic-index diet that focuses on slow-release carbohydrates instead of simple sugars, might provide at least some of the benefits, says Palmer. “A low-glycaemic-index diet is not necessarily ketogenic, but it’s certainly having anti-inflammatory and insulin-signalling effects and probably affects the gut microbiome as well,” he says.
Other changes, however, do seem to require switching to ketosis. One example is the way ketone bodies appear to act directly on the brain to balance two key neurotransmitters: glutamate, which excites neurons to fire, and GABA, which inhibits their firing. An excess of glutamate, relative to GABA, is associated with the uncontrolled firing seen in epileptic seizures and the erratic brain activity implicated in psychosis. Some of the anticonvulsant medications that are used to treat epilepsy, schizophrenia and bipolar disorder boost GABA relative to glutamate. Evidence from mouse studies suggests that keto diets do something similar.
Ketone bodies
How exactly ketone bodies rebalance these neurotransmitters isn’t clear. One possibility, however, is that they simply provide enough energy for the brain to do its job properly. Ketone bodies are harder to produce in the body than glucose, but, once formed, are a more efficient fuel source for the mitochondria, netting 27 per cent more ATP per molecule.
A boost of energy in the brain could do more than just even out neurotransmitter levels. Studies focusing on schizophrenia, bipolar disorder and depression, as well as Alzheimer’s disease and anorexia nervosa, have found evidence of mitochondrial dysfunction. And while there are many routes to malfunctioning mitochondria – from genetics to diet and other lifestyle factors – it does suggest that a problem with releasing energy from glucose may play a role in many brain-related issues.
Carmen Sandi, a neuroscientist at the Swiss Federal Institute of Technology in Lausanne, studies the connection between mitochondrial health and mental illness. She points out that the brain is the most energy-hungry organ, demanding 20 per cent of the body’s fuel at rest, despite only accounting for 2 per cent of body weight. But “that’s only part of the story”, she says.
Ketone bodies are tiny enough to cross the blood-brain barrier, which means they can be used as fuel for the brain, in place of glucose
JAMES BELL/SCIENCE PHOTO LIBRARY
“Mitochondria are not just the energy producers – they also contribute to the precise functioning of neurons and brain circuits”, with a role in making hormones and other signalling molecules, and in regulating inflammation and managing oxidative stress. There is some evidence that ketone bodies generate less oxidative stress than glucose, says Sandi, so reduce the demand for metabolic clean-up.
For Palmer, all of this evidence points to a common underlying cause for mental health conditions: that they are due to metabolic problems in the brain. He points to the fact that physical metabolic conditions, such as diabetes, obesity and insulin resistance, substantially increase the risk of depression. The reverse is also true: people with mental health conditions are at greater risk of diabetes, obesity and heart disease.
That ketogenic diets might help treat metabolic problems in the brain first occurred to Palmer in the late 2010s when he was treating a women in her 70s who had experienced debilitating, drug-resistant schizophrenia for more than 50 years.
As is common in severe mental illness, in addition to being extremely mentally unwell, the woman, Mildred, had obesity and her physical health was deteriorating. She was advised to try the keto diet to lose weight. Within weeks, in addition to weight loss, she started to notice improvements in her schizophrenia symptoms. The voices in her head became quieter, her mood improved and, then, after decades of being affected by the condition, she went into full remission. Palmer was amazed, and in 2019 published a paper describing Mildred’s experience and a similar remission result from a second person with schizophrenia.
It was this research that caught the attention of Robert F. Kennedy Jr., and spawned a grassroots movement spearheaded by the philanthropist Jan Ellison Baszucki and her husband David Baszucki, founder and CEO of the tech company Roblox. In 2021, the couple’s son, Matthew, had been struggling with treatment-resistant bipolar disorder for five years. Having run out of other treatment options, he went on the ketogenic diet, under the guidance of Palmer. Within months, he, too, was in remission. The family went on to set up a foundation to fund research in metabolic psychiatry and to share stories from people who have had a positive experience with keto. At the last count, the foundation’s Metabolic Mind YouTube account had more than 97,000 subscribers.
When eating keto, carbohydrates like bread are firmly off the menu
Patrick Chatelain/www.plainpicture.com
Meanwhile, research by other groups added to the excitement, including one 2022 study in 31 people, all of whom had previously been hospitalised with severe depression, bipolar disorder or schizoaffective disorder. Of the 31 volunteers who agreed to try the ketogenic diet, 28 managed to stick to it for two weeks or more. All 28 saw some improvement in their symptoms and almost half reached the criteria for clinical remission. However, the study had no control group.
If there is one mental health condition where a fat-burning diet wouldn’t seem to apply, it would be anorexia. Suggesting that people who have a history of disordered eating cut a major food group out of their diet sounds irresponsible and potentially dangerous.
Yet evidence shows that, when people are properly supported and under medical supervision, ketogenic diets might just help. Frank was involved in a 2022 pilot study in five people with anorexia that reported that they were able to maintain a healthy weight on the ketogenic diet with fewer food-related anxieties. Four of the five kept the diet up after the study and continued to improve. “It was incredible,” says Frank. “I hadn’t seen that before in 20 years of working in this field.”
As with other mental health conditions, there are plausible reasons why going keto might help. For one, studies by Cynthia Bulik, a clinical psychiatrist at the Karolinska Institute in Sweden, and her colleagues have shown that anorexia is associated with gene variants linked to inefficient energy release in the mitochondria.
As such, one possibility is that when someone with a genetic metabolic vulnerability starts dieting, the switch to ketosis brings a boost of energy and lowers anxiety. This, in turn, may reinforce the compulsion to restrict food further, trapping people in a cycle of weight loss that gets out of control. “People with anorexia nervosa may have a goal weight, but for many of them, it’s never enough,” says Frank. “It’s almost like an addictive process.”
Now, researchers are wondering if a properly balanced ketogenic diet could help people with anorexia to find a delicate balance – allowing them to get to a healthy weight while removing the compulsion to restrict food. If going into nutritional ketosis can reduce anxiety in a similar way to self-starvation, then “mimicking the underweight state by providing ketone bodies for energy creation might make the need to restrict unnecessary”, says Frank.
It is early days, says Sahib Khalsa, a psychiatrist who researches and treats anorexia at the University of California, Los Angeles. He adds that keto diets shouldn’t be tried for mental health conditions without a doctor’s support. “There’s a difference between trying it with an eating disorder psychiatrist who’s monitoring you carefully, and reading about a ketogenic diet and then deciding spontaneously to do it,” he says. “From a safety standpoint, I think it’s definitely premature for that.”
Filling the gaps
For all the case studies and testimonials, keto for the brain is far from a done deal. Smith points out that there have been no properly controlled, randomised trials in large numbers of individuals, so it is impossible to know what proportion of people will respond as dramatically as Mildred and Matthew Baszucki. “There might be two people who have an excellent response, and that’s great,” he says. “But there might be 98 other people who don’t get any response.”
To try to fill this gap, Smith, along with Steven Marwaha at the University of Birmingham, UK, is beginning a large-scale, randomised controlled trial in 200 people with bipolar depression. The study will compare a nutritional ketogenic diet with a diet based on UK healthy eating guidelines. The results won’t be in for at least five years, says Smith. In the meantime, the results of a pilot study with 27 people that Smith and his colleagues published in 2025 were encouraging, finding a correlation between ketone levels and improved mood and energy levels. Brain imaging also showed a decrease in glutamate levels in brain regions involved in emotional processing.
Another unknown is whether any of the many mechanisms are more important than others for people who might benefit from the keto diet. “It is plausible that different individuals derive benefit through different dominant mechanisms, depending on their underlying metabolic and neurobiological vulnerabilities. However, in many cases, the therapeutic effects likely arise from their combined impact,” says Shebani Sethi, a metabolic psychiatrist at Stanford University in California.
As larger clinical trials get under way, and the results continue to roll in, metabolic psychiatry could go a number of ways. Keto diets might turn out to work very well for some people, and not at all for others, in which case research will focus on identifying markers that indicate who they might benefit. Or further research may allow us to extract the special sauce from ketogenic diets, which could then inform new drug treatments and make it unnecessary to stick to a restrictive diet.
For now, though, says Palmer, the important thing is to make people aware that, even when they have tried everything, there is still hope. “Some people respond really well to existing treatments, but it’s heartbreaking to see patients year after year, decade after decade, who are doing everything we’re asking them to do and they are profoundly suffering. Offering even one additional tool that might work for some patients is my passion. This is our moment for metabolism and mental health. That’s what I’m hoping.”
Topics: