Brett Ryder
In February,听Robert F.聽Kennedy Jr., the US secretary of health,听made a聽characteristically聽bold claim.聽A doctor聽at聽Harvard University,听he聽proclaimed,听.
If you happened to be passing Harvard University that day, you might have heard the sound of that doctor鈥檚 palm hitting his forehead. 鈥淔or the record, I have never ever once used the word 鈥榗ure鈥欌痠n any of my work,鈥 says , a psychiatrist at Harvard Medical School. 鈥淣onetheless, I have聽used the word聽鈥榬emission鈥欌︹
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 聽and coffee enemas聽in the annals of terrible聽suggestions.
But聽there are聽a number of聽reasons why聽the idea of聽using聽the聽diet聽for聽conditions affecting聽the brain聽deserves聽closer inspection.聽For聽one thing,听over聽100聽years鈥 worth of聽research has shown聽that ketogenic diets聽have real, measurable effects on聽the body聽in general, as well as on the organ between your ears.聽For another,听many of聽these changes聽鈥撀爏ome at the cellular level, others throughout the whole body聽鈥撀燼re聽known聽treatment targets聽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.
鈥淲e鈥檝e wasted 30 years thinking about dopamine and serotonin as the sole targets for psychiatric medications,鈥 says聽,听a psychiatrist at the University of Edinburgh, UK.聽鈥淭his is聽a new paradigm.聽It鈥檚聽exciting.鈥
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 for several days at a time, which significantly reduced seizures and sometimes stopped them altogether. The problem was, it wasn鈥檛 sustainable. Sooner or later, people would need to eat and when they did, their seizures would return.
Researchers set out to find a solution,听and in聽the聽1920s,听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鈥檚 energy currency. What isn鈥檛 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聽aren鈥檛聽so easy to come by, the body聽reverses the process.聽First聽it聽releases stored glycogen, which can keep us ticking over for up to a day. When that runs out, the body聽begins聽to break聽into its聽fat reserves聽for energy.
Some of the fatty acids聽released聽are聽sent to be聽burned in the mitochondria, while others are聽passed聽to the liver,听where they are聽converted into ketone bodies.聽Ketone bodies are smaller聽than fatty acids聽and, because they are water-soluble, are聽easier to transport in the blood聽to where they are needed.聽They also聽have the advantage of being small enough to cross the blood-brain barrier,听allowing them to be聽used in place of glucose as聽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鈥檚 idea was for a聽diet聽designed to聽flick聽the聽switch to fat聽burning,听while聽providing enough fat in the diet聽so the body聽didn鈥檛聽need to break down its own聽fat聽reserves. If this state聽of聽鈥渘utritional ketosis鈥澛爓orked, it could be used as a more sustainable alternative to fasting.
In 1921,听Wilder published聽a paper showing聽that聽it聽did indeed聽work. In three people with epilepsy,听the ketogenic聽diet reduced聽seizures as聽effectively聽as fasting,听and could be聽maintained聽for longer.聽Later聽research聽backed him聽up聽and the keto diet聽became an聽epilepsy treatment.聽When new anticonvulsant medications聽came along in the 1930s,听though,听Wilder鈥檚 diet聽fell out of聽favour,听only to be聽used聽in聽young children and those聽who聽don鈥檛聽respond to any available medications.
Nevertheless, the fact that it worked suggested that there鈥檚 something about 鈥済oing keto鈥 that corrects problems with brain function. Several decades of research later, we have a better idea of what鈥檚 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鈥檚 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 .
It聽is possible, then, that some of the聽keto diet鈥檚聽effects come down to bringing us closer to the diet our bodies evolved to expect. 鈥淲e are wired to like sugar,听but in nature,听sugar聽wasn鈥檛 around that much,鈥澛爏ays聽,听a psychiatrist at the University of California, San Diego. 鈥淚t’s not that sugar聽is聽[always]聽bad for us, it鈥檚 about the quantity.鈥
One upshot of reducing carbs聽is a change in the microbiome.聽Ketogenic diets have been shown to聽,听which may聽reduce inflammation聽throughout the body and brain. The聽well-known link between the聽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. 鈥淎 low-glycaemic-index diet is not necessarily鈥痥etogenic, but it’s certainly having anti-inflammatory and insulin-signalling effects and probably affects the gut microbiome as well,鈥 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 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聽.
Ketone bodies
How exactly聽ketone聽bodies聽rebalance聽these聽neurotransmitters聽isn鈥檛聽clear.聽One possibility, however,听is that聽they simply provide enough energy for the聽brain聽to do聽its聽job properly.聽Ketone bodies聽are聽harder to聽produce in the body聽than glucose,听but, once formed, are聽a more efficient fuel source for the mitochondria,听聽per molecule.
A boost of energy in the brain could do more than just聽even out聽neurotransmitter levels. Studies聽focusing on聽,听听补苍诲听, as well as Alzheimer鈥檚 disease and anorexia nervosa, have found evidence of mitochondrial dysfunction. And while there are many routes to malfunctioning mitochondria 鈥 from genetics to diet and other lifestyle factors 鈥 it does suggest that a problem with releasing energy from glucose may play a role in many brain-related issues.
, 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鈥檚 fuel at rest, despite only accounting for 2 per cent of body weight. But 鈥渢hat鈥檚 only part of the story鈥, 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
鈥淢itochondria are not just the energy producers 鈥 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,听all of聽this evidence points to a common underlying cause for mental health聽conditions: that聽they聽are聽due to聽 in the brain. He points to the fact that physical metabolic conditions, such as diabetes, obesity and聽, substantially increase the risk of depression. The reverse is also true: people with 聽of diabetes,听obesity聽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聽describing聽Mildred鈥檚 experience and a similar聽remission result from a second聽person聽with schizophrenia.
It was this research that caught the attention of Robert F. Kennedy Jr., and spawned a grassroots movement spearheaded by the philanthropist聽, 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鈥檚 had more than 97,000 subscribers.
When eating keto, carbohydrates like bread are firmly off the menu Patrick Chatelain/www.plainpicture.com
Meanwhile,听research by聽other groups聽added to the excitement, including聽, 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鈥檛 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 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. 鈥淚t was incredible,鈥 says Frank. 鈥淚 hadn’t seen that before in 20 years of working in this field.鈥
As with other mental health conditions, there are plausible reasons why going keto might help. For one,听studies by聽, a clinical psychiatrist at the Karolinska Institute in Sweden,听and her colleagues聽have shown that anorexia is associated with 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聽lowers聽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. 鈥淧eople with anorexia nervosa may have a goal weight,听but for many of them,听it’s never enough,鈥 says Frank. 鈥淚t鈥檚 almost like an addictive process.鈥
Now, researchers are wondering if a properly balanced ketogenic diet could help people with anorexia to find a delicate balance 鈥 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 鈥渕imicking the underweight state by providing ketone bodies for energy creation might make the need to restrict unnecessary鈥, says Frank.
It聽is early days, says聽, 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. 鈥淭here’s a difference between trying it with an鈥痚ating disorder psychiatrist who’s monitoring you carefully, and reading about a ketogenic diet and then deciding spontaneously to do it,鈥 he says. 鈥淔rom a safety standpoint, I think鈥痠t’s definitely premature for that.鈥
Filling the gaps
For all the case studies and testimonials,听keto for the brain is far from聽a done deal.聽Smith points out that there have been no properly controlled,听randomised聽trials in large numbers of聽individuals, so it聽is impossible to聽know聽what proportion of people will respond as dramatically as Mildred and Matthew聽Baszucki. 鈥淭here might be two people who have an excellent response, and that鈥檚 great,鈥 he says.鈥淏ut there might be 98 other people who don鈥檛 get any response.鈥
To try聽to聽fill this gap,听Smith, along with聽Steven Marwaha聽at the聽University of Birmingham, UK,听is聽beginning聽聽in聽200 people with bipolar depression. The study will聽compare聽a nutritional ketogenic diet with聽a diet based on聽. The results won鈥檛 be in for at least five years, says Smith. In the meantime, the results of a 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聽mechanisms聽are more聽important聽than others聽for people聽who might聽benefit聽from the keto diet. 鈥淚t 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聽effects聽likely arise聽from their combined impact,鈥 says聽, a metabolic psychiatrist at Stanford University聽in California.
As larger clinical trials get under聽way, and the results continue to roll in, metabolic psychiatry could go聽a number of聽ways.聽Keto diets聽might turn out to聽work very well for some people, and not at all for others, in which case research will focus on聽identifying聽markers that聽indicate聽who聽they聽might聽benefit.聽Or聽further聽research may聽allow us to extract the special sauce from ketogenic diets,听which could then聽inform new聽drug treatments聽and make聽it unnecessary to聽stick to聽a聽restrictive聽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. 鈥淪ome people respond really well to existing treatments, but it’s heartbreaking to see patients year after year, decade after decade,鈥痺ho 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鈥痠s my passion. This is our moment for metabolism and mental health. That鈥檚 what I’m hoping.鈥
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