Research on ketogenic diets for the treatment of mental health conditions

How did the Ketogenic diet start?

Ketogenic diets have been around for over 100 years, but many people are surprised to learn that ketogenic diets were initially used to treat epilepsy. In the 1920s, ketogenic diets were initially used to reduce and prevent seizures in children and adults with treatment-resistant epilepsy.

Ketogenic diets gained popularity as a tool for weight loss in the 1970s after Dr Robert Atkins published his now-famous dietary programme, the ‘Atkins Diet’, which is a modified version of the ketogenic diet. Ketogenic, Atkins and other low-carbohydrate diets became increasingly popular throughout the 1990s.

During the last two decades, a number of celebrities endorsed the ketogenic diet as a weight loss ‘miracle’, while the public filled internet forums with anecdotal success and horror stories about their experience of the ketogenic diet. This increased media coverage led to the ‘keto diet’ being the most googled diet trend in 2018.

Understandably, the exaggerated claims and celebrity endorsements led many people to consider ketogenic diets as nothing more than another extreme weight-loss fad. However, this also led the scientific community to show a renewed interest in ketogenic diets as a potential treatment for mental health conditions. Over the last 20 years, a rapidly increasing number of studies began investigating whether ketogenic diets could treat conditions such as schizophrenia, depression and bipolar disorder.

Ketogenic diets in epilepsy

Ketogenic diets have been used as an alternative treatment for seizures in patients with drug-resistant epilepsy (who don’t respond to medication) since the 1920s. However, ketogenic diets only seem to work for some patients with epilepsy, with studies showing not all patients experience an improvement in seizure occurrence or frequency.

How do ketogenic diets prevent seizures?

Ketogenic diets alter how the body absorbs energy from food, which is a metabolic process known as ketosis. During ketosis, the body switches from using glucose (from carbohydrates) as its main source of energy and starts converting ketones from fat instead. Ketones can also enter the brain to partially replace glucose as a source of fuel, which can significantly affect brain function.

Scientists believe that the ability of ketogenic diets to change how cells inside the brain use energy is the reason why it can help to prevent seizures. However, we still don't fully understand precisely how ketogenic diets alter brain function or why this helps prevent seizures in some (but not all) patients with epilepsy.

Latest research in epilepsy

The most recent Cochrane review of ketogenic diets for drug-resistant epilepsy, published in 2021, found that ketogenic diets completely stopped seizures in up to 55% of children with drug-resistant epilepsy and reduced the frequency of seizures in 85% of children with drug-resistant epilepsy. In adults with drug-resistant epilepsy, it was unclear if ketogenic diets reduced seizure frequency or prevented them altogether due to the limited number of studies and small sample size of patients.

Why are ketogenic diets being used in psychiatry?

The discovery that ketogenic diets could prevent seizures in patients with epilepsy led scientists to start exploring whether ketogenic diets could also improve brain function in people with mental health conditions. Scientists believe that if ketones are capable of preventing seizures by changing mechanisms inside the brain, ketones may also be able to treat the symptoms of some mental health conditions.

The theory underlying this research is based on the observation that some patients with mental health conditions show similar brain abnormalities as patients with neurological conditions. Ultimately, discovering how ketogenic diets influence brain function could potentially lead to a breakthrough in our understanding and treatment of mental health conditions.

Can ketogenic diets improve brain function?

New research suggests that understanding how ketogenic diets influence brain function could eventually lead to new treatments to prevent cognitive decline in mental health conditions. Very few psychiatric medications can target the underlying cause of cognitive decline, meaning that cognitive symptoms are significantly more challenging to treat and manage than other symptoms (such as low mood or anxiety).

Mental health conditions such as schizophrenia, bipolar and depression are increasingly being recognised as neuro-progressive disorders, meaning that damage to the structure and function of the brain worsens over time. As the damage to the brain progresses, symptoms become more severe and difficult to treat. Damage to the brain is known to cause cognitive decline and increase vulnerability to stress.

Cognitive decline is a normal part of ageing that leads to difficulties in storing and retrieving memories, learning information and decision making. However, the speed and severity of decline are accelerated in severe mental illness, making it more difficult for patients to care for themselves and live independently. Sadly, a large proportion of patients with neuro-progressive disorders go on to develop treatment-resistant conditions, with severe symptoms that show little to no improvement from medication or conventional treatments (such as psychotherapy).

Ketogenic diets: mechanisms of action

A recent review, published in the International Journal of Neuropsychopharmacology, suggested that ketogenic diets seem to improve brain function and cognition by targeting the underlying biological mechanisms linked to mental health symptoms.

Some of the mechanisms through which ketogenic diets may affect brain function include:

• Reducing inflammation
• Improving oxygen utilisation
• Regulating key neurotransmitters
• Changing gut bacteria in the microbiome

Learn more about the basic mechanisms of a ketogenic diet on metabolism here.

Ketogenic diets and the microbiome

Scientific studies have shown that ketogenic diets can significantly influence altering the diversity of gut bacteria in the microbiome. Changes in the gut microbiome caused by the ketogenic diet may only be helpful for patients with certain conditions, such as autism and schizophrenia. In contrast, other studies have found that ketogenic diets are associated with a reduction in beneficial gut bacteria and increased harmful gut bacteria. However, the quality and content of the type of foods consumed on a diet can vary considerably between individuals, which may significantly impact the gut microbiome more than ketosis itself. Additionally, new research shows that some patients may experience more benefit depending on their baseline blood ketone levels and individual differences in gene expression.

What are the limitations of ketogenic diet research?

The evidence for ketogenic diets in treating mental health conditions is currently limited due to a lack of high-quality clinical studies with long follow-up periods. The ketogenic diet's short-term effects (up to 2 years) are better established in conditions such as epilepsy or weight loss. Still, the effects of the diet are highly variable across all conditions and between individuals.

However, these limitations aren’t unique to ketogenic diet research. The results of studies investigating diet and nutrition are inherently complex to interpret. It’s challenging for scientists to accurately measure people’s food consumption on a daily basis, as well as the nutritional quality of their diets and macronutrient ratios. Additionally, people also respond differently to diets due to complex interactions between the microbiome, neurotransmitters, hormones, genes and immune system, and environmental factors. This means what works for one person may have a completely different effect on someone else.

Although there is emerging evidence that a ketogenic diet might be helpful for some people, unfortunately, scientists don't have a way to predict which conditions or individuals will benefit most from ketogenic diets. As with any medical treatment, ketogenic diets might only benefit a subset of patients with severe or treatment-resistant disorders, such as epilepsy or schizophrenia.

Ketogenic diets for weight loss

Currently, it’s unclear whether ketogenic diets offer any substantial benefits for long-term weight loss compared with other more widely researched diets, such as the Mediterranean diet. For a more comprehensive overview of the evidence for ketogenic diets as a weight-loss tool, readers are directed to these external evidence-based articles:

• Keto diet: a dietitian on what you need to know.
• Ketogenic diet: Is the ultimate low-carb diet good for you?
• It's advertised as a weight-loss wonder, but this eating plan is actually a medical diet that comes with serious risks.

Do ketogenic diets have any risks?

Ketogenic diets are associated with many risks, and the long-term health effects of ketogenic diets are not known. Due to the limited number of long-term studies, there are concerns about the safety and ease of maintaining a strict ketogenic diet for an extended period of time. A recent review evaluating the safety and efficacy of ketogenic diets across a wide range of chronic health conditions warned that the risks of a ketogenic diet could outweigh the benefits for most people. Some people also report experiencing a ‘keto flu’ after beginning the diet, which includes symptoms such as fatigue, headaches, nausea and digestive issues.

Scientific reviews have found that people on ketogenic diets can develop vitamin and nutritional deficiencies over time. One of the major factors that contribute to the safety of ketogenic diets is the nutritional quality and content of the food people consume while they are on a diet. People who embark on a ketogenic diet without the supervision of a healthcare professional may end up swapping healthy carbohydrates (from vegetables) in favour of processed animal products or saturated fats. Reducing your intake of vegetables, fruits, legumes, and whole grains increases the risk of vitamin and mineral deficiencies. A lack of fibre can also reduce beneficial gut bacteria in the microbiome. Diets high in processed meat and saturated fat are associated with increased inflammation and risk of developing conditions such as diabetes, cardiovascular disease, some cancers, and Alzheimer’s disease.

Ketogenic diets are also considered dangerous for people with existing health conditions or specific symptoms, including suicidal ideation, anorexia, acute trauma (death, separation, accident, abuse), acute intoxication, chronic alcohol use, drug dependence, mental status changes (confused, delirious, disoriented), agitation and violent behaviour, poor insight, poor self-care, new or worsening psychosis, disordered eating, during pregnancy, lactation, use of SGLT-2 inhibitors, post-surgery malignant conditions, children and growing kids, Type I diabetes, Type II diabetes on medication, elite athletes, patients on blood pressure medication, bariatric surgery patients, gallbladder disease, no gallbladder, underweight, kidney disease, kidney stones, heart failure, pancreatic insufficiency, pancreatitis, whipple surgery, liver disorders, cardiomyopathy, and gout, among others. A full list of ketogenic diet contraindications can be found here: Scientific evidence underlying contraindications to the ketogenic diet: An update.

Could ketone supplements replace ketogenic diets?

Ketone supplements are theoretically designed to put your body into ketosis without needing to go on a ketogenic diet. Due to the restrictive nature of ketogenic diets, many people, and particularly patients with mental health conditions, struggle to stick with strict diets in the long term. To address this, scientists are investigating whether ketone supplements are a viable alternative to ketogenic diets. Ketone supplements would make it significantly easier for patients to experience the benefits of ketosis without patients having to adhere to a strict diet.

Research into ketone supplementation is still in the early stages of development, as the dosage and timing of ketones needed may vary by condition, symptom severity and illness stage. Researchers must also consider whether ketone supplements are influenced by individual patient differences, such as height, weight, body fat percentage, gender, etc. If ketone supplements are proven to be beneficial, the improvement in symptoms must outweigh the possible side effects of a supplement before it can be approved as a medical treatment.

While there are many ketone supplements available that claim to do this, none have yet been approved for the treatment of any condition or for weight loss.