Adopting a therapeutic nutritional ketosis diet shifts the body's fuel source from glucose to fat and ketones and can significantly treat mental illness symptoms. However, it should be undertaken with professional guidance, especially for those with psychiatric conditions, as it involves complex metabolic changes. This diet has shown potential in improving brain energy efficiency, reducing neuroinflammation, balancing neurotransmitters, and enhancing mitochondrial function, all crucial factors in mental health. Read on for highlights from a conversation between Bret Scher, MD and Chris Palmer, MD.

Fueling the mind

Let’s begin with dietary advice for everyone: get off the Standard American Diet. This combines high-carb, high-fat, high-calorie, highly processed foods. Instead, focus on whole, natural food sources, and avoid almost anything that’s refined, processed, or composed of added calories with little nutritional value. The added calories and the low nutritional value of ultra processed foods are a recipe for insulin resistance, metabolic dysfunction, and a roller coaster of rising and falling glucose and rising insulin levels.

The advice to eat all things in moderation and simply reduce your calories is often destined to fail, thanks to the ubiquitously easy availability of cheap, tasty, potentially addictive refined and processed products. It’s no secret that almost any diet that focuses on whole food sources is going to be better for metabolic and mental health than the standard industrialized diet.

We hypothesize that therapeutic nutritional ketosis may be the most effective nutritional approach for mental health and treating symptoms of mental illness. Nutritional ketosis refers to any nutritional approach that reduces carbohydrate intake low enough so your body changes from using glucose for fuel to using fat for fuel. That can be the fat you store in your body or the fat you eat. As a result, your body produces ketones, which the brain can specifically use for energy production.

If you have a psychiatric diagnosis, symptoms of one, or take psychiatric medications, you should not start a ketogenic diet alone. Instead, you should only consider starting a therapeutic ketogenic intervention with careful monitoring from your health care provider or an experienced clinician.

Therapeutic nutritional ketosis benefits mental illness from a direct effect from ketones. Scientific studies have shown that, with a diagnosis of serious mental illness, seizures, or even dementia, brain cells have trouble efficiently using glucose for fuel. Essentially, there’s a disruption to the brain’s energy production. Ketones supply a completely different fuel that doesn’t depend on insulin or the cell’s ability to metabolize glucose. This can result in more efficient energy production for the brain.

Ketones are not enough

You may have heard that the brain can’t run 100% on ketones, and that’s true. Your brain will always require some glucose, which your body can produce by itself, even when you’re not eating carbohydrates. The best scientific evidence suggests that ketones can supply up to 70% of total brain energy. That’s a potentially huge benefit compared to the brain running 100% on glucose, which is what frequently happens in the setting of insulin resistance and metabolic dysfunction, especially on the standard industrialized diet.

But more efficient energy production isn’t the only benefit making ketones offers. When the brain switches from glucose to ketones for the majority of its energy, there’s evidence of decreased neuroinflammation, something else that’s been implicated in the cause of mental illness.

There’s also a change in neurotransmitters with an increase in GABA and a decrease in glutamate. That combination can reduce the hyper-excitability of sick or diseased nerve cells. Furthermore, using ketones for fuel can improve the function of mitochondria, the energy- producing part of the cell.

The role of metabolism and mitochondria in mental illness

We have known since the 1800s that diabetes and serious mental disorders are strongly connected, and that families who have high rates of diabetes are more likely to have serious mental disorders and vice versa. Beginning in the 1940s, researchers began to identify all sorts of metabolic abnormalities in the bodies of people with mental illness. They took samples of blood from their veins and noticed increased levels of lactate, which is a biomarker of metabolic stress. Usually, we have increased lactate when we exercise, but they were noticing these increased levels of lactate in people with schizophrenia and bipolar disorder, even when they were relaxing.

That research continued to escalate, and then, in the 1990s, we had neuroimaging studies and all sorts of evidence that all converged on metabolism. Metabolism is extraordinarily complicated, though, and so is the brain. Researchers have been puzzled and overwhelmed by this complexity. Only over the last 20 years have we begun to see an entirely new body of research that helps us understand this complexity, and that body of research is focused on mitochondria. Most people know mitochondria as the powerhouse of the cell, but actually they do so much more than that. When you do a deep dive of the science of mitochondria and all of the different roles they play in cells and the human body, you can connect the dots of all the factors that we know play a role in mental illness.

Mitochondria are involved not only in metabolic disorders like obesity, diabetes, and cardiovascular disease, but mitochondria are also directly involved in the production and regulation of neurotransmitters like serotonin and dopamine as well as some important hormones like cortisol, estrogen, and testosterone. They play a role in gene expression and inflammation as well.

Ketosis as a prescription

Nutritional ketosis is a medical intervention that changes your metabolism. In reality, therapeutic ketosis should be prescribed just like a medication and should include a discussion of the risks and benefits as well as clear instructions on how to do it, and it should be used in conjunction with other psychiatric medications. In fact, nutritional interventions like ketogenic diets are typically initiated while keeping medication regimens the same, at least for some time, and in some cases as needed. Medications for sleep may be required during the initial transition into ketosis, which can occasionally cause insomnia.

If you enjoyed reading this, take some time to watch the full conversation between Dr. Bret Scher and Dr. Chris Palmer on our YouTube channel.

Sources

• Jiang, Ziying, et al. “Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases.” Aging and Disease. (2022).

• Pinto, Alessandro, et al. “Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New Perspectives for Neuroprotection in Alzheimer’s Disease.” Antioxidants. (2018).