Brain Energy

Mitochondrial Dysfunction and Chronic Disease

I recently had the privilege of attending a conference where the keynote speaker was Christopher Palmer, MD. Dr. Palmer is a psychiatrist at Harvard who pioneered the theory that both mental and physical health are rooted in metabolic and mitochondrial function. I’ve heard him speak on numerous podcasts, but after meeting him in person and reading his book Brain Energy, I’m compelled to believe his theory, and I wanted to share it with you.

Dr. Palmer suggests that mental and physical health have the same root cause. Mental disorders are metabolic disorders of the brain, just as diseases like diabetes, heart disease, and obesity are metabolic disorders of the body. Indeed, there is a correlation between people with mental disorders and those with metabolic disease. Obese individuals are 50-300% more likely to be diagnosed with a mental health disorder, and diabetics are 3-5 times more likely to have depression. In fact, in 1879, diabetes was characterized as a “disease that often shows itself in families in which insanity prevails.”

It would be natural to say, “Of course people with chronic diseases would be more depressed or anxious,” but let’s look at the flip side of the coin. People with mental illness die from 7 to 30 years earlier than those without mental illness, and these increased deaths are not all due to suicide. Suicide is higher in the mentally ill, but the vast majority of added deaths are actually due to cardiac disease, diabetes, and cancer. In other words, the mentally ill are more likely to also have chronic diseases that ultimately threaten their lives.

So if you’re convinced that mental and physical disorders just might be connected, let’s explore what this connection might be. In each of these disorders, there appears to be some problem at the level of metabolism. Metabolic dysfunction means that there are problems with glucose utilization, reactive oxygen species, energy markers (ATP/ADP), inflammation, insulin, cortisol, and (as we’ll see in a moment) this is all related to mitochondrial dysfunction.

Anyone who’s ever taken a biology course might remember the mitochondrion as the “powerhouse of the cell.” Each cell contains hundreds to thousands of mitochondria, and they even have their own set of DNA. Beyond taking food and turning it into energy, mitochondria are responsible for getting rid of waste products, deciding what genes get expressed, making and releasing hormones, turning on (and off) our immune system, making proteins and getting rid of dysfunctional proteins, and basically every aspect of our biology. Without mitochondria, we would die. And when our mitochondria get sick, we do, too.

Much like the bidirectional relationship between mental and physical health, there is also a bidirectional relationship between the factors that affect mitochondria and how mitochondria affects us. Stress, trauma, and lack of sleep, for example, have all been shown in studies to damage mitochondria. This causes the mitochondria to turn on the pathways that produce more of the stress hormone cortisol, which can wreak havoc when elevated for long periods of time. Conversely, when we restore balance to our hormones (by replacing deficiencies in estrogen and thyroid hormone, for example) or improve our gut microbiome (by eating a gut-healthy diet), our mitochondria can actually be enhanced. At best, something called mitochondrial biogenesis can occur, which means that we can even make new mitochondria.

So how do we make sure that our mitochondria are healthy? We can look at optimizing sleep and stress, removing alcohol and getting enough exercise, but the punchline of the book Brain Energy has to do with diet.

The ketogenic diet is a high fat, low carbohydrate, moderate protein diet that was developed in the 1920s for the treatment of epilepsy. By following this diet, you get into a state called ketosis, which means that your body and brain starts using ketones as fuel instead of glucose. By reducing glucose and elevating fatty acids in our bloodstream, the “keto” diet mimics a fasting state, turning on pathways in the body responsible for repair and recovery, and reducing inflammation. It also improves mitochondrial function. It has been used to treat obesity, type 2 diabetes, Alzheimer’s disease, alcohol use disorder, schizophrenia, bipolar disorder, and depression.

I’m not suggesting the keto diet is the fix for everyone, nor that it’s without risk. Adaptation to the keto diet, or “keto flu” can be dangerous, and the first few months can be risky, especially in the mentally ill, who may experience hyperactivity and mania associated with ketosis. And if the diet is stopped abruptly, symptoms of a patient’s mental disorder can come rushing back. But in conjunction with a team of physicians, nutritionists, and coaches, the keto program has been implemented successfully for many patients, and Dr. Palmer recently received a $3M grant to continue studying its effects.

I wanted to share with you the story of a woman named Doris, a patient of Dr. Palmer’s, to illustrate the profound impact of the keto diet on mental health. Doris suffered from debilitating schizophrenia from young adulthood. She was unable to live independently and attempted suicide six times in the two-year span between the time she was 68 to 70 years old. She was on multiple psychiatric medications and was gaining weight as a side effect. At age 70, Doris started a keto diet for weight loss. Within two weeks her hallucinations had decreased, and within six months, she was symptom-free. She lived 15 years longer independently.

Stories like Doris’ – and the others in Brain Energy – give me hope that we can find solutions to reversing the burden of chronic mental and physical disease. I love the perspective of addressing a disorder at its root cause, rather than just treating its symptoms. There is far more in the book, and much more elegant explanations of mitochondrial function, than I can convey here, but I hope you’ll give it a read if this topic interests you at all.

In good health,

Gina