Brain Energy, Mitochondria, and Mental Health
Dr Chris Palmer, MD, Harvard Psychiatrist
A major change in psychiatry has been going on for awhile now in which more and more clinicians and researchers are recognizing mental health disorders as related to, and sometimes caused by, physical states in the body and therefore using therapies that are meant to address these states. A primary example of this is looking at brain metabolism (mitochondrial function in the brain).
The Keto diet is a 100 year old, evidence based therapy that can stop seizures that medication can't stop. This is evidence of how powerful nutrition and diet can be in treating and altering brain function. Psychiatrists use epilepsy medications to treat people with other mental mental health conditions often, usually off-label, so there's nothing new about using the ketogenic diet to treat other mental health conditions. Seizure meds are used to treat dementia, eating disorders, anxiety, psychosis, mood disorders, substance use disorders, and others.
The Brain Energy Theory- Mitochondria do more than just produce energy for cells "mitochondria play a role in directing and allocating resources for cells". Not all of the food that mitochondria in the brain process is turned into ATP- some is turned into serotonin, dopamine, or cortisol, and they also play a part in regulating those molecules. Mitochondrial function is one way of understanding the imbalances of the neurotransmitters and hormones in the brain. They are also involved in regulating inflammation (turning it both on and off) and epigenetics by signaling the nucleus of the cell to regulate the transcription of gene. They monitor our outer and inner environment; sensing stress levels, food intake, blood sugar levels, and oxygen levels.
"Mitochondria play a role in our response to trauma- psychological and social stressors." Trauma and stressors play a role in mental illness, so this connection could be very significant, because while people have known that there is a connection they haven't known exactly what that connection is on a biological level. He points out that mitochondria seem to be a way to "connect the dots" in the mental health puzzle between factors like trauma, neurotransmitters, sleep, substances like drugs and alcohol (I would add exercise and sunlight too). These are all things that affect mitochondrial and metabolic health or are affected by it or both. People with mental health conditions have higher rates of many physical disorders including diabetes, obesity, heart attacks, strokes, and generally have a shorter life expectancy. This connection also opens up the possibility of more and better treatments.
For people who struggle to believe this connection is real, he explains that mitochondria are what drives metabolism, which is how we take food and oxygen and transform them to keep ourselves alive. If these processes are disturbed it means illness, and if they are disturbed enough or stop, we die. Most poisons work by harming mitochondria- that's how they harm or kill you. Other cellular components can be harmed without nearly as much danger to the organism. It makes sense that since mitochondria are the most important part of the cell and what keeps it able to perform its function, if they aren't functioning right the cell won't be able to function right.
Mitochondria can become both under-active AND overactive. This makes sense because there are mental health disorders involving areas of the brain becoming overactive as well as areas becoming under-active. If the health of mitochondria impacting the cell's functioning is the cause or major contributing factor to many mental health disorders that would explain why they can be better or worse at different times of day (or different seasons), why they can be worsened by stress and sleep deprivation. A lot of the details aren't known yet but already the basic insight that mitochondria are central to mental health is transformative of the fields of psychiatry and psychology.
What options are available to support mitochondrial functioning?
There are a huge variety of things available to help mito function including sun exposure, red light therapy, various supplements, glutathione, methylene blue, and more, but these can only help so much if core lifestyle issues aren't addressed. For example, alcohol is a potent mito toxin so a person drinking a large amount daily is poisoning their mitochondria far beyond what those things can help. Having healthy mitochondria requires lifestyle changes- eating well and avoiding highly processed foods, sleeping well, exercising, and avoiding excess stress.
The ketogenic diet and its effect on brain function has been studied for a long time, its known to change neurotransmitter levels, inflammation, the gut microbiome, but Dr Palmer says that he believes the impact it has on mitochondria is its most important therapeutic effect. The keto diet creates a state in the body similar to fasting, which is known to trigger mitophagy (when the cell breaks down old and defective mitochondria that are replaced by new, healthy ones) and mitogenesis (which is the production of new, healthy mitochondria). Dr Palmer suggests that these two processes that remove old, defective mitochondria and replace them with more and healthier ones, might lead to long-term healing where a person could potentially go off the keto diet and remain healthy. People who are on the diet to control seizures will usually be kept on the diet for 2 to 5 years after the point at which their seizures completely stop (some people with seizures must stay on keto for life). People can experience improvement of mental health symptoms, even very significant improvement or remission in weeks or months. Psychotic symptoms tend to take weeks if not months to improve especially if severe. People often wonder if making some changes in their diet, such as eating more fatty fish, will be enough. Dr Palmer says maybe for people with relatively mild symptoms or conditions, some changes such as eating more fatty fish can help, but he points out that those changes don't stop seizures but the keto diet does, he says "ketogenic therapy is a unique and powerful intervention".
What about other interventions to support mito health?
Exercise is a really important factor also and should be part of a treatment plan. The two types of exercise for which there is the most evidence of benefit for mito health are strength training (aka lifting weights, working out to build muscle) and level 2 cardio (which he defines as 3-60 minutes of running, cycling, etc that gets you breathing hard but not out of breath). Those types of exercise increase the number and health of mitochondria in muscles which then send endocrine signals to your brain that improve brain function. Exercise alone isn't enough to heal mito, lose weight, or heal type 2 diabetes. If people exercise more but don't change how they eat they don't get significant or sustained weight loss. There has been one very well-done study of middle-aged adults who were prescribed exercise. In addition, half were given the drug metformin to take and the other half were given a placebo. The group that got metformin didn't get the mito and metabolic benefits of exercise the way the other group did, which is evidence that metformin interferes somehow with mitochondrial biogenesis. Many other medications, including many psych meds, are known to interfere in mito function and biogenesis, so this should be considered. Lifestyle behaviors such as drinking alcohol and smoking cigarettes and marijuana are also mito toxins.
The psych drugs that can do this are mostly the anti-psychotics, which have been known to have metabolic side-effects and neurological side effects. They can cause significant weight gain (he has seen people gain as much as 100 pounds in 6 months), they can cause type 2 diabetes, they worsen every known risk factor for cardiovascular disease (raise blood pressure, raise triglycerides, worsen LDL levels), and increase inflammatory biomarkers.
This represents a new way to understand mental illness and what might be happening in the brain, and a new way to treat it. This is especially important as mental health remains highly stigmatized in the US and research around it receives very little funding in comparison to disorders considered to be physical. Many mentally ill people are in prisons, shelters, or even on the street. "There is tremendous injustice, in my mind, in how we treat people with mental illness". Dr Palmer points out that while psychological and social factors play a role in mental illness, it's no less physical and "real" in that way. People with mental illness "deserve medically necessary treatment". If we can get needed care to people in prison or who are homeless and who have mental illness, they won't be in prison or homeless anymore, they can live enjoyable, productive lives.
