Reprinted with permission from Brain Energy by Christopher M. Palmer, MD (BenBella Books, Inc., 2022)
What we eat, when we eat, and how much we eat have direct effects on metabolism and mitochondria. Everyone knows that diet plays a role in obesity, diabetes, and cardiovascular disease. What most people might not know is that diet also has profound effects on mental health and the brain.
This field is massive. Tens of thousands of research articles and countless textbooks have explored the effects of diet on metabolism and mitochondria. Most of this research has focused on obesity, diabetes, cardiovascular disease, Alzheimer’s disease, aging, and longevity. However, these researchers don’t usually see the connection with mental health.
The connections go far beyond correlations. They overlap at the level of neural circuits in the brain and, of course, the entire network of metabolism and mitochondria within the human body. For example, the neural circuits that drive appetite and eating behaviors have also been directly implicated in addiction to tobacco, alcohol, and heroin. That’s not too surprising to most people. What might be more surprising is that the neural circuits for loneliness overlap directly with the neural circuits that warn of starvation. This study, published in Nature, showed that chronic social isolation in the fruit fly led to increased eating and decreased sleep. A “social” problem led to changes in appetite and sleep. When the researchers artificially stimulated the neural circuit for social isolation, it caused the flies to eat more and sleep less. Another study identified specific GABA and serotonin neural circuits that were directly involved in obesity and anxiety and depression. One neural circuit plays a role in how much you weigh and how you feel.
Some people call this field nutritional psychiatry, one that looks at the role of diet in mental health. Personally, I feel this is too narrow. It’s more than how diet affects brain function. It’s also about how our mental states affect our metabolism, which can impact appetite and feeding behavior, which can affect overall health. It’s a bidirectional relationship. Metabolic affects mental, and mental affects metabolic.
There are at least seven different ways that dietary interventions can be helpful in addressing mental symptoms:
- Addressing nutritional deficiencies, such as folate, vitamin B12, and thiamine deficiency.
- Removing dietary allergens or toxins. For example, some people have an autoimmune disorder called Celiac disease that results in inflammation and other metabolic problems in response to gluten. This can also affect brain function. I’ve described the toxic effects of TFAs. There are many other dietary ingredients that can also impair mitochondrial function.
- Eating a “healthy diet,” such as the Mediterranean diet, may play a role for some people.
- Improving the gut microbiome.
- Improving metabolism and mitochondrial function with a dietary intervention. This includes changes in insulin resistance, metabolic rate, the number of mitochondria in cells, the overall health of mitochondria, hormones, inflammation, and many other known regulators of metabolism.
- Losing weight can help to mitigate the problems associated with obesity.
- Gaining weight can be a life-saving intervention for those who are severely underweight.
There is also evidence that fasting, intermittent fasting (IF), and fasting-mimicking diets may play a role in treating mental disorders. They all result in the production of ketone bodies, which are made when fat is being used as an energy source. Fat gets turned into ketones. And, interestingly, this process occurs exclusively in mitochondria, yet another role for these magnificent organelles.
We have evidence that IF improves mood, cognition, and protects neurons from damage in animal models of epilepsy and Alzheimer’s disease. One group of researchers set out to understand how and why. You’ll never guess what they found — it’s mitochondria! The researchers put mice on an IF routine. They found that the hippocampus, a brain region often involved in depression, anxiety, and memory disorders, was largely driving the improvements from IF. It appeared to be due primarily to higher levels of GABA activity, which reduced hyperexcitability. Then, the researchers went further to understand what was causing this change in GABA activity. They removed Sirtuin 3 from the mice in two different ways. This protein is exclusive and essential to mitochondrial health. When they did this, all the benefits were lost. This clearly implicates mitochondria directly in the benefits of IF on brain health.