Food is Medicine, Food is Poison

Exploring the field of metabolic psychiatry

Photo by Taylor Harding on Unsplash

Are you feeling stressed or burnt out? Having trouble fitting into your pre-pandemic pants? Maybe you just can’t focus like you used to? You’re not alone. Rates of mental illness have reached alarming levels in the United States: 1 in 5 American adults will experience mental illness in a given year, and research has shown that number rose to 1 in 4 during the pandemic. At the same time, rates of obesity have climbed even higher, with over 40% of Americans classified as obese, up from just 13% in 1980.

These two seemingly unrelated — yet equally alarming — statistics are actually very much connected to each other. New research is showing how significantly metabolism and mental health are related. “Metabolic psychiatry” is the name being used for this new field at the intersection of mental health and metabolic health, and at Able Partners we have been digging into the research — which has promising implications for future treatments of both. Last week, we hosted a dinner in our salon series dedicated to the latest research in the fast moving and important metabolic psychiatry space.

From Dr. Chris Palmer sharing insights from his clinical practice, to Dr. Martin Picard explaining the role of mitochondria, a group of researchers, practitioners, entrepreneurs and investors gathered to connect over this emerging field. We discussed how being overweight is about so much more than not being able to squeeze into your favorite jeans — it is both a symptom and cause of metabolic disease, which is defined as unhealthy levels of blood sugar, triglycerides, HDL cholesterol, blood pressure and/or waist circumference. Those at a healthy weight are not spared — according to some studies, just 1 in 8 Americans is metabolically healthy. This is significant because the relationship between metabolic health and mental illness is strong and bidirectional. A 2010 systematic review found that people who were obese had a 55% increased risk of developing depression over time, and people experiencing depression had a 58% increased risk of becoming obese. When looking at metabolic and mental health, it’s hard to untangle the relationships and pinpoint cause and effect; many medications for mental illness cause weight gain, and weight gain can lead to conditions such as joint pain or diabetes, which are likely to impact mood. What is clear is that good metabolic health is associated with better mental health, and vice versa.

Why are metabolism and mental health so closely linked? Metabolism changes food into energy. The brain uses more energy than any other organ in the human body, so if you have a problem with metabolism, it makes sense that your brain function is impacted, not just your waistline. Human brains evolved to use two forms of energy: glucose and ketones. Our modern diets, with abundant food and much heavier in processed carbohydrates than at any time in our evolutionary history, mean that virtually everyone’s brain relies on glucose alone. For some people, this diet causes metabolic dysfunction, eventually leading to serious disease. Mitochondria are the important mediator here — they produce energy in cells, and they are fueled by the food you eat. When mitochondria rely on ketones instead of glucose for fuel, they may be able to produce more energy, which could lead to healthier brains. And it’s not just about mental illness like bipolar disease, schizophrenia, or depression. Energy metabolism is implicated in Alzheimer’s disease, chronic migraines, multiple sclerosis and many other conditions, and nutritional treatments are similarly being studied for these diseases.

Metabolic psychiatry suggests using dietary interventions to improve mental health, primarily through reducing simple carbohydrates while increasing healthy fats. However, it’s important to note that other lifestyle interventions, such as exercise and sleep, can also impact metabolism and mitochondria. Early pioneers like Dr. Chris Palmer from Harvard, Dr. Shebani Sethi at Stanford, and Dr. Uma Naidoo at Massachusetts General Hospital are already using nutritional interventions to successfully treat patients with severe mental illness. Companies like Season allow providers to write evidence based food prescriptions; PYM, CookKeto and Bulletproof offer products to help consumers develop metabolic flexibility; KetoSwiss and Audacious Nutrition have developed exogenous ketones that can be taken in the context of a carbohydrate rich diet and still offer brain health benefits; Biolinq is developing a next gen continuous glucose monitor to manage blood sugar levels; Twin Health integrates lifestyle changes to reverse and prevent chronic metabolic diseases; and Found and Calibrate offer counseling and medications (such as the recently popular GLP-1 inhibitors, like Ozempic) to individuals suffering from metabolic challenges. However, it’s important to call out that the private sector will not solve this problem alone, and we need to advocate for policy changes to improve our food systems at the population level.

As exciting as the early evidence is, a lot more research needs to be done to validate potential treatments in nutritional psychiatry. It’s unlikely there will be a one size fits all approach to metabolic dysfunction. Just as one diet or one depression drug doesn’t work for most people, there is a need for personalized approaches here. One of the biggest questions in this field is scalability. How do you take a seriously ill, possibly delusional, person, and get them to adhere to a very restrictive diet? Many severely mentally ill patients cannot be relied on to take medications, much less to pass up the hundreds of sweet and savory food triggers we are exposed to every week. Interesting approaches to this issue could include using exogenous ketones, or possibly even other drugs that impact glucose metabolism such as GLP-1 inhibitors. But until we have solutions that can meet the size of the need, we at Able Partners, remain curious and committed to learning, sharing and collaborating with other founders, investors, and researchers looking for innovative approaches to the metabolic health crisis.