The Science: How Food and Metabolism Impact Mood — Q+A with Dr. Shebani Sethi

Valerie Hoffmann, PhD. is the Head of Research at Meru Health Dr. Shebani Sethi, MD is the founding director of Stanford Metabolic Psychiatry and Silicon Valley Metabolic Psychiatry. She is also a Scientific Advisor to Meru Health.

We know that a steady diet of chips and cookies is bad for our physical health. But can our diet also impact our mood? If so, which comes first, a poor diet or depression? Meru Health’s Head of Research, Dr. Valerie Hoffman, sat down with Dr. Shebani Sethi, Stanford and Duke trained physician, double board certified in obesity medicine and psychiatry, and the founding director of both Stanford Metabolic Psychiatry and Silicon Valley Metabolic Psychiatry Center. She also serves as a scientific advisor to Meru Health. In this interview, Dr. Sethi demystifies the complex ways our food intake and metabolic state impacts how we feel, and offers tangible suggestions for brain-healthy diet patterns.


How does nutrition affect our mental health?


Most people know ultra-processed foods and highly refined carbohydrates (like sugar) can negatively affect our physical health. They can lead to obesity, type 2 diabetes, metabolic issues, and even cancer. But, we don’t typically think about how these foods affect the brain and our metabolism.

The body is really one whole system. So, what happens in the body also affects the brain. The brain uses a lot of energy — it’s always on — and it depends on fuel. So, you want to give it high quality fuel, not just any fuel. Foods with the right nutrients, vitamins, and sources of protein form the building blocks for the neurotransmitters, the cellular structure, and enzymes in the brain. Food affects both the structure and function, really, of the brain itself.

The brain has a delicate balance of neurotransmitters (or chemical messengers) which are needed for signaling and critical communication. With more sugar and processed foods, these levels change, become unbalanced and thus affect communication in the brain.

The brain is composed of electrical cells. And you need a proper speed of transmission between them. So, you need ample fat in your diet, which covers neurons (this is called myelin) in order to be working properly.

The research is still currently underway, but we are preliminarily finding that improving these cardiometabolic risk factors that we think of — like inflammation, insulin, blood sugar —  can lead to brain symptom improvements. We think it may have to do with reducing inflammation in the brain, reducing oxidative stress, and rebalancing excitatory and inhibitory neurotransmitters (essentially, the gas and the brakes).


Interesting! Okay, let’s start with the bad news. Which foods have the most negative impact on mental health?


I get this question often. I try to focus on the pattern of eating and the removal of harmful foods. So, everyone’s specific or trigger foods may be different. Ultra-processed or man-made foods are “food-like” substances that our brains and bodies were not designed to process.

And we’re beginning to understand that there are consequences. If you eat ultra-processed foods (like cookies, cake, ice cream, the kinds of things that we know are unhealthy) they’re usually packed with high amounts of sugar and can lead to binge eating or addictive behaviors. In fact, we think removing them may help with binge eating and cravings. So, chances are you’re not getting those important vitamins and minerals that you need. Nor are you actually absorbing them even if you’re consuming them, because sugar also directly affects hormone levels, inflammation, and the delicate balance of neurotransmitters that are critical for optimal function.


Now, let’s talk about what we should be eating. Are there any foods or diets that have been shown to improve mental health?


The Ketogenic Diet

The ketogenic or “keto” diet is a high fat, low carbohydrate, and moderate protein diet. This diet is designed to burn fat as a primary energy source, rather than glucose or carbohydrates.

It’s being studied as a metabolic intervention in mental illness because of its anti-inflammatory properties. It decreases what we call reactive oxygen species, which can destabilize and damage DNA and proteins. The ketogenic diet also increases a protein called brain-derived neurotrophic factor, which you can think of in essence as Miracle-Gro in the brain — it forms more connections.

Research is showing that there are energy deficits in some mental illness. For example, we’re seeing that mitochondria are not functioning optimally which causes downstream signaling changes. A Ketogenic diet is also thought to circumvent these deficits, acting as alternative fuel, while also treating metabolic disease, insulin resistance, and inflammation simultaneously. Research studies are exploring the ketogenic diet’s impacts on depression, schizophrenia, migraines, bipolar disorder, and overeating.

A ketogenic diet is not right for everyone and one should be monitored by a specialist with expertise in prescribing this metabolic intervention, especially when one is on medications. The ketogenic diet for mental illness needs further research and is currently underway with our metabolic psychiatry group at Stanford and our colleagues globally.

The Mediterannean Diet

The Mediterranean Diet is based on traditional eating patterns from Mediterranean countries, like Greece and Italy.

This diet encourages the consumption of vegetables, fruits, whole grains, seafood, olive oil, and legumes, among other things. Poultry, eggs, cheese, and yogurt are to be eaten in moderation, with limited red meat. With this diet, it’s recommended to avoid added sugars, processed foods, and refined grains or oils.

The Mediterranean Diet has been studied and shown to reduce the risk of depression.

Vitamins & Nutrients

And then there are different vitamins and nutrients that are generally good for your brain, like: vitamin B, vitamin D, omega 3, iron, zinc, magnesium, folate, choline, probiotics, and prebiotics.

The takeaway here is: real foods (minimally processed foods) protect the brain.


Okay, so you probably get this next question a lot. Which comes first: having a poor diet, or depression?


This is a “what comes first, the chicken or the egg” type question, right? There’s no controversy that diet and mental health are linked. Poor dietary choices can lead to depression or anxiety, and depression can lead to poor eating as well. The relationship between mental health and metabolic disease is also bidirectional, which means if you have a mental illness, you’re more likely to have a metabolic disease and vice versa. (This is one focus of metabolic psychiatry.)

There is something about this relationship that we don’t yet completely understand, but we know there is a relationship. Whether it’s increased brain inflammation that leads to downstream changes in chemical messenger signaling, or some other process that leads to worsening symptoms, further mechanisms are being explored and investigated. And Valerie, I really appreciate the work that you do investigating that.


Thank you! I guess the old adage “an apple a day keeps the doctor away” is at least partly true. So, any take-home advice for us?


Take it one step at a time and don’t overwhelm yourself. Set small achievable goals you are more likely to stick with. Try making substitutions of healthier foods you may enjoy. Also, look at nutrition labels — if you don’t understand what you’re reading, chances are it’s not the right food for your brain.

Try to start the day right with protein and healthy fat in the morning, which can really leave you feeling satisfied and full (and can even decrease cravings through the day). For example, in the morning, you might have eggs as your protein and then add in a healthy fat, like an avocado. It’s great to incorporate other fats that wouldn’t necessarily think of as “breakfast” foods, too.

Of course, if you have chronic medical conditions or are on medications for diabetes or high blood pressure, please see your doctor first for medical monitoring.

Really, it’s all about finding what works well for you and your body (and mind). We are here to guide you clinically and to do the hard research in pursuit of knowledge.

Dr. Shebani Sethi is a Stanford and Duke trained physician double boarded certified in obesity medicine and psychiatry. She is a Scientific Advisor for Meru Health, and the founding director of Stanford Metabolic Psychiatry and Silicon Valley Metabolic Psychiatry, which is focused on optimizing brain health by treatment and prevention of metabolic disease. She also conducts research investigating medications and dietary interventions to improve metabolic and psychiatric health outcomes.

Valerie Hoffman holds a Ph.D. in Psychiatric Epidemiology from Johns Hopkins Bloomberg School of Public Health, and a Master’s degree in Public Health from Yale University. She has been studying psychiatric epidemiology for two decades and published over 70 peer-reviewed research papers. Valerie is the Head of Research at Meru Health, where she is part of developing a novel, technology-based integrated mental health solution to battle depression, anxiety, and burnout.


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