Overview of How your metabolism could alter your mental health
This NPR Short Wave episode explores metabolic psychiatry, an emerging field that examines how the body’s energy systems—especially glucose, insulin, and fat metabolism—may influence mental health. Host Emily Kwong speaks with psychiatrist Dr. Shabani Sethi, who was drawn to this work after seeing a patient with schizophrenia improve after a dietary intervention. The conversation focuses on possible metabolic links to schizophrenia, bipolar disorder, and depression, and on how ketogenic metabolic therapy may help some patients when used carefully and under medical supervision.
The origin of metabolic psychiatry
A patient who changed Sethi’s career
- During medical school, Sethi treated a patient with long-standing schizophrenia and obesity.
- After a dietary intervention, the patient lost weight and her schizophrenia symptoms improved.
- That result prompted Sethi to investigate whether metabolism might play a deeper role in psychiatric illness.
A historical idea revived
- Sethi notes that a century ago, medicine more openly recognized links between metabolism and brain health.
- Modern medicine often separates physical and psychiatric conditions, but metabolic psychiatry tries to reunite them.
Mental health conditions with possible metabolic links
Schizophrenia
- Sethi says that glucose and insulin signaling problems can appear before diagnosis or before the first psychotic episode.
- In her framing, brain cells may be surrounded by glucose but unable to use it effectively.
- This is described as cerebral glucose hypometabolism—the brain is essentially “starving” despite available fuel.
- Importantly, she argues this is not just a medication side effect; it may be part of the illness itself.
Bipolar disorder
- Bipolar illness is also associated with:
- altered glucose utilization
- insulin signaling issues
- imbalance in GABA and glutamate
- Sethi compares GABA and glutamate to the brain’s “brakes and gas.”
- Some bipolar medications work in part by restoring that balance, especially to reduce mania.
Depression
- The episode highlights a strong association between insulin resistance and major depression.
- Sethi says that in the U.S., about one in three people have insulin resistance.
- People with insulin resistance are described as being about twice as likely to develop major depression.
- The broader point: depression may be connected not just to “brain chemistry,” but to whole-body energy metabolism.
Ketogenic metabolic therapy (KMT)
What it is
- The episode distinguishes ketogenic metabolic therapy from trendy “keto” dieting.
- KMT is presented as a strictly monitored medical intervention, not a self-directed fad diet.
- It shifts the body from burning glucose to producing ketone bodies from fat.
- These ketones can cross the blood-brain barrier and serve as fuel for the brain.
Why it may help
Sethi says KMT may have several effects:
- improved blood glucose regulation
- anti-inflammatory effects
- possible benefits for mood, energy, and cognition
Medical caution
- She strongly warns that people should not stop medications and try keto on their own.
- The treatment should be used with professional oversight and as part of a broader risk-benefit approach.
What the research suggests so far
Early findings are promising
- Sethi says trials have shown improvements in:
- metabolic markers
- psychiatric symptoms
- mood
- energy
- cognition
- She emphasizes that the field is still developing, but the results are encouraging.
A small clinical study she cited
- In a pilot study she published, participants who had metabolic syndrome at the beginning no longer met criteria four months later.
- She uses this to argue that the science is real and can produce meaningful changes fairly quickly.
Limitations and open questions
Long-term effects still need more study
- The host raises concerns about animal research suggesting long-term high-fat ketogenic diets may worsen liver and blood sugar outcomes.
- Sethi responds that:
- mouse studies don’t necessarily translate directly to humans
- some diets labeled “ketogenic” may not be true ketogenic diets
- the long-term effects of the current standard diet are also poor, given widespread obesity and insulin resistance
The field still needs better evidence
- Sethi says the research should continue to clarify:
- who responds best
- why some patients improve and others don’t
- what biomarkers matter most
- what levels and protocols are optimal
Main takeaway
Metabolism may be a major lever for mental health, not just a physical health issue. The episode’s central message is hopeful: for some people, improving metabolic health may help improve psychiatric symptoms too. But the science is still emerging, and treatments like ketogenic metabolic therapy should be approached carefully, medically, and without hype.
Notable insight
“Metabolism is one of the biggest levers that we can use in improving our mental health.”
Additional notes
- The episode references Sethi’s article in Nature Mental Health for readers who want to learn more.
- Production credits include Emily Kwong as host, with reporting and editing by the NPR Short Wave team.