How Diet Alters Brain Chemistry to Cause (or Battle) Depression

The right foods can reverse damaging effects of genetics and inflammation on the mind

Brent R. Stockwell, Ph.D.
Wise & Well


Image of a couple looking at a brain with chemical structures
Image Credit: Brent Stockwell

This article is part of a Wise & Well Special Report: The United States of Depression.

After he was born in 2020, Oliver’s doctors told his mother that he had a metabolic disorder that would damage his brain — and later in life, he was at risk for depression. The way depression develops in people with this genetic change — a deficit in specific brain chemicals — reveals much about mood in the wider population. Happily, kids such as Oliver and many other people at risk for depression can benefit from dietary changes that counteract these brain changes.

Depression is widespread and enigmatic — some people succumb, whereas others never do; some recover, others can’t. Cracking the mystery of its origins requires understanding the chemistry of the brain, and how the rest of the body can control what happens in the mind.

Baby Oliver’s blood had too much phenylalanine, a bulky amino acid that’s one of the building blocks used to make proteins in the body. The thickening of Oliver’s blood with phenylalanine would distort his developing brain, as explained in a recent article about his stay at Akron Children’s Hospital.

Oliver was diagnosed with phenylketonuria (PKU) — a genetic disease caused by an inability to convert phenylalanine, needed for making proteins, into the related amino acid tyrosine. The gene altered in PKU kids is like a release valve, normally limiting the amount of phenylalanine in the blood. PKU is uncommon, affecting about 1 in 25,000 babies, but has revealed important aspects of human biochemistry relevant to everyone.

From genetics to depression

PKU patients have too much phenylalanine, which fills up the tunnel that other molecules use to get into the brain. The net effect is that phenylalanine is like what New Yorkers can’t stand — a slow walker on a narrow sidewalk preventing anyone else from getting past.

Phenylalanine shuts out other molecules from the brain that are needed to make dopamine and serotonin. These brain chemicals are crucial for setting mood. Too little dopamine and serotonin contributes to depression. And these brain molecules are crucial for everyone, not just PKU patients.

Mood and brain chemicals can also be changed by brain inflammation. Changes in a gene called PDE1A cause harmful bacteria to make a home in the gut. These bacteria send chemicals through the blood into the brain to fuel fiery inflammation. There are ultimately several effects of this cascade, including depletion of serotonin, the same brain chemical affected in PKU kids.

Fat in the liver can make you depressed

Inflammation can also be caused by damage to body organs, such as the liver. A diet high in sugar and saturated fat — the typical Western diet — causes a fatty and damaged liver, which leads to inflammation. As a result, patients with fatty liver have an increased risk of depression. A fatty liver is much more common than genetic diseases like PKU — one in four adults has too much fat in their liver.

Fat deposits damage the liver, and increase death of liver cells. These dying cells spill their guts, which causes inflammation that spreads to the brain, leading to loss of serotonin, and then depression.

Thus, both genetic changes and poor diet can drive chemical changes in the brain that lead to long-term destructive changes and ultimately depression.

Diets that prevent depression

The good news is that the right diet can also prevent the destructive effects of genetics, inflammation, and fatty liver. Diets high in certain fatty acids found in foods such as fish and olive oil reduce inflammation. This could be the explanation for why the Mediterranean and MIND diets — patterns of eating that lean into fruits, vegetables, legumes, and whole grains, and away from red meat — reduce the risk of depression.

Cutting back on saturated fat and sugar lessens liver damage and inflammation. Gut bacterial composition can be reprogrammed like a computer, using a diet high in fiber and low in sugar.

The right diet can even rewrite the effects of genetics. If patients with PKU maintain a diet low in protein — and specifically low in phenylalanine — they can prevent brain damage associated with the disease. Since Oliver’s doctors at Akron Children’s Hospital know the right diet for him, they now expect him to lead a normal and rich life. The right diet can likely restore a balanced mood in many people.

Unraveling brain and body chemistry is creating exciting opportunities to reverse depression, opening up new potential treatments and lifestyles for millions of people beyond just those with genetic diseases. Aristotle wrote that “the brain is an organ of minor importance.” Perhaps his gut told him that there was something more important than the brain for controlling the mind.

This article is part of a Wise & Well Special Report: The United States of Depression. If you or a loved one is depressed, it’s vital to talk about it. Because depression increases the risk of suicide, consider calling the confidential National Suicide Prevention Lifeline at 1–800–273-TALK (8255) for English, 1–888–628–9454 for Spanish, or call or text 988. Global support in 44 languages is available from Befrienders Worldwide.



Brent R. Stockwell, Ph.D.
Wise & Well

Chair and Professor of Biological Sciences at Columbia University. Top Medium writer in Science, Creativity, Health, and Ideas