Can ultra-processed food make us anxious?

What happens when you cross endocrinology and psychiatry? You get metabolic psychiatry, a new way to research and treat mental disorders. The practice is booming in Silicon Valley and may herald a revolution in understanding the mind.

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Not just correlation

On average, 15–25% of the population suffers from metabolic syndrome (which includes endocrine disorders, obesity in the waist, hypertension, elevated sugar and cholesterol levels and other increased risks for heart disease). For people with mental disorders, the percentages are much higher:

• Depression: twice as likely to have metabolic syndrome.
• Anxiety disorders and phobias: up to 45% of people with this diagnosis are obese.
• Schizophrenia: more than 42% of men and 54% of women schizophrenics have metabolic syndrome.
• Bipolar Disorders: for this community, the prevalence of metabolic syndrome reaches 67%

Traditionally, the presence of metabolic disorders in these cohorts has been attributed either to the side effects of antipsychotic drugs, which can cause metabolic disorders, or to disease-related physical inactivity and the habit of seizing stress. Either way, a mental disorder is considered the cause, and a metabolic disorder seen as the consequence. But what if it's the other way around?

A growing number of experts are inclined to believe that the connection may be bidirectional. One of them is Shebani Sethi, a chartered endocrinologist (obesity expert) and psychiatrist who founded the world's first metabolic psychiatry clinic at Stanford University's Department of Behavioral Sciences. In her opinion, research on the influence of metabolism on the psyche is a real chance to uncover the causes of the development of mental disorders.

Illness for no reason

More than 10% of the world's population suffers from mental disorders, with anxiety (3.8%) and depression (3.4%) accounting for a majority of the cases. Given the prevalence of these disorders, it is hard for many to believe that their cause is still unknown. After all, psychiatry is a branch of medicine, and any branch of medicine has clear criteria and diagnostic algorithms. Based on a patient's complaints, a doctor will conduct tests and studies to find the organic causes of symptoms and make a diagnosis.

Diseases are generally classified according to the damage they inflict on body tissues and their violations of physiological processes. Only mental disorders are united not by a common biological basis, but by its absence.

Depression, bipolar disorder and even schizophrenia are diagnosed solely on the basis of external signs, complaints and patient behavior. It is these symptoms, and not objective biomarkers, that are listed in the Diagnostic and Statistical Manual of Mental Disorders, which is considered the "gold standard" of psychiatric diagnoses. A physical examination of a patient is usually ordered only to rule out other health problems.

When we call an illness "mental," Sethi says, we are effectively admitting that we cannot find the organic changes in the body or brain that have caused it. But that doesn't mean they don't exist.

Many diseases that were once considered "mental" (including epilepsy and multiple sclerosis) are now classified as neurological due to the discovery of their biological basis. Similarly, scientists should not abandon attempts to detect biomarkers of mental disorders.

According to Sethi, metabolic disorders are by far the most reliable biomarkers of different mental disorders. Given how strongly metabolism affects the functioning of the body, she says it is logical to assume that its changes can also affect the state of our main organ - the brain.

Is depression an addiction?

About half of obese people complain about being addicted to ultra-processed foods, Sethi says. They support themselves throughout the day with lollipops or chocolate almonds, and satisfy their hunger with ice cream, burgers, butter bars, cookies or chips, and their thirst with sugary sodas and juices. In the evening, semi-finished products are heated in the microwave. Many are aware of how harmful this diet is to the body, but they cannot change it. 

At first glance, ultra-processed foods seem to be as diverse as the symptoms of mental disorders. These foods differ in composition and ratio of nutrients, the variety of flavors and in their calorie content.

Ultra-processed foods do all have one common ingredient - added sugar. It may hide under various names, but it is always present and, as many studies have shown, can create a dependence similar to drug addiction.

Some scientists have advanced the receptor hypothesis as a biological basis for mental disorders. In short, the idea is that mental disorders are caused by an increase or decrease in the sensitivity of receptors in brain cells to various neurotransmitters (substances that supply chemical signals to transmit, accelerate or inhibit impulses between neurons). There is no change to the anatomical structure of the brain, but there is a change to how it works.

There may also be problems with the connection of neural networks in different parts of the brain. For example, there can be a disconnect between the amygdala, which is called the "emotion processor", and the prefrontal cortex, which normally provides emotional regulation. This disrupts the coordinated interaction of the different systems responsible for self-control, movement, emotionality, cognition, thinking, memory, sexuality and perception. Depending on the type of disruption in the connection between neurons, a characteristic picture of schizophrenia or depression can arise.

In depression, for example, the sensitivity of dopamine receptors is reduced, which may well explain emotional depression, loss of strength, and loss of interest in life. Similar changes in the brain occur during the formation of an addiction to drugs, alcohol and sugar.

Sugar primarily affects the reward system of the brain by desensitizing the dopamine and opioid receptors. These receptors are distributed throughout the brain, but most of them are located in the areas that regulate the pleasure of eating. After studying the effects of sugar on pigs’ brains, neuropsychiatrist Ann Landau says:‍

“Sugar changes brain patterns in much the same way as cocaine, which is also known to affect the dopamine and opioid systems”

Moreover, sugar can change a brain’s reward system in just 12 days. According to the mechanism of formation,

“Sugar addiction” does not practically differ from other addictions

When refined sugar is consumed, a sharp release of “pleasure hormones” occurs, to which the corresponding receptors respond.

A study in rats showed that brain receptors are not adapted to withstand constantly high sugar levels. The more often sugar enters the body, the less sensitive the receptors become and the greater the dose required to activate them. “For example,” Sethi says, “ I drink a glass of wine and have difficulty getting to bed. And a person suffering from alcoholism can drink a bottle and need more.” The same thing happens to the pleasure center in the brain when we overuse added sugar.

The more we eat, the less pleasure we get from the less intense stimulation of our dopamine receptors.

So we have to replace other pleasures with increasing doses of sugar, which further disrupts the metabolism and makes us even less sensitive to everything else. 

Fat and protein instead of drugs

In 2008, Sethi's colleague Christopher Palmer, a professor of psychiatry at Harvard, suggested that a patient with a 53-year history of schizophrenia give up sugar and go on a keto diet. After two weeks, her condition improved, her auditory hallucinations began to disappear and she was soon able to live without antipsychotics at all. This method was then tested on a 39-year-old patient who had suffered from depression with suicidal tendencies and signs of schizophrenia for more than 20 years. She also improved a month after the start of the experiment. Dr. Sethi has used the keto diet with similar success, both by itself and in combination with drugs and traditional psychotherapy, to treat ADHD and bipolar disorder.

Most people are familiar with the keto diet as a way to lose weight. But it was originally created to treat epilepsy.

In the original plan, a follower of the diet got 80-90% of his calories from fat, 5-15% from protein, and 5-10% from (slow) carbs. The diet also required dieters to completely give up added sugar. The diet mimics the stages of hunger to switch the metabolism into an unusual mode - ketosis. As a result of  the lack of carbohydrates, the body begins to use fat for energy production. The liver converts the fat into ketone bodies, which serve as fuel for brain cells instead of the usual glucose. This is how the keto diet can affect the metabolism of nerve cells.

A number of studies have shown the keto diet to be effective in the treatment of epilepsy in children

Up to 15% of those who followed the diet were able to completely rid themselves of seizures. Although the mechanism that causes this effect is not exactly known, some assume that the change in the degree of “excitability” of the brain is associated with two factors at once: a decrease in sugar levels and an increase in fat levels.

Shebani Sethi believes that ketosis affects the brain in three ways:

• Increased neuroplasticity The growth, development, repair, operation and interaction of neurons depends on a special protein - brain-derived neurotrophic factor (BDNF). According to animal experiments, consumption of refined sugar suppresses this protein, while the transition to ketones, on the contrary, stimulates the production of BDNF. The higher the level of BDNF, the more new neural connections and the better the interaction between different parts of the brain.
• Optimization of the energy system of the brain In schizophrenia, bipolar disorder and depression, biopsy findings often show a disruption of energy metabolism in the brain and an energy deficit. The reason, most likely, is a decrease in the performance of neuron energy generators - mitochondria. Ketones may be a more efficient fuel for them than glucose. And thanks to an increase in the supply of energy, neurons are better able to cope with stress factors.
• Decreased levels of inflammation. Special brain immune cells (microglia) play an important role in the development of schizophrenia, borderline disorders and depression. By activating the production of inflammatory proteins, they disrupt the balance of excitatory and inhibitory neurotransmitters, as well as the functioning of mitochondria. Fatty acids and ketones as the main source of energy are able to switch microglia from an aggressive to a neuroprotective mode by blocking inflammatory proteins.

Does this mean that all people suffering from depression should go on a keto diet? Sethi says not always and those who pursue it should do so under the supervision of a specialist. The keto diet has serious contraindications, and even in her metabolic psychiatry center, she is still only using this method in an experimental mode. But for anyone who wants to minimize the risk of mental problems associated with metabolic disorders, she has some recommendations. She says:

“Try to gradually move from ultra-processed to healthier foods and set modest, easily achievable goals for yourself. For starters, try eating more protein and vegetable fat in the morning. For example, eggs, avocados or nuts. This will ensure satiety and reduce the risk of overeating during the day. It does not matter that it will not look like a classic breakfast. Your brain will thank you for it."

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