How diet and gut bacteria may point to new treatments for depression

Written by Katharine Lang on May 17, 2022 — Fact checked by Hannah Flynn

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A diet rich in the amino acid proline has been linked to a higher prevalence of depression. Guillermo de la Torre/Stocksy
  • Antidepressants are often one of the first lines of treatment for depression but they can have side effects or not work for many people.
  • Research has been trying to establish if altering one’s diet might have some effect in countering depressive symptoms.
  • New findings suggest that some people with high levels of the amino acid proline in their diet may experience more severe depression, but this is largely dependent on a person’s microbiome.

Worldwide, some 280 million peopleTrusted Source, or 5% of the adult population, have depression. The World Health Organization has called it a “leading cause of disability worldwide”Trusted Source. The currently available treatments such as antidepressants and behavioral therapies are effective for many people but are not suitable or available to all.

Some research has suggested that diet may have an impact on depression. A diet high in processed foodsTrusted Source has been linked to more severe symptoms, while eating more fresh, plant-based foods may decrease symptomsTrusted Source.

Now, a study, published in Cell MetabolismTrusted Source, suggests that the severity of depression may be influenced by one specific amino acid — proline.

The research also indicates that a person’s gut bacteria may affect how that amino acid is processed, and how it can counter its depressive effects in some people.

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Proline linked to more severe depression

The researchers used a multi-omicsTrusted Source approach to the analysis — an integrated analysis of many different molecules. They controlled for antidepressant and anti-anxiety medication in their sample.

First, they analyzed the type and amount of amino acids in the diets of those participating in the study. They also analyzed blood plasma and fecal samples from the participants.

Those who had a higher level of proline in their diet reported more severe depression.

Proline can be metabolized to GABA, a neurotransmitter that is thought to help combat depression. However, high levels of proline can disrupt GABA productionTrusted Source.

The participants who reported more severe depression also tended to have higher levels of plasma proline, suggesting that the proline in their diet was not being metabolised effectively.

What is proline?

Amino acids are the building blocks of proteins. There are two types: essential amino acids, which must be consumed through the diet, and non-essential amino acids which are found in food but are also synthesized in the body.

Proline is a non-essential amino acid. It is used to make collagen, the protein that forms connective fibers in our skin, bones, and muscles. It is mainly found in animal-derived foods that are rich in collagen. These include:

  • Meat
  • Fish
  • Dairy
  • Eggs

A plant-based diet will contain lower levels of proline, but vegans can get the amino acid from dietary supplements or from some vegetables, including:

  • Asparagus
  • Cabbage
  • Pulses
  • Buckwheat
The microbiome effect

Some people with high proline intake did not report worse symptoms. The researchers found that these people had lower levels of plasma proline.

On analyzing their gut bacteria, they found that their microbiota was similar to that of participants reporting low levels of depression.

The gut bacteria in those with high proline intake and low levels of depression contained species involved in transport and metabolism of proline.

“Without a doubt, the microbiome affects levels of proline, but what levels and how this affects mood/depression or other aspects of the body are to be determined.”

— Dr. John Tsai, board certified gastroenterologist at Austin Gastroenterology

Testing 2 gut bacteria

To test their theory, the researchers transplanted fecal samples from participants in the study into mice. The mice that received microbiota from more depressed participants with high proline levels showed behaviors associated with depression.

To further test the effect of proline, the researchers isolated the gut bacteria they thought might be making the difference.

They found higher levels of Bifidobacterium in participants with fewer depressive symptoms along with some strains of Lactobacillus. Another gut bacterium, EnterobacterTrusted Source, was associated with more severe depression.

They gave food containing Lactobacillus or Enterobacter to fruit flies (Drosophila melanogaster). The flies given the Lactobacillus were much more motivated to eat and climb than those given the Enterobacter.

In their final experiment, the researchers genetically modified the flies so that proline could not be transported to the brain — these flies proved highly resilient to depression.

More research needed

Dr. Tsai, however, said he was not convinced by the study’s conclusions.

“I feel this study is interesting but has many limitations in study design as well as extrapolating mice/fly results to humans. There may be a correlation but this study far from proves causation,” he pointed out.

“I think the most interesting aspect of this study came from the fruit flies and how proline channels in their brains adapted. Using proline or proline-rich/depleted foods in humans and functional PET scanning of the brain (specifically the prefrontal cortex and hippocampus) may be a very interesting study to consider,” he added.

The researchers suggest that diets with reduced proline content may be effective in reducing depressive symptoms.

Alternatively, they suggest that adjusting the microbiome to contain higher levels of the bacteria that metabolize proline, thereby reducing the amounts reaching the blood plasma may be a route to treating depression without modifying the diet.

“I don’t think there is enough here to directly link dietary proline levels with depression based upon this study. It is worth investigating more diligently with a human experiment that is randomized, controlled, prospective and double-blinded,” Dr. Tsai concluded.

Written by Katharine Lang on May 17, 2022 — Fact checked by Hannah Flynn

Does diet influence mental health? Assessing the evidence

Can diet impact mental health? A new review takes a look at the evidence. Overall, the authors conclude that although nutrition certainly does appear to have an impact, there are still many gaps in our knowledge.

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A recent review looks into food and its effect on mental health.

Nutrition is big business, and the public is growing increasingly interested in how food affects health. At the same time, mental health has become a huge focus for scientists and the general population alike.

It is no surprise, then, that interest in the impact of food on mental health, or “nutritional psychiatry,” is also gathering momentum.

Supermarkets and advertisements inform us all, at great volume, about superfoods, probiotics, prebiotics, fad diets, and supplements. All of the above, they tell us, will boost our body and our mind.

Despite the confidence of marketing executives and food manufacturers, the evidence linking the food we eat to our state of mind is less clear-cut and nowhere near as definitive as some advertising slogans would have us believe.

At the same time, the authors of the new review explain, “neuropsychiatric disorders represent some of the most pressing societal challenges of our time.” If it is possible to prevent or treat these conditions with simple dietary changes, it would be life changing for millions of people.

This topic is complex and convoluted, but trying to understand the nuances is vital work.

Recently, a group of researchers reviewed the existing research into nutrition and mental health. They have now published their findings in the journal European Neuropsychopharmacology.

The authors assessed the current evidence to gain a clearer understanding of the true influence of food on mental health. They also looked for holes in our knowledge, uncovering areas that need increased scientific attention.

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It makes sense

That diet might affect mood makes good sense. First and foremost, our brains need nutrients to function. Also, the food we eat directly influences other factors that can impact mood and cognition, such as gut bacteria, hormones, neuropeptides, and neurotransmitters.

However, gleaning information about how specific types of diet influence specific mental health issues is incredibly challenging.

The reviewers found, for instance, that a number of large cross-sectional population studies demonstrate a relationship between certain nutrients and mental health. However, it is impossible, from this type of study, to determine whether or not food itself is driving these changes in mental health.

At the other end of the scale, well-controlled dietary intervention studies that are better at proving causation tend to recruit smaller numbers of participants and only run for a short period of time.

Lead author Prof. Suzanne Dickson, from the University of Gothenburg in Sweden, explains the overarching theme of the team’s findings:

“We have found that there is increasing evidence of a link between a poor diet and the worsening of mood disorders, including anxiety and depression. However, many common beliefs about the health effects of certain foods are not supported by solid evidence.”

Some specifics

One diet that has received a great deal of attention during the past few years is the Mediterranean diet. According to the recent review, there is some relatively strong evidence to suggest that the Mediterranean diet can benefit mental health.

In their review, the authors explain how “a systematic reviewTrusted Source combining a total of 20 longitudinal and 21 cross-sectional studies provided compelling evidence that a Mediterranean diet can confer a protective effect against depression.”

They also found strong evidence to suggest that making some dietary changes can help people with certain conditions. For instance, children with drug resistant epilepsy have fewer seizuresTrusted Source when they follow a ketogenic diet, which is high in fat and low in carbohydrates.

Also, people with vitamin B-12 deficiencies experience lethargy, fatigue, and memory problems. These deficiencies are also linked with psychosis and mania. For these people, vitamin B-12 supplementation can significantly improve mental well-being.

However, as the authors point out, it is not at all clear if vitamin B-12 would make a significant difference to people who are not clinically defined as deficient.

For many of the questions the researchers explored in this review, it was not possible to reach firm conclusions. For instance, in the case of vitamin D, some researchTrusted Source has concluded that supplementation improves working memory and attention in older adults. Other studiesTrusted Source have found that using vitamin D supplements might reduce the risk of depression.

However, many of these studies were small, and other, similar studies have concluded that vitamin D does not have any impact on mental health.

As the review’s authors point out, because “a substantial proportion of the general population has a vitamin D deficiency,” understanding its role in mental health is important.

Similarly, the evidence for a nutritional role in attention deficit hyperactivity disorder (ADHD) was quite mixed.

As Prof. Dickson outlines: “[W]e can see [that] an increase in the quantity of refined sugar in the diet seems to increase ADHD and hyperactivity, whereas eating more fresh fruit and vegetables seems to protect against these conditions. But there are comparatively few studies, and many of them don’t last long enough to show long-term effects.”

There is a general belief that dietary advice for mental health is based on solid scientific evidence. In reality, it is very difficult to prove that specific diets or specific dietary components contribute to mental health.”

Prof. Suzanne Dickson

The authors go on to explain some of the inherent difficulties in studying the impact of diet on mental health, and they offer some ideas for the future. Overall, Prof. Dickson concludes:

“Nutritional psychiatry is a new field. The message of this paper is that the effects of diet on mental health are real, but that we need to be careful about jumping to conclusions on the base of provisional evidence. We need more studies on the long-term effects of everyday diets.”

Written by Tim Newman on January 8, 2020 — Fact checked by Jasmin Collier

What is the best diet for mental health?

Researchers have increasingly been studying the effects of diet and nutrition on mental health.

Many of them have noticed that people who follow a standard Western diet, which includes highly processed foods and added sugars, have higher risks of developing anxiety and depression.

Although the majority of the research to date has focused on the benefits of the Mediterranean diet, other dietary patterns may also have a positive effect on mental health.

In this article, we review some of the evidence suggesting that a healthful diet can improve mental health and help treat or prevent certain conditions. We also explore how food affects our mood.

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Can diet help with mental health?
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Changes to a person’s diet may improve their mental health.

Nutritional psychiatry, which some refer to as psychonutrition, is a new field of study that focuses on the effect of diet on mental health.

Most studies have focused on the effects of the standard Western diet and the Mediterranean diet. An article in the Proceedings of the Nutrition Society reviewed the existing body of research on diet, nutrition, and mental health.

The research suggests that the more closely a person follows a Western diet, with its highly processed foods, the more at risk they are for depression and anxiety. People who follow a Mediterranean diet, on the other hand, seem to be less likely to have mental health conditions.

Researchers from the Institute of Psychiatry at the King’s College in London in the United Kingdom investigated exactly how nutrition might affect mental health. They focused their researchTrusted Source on the effects of diet on the hippocampus.

The hippocampus is an area of the brain that generates new neurons in a process called neurogenesis. Research has linked neurogenesis in the hippocampus to a person’s mood and cognition.

Stressful experiences reduce neurogenesis in the hippocampus, while antidepressant drugs appear to promote this process.

Factors that can negatively affect neurogenesis in adults include:

  • aging
  • oxidative stress
  • high fat diets
  • high sugar diets
  • alcohol
  • opioids

Healthful foods and habits appear to promote neurogenesis. These include:

  • diets that include polyunsaturated fatty acids (PUFAs), curcumin, and polyphenols
  • a diet that meets calorie needs without a person overeating or undereating
  • physical exercise
  • learning

For more science-backed resources on nutrition, visit our dedicated hub.

Best diets

There is no specific diet that is best for mental health, but some eating patterns appear to be better than others.

Mediterranean diet

Among common diet plans, the Mediterranean diet has the strongest evidenceTrusted Source supporting its ability to reduce the symptoms of depression. It is also a diet that experts routinely recommendTrusted Source for overall health and well-being.

Compounds in the Mediterranean diet that have links to lower depression rates include:

The Mediterranean diet consistsTrusted Source of:

  • plenty of fruits and vegetables
  • whole grains
  • potatoes
  • cereals
  • beans and pulses
  • nuts and seeds
  • olive oil
  • low-to-moderate amounts of dairy products, fish, and poultry
  • very little red meat
  • eggs up to four times a week
  • low-to-moderate amounts of wine

Learn more about how to eat a Mediterranean diet in this article.

Low calorie diet

Short-term calorie restriction has shown some promise for treating the symptoms of depression.

Experts have definedTrusted Source calorie restriction as “a reduction in energy intake well below the amount of calories that would be consumed ad libitum.” The extent of the restriction will vary depending on the individual’s needs.

One study that looked at the relationship between food intake and depression defined calorie restriction as a 30–40% decrease in calorie intake while retaining protein, vitamin, mineral, and water intake to maintain proper nutrition. According to this definition, a person who usually eats 2,000 calories per day would eat between 1,200 and 1,400 calories instead.

A person may not need to reduce their calorie intake by this much, however. ResearchersTrusted Source also noted that in an earlier study, otherwise healthy people who reduced their calorie intake by 25% for 6 months also had reduced depressive symptoms.

It is vital to note that calorie restriction can sometimes lead to the development of an eating disorder. It is also not safe for people who have an existing eating disorder or behaviors relating to disordered eating.

Anyone who wishes to try calorie restriction should also speak to a doctor or a registered dietitian about how to ensure that they are getting enough nutrients.

It is also important not to restrict calories or follow a low calorie diet in the long term, as this can damage neurons and make depressive symptoms worseTrusted Source.

Intermittent fasting

There is some evidence that intermittent fasting can help improve mood and mental well-being.

Clinicians have noted that fasting could contribute to improvements in mood, as well as people’s subjective sense of well-being, alertness, tranquility, and, in some cases, euphoria.

small 2013 studyTrusted Source involving men over the age of 50 years found that in comparison with a control group, those who participated in intermittent fasting had significant decreases in:

  • anger
  • tension
  • confusion
  • mood disturbances

However, other research has produced contradictory results. A studyTrusted Source in amateur weightlifters found that 48 hours of fasting caused negative mood changes, including significantly increased anger and slightly raised confusion and fatigue.

As with calorie restriction, intermittent fasting is not safe for everyone. People with a history of eating disorders or blood sugar issues, such as hypoglycemia, should not attempt intermittent fasting without a doctor’s guidance.

Learn more about the potential benefits of intermittent fasting in this article.

Polyphenols

Another study showed an association between polyphenols and both the prevention of depression and the improvement of depressive symptoms. The polyphenols that the researchers studied came from:

Foods or diets to avoid

Several studies have shown that people who follow a Western diet comprising highly processed foods are more likely to have major depression or persistent mild depression.

2010 studyTrusted Source showed that women who ate unhealthful Western-style diets had more psychological symptoms. The foods that these participants were eating included:

  • processed foods
  • fried foods
  • refined grains, such as white bread
  • sugary products
  • beer

Similar unhealthful dietary patterns that typically lead to obesitydiabetes, and other physical health problems can also contribute to poor mental health.

Summary

Researchers are still determining how diet affects mood.

A Mediterranean diet is one healthful diet that can positively affect a person’s weight, blood pressurecholesterol, and other measures of health. Calorie restriction and fasting may also affect a person’s mental health.

While a healthful diet may aid treatment for poor mental health, anyone experiencing the symptoms of a mental health condition, such as depression or anxiety, should speak to a doctor.

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