Linking Depression to Nutrition

Dr. David Wiss

June 10, 2022

Mental Health

Major depression is a commonly occurring and seriously impairing disorder, distinct from unhappiness or typical feelings of sadness. Symptoms of depression include:[1]

  • Depressed mood

  • Anhedonia (inability to feel pleasure)

  • Feelings of worthlessness or guilt

  • Suicidal ideation (plan or attempt)

  • Fatigue or loss of energy

  • Sleep decrease or increase

  • Weight or appetite decrease or increase

  • Decreased ability to think or concentrate (or indecisiveness)

  • Psychomotor agitation

Interestingly, the lifetime prevalence estimates are generally higher in high-income countries [2]. Projections have speculated that depressive disorders will become the leading cause of disability-adjusted life years lost by the year 2030 [4]. During the COVID-19 outbreak, the prevalence of depression has skyrocketed to 25% [5]. It is reasonable to expect that the burden of depression will continue to place high demands on the healthcare system, and compromise the quality of life in our communities.

Women have a lifetime risk of major depression roughly twice as high as men, and this gender gap is increasing among adolescents [3]. This difference is also likely due to how depression is measured in research. Mental health issues among teenagers are a growing problem that warrants aggressive public health attention. 

There are many causes of declining mental health, and this article discusses the possibility that nutrition is a contributor, as well as a solution, to some forms of depression. Below, we highlight the evidence suggesting that an anti-inflammatory diet for depression (e.g., olive oil, fruits, and vegetables) can help in certain presentations of depressive disorders. 


A Biopsychosocial Model of Nutrition and Depression

At Wise Mind Nutrition, we examine health and disease through a biopsychosocial model which integrates lenses of biology, psychosocial, and social/environmental context. Using this approach, depression can be analyzed in parts and then integrated into an overall model which examines the dynamic and synergistic interplay between the parts. The biology of depression is complex, and no single model or mechanism can satisfactorily explain all aspects of its presentation. Biological factors include:[1]

  • Monoamine hypothesis (the primary basis for anti-depressant medications)

  • Hypothalamic-pituitary-adrenal (HPA) axis (responsible for stress response via cortisol)

  • Neuroplasticity and neurogenesis (which facilitates resilience against stress)

  • Inflammation (a hot topic discussed further below)

  • Structural and functional brain changes (measured through neuroimaging)

  • Genetics (which investigates multiple genes- termed polygenic)

  • Epigenetics (modification of genes that do not alter the genetic code itself)

The psychology of depression might seem even more complex since it is more difficult to measure pathways. One known contributor is early life adversity. Many of the biological aspects of depression are also consequences of early life trauma, but not all depression cases have clear origins in developmental processes.

The experience of being stigmatized based on weight is a known contributor to depression [6]. Efforts to diet can be extremely stressful and perpetuate a vicious cycle leading to weight gain and depression [7,8], which is one reason the nutrition field is moving toward non-diet approaches. Body comparison through social media use can also contribute to depression, but this relationship has been suggested to be bidirectional (depression can also lead to more social media use) [9].

Social and environmental factors of depression can include stressful life events, socioeconomic status, and the presence of social inequality [10]. Environmental exposures (e.g., airborne pollution) also contribute to depression through biological mechanisms [11]. Clearly, there are multiple risk factors for depression and several potential avenues of treatment. Can nutrition be part of the solution?


Ultra-Processed Food Consumption

It’s no secret that the consumption of ultra-processed foods has risen dramatically since 1980. The scale of change in dietary patterns since the 1980s has been rapid, which has stimulated much debate in public health. The most concerning rise in the consumption of ultra-processed foods may be among minoritized youth in the United States [12].

Dysfunctional eating patterns due to COVID-19 circumstances and related distress have been documented [13]. In high-quality longitudinal studies, ultra-processed food consumption increases the risk of developing depression [14,15]. So, what can we do about it?


Evidence Supporting Nutrition as a Treatment for Depression

It is important to point out that most of the work in this area is outside of the United States. Australia, the United Kingdom, Canada, and South America have done some groundbreaking work in the domain of nutrition for mental health, often referred to as “nutritional psychiatry” [16]. To date, much of this research has focused on the role of vitamins and minerals, but as you will see, there is so much more to it! 

With respect to mental health, early life development sets the stage for later development and may influence susceptibility. One example is adverse childhood experiences. Thus, personalization of nutrition for mental health should take early life development into account. This is a foundational philosophy of Wise Mind Nutrition. 

It is also important to acknowledge that nutrients and their metabolites act upon multiple targets in multiple organs [16]. Most research has used dietary supplements rather than food because it is much easier to draw conclusions about their impact (randomized controlled trials). Dietary studies can investigate ways to modulate brain function by altering specific bacterial strains known for producing centrally active metabolites (i.e., “postbiotics”).

The mechanisms of action of associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. In nutrition studies, we add some pathways to the list of biological factors offered above:[17]

  • Gut microbiota (collection of microbes colonizing the gastrointestinal tract)

  • Oxidative stress (related to inflammation)

  • Mitochondrial dysfunction (responsible for energy production)

  • Tryptophan-kynurenine metabolism (related to the monoamine hypothesis)

  • Brain-derived neurotrophic factor (BDNF; related to synaptic plasticity)

The following figure summarizes these potential pathways, previously published by Marx et al. (2021):[17]


Marx et al. 2021

A common factor of depressive disorders is the production and overall effects of inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) [18]. Again, many of these inflammatory cascades are also implicated in early life trauma. The basis for this etiological hypothesis of depression is through the disruption of the blood-brain barrier caused by the convergence of oxidative stress and pro-inflammatory signaling. It has been suggested that “leaky gut” can lead to a “leaky brain” [19].

The most studied dietary intervention for the alleviation of depressive symptoms is the Mediterranean Diet. A summary of the interactions between the Mediterranean Diet and the unipolar depressive disorder hypothesis has been published in a figure by Pano et al. (2022):[18]


Pano et al. 2022

Depression: Is it Treatable in Adults Utilizing Dietary Interventions? A Systematic Review of Randomized Controlled Trials [20]

I was very pleased to read the latest systematic review on this topic. To date, most studies showing positive associations with nutrition for depression have been cross-sectional, with only a handful of longitudinal studies. But now there are seven randomized controlled trials using dietary interventions for depression that met the criteria for this systematic review!

I was particularly impressed with their methodology because the studies used to assess whole-food intervention had no intention of causing weight loss as an outcome. It’s about time we focus on mental health outcomes rather than BMI. This is the future of nutrition! 

Furthermore, studies examining supplements (such as fish oil or single micronutrients) were also excluded. As humans do not consume micronutrients in isolation, it is more meaningful to consider the effects of whole foods and dietary patterns in relation to depression. Food finally gets the spotlight it deserves! 

At the conclusion of the interventions, all seven studies revealed a decrease in depressive symptomatology. WOW. Interventions were dietary and included counseling and monitoring, ranging in length from ten days to one year. Results show positive results for eating patterns that promote an intake of fresh produce, whole grains, low-fat dairy, and lean protein sources, while simultaneously decreasing the intake of processed and high-fat foods. 

In my opinion, future studies should disentangle the types of fats used in interventions. We know that high-fat foods such as nuts, seeds, avocado, coconuts, and olives have benefits for mental health therefore the promotion of “low-fat” foods can be misleading.

The authors concluded that the consumption of high-quality diets with anti-inflammatory properties and an increased supply of antioxidants may reduce systemic inflammation and oxidative stress, thereby potentially decreasing depressive symptomatology [20]. Amazing.


Conclusions and Future Directions

Depression is complex and multifactorial. Nutrition interventions hold great promise for some presentations of depression, particularly if the pathophysiology is rooted in inflammatory processes. The era of “diet for depression” is here (although we don’t love the term “diet”).

Other mechanisms of action of nutrition can include epigenetic change, which will be discussed in a future article. The role of gut microbiota is likely to play an important role in the nutrition-depression connection, through inflammatory processes as well as in the production of “postbiotics” (e.g., short-chain fatty acids) which we can all expect to learn more about soon! 

Nutrition intervention for depression may be particularly warranted among those who do not respond well to medication. And for those that do, nutrition should be an adjunctive treatment.

At Wise Mind Nutrition, we are here to support you in your quest for recovery. Our program utilizes evidence-based lifestyle interventions focused on nutrition to improve mood and brain health. Knowing what to eat is one thing. Knowing how to take the necessary steps to get there is a whole other challenge. We are experts in nutrition-related behavior change and are here to walk you through the entire journey, one bite at a time!


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