Antidepressant foods: An evidence-based system for nutrient profiling in depression

What was the study about?

To investigate which foods are the most nutritious sources of nutrients whose importance in preventing and promoting recovery from depressive disorders has been established in the scientific literature.

Methods:

A systematic literature review was conducted to compile a list of antidepressant nutrients from the 34 nutrients known to be essential for humans based on evidence criteria. For a subset of foods high in at least one antidepressant nutrient, nutritional information was extracted using a USDA database. These foods were analyzed for their antidepressant nutrient density, resulting in an antidepressant food score (AFS). Plant and animal foods were analyzed separately.

Results:

Twelve antidepressant nutrients relate to the prevention and treatment of depressive disorders: Folate, iron, long-chain omega-3 fatty acids (EPA and DHA), magnesium, potassium, selenium, thiamine, vitamin A, vitamin B6, vitamin B12, vitamin C and zinc. In the animal food category, shellfish such as oysters and mussels, various seafood and organ meats scored the highest. The best plant foods were leafy vegetables, lettuce, peppers and cruciferous vegetables.

Conclusions:

The AFS is based on a nutrient profiling system developed to identify foods with the highest nutrient density of nutrients with a clinically proven role in depressive disorders. This list of foods and food categories with the highest density of the 12 antidepressant nutrients, the Antidepressant Foods, should be considered by researchers when designing future intervention studies and by clinicians as a dietary option to support prevention and recovery from depressive disorders.

Keywords:

Depressive disorder, mental disorders, nutrition, nutrition therapy, food

Key message:

The Antidepressant Food Score was developed to identify the most nutritious foods to prevent and promote recovery from depressive disorders and symptoms. The results can be used as a basis for future research studies or clinical nutritional recommendations. This tool is based on a systematic literature review, an evidence-based list of antidepressant nutrients and a calculation of nutrient density. The animal foods with the highest scores were shellfish such as oysters and mussels, various seafood and organ meats. The plant foods with the highest scores included leafy vegetables, lettuce, peppers and cruciferous vegetables. These foods can be integrated into any diet.

Introduction:

Mental illnesses are widespread, disabling, cost-intensive and inadequately treated. Among 15- to 44-year-olds, depressive disorders are the most common cause of disability worldwide [1]. Improving public awareness and expanding treatment options for psychiatric disorders is crucial for public health. A growing body of evidence, including the first randomized controlled trial [2], suggests that dietary behavior and food choices may play a role in the treatment and prevention of brain disorders, particularly depression. The first nutritional guidelines for the prevention of depression were published this year. It recommends following a traditional dietary pattern such as the Mediterranean diet, consuming sufficient amounts of omega-3 fatty acids and avoiding processed foods that contain a lot of refined carbohydrates or sugar, for example [3]. In addition, an international consortium of psychiatry and nutrition researchers recently recommended that ‘nutritional psychiatry’ should become a routine part of clinical practice in mental health [4].

A number of nutrients have been linked to the pathophysiology of depression, such as long-chain omega-3 fatty acids, B vitamins, zinc, magnesium and vitamin D [5,6]. A deficiency of these nutrients can cause depressive symptoms and is used in the form of nutritional supplements in clinical treatment [7-9]. Recent literature on nutrition and psychiatry has shifted from the study of individual nutrients to the assessment of general dietary patterns. Prospective epidemiological studies have repeatedly found that “traditional” or “whole food” dietary patterns are significantly correlated with a lower prevalence and incidence of depressive disorders or symptoms. Western dietary behavior has been associated with an increased relative risk of depression [4,10-12]. The SUN cohort study followed 10094 university students for four years and found that those who followed the Mediterranean dietary pattern (MDP) the most had a more than 30% reduced risk of developing depression during the study period compared to participants who followed the Mediterranean dietary pattern the least [13]. Studies on traditional diets in Japan, Norway and China came to similar conclusions [14-16]. A study by Opie et al. [17] systematic review and meta-analysis of whole food interventions for the treatment of depression and anxiety symptoms revealed that the heterogeneity of the studies did not permit an analysis. However, in the 47% of studies that found a positive effect of a dietary intervention, it was often recommended to increase the intake of fruit, vegetables, fiber and fish [17]. Nutritional counseling used as an active control in a study of problem-focused therapy for the prevention of depression in 122 older adults with sub-syndromal depressive symptoms resulted in a significant and sustained 40% reduction in Beck Depression Inventory scores after two years in participants who received 5.5 hours of nutritional counseling over a 6-12 week period [18]. The SMILES (Supporting the Modification of Lifestyle in Lowered Emotional States) study, the first randomized, controlled trial of a nutritional intervention for the treatment of major depressive disorder, found that prescribing a modified Mediterranean diet as an add-on treatment led to remission in 31% of cases compared to placebo, and the number needed to treat was 4.1 [19].

Brain health and mental illness are influenced by diet through various mechanisms. A detailed discussion is beyond the scope of this paper, but we would like to highlight a few relevant mechanisms here. Nutrients such as long-chain omega-3 fatty acids, zinc, magnesium and a range of phytonutrients promote the expression of Brain Derived Neurotropic Factor (BDNF) and thus influence neuroplasticity [20]. In addition, diet is a modifiable determinant of systemic inflammation, which has been described as one of the main causes and consequences of depression according to the neuroinflammatory hypothesis of this disorder [21]. Finally, the emerging role of gut flora (i.e. the microbiome) as a possible key player in regulating mood, cognition and anxiety suggests that we are only at the beginning of discovering the potential of food as medicine [22]. Dietary fibers are prebiotics and their consumption can change the composition of the microbiota [22].

Prescribing a dietary pattern that is unfamiliar to a person presents some challenges. A Japanese diet plan or MDP is not practical or palatable for many patients. Instead, categorizing foods and highlighting food categories with a high density of nutrients that have been shown to have a positive effect on depression could lead to specific food recommendations that can be integrated into a whole food dietary pattern of the patient’s choice [3]. For the purposes of this paper, nutrient density is defined as the ratio between the nutritional value of a food and its calorie content.

A review of 23 existing nutritional profiles found that they are designed to improve a range of health outcomes. While there are currently many nutrient profiling scales created by government agencies, researchers and the food industry, none of them focus on mental disorders or brain health [23]. Furthermore, no scale is based on nutrients whose importance for the prevention and cure of psychiatric disorders has been proven in the scientific literature. The aim of this study is to determine which foods are the most nutritious sources of nutrients whose importance for the prevention and recovery of depressive disorders is supported by human studies published in the current scientific literature.

Materials and methods:

Based on the Dietary Reference Intakes of the Institute of Medicine [24], a list of 34 essential nutrients for humans was compiled. A Columbia University librarian was consulted to develop a systematic search strategy to further refine an evidence-based list of antidepressant nutrients. In February 2017, computerized searches were conducted in OVID Medline, Embase and Embase Classic back to 1946 using the search terms “Depressive Disorder, Major (MeSH)” and “Depression (MeSH)” in combination with the following nutrients: Arsenic, biotin, boron, calcium, carotenoids, choline, chromium, copper, fiber, fluoride, folic acid, iodine, long-chain omega-3 fatty acids (docosahexanoic acid and eicosapentanoic acid), magnesium, manganese, molybdenum, niacin, nickel, phosphorus, potassium, pyridoxine, riboflavin, selenium, sodium, silicon, sulphates, vanadium, vitamin A, vitamin B12, vitamin C, vitamin E, vitamin K and zinc. The search terms have been adapted to the various databases. The titles and abstracts were read by both authors of the study to determine whether the papers found were relevant to the topic under investigation according to the following inclusion criteria: Observational or experimental studies on an essential nutrient for the treatment or prevention of depressive disorders or symptoms (unipolar) in humans. The exclusion criteria included non-English language articles, review articles and opinion pieces. Subsequently, the relevant articles were subjected to a full-text review and data extraction by both study authors, nutrient by nutrient. The study results were coded as positive, negative or equivocal with regard to the prevention or cure of depressive disorders. Discrepancies were clarified by both authors by consensus.

Statistical analysis:

A system for grading the level of evidence for each potential antidepressant nutrient was developed, based on the level of evidence criteria used in various clinical practice guidelines in psychiatry [25]. The level of evidence was determined for both observational and experimental human studies for each nutrient considered using the following guidelines (see Table 1.1). Nutrients were included in the list of antidepressant nutrients if they had a combined score of less than or equal to 5. Magnesium, for example, received an overall score of 4. There was one positive RCT and one positive prospective cohort study, both with sufficient sample size, resulting in an evidence level of 2 for both experimental and observational studies.

Table 1

Levels of evidence

Levels of evidence: Observational studies Levels of evidence: Experimental studies

1. At least 2 prospective cohort studies with adequate sample size and/or meta-analysis with narrow confidence intervals
2. At least 2 RCTs with adequate sample size, preferably placebo-controlled, and/or meta-analysis with narrow confidence intervals
3. At least 1 prospective cohort study with adequate sample size and/or meta-analysis with wide confidence intervals
4. At least 1 RCT with adequate sample size and/or meta-analysis with wide confidence intervals
5. Cross-sectional or case-control studies
6. Non-randomized, controlled prospective studies (open-label) or high-quality retrospective studies (i.e. case series)
7. Expert opinion/consensus
8. Evidence is not clear/unavailable
9. Evidence is unclear/unavailable

In July 2017, lists of the top 20 plant and animal whole food sources for each antidepressant nutrient were created based on the USDA’s nutrient database [26]. After duplicates were removed, this preliminary list comprised 213 foodstuffs. Another 23 commonly recommended healthy foods such as whole grains, blueberries and yogurt were added to this list to assess their AFS.

For each of the 236 foods, the nutrient content for each antidepressant nutrient was recorded in the database. The nutrient content was given as a percentage daily value. If no percentage daily values were available, e.g. for long-chain omega-3 fatty acids, the absolute amount of nutrients per 100 g portion of raw food was determined. This was then later converted into a percentage daily value. For long-chain omega-3 fatty acids, we based this calculation on a recommended daily intake of 1000 mg of long-chain omega-3 fatty acids (EPA + DHA) based on a review of available guidelines [27].

The data was collected for a 100 g portion of each food in raw form. This was done because different preparation methods can change the nutrient content, the bioavailability of nutrients and the water content of the food. In addition, nutrients differ considerably between plant and animal foods in terms of bioavailability and form. Heme iron, for example, is only found in animal foods, and long-chain omega-3 fatty acids are not found in plant foods – with the exception of certain sea vegetables. The separation of plant and animal foods also served to minimize the heterogeneity of bioavailability and nutrient content in the different foods.

The average antidepressant nutrient density was calculated for each food included in our list. This resulted in a nutrient density value expressed as a percentage. The percentage daily value for each nutrient was limited to 100 % so that a single nutrient does not influence the AFS too strongly. Our methods were adapted from a recent study on nutrient profiling of powerhouse fruits and vegetables [28]. The following formula was used to calculate the antidepressant nutrient score: [(Σ % daily value per antidepressant nutrient / 12 ) / calories per 100 g serving ] × 100.

RESULTS

Literature review

Our initial searches yielded 1628 results, and screening by title and abstract yielded 213 relevant results that were eligible for full-text review. The following 12 nutrients met the evidence level criteria and were classified as antidepressant nutrients: Folate, iron, long-chain omega-3 fatty acids (EPA, DHA), magnesium, potassium, selenium, thiamine, vitamin A, vitamin B6, vitamin B12, vitamin C and zinc.

Foods with an antidepressant effect

The best antidepressant foods based on the AFS are listed in Table 2.2. The foods were divided into categories and ranked in Table 3.3. The categorization of foods facilitates the implementation of the results, as it offers the researcher or clinician more flexibility [29]. The full list of foods analyzed, the antidepressant nutrient content per 100 g serving, the AFS and the level of evidence per nutrient are provided in the supplementary materials. The authors excluded the following 6 foods from the analysis because no data were available for more than two nutrients: Walleber, caribou liver, blackfish, wild boar, antelope and longan.

Table 2: Antidepressant foods

Table 3

Food categories and mean value for antidepressant foods

AFS: Value for antidepressant foods.

DISCUSSION

To our knowledge, the Antidepressant Food Score (AFS) is the first nutrient profiling system created to provide nutritional recommendations for mental health. This evidence-based approach is unique in that it is based on antidepressant nutrient density. That is, nutrients that have been shown in human studies to be beneficial for the treatment or prevention of depressive disorders. Our findings include a list of individual foods and a ranking of foods within categories that can be incorporated into the design of subsequent research studies or recommended to patients as part of a healthy dietary pattern of their choice.

Interestingly, many foods with a high AFS value are not frequently consumed as part of the Western diet. In particular, the majority of the adult population in the United States does not meet the daily recommendations for vegetables. The Healthy People 2010 initiative, which aimed to increase vegetable consumption among adults, found that only 27.2 percent consumed three or more servings of vegetables per day [30]. The average annual seafood consumption for Americans is 14.6 pounds, and the USDA estimates that 80-90 percent of the population does not meet the recommendation of two servings of seafood per week [31]. On the contrary, the foods that score highest on the AFS, namely seafood, leafy greens, cruciferous vegetables and nuts, are commonly consumed as part of a variety of traditional diets. The Mediterranean diet pattern is just one example of a consistent pattern: traditional diets contain more nutrient-rich foods and less highly processed foods. The evidence for a link between dietary patterns and depressive disorders supports the consumption of a whole-food based traditional diet as opposed to a Western dietary pattern to prevent and promote recovery from depression. This new literature lends some external validity to the findings of the AFS, while our study serves to identify some of the “active ingredients” of these traditional diets.

Choosing foods according to their nutrient density is one way to meet daily nutrient requirements without consuming excessive calories, which can be beneficial for more than just mental health [32]. This is particularly important when you consider that for a number of antidepressant nutrients there are high rates of dietary inadequacy, meaning that many people do not reach the Recommended Dietary Allowance (RDA). For example, 55% of the American population does not reach the RDA for vitamin A, 75% for folic acid and 68% for magnesium [33].

It is worth discussing how our results differ from certain currently accepted dietary guidelines and nutrient profiles [28,32,34]. For example, the AFS focuses on depression and does not take into account food components to be avoided such as saturated fats, cholesterol and sodium. A recent review suggests that nutrient profiling scales designed to improve consumer food choice should be based on nutrients that are known to be beneficial to health, rather than nutrients that should be avoided [29]. In addition, the harmfulness and potential benefits of nutrients such as saturated fat, cholesterol and sodium to physical and mental health are being questioned based on recent research, and cholesterol is no longer considered a nutrient of concern under the most recent Dietary Guidelines for Americans [35-37]. Finally, only whole, unprocessed foods with no added sodium or fat are assessed in the AFS. The recommendation to continue to avoid fat, cholesterol and sodium may discourage patients from eating whole, potentially nutritious food categories, such as seafood.

Certain nutrients such as long-chain omega-3 fatty acids, vitamin B12 and heme iron are only found in animal foods such as seafood, meat, eggs and dairy products, and these foods are generally not included in existing nutritional profiles. This may be because a particular scale includes cholesterol, saturated fat or sodium as nutrients to avoid, while other scales simply omit animal foods altogether. As health recommendations are increasingly moving towards a “plant-based” diet, the higher rates of B vitamin deficiency in vegetarian and vegan populations must be taken into account. In a recent large study, vegetarian men were found to have higher rates of depressive symptoms [38]. Our findings underline the importance of considering animal foods as an important part of a healthy diet to prevent depressive disorders and promote recovery. However, there is a discrepancy between the animal foods that rank high on our scale, such as organ meats and seafood, and the processed meats that are typically consumed as part of the Western diet. The results of our study supplement the current discussion in the nutrition literature on the importance of a “plant-based” diet with a supplementary recommendation: Eating animal products such as seafood, organ meats and small amounts of other traditionally farmed, minimally processed meats is an important part of a healthy diet for depression. This is significant in that the majority of eaters consume animal products.

Certain nutrients such as long-chain omega-3 fatty acids, vitamin B12 and heme iron are only found in animal foods such as seafood, meat, eggs and dairy products, and these foods are generally not included in existing nutritional profiles. This may be because a particular scale includes cholesterol, saturated fat or sodium as nutrients to avoid, while other scales simply omit animal foods altogether. As health recommendations are increasingly moving towards a “plant-based” diet, the higher rates of B vitamin deficiency in vegetarian and vegan populations must be taken into account. In a recent large study, vegetarian men were found to have higher rates of depressive symptoms [38]. Our findings underline the importance of considering animal foods as an important part of a healthy diet to prevent depressive disorders and promote recovery. However, there is a discrepancy between the animal foods that rank high on our scale, such as organ meats and seafood, and the processed meats that are typically consumed as part of the Western diet. The results of our study add to the current discussion in the nutrition literature about the importance of a “plant-based” diet with a complementary recommendation: eating animal products such as seafood, organ meats, and small amounts of other traditionally raised, minimally processed meats is an important part of a healthy diet for depression. This is significant in that the majority of eaters consume animal products.

Gut health is increasingly seen as crucial for brain health [22]. Plants are not only nutrient-rich sources of vitamins and minerals, but also two components that are important for mental health but are not sufficiently considered in the literature: Dietary fiber and phytonutrients. In general, the Western diet lacks fiber, which affects the population and diversity of bacterial species that make up the microbiome, the collection of bacteria in the gut [39]. Phytonutrients are plant compounds such as lycopene and quercetin that are traditionally thought of as “antioxidants” but clearly play a role in cell signaling, affecting gene expression and modulating inflammation [40]. It was not possible to rank foods according to phytonutrient content, and there is insufficient evidence of a link between individual phytonutrients and brain health. Dietary fiber did not reach the level of evidence required for inclusion and further studies are clearly needed.

The AFS lists foods and nutrients with a defined reference intake that is included in the USDA database as a standard reference at the time of analysis. The antidepressant nutrients were determined on the basis of the scientific literature available at the time of the literature search using our search strategy. Thus, certain nutrients such as phytonutrients and other antioxidants were automatically excluded from our algorithm either because there is no established reference intake, they are not included in the USDA database, or there are no human studies demonstrating their efficacy in treating or preventing depressive disorders. Finally, clinical studies on nutrients often use doses of supplements that far exceed what can be ingested through food. If a high dose of vitamin B12 can promote recovery from depression, it does not necessarily follow that foods with a high nutrient density of vitamin B12 will do the same.

The results of the current study can be incorporated into the design of further research studies. Thus, when developing a dietary intervention to treat depression, researchers should consider including and emphasizing foods that score high on the AFS. In addition, the authors plan to make our database publicly available online after the publication of this paper so that it can be used by physicians, researchers and patients alike. The next steps include expanding our database to include all foods listed in the USDA database.

In summary, a nutrient profiling system focused on mental health resulted in a ranking of plant and animal foods according to the nutrient density of the 12 nutrients supported by current evidence: Folate, iron, long-chain omega-3 fatty acids (EPA, DHA), magnesium, potassium, selenium, thiamine, vitamin A, vitamin B6, vitamin B12, vitamin C and zinc. Evidence-based nutritional recommendations are crucial for the use of nutritional psychiatry in clinical practice. Considering the cost, stigma and access, nutritional interventions offer a unique treatment option for the mentally ill. In addition, mental health professionals are well versed in supporting behavioral change, of which dietary change is just one example. As the evidence base for diet as a modifiable factor influencing both the risk and prognosis of mental illness continues to grow, the AFS a tool to help researchers refine dietary recommendations to inform the design of future studies and help clinicians guide patients to make healthier food choices today.

ARTICLE HIGHLIGHTS

Background to the research

The Western diet is deficient in a number of important nutrients. There is evidence that diet is key to the prevention and treatment of depressive disorders, but treatment rarely includes dietary recommendations. Nutrient profiling systems classify foods according to their nutrient density and provide guidance for clinical recommendations, research study design and patient selection. No current food rating scale focuses on the nutrients needed for mental health.

Research objectives

The aim of this study is to find out which foods have the highest nutrient density and which nutrients play a role in preventing and promoting recovery from depressive disorders according to scientific literature.

Research methods

A systematic literature review was conducted to compile a list of antidepressant nutrients from the 34 nutrients known to be essential for humans based on evidence criteria. Nutritional information was extracted for a subset of foods high in at least one antidepressant nutrient using a USDA database. These foods were analyzed for their antidepressant nutrient density, resulting in an antidepressant food score (AFS). Plant and animal foods were analyzed separately.

Research results

Twelve antidepressant nutrients relate to the prevention and treatment of depressive disorders: Folate, iron, long-chain omega-3 fatty acids (EPA and DHA), magnesium, potassium, selenium, thiamine, vitamin A, vitamin B6, vitamin B12, vitamin C and zinc. In the animal food category, shellfish such as oysters and mussels, various seafood and organ meats scored the highest. The best plant foods were leafy vegetables, lettuce, peppers and cruciferous vegetables.

Conclusion of the research

The AFS is based on a nutrient profiling system developed to identify foods with the highest nutrient density of nutrients clinically proven to play a role in depressive disorders. This list of foods and food categories with the highest density of the 12 antidepressant nutrients, the Antidepressant Foods, should be considered by researchers when designing future intervention studies and by clinicians as a dietary option to support prevention and recovery from depression.

Research perspectives

The AFS was developed to identify the most nutritious individual foods to prevent and promote recovery from depressive disorders and symptoms. The results can serve as a basis for future research studies or clinical nutritional recommendations. This tool is based on a systematic literature review, an evidence-based list of antidepressant nutrients and a calculation of nutrient density. The animal foods with the highest scores were shellfish such as oysters and mussels, various seafood and organ meats. The plant foods with the highest scores included leafy vegetables, lettuce, peppers and cruciferous vegetables. These foods can be integrated into any diet.