Julia J. Rucklidge, PhD

Over the last decade, we have seen an exponential increase in research relating diet quality to mental health. The typical Western diet of ultra-processed foods does not adequately meet the brain’s nutritional requirements and is a proven risk factor for the subsequent emergence of mental disorders in both adults and children.

 Given the strength of the data supporting the role of optimal nutrition for good mental health, psychiatrists are well positioned to introduce their patients to the topic of diet for mental health and the possible benefit of nutrient supplements for psychiatric conditions.

Evidence for Dietary Impact on Mental Health

A wealth of research shows that diet affects mental health, including observational and epidemiological studies, prospective longitudinal studies, randomized controlled trials (RCTs), and meta-analyses.

 The results demonstrate that consuming a whole-foods, Mediterranean-style diet can improve emotional 

 and lower the risk of mental health disorders. Shifting to this diet brought improvements in depression, 

 (ADHD), and age-related cognitive decline in several RCTs. Research also shows that an ultra-processed diet, characterized by packaged or fast foods that are high in sugar, salt, and unhealthy fats, generally 

 poor mental health. Unfortunately, ultra-processed foods constitute more than 50% of Americans’ caloric intake.

Dietary Intake of Nutrients May Be Insufficient

Although a whole-foods dietary pattern forms the foundation for good mental health, we can no longer be confident that it covers all nutritional needs. Food labeling mostly focuses on the 3 

nutrient categories of carbohydrates, proteins, and fats, overshadowing the importance of the much smaller but essential 

. Micronutrients contribute to healthy brain functioning in a variety of ways, including supporting the brain’s metabolism, optimizing mitochondrial function, modifying genetic expression, fighting excess inflammation, and protecting from environmental toxins.

Why and When Supplementation May Be Beneficial

Both environmental and individual factors may contribute to the necessity of additional nutrients relative to those supplied in a person’s usual diet.

 Environmental factors include decreased nutrient density in our food due to changes in agricultural practices, heavy use of herbicides and pesticides that decrease soil health and plant nutrient density, and increasing levels of carbon dioxide in the atmosphere that can lower vitamins, minerals, and protein in crops.

Individual factors, including genetics, medication use, and gut health, may influence the amount of 

 a person needs to maintain mental health. These considerations include inheriting a need for unusually high amounts of the cofactors required for optimal function of brain metabolic pathways, taking medication that may deplete nutrients (eg, proton pump inhibitors), and developing gut health problems that compromise absorption of micronutrients. Chronic stress may lead to nutrient depletion as well.

These environmental and individual factors have fostered the scientific study of nutrient supplementation to improve brain health and mental functioning. Studies began in the 1920s with 1 nutrient at a time (eg, thiamine, selenium, or calcium) and reported only occasional modest benefits.

 Because nutrients work together, a more logical and physiologically sound approach to treating psychiatric disorders is to provide them all in combination. Therefore, in reviewing the evidence base for nutrient supplementation, we focus on those studies using the full array of micronutrients identified as essential for brain health (about 30 of them)

 which we will refer to as “broad-spectrum micronutrients.”

Evidence Supporting Nutrient Supplementation for Mental Health

 Nature ensures that micronutrient-dependent functions required for short-term survival (like the fight-or-flight response) are protected at the expense of longer-term functions (like mood regulation). RCT data show that supplementing with a broad spectrum of micronutrients can be an effective way to improve mental resilience following environmental and manmade disasters.

Micronutrients (sometimes combined with omega 3s) can also reduce aggression and violence, as demonstrated with case studies, open-label studies, and multiple RCTs. The results have been reported across a range of populations, from aggressive children to incarcerated adults.

. Three RCTs confirmed the benefit of micronutrients for the treatment of symptoms associated with ASD, with documented benefits ranging from improved sleep and gastrointestinal problems in one study, to positive effects on reducing tantrums and hyperactivity, to improving receptive language and overall functioning in another RCT.

 systematically followed 88 children and adults; half took micronutrients, and half took medications. Those taking micronutrients showed greater improvement in ASD symptoms as well as a significant reduction in self-injurious behaviors, while there were no changes in the medication group.

Figure. Percent Identified as “Much” to “Very Much” Improved Across Groups Based on the Clinician Global Impression 

. Three RCTs demonstrated significant improvements with medium effect sizes in multiple areas of functioning, including ADHD symptoms (particularly inattention) as well as aggression and emotion regulation/mood for adults and children with ADHD.

 Clinician CGI-I ratings were remarkably similar across these 3 studies (

). In the third RCT, the micronutrient group also grew 6 mm more than the placebo group over 8 weeks (ES=1.15). A meta-analysis confirmed the consistency of findings across 2 of the RCTs, noting a significant effect on clinician-rated inattention, global functioning, CGI-I, and CGI-I-ADHD.7 The participants in 2 of the RCTs were followed for 1 year, with about 80% of those still taking the micronutrients meeting criteria for remission from their ADHD symptoms, versus about 40% of those on medications and about 20% of those who stopped all treatments.

. Post-hoc analyses of RCT data, small RCTs, and open-labelled trials highlight potential benefit for depression,

Safety and Other Clinical Concerns of Broad-Spectrum Micronutrients

To date, no serious adverse effects have been attributed to micronutrient treatment when administered as a broad spectrum. Adverse effects are typically mild and transitory (eg, headaches, stomachaches) and can be avoided by taking capsules on a full stomach and with plenty of water, with no group differences between active and placebo on adverse event reporting. In addition to participant or parent reports, several studies have collected biological safety data (eg, blood samples, heart rate, blood pressure)—some for 2 to 3 months, and some over several years—with no evidence of clinically meaningful short-term or long-term concerns.

As most broad-spectrum micronutrient trials have been conducted with medication-free individuals, caution is warranted in using them as an adjunct to psychiatric medication (

). Theoretically, micronutrients can potentiate medication effects; for example, by increasing neurotransmitter synthesis or interacting with CYP enzymes.

 For these reasons and others, medication dose reductions may be needed when combined with micronutrient supplementation.

Table. Clinical Considerations When Using Broad-Spectrum Micronutrient Treatments

Baseline laboratory testing is not necessary before considering nutrient treatment because research has shown that clinical response did not depend on whether an individual had within-range or deficient nutrient levels. Most laboratory-defined normal ranges are based on population requirements for physical health. More importantly, lab values provide a comparison to the general population, thus they do not identify individuals who are deficient relative to their own individual metabolic needs.

Although a whole-foods diet is essential for mental health, empirical studies support the benefit of micronutrient supplementation as an addition to a whole-foods diet in individuals with a range of mental health concerns. Nutritional psychiatry is rapidly expanding as a field. Additional studies are underway to replicate and increase methodological rigor to the existing literature, widen the range of disorders evaluated for potential clinical benefits of nutrient supplementation, determine whether specific subgroups have the greatest probability of clinical benefit, and to expand our understanding of the interface between micronutrient treatment and gastrointestinal integrity. As such, psychiatrists and other mental health professionals will have a wealth of additional data to inform their clinical work relating diet to mental health.

is a professor at the University of Canterbury. 

is an assistant professor at Oregon Health & Science University. 

is Professor Emerita at the University of Calgary.

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Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial.

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Micronutrients for attention-deficit/hyperactivity disorder in youths: a placebo-controlled randomized clinical trial.

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Articles

Here’s how nutrients can ameliorate psychiatric conditions. 

Nutritional Treatments: The Next Frontier in Psychiatry 

Psychiatrists and other mental health professionals are often asked about the role that diet and nutrition play in ADHD etiology and symptom management. This article examines the contributory role of diet on ADHD symptoms, including how the elimination of certain foods and additives, as well as the consumption of other foods or nutrients, may impact symptoms. The role of nutrient supplementation will be reviewed as well, including the potential mechanisms behind why nutrient supplementation may alleviate some symptoms of the disorder.

Elimination diets have been a consideration in managing ADHD symptoms since the 1970s, beginning with the work of Feingold,

 a pediatric allergist, who recommended eliminating food additives such as dyes and preservatives alongside other foods. Feingold theorized that highly antigenic foods (those often associated with allergies and intolerance) negatively influenced the behavior of children with ADHD (hyperkinesis). Despite anecdotal reporting from many families that the elimination of these foods, based on Feingold’s diet, significantly improved their children’s behavior, initial results from effectiveness studies were inconclusive. In the decade that followed these mixed results, stimulant medication came to the fore as a primary treatment for ADHD, which likely contributed to diminished scientific interest in dietary interventions for ADHD.

Over the past two decades there has been renewed scientific interest in dietary interventions for ADHD. In randomized, double-blind, placebo-controlled studies from the University of Southampton, the consumption of food coloring and preservatives was found to be associated with hyperactive behavior in community samples of 3 year olds and 8 and/or 9 year olds.

 Although the study comprises a community rather than a clinical sample, the findings led to a reconsideration of the theoretical underpinnings of Feingold’s diet, at least for some hyperactive children.

Further investigation into the genotypes of the Southampton study participants highlighted possible mechanisms that may contribute to individual responses to food additives. Stevenson and colleagues

 suggest that in children with ADHD, histamine gene polymorphisms associated with alterations in the histaminergic system, explain differential responses to certain food additives.

Meta-analyses have shown that for about 8% of children, elimination of certain foods, additives, and food colors resulted in significant improvement in ADHD symptoms. In response to these findings, several European nations have banned the use of certain artificial food colors due to the strength of the evidence that these colors may have adverse effects on childhood behavior, while offering no nutritional value to the child. It is important to note though that in the study by Nigg and colleagues,6 effects were not significant on teachers’ reports and observer measures.

Overall, the clinical utility of removing food dyes and additives should be weighed against difficulty and expenses. Ideally ingredients such as food dyes and preservatives should be minimized in the food supply rather than expecting families to navigate the exclusion of these food additives, especially dyes. While removing food dyes and additives requires patient burden, these ingredients confer no health benefit and are purely “aesthetic,” used by food manufacturers to entice children to eat more processed food.

One study that went further than investigating the effects of food additives and colors on ADHD symptoms is The Impact of Nutrition on Children with ADHD (INCA) study.

 The study also included the effects of full oligoantigenic diets or a “few foods diet” (the elimination of other potential allergens as well, such as wheat, dairy, certain meats, carbohydrates, fruits, and vegetables). In few foods diets, food restrictions remain for some weeks (2-5 weeks) in which the individual is only allowed to eat a few different hypo-allergenic foods (eg, rice, turkey, lettuce, pears, water), then a broader range of foods are gradually reintroduced.

Administering such diets is problematic because the food restrictions render blinding difficult. In addition, providing support or guidance for such an intervention is outside the expertise for most mental health professionals. For families, this level of dietary restriction can be challenging to maintain. Nevertheless, the INCA study demonstrated significant symptom reduction in individuals with ADHD. The mechanisms are uncertain however, as the study was unable to demonstrate a relationship between immunoglobulin E (IgE) and IgG levels and exposure to the highly restrictive diet.

An effect size of 0.29 was reported for the elimination/oligoantigenic diets across 6 controlled trials that included 195 participants.

 Findings indicate that about one-third of the children with ADHD had an excellent (>40% symptom reduction) response. However, according to CatalÃ¡-LÃ³pez and colleagues,

 the elimination diet research is significantly hampered by methodological heterogeneity rendering small or imprecise effect sizes that need to be interpreted with caution. While few foods diets may result in behavioral and/or cognitive changes for a minority of children with ADHD, identifying the subgroup for whom this treatment works is proving elusive and again, the diet represents a significant burden to families.

Despite anecdotal reports of an increased prevalence of food allergies among ADHD patients, systematic reviews examining the association between ADHD and dairy or casein intolerance have been inconclusive. Similarly, despite an association between gluten intolerance and hyperactivity symptoms in those with celiac disease, evidence does not support a clear link between ADHD and celiac disease.

 As part of oligoantigenic diets, behavioral improvements have been found from the exclusion of dairy and wheat/gluten. However, it is not clear whether these effects are the result of removing these or other antigenic foods themselves, or due to secondary factors such as an alteration of gut microbiota.

Consideration of sugar’s role in the expression of ADHD symptoms arose from observations of increased hyperactivity among children after consuming sugar. Cross-sectional studies show a linear association between consumption of sugar-containing soft drinks and hyperactivity.

 However, given the context for this association (eg, children’s birthday parties), the true relationship between sugar consumption and hyperactivity may be influenced by the environmental and situational factors in which large amounts of sugar are consumed.

While it is reasonably well established that short-term consumption of sugar is not associated with ADHD symptoms, Johnson and colleagues

 theorize that chronic overconsumption of sugar may influence dopamine regulation and therefore may be an etiological factor in ADHD. Indeed, the American Academy of Pediatrics recommends limiting sugar to less than 10% of total calories per day (roughly 6 teaspoons per day for children ages 2 to 19 years) to support good mental and physical health.

Many families ask whether simply eating a healthy diet will help ADHD symptoms. For some, that may be true. Certain dietary patterns have been associated with ADHD symptoms. Adolescents who consume a Western diet, characterized by a high intake of refined carbohydrates, sugars and sodium, total and saturated fats, and lower intake of omega-3 fatty acids, fiber and folate, showed a higher prevalence of ADHD, even after controlling for confounding variables.

 The observed relationship between ADHD and poor diet quality may be bi-directional in that individuals with ADHD may make poorer dietary choices compared with non-affected peers as a result of higher impulsivity and reward preference.

While eating a healthy diet is one consideration, another factor to consider is the nutrient composition of the foods consumed in the 21st century compared with 50 or 100 years ago. The mineral composition of 20 fruits and vegetables in the 1940s compared with the same fruits and vegetables in the 1990s, was significantly lower.

 High yield crops produced with fertilizers, pesticides, and heavy irrigation may lead to significant soil depletion of these nutrients.

For some families, eating a healthy diet is difficult because of inaccessibility of supermarkets that sell unprocessed foods including fresh produce. “Food deserts” are geographic regions where residents, typically in lower socioeconomic brackets, are limited by the selection available at convenience stores and fast food restaurants. In food deserts, dietary options tend to be limited to processed foods that are high in salt, unhealthy fat, and sugar, with low or no availability of fresh fruit, vegetables or whole grains. As such, even well-meaning parents may struggle to address poor diet. This is where the supplementation research may be of particular interest.

Supplementation with individual nutrients

Lower serum levels of omega-3 and omega-6 in children with ADHD suggest either poorer absorption and/or increased metabolism of polyunsaturated fatty acids (PUFAs). Because of their neurophysiological properties, PUFAs may have a protective or modulatory role in neurological processes including neural signaling, synaptic functioning, and neurotransmitter regulation.

Findings from controlled treatment trials of PUFAs in individuals with ADHD indicate that the symptom changes appear to be significant for a sizeable minority, regardless of the overall small effect sizes for this population. Given that research has shown a reduction in omega-3 fatty acids in children with ADHD and a modest improvement (effect size estimates range from 0.18 to 0.31) in symptoms, it is a reasonable option alongside established therapies.

The results for other micronutrient supplements such as single vitamins, minerals, amino acids have been inconsistent. A number of researchers have concluded that single nutrient interventions may not be effective for improving ADHD symptoms, perhaps due to the complex interplay between aberrant biochemical pathways in people with ADHD. Considering the range of nutrients that are necessary to sustain a highly metabolically active brain, it is logical to supplement with a combination of nutrients to provide the building blocks required for optimal brain functioning.

Multi-ingredient, broad spectrum micronutrients

Historically, trials of broad spectrum micronutrients (BSM) in the treatment of ADHD have been surrounded by controversy, likely resulting from the administration of very small doses resulting in nonsignificant effect; or mega-doses, leading to problems with toxicity and adverse effects. However, over the last decade a number of trials have utilized BSM in doses that were both adequate enough to treat core ADHD symptoms, and also below toxic levels. Although the trials varied in BSM composition and duration, all resulted in significant improvements in behavioral functioning, including core ADHD symptoms and/or emotional regulation. Reassuringly, very few adverse effects (AEs) were reported, with no differences in AEs between active and placebo treatment.

Two randomized clinical trials demonstrated significant improvements with small to medium effect sizes in multiple areas of functioning, including ADHD symptoms (particularly inattention) as well as emotional regulation for adults and children with ADHD.

Follow up at one year of the adult participants with ADHD revealed that among the 20% who continued with the BSM formula, ADHD symptoms were in the nonclinical range-a significant improvement from baseline.

Regarding the effectiveness of BSM for ADHD, it is important to note that the majority of BSM trials for ADHD have been conducted with medication-free individuals. While, caution is warranted in using BSM as an adjunctive treatment to stimulant medication, early research suggests that in some cases, medication doses may need to be reduced (with physician monitoring) when taken alongside nutrients.

 Reduction in dose is thought to be possible because of the nutrients’ potentiation of the medication, hence the caution for combining and the need for medical oversight.

Although the multi-ingredient trials described here have all shown promise, replication and longer-term studies, including clinical populations who are taking medication, are required to make more definitive recommendations about efficacy. No significant safety concerns were raised in the trials, which suggests that at least in the short-term, the nutrients are not having a negative effect on functioning or blood markers of general health (eg, hematology, liver or kidney functioning). Adverse effects such as gastrointestinal upset are typically mild, short-lived, and alleviated by taking pills with food and water.

A growing body of research suggests that diet, both the elimination of certain additives and/or allergens, and the consumption of nutrient-rich foods, plays a role in ADHD. The effects of these dietary changes are small, and may be due to inter-individual differences such as genetic polymorphisms and food sensitivities. More persuasive than dietary interventions alone, however, are the supplementation studies of omega-3 fatty acids and/or BSM formulas that provide the nutritional building blocks needed for optimal brain functioning at high, but safe, doses.

Dr Johnstone is supported by an NIH-NCCIM 5R90AT00892403 through the National University for Natural Medicine and Helfgott Research Institute in Portland, OR; she also received support from the Department of Child and Adolescent Psychiatry, Oregon Health & Science University.

Dr Rucklidge is Professor of Clinical Psychology, Department of Psychology, University of Canterbury, Christchurch, New Zealand. Dr Taylor is a Research Specialist, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan. Dr Johnstone is a Research Investigator, National University of Natural Medicine, Helfgott Research Institute, and Psychologist and Clinical Researcher, Department of Child and Adolescent Psychiatry, Oregon Health & Science University, Portland, OR.

The authors report no conflicts of interest concerning the subject matter of this article.

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This article examines the contributory role of diet on ADHD symptoms, including how the elimination of certain foods and additives, as well as the consumption of other foods or nutrients, may impact symptoms.

Julia J. Rucklidge, PhD

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