The Next Frontier in Psychiatry

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.1 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.1,2 The results demonstrate that consuming a whole-foods, Mediterranean-style diet can improve emotional resilience and lower the risk of mental health disorders. Shifting to this diet brought improvements in depression, attention-deficit/hyperactivity disorder (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 precedes poor mental health. Unfortunately, ultra-processed foods constitute more than 50% of Americans’ caloric intake.3

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 macronutrient categories of carbohydrates, proteins, and fats, overshadowing the importance of the much smaller but essential micronutrients: minerals and vitamins. 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.1

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.1 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 nutrients 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.1

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.4 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

Stress and aggression. 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.5,6

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.7

Autism spectrum disorders (ASD). 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.7,8 A case-control study9 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.

ADHD. 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.10-12 Clinician CGI-I ratings were remarkably similar across these 3 studies (Figure). 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.13,14

Other disorders. Post-hoc analyses of RCT data, small RCTs, and open-labelled trials highlight potential benefit for depression,11 premenstrual dysphoric disorder,15 nicotine addiction,16 and bipolar disorder and psychosis,17 with others underway.18

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.10-12,19 

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 (Table). Theoretically, micronutrients can potentiate medication effects; for example, by increasing neurotransmitter synthesis or interacting with CYP enzymes.7 For these reasons and others, medication dose reductions may be needed when combined with micronutrient supplementation.20

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.1

Concluding Thoughts

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.

Dr Rucklidge is a professor at the University of Canterbury. Dr Johnstone is an assistant professor at Oregon Health & Science University. Dr Kaplan is Professor Emerita at the University of Calgary.

References

1. Rucklidge JJ, Johnstone JM, Kaplan BJ. Nutrition provides the essential foundation for optimizing mental health. Evidence-Based Practice in Child and Adolescent Mental Health. 2021;6(1):131-154.

2. Marx W, Lane M, Hockey M, et al. Diet and depression: exploring the biological mechanisms of action. Mol Psychiatry. 2021;26(1):134-150.

3. Wang L, Martínez Steele E, Du M, et al. Trends in consumption of ultraprocessed foods among US youths aged 2-19 years, 1999-2018. JAMA. 2021;326(6):519-530.

4. Kaplan BJ, Crawford SG, Field CJ, Simpson JSA. Vitamins, minerals, and mood. Psychol Bull. 2007;133(5):747-760.

5. Young L, Pipingas A, White D, et al. A systematic review and meta-analysis of b vitamin supplementation on depressive symptoms, anxiety, and stress: effects on healthy and ‘at-risk’ individuals. Nutrients. 2019;11(9):2232.

6. Rucklidge JJ, Afzali MU, Kaplan BJ, et al. Massacre, earthquake, flood. International Perspectives in Psychology. 2021;10(1):39-54.

7. Johnstone J, Hughes A, Goldenberg JZ, et al. Multinutrients for the treatment of psychiatric symptoms in clinical samples: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2020;12(11):3394.

8. Adams JB, Audhya T, Geis E, et al. Comprehensive nutritional and dietary intervention for autism spectrum disorder—a randomized, controlled 12-month trial. Nutrients. 2018;10(3):369.

9. Mehl-Madrona L, Leung B, Kennedy C, et al. Micronutrients versus standard medication management in autism: a naturalistic case-control study. J Child Adolesc Psychopharmacol. 2010;20(2):95-103.

10. Rucklidge JJ, Eggleston MJF, Johnstone JM, et al. Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial. J Child Psychol Psychiatry. 2018;59(3):232-246.

11. Rucklidge JJ, Frampton CM, Gorman B, Boggis A. Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: double-blind randomised placebo-controlled trial. Br J Psychiatry. 2014;204(4):306-315.

12. Johnstone JM, Hatsu I, Tost G, et al. Micronutrients for attention-deficit/hyperactivity disorder in youths: a placebo-controlled randomized clinical trial. J Am Acad Child Adolesc Psychiatry. 2022;61(5):647-661.

13. Rucklidge JJ, Frampton CM, Gorman B, Boggis A. Vitamin-mineral treatment of ADHD in adults: a 1-year naturalistic follow-up of a randomized controlled trial. J Atten Disord. 2017;21(6):522-532.

14. Darling KA, Eggleston MJF, Retallick-Brown H, Rucklidge JJ. Mineral-vitamin treatment associated with remission in attention-deficit/hyperactivity disorder symptoms and related problems: 1-year naturalistic outcomes of a 10-week randomized placebo-controlled trial. J Child Adolesc Psychopharmacol. 2019;29(9):688-704.

15. Retallick-Brown H, Blampied N, Rucklidge J. A pilot randomized treatment-controlled trial comparing vitamin B6 with broad-spectrum micronutrients for premenstrual syndrome. J Altern Complement Med. 2020;26(2):88-97.

16. Reihana P, Blampied N, Rucklidge J. Novel mineral–vitamin treatment for reduction in cigarette smoking: a fully blinded randomized placebo-controlled trial. Nicotine Tob Res. 2018;21(11):1496-1505.

17. Mehl-Madrona L, Mainguy B. Adjunctive treatment of psychotic disorders with micronutrients. J Altern Complement Med. 2017;23(7):526-533.

18. Bradley HA, Campbell SA, Mulder RT, et al. Can broad-spectrum multinutrients treat symptoms of antenatal depression and anxiety and improve infant development? Study protocol of a double blind, randomized, controlled trial (the ‘NUTRIMUM’ trial). BMC Pregnancy Childbirth. 2020;20(1):488.

19. Rucklidge JJ, Eggleston MJF, Ealam B, et al. An observational preliminary study on the safety of long-term consumption of micronutrients for the treatment of psychiatric symptoms. J Altern Complement Med. 2019;25(6):613-622.

20. Popper C, Kaplan BJ, Rucklidge JJ. Single and broad-spectrum micronutrient treatments in psychiatry practice. In: Gerbarg PL, Muskin PR, Brown RP, eds. Complementary and Integrative Treatments in Psychiatric Practice. American Psychiatric Association Publishing; 2017:75-104.

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