Abstract
This systematic review and meta-analysis focused on randomized controlled trials (RCT) of multinutrients consisting of at least four vitamins and/or minerals as interventions for participants with psychiatric symptoms. A systematic search identified 16 RCTs that fit the inclusion criteria (n = 1719 participants) in six psychiatric categories: depression, post-disaster stress, antisocial behavior, behavioral deficits in dementia, attention-deficit/hyperactivity disorder, and autism. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the evidence base. Significant clinical benefit was assessed using minimal clinically important differences (MIDs). Due to heterogeneity in participants, multinutrient formulas, outcome measures, and absence of complete data, only the Attention-Deficit/Hyperactivity Disorder (ADHD) category was eligible for meta-analyses. In ADHD populations, statistically and clinically significant improvements were found in global functioning, Mean Difference (MD) −3.3, p = 0.001, MID −3.26; Standardized Mean Difference (SMD) −0.49 p = 0.001 MD −0.5), clinician ratings of global improvement (MD −0.58, p = 0.001, MID −0.5) and ADHD improvement (MD −0.54, p = 0.002, MID −0.5), and clinician (but not observer) measures of ADHD inattentive symptoms (MD −1.53, p = 0.05, MID −0.5). Narrative synthesis also revealed a pattern of benefit for global measures of improvement, for example: in autism, and in participants with behavioral deficits in dementia. Post-natural disaster anxiety and the number of violent incidents in prison populations also improved. Broad-spectrum formulas (vitamins + minerals) demonstrated more robust effects than formulas with fewer ingredients. This review highlights the need for robust methodology-RCTs that report full data, including means and standard deviations for all outcomes-in order to further elucidate the effects of multinutrients for psychiatric symptoms.
Highlights
Poor nutrition is increasingly identified as a modifiable risk factor for the development and persistence of psychiatric problems [1], with research identifying that the Western diet, high in salt, saturated fat, ultra-processed ingredients, and sugar is most consistently associated with poor mental health [2,3]
Because of the heterogeneity among study samples, nutrient formulas, and outcome measures, and due to unavailability of sufficient data to meta-analyze, only two studies were included in a quantitative synthesis meta-analysis [26,27]
Compared to multinutrient formulas with fewer ingredients delivered at lower doses, broad-spectrum multinutrients demonstrated more consistent benefits for a range of mental health issues
Summary
Poor nutrition is increasingly identified as a modifiable risk factor for the development and persistence of psychiatric problems [1], with research identifying that the Western diet, high in salt, saturated fat, ultra-processed ingredients, and sugar is most consistently associated with poor mental health [2,3]. A common hypothesis across these diet improvement studies is that nutrient density is increased through higher consumption of vegetables and fruit, and lower consumption of ultra-processed foods. Several factors may contribute to the need for more nutrients than what might be available in one’s diet, even if characterized as a “healthy” diet. These factors include poor gut health and microbiome composition [11–13], the presence of inflammation [14], genetic variation leading to possible in-born errors of metabolism, which slow metabolic activity due to suboptimal availability of vitamin and mineral cofactors [15], and mitochondrial dysfunction that may result in decreased production of cellular energy in psychiatric disorders [13,16,17]. The presence of any of these factors may effectively reduce the availability of nutrients necessary for optimal brain health
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