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Abstract

French

Objective

In recent years, the relationship between nutrition and mental health has gained considerable interest. We identified, synthesized, and appraised all meta-analyses of randomized controlled trials (RCTs) and observational studies reporting on the efficacy of dietary patterns and nutrient supplements in the prevention and treatment of mental disorders in children and adolescents.

Methods

Systematic research in MEDLINE, PsycINFO, Scopus, and Cochrane Database of Systematic Reviews was completed on 8 January 2024.

Results

Our research found 24 meta-analyses: 14 on RCTs, 8 on observational studies, and 2 combining both. Emerging evidence suggests that omega-3, in particular eicosapentaenoic acid, and Vitamin D may have adjunctive benefits in the treatment of attention deficit hyperactivity disorder (ADHD), while no evidence was found for autism spectrum disorder (ASD). Observational data also indicated that prenatal folic acid supplementation (>400 μg daily) was associated with a reduced risk of ASD in offspring. In terms of dietary habits, several meta-analyses of observational data revealed that healthy dietary patterns (rich in fruits, vegetables, and fibre, low in saturated fats) during the prenatal period, childhood, and adolescence were linked to a significantly reduced risk of internalizing disorders and externalizing disorders. Conversely, unhealthy dietary habits (high in sugars, saturated animal fats, and industrial foods, low in fruits, vegetables, and fibre) are associated with an elevated risk of these mental health issues. However, the number of available studies on dietary interventions for the treatment of depression, ASD, and ADHD was limited, and the results obtained were either nonsignificant or contradictory.

Conclusion

Our findings emphasize the need to establish clear causal relationships between dietary habits and the risk of mental illness in children and adolescents. Moreover, further investigation of the benefits observed with some nutrient supplements (such as omega-3 and vitamin D for ADHD) through larger-scale RCTs is imperative to establish more robust conclusions.

Plain Language Summary

We investigated the link between nutrition and mental health in children and adolescents through a meta-review of 24 relevant meta-analyses. Emerging evidence suggests potential benefits of Omega-3 and Vitamin D in treating ADHD, while no evidence supports their effectiveness in ASD. Observational data also indicate that prenatal folic acid supplementation may lower ASD risk. Healthy dietary patterns reduce the risk of internalizing and externalizing disorders, whereas unhealthy habits elevate the risk. Limited studies on dietary interventions for depression, ASD, and ADHD provide inconclusive results. In summary, our results emphasize the need to clearly understand the cause-and-effect relationships between dietary habits and mental health risks in young individuals. Larger-scale randomized controlled trials are essential for confirming the observed benefits of nutrient supplements such as omega-3 and vitamin D in treating ADHD and for forming more reliable conclusions.

Keywords

Dietary patterns dietary supplements neurodevelopmental disorders child and adolescent psychiatry

Introduction

In recent years, the relationship between diet and mental health has gained considerable interest.^1–3 The International Society For Nutritional Psychiatry Research (ISNPR), founded in 2013 reflects emerging research on nutritional approaches in the prevention and treatment of mental disorders, and the importance of conducting high-quality research in this field.⁴

Changes in the food habits of children and adolescents over the past century, driven by economic and social development, have resulted in an unbalanced diet.¹ Unhealthy eating patterns, characterized by consumption of processed foods high in sugar, saturated fats, and refined carbohydrates, along with malnutrition, are major risk factors for noncommunicable diseases such as childhood obesity, cardiovascular and respiratory diseases, and diabetes.^5–7 Furthermore, these chronic diseases, which are strongly associated with lifestyle, are highly comorbid with mental disorders such as depression, anxiety, sleep disorders, and eating disorders.^1,6

Diet directly impacts brain development and function across all age groups, starting from the first 1,000 days, which include 270 days of pregnancy and the initial 2 years of life.⁸ This period of vulnerability is characterized by rapid brain growth,^9–11 involving processes such as neurogenesis, axonal and dendritic growth, synaptogenesis, cell death, synaptic pruning, myelination, and gliogenesis.¹² The rapidly growing brain during critical developmental phases is particularly prone to nutrient deficiencies, including protein, energy, specific fats, folic acid, vitamin A, iron, zinc, copper, iodine, selenium, and choline.^13,14 Notably, epidemiological studies of populations exposed to famine such as the Dutch Hunger Winter of 1944 to 1945 or the Chinese famine of 1959 to 1961 have shown that moderate to severe nutritional deficiencies during pregnancy and early childhood could increase the risk of mental disorders in later adulthood,¹⁵ such as schizophrenia,¹⁶ schizoid personality disorder,^17,18 or affective disorders.¹⁹

Along with regular food intake, nutrients can also be consumed in supplement form. Supplements are commonly used for several purposes: (a) to complement an insufficient diet or address nutrient deficiencies, especially during pregnancy to support the child's brain development¹³; (b) to provide nutrients at higher doses than typically found in regular diets for potential physiological benefits; (c) to offer nutrients in more easily absorbable forms, suitable for individuals with genetic variations or health issues affecting nutrient absorption.²⁰

There is a growing interest in using dietary patterns and nutrient supplements in the prevention and treatment of mental disorders, driven by advances in our understanding of the neurobiological basis underlying them. This emerging research suggests that certain nutrients or dietary patterns could influence mental health including during the sensitive stages of development, via different biological pathways such as gut microbiota, oxidative stress, inflammation, hypothalamus–pituitary adrenal axis, mitochondrial dysfunction, neuroplasticity, or epigenetics.²¹ For instance, diet and pre/probiotics influence the composition and diversity of the gut microbiota and can modulate brain structure and function via anti-inflammatory effects mediated by the microbial metabolites of dietary fibre and polyphenols.²² This implies that certain dietary patterns and pre/probiotic supplements might offer promising new therapeutic options that should be explored further.²⁰

Despite the available research findings, the link between diet and children's behaviour is complex, with many conflicting studies.^2,23,24 To our knowledge, the broader role of dietary factors, across the spectrum of paediatric mental disorders, has yet to be established. Some meta-reviews of meta-analyses about the role of nutrition (diet and nutrient supplements) have been published in the adult population,^20,25 but none in the paediatric population. Recognizing and investigating this area in both research and routine clinical practice is crucial for advancing our approach to managing mental disorders in this age group.

The present paper aims to establish the current evidence regarding the efficacy of dietary factors, including eating habits and dietary supplements, in both preventing and treating psychiatric disorders in children and adolescents. To do this, we identified, synthesized, and appraised all available data from meta-analyses of randomized controlled trials (RCTs) and observational studies examining mental health outcomes for all dietary factors across various paediatric mental disorders.

Methods and Materials

This meta-review aimed to systematically gather the most recent high-quality evidence regarding the role of “dietary factors” in preventing and treating mental disorders in children and adolescents. The literature search (Supplemental Appendix 1) was performed with the assistance of an academic health sciences librarian (Valérie Durieux) and followed the Peer Review of Electronic Search Strategies (PRESS) method.²⁶ Additionally, our reporting adhered to the PRISMA statement²⁷ for comprehensive and transparent reporting, and we followed a preregistered protocol (PROSPERO: CRD42023390196).

Literature Search Strategy

All references were exported and managed using Endnote x9.3.3. The systematic search was conducted using Ovid MEDLINE®, PsycINFO, Scopus, and Cochrane Database of Systematic Reviews, from inception until 8 January 2024. We have expanded our search to include all languages except for Chinese and Japanese.

Eligibility Criteria

This meta-review included previously published meta-analyses. The eligibility criteria for the included meta-analyses were organized following the participants, interventions, comparisons, outcomes, and study design reporting structure.

Participants

- Included: Children and adolescents aged 18 years and younger, from the prenatal period, with common mental disorders, for example, depressive disorders, anxiety disorders, schizophrenia, and other psychotic disorders, neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability, and learning disability; or those exhibiting psychiatric symptoms, for example, internalizing symptoms (low mood, depressive or anxious symptoms, and emotional problems) and externalized symptoms (impulsivity, hyperactivity, and aggression), regardless of a formal diagnosis.

- Excluded: Studies exclusively focusing on nutritional interventions for malnutrition associated with eating disorders or substance use disorders, and studies involving individuals with medical conditions known to affect brain functioning (e.g., epilepsy, diabetes, and heart disease).

Comparisons

- Included: Specific nutritional exposures versus nonexposed control; high versus low adherence to diets; and dietary supplementation versus placebo or alternative treatments.

Interventions

- Included: Various “dietary factors” such as healthy diets like the “Mediterranean diet” or Dietary Approaches to Stop Hypertension Diet (DASH) (rich in fruits, vegetables, and fibre, and low in saturated fats), unhealthy diets like the “Western Diet” or pro-inflammatory diet (high in sugars, saturated animal fats, and industrial foods, and low in fruits, vegetables, and fibre), specific diets (e.g., gluten-free casein-free diet [GFCF diet], carbohydrate-restricted diet, reduction of artificially sweetened and highly refined foods, elimination of “artificial food colouring”), specific foods (e.g., olive oil, fruits, and foods rich in antioxidants), nutrient supplements (used as adjunctive treatment or monotherapy, including vitamins, minerals, macronutrients, fatty acids, or amino acids), and prebiotics or probiotics treatments.

- Excluded: Studies related to nutritional deficiencies, including malnutrition and isolated nutritional deficiencies (e.g., vitamins/minerals/fatty acids), as well as herbal supplements or phytochemicals supplements.

Outcomes

- Included: All data on mental health outcomes, including changes in clinical measures and response rates.

- Excluded: Studies related to maternal mental disorders during the prenatal period, such as depression.

Study Design

- Included: Meta-analyses included RCTs and observational studies, encompassing cohort, cross-sectional, case-control, or prospective studies.

- Excluded: No meta-analysis studies (e.g., the cases report, narrative review, epidemiologic studies, cohort studies, and case-control studies).

To prevent potential bias resulting from overlap in our meta-analysis selection, we calculated the corrected covered area (CCA) and utilized a Graphical Representation of Overlap for Overviews (GROOVE) using the freely available tool developed by Bracchiglione et al.²⁸

We systematically assessed the degree of overlap between each pair of meta-analyses, categorizing it as follows: slight overlap (<5%), moderate overlap (>5% and <10%), high overlap (10% to <15%), and very high overlap (≥15%).²⁸

Where meta-analyses analyses with a very high overlap (≥15%), the most recently updated meta-analysis was used. Older meta-analyses, providing unique insights such as a larger study pool or specific subgroup analyses, were used as secondary analyses.

Data Extraction

Two authors (MT and MR) independently screened titles and abstracts of all publications that were obtained by the search strategy. Full texts identified in the first step were by one author (MT) and then verified by another author (MR). If differences in opinion existed, they were resolved until the two authors agreed with each other. The remaining disagreements were discussed with a third author (HN) until a consensus was reached.

Results of the eligible meta-analysis were extracted narratively to present the association of dietary factors (nutritional supplementation or dietary pattern) and the risk of child mental illness, as well as the effects of nutritional interventions on psychiatric outcomes in the paediatric population.

When associations between dietary factors and child mental disorders were quantified as categorical variables, these were extracted as odds ratios (ORs) or relative risks (RRs) with their confidence intervals (CI) to 95%.

When data on effect size were quantified as a continuous variable (i.e., effect size on psychiatric symptoms), these were extracted as the standardized mean difference (SMDs) (Cohen's d or Hedges’g), and their 95% CIs. Following conventional interpretations, SMDs were categorized as negligible (<0.2), small (0.2–0.4), moderate (0.4–0.8), or large (>0.8).^20,25 Some meta-analyses did not provide SMDs but weighted mean differences or raw mean differences, and we also extracted these data.

For all meta-analyses, data on the degree of between-study heterogeneity (quantified as I² values) were also extracted and categorized as low (I²< 25%), moderate (I²= 25% to 50%) or high (I²> 50%).^20,25

Quality Assessment of Included Studies

Authors (MT and MR) independently assessed the methodological quality of the included meta-analyses using “A Measurement Tool to Assess Systematic Reviews” Version 2 (AMSTAR-2),²⁹ allowing for the consideration of specific methodological biases in the results. An overall confidence rating in the results of the review was categorized as high, moderate, low, or critically low, following the method defined by Shea et al.²⁹ The details of this process are provided in Supplemental Appendix 2.

Results

We identified 625 potential records from databases. After the removal of duplicates, 431 studies were screened from which 56 full-text documents were reviewed, and 24 studies were included; see Figure 1 and Supplemental Appendix 3 for details of papers excluded.

Figure 1.

PRISMA 2020 flow diagram.

Characteristics and Methodological Quality of the Included Meta-Analyses

Study characteristics are presented in Tables 1 to 3. Out of the 24 included meta-analyses, 8 were meta-analyses of observational studies, 14 were meta-analyses of RCTs, and 2 were meta-analyses including both observational studies and RCTs.

Table 1.

Diet and Risk of Paediatric Mental Disorders.

Author/[certainty of the evidence according to AMSTAR-2]*	Type of included studies	k	Outcome	n	Population	Exposure	Main results	Summary
Orlando et al.³¹ [moderate-certainty evidence]	Observational studies (26 cross-sectional, 12 prospective, and 1 case-control)	31	Internalizing symptoms	116,546	Children and adolescents (3.9 to 18 years)	Healthy dietary patterns	Pooled correlations = −0.09; 95% CI, −0.12 to 0.06; p < 0.001; I²= 96.777	Greater depression and internalizing symptoms are associated with greater unhealthy dietary patterns and lower healthy dietary intake among children and adolescents.
		19	Depressive symptoms	77,512		Healthy dietary patterns	Pooled correlations = −0.13; 95% CI, −0.18 to −0.08; p < 0.001; I²= 94.944
		25	Internalizing symptoms	116,044		Unhealthy dietary patterns	Pooled correlations = 0.10; 95% CI, 0.06 to 0.14; p = 0.05; I²= 97.928
		13	Depressive symptoms	73,736		Unhealthy dietary patterns	Pooled correlations =0.11; p = 0,001, 95% CI, 0.05 to 0.17; I²= 98.175
Liu et al.³² [critically low–certainty evidence]	Observational studies (cross-sectional)	25	Depressive symptoms	65,267	Adolescents (12 to 15 years)	FVI of <5 times/day (vs. higher)	OR = 1.10; 95% CI, 1.02 to 1.18; p = 0.028; I²= 38,34%	A meta-analysis indicated that FVI of <5 times/day (vs. higher) was associated with an increased risk of depressive symptoms.
			Anxiety symptoms			Eating fruit >2 times/day compared to not eating fruit	OR = 0.61; 95% CI, 0.54 to 0.68; p = NR; I²= NR
			Depressive symptoms			Eating fruit >2 times/day compared to not eating fruit	OR = 0.75; 95% CI, 0.68 to 0.82; p = NR; I²= NR
Polanska et al.³⁰ [moderate–certainty evidence]	Observational studies (cohort studies)	4	Depressive and anxiety symptoms	11,817 mother–child pairs	Prenatal period and children's offspring (7 to 10 years)	Dietary approaches to stop hypertension (DASH)	OR = 0.97; 95% CI, 0.95 to 0.99; p = NR; I²= 24%	These findings suggest that a maternal low-quality and proinflammatory diet may increase the risk of emotional and behavioural symptoms in children.
		4	Aggressive behaviour symptom	11,829 mother–child pairs			OR = 0.97, 95% CI, 0.94 to 0.99; p = NR; I²= 61%
		4	ADHD symptoms	11,829 mother–child pairs			OR = 0.97; 95% CI, 0.95 to 0.98; p = NR; I²= 2%
		4	Depressive and anxiety symptoms	11,817 mother–child pairs		Proinflammatory diet	OR = 1.07, 95% CI, 1.03 to 1.11; p = NR; I²= 0%
		4	Aggressive behaviour symptoms	11,829 mother–child pairs			OR = 1.07; 95% CI, 1.02 to 1.13; p = NR; I²= 24%
		4	ADHD symptoms	11,829 mother–child pairs			OR = 1.07, 95% CI, 1.01 to 1.13; p = NR; I²= 33%
Del-Ponte et al.³⁵ [moderate–certainty evidence]	Observational studies (4 cohorts, 5 case-control, and 5 cross-sectional studies)	14	ADHD	52,336	Children and adolescents (3 to 14 years)	Healthy dietary patterns (FFQ)	OR = 0.65; 95% CI, 0.44 to 0.97; p = NR; I²= NR	This study suggests that an unhealthy can increase the risk, whereas a healthy diet would protect against ADHD.
		11	By design (cohort/case-control or cross-sectional)				OR = 0.59; 95% CI, 0.46 to 0.74; p = NR; I²= 73%
		11	By continent (Europe or Asia/Oceania)				OR = 0.59; 95% CI, 0.46 to 0.74; p = NR; I²= 73%
		11	By sample size (≥1,000 or <1,000)				OR = 0.66; 95% CI, 0.60 to 0.72; p = NR; I²= 73%
		14	ADHD			Unhealthy dietary patterns	OR = 1.41; 95% CI, 1.15 to 1.74; p = NR; I²= NR
		14	By design (cohort/case-control or cross-sectional)				OR = 1.41; 95% CI, 1.25 to 1.58; p = NR; I²= 86.2%
		13	By continent (Europe or Asia/Oceania)				OR = 1.41; 95% CI, 1.25 to 1.58; p = NR; I²= 86.2%
		13	By sample size (≥1,000 or <1,000)				OR = 1.41; 95% CI, 1.25 to 1.58; p = NR; I²= 86.2%
Shareghfarid et al.³⁴ [low-certainty evidence]	RCTs	6	ADHD	4,886	Children and adolescents (6 to 14 years)	Healthy dietary patterns (FFQ)	OR = 0.63; 95% CI, 0.41 to 0.96; p = NR; I²= 46.5%	A healthy dietary pattern has decreased the odds of ADHD by up to 37%. In addition, adherence to “junk food” patterns containing sweetened beverages and desserts as well as “Western” dietary patterns including red meat, refined grains, processed meats, and hydrogenated fat increased it.
Shareghfarid et al.³⁴ [low-certainty evidence]	RCTs	6	ADHD	3,243	Children and adolescents (6 to 14 years)	Unhealthy dietary patterns	OR = 1.92; 95% CI, 1.13 to 3.26; p = 0.016, I²= 0.0%
Farsad-Naeimi et al.³⁶ [moderate–certainty evidence]	Observational studies (2 cohorts, 2 cross-sectional, 2 case-control)	8	ADHD	25,945	Children and adolescents (7 to 16 years)	Sugar and soft drink consumption (FFQ, PQ-prepared questionnaire)	Pooled effect size^a: 1.22; 95% CI, 1.04 to 1.42; p = 0.01; I²= 81.9%	This meta-analysis indicated a positive relationship between overall sugar and sugar-sweetened beverages consumption and the risk of ADHD symptoms.

Note. ADHD = attention deficit hyperactivity disorder; DASH = the dietary approaches to stop hypertension score; E-DII = energy-adjusted dietary inflammatory index score; FVI = fruit and vegetable intake; k = number of studies included in the meta-analysis; n = sample size; NR = not reported; NIH = quality of the study evaluated by the National Institutes of Health's Quality Assessment Tool for Systematic Reviews and Meta-Analyses (good: 7 or 8; fair: 4–6; poor: 0–3); OR = odds ratio; RCT = randomized controlled trial; FFQ = food frequency questionnaire.

*The details regarding the establishment of certainty of the evidence according to AMSTAR-2 are provided in Supplemental Appendix 3.

The association between sugar and soft drink consumption and the risk of ADHD symptoms was provided based on the random-effects model.

Table 2.

Effect of Dietary Interventions in Paediatric Mental Disorders.

Author/[certainty of the evidence according to AMSTAR-2]*	Type of included studies	k	Outcome	n	Population	Exposure	Main results	Summary
Campisi et al.³³ [high-certainty evidence]	RCTs	7	Clinical depression or depressive symptoms	484	Children and adolescent (mean age = 12.4 ± 2.2 years)	Healthy dietary patterns	SMD = 0.05; 95% CI, −0.25 to 0.35; p = 0.70; I²= NR	The current meta-analysis demonstrates that healthy dietary interventions for children or adolescents in the community have little impact on nonclinical depression.
Campisi et al.³³ [high-certainty evidence]	Quasi-experimental pre–postintervention	9	Clinical depression or depressive symptoms	936	Children and adolescent (mean age = 12.4 ± 2.2 years)	Healthy dietary patterns	SMD = −0.45; 95% CI, −0.64 to −0.27; p = 0.001; I²= NR
Sonuga-barke et al.³⁷ [high-certainty evidence]	RCTs	8	ADHD Teacher/parent reports	407	Children (3 to 12 years)	Restricted elimination diets (known antigenic foods, elimination of specific provoking foods, general elimination diets, and oligoantigenic diets)	SMD = 1.48, 95% CI, 0.35 to 2.61; p = 0.01; I²= 95%	While the most proximal assessment data on restrictive elimination diets were potentially more positive, there is statistically significant between-study heterogeneity in SMDs.
Sonuga-barke et al.³⁷ [high-certainty evidence]	RCTs	8	ADHD Teacher/parent reports	294	Children (3 to 13 years)	Artificial food colour exclusions	SMD = 0.32, 95% CI, 0.06 to 0.58, p = 0.02; I²= 0%	Artificial food colour exclusion produced larger effects but often in individuals selected for food sensitivities.
Quan et al.⁴³ [low-certainty evidence]	RCTs	5	ASD Clinician reports Stereotypical behaviours	297	Children and adolescents (3 to 18 years)	GFCF 4 weeks to 12 months	SMD = −0.41; 95% CI, −0.68 to 0.15; p = 0.006; I²= 0	This meta-analysis showed that a GFCF diet can reduce stereotypical behaviours and improve the cognition of children with ASD.
Quan et al.⁴³ [low-certainty evidence]	RCTs	3	Cognition	90	Children and adolescents (3 to 18 years)	GFCF 4 weeks to 12 months	SMD = −0.46; 95% CI, −0.91 to −0.01; p = 0.045; I²= 50%

Note. ADHD = attention deficit hyperactivity disorder; ASD = autism spectrum disorder; GFCF diet = gluten-free casein-free diet; k = number of studies included in the meta-analysis; n = sample size; NR = not reported; NIH = quality of the study evaluated by the National Institutes of Health's Quality Assessment Tool for Systematic Reviews and Meta-Analyses (good: 7 or 8; fair: 4–6; poor: 0–3); RCT = randomized controlled trial; SMD = standardized mean difference.

*The details regarding the establishment of certainty of the evidence according to AMSTAR-2 are provided in Supplemental Appendix 3.

Table 3.

Effects of Nutrient Supplements in Paediatric Mental Disorders.

Author/[certainty of the evidence according to AMSTAR-2]*	Type of included studies	k	Outcome	n	Population	Exposure	Comparison	Main results	Summary
Gillies et al.³⁸ [high-certainty evidence]	RCTs and quasi-randomized controlled trials	37	ADHD Clinician reports	2,374	Children and adolescents (6 to 18 years)	PUFAs (omega-3 and/or omega-6) 2 weeks to 6 months	Placebo		Although low-certainty evidence suggests that children and adolescents receiving PUFA may be more likely to improve compared to those receiving a placebo, there is high-certainty evidence indicating that PUFA has no effect on total parent-rated ADHD symptoms. Additionally, there is high-certainty evidence showing that inattention and hyperactivity/impulsivity do not differ between the PUFA and placebo groups.
		3	ADHD symptoms	191				Low-certainty evidence RR = 1.95; 95% CI, 1.47 to 2.60; I²= 0% ; p < 0.05
		16	ADHD symptoms (parents reports—medium term)	1,166				High-certainty evidence SMD = −0.08; 95% CI, −0.24 to 0.07; p > 0.05 ; I²= 39%
		12	Inattention (parents reports—medium term)	960				High-certainty evidence SMD = −0.01, 95% CI,−0.20 to 0.17; p > 0.05 ; I²= 42%
		10	Hyperactivity/impulsivity (parents reports—medium term)	869				SMD = 0.09, 95% CI, −0.04 to 0.23; p > 0.05; I²= 0%
Chang et al. ³⁹ [critically low-certainty evidence]	RCTs and observational studies (case-control)	7	ADHD clinical symptom scores (parents' reports)	534	Children (4–12 years) and adolescents (13–17 years)	Omega-3 (EPA + DHA) EPA > or <500 mg/day	Placebo	SMD = 0.38; 95% CI, 0.20 to 0.56; p < 0.0001; I²= 0%	There is evidence that omega-3 supplementation monotherapy improves clinical symptoms and cognitive performances in children and adolescents with ADHD.
		3	Cognitive measures: for errors of omission (parents’ reports)	214				SMD = 1.09; 95% CI, 0.43 to 1.75; p = 0.001; I²= 75%
		2	Cognitive measures: for errors of commission	NR				SMD = 2.14; 95% CI,1.25 to 3.03; p = NR; I²= 63%
		7	Inattention	590				SMD = 0.42; 95% CI, 0.23 to 0.62; p < 0.0001; I²= 19%
Sonuga-Barke et al.³⁷ [high-certainty evidence]	RCTs	11	ADHD (teacher/parent reports)	723	Children (6–13 years)	PUFA (5 omega-3 supplements, 2 omega-6 supplements, and both omega-3 and omega-6 supplements)	Placebo	Overall SMD = 0.21, 95% CI, 0.05 to 0.36; p = 0.007; I²= 0%	PUFA supplementation produced small but significant reductions in ADHD symptoms.
Gan et al.⁴¹ [high-certainty evidence]	RCTs, quasi-randomized trials, and cluster randomized trials.	3	ADHD total scores (parents reports)	221	Children and adolescents (2 to 18 years)	Vitamine D + methylphenidate Vitamin D: 1,000 to 2,000 IU/day during 6 weeks to 3 months	Methylphenidate + placebo	SMD = 0.39; 95% CI, 0.12 to 0.65; p = 0.005; I²= 41%	Vitamin D supplementation demonstrated a small but statistically significant improvement in ADHD total scores, inattention scores, hyperactivity scores, and behaviour scores. There was no statistically significant improvement in oppositional scores.
		3	Inattention scores (parents reports)	184				SMD = 0.67; 95% CI, 0.12 to 1.23; p = 0.02; I²= 67%
		4	Hyperactivity scores (parents reports)	256				SMD = 0.60; 95% CI, 0.07 to 1.13; p = 0.03; I²= 75%
		2	Behaviour scores (parents reports)	125				SMD = 0.54; 95% CI, 0.18 to 0.90; p = 0.003; I²= 0%
		2	Oppositional scores (parents reports)	89				pooled MD = −9.76; 95% CI, −20.13 to 0.62; p = 0.07; I²= NR
Cooper et al.⁴⁰ [high-certainty evidence]	RCTs	4	Behavioural comorbidities of ADHD: emotional lability (parent-rated)	515	Children (4 to 12 years)	PUFAs (omega-3: EPA, DHA, and ALA)	Placebo	SMD = 0.25; 95% CI, 0.08 to 0.43; p = 0.005; I²= 0%	These results provide suggestive evidence of the small effects of omega-3 on reducing EL and oppositional behaviour in subgroups of children with ADHD.
Cooper et al.⁴⁰ [high-certainty evidence]	RCTs	3	Oppositional behaviour (parent-rated)	532	Children (4 to 12 years)	PUFAs (omega-3: EPA, DHA, and ALA)	Placebo	SMD = 0.20; 95% CI, 0.03 to 0.38; p = 0.02; I²= 0.2%
Talebi et al.⁴² [high-certainty evidence]	RCTs	3	ADHD total scores	305	Children (7 to 10 years)	Zinc: 10 to 40 mg/day for 6 to 12 weeks	Placebo	SMD = 0.62; 95% CI, −1.24 to −0.002; p = 0.04; I²= 89.9%	These findings showed a significant effect of zinc supplementation on ADHD total scores but not on hyperactivity scores and inattention scores compared to the control group.
		3	Hyperactivity scores	305				SMD = −0.93; 95% CI, −3.31 to 1.45; p = 0.44; I²= 98.6%
		3	Inattention scores	305				SMD = −0.21; 95% CI, −0.09 to 0.51; p = 0.17; I²= 34.4%
Horvath et al.⁴⁸ [low-certainty evidence]	Observational studies (prospective studies and case-control studies)	2	ASD: externalizing behaviour parent's ratings	62	Children and adolescents 2 to 17 years	Omega-3 (DHA and/or EPA) 6 weeks to 6 months: 0.7 g DHA/day and 0.84 g EPA; and 0.46 g DHA/day and 0.7 g EPA; 0.46 g DHA/day and 0.7 g EPA; 0.2 g DHA + 0.83 g EPA; 0.75 g DHA + EPA; 0.2 g DHA/day	Placebo	Pooled MD: −6.22; 95% CI, −10.86 to −1.59; p = 0.0009; I²= 0%	The limited data currently available suggest that omega-3 supplementation does not enhance the performance of children with ASD.
		2	Lethargy symptoms Parent's ratings	82				Pooled MD: 1.98; 95% CI, 0.32 to 3.63; p = 0.02; I²= 0%
		1	ASD: social skills Parent's ratings	37				MD: −7; 95% CI, −13.62, −0.38; p = 0.09; I²= NR
De Crescenzo et al.⁴⁷ [low-certainty evidence]	RCTs	9	ASD Anxiety comorbidity	405	Children and adolescents mean age of 6.7 years.	PUFAs 6 weeks to 52 weeks PUFAs: 200 to 1,540 mg/day. EPA: 693 to 840 mg/day. DHA 200 to 722 mg/day	Placebo	SMD = −1.01; 95% CI, −1.86 to −0.17; p = NR; I²= NR	PUFAs were superior compared to placebo in reducing anxiety in individuals with ASD. Moreover, PUFAs worsened the quality of sleep compared to a healthy diet.
De Crescenzo et al.⁴⁷ [low-certainty evidence]	RCTs	9	Quality of sleep	405	Children and adolescents mean age of 6.7 years.		Placebo	SMD = 1.11; 95% CI, 0.21 to 2.00; p = NR; I²= NR
Li B et al.⁵⁰ [low-certainty evidence]	RCTs	3	ASD Hyperactivity scores	104	Children: 2.5 to 8 years	Vitamin D3 5–12 months 2,000 IU/day; 300 IU/day/kg to 5,000 IU/day	Placebo	Pooled MD: −3.20; 95% CI, −6.06 to −0.34; p = 0.03; I²= 10%	Vitamin D supplementation appears to be beneficial for hyperactivity but not for core symptoms or other coexisting behaviours and conditions of ASD.
		3	Social interaction	104				Pooled MD: −1.54; 95% CI,−4.09 to 1.01; p = 0.24 ; I²= 0%
		2	Communication	66				pooled MD: −0.05; 95% CI, −1.79 to 1.69; p = 0.96; I²= 60%
Zhang et al.⁴⁹ [low-certainty evidence]	RCTs	6	ASD Stereotypical behaviour scores of the GARS-2	266	Children 2.5 to 14 years	Vitamin D3 10 weeks to 12 months 2,000 to 6,000 IU/day; 50,000 UI/week or 50,000 UI/2 weeks	Placebo	Pooled MD: −1.39; 95% CI, −2.7 to −0.07; p = 0.04; I²= 34%	There were no significant differences in restrictive and repetitive behaviours between the intervention and placebo groups as assessed by changes in the mean scores of the Aberrant Behaviour Checklist
			Social interaction					Pooled MD: −0.07; 95% CI, −1.70 to 1.57; p = 0.93; I²= 0%	The pooled effect estimates for social interaction did not differ between the intervention and placebo groups in changes in the mean scores.
			Communication					Pooled MD: −0.04; 95% CI, −1.19 to 1.10; p = 0.94; I²= 57%	The communication scores did not differ between the intervention and placebo groups in changes in the mean scores
Song et al.⁵³ [low-certainty evidence]	RCTs	3	ASD Severity of overall ASD symptoms	144	Children with mean ages ranging from 4 to 10 years old	Probiotic and prebiotic	Placebo	SMD: −0.23; 96% CI, −0.56 to 0.11; p > 0.05; I²= 0.0%	The results of the meta-analysis indicated that probiotics and prebiotics did not significantly improve the severity of ASD symptoms, gastrointestinal problems, or comorbid psychopathology in ASD.
		2	The severity of gastrointestinal problems (e.g., constipation, diarrhea or abdominal pain)	73				SMD = −1.14; 95% CI, −3.59 to 1.31; p > 0.05; I²= 85%
		2	The comorbid psychopathology in ASD (e.g., anxiety, internalization, attention problems, or aggressive behaviour)	156				SMD = −0.06; 95% CI,−0.37 to 0.25; p > 0.05; I²= 0%
He et al.⁵² [high-certainty evidence]	RCTs and crossover controlled trials	7	ASD	450	Children and adolescents 1.5 to 15 years	Probiotic (e.g., Bifidobacterium longum, Lactobacillus acidophilus, Enterococcus faecalis, Lactobacillus plantarum, Streptococcus thermophilus, etc.) 4 weeks to 6 months	Placebo	SMD = −0.24, 95% CI, −0.60 to 0.11, p = 0.18; I²= 54%	A nonsignificant overall effect size of probiotics on behavioural symptoms in children with ASD. However, a significant overall effect size was found in the subgroup of the probiotic blend.
He et al.⁵² [high-certainty evidence]	RCTs and crossover controlled trials	7	ASD	450	Children and adolescents 1.5 to 15 years	Subgroup of the probiotic blend	Placebo	SMD = −0.42, 95% CI, −0.83 to −0.02, p = 0.04; I²= 51%
Abraham et al.⁵¹ [low-certainty evidence]	RCTs	2	ASD Gilliam Autism Rating Scale scores	74	Children and adolescents 0 to 18 years	L-Carnosine 8 weeks 500 mg; 800 mg/day; 15 mg/kh/day	Placebo or other treatment (risperidone, psychotherapy)	MD = − 2.57; 95% CI, −10.30 to 5.16; p = 0.52; I²= 8%	Results from this meta-analysis showed no significant difference between L-carnosine and placebo groups in the Gilliam autism rating scale and its socialization, behaviour and communication subscales as well as the childhood autism rating scale.
		2	Socialization	74				MD = − 1.51; 95% CI, −6.16 to 3.14; p = 0.53; I²= 0%
		2	Behaviour	74				MD = − 0.48; 95% CI, −4.82 to 3.87; p = 0.83: I²= 0%
		2	Communication	74				MD = − 3.94; 95% CI, −10.00 to 2.11, p = 0.20; I²= NR
		2	Childhood autism rating scale	94				MD = − 0.88; 95% CI, −6.96 to 5.20; p = 0.78; I²= 0%
Wang et al.⁴⁶ [high-certainty evidence]	RCTs	12	ASD	4,514 ASD cases	Prenatal period and childhood	Folic acid NR 80 to 1000 µg/day	No supplementation	RR = 0.77; 95% CI, 0.64 to 0.93; p = NR; I²= 59.7%	It was found that supplementation with folic acid during pregnancy could reduce the risk of ASD as compared to those women without folic acid supplementation.
Liu⁴⁵ [critically low-certainty evidence]	Observational studies (prospective studies and case-control studies)	10	ASD	9,795 ASD cases	Prenatal period +24 months to 15 years	Folic acid (with or without other nutrients) Variable dose of folic acid	No supplementation	OR = 0.57; 95% CI, 0.41 to 0.78; p = NR; I²= NR	Folic acid supplementation during early pregnancy was associated with a lower risk of offspring's ASD
Liu⁴⁵ [critically low-certainty evidence]		1	ASD	466	Prenatal period +24 months to 15 years	≥400 μg folic acid per day	No supplementation	OR = 0.55; 95% CI, 0.36 to 0.83; p = NR; I²= NR
Friel et al.⁴⁴ [high-certainty evidence]	Observational studies (6 cohort studies, 4 case-control)	10	ASD	904,947 children/8,159 ASD cases	Prenatal period + 24 months to 17 years	Folic acid and multivitamin	No supplementation	RR = 0.74; 95% CI, 0.53 to 1.04; p = 0.44; I² = 94.3%	The overall analysis showed no robust association with offspring autism. A reduced risk was observed in the subgroup of high-quality observational studies, early pregnancy and prospective studies.
	In the subgroup of high-quality observational studies	NR		NR				RR = 0.77; 95% CI, 0.62 to 0.96; p = NR; I² = 62.4%
		NR		NR	In the subgroup of early pregnancy			RR = 0.76; 95% CI, 0.58 to 0.99; p = NR; I² = 79.8%
	In the subgroup of prospective studies	NR		NR				RR 0.69, 95% CI, 0.48 to 1.00; p = NR; I² = 95.9%

Note. ADHD = attention deficit hyperactivity disorder; ALA = alpha-linolenic acids; ASD = autism spectrum disorder; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; EL = emotional lability; FA = fatty acid; GARS-2 = Gilliam Autism Rating Scale-Second Edition; k = number of studies included in the meta-analysis; n = sample size; NR = not reported; NIH = quality of the study evaluated by the National Institutes of Health's Quality Assessment Tool for Systematic Reviews and Meta-Analyses (good: 7 or 8; fair: 4–6; poor: 0–3); OR = odds ratio; Pooled MD = pooled mean difference; PUFA = polyunsaturated fatty acid; RCT = randomized controlled trial; RR = risk ratio; SMD = standardized mean difference.

*The details regarding the establishment of certainty of the evidence according to AMSTAR-2 are provided in Supplemental Appendix 3.

All data regarding specific psychiatric conditions or psychiatric symptoms considered in this meta-review include depressive disorders, internalizing disorders, externalizing disorders, ADHD, ASD, and behavioural comorbidities such as emotional lability (EL), aggression, oppositional behaviour and cognitive outcomes.

Sixteen meta-analyses examined nutritional supplementation including PUFAs, vitamins, minerals, amino acid supplements and pre/probiotics. These data were based on nutritional supplementation administered as an adjuvant treatment to conventional therapy such as a specific class of psychotropics (e.g., methylphenidate in ADHD) or as a monotherapy. On the other hand, 9 meta-analyses assessed dietary patterns or specific diets including healthy dietary patterns and unhealthy diet (n = 6); restriction diet and artificial food colour exclusion (n = 1); GFCF diet (n = 1), and sugar and soft drink consumption (n = 1).

Figure 2 depicts the CCA and GROOVE specific to each identified psychiatric disorder after excluding studies with a very high overlap (≥15%). This provides a representation of the degree of overlap among different meta-analyses. Meta-analyses with a high degree of overlap (≥15%) that were excluded are detailed in Supplemental Appendices 3 and 4.

Figure 2.

CCA and GROOVE for included meta-analysis.

The CCA reveals slight overlap, specifically 2.84% for ADHD, 2.71% for ASD, and 0% for internalized symptoms.

The quality assessment of the meta-analyses included using AMSTAR-2 is presented in Tables 1 to 3 and Supplemental Appendix 2. The overall confidence rating categorized 10 studies as “high,” 8 studies as “low,” 4 with a “moderate” rating, and 2 classified as “critically low.”

Nineteen of the 24 included meta-analyses were published between 2019 and 2023.

Results of Syntheses

Detailed study findings are presented in Tables 1 to 3.

Internalizing and/or Externalizing Disorders

(a) Diet and risk of internalizing and/or externalizing disorders. The relationship between dietary patterns and internalizing disorders and/or externalizing disorders was assessed through three meta-analyses of observational studies.

During prenatal period, higher maternal DASH scores, indicating better dietary quality, are associated with a lower risk of depressive and anxiety symptoms (k = 4; n = 11,817; OR = 0.97; 95% CI, 0.95 to 0.99; I²= 24%), aggressive behaviour symptoms (k = 4; n = 11,829; OR = 0.97, 95% CI, 0.94 to 0.99; I²= 61%), and ADHD symptoms (k = 4; n = 11,829; OR = 0.97; 95% CI, 0.95 to 0.98; I²= 2%) in children. Conversely, a proinflammatory diet was associated with an increased risk of depression and anxiety symptoms (k = 4; n = 11,817; OR = 1.07, 95% CI, 1.03 to 1.11; I²= 0%), aggressive behaviour symptoms (k = 4; n = 11,829; OR = 1.07; 95% CI: 1.02 to 1.13; I²= 24%), and ADHD symptoms (k = 4; n = 11,829; OR = 1.07; 95% CI: 1.01 to 1.13; I²= 33%).³⁰

During childhood and adolescence, meta-analyses of observational studies with a total number of participants enrolled ranging from 73,726 to 116,546, found that healthy dietary patterns were negatively associated with internalizing symptoms (anxiety and emotional problems) (k = 31; pooled effect size = −0.09; 95% CI, −0.12 to 0.06; p < 0.001; I²= 96.777) and particularly depressive symptoms (k = 19; pooled effect size = −0.13; 95% CI, −0.18 to −0.08; p < 0.001; I²= 94.944). However, unhealthy dietary patterns were positively associated with internalizing (anxiety and emotional problems) (k = 25; pooled effect size = 0.10; 95% CI, 0.06 to 0.14; p = 0.05; I²= 97.928) and depressive symptoms (k = 13; pooled effect size = 0.11; 95% CI, 0.05 to 0.17; p = 0.001; I²= 98.175).³¹ A meta-analysis of cross-sectional studies indicated that dietary fruit and vegetable of <5 times/day (versus higher) was associated with an increased risk of depressive symptoms (k = 25; n = 65,267; OR = 1.10; 95% CI, 1.02 to 1.18; p = 0.028; I²= 38.34%).³²

(b) Efficacy of dietary interventions for depression. One eligible meta-analysis examined dietary interventions in the treatment of depression in children and adolescents, specifically the effects of a healthy diet. Seven included RCTs demonstrated a nonsignificant effect of dietary intervention (n = 484; SMD = −0.05; 95% CI, −0.25 to 0.35; p = 0.70; I²= 23%) whereas 9 quasi-experimental pre–postintervention studies demonstrated a significant small-to-medium effect favouring dietary intervention for reducing depression (n = 936; SMD = 0.45; 95% CI, 0.27 to 0.64; p = 0.001; I²= 51%). Then, this meta-analysis demonstrates that “healthy” dietary interventions for children or adolescents have little impact on nonclinical depression.³³

(c) Efficacy of dietary supplements for depression. We did not identify any meta-analysis evaluating the efficacy of dietary supplements for depression.

Attention Deficit Hyperactivity Disorder (ADHD)

(a) Diet and risk of ADHD. The association between dietary patterns and longitudinal risk for ADHD was examined in 3 meta-analyses.

A meta-analysis of 6 RCTs, involving a total of 8,129 participants, revealed that a healthy dietary pattern, rich in vegetables, fruits, legumes, and fish, decreased the odds of ADHD by up to 37% (k = 5; n = 8,816; OR = 0.63; 95% CI, 0.41 to 0.96; I²= 46.5%). Conversely, a “Western diet” comprising red meat, refined grains, processed meats, and hydrogenated fat (k = 2; n = 3,243; OR = 1.92; 95% CI, 1.13 to 3.26; p = 0.016, I²= 0.0%), as well as a “junk food” pattern consisting of sweetened beverages and desserts (k = 5; OR = 1.51; 95% CI, 1.06 to 2.16; p = 0.024, I²= 48.7%), were found to increase the risk of ADHD.³⁴

Similar effects were observed in a pooled analysis, indicating a significantly decreased risk of ADHD (OR = 0.65; 95% CI, 0.44 to 0.97; p < 0.05). The effects remained consistent after stratifying the studies by design (cohort/case-control or cross-sectional) (k = 11; OR = 0.59; 95% CI, 0.46 to 0.74; I²= 73%), by continent (Europe or Asia/Oceania) (k = 11; OR = 0.59; 95% CI, 0.46 to 0.74; I²= 73%), and sample size (≥1000 or <1000) (k = 11; OR = 0.66; 95% CI, 0.60 to 0.72; I²= 73%). Conversely, an unhealthy dietary pattern can increase the risk of ADHD (OR = 1.41; 95% CI, 1.15 to 1.74). The effects remained consistent after stratifying the studies by design (cohort/case-control or cross-sectional) (k = 14; OR = 1.41; 95% CI, 1.25 to 1.58; I²= 86.2%), by continent (Europe or Asia/Oceania) (k = 13; OR = 1.41; 95% CI, 1.25 to 1.58; I²= 86.2%), and sample size (≥1000 or <1000) (k = 13; OR = 1.41; 95% CI, 1.25 to 1.58; I²= 86.2%).³⁵

Another meta-analysis indicated a positive relationship between overall sugar and sugar-sweetened beverages consumption and the risk of ADHD symptoms (k = 8; n = 25,945; pooled effect size: 1.22; 95% CI, 1.04 to 1.42, p = 0.01, I²= 81.9%).³⁶

(b) Efficacy of dietary interventions for ADHD. Restricted elimination diets (including known antigenic foods, specific provoking foods, general elimination diets, and oligoantigenic diets) showed a reduction in ADHD symptoms (k = 8; n = 407; SMD = 1.48, 95% CI, 0.35 to 2.61; p = 0.01; I²= 95%), but there is statistically significant between-study heterogeneity in SMDs. Similarly, the exclusion of artificial food colours produced modest effects (k = 8; n = 294; SMD = 0.32; 95% CI, 0.06 to 0.58; p = 0.02; I²= 0%).³⁷

(c) Efficacy of dietary supplements for ADHD. The most recent and largest meta-analysis provided insights into the efficacy of polyunsaturated fat (PUFA) supplementation (including omega-3 and/or omega-6 supplements, at varying doses, administered for durations ranging from 2 weeks to 6 months) in the treatment of ADHD in children and adolescents. Although low-certainty evidence suggests that children and adolescents receiving PUFA may be more likely to improve compared to those receiving a placebo (k = 3; n = 191; RR = 1.95; 95% CI, 1.47 to 2.60; I²= 0%; p < 0.05), there is high-certainty evidence indicating that PUFA has no effect on total parent-rated ADHD symptoms (k = 16; n = 1,166; SMD = −0.08; 95% CI, −0.24 to 0.07; p > 0.05; I²= 39%). Additionally, there is high-certainty evidence showing that inattention (k = 12; n = 10; SMD = −0.01; 95% CI, −0.20 to 0.17; p > 0.05; I²= 42%) and hyperactivity/impulsivity (k = 10; n = 869; SMD = 0.09; 95% CI, −0.04 to 0.23; I²= 0%) do not differ between the PUFA and placebo groups.³⁸

A subsequent meta-analysis, incorporating 11 trials (5 on omega-3 supplements, 2 on omega-6 supplements, and 4 on both omega-3 and omega-6 supplements), showed small but significant reductions in ADHD symptoms (SMD = 0.21; 95% CI, 0.05 to 0.36; p = 0.007; I²= 0%).³⁷

More specifically, omega-3 supplements demonstrated a significant reduction in both inattention (k = 7; n = 590; SMD = 0.42; 95% CI, 0.23 to 0.62; p < 0.0001; I²= 19%) and total ADHD score (k = 7; n = 534; SMD = 0.38; 95% CI, 0.20 to 0.56; p < 0.0001; I²= 0%). These effects were also found for the total ADHD score to be significant in subgroup analyses that separately tested studies with eicosapentaenoic acid (EPA) dosage of 500 mg/day or greater, as well as studies with an EPA dosage <500 mg (k = 7; n = 590; SMD = 0.42; 95% CI, 0.23 to 0.62; p < 0.0001; I²= 19%). Moreover, for hyperactivity symptoms, studies with an EPA dosage of 500 mg per day or greater showed a significant effect (k = 3; n = 277; SMD: 0.81; 95% CI, 0.12 to 1.49; p = 0.02; I²= 87%).³⁹

Regarding behavioural comorbidities, studies have shown that omega-3 supplementation can lead to small improvements in measures of EL and oppositional behaviour. Indeed, subgroup analyses of higher quality studies and those meeting strict inclusion criteria have revealed significant reductions in parent-rated EL (k = 4; n = 515; SMD = 0.25; 95% CI, 0.08 to 0.43; p = 0.005; I²= 0%) and oppositional behaviour (k = 3; n = 532; SMD = 0.20; 95% CI, 0.03 to 0.38; p = 0.02; I²= 0.2%) when omega-3 supplementation is used.⁴⁰

A meta-analysis of RCTs was conducted to assess the effects of vitamin D supplementation (1000 to 2000 IU/day during 6 weeks to 3 months) as an adjunctive therapy to methylphenidate on ADHD symptoms in children. The results indicated that vitamin D supplementation led to a small but statistically significant improvement in ADHD total scores (k = 3; n = 221; SMD = 0.39; 95% CI, 0.12 to 0.65; p = 0.005; I²= 41%), inattention scores (k = 3; n = 185; SMD = 0.67; 95% CI, 0.12 to 1.23; I²= 67%; p = 0.02), hyperactivity scores (k = 4; n = 256; SMD = 0.60; 95% CI, 0.07 to 1.13; I²= 75%; p = 0.03), and behaviour scores (k = 2; n = 125; SMD = 0.54; 95% CI, 0.18 to 0.90; p = 0.003; I²= 0%). However, no statistically significant improvement was observed in oppositional scores (k = 2; n = 89; pooled mean difference [MD] = −9.76; 95% CI, −20.13 to 0.62; p = 0.07).⁴¹

In a meta-analysis of RCTs involving school-aged children with ADHD, zinc supplementation was found to significantly reduce ADHD total scores (k = 3; n = 305; SMD = 0.62; 95% CI, 0.002 to 1.24; p = 0.04; I²= 89.9%). However, zinc supplementation did not show a significant effect on hyperactivity scores (k = 3; n = 305; SMD = −0.93; 95% CI, −3.31 to 1.45; p = 0.44; I²= 98.6%) or inattention scores (k = 3; n = 305; SMD = −0.21; 95% CI, −0.51 to 0.09; p = 0.17; I²= 34.4%) compared to the control group.⁴²

Autism Spectrum Disorder (ASD)

(a) Diet and risk of ASD. We did not identify any meta-analysis evaluating the association between diet and ASD risk.

(b) Efficacy of dietary intervention for ASD. One recent meta-analysis of RCTs assessed the elimination of gluten and casein from the diet (GFCF) among children with ASD. A significant reduction in stereotypical behaviours (k = 5; n = 297; SMD = 0.41; 95% CI, 0.15 to 0.68; p = 0.006; I²= 0%), and improvements in cognition (k = 3; n = 90; SMD = 0.46; 95% CI, 0.01 to 0.91; p = 0.045; I²= 50%) following GFCF dietary intervention were reported. However, no statistically significant changes were observed in social behaviour or communication (all p > 0.05).⁴³

(c) Efficacy of dietary supplements for ASD. Overall, there was no robust evidence to support an association between prenatal intake of multivitamins and autism risk compared to no or low intakes (k = 10; n = 8,159 ASD cases/904 947 children; RR = 0,74; 95% CI, 0.53 to 1.04; p = 0.44; I²= 94.3%; p < 0.05). However, a reduced risk was observed in the subgroup of high-quality observational studies (RR = 0.77; 95% CI, 0.62 to 0.96; p < 0.05; I² = 62.4%), studies focused on early pregnancy (RR = 0.76; 95% CI, 0.58 to 0.99; I² = 79.8%), and prospective studies (RR = 0.69, 95% CI, 0.48 to 1.00; I² = 95.9%).⁴⁴

More specifically, folic acid supplementation during early pregnancy was associated with a lower risk of offspring's ASD (k = 10; n = 9,795 ASD cases; OR = 0.57; 95% CI, 0.41 to 0.78). The consumption of a daily amount of at least 400 μg folic acid from dietary sources and supplements, was associated with a reduced risk of offspring ASD (k = 1; n = 466; OR = 0.55; 95% CI, 0.36 to 0.83).⁴⁵

Supplementation with folic acid during pregnancy could reduce the risk of ASD in children (k = 12; n = 4,514 ASD cases; RR = 0.77; 95% CI, 0.64 to 0.93; I²= 59.7%), irrespective of ethnicity, when compared to women who did not supplement with folic acid. Notably, significant associations were observed in Asian, European, and American populations.⁴⁶

In children and adolescents with ASD, supplementation with PUFAs (omega-3 and/or omega-6) was found to be superior to placebo or a healthy diet in reducing anxiety comorbidity (k = 9; n = 405; SMD = 1.01; 95% CI, 0.17 to 1.86; very low certainty of the evidence). However, it should be noted that PUFAs were associated with worsened quality of sleep when compared to a healthy diet (SMD = −1.11; 95% CI, −2.00 to −0.21; very low certainty of evidence). Additionally, PUFAs did not show superiority over placebo in reducing aggression, hyperactivity, adaptive functioning, irritability, restricted and repetitive interests and behaviours, and communication in individuals with ASD.⁴⁷

Similarly, supplementation with omega-3 (docosahexaenoic acid [DHA] and/or EPA) does not any improvement in the performance of children with ASD compared to placebo, based on findings from 5 RCTs including 183 participants. However, parent's ratings indicated a significant improvement in lethargy symptoms (k = 2; n = 82; pooled MD: 1.98; 95% CI, 0.32 to 3.63; p = 0.02; I²= 0%), but worsening of externalizing behaviour (k = 2; n = 62; pooled MD: −6.22; 95% CI, −10.86 to −1.59; p = 0.0009; I²= 0%) and social skills (k = 1; n = 37; pooled MD: −7; 95% CI, −13.62 to −0.38; p = 0.09) in the omega-3 group compared to the placebo group.⁴⁸

Vitamin D supplementation showed no significant differences in restrictive and repetitive behaviours between the intervention and placebo groups (k = 6; n = 266; pooled MD: −1.39; 95% CI, −2.7 to −0.07; p = 0.04; I²= 34%). Furthermore, vitamin D did not demonstrate improvement in other core ASD symptoms such as social interaction (pooled MD: −0.07; 95% CI, −1.70 to 1.57; p = 0.93; I²= 0%) and communication (pooled MD: −0.04; 95% CI, −1.19 to 1.10; p = 0.94; I²= 57).⁴⁹ However, Vitamin D supplementation indicated a small but significant improvement in coexisting hyperactivity scores (k = 3; n = 104; pooled MD: 3.20; 95% CI, 0.34 to 6.06; p = 0.03; I²= 10%).⁵⁰

Supplementation with L-carnosine for 8 weeks did not show any significant difference compared to the placebo groups in the Gilliam Autism Rating Scale scores (k = 2; n = 74; MD = −2.57; 95% CI, −10.30 to 5.16; p = 0.52; I²= 8%), including its socialization (k = 2; n = 74; MD = −1.51; 95% CI, −6.16 to 3.14; p = 0.53; I²= 0%), behaviour (k = 2; n = 74; MD = −0.48; 95% CI, −4.82 to 3.87; p = 0.83; I²= 0%), and communication (k = 2; n = 74; MD = −3.94; 95% CI, −10.00 to 2.11; p = 0.20) subscales, as well as the childhood autism rating scale (k = 2; n = 94; MD = −0.88; 95% CI, −6.96 to 5.20; p = 0.78; I²= 0%).⁵¹

Regarding probiotics (e.g., Bifidobacterium longum, Lactobacillus acidophilus, Enterococcus faecalis, etc.), our study identified a meta-analysis of RCTs that showed no significant improvement in the behavioural symptoms in children with ASD (k = 3; n = 450; SMD = −0.24; 95% CI, −0.60 to 0.11; p = 0.18; I²= 54%). However, a significant overall effect size was found in the subgroup of the probiotic blend (SMD = −0.42; 95% CI, −0.83 to −0.02; p = 0.04; I²= 51%).⁵² Another meta-analysis revealed that prebiotics and probiotics (e.g., Streptococcus thermophilus, Lactobacillus plantarum, Bifidobacterium infantis, etc.) did not show a significant improvement in the severity of gastrointestinal problems (e.g., constipation, diarrhea, or abdominal pain) (k = 2; n = 73; SMD = −1.14; 95% CI, −3.59 to 1.31; p > 0.05; I²= 85%) or the comorbid psychopathology in ASD (e.g., anxiety, internalization, attention problems, or aggressive behaviour) (k = 2; n = 156; SMD = −0.06; 95% CI, −0.37 to 0.25; p > 0.05; I²= 0%).⁵³

Discussion

This meta-review aggregated and evaluated all the recent evidence from meta-analyses of RCTs and observational studies examining the efficacy of dietary patterns and nutritional supplements in the prevention and treatment of mental disorders in children and adolescents.

In the field of nutritional psychiatry in children and adolescents, the most extensively studied mental disorders are ASD,^43–53 followed by ADHD.^34–42 These results are consistent with the observed increase in the prevalence of these disorders.^54,55

Several meta-analyses of observational data have shown that healthy dietary patterns during the prenatal period, childhood and adolescence are associated with a significantly reduced risk of certain mental disorders including internalizing disorders and externalizing disorders, whereas the opposite is observed for unhealthy dietary habits.^{30–32,34–36} The included studies in these meta-analyses attempted to control for the impact of important confounding factors, such as participant sex, unfavourable socio-economic status, obesity, physical inactivity, or family conflicts.^{30,32,34–36} However, prospective links with diagnosed mental disorders were not established.

Dietary Interventions

In depression, dietary interventions showed promise in reducing depressive symptoms in some studies, but RCTs did not consistently support their efficacy in the paediatric population.³¹ It is important to note that the included studies focused on promoting healthy habits in overweight or obese children. As a result, the generalizability of these findings to individuals of normal weight is limited. Also, they differ from adult research where dietary interventions had a small but significant effect on reducing depressive symptoms.⁵⁶

Restriction diets eliminating synthetic food colours appeared to significantly reduce ADHD symptoms but often in individuals selected for food sensitivities.³⁷

Among children with ASD, the dietary interventions identified in our paper are limited to the GFCF diet. While this diet may lead to improved cognition and reduced stereotypical behaviours,⁴³ it is important to note that further research with larger samples is necessary.

Nutrient Supplements

Regarding the role of dietary supplements in the prevention of paediatric mental disorders, ASD has been most widely studied. Prenatal folic acid (>400 μg daily) and multivitamin supplementation have shown potential in reducing the risk of ASD in children,^44–47 especially in high-quality observational and prospective studies.^44,45

Vitamin D supplementation in ASD, as revealed in 2 meta-analyses, showed no improvements in core autism symptoms. Both meta-analyses included RCTs with small sample sizes, making it difficult to draw definitive conclusions.^49,50

Additionally, probiotic and prebiotic supplementation did not demonstrate a significant effect on ASD symptoms in a recent meta-analysis of 7 RCTs, though more extensive trials are necessary.⁵²

PUFAs have been the most widely evaluated dietary supplement in the treatment of paediatric mental disorders, particularly in the context of ADHD.^37–40 Omega-3 supplementation with high-EPA formulas (>500 mg/day) for 3 months was identified as potentially beneficial for hyperactivity symptoms and comorbidities in ADHD, including EL or oppositional behaviour in high-quality meta-analyses of RCTs.^39,40 Moreover, vitamin D supplementation (400 to 2000 IU/day) as an adjunct to methylphenidate appeared effective in treating ADHD symptoms,⁴¹ while zinc supplementation may also have beneficial effects.⁴²

Strengths and Limitations

Our data should be considered in the light of some limitations. Firstly, meta-analyses of observational studies included in our work may show associations between nutrition and mental health but establishing a causal relationship can be challenging due to the observational nature of these studies and the possibility of residual confounding. Intervention studies, using an overall diet strategy, are a robust way to support the causal roles of dietary patterns in the onset of any mental illness.² However, meta-analyses of intervention trials are often limited to nutritional supplementation, and studies corresponding to dietary patterns are scarce. Moreover, studies evaluating the impact of nutritional supplementation in the treatment of mental diseases often lack data on serum levels of the nutrients studied before and after treatment. This can make it difficult to establish a clear link between supplementation and therapeutic response.

Moreover, many of the outcomes included in this meta-review exhibited significant heterogeneity between the included studies or were based on a small number of samplers. This may limit the generalization of the results of the meta-review and make it difficult to draw definitive conclusions. Finally, the execution of a meta-analysis was not possible due to the diversity of extracted data (OR, RR, SMD, and pooled mean difference).

Despite these limitations, our study has notable strengths. It is the first comprehensive review providing a complete overview of available evidence in the field of nutritional psychiatry in the paediatric population. Our approach to include the results of several meta-analyses facilitates a thorough examination of the available evidence. Furthermore, to mitigate bias related to the overlap of included meta-analyses, we minimized the overall CCA by excluding the majority of meta-analyses with significant overlap (≥15%). This approach reduced overlap for each studied disorder, allowing for a more accurate assessment of our data. Additionally, we systematically assessed the risk of bias for each included meta-analysis using the AMSTAR tool, enhancing the reliability and validity of our findings.

Future Perspective

A potential next step in this field of research is to shift from a categorical diagnostic approach to a dimensional one with a transdiagnostic perspective such as the Research Domain Criteria approach framework.⁵⁷ For example, research can be conducted to understand how specific components of the diet, such as nutrients, antioxidants, omega-3 fatty acids, etc., may modulate emotional responses, cognitive processes, and stress responses, and influence psychiatric symptoms. This future research should be reported to the ISNPR to promote research in the field of nutritional medicine for child and adolescent psychiatry.

Conclusion

Our results emphasize the necessity of establishing clear causal relationships between dietary habits and the risk of mental illness through interventional studies relying on comprehensive dietary strategies, such as the Mediterranean diet or a healthy diet, particularly in the paediatric population. Furthermore, emerging evidence suggests that omega-3 and vitamin D may be beneficial for ADHD in children and adolescents. However, it is essential to interpret these results with caution, and conducting larger-scale RCTs is imperative to establish more robust conclusions.

Supplemental Material

sj-docx-1-cpa-10.1177_07067437241248070 - Supplemental material for The Role of Dietary Patterns and Nutritional Supplements in the Management of Mental Disorders in Children and Adolescents: An Umbrella Review of Meta-Analyses: Le rôle des habitudes alimentaires et des suppléments nutritionnels dans la prise en charge des troubles mentaux chez les enfants et les adolescents : une méta-revue de méta-analyses

Supplemental material, sj-docx-1-cpa-10.1177_07067437241248070 for The Role of Dietary Patterns and Nutritional Supplements in the Management of Mental Disorders in Children and Adolescents: An Umbrella Review of Meta-Analyses: Le rôle des habitudes alimentaires et des suppléments nutritionnels dans la prise en charge des troubles mentaux chez les enfants et les adolescents : une méta-revue de méta-analyses by Maria Talib, Majda Rachdi, Anna Papazova and Hélène Nicolis in The Canadian Journal of Psychiatry

Footnotes

Acknowledgments

We express our sincere appreciation to Valérie Durieux for her assistance in conducting the literature search. Additionally, we extend our thanks to Professor Stamatios Nicolis for reviewing the English language of the present article.

Data Availability

Data and materials associated with this rapid review are available upon request.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Maria Talib

Supplemental Material

Supplemental material for this article is available online.

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