The Efficacy of Nutritional Interventions in Reducing Childhood/Youth Aggressive and Antisocial Behavior: A Mixed-Methods Systematic Review and Meta-Analysis

Implementation Barriers

One key area of consideration concerns awareness of healthy food and nutrition guidelines in schools and other institutions. A systematic review on school-based food policies aiming to improve youths' food consumption through modifications to the food environment such as through the provision of nutritious foods and marketing restrictions for unhealthy ones indicated that stakeholders often lack knowledge and understanding of healthy food policy requirements due to the lack of clarity of the policy guidelines or lack of communication (Ronto et al. 2020). Such a barrier has been highlighted in school settings in low- and middle-income countries as well (Meshkovska et al. 2023). In publicly funded institutions, it has been found that there was a disparity between individuals' understanding of what is considered “healthy” and what the organization's specific policy guidelines stated, while at the governance level, there was a lack of motivation to enforce guidelines or take them seriously because they were voluntary (Rosewarne et al. 2022).

The above barriers to implementation may be influenced by other individual-level factors such as mental health status. For example, one study that investigated dietary habits and knowledge among adults with severe mental health issues found that they were less likely to consider diet and exercise as a relevant part of their lifestyles and that their lower levels of knowledge about nutrition were often associated with their poor nutritional habits and physical activity, compared to adults without a severe mental illness (Osborn et al. 2007).

Perceptions about dietary changes can also affect interest in adopting such interventions. A systematic review that focused on food-environment policy implementation noted that at the individual level, consumers often had perceived notions that unhealthy foods are more popular and that healthy options were more expensive and thus less appealing (Middel et al. 2019). A review of healthy food policy in public sector workplaces reported that customers' perceived, expected, or actual negative reactions to removal of or restrictions on unhealthy items were disheartening to managers and food service staff at all levels and reinforced their negative perception of implementation (Rosin et al. 2024).

Food providers, on the other hand, often felt that the responsibility of managing consumer expectations was burdensome, and that changing behaviors or forcing individuals to eat healthily should not be placed on their shoulders (Rosin et al. 2024). The implementation is often experienced as being overwhelming or confusing by individual food providers, due to the stakeholders' limited nutritional background and lack of communication efforts (Rosin et al. 2024). This view is supported by findings that in schools, staff had negative perceptions of policies focused on healthy initiatives because they felt burdened about the additional responsibilities of having to implement them (Ronto et al. 2020). Schools also often prioritize academic performance over the implementation of nutritional policies for their students due to the concern that healthy policies might cause dissatisfaction among students and interfere with their learning outcomes, and parents may not agree with the policies restricting food choice options (Ronto et al. 2020). Additionally, a more prescriptive than collaborative approach towards healthy food policies can result in negative attitudes towards implementation in general (Rosin et al. 2024).

Implementation Facilitators

At the individual level, the primary facilitators are consumer attitudes towards healthy products. This may be influenced by obtaining information related to nutrition from reliable sources. A study on nutrition and physical activity in young people attending mental health services reported that most young people found it preferable to obtain their nutrition-related information from reputable healthcare providers such as general practitioners and dietitians (Mawer et al. 2022). An investigation of facilitators and barriers to implementation of nutritional interventions in early childcare settings further revealed that children's positive reactions to the intervention influenced educators' positive attitudes towards it, as well as their beliefs and motivations for engaging with the intervention, which constitute critical factors in adoption and implementation success (Asada et al. 2023). Positive consumer feedback, especially on initial changes to usual food offerings, can additionally increase food providers' willingness to implement a new policy. This can be done by conducting customer surveys before and during implementation to identify consumer preferences, such as desirable healthy options (Rosin et al. 2024).

Other facilitators that have been identified include (1) networking with organizations to help minimize the disparity between consumers' understanding of healthy foods and information provided in the nutrition guidelines (individual level), (2) an improvement in upper management's support (organizational level), (3) staff buy-in/support towards initiatives (community level), (4) positive relationship with suppliers/retailers and having suppliers/retailers who are motivated to provide healthier foods (supplier level), and finally, (5) integrating policy/guidelines into contractual obligations with suppliers and retailers (governance level) (Rosewarne et al. 2022).

Furthermore, having tasty and acceptable food and drink in place before limiting or removing popular unhealthy options, especially in the early stages of implementation, can allow consumers to make their own food choices while gradually exposing them to healthier options using active engagement methods (Rosin et al. 2024). Multi-component marketing strategies such as regular informative and promotional messages directed at consumers has also been suggested to improve awareness, support, and, ultimately, demand for healthier options (Rosin et al. 2024).

It has also been found in a school environment that (1) creating diverse menus that were conscious of dietary restrictions or specific preferences, (2) providing proper health education to children or incorporating programs dedicated to nutritional education as part of the overall academic health curriculum, (3) making easier-to-follow guidelines that are not burdensome to staff, and (4) giving information to teachers regarding the negative consequences of unhealthy foods such as damage that sugar-sweetened beverages and processed foods cause all served as facilitators of nutrition-related actions (Meshkovska et al. 2023; Ronto et al. 2020). The use of videos and diverse educational activities as part of these types of actions was also a potential facilitator (Meshkovska et al. 2023).

Implementation Barriers

A study by Middel et al. (2019) found that fluctuating demands for healthier options, along with the geographical limitations of shipping goods, can potentially hinder the supply of healthy food items. The same authors noted that physical limitations such as limited storage capacity for fresh products, high operational costs, as well as a waste of fresh product due to spoilage were potential barriers to access. Furthermore, limited available space and impracticality in the physical arrangements of layouts in institutions often pose challenges in the implementation of healthy food policies, as suppliers may have to make significant changes to accommodate the healthy food offerings (e.g., making changes to shelving and equipment) (Rosin et al. 2024).

Another study focusing on the policy of implementing dietary interventions in publicly funded institutions determined that the existence of multiple site locations and methods of food provision were barriers that influenced implementation at the organizational level (Rosewarne et al. 2022). Insufficient funding given the high costs associated with healthier foods, limited infrastructure (e.g., a lack of canteen and kitchen facilities that hinder the ability to prepare healthy lunches), and limited administrative time, all posed significant obstacles to the development of healthier food environment policies (Meshkovska et al. 2023; Ng et al. 2022; Ronto et al. 2020). Additionally, due to minimum product order requirements, smaller food providers may not have enough buying authority to purchase healthier, less popular options, and there may be restrictions in contracts that limit product sourcing from various suppliers (Rosin et al. 2024).

Implementation Facilitators

Strategies to increase community engagement (e.g., organizing cooking demonstrations), self-sustaining fresh produce, and improvements in menu planning, can all help facilitate access to healthier food options (Ng et al. 2022). Moreover, practices utilizing methods of conserving products such as freezing products prone to spoilage and methods of product stocking, such as transforming near-expiry products into daily offering items alleviated the problem of food waste due to product spoilage (Middel et al. 2019).

To overcome logistical challenges, governments could provide financial support, which could also support training programs for staff, which were shown to improve the implementation of healthy food policies in schools (Ng et al. 2022). Stakeholders should also consider taxing unhealthy food items and from the generated revenue, subsidize healthy but more costly food options in as many settings as possible (Mulder and Rucklidge 2023). Furthermore, implementation was more successful when in addition to the government, local farmers and cooperatives invested their funds in participating in food provision programs, such as purchasing trucks to deliver food to schools (Meshkovska et al. 2023). To overcome the challenges associated with contractual restrictions, food providers may collaborate and renegotiate their contracts with suppliers to stock healthier items. Lastly, a culture focused on innovation and experimentation is considered a potential facilitator: if a retailer has close ties to the community, its participation in efforts to test interventions involving dietary improvements is more likely (Middel et al. 2019).

Implementation Barriers

One important barrier to improving diet is that the definition of a “healthy diet” is often unclear (e.g., what exactly fits into it and what does not) and may vary across cultural contexts, individual needs, and even dietary guidelines (Nemec 2020). Dietary recommendations often do not consider these cultural variations, making it difficult for diverse populations to adhere to suggested diets. Another discrepancy is evident in that the US dietary guidelines describe a healthy diet as one that is comprised of whole grains, fruits and vegetables, fat-free and low-fat dairy products, lean meats, and foods low in fat, sodium, and added sugars. These guidelines are directed towards the general public (ages 2 years and above) (Branscum and Sharma 2020). In contrast, the World Health Organization (WHO) describes healthy diets as dietary patterns that balance energy to maintain a healthy weight, limit energy from fats (consuming more unsaturated fats), and reduce intake from sugars and salts (e.g., using iodized salts). If all foods can generally be part of a healthy diet when consumed in moderation, then identifying what dietary manipulations should include constitutes a challenge (Branscum and Sharma 2020).

Implementation Facilitators

Culturally tailored dietary interventions may need to be considered. This includes placing a larger focus on cultural humility (i.e., understanding participants' cultural beliefs as well as cultural dimensions of diet) and integrating this into the administration of dietary interventions (Zeda 2024).

Implementation Barriers

The overall drop-out rate from dietary manipulation in the studies included in this review was 11.62% on average (with a standard deviation of 16.42%). Of the data collected from our included studies, the healthy gluten-free, casein-free, soy-free diet had the lowest compliance rate (Adams et al. 2018). Side effects may affect compliance; for instance, some participants reported temporary mild nausea, and one child had loose stools as a side-effect of this specific diet. In other studies, side effects were similar and included irregular bowel movements, stomach aches, vomiting, night wakings, and decreased appetite (Johnson et al. 2011). These complaints were rare though (or completely missing, cf. Pelsser et al. 2011), and due to their non-specific nature, it is hard to know whether they were indeed related to the intervention or other factors (e.g., mild infection). Further, when unwanted effects were monitored in both study arms, the control and intervention groups often did not differ significantly (e.g., Johnson et al. 2011). However, if these minor side effects are perceived by participants or caregivers as related to the dietary intervention, they may reduce compliance.

Besides side effects, a study investigating the challenges with implementation of nutrition-related actions in school settings found that the quality of food was a barrier to compliance, where food was generally of low quality (Meshkovska et al. 2023). Furthermore, the unappealing taste and appearance of healthy food were common barriers to compliance. It has been suggested that many individuals do not want to accept healthier options and their dissatisfaction with restrictions on unhealthy items often leads food providers to justify non-compliance (Rosin et al. 2024).

Another barrier to user compliance concerns competing priorities (e.g., family, work, or hobbies), and difficulties adjusting existing habits to ones that are favorable to a healthier diet (Domosławska-Żylińska et al. 2024). Factors such as emotional eating, food cravings, and hunger have also been identified to hinder adherence to healthy diets in interventions (Deslippe et al. 2023), while unhealthy eating patterns in the family and difficulties in avoiding unhealthy foods in family gatherings and community settings can be barriers to implementing healthy eating (Domosławska-Żylińska et al. 2024). In addition, women were more likely to indicate factors such as a lack of support from friends and family, and healthcare professionals (e.g., physicians) as a hindrance to practicing a healthy diet (Domosławska-Żylińska et al. 2024). Moreover, negative attitudes towards interventions involving dietary manipulation such as previous failure to change eating habits (Deslippe et al. 2023) or selective, “picky” eating (aka Avoidant Restrictive Food Intake Disorder) especially in children with autism, can be major barriers to compliance with dietary changes.

Implementation Facilitators

Findings from Meshkovska et al. (2023) suggest that a potential facilitator to the successful implementation of the various nutrition-related initiatives could be the provision of fresh/healthy products of good quality. The use of home-made food, local products, and products with fewer chemicals due to organic fertilizers being used was a solution to concerns of taste and agrochemicals. Participants could also be provided with healthy food samples and taste-testing sessions before the intervention to gather feedback in the early stages of implementation and overcome the negative perceptions around the taste of healthy foods (Rosin et al. 2024). Using consistent, informative messages to engage customers in accepting more nutritious options and raise awareness may also improve compliance with dietary interventions (Rosin et al. 2024).

Strategies that validate the healthier options, such as the inclusion of a clear, consistent, and mandatory policy, promoted by the national or local government and senior workplace management, may help improve adherence, as it becomes a priority to implement. Support structures (both internal and external) throughout implementation, such as positive management attitudes, committed leadership teams, and personalized ongoing assistance from dietitians, are all potential facilitators to compliance (Rosin et al. 2024). Community support and the awareness of health benefits can also be important to help facilitate implementation.

An increased public understanding of the importance of healthy eating in terms of mental and behavioral health is likely to increase both the demand and adherence to healthy food options (Ng et al. 2022). Findings from Deslippe et al. (2023) similarly identified social support and social accountability as major facilitators in adhering to healthy diets; support systems included support from the intervention providers (e.g., by health experts such as physicians, dietitians, trainers, or intervention staff), within the home (e.g., by parents), and outside the home (e.g., by colleagues or peers). Being able to actively participate alongside someone aiming for the same goals may also facilitate healthy eating. With regard to social accountability, factors such as wanting to become a role model, and wanting to change others for the better (e.g., family and friends) also promoted adherence to a healthy diet (Deslippe et al. 2023).

Implementation Barriers

Many individual characteristics such as age, sex, weight, health conditions, and lifestyle behaviors, can also influence the effect of dietary interventions. Dietary manipulations have varied effects on behavior due to individual differences, medications used, gut health, and levels of stress and anxiety, which may result in above-average nutritional needs in many individuals (Rucklidge et al. 2021). For example, various antipsychotic drugs, anticonvulsants, and antidepressants are known to inhibit the absorption of several micronutrients (e.g., vitamin B12, B2, B6, D, K, calcium, etc.), as well as cause depletion in minerals such as magnesium, zinc, or selenium (Pelton et al. 2001). Certain mood stabilizers can also deplete the levels of folic acid, vitamin D, vitamin B6, and vitamin B12, as well as minerals such as copper, selenium, and zinc (Rucklidge et al. 2021). Another factor to note is the possible untreated issues related to an illness that can influence the effectiveness of dietary interventions. For example, many studies suggest that individuals with autism might also have poor digestive health, which can lead to symptoms like diarrhea, constipation, and abdominal pain (Chaidez et al. 2014) and the effectiveness of a dietary intervention could be diminished by such underlying issues if they are not treated first.

Another issue to consider is the nutritional depletion of the foods themselves. Environmental factors (such as climate change, depletion of minerals in soil, or the increasing levels of CO₂ in the atmosphere) may decrease the density of nutrients found in our foods. This can result in crops that are higher in carbohydrates and lower in proteins and micronutrients (Rucklidge et al. 2021).

Implementation Facilitators

A diet rich in plant-based and fermented foods is known to support microbial biodiversity and restore gut health, providing the basis for other dietary interventions aiming to improve mental and behavioral health. For example, one study found that people with an increased consumption of natural sources of pro- and prebiotics showed significantly lower levels of anxiety, stress, and neuroticism (Johnson 2020). Another study reported that the higher consumption of natural probiotics through fermented foods related to fewer symptoms of social anxiety in females (Hilimire et al. 2015). Assessing gut health as a factor when implementing dietary interventions can help improve their overall effectiveness. Working on providing foods of higher quality and reducing the intake of highly processed foods is key, when tackling the challenges of poor gut health (Rucklidge et al. 2021).

To resolve the challenges of nutrient deficiencies that arise from certain medications (even with reasonable dietary intake), nutritional supplements with above-average dosages can be considered. Addressing underlying health issues and individual factors by engaging professionals such as physicians, dietitians, gastroenterologists can help improve the overall effectiveness of dietary interventions.

Implementation Barriers

One barrier to implementing nutritional supplementation is the lack of accessible information about nutritional interventions, which is evident across countries. For example, a study in Iran found that only 28% of female high school students received educational information about the iron supplements provided to them as part of a program aimed at addressing iron deficiency anemia (Jafari et al. 2023). Most of the students also did not use the iron supplements despite their free provision, due to their belief that because they did not have a disease, the iron supplementation was completely unnecessary. Similarly, in a South African study, participants aged 18–28 years shared that they were unaware of the purpose of receiving multiple micronutrient supplementation. This lack of understanding resulted in suspicions of the supplementation program among family members, which also contributed to women discontinuing their participation (Silubonde et al. 2022). This was consistent with findings from a study on vitamin A supplementation in Sub-Saharan African children aged 6–59 months where one of the major barriers to supplementation was a lack of awareness about its availability (Janmohamed et al. 2017).

From the data collected from our included studies in this review, one study particularly highlighted limited nutritional literacy: some prisoners did not have even the most basic knowledge of choosing a healthy diet and some were not aware of what vitamins were at all (Gesch et al. 2002). Moreover, skepticism among health and educational professionals, limited knowledge about vitamin intake recommendations, heavy workloads, and infrequent appointments with the target population contributed to the minimal promotion of vitamin supplement use in a sample of parents and professionals recruited in the United Kingdom (Jessiman et al. 2013).

The level of awareness and knowledge of the use and effectiveness of nutritional supplementation is, in part, influenced by where individuals obtain the information from. A US study on dietary supplement use in children found that most supplements used by children are not suggested by a healthcare professional. Rather, they are suggested by other parents, families, and friends (Bailey et al. 2013). Many adolescents also obtain their information about dietary supplements from internet searches, which are often inaccurate or insufficient (Kärkkäinen et al. 2019). This is confirmed by findings showing that due to obtaining information through unofficial means, such as relying heavily on parents' opinions when addressing their nutritional needs, adolescents end up having several misconceptions about the health benefits of nutritional supplements (O'Dea 2003).

Implementation Facilitators

Nutrition education initiatives foster a greater understanding of the importance of supplementation and nutrition services (Handiso 2023). One example of this approach is the use of the socio-scientific issue method (Kärkkäinen et al. 2019). Developers of this method evaluated its effectiveness in improving 7th grade students' knowledge of dietary supplements. The 7-h-long health education intervention was delivered through an e-learning environment and involved three stages: the scenario, the inquiry, and the decision-making stage, where students acquainted themselves with an imaginary person's nutritional status, looked for information on dietary supplement needs, and applied their knowledge by counseling the imaginary adolescent. This method increased students' knowledge of the rationale for the use of dietary supplements, engaged them in decision-making, challenged their social and emotional skills, and was positively received by students (Kärkkäinen et al. 2019).

Engaging adolescents in active bidirectional problem-solving discussions, such as involving facilitators and family members regarding any issue that may have arisen during the implementation of nutrition services further increased adolescents' interest in the intervention (Handiso 2023). Social and community networks were also found to motivate adolescent girls to access nutrition services (Handiso 2023). Improving the general knowledge base of educational and correctional service workers regarding nutrition and supplementation (as part of their university studies and/or postgraduate/continuing education) would also be helpful. Such training for health professionals in the United Kingdom, for example, is required to enhance professionals' understanding of nutritional supplements and to develop strategies for effectively promoting interventions to eligible families (Jessiman et al. 2013).

Implementation Barriers

One study in England collected data from health and children's care professionals, as well as parents to determine why few eligible families were accessing the free vitamin supplements provided by the Healthy Start Scheme (Jessiman et al. 2013). Less than 10% of those eligible used the vitamin supplements. Approximately 20% of eligible families could not access vitamins as they were not formally registered with the specific program. Shedding light on other barriers to supplementation, some parents cited inconvenience and distance from distribution sites. Although the vitamin supplements were often distributed in health and children's centers, many health professionals were unaware of this fact, which contributed to confusion among parents about where to go to collect the vitamins. Delays in processing eligibility applications also prevented mothers from receiving early access to free vitamins for themselves and their young children in this study (Jessiman et al. 2013).

The unavailability of products as a reason for not taking nutritional supplements is also documented in many countries. In Southern Ethiopia, for example, the shortage of iron-folate supplements meant that the demand for these tablets among adolescent girls was unmet (Handiso 2023). In addition, the economic status of adolescent girls' families impacted their access to nutritional supplements, as tablets were provided at school, which prevented adolescent girls, with a low socioeconomic status, not attending school from receiving the supplementation (Handiso 2023). These findings were corroborated in a study in Sub-Saharan Africa where although distance to distribution sites was not a significant barrier, household wealth was a potential factor affecting access due to costs associated with traveling to distribution sites (Janmohamed et al. 2017). School-based supplementation programs may be challenged by the fact that in many societies, individuals who do not regularly attend school may be the same children who are in the deepest need for supplements due to their poor diet resulting from very low socioeconomic status.

Financial barriers also significantly contribute to the target populations' lack of access to nutritional supplements. Although psychiatric medications are typically subsidized in many countries, this is not the case for nutritional supplements (Darling et al. 2019). As a result, the cost of nutritional supplements is one of the greatest barriers to longer-term, consistent micronutrient use. In Portugal, 53% of interviewed pharmacists cited the high cost of oral nutritional supplements as the main barrier to access (Gregório et al. 2023).

Of note is that almost all studies on micronutrient supplementation included in this review excluded participants who were taking psychiatric medications at the time of the interventions (see study-level details on that in the Supporting Information S1). One of the reasons for this is that – according to anecdotal evidence – effective micronutrient supplements (especially broad-range ones) seem to enhance the effect of psychiatric medications (potentiation) leading to a need for medication dose reduction. However, prescribing clinicians typically do not decrease the medication dosage when this happens due to lack of knowledge regarding medication-supplement interactions or fear of relapse. Excluding people on medication however proves to be a significant barrier to both recruitment for research purposes as well as general use of supplements among people taking psychiatric medications. It is also worth mentioning though that in comparison to the few studies where medicated participants were actually included, trials that excluded participants using psychotropic medications tended to show a larger beneficial effect (Gast et al. 2023). At this point, it is unclear if that is because psychotropic medications interfere with the beneficial effects of nutritional supplements [cf. in a study of psychiatric inpatients, those individuals not on antipsychotics experienced larger reduction in aggression than those on antipsychotics; (de Bles et al. 2022)] or this phenomenon is related to selection bias: that is, in people with more severe mental health challenges (who more likely take antipsychotics), nutritional supplements are less effective (regardless of whether they take antipsychotics or not).

Implementation Facilitators

To increase the accessibility of nutritional supplements, some provisioning and innovative distribution approaches are potential facilitators to the logistical and economic challenges. The free provision of iron folate supplements to a population of adolescent girls was shown to facilitate access to nutrition services (Handiso 2023). The use of supplements from produce readily available in the given region is another potential solution to the unavailability of supplements (Lentjes et al. 2014).

Having distribution sites, where supplements are handled directly by a professional, is known to facilitate access and increase their usage. In distribution sites that tested the universal provisioning of free vitamins and where information and training for health professionals were offered, parents were more likely to use vitamins (Jessiman et al. 2013). Health professionals were also more likely to support and advise parents in using vitamin supplements at these locations. Additionally, door-to-door distribution has been shown to be more effective than the fixed-site plus outreach approach, which required caregivers to be aware of the supplementation program and to attend outreach sites with their children (Janmohamed et al. 2017). Door-to-door distribution also alleviates the issues of inconvenience to reach a site due to distance and lack of knowledge of their location. Reducing administrative burden for schools, which sometimes serve as distribution sites, can also improve compliance with an intervention (Bommer et al. 2020).

Collaboration across sectors to expand supplementation programs beyond schools and recruit trained experts to reach more people in the target population, regardless of socioeconomic status, can help overcome the socioeconomic barriers to access (Handiso 2023). Addressing constraints in financial resources is key to ensuring that nutritional supplementation programs effectively promote child health and development. Recognizing that cost is a significant barrier to continuing micronutrient treatment, the public healthcare system and private insurers may consider improving access by providing government-funded or extended-health-insurance-based coverage for the costs of supplements (Darling et al. 2019; Rucklidge et al. 2021). With the contribution of private health insurers, supplement costs could be on par with medication costs to families. To enhance government engagement, it may be important to convey the information that nutritional supplements cost far less than standard mental health treatments (especially if they can prevent hospitalization), as demonstrated through some Canadian case studies (Kaplan et al. 2017; Rodway et al. 2012).

A potential solution to prescribers' hesitancy to reduce psychiatric medication dosages taken parallel to nutritional supplementation is to start treatment with nutrients and add medications only thereafter if necessary. Even in this case, prescribers may want to begin with medication doses lower than what would be prescribed without nutritional supplementation to prevent adverse outcomes resulting from the potentiating effects of nutritional supplements. Psychiatric medication prescribers should seek and be offered reliable and in-depth information on supplement-medication interactions to provide them with the necessary knowledge base to serve their clients best. Some supplement producers offer such trainings (e.g., https://try.hardynutritionals.com/syllabus/) or written materials to prescribers (Hardy Nutritionals 2019). ⁸

Implementation Barriers

The complexity of the evidence on the associations between nutritional factors and aggressive/antisocial behavior (Choy 2023) renders decisions for which nutrients to supplement challenging. An additional issue in nutritional supplementation concerns dosage, which can significantly influence effectiveness (a comparison of targeted nutrients and dosages can be found in the Appendix of the work of Gast et al. 2023). While “Daily Reference Values” (DRV) or “Daily Recommended Intake (DRI) Values” exist for the most important nutrients, these values were established with an eye on the prevention of severe somatic diseases (scurvy, iron-deficiency anemia, osteoporosis, etc.), not on the optimization of mental health. Consequently, supplementation considering these thresholds may not be sufficient, and accordingly, many supplements used in the field of nutritional mental health contain much higher doses than suggested by the Daily Reference or Daily Recommended Intake values. Given that individuals' idiosyncratic nutrient needs may differ significantly, it is not easy to establish universally effective but still safe absolute and relative (balance of different nutrients with each other) dosages for supplementation. The relative imbalance of certain nutrients as a result of narrow-range supplementation (e.g., omega-3 vs. omega-6 fatty acid ratio in relation to omega-3 fatty acid supplementation) might be a factor in the background of below-expected efficacy or even treatment harm (cf. data on supplementation with amino acids in Section 5.3.1.3; amino acid supplementation is now not recommended due to risks from toxic catabolic products resulting from increased neurotransmitter turnover [Hurt and Arnold 2014]).

A related issue is the duration of the intervention: that is, how long supplements should be taken to reach some or their maximum effect. While most studies in this field use an intervention duration of 3 months (Qamar et al. 2023), some studies indicate that additional, new improvements in mental health outcomes occur even after 12–15 months of supplementation (Mehl-Madrona and Mainguy 2017). Of the data collected from our included studies, three studies noted that limitations were low dosages and the short duration of supplementation. In one of these studies, vitamin D (2000 IU/d) supplementation for 8 weeks did not correct vitamin D deficiency in about 30% of participants (Mohammadpour et al. 2018). On the other hand, the quantitative results of the present review regarding omega-3 fatty acid supplementation to reduce antisocial behaviors indicated that shorter intervention duration was more effective than longer supplementation (see Section 5.3.2.2). Further research, therefore, is clearly needed to clarify the optimal duration and dosage of supplementation in different populations.

Additional insights from our authors revealed that country-specific regulatory issues might also influence the use and especially the study of nutritional supplements, leading to suboptimal doses used in interventions. In some countries, supplements containing nutrients in doses above the daily recommended value need to undergo more rigorous approval processes than general food supplements. Their producers, however, may not have the intent or the financial means to do so; therefore, using higher-dose supplements would be illegal in such contexts, leading to the use of suboptimally low dosages.

Implementation Facilitators

We propose that continued research efforts in nutritional mental health sciences are needed to build an evidence base, which could inform the public, clinicians, and other stakeholders about the optimal nutritional targets, doses, and treatment durations in the case of various mental health concerns or behavioral problems, including aggression. Psychiatric medication prescribers should be provided with essential training and education on the benefits and management of nutritional interventions in general and supplements specifically, through the available guides for medication prescribers on supplementation or online training modules.

Of the data collected from our included studies, one study reported that the number of pills required per day was a concern for some families with younger children; splitting them up to 2–3 times/day made it manageable for most participants (Adams et al. 2018). Even though most of the vitamins were well-absorbed, for some vitamins, it was beneficial to use larger doses and/or more bioavailable forms, to exert a significant effect on blood levels; larger doses/increased absorption may result in a greater therapeutic benefit (Adams et al. 2018).

Implementation Barriers

There are numerous practical challenges influencing compliance with nutritional supplementation. One concerns the inconvenience of managing the time to visit healthcare settings/pharmacies to purchase the product. An insight from the authors of one study included in the present review revealed that as capsules were taken three times a day, some schools had trouble allowing students to take these without a doctor's note, posing a barrier to taking multi-nutrients.

Furthermore, a lack of social support also affects compliance. Among South African women, lack of family support, including discouragement from key family members acted as a barrier to nutritional supplementation adherence (Silubonde et al. 2022). Iranian students also listed influence from family and friends as reasons for non-compliance with nutritional supplementation (Khammarnia et al. 2016).

Individual-level factors can also serve as barriers to compliance. Forgetfulness has been identified as a challenge to complying with nutritional supplementation (Food Standards Agency 2018; Schultink et al. 1993). An original author we contacted for their expert opinion further noted that forgetting remained an issue despite families receiving regular reminders. This is tied to the issue that the large number of daily capsules was one of the leading factors behind poor adherence and discontinuation of micronutrient supplementation in a randomized trial of children with ADHD (Darling et al. 2019). Longer intervention durations can also pose a greater risk for non-compliance (Chang et al. 2019).

The way nutritional supplements are administered can also affect compliance. In the United Kingdom, participants who took gels and sprays found it challenging to ensure that they were taking the recommended dosage (Food Standards Agency 2018). Furthermore, the large size of multivitamin and mineral capsules proved to be a challenge for swallowability (de Bles et al. 2022), especially for younger children. Similarly, a cross-sectional study on adherence to oral nutrition supplements in Sweden cited swallowing difficulties, as well as taste and texture, as reasons why consuming supplements was sometimes challenging (Liljeberg et al. 2019).

In the current review, the overall drop-out rate from nutritional supplementation in the included studies was 10.55% on average (with a standard deviation of 10.44%). In one of the studies, five families did not participate due to objections against pork-gelatin-containing capsule casings (Widenhorn-Müller et al. 2014). Another study reported that approximately 20% of the participants had problems with the taste of the fish oil and/or the unflavored vitamin/mineral supplement (Adams et al. 2018). Additional insights from authors of our included studies also included unfavorable sensory characteristics of food supplements with high omega-3 content (e.g., smell). Another author reflected on the link between low compliance and conduct problems, where non-adherence with expectations is a defining feature of the disorder itself (cf. oppositional defiant disorder, antisocial personality disorder).

Although side effects are typically minor and transient (Rucklidge et al. 2023) and they differ from supplement to supplement (depending on nutrient, dosage, and supplementation format), their effect on compliance is also important to consider. Regarding omega-3 fatty acid supplementation, most of the original studies included in the quantitative section of this review reported no adverse events or a side effect profile not significantly different from that of the placebo group (Crippa et al. 2019; Dean et al. 2014; Gustafsson et al. 2010; Johnson et al. 2010; Mankad et al. 2015; Richardson and Montgomery 2005; Widenhorn-Müller et al. 2014). Those authors who did observe intervention-specific side effects typically reported mild gastrointestinal symptoms or rarely nose bleeding (Manor et al. 2012; Milte et al. 2013; Sinn and Bryan 2007; Young et al. 2017). Similar trends emerged regarding broad-range-nutrient and vitamin D supplementation: most studies did not find evidence for intervention-specific side effects (Gast et al. 2023; Gesch et al. 2002; Hemamy et al. 2021; Johnstone et al. 2022; Mohammadpour et al. 2018; Rucklidge et al. 2018), and investigators of those studies that did, primarily reported mild gastrointestinal symptoms (Elshorbagy et al. 2018; Raine et al. 2016). While these data overall suggest that the side effect burden of nutritional supplements is minor, occasionally they may act as a barrier towards the successful implementation of the intervention. For instance, authors of the only study on zinc supplementation reported that of the total number of individuals who dropped out of the study (12.5%), half did so due to gastrointestinal discomfort caused by zinc sulfate (Arnold et al. 2011).

Healthcare providers' lack of knowledge is also a known factor to influence overall intervention compliance. Pharmacists in Portugal, who considered themselves the main facilitators for patient follow-up, believed that their lack of knowledge about the characteristics of nutritional supplements for children hindered counseling opportunities and acted as a barrier to adherence (Gregório et al. 2023).

Implementation Facilitators

Health and nutrition professionals can utilize appropriate communication networks to convey nutrition information and health promotion to overcome the challenges of the misconceptions surrounding nutritional supplements (Zoellner et al. 2009). For example, combining the administration of oral nutrition supplements with dietary counseling is recommended and may increase adherence to these supplements (Liljeberg et al. 2019; Stratton and Elia 2010). To address concerns regarding the misconceptions among parents, increasing their understanding of nutritional supplements and their children's health by providing proper education and support may help reduce the impact of misguided beliefs on treatment compliance (López-Flores et al. 2012). Addressing the concern that many people are not able to receive an adequate amount of nutrition from their diet alone, the reasons behind this fact, as well as sharing information on the health benefits of supplements, are a few suggestions for improving compliance (van der Wurff et al. 2017). It has been shown that inviting a healthcare professional to provide information and using audiovisual materials can increase students' engagement with nutritional supplements (Jafari et al. 2023).

Incorporating incentives into intervention design is one approach that may be used to address concerns with compliance in research studies (Bommer et al. 2020). One study showed that providing study participants with non-monetary incentives such as cinema vouchers improved their response rates and increased their motivation to participate in studies (van der Wurff et al. 2017).

Nowadays, most supplements are readily available for purchase online, which may reduce the inconvenience related to the purchase/pick up of supplements. A study investigating the compliance of supplementation showed a higher compliance rate in studies conducted in community settings versus hospital settings (80.9% vs. 67.2%) (Hubbard et al. 2012). The use of school settings compared to hospital settings for interventions also showed a somewhat higher compliance rate (86% vs. 82.9%) (van der Wurff et al. 2017). This notion was supported by an author of one of our included studies, who indicated that the school setting (in the United States) seemed to result in excellent compliance and follow-up rates (Schoenthaler and Bier 2000).

Support from treatment providers and the community can also facilitate user compliance. Higher compliance with nutritional supplementation has been found among children of indigenous origin in a semi-rural community, most likely because the supplement distributors in the study were from within the community and were able to better address any concerns and hesitations among community members (López-Flores et al. 2012). There is also evidence of a positive association between motivation and higher treatment compliance, where the healthcare providers used a more empathetic and affective approach to treatment, addressing the needs and concerns of the client (López-Flores et al. 2012). Other studies have highlighted that adherence to supplementation was higher in children and adolescents who were supported by family and friends (van der Wurff et al. 2017). An author from our included studies suggested that many of their study participants had previously been patients at their institute, which acted as a significant facilitator due to the trust developed over the course of treatment. Thus, taking supplementation within the context of an existing collaborative or therapeutic relationship—such as one with a family physician, midwife, nurse practitioner, psychologist, or teacher—may enhance compliance.

Several studies also highlight that regularly communicating with parents and participants of research studies via phone calls, emails, or in-person was important in increasing adherence (de Bles et al. 2022), which can be particularly important in addressing concerns about forgetfulness. In a study, between each visit, parents were contacted through email or phone calls at least 3 times by the researchers to reduce dropouts and informally check compliance (Milte et al. 2013). An additional potential facilitator for improving compliance rates is giving consumers feedback on the effect of their compliance based on biochemical analyses (e.g., blood or urine analysis) or mental health outcome data (e.g., if users regularly report their symptoms in a phone app/online portal, which also provides feedback on their health outcomes).

To increase convenience, keeping the supplementation regime simple and easy-to-follow is also an important facilitator. This may involve, for example, the use of one concentrated capsule instead of many throughout the day (van der Wurff et al. 2017). Potential strategies such as postural adjustment, the use of pill-swallowing aids, and teaching pill-swallowing techniques help improve compliance in clients with pill-swallowing difficulties (de Bles et al. 2022; Kaplan et al. 2010). Several authors of our eligible studies specifically mentioned an easy-to-access (YouTube) training video from Professor Bonnie Kaplan (https://youtu.be/Zxqs7flHJQc) as a key and effective aid with pill-swallowing difficulties. Authors of some studies reported that they had clinicians on their team who used a pill-swallowing protocol to help children learn how to swallow pills.

The method of administration of nutritional supplements should also be considered. Alternative approaches, such as the modification of pills by crushing them and mixing them in foods or drinks, can also help with swallowing (de Bles et al. 2022). Particularly for younger children who cannot describe their symptoms, mothers have reported that when using drops to administer iron, 74% rejected the supplement (crying, spit drops, gestures), but this percentage went to only 16% when administered as a powder mixed with food (Galloway and McGuire 1994). Authors of a Japanese study on school children's aggression argued for fortification as a helpful way of increasing compliance: fish oil was added to bread, sausage, and spaghetti, which seemingly led to excellent compliance among the 9–12-year-old children (Itomura et al. 2005).

Some authors suggested the use of soft gel capsules to deliver the supplements as they proved to be easier to swallow, and this format also helped mask unpleasant tastes and odors (Benza and Munyendo 2011). An additional author insight revealed that to overcome the challenges of swallowing the fatty acid capsules in some participants, squeezing the oil out from the capsule directly into the mouth was a potential solution that worked effectively. Cultural, religious, or personal preferences also need to be considered; vegan versions of supplements are often available and thus should be offered to increase compliance (e.g., algae instead of fish-oil-based omega-3 fatty acid supplements; capsule materials not containing animal ingredients).

If capsules still prove to be a challenge, other options such as chewable tablets with an appealing taste could be used to administer the supplementation (Benza and Munyendo 2011). Some producers offer various other child-friendly forms of supplementation (e.g., lollipop stick for broad-range micronutrients, “EMPowerplus Ultimate Sticks” ⁹ ). Of the data collected from our included studies, two studies used a fruit-flavored drink to supplement with omega-3 fatty acids. The investigators argued that such products contain high enough doses of omega-3 fatty acids in a relatively small amount of liquid, and they are better tolerated due to their fruit flavor, resulting in higher compliance in children than standard capsules (on average 6.1 drinks per week out of 7 offered) (Raine et al. 2016; Raine et al. 2020). In a study from Sweden, participants were given a choice of flavors for their nutritional supplement; therefore, many participants actually liked the taste of their supplement, which likely contributed to the high adherence rate (Liljeberg et al. 2019). One study from Ghana investigated the use of sprinkles as a means of supplementation; when added to the food, these do not alter taste or color (Zlotkin et al. 2001). Furthermore, when they are manufactured in single-dose sachets, they reduce the likelihood of an accidental overdose from too much ingestion because each sachet would have to be opened separately to do so. Another advantage to using sprinkles over capsules or drops is that multiple micronutrients can be included in the sachet depending on the needs of specific individuals (Zlotkin et al. 2001).

While some studies have found that side effect burden can negatively impact compliance to multi-nutrient supplements, some authors noted that participants who used supplements long-term experienced symptom improvement, leading to improved compliance (Rucklidge et al. 2021; Silubonde et al. 2022). This finding highlights the importance of communicating the fact that it takes time for benefits to manifest to individuals receiving multi-nutrient treatment (Rucklidge et al. 2021). With regard to supplement formulations, administering a controlled-release format of certain supplements may decrease supplement side effects (Galloway and McGuire 1994). To reduce potential side effects, the authors of one included study reported that taking omega-3 fatty acid supplements at bedtime or with meals reduced burping and improved adherence. Of the data collected from our included studies, one study noted that choosing lunchtime for broad-range supplementation minimized possible side effects such as nausea and belching (Zaalberg et al. 2010). Another study determined that using zinc glycinate instead of zinc sulfate reduced side effects such as gastrointestinal discomfort (Arnold et al. 2011). These findings suggest that often there are supplement-specific ways of reducing the chances of side effects, which are important to consider when planning a supplementation regimen.

Implementation Barriers

Illnesses that affect body weight or gut health may influence the effectiveness of treatment with nutritional supplements. For example, individuals with inflammatory bowel disease or Crohn's disease are shown to have deficiencies in a wide range of micronutrients, also due to malabsorption (Berger et al. 2019). Certain medications or conditions can also cause micronutrient deficiencies due to their interference with absorption or excretion. For instance, certain antidepressants influence gut motility or the gut microbiome, leading to changes in nutrient absorption, while stimulant ADHD medications increase the excretion of certain minerals. Further, some antibiotics can cause deficiency in magnesium and various B vitamins, while certain drugs containing sulfhydryl can cause zinc excretion disturbances (D'Alessandro et al. 2022). Antipsychotic medications can also cause depletion in vitamin B12, and deficiencies in vitamin D can be caused by antacids and certain anticonvulsants (D'Alessandro et al. 2022). Taking such medications in combination with a nutritional supplement may negatively influence the effectiveness of the nutritional intervention. Moreover, children with ADHD may have a zinc-wasting metabolism such that zinc administered in the morning is excreted soon, but while in the system, the supplemented zinc may (temporarily) improve ADHD symptoms (acting as an immediate-release stimulant) (Arnold et al. 2011).

Heterogeneity in response to omega-3 supplementation has also been linked to genetic factors. A specific gene cluster (FADS) is shown, for example, to significantly impact omega-3 biosynthesis and metabolism, and it has been proposed to be a major factor behind the heterogeneity in the results of clinical trials on omega-3 supplementation and heart disease (Fernandez et al. 2021). It is possible, therefore, that specific genetic polymorphisms significantly influence the effectiveness of nutritional supplements more broadly.

The interaction of nutritional factors also warrants consideration. For example, in a study on omega-3 fatty acid supplementation in ADHD, the authors noted that the arachidonic acid (an omega-6 fatty acid) levels of the children were also low, interfering with beneficial treatment outcomes requiring an optimal balance of the two groups of fatty acids (Voigt et al. 2001). Therefore, aiming for an optimal ratio of supplemented nutrients should be a crucial consideration when planning interventions.

Implementation Facilitators

For interventions using fish oil, it is important to ensure that it is refined to eliminate contaminants such as mercury, since heavy metals also tend to increase aggression (Yıldız et al. 2023). Combining DHA (an omega-3 fatty acid) supplementation with arachidonic acid (an omega-6 fatty acid) supplementation can account for the reduced level of arachidonic acid in certain populations (Voigt et al. 2001). The absorption of several nutrients requires the digestion of fat; consequently, taking supplements containing such nutrients is better in conjunction with meals of adequate fat content.

Developmental factors (pubertal development) and physical activity level should also be considered when managing nutritional disturbances in adolescents, especially with eating disorders (Nicholls and Viner 2005). Ongoing monitoring by a dietitian is a helpful part of any nutritional intervention, including supplementation, which should be obligatory in certain physical health conditions. Dietitians can help supplement users select the most appropriate nutrient amounts and balance nutrient and fluid intake, as well as counsel regarding food-related behaviors and attitudes. Furthermore, it is helpful if dietitians and physicians are aware of the possible food-drug interactions that could occur and should consider using adequate supplements and dosages when combining supplementation with certain pharmacological treatments.