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Diet and food in attention-deficit hyperactivity disorder

Diet and food in attention-deficit hyperactivity disorder
Klaus W. Lange*, Yukiko Nakamura, Andreas Reissmann
Klaus W. Lange*, Yukiko Nakamura, Andreas Reissmann
Department of Experimental Psychology, University of Regensburg, Regensburg 93040, Germany
Department of Experimental Psychology, University of Regensburg, Regensburg 93040, Germany

ARTICLE INFO ABSTRACT

ARTICLE INFO ABSTRACT
Article history: Deficiencies of nutrients, including vitamins, minerals and polyunsaturated fatty acids, and surpluses of food
Article history:
Received 23 December 2021 Deficiencies
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nature The identification
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nature of ADHD.
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to subpopulations disorder,
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with ADHD therapeutic benefied.
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Keywords: of nutritional
The cumulative interventions
benefits of could be confi
the range ned to subpopulations
of ingredients comprising of children
healthy dietswith
mayADHDresult as
in yet unidentifi
better outcomes ed.
Keywords: cit hyperactivity disorder
Attention-defi The cumulative benefits of the range of ingredients comprising
compared to a supplementation of individual nutrients. Diet healthy diets may
and nutrition resultwith
interact in better
otheroutcomes
lifestyle
Attention-defi
Dietary cit hyperactivity disorder
patterns compared to as
a physical
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Diet and nutrition
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Food factors, such
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on treatment interrelationship
approaches to ADHD. between nutrition or
The few-foods andoligoallergenic
lifestyle should play
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design of individually tailored diets andapproaches to ADHD.opportunities
may offer treatment The few-foods or oligoallergenic
in subgroups diet diagnosed
of children allows the
Nutrition
Oligoallergenic diet design of individually tailored isdiets and may offer treatment
with ADHD. Further research required to demonstrate the opportunities in subgroups interventions
utility of nutrition-related of children diagnosed
alone or
Oligoallergenic diet with ADHD. Further research is required to demonstrate
in combination with other treatment approaches in ADHD.the utility of nutrition-related interventions alone or
in combination
© 2022 Beijing
with other treatment
Academy approaches in ADHD.
of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi
© 2022
© 2022 Beijing
Beijing Academy of
Academy
Communications of Food
Food
Co., Ltd.Sciences.
Sciences.
This is anPublishing
Publishing
open accessservices
services byunder
articleby Elsevier
Elsevier B.V.BY-NC-ND
B.V.
the CC on behalf oflicense
KeAi
Communications Co.,
Communications Co., Ltd.
Ltd. This
This is
is an
an open
open access article
access article under
under the
the CC
CC BY-NC-ND
BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/). license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction ADHD has become one of the most common diagnoses in child
1. Introduction and ADHD has psychiatry,
adolescent become onewith of the most common
a prevalence diagnoses
estimated at 3.4% in in
child
the
Considerable evidence points to an important role of nutrition and adolescent psychiatry, with a prevalence estimated
general population [5]. ADHD is increasingly diagnosed in adults and at 3.4% in the
Considerable
in brain evidence
development points to an Observational
and functioning. important rolestudiesof nutrition
have general population [5]. ADHD is increasingly diagnosed in adults and
is regarded by some clinicians as a lifespan condition [5]. The disorder
in brain development and functioning. Observational studies have is
consistently shown that the risk for mental disorders is associated is regarded
complex,by some clinicians
multifactorial andasheterogeneous,
a lifespan condition
with [5].
a wideThediversity
disorder
consistently shown that the risk for mental disorders is associated
with diet quality, and various nutrients have been linked to behavioral, is complex, multifactorial and heterogeneous, with a wide diversity
of behavioral, cognitive, emotional and motivational profiles. The
with diet quality, and various nutrients
as have
well been
as tolinked to behavioral, of behavioral,
affective and cognitive functions the incidence and core symptoms cognitive,
of ADHD emotional and motivational
are age-inappropriate levels of profiles. The
inattention,
affective
prevalence of mental disorders [1,2]. Nutritional deficiencies and
and cognitive functions as well as to the incidence and core symptoms of ADHD are age-inappropriate levels of inattention,
hyperactivity and impulsivity [5]. The disorder is frequently comorbid
prevalence
other dietary of factors
mental disorders
have been[1,2]. Nutritional
suggested to be deficiencies
involved in and the hyperactivity and impulsivity [5]. [6].
The Andisorder is frequently comorbid
with other psychiatric conditions interaction between genetic
other dietaryand
pathogenesis factors have been
management suggested
of common to bedisorders,
mental involvedsuch in the
as with other psychiatric conditions [6]. An interaction between genetic
susceptibility and environmental and social factors is believed to
pathogenesis and management
depression, schizophrenia, of common
autism spectrummental
disorderdisorders, such as
and attention- susceptibility and environmental and social factors is believed to
contribute to the etiology of ADHD. However, biological markers
depression, schizophrenia,
deficit hyperactivity disorderautism
(ADHD)spectrum disorder and
[3,4]. Research attention-
on nutritional contribute to the etiology of ADHD. However, biological markers
underpinning the validity of the concept of ADHD are lacking, and
defi cit hyperactivity disorder (ADHD) [3,4]. Research on nutritional underpinning
approaches in the treatment of ADHD and other mental disorders has no structural orthefunctional
validity of the alterations
brain concept ofcan ADHD are lacking,
be consistently and
found
approaches in the treatment
therefore attracted increasingofscientifi
ADHDc and other
interest mental disorders has
[1]. no structural or functional brain alterations can be consistently found
in individuals diagnosed with ADHD [7]. Since there are no viable
therefore attracted increasing scientific interest [1]. in individuals diagnosed with
biological diagnostic tools, theADHD
diagnosis [7].ofSince
ADHD there are no
relies viable
solely on
*
Corresponding author at: Institute of Psychology, University of Regensburg, Regensburg biological diagnostic tools, the diagnosis of ADHD
clinical symptoms and behavioral assessment. ADHD is diagnosed relies solely on
clinical symptoms and behavioral assessment. ADHD is diagnosed
*
Corresponding author at: Institute of Psychology, University of Regensburg, Regensburg
93040, Germany.
93040, Germany.
above a certain degree of symptom severity combined with significant
E-mail address: [email protected] above a certain degree
life,ofincluding
symptomsocial,severity combined with significant
(K.W. Lange).
E-mail
Peer address:
review [email protected]
under responsibility of (K.W. Lange).
KeAi Communications Co., Ltd. problems in daily academic and occupational
Peer review under responsibility of KeAi Communications Co., Ltd. problems in
dysfunctioning. daily life, including social, academic and occupational
dysfunctioning.

Publishing services by Elsevier

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10.1016/j.jfutfo.2022.03.008
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2772-5669 © 2022 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the
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 Klaus W. Lange et al. / Journal of Future Foods 2-2 (2022) 112–118 113

K.W. Lange et al. / Journal of Future Foods 2 (2022) 112-118 113

Pharmacotherapy with stimulant medications, behavior therapy 2. Dietary patterns in ADHD

and parent management training have consistently been shown to
yield short-term symptom reductions in children and adolescents The role of dietary patterns and whole diets in ADHD has been
with ADHD. However, the extent of efficacy of these therapeutic explored in several cross-sectional and case-control studies (Table 1).
approaches is a matter of debate [8]. Many studies have found A systematic review and meta-analysis of six dietary pattern studies
that ADHD medications administered for several weeks produce (n = 8 816) found that a “healthy” dietary pattern (high in vegetables,
fruits, sea food, polyunsaturated fatty acids, magnesium, zinc and
statistically significant improvement of core symptoms compared
phytochemicals) was associated with a significant decrease in the risk
to placebo, as assessed using rating scales. However, small though
of ADHD (odds ratio: 0.63; 95% confidence interval: 0.41–0.96),
statistically significant effects on symptom scores may not be
while the “Western” (large amounts of confectionery, red meat,
noticeable by patients or physicians and do not therefore necessarily
refined grains, processed meats, fried potatoes, crisps, soft drinks,
equate to any clinically relevant improvements in subjective
animal and hydrogenated fats) (odds ratio: 1.92; 95% confidence
wellbeing or difficulties in daily life [8]. Furthermore, the minimum
interval: 1.13–3.26; P = 0.016) and “junk food” (consisting of
difference in rating scale scores indicating an ecologically relevant chocolate, biscuits, chocolate bars, cakes/buns, pizza, sweets, crisps
effect remains unknown. In particular, the impact of medications on and fizzy drinks) (odds ratio: 1.51; 95% confidence interval: 1.06–2.16;
academic performance and quality of life in children and adolescents P = 0.024) dietary patterns were associated with an increase in the
with ADHD has been found to be low [9]. risk [22]. While the findings of these observational studies emphasize
The pharmacotherapy of ADHD using drugs such as a potential role of dietary patterns in ADHD, the observational study
methylphenidate almost certainly provides some short-term symptom designs are unable to establish a causal relationship between diet and
reduction in children and adolescents with ADHD. However, ADHD. Moreover, associations between adherence to healthy diets
systematic reviews of randomized controlled trials investigating and low prevalence of ADHD do not necessarily imply protective
benefits and harms of methylphenidate for children and adolescents effects of healthy foods consumed during childhood. The mothers of
with ADHD concluded, in view of low quality of outcome measures children consuming a healthy diet may also have adhered to healthy
and possible bias of studies, that the extent of therapeutic efficacy is diets during pregnancy and have provided their children with essential
unclear [8,10]. Randomized controlled trials supporting the long-term nutritional compounds during critical phases of brain development.
administration of psychostimulants for more than a few months are The correlations between dietary habits and ADHD risk may be
lacking [8,10]. Short-term administration of stimulant medications caused by other factors, which were not recorded but were, in fact, the
in ADHD seems to be relatively safe, but little is known about long- causal influences. For example, physical activity and other lifestyle
term safety. Long-term observations have suggested that children factors may correlate with dietary patterns and may be more important
with ADHD who received psychostimulants into adulthood may factors in ADHD symptomatology. Furthermore, reverse causation,
present with reduced height as adults with no ongoing improvement with ADHD behaviors leading to a preference for certain diets,
may also explain the associations observed. Even when statistical
in symptomatology [11]. Given the unproven long-term benefits
adjustment for potential confounding variables was performed,
of medications in the treatment of ADHD, their value may be
residual confounding was still unavoidable. The commonly used
outweighed by their risks [8,10].
food frequency questionnaires are known to contain some degree of
The lack of evidence demonstrating the ability of medications to
measurement error. Moreover, in many studies, the dietary patterns
address the broader clinical needs of many individuals with ADHD
derived from food component analysis explained less than 50% of
has led to a search for improved or alternative therapeutic options.
total variance, suggesting the existence of other patterns.
In particular, lifestyle factors, including diet and nutrition, have
been suggested to play a role in the pathogenesis and management
3. Micronutrients in ADHD
of ADHD [1,12]. For example, greater hyperactivity in hyperactive
children was reported following the consumption of large amounts Brain development requires a sufficient supply of macronutrients
of sucrose [13]. Several observational studies examined this and micronutrients. Dietary deficiencies in essential nutrients may
issue and found that sucrose intake was associated with ADHD contribute to dysfunctioning of brain regions (e.g. prefrontal cortex)
symptoms in children and adolescents [14-16]. It remained unclear, believed to be involved in the pathophysiology of ADHD [31].
however, whether hyperactive behavior was caused by sucrose or Dietary supplementation of certain nutrients rests on the assumption
by the circumstances associated with high sucrose consumption. that individuals with ADHD may be deficient in these nutrients due
Several subsequent studies provided convincing evidence that to low intake or elevated requirement. Investigations in this field
sucrose consumption is not related to ADHD symptoms [17-20]. A have focused mainly on minerals, vitamins and PUFAs. Since several
meta-analysis of relevant trials, which were mainly challenge studies micronutrients serve as cofactors of enzymes required in the synthesis,
using sucrose, glucose or fructose, concluded that sucrose normally has uptake and metabolism of neurotransmitters, metabolic dysfunction
no effects on the behavior or cognitive performance of children [17]. resulting from a reduction in the availability of mineral and vitamin
More recently, dietary patterns and some nutrients, such as such as cofactors may be linked to the symptoms of mental disorders [32].
vitamins, minerals and polyunsaturated fatty acids (PUFAs), have The findings of several observational studies suggest the
been proposed to be helpful in the treatment of ADHD [3,21]. The importance of vitamin D in the pathogenesis of childhood mental
present short review summarizes the currently available evidence for disorders [33]. For example, the mean levels of 25-hydroxyvitamin D
food-based approaches to ADHD. have been shown be significantly reduced in children and adolescents
114 Klaus W. Lange et al. / Journal of Future Foods 2-2 (2022) 112–118

114 K.W. Lange et al. / Journal of Future Foods 2 (2022) 112-118

Table 1
Studies of dietary patterns in ADHD.
Authors, country Sample Findings Conclusion
Two major dietary patterns: “Western” (heavily processed foods rich in total fat, saturated fat, sodium
Population-based cohort
Howard et al., 2011 and refined sugars) and “healthy” (rich in omega-3 fatty acids, fiber and folate; low content of total fat, Positive association of
study. Total of 1 799
[23], saturated fat and refined sugars). Association of Western dietary pattern with ADHD diagnosis (odds Western-style dietary pattern
adolescents; 115 adolescents
Australia ratio: 2.21; 95% confidence interval: 1.18–4.13) after adjusting for known confounding factors. No with ADHD.
with ADHD diagnosis
association of ADHD diagnosis with the healthy dietary pattern.
Four major dietary patterns: “healthy”, “Western”, “sweet” and “fast food”. Greater odds of having
ADHD for children in the top quintile of sweet dietary pattern score compared to those in the lowest
Azadbakht and Positive associations between
Cross-sectional study. quintile (odds ratio: 3.95; 95% confidence interval 1.16–15.31; P = 0.03). Significant association of
Esmaillzadeh sweet and fast-food dietary
375 school-age children greater adherence to fast-food dietary pattern with increased risk of ADHD (odds ratio: 3.21, 95%
2012 [24], Iran patterns and ADHD prevalence.
confidence interval: 1.05–10.90, P = 0.03). No overall significant associations between healthy or
Western dietary patterns and ADHD.

Positive correlation between hyperactivity and dietary intake of processed meat and salty snacks
Cross-sectional study.
Liu et al., 2014 [25], (P < 0.05). Negative correlation between hyperactivity and dietary intake of vegetables, coarse cereals, Association of certain dietary
417 kindergarten-age
China aquatic products, beef, mutton and milk (P < 0.05). Negative correlation between hyperactivity and patterns with hyperactivity.
children
calcium intake (P < 0.05).

Four major dietary patterns: “traditional”, “seaweed-egg,” “traditional-healthy” (high consumption

of kimchi, grains and bonefish, low consumption of fast foods and beverages) and “snack” pattern.
Case-control study. Association of traditional-
Woo et al., 2014 [26], Lower odds ratio for the highest tertile of the traditional-healthy pattern compared to the lowest tertile
192 elementary school healthy dietary pattern with
Korea (odds ratio: 0.31, 95% confidence interval: 0.12–0.79). Positive association between the snack pattern
students aged 7–12 years lower odds of having ADHD
score and ADHD risk. No significant association between ADHD and the traditional and seaweed-egg
dietary patterns.
Case-control study. Inverse association of fish-white meat dietary pattern (rich in shellfish, deep water fish, white meat,
Association of fish-white meat
Zhou et al., 2016 [27], 592 children aged 6–14 freshwater fish, organ meat, fungi and algae) with ADHD (P = 0.006). Inverse association of mineral-
and mineral-protein
China years (296 ADHD, protein nutrient pattern (rich in zinc, protein, phosphorus, selenium, calcium and riboflavin) with
nutrient patterns with ADHD.
296 non-ADHD) ADHD (P = 0.014).
Association of ADHD diagnosis with lower adherence to a Mediterranean diet (odds ratio: 7.07; 95%
Case-control study.
confidence interval: 2.65–18.84; relative risk: 2.80; 95% confidence interval: 1.54–5.25).
Total of 120 children and Association of low adherence
Rios-Hernandez et al., Association of ADHD diagnosis with lower frequency of consuming fruit, vegetables, pasta and rice
adolescents (60 with newly to a Mediterranean diet with
2017 [28], Spain and higher frequency of skipping breakfast and eating at fast-food restaurants (P < 0.05). Association
diagnosed ADHD and 60 ADHD.
of higher prevalence of ADHD diagnosis with high consumption of sugar, candy, cola beverages and
controls)
non-cola soft drinks (P < 0.01) and low consumption of fatty fish (P < 0.05).
Two major dietary patterns: “healthy” (rich in fruits, vegetables, vegetable oils, whole grains, legumes
Association between Western
Case-control study. and dairy products) and “Western” (rich in processed meat, red meat, pizza, eggs, snacks, animal fat,
dietary pattern and odds of
Abbasi et al., 500 preschool- and hydrogenated fat and salt). Greater odds of having ADHD in children in the top quintile of
ADHD. Association of healthy
2018 [29], Iran school-aged children the Western dietary pattern score compared to those in the lowest quintile (odds ratio: 3.45; 95%
dietary pattern with lower odds
(4–12 years) confidence interval: 1.17–18.3; P = 0.03). Inverse association of healthy dietary pattern with ADHD
of ADHD.
(odds ratio: 0.46; 95% confidence interval: 0.38–0.91; P = 0.01).
Five dietary patterns explaining 47.96% of total diet variation.
Positive correlation of processed
Greater odds of ADHD symptoms for preschoolers in the top quintile of the “processed” (odds ratio:
Cross-sectional study. and snack dietary patterns with
Yan et al., 2018 [30], 1.56, 95% confidence interval: 1.31–1.86) and “snack” (odds ration 1.76; 95% confidence interval:
14 912 children aged ADHD symptoms. Negative
China 1.49–2.07) dietary pattern scores compared to those in the lowest quintile. Significantly higher
3–6 years correlation of vegetarian dietary
likelihood of ADHD symptoms in preschoolers with lowest scores on the “vegetarian” dietary pattern
pattern with ADHD symptoms.
(odds ratio: 0.67; 95% confidence interval 0.56–0.79).

with ADHD compared to controls [34-36]. A meta-analysis analysis, undermine their scientific value [39,40]. Other well-designed
of randomized controlled trials, using vitamin D as adjunctive randomized controlled studies found no effects [41,42]. In summary,
intervention to methylphenidate in children with ADHD, showed the available results provide no evidence that the administration of
small, statistically significant improvements in behavior, inattention vitamin mega-doses can ameliorate ADHD symptoms in children.
and hyperactivity [37]. However, these effects were limited by the Possible associations between the status of several minerals, such
low to very low quality of evidence provided by the available as magnesium, iron, zinc, copper and selenium, and the occurrence
studies [37]. Since B vitamins (B6, B9 and B12) are involved of ADHD have been proposed, as has the potential efficacy of
in monoaminergic neurotransmitter synthesis and fatty acid supplementation of these minerals in treating ADHD [43]. Zinc
metabolism [38], deficiencies in these compounds may impair is involved in the synthesis of monoaminergic neurotransmitters,
cognitive functions. Furthermore, the anti-oxidative effects of and deficiencies in zinc and iron may cause cognitive impairment
vitamin C may reduce oxidation in the brain and improve iron in children [44,45]. Observational studies have found trends
absorption. Various studies have examined the potential benefits of towards decreased blood levels of zinc, magnesium and ferritin
the administration of vitamins, which were administered in some in children with ADHD [46-48]. However, the available findings
trials in doses many times above the commonly recommended were inconsistent, possibly resulting from different diagnostic
daily allowance. While some studies reported beneficial effects, parameters [49], heterogeneity of studies or variation in daily intake
severe methodological limitations, such as extremely short of the minerals. It is unknown whether differences in mineral status
intervention periods as well as lack of randomization and statistical are a cause or a consequence of ADHD.
 Klaus W. Lange et al. / Journal of Future Foods 2-2 (2022) 112–118 115

K.W. Lange et al. / Journal of Future Foods 2 (2022) 112-118 115

The effects of supplementation with zinc [50-52], magnesium [53,54] during pregnancy with a high ratio of omega-6 to omega-3 PUFAs
and iron [55,56] have been assessed in several studies. A meta- may increase the risk of subclinical ADHD symptoms in the offspring
analysis of six randomized clinical trials with 489 school-aged during childhood [73].
children diagnosed with ADHD reported a significant effect of zinc A large number of interventional studies have investigated the
supplementation on ADHD total scores, but not on hyperactivity effects of omega-3 fatty acid supplementation on ADHD symptoms.
and inattention scores in comparison with controls [57]. However, As can be seen from the results of meta-analyses of randomized
the certainty of evidence was rated moderate to very low for all controlled trials (Table 2), the evidence for therapeutic efficacy of
outcomes. A significant effect of iron supplementation was found in omega-3 PUFAs regarding the core symptoms of ADHD in children
a small uncontrolled intervention [55,56], while a small randomized and adolescents is marginal or non-existent. Major limitations of the
controlled trial showed no effect on ADHD symptoms [56]. available trials include small sample sizes, short intervention periods,
Magnesium supplementation was found to produce an improvement low dosages of omega-3 PUFAs and multiple testing using many
in ADHD symptoms, but the evidence was undermined by severe evaluation scales without adequate statistical correction. Pre-treatment
methodological flaws, such as lack of randomization and problematic PUFA status may influence the effects of supplementation, and
assessment of ADHD symptoms [53,54]. Taken together, the evidence therapeutically relevant effects may be confined to individuals with
for therapeutic supplementation of minerals in ADHD is insufficient. PUFA deficiency. Taken together, PUFAs cannot be recommended
Several studies used combinations of various vitamins and in the treatment of ADHD. Potential adverse effects of long-term
minerals in children with ADHD and reported improvements in omega-3 PUFA supplementation should be considered [74].
behavioral, cognitive and emotional symptoms [58,59]. However,
these studies used small sample sizes and were highly heterogeneous 5. Future directions
in regard to the individuals included.
It is unclear whether deficiencies in minerals, vitamins or PUFAs
4. PUFAs in ADHD are involved in the pathophysiology of ADHD. Potential effects of
these food compounds may be confined to subgroups of individuals
Deficiencies in and supplementation of omega-3 fatty acids diagnosed with ADHD.
have been demonstrated to affect monoaminergic neurotransmitter Since gut microbiota and probiotics may influence brain activity,
concentrations in the brain [60]. The role of PUFAs in the etiology behavior and mental health [80], the search for factors involved in the
and treatment of ADHD is controversial [21,61,62]. The main focus of pathogenesis of ADHD has recently included the intestinal microbiota
interest has been the long-chain omega-3 fatty acids, docosahexaenoic and the gut-brain axis [81,82]. On the basis of findings in animals,
acid (DHA) and eicosapentaenoic acid (EPA), from fish oil. In both the gut microbiota has been proposed as a potential therapeutic target
animal and human studies, maternal fish oil supplementation during in ADHD [83,84]. Individuals diagnosed with ADHD have been
lactation has been found to be associated with physical activity and found to have a different composition of the intestinal microbiota
attention in the offspring [63,64]. Blood plasma concentrations compared to healthy controls, with certain bacteria being more
of DHA, EPA and arachidonic acid have been reported to be and others being less abundant [85]. Preliminary evidence derived
significantly reduced in children and adolescents with ADHD [65-70]. from a few intervention studies suggests preventive and possibly
Furthermore, children with ADHD symptoms have been found therapeutic effects of probiotics in ADHD [86,87]. However,
to have elevated ratios of omega-6 to omega-3 PUFAs compared the potential role of the microbiome in the pathophysiology of
to children without symptoms [65,70-72]. The results of a ADHD and of probiotics in the prevention and treatment of ADHD
population-based birth cohort study suggest that a maternal diet requires further large-scale trials.

Table 2
Meta-analyses of intervention trials of PUFAs in ADHD.
Authors Studies included Findings
Small but significant effect in improving ADHD symptoms following
Bloch and Qawasmi, 2011 10 randomized controlled omega-3 PUFA trials
omega-3 PUFA supplementation.
[75] (699 children).
EPA dosage significantly correlated with supplement efficacy.

No statistically significant differences in parent-rated ADHD symptoms,

Total of 13 randomozed controlled trials (1011 children and adolescents):
inattention or hyperactivity/impulsivity between PUFA supplements
8 trials with parallel design; 5 comparisons of omega-3 PUFA supplement with
and placebo. No statistically significant differences in teacher ratings of
Gillies et al., 2012 [76] placebo; 2 comparisons of combined omega-3 and omega-6 supplement to
overall ADHD symptoms, inattention or hyperactivity/impulsivity. Overall
placebo; 1 comparison of omega-3 PUFA to dietary supplement. 5 trials with
little evidence of any benefit for the symptoms of ADHD in children and
cross-over design.
adolescents following PUFA supplementation.

11 randomized controlled PUFA supplementation trials (5 using omega-3

Small but significant reductions in ADHD symptoms following PUFA
Sonuga-Barke et al., 2013 [77] supplements, 2 using omega-6 supplements, 4 using both omega-3 and omega-6
supplementation. Clinical significance of effects unclear.
supplements). All trials probably blinded.

Improvement of ADHD composite symptoms following omega-3 PUFA

16 randomized, single or double blind trials using
Hawkey and Nigg, 2014 [78] supplementation; reliable effects on hyperactivity by parent and teacher
omega-3 PUFAs (1,408 children).
report; reliable effects on inattention only by parent report.
Pooling of results of new randomized controlled study (148 children) with those
Cornu et al., 2018 [79] No overall effect of DHA + EPA in ADHD rating scale.
reported by Gillies et al. [76] and Hawkey and Nigg [78].
116 Klaus W. Lange et al. / Journal of Future Foods 2-2 (2022) 112–118

116 K.W. Lange et al. / Journal of Future Foods 2 (2022) 112-118

Following first studies in the 1970s, more recent evidence based on to subpopulations of children with ADHD as yet unidentified. The
a large, well-designed randomized controlled study has sparked interest cumulative benefits of the range of ingredients comprising healthy
in the idea that food additives, such as artificial colors or a sodium diets, such as the Mediterranean diet, may result in better outcomes
benzoate preservative, may trigger hyperactivity in children [88]. compared to a supplementation of individual nutrients. However,
Several meta-analyses have reported that artificial food colors establishing and maintaining adherence to longer-term changes
have small, but statistically significant adverse effects on ADHD in whole diets beyond nutrient supplementation would be a major
symptoms in some children [77,89-91]. However, the exclusion challenge. Diet and nutrition interact and overlap with other lifestyle
of artificial food colorants may be limited to children selected for factors, such as physical activity. Children with ADHD may benefit
food sensitivities [77]. Future studies should attempt to identify from generally improved lifestyle choices, and the interrelationship
subgroups of individuals diagnosed with ADHD who may benefit between nutrition and lifestyle should play a more prominent role in
from the exclusion of food additives. research on treatment approaches to ADHD.
Some children with ADHD have been hypothesized to show In summary, there is no conclusive evidence supporting the
sensitivity or allergic reactions to various other food items [92]. efficacy of dietary interventions eliminating or supplementing single
This hypothesis has led to the development of the few-foods or nutrients in reducing symptoms of ADHD. However, the few-foods
oligoallergenic diet. A strict elimination diet excluding many food or oligoallergenic diet provides a diagnostic tool in the identification
items has been found to be a valuable tool in assessing whether of children with sensitivity to certain foods. This diet holds some
symptoms of ADHD are induced by individual foods [93]. The promise in improving symptoms of ADHD and providing a novel
few-foods or oligoallergenic diet eliminates and subsequently re- personalized dietary treatment approach.
introduces single foods one at a time. The initial elimination of the
majority of food items from the diet for a limited period of time helps Declaration of interest
determine whether food is a trigger of ADHD. Children responding
to the few-foods diet show improvements in behavior or cognitive We declare that there is no conflict of interest. In particular,
performance following a few weeks on this diet. In responders, there are no financial and personal relationships with other people or
food items are consecutively added in a controlled way in order to organizations that could inappropriately influence (bias) our work.
determine which foods are related to adverse reactions or symptoms.
Finally, an individualized diet eliminating the incriminated foods References
only is composed. Several double-blind placebo-controlled studies
[1] K.W. Lange, Diet, exercise, and mental disorders - public health challenges
assessing the effects of the few-foods diet in children with ADHD of the future, Mov. Nutr. Health Dis. 2 (2018) 39-59. https://doi.org/10.5283/
have consistently demonstrated the role of foods in triggering ADHD, MNHD.12.
suggesting the existence of a food-related subtype of ADHD [94]. [2] W. Marx, G. Moseley, M. Berk, et al., Nutritional psychiatry: the
present state of the evidence, Proc. Nutr. Soc. 76 (2017) 427-436.
Furthermore, in a randomized controlled trial, considerable effects https://doi.org/10.1017/S0029665117002026.
of the few-foods diet have been reported in an unselected sample of [3] K.W. Lange, Micronutrients and diets in the treatment of attention-deficit/
children diagnosed with ADHD [93]. The major point in favor of the hyperactivity disorder: chances and pitfalls, Front. Psychiatry 11 (2020) 102.
https://doi.org/10.3389/fpsyt.2020.00102.
few-foods approach is the design of an individually tailored diet. The
[4] J. Sarris, A.C. Logan, T.N. Akbaraly, et al., Nutritional medicine
available evidence suggests that this promising personalized diet- as mainstream in psychiatry, Lancet Psychiatry 2 (2015) 271-274.
based therapeutic approach deserves further systematic investigation. https://doi.org/10.1016/S2215-0366(14)00051-0.
[5] A. Thapar, M. Cooper, Attention deficit hyperactivity disorder, Lancet 387
(2016) 1240-1250. https://doi.org/10.1016/S0140-6736(15)00238-X.
6. Conclusion [6] C.M. Jensen, H.C. Steinhausen, Comorbid mental disorders in children
and adolescents with attention-deficit/hyperactivity disorder in a large
The current pharmacological treatment of people diagnosed with nationwide study, Atten. Defic. Hyperact. Disord. 7 (2015) 27-38.
https://doi.org/10.1007/s12402-014-0142-1.
ADHD is unsatisfactory. Insufficient evidence of the effectiveness of
[7] B. Wankerl, J. Hauser, E. Makulska-Gertruda, et al., Neurobiology of
commonly used ADHD medications on clinically and ecologically attention deficit hyperactivity disorder, Fortschr. Neurol. Psychiatr. 82 (2014)
relevant outcome measures as well as the unproven long-term efficacy 9-29. https://doi.org/10.1055/s-0033-1355710.
and potentially problematic adverse effects of drug treatment have [8] K.W. Lange, The treatment of attention deficit hyperactivity disorder has no
proven long-term benefits but possible adverse effects, Mov. Nutr. Health
led to a search for alternative treatment options such as dietary Dis. (2017) 11-25. https://doi.org/10.5283/mnhd.4.
interventions. [9] A.F. Kortekaas-Rijlaarsdam, M. Luman, E. Sonuga-Barke, et al., Does
Deficiencies of nutrients, including vitamins, minerals and methylphenidate improve academic performance? A systematic review
and meta-analysis, Eur. Child Adolesc. Psychiatry 28 (2019) 155-164.
PUFAs, and surpluses of food items, such as sucrose and artificial
https://doi.org/10.1007/s00787-018-1106-3.
food additives, have not convincingly been shown to be involved in [10] O.J. Storebø, E. Faltinsen, M. Zwi, et al., The jury is still out on the benefits
the etiology of ADHD. Evidence supporting the therapeutic efficacy and harms of methylphenidate for children and adolescents with attention-
of single nutrients, including vitamins, minerals and PUFAs, in deficit/hyperactivity disorder, Clin. Pharmacol. Ther. 104 (2018) 606-609.
https://doi.org/10.1002/cpt.1149.
ADHD is unavailable. The identification of a role of food compounds [11] J.M. Swanson, L.E. Arnold, B.S.G. Molina, et al., Young adult outcomes
in ADHD is hindered by the complex and ill-defined nature of ADHD in the follow-up of the multimodal treatment study of attention-deficit/
as well as the lack of biological markers underpinning the validity of hyperactivity disorder: symptom persistence, source discrepancy, and
height suppression, J. Child Psychol. Psychiatry 58 (2017) 663-678.
the diagnosis. In view of the heterogeneity of the disorder in terms
https://doi.org/10.1111/jcpp.12684.
of etiology, pathophysiology and clinical presentation, potential [12] K.W. Lange, Lifestyle and attention deficit/hyperactivity disorder, Mov.
therapeutic benefits of nutritional interventions could be confined Nutr. Health Dis. 2 (2018) 22-30. https://doi.org/10.5283/mnhd.10.
 Klaus W. Lange et al. / Journal of Future Foods 2-2 (2022) 112–118 117

K.W. Lange et al. / Journal of Future Foods 2 (2022) 112-118 117

[13] R.J. Prinz, W.A. Roberts, E. Hantman, Dietary correlates of hyperactive [35] E. Kotsi, E. Kotsi, D.N. Perrea, Vitamin D levels in children and adolescents
behavior in children, J. Consult. Clin. Psychol. 48 (1980) 760-769. with attention-deficit hyperactivity disorder (ADHD): a meta-analysis, Atten.
https://doi.org/10.1037//0022-006x.48.6.760. Defic. Hyperact. Disord. 11 (2019) 221-232. https://doi.org/10.1007/s12402-
[14] Y. Kim, H. Chang, Correlation between attention deficit hyperactivity 018-0276-7.
disorder and sugar consumption, quality of diet, and dietary behavior in [36] T. Meyer, A. Becker, J. Sundermann, et al., Attention deficit-hyperactivity
school children, Nutr. Res. Pract. 5 (2011) 236-245. https://doi.org/10.4162/ disorder is associated with reduced blood pressure and serum vitamin D levels:
nrp.2011.5.3.236. results from the nationwide German Health Interview and Examination Survey
[15] L. Lien, N. Lien, S. Heyerdahl, et al., Consumption of soft drinks for Children and Adolescents (KiGGS), Eur. Child Adolesc. Psychiatry 26
and hyperactivity, mental distress, and conduct problems among (2017) 165-175. https://doi.org/10.1007/s00787-016-0852-3.
adolescents in Oslo, Norway, Am. J. Public Health 96 (2006) 1815-1820. [37] J. Gan, P. Galer, D. Ma, et al., The effect of vitamin D supplementation
https://doi.org/10.2105/AJPH.2004.059477. on attention-deficit/hyperactivity disorder: a systematic review and meta-
[16] J.A. Goldman, R.H. Lerman, J.H. Contois, et al., Behavioral effects of analysis of randomized controlled trials, J. Child Adolesc. Psychopharmacol.
sucrose on preschool children, J. Abnorm. Child Psychol. 14 (1986) 565- 29 (2019) 670-687. https://doi.org/10.1089/cap.2019.0059.
577. https://doi.org/10.1007/BF01260524. [38] D.O. Kennedy, C.F. Haskell, Vitamins and cognition: what is the evidence?,
[17] M.L. Wolraich, D.B. Wilson, J.W. White, The effect of sugar on behavior Drugs 71 (2011) 1957-1971. https://doi.org/10.2165/11594130-000000000-
or cognition in children. A meta-analysis, JAMA 274 (1995) 1617-1621. 00000.
https://doi.org/10.1001/jama.1995.03530200053037. [39] K.L. Harding, R.D. Judah, C. Gant, Outcome-based comparison of ritalin
[18] M.L. Wolraich, S.D. Lindgren, P.J. Stumbo, et al., Effects of diets high versus food-supplement treated children with AD/HD, Altern. Med. Rev. 8
in sucrose or aspartame on the behavior and cognitive performance of (2003) 319-330.
children, N. Engl. J. Med. 330 (1994) 301-307. https://doi.org/10.1056/ [40] A. Brenner, The effects of megadoses of selected B complex
NEJM199402033300501. vitamins on children with hyperkinesis: controlled studies with
[19] M. Wolraich, R. Milich, P. Stumbo, et al., Effects of sucrose ingestion long-term follow-up, J. Learn. Disabil. 15 (1982) 258-264.
on the behavior of hyperactive boys, J. Pediatr. 106 (1985) 675-682. https://doi.org/10.1177/002221948201500501.
https://doi.org/10.1016/s0022-3476(85)80102-5. [41] R.H. Haslam, J.T. Dalby, A.W. Rademaker, Effects of megavitamin therapy
[20] J.W. White, M. Wolraich, Effect of sugar on behavior and on children with attention deficit disorders, Pediatrics 74 (1984) 103-111.
mental performance, Am. J. Clin. Nutr. 62 (1995) 242S-247S. [42] L.E. Arnold, J. Christopher, R.D. Huestis, et al., Megavitamins for minimal brain
https://doi.org/10.1093/ajcn/62.1.242S. dysfunction. A placebo-controlled study, JAMA 240 (1978) 2642-2643.
[21] K.W. Lange, Dietary factors in the etiology and therapy of attention deficit/ [43] H. Robberecht, A.A.J. Verlaet, A. Breynaert, et al., Magnesium, iron,
hyperactivity disorder, Curr. Opin. Clin. Nutr. Metab. Care 20 (2017) 464- zinc, copper and selenium status in attention-deficit/hyperactivity
469. https://doi.org/10.1097/MCO.0000000000000415. disorder (ADHD), Molecules 25 (2020) 4440. https://doi.org/10.3390/
[22] E. Shareghfarid, Z.S. Sangsefidi, A. Salehi-Abargouei, et al., Empirically
molecules25194440.
derived dietary patterns and food groups intake in relation with attention
[44] B. Lozoff, J. Beard, J. Connor, et al., Long-lasting neural and behavioral
deficit/hyperactivity disorder (ADHD): a systematic review and meta-
effects of iron deficiency in infancy, Nutr. Rev. 64 (2006) S34-S43.
analysis, Clin. Nutr. ESPEN 36 (2020) 28-35. https://doi.org/10.1016/
https://doi.org/10.1301/nr.2006.may.s34-s43.
j.clnesp.2019.10.013.
[45] A.M. DiGirolamo, M. Ramirez-Zea, Role of zinc in maternal and child
[23] A.L. Howard, M. Robinson, G.J. Smith, et al., ADHD is associated with a
mental health, Am. J. Clin. Nutr. 89 (2009) 940S-945S. https://doi.
“Western” dietary pattern in adolescents, J. Atten. Disord. 15 (2011) 403-
org/10.3945/ajcn.2008.26692C.
411. https://doi.org/10.1177/1087054710365990.
[46] T. Kozielec, B. Starobrat-Hermelin, Assessment of magnesium levels in
[24] L. Azadbakht, A. Esmaillzadeh, Dietary patterns and attention deficit
children with attention deficit hyperactivity disorder (ADHD), Magnes. Res.
hyperactivity disorder among Iranian children, Nutrition 28 (2012) 242-249.
10 (1997) 143-148.
https://doi.org/10.1016/j.nut.2011.05.018.
[47] M. Juneja, R. Jain, V. Singh, et al., Iron deficiency in Indian children with
[25] J. Liu, P. He, L. Li, et al., Study on the association between diet, nutrient
attention deficit hyperactivity disorder, Indian Pediatr. 47 (2010) 955-958.
and attention deficit hyperactivity disorder among children from three
https://doi.org/10.1007/s13312-010-0160-9.
kindergartens in Shanghai, Kunshan and Wuxi, J. Hygiene Res. (Wei Sheng
[48] L.E. Arnold, H. Bozzolo, J. Hollway, et al., Serum zinc correlates with
Yan Jiu) 43 (2014) 235-239.
[26] H. Woo, D. Kim, Y.-S. Hong, et al., Dietary patterns in children with parent- and teacher-rated inattention in children with attention-deficit/
attention deficit/hyperactivity disorder (ADHD), Nutrients 6 (2014) 1539- hyperactivity disorder, J. Child Adolesc. Psychopharmacol. 15 (2005) 628-
1553. https://doi.org/10.3390/nu6041539. 636. https://doi.org/10.1089/cap.2005.15.628.
[27] F. Zhou, F. Wu, S. Zou, et al., Dietary, nutrient patterns and blood [49] S.V. Faraone, C. Bonvicini, C. Scassellati, Biomarkers in the diagnosis
essential elements in chinese children with ADHD, Nutrients 8 (2016) 352. of ADHD--promising directions, Curr. Psychiatry Rep. 16 (2014) 497.
https://doi.org/10.3390/nu8060352. https://doi.org/10.1007/s11920-014-0497-1.
[28] A. Rios-Hernandez, J.A. Alda, A. Farran-Codina, et al., The Mediterranean [50] M. Bilici, F. Yildirim, S. Kandil, et al., Double-blind, placebo-controlled
diet and ADHD in children and adolescents, Pediatrics 139 (2017) study of zinc sulfate in the treatment of attention deficit hyperactivity
e20162027. https://doi.org/10.1542/peds.2016-2027. disorder, Prog. Neuropsychopharmacol. Biol. Psychiatry 28 (2004) 181-190.
[29] K. Abbasi, S. Beigrezai, R. Ghiasvand, et al., Dietary patterns and attention deficit https://doi.org/10.1016/j.pnpbp.2003.09.034.
hyperactivity disorder among Iranian children: a case-control study, J. Am. Coll. [51] L.E. Arnold, R.A. DiSilvestro, D. Bozzolo, et al., Zinc for attention-deficit/
Nutr. 38 (2019) 76-83. https://doi.org/10.1080/07315724.2018.1473819. hyperactivity disorder: placebo-controlled double-blind pilot trial alone and
[30] S. Yan, H. Cao, C. Gu, et al., Dietary patterns are associated with combined with amphetamine, J. Child Adolesc. Psychopharmacol. 21 (2011)
attention-deficit/hyperactivity disorder (ADHD) symptoms among 1-19. https://doi.org/10.1089/cap.2010.0073.
preschoolers in mainland China, Eur. J. Clin. Nutr. 72 (2018) 1517-1523. [52] S. Akhondzadeh, M.-R. Mohammadi, M. Khademi, Zinc sulfate as an
https://doi.org/10.1038/s41430-018-0131-0. adjunct to methylphenidate for the treatment of attention deficit hyperactivity
[31] M.M. Glanzman, ADHD and nutritional supplements, Curr. Atten. Disord. disorder in children: a double blind and randomized trial ISRCTN64132371,
Rep. 1 (2009) 75-81. https://doi.org/10.1007/s12618-009-0011-6. BMC Psychiatry 4 (2004) 9. https://doi.org/10.1186/1471-244X-4-9.
[32] B.N. Ames, I. Elson-Schwab, E.A. Silver, High-dose vitamin therapy [53] B. Starobrat-Hermelin, T. Kozielec, The effects of magnesium physiological
stimulates variant enzymes with decreased coenzyme binding affinity supplementation on hyperactivity in children with attention deficit
(increased K(m)): relevance to genetic disease and polymorphisms, Am. J. hyperactivity disorder (ADHD). Positive response to magnesium oral loading
Clin. Nutr. 75 (2002) 616-658. https://doi.org/10.1093/ajcn/75.4.616. test, Magnes. Res. 10 (1997) 149-156.
[33] M. Föcker, J. Antel, S. Ring, et al., Vitamin D and mental health in children [54] M. Mousain-Bosc, M. Roche, A. Polge, et al., Improvement of
and adolescents, Eur. Child Adolesc. Psychiatry 26 (2017) 1043-1066. neurobehavioral disorders in children supplemented with magnesium-vitamin
https://doi.org/10.1007/s00787-017-0949-3. B6. I. Attention deficit hyperactivity disorders, Magnes. Res. 19 (2006) 46-52.
[34] A.M. García-Serna, E. Morales, Neurodevelopmental effects of prenatal [55] Y. Sever, A. Ashkenazi, S. Tyano, et al., Iron treatment in children
vitamin D in humans: systematic review and meta-analysis, Mol. Psychiatry with attention deficit hyperactivity disorder. A preliminary report,
25 (2020) 2468-2481. https://doi.org/10.1038/s41380-019-0357-9. Neuropsychobiology 35 (1997) 178-180. https://doi.org/10.1159/000119341.
118 Klaus W. Lange et al. / Journal of Future Foods 2-2 (2022) 112–118

118 K.W. Lange et al. / Journal of Future Foods 2 (2022) 112-118

[56] E. Konofal, M. Lecendreux, J. Deron, et al., Effects of iron supplementation [76] D. Gillies, J.K. Sinn, S.S. Lad, et al., Polyunsaturated fatty acids
on attention deficit hyperactivity disorder in children, Pediatr. Neurol. 38 (PUFA) for attention deficit hyperactivity disorder (ADHD) in children
(2008) 20-26. https://doi.org/10.1016/j.pediatrneurol.2007.08.014. and adolescents, Cochrane Database Syst. Rev. (2012) CD007986.
[57] S. Talebi, M. Miraghajani, A. Ghavami, et al., The effect of zinc https://doi.org/10.1002/14651858.CD007986.pub2.
supplementation in children with attention deficit hyperactivity disorder: a [77] E.J.S. Sonuga-Barke, D. Brandeis, S. Cortese, et al., Nonpharmacological
systematic review and dose-response meta-analysis of randomized clinical interventions for ADHD: systematic review and meta-analyses of randomized
trials, Crit. Rev. Food Sci. Nutr. (2021) 1-10. https://doi.org/10.1080/104083 controlled trials of dietary and psychological treatments, Am. J. Psychiatry
98.2021.1940833. 170 (2013) 275-289. https://doi.org/10.1176/appi.ajp.2012.12070991.
[58] M. Hemamy, M. Heidari-Beni, G. Askari, et al., Effect of vitamin D [78] E. Hawkey, J.T. Nigg, Omega-3 fatty acid and ADHD: Blood level analysis
and magnesium supplementation on behavior problems in children with and meta-analytic extension of supplementation trials, Clin. Psychol. Rev. 34
attention-deficit hyperactivity disorder, Int. J. Prev. Med. 11 (2020) 4. (2014) 496-505. https://doi.org/10.1016/j.cpr.2014.05.005.
https://doi.org/10.4103/ijpvm.IJPVM_546_17. [79] C. Cornu, C. Mercier, T. Ginhoux, et al., A double-blind placebo-controlled
[59] K.A. Darling, M.J.F. Eggleston, H. Retallick-Brown, et al., Mineral-vitamin randomised trial of omega-3 supplementation in children with moderate
treatment associated with remission in attention-deficit/hyperactivity disorder ADHD symptoms, Eur. Child Adolesc. Psychiatry 27 (2018) 377-384.
symptoms and related problems: 1-year naturalistic outcomes of a 10-week https://doi.org/10.1007/s00787-017-1058-z.
randomized placebo-controlled trial, J. Child Adolesc. Psychopharmacol. 29 [80] K.W. Lange, K.M. Lange, Y. Nakamura, et al., Is there a role of
(2019) 688-704. https://doi.org/10.1089/cap.2019.0036. gut microbiota in mental health?, J. Food Bioact. 9 (2020) 4-9.
[60] C. Transler, S. Mitchell, A. Eilander, Could polyunsaturated fatty https://doi.org/10.31665/JFB.2020.9213.
acids deficiency explain some dysfunctions found in ADHD? [81] K.M.J. van Loo, G.J.M. Martens, Genetic and environmental factors in
Hypotheses from animal research, J. Atten. Disord. 17 (2013) 20-28. complex neurodevelopmental disorders, Curr. Genomics 8 (2007) 429-444.
https://doi.org/10.1177/1087054711401345. https://doi.org/10.2174/138920207783591717.
[61] K.W. Lange, J. Hauser, K.M. Lange, et al., The role of nutritional [82] M.C. Cenit, I.C. Nuevo, P. Codoñer-Franch, et al., Gut microbiota and
supplements in the treatment of ADHD: what the evidence says, Curr. attention deficit hyperactivity disorder: new perspectives for a challenging
Psychiatry Rep. 19 (2017) 8. https://doi.org/10.1007/s11920-017-0762-1. condition, Eur. Child Adolesc. Psychiatry 26 (2017) 1081-1092. https://doi.
[62] K.W. Lange, Do food bioactives play a role in attention-deficit/ hyperactivity org/10.1007/s00787-017-0969-z.
disorder? J. Food Bioact. 4 (2018) 1-7. https://doi.org/10.31665/ [83] P. Luczynski, K.A. McVey Neufeld, C.S. Oriach, et al., Growing up in a
JFB.2018.4160. bubble: using germ-free animals to assess the influence of the gut microbiota
[63] M.F. Delgado-Noguera, J.A. Calvache, X. Bonfill Cosp, Supplementation on brain and behavior, Int. J. Neuropsychopharmacol. 19 (2016) 1-17.
with long chain polyunsaturated fatty acids (LCPUFA) to breastfeeding mothers https://doi.org/10.1093/ijnp/pyw020.
for improving child growth and development, Cochrane Database Syst. Rev.
[84] J.F. Cryan, T.G. Dinan, More than a gut feeling: the microbiota regulates
(2010) CD007901. https://doi.org/10.1002/14651858.CD007901.pub2.
neurodevelopment and behavior, Neuropsychopharmacology 40 (2015) 241-
[64] M. Asserhøj, S. Nehammer, J. Matthiessen, et al., Maternal fish oil
242. https://doi.org/10.1038/npp.2014.224.
supplementation during lactation may adversely affect long-term blood
[85] S. Bull-Larsen, M.H. Mohajeri, The potential influence of the bacterial
pressure, energy intake, and physical activity of 7-year-old boys, J. Nutr. 139
microbiome on the development and progression of ADHD, Nutrients 11
(2009) 298-304. https://doi.org/10.3945/jn.108.095745.
(2019) 2805. https://doi.org/10.3390/nu11112805.
[65] L.J. Stevens, S.S. Zentall, J.L. Deck, et al., Essential fatty acid metabolism
[86] H.G. Kumperscak, A. Gricar, I. Ülen, et al., A pilot randomized control trial
in boys with attention-deficit hyperactivity disorder, Am. J. Clin. Nutr. 62
with the probiotic strain Lactobacillus rhamnosus GG (LGG) in ADHD:
(1995) 761-768.
children and adolescents report better health-related quality of life, Front.
[66] E.A. Mitchell, M.G. Aman, S.H. Turbott, et al., Clinical characteristics and
Psychiatry 11 (2020) 181. https://doi.org/10.3389/fpsyt.2020.00181.
serum essential fatty acid levels in hyperactive children, Clin. Pediatr. 26
[87] A. Pärtty, M. Kalliomäki, P. Wacklin, et al., A possible link between
(1987) 406-411.
early probiotic intervention and the risk of neuropsychiatric disorders
[67] A.L. Colter, C. Cutler, K. Meckling, Fatty acid status and behavioural
later in childhood: a randomized trial, Pediatr. Res. 77 (2015) 823-828.
symptoms of attention deficit hyperactivity disorder in adolescents: a case-
https://doi.org/10.1038/pr.2015.51.
control study, Nutr. J. 7 (2008) 8. https://doi.org/10.1186/1475-2891-7-8.
[88] D. McCann, A. Barrett, A. Cooper, et al., Food additives and hyperactive
[68] J.R. Chen, S.F. Hsu, C.D. Hsu, et al., Dietary patterns and blood fatty
acid composition in children with attention-deficit hyperactivity disorder behaviour in 3-year-old and 8/9-year-old children in the community: a
in Taiwan, J. Nutr. Biochem. 15 (2004) 467-472. https://doi.org/10.1016/ randomised, double-blinded, placebo-controlled trial, Lancet 370 (2007)
j.jnutbio.2004.01.008. 1560-1567. https://doi.org/10.1016/S0140-6736(07)61306-3.
[69] J.R. Burgess, L. Stevens, W. Zhang, et al., Long-chain polyunsaturated fatty [89] D.W. Schab, N.H.T. Trinh, Do artificial food colors promote hyperactivity
acids in children with attention-deficit hyperactivity disorder, Am. J. Clin. in children with hyperactive syndromes? A meta-analysis of double-
Nutr. 71 (2000) 327S-330S. https://doi.org/10.1093/ajcn/71.1.327S. blind placebo-controlled trials, J. Dev. Behav. Pediatr. 25 (2004) 423-434.
[70] C.J. Antalis, L.J. Stevens, M. Campbell, et al., Omega-3 fatty acid status in https://doi.org/10.1097/00004703-200412000-00007.
attention-deficit/hyperactivity disorder, Prostaglandins Leukot. Essent. Fatty [90] J.T. Nigg, K. Lewis, T. Edinger, et al., Meta-analysis of attention-
Acids 75 (2006) 299-308. https://doi.org/10.1016/j.plefa.2006.07.004. deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder
[71] N. Parletta, T. Niyonsenga, J. Duff, Omega-3 and omega-6 polyunsaturated symptoms, restriction diet, and synthetic food color additives, J. Am.
fatty acid levels and correlations with symptoms in children with attention Acad. Child Adolesc. Psychiatry 51 (2012) 86-97. https://doi.org/10.1016/
deficit hyperactivity disorder, autistic spectrum disorder and typically j.jaac.2011.10.015.
developing controls, PLoS ONE 11 (2016) e0156432. [91] K.A. Kavale, S.R. Forness, Hyperactivity and diet treatment: a meta-
[72] L. LaChance, K. McKenzie, V.H. Taylor, et al., Omega-6 to omega-3 fatty analysis of the Feingold hypothesis, J. Learn. Disabil. 16 (1983) 324-330.
acid ratio in patients with ADHD: a meta-analysis, J. Can. Acad. Child https://doi.org/10.1177/002221948301600604.
Adolesc. Psychiatry 25 (2016) 87-96. [92] L.M.J. Pelsser, J.K. Buitelaar, H.F.J. Savelkoul, ADHD as a (non) allergic
[73] M. López-Vicente, N. Ribas Fitó, N. Vilor-Tejedor, et al., Prenatal omega- hypersensitivity disorder: a hypothesis, Pediatr. Allergy Immunol. 20 (2009)
6:omega-3 ratio and attention deficit and hyperactivity disorder symptoms, J. 107-112. https://doi.org/10.1111/j.1399-3038.2008.00749.x.
Pediatr. 209 (2019) 204-211. https://doi.org/10.1016/j.jpeds.2019.02.022. [93] L.M. Pelsser, K. Frankena, J. Toorman, et al., Effects of a restricted
[74] K.W. Lange, Y. Nakamura, A.M. Gosslau, et al., Are there serious adverse elimination diet on the behaviour of children with attention-deficit
effects of omega-3 polyunsaturated fatty acid supplements?, J. Food Bioact. hyperactivity disorder (INCA study): a randomised controlled trial, Lancet
7 (2019) 1-6. https://doi.org/10.31665/JFB.2019.7192. 377 (2011) 494-503. https://doi.org/10.1016/S0140-6736(10)62227-1.
[75] M.H. Bloch, A. Qawasmi, Omega-3 fatty acid supplementation for [94] L.M. Pelsser, K. Frankena, J. Toorman, et al., Diet and ADHD, reviewing
the treatment of children with attention-deficit/hyperactivity disorder the evidence: a systematic review of meta-analyses of double-blind
symptomatology: systematic review and meta-analysis, J. Am. Acad. placebo-controlled trials evaluating the efficacy of diet interventions on
Child Adolesc. Psychiatry 50 (2011) 991-1000. https://doi.org/10.1016/ the behavior of children with ADHD, PLoS ONE 12 (2017) e0169277.
j.jaac.2011.06.008. https://doi.org/10.1371/journal.pone.0169277.