Efficacy of vitamin/mineral supplement on children with Down syndrome and autism spectrum disorder

Abstract

Objectives

The management of language deficits and therapeutic efficacy of micronutrients supplementation in improving presentations in Down syndrome (DS) and autistic children are very challenging. The aim of this open-label study is to explore the effect of micronutrients supplementation together with language stimulating environment on language abilities, the severity of autism spectrum spectrum (ASD) presentations, and on serum levels of some micronutrients and serotonin in these children.

Methods

DS and autistic children (N = 57) who presented with intellectual disability and developmental language delay were subjected to assessment of the language abilities, severity of autism in ASD participants, in addition to measuring of serum levels of iron, magnesium, B6, B12, and serotonin level by ELISA before and after 16 wk of an oral once-per-day dietary supplementation, together with a home-based language stimulation. The supplement included vitamins (B complex, E, C), trace minerals (Iron, magnesium, zinc), and other nutrients.

Results

All the participants showed improved language abilities (p = 0.01). Autistic children showed reduced autism severity (p = 0.005). Increased levels of iron, magnesium, vitamin B6, and serotonin in the serum after supplementation have been observed (p ≤ 0.05).

Conclusions

This research provides further support for the benefits of dietary supplementation with home-based language stimulation for DS and autistic children.

Introduction

Despite differences in the symptoms defining children having Down syndrome (DS) and autism spectrum disorder (ASD), both disorders share some presentations and biochemical alterations. The etiology of DS has been determined and attributed to the extra copy of chromosome 21. Being the most common neurodevelopmental genetic disorder brings with it a challenge for health professionals to optimize the health of children with DS throughout their lives (Bull et al. 2022). On the other hand, the etiology of ASD is still mysterious despite linking some genetic and environmental factors to its occurrence (Nasser et al. 2022). Many children with DS and ASD present with co-occurring intellectual disability (ID), developmental language delay (DLD), behavioral problems, anxiety, and sleep disorder. Moreover, autistic patterns of behavior have been previously reported in some individuals having DS (Bull et al. 2022). Furthermore, both disorders exhibit a rise in oxidative stress markers and alterations in some neurotransmitters level. Serotonin (5-HT) is one of the neurotransmitters which was reported to be altered in both DS and ASD (Das et al. 2014; Garbarino et al. 2019).

In developing brains, 5-HT was found to act as a growth factor in addition to a neurotransmitter, which influence cortical organization, axonal growth, synapse formation, and neuronal and glia proliferation (Abdulamir, Abdul-Rasheed, and Abdulghani 2018). Low level of 5-HT was linked to depression and regression of cognitive abilities in DS individuals (Mircher et al. 2017). Furthermore, low blood serotonin levels were detected in some children having ASD (Meguid, Gebril, and Khalil 2015). Low levels of serotonin were found to be linked to disturbed sleep, social and cognitive problems described in autistic children (Garbarino et al. 2019).

Intellectual disability (ID) and DLD are considerable concerns, which are commonly reported in DS and autistic children. ID is a disorder in intellectual and adaptive functioning of individuals, which develop before the age of eighteen years. DLD is impairment in the processing of linguistic information, which affects the child’s ability in receptive and/or expressive language (American Psychiatric Association, 2013). These co-morbid disorders have a negative impact on the children and their families leading to learning disorders and academic challenges. Management of children having DS and ASD is a multifaceted process especially with co-morbid ID/DLD. Interventions introduced to these children focus on improving their communication abilities (e.g. verbal, non-verbal, social), attention, executive functions, sensory processing, and adaptive behavior (Nasser et al. 2022; Filipe et al. 2022). Many abilities could improve overtime as these children grow up. However, language abilities remain challenging issues in their rehabilitation and one of the first priorities for their families, especially expressive language abilities (Meguid et al. 2021; Moraleda-Sepúlveda et al. 2022).

The nutritional status of individual with DS and ASD have been gaining focus in this particular area. Children with DS and ASD were reported to exhibit deficiency in important micronutrients including vitamins, minerals, and cofactors such as vitamin B complex, vitamin C, vitamin E, iron, magnesium, zinc, and carnitine (Antonaros et al. 2021; Bjørklund et al. 2019; van der Haar and Zeinstra 2021). These vitamins were reported to be essential for neuronal maturation, cellular differentiation, myelin formation, enzymatic functions, nucleic acid synthesis, immune regulation, bone integrity, mental health and adjustment of the serotonergic, dopaminergic, glutaminergic, cholinergic, and catecholinergic systems (Denniss, Barker, and Day 2019; Indika et al. 2023). Vitamin B6 and magnesium act as cofactors for neurotransmitters such as 5-HT (Noah et al. 2021). Deficiency in such nutrients was linked to cognitive decline in some studies, which targeted adults and children with some neuropsychiatric disorders (Antonaros et al. 2021; Ueno et al. 2022). Deficiency in these nutrients in individuals having DS or ASD were attributed to unhealthy or restrictive dietary habits, reduced sun exposure, and gastrointestinal abnormalities, together with swallowing disorders in some children with DS (Bjørklund et al. 2019; Ravel et al. 2020). Supplementation of individuals presenting with cognitive impairments, neurodevelopmental disorders or even healthy ones were reported to improve cognitive functioning (Denniss, Barker, and Day 2019; Ueno et al. 2022). A recent systemic review conducted by Pancheva et al. (2024) to investigate the effects of nutritional supplements on ASD symptoms analyzed a number of randomized controlled trials (RCTs) with different studies designs (double-blind, placebo-controlled designs and open-label studies). Their findings emphasized effect of supplementation on many symptoms of ASD. However, the influence on language abilities and severity of ASD with monitoring serum level of these nutrients has not been adequately investigated. Therefore, this open-label study aimed at investigating the influence of dietary supplementation for children having DS or ASD concerning their language abilities, severity of ASD, and the serum levels of iron, magnesium, B6, B12, and serotonin.

Patients and methods

The guidelines reported in strengthening the reporting of observational studies checklist (STROBE) (Cuschieri 2019) were followed in this interventional open-label study. This study was conducted in the autism spectrum disorder research clinic, and children with special needs research clinic, Medical Research Centre of Excellence affiliated to the National Research Centre. The preliminary number of the included participants was 70 children, 35 in each group. However, the data of 13 children were not added to the study (8 in the DS group and 5 in the ASD group). Some children were non-compliant with the supplement intake. The parents of other children did not provide the post-supplementation blood samples or did not follow the home-based language stimulation advice. Therefore, the participants became 57 children with DS and ASD (45 males, 12 females). Their chronological age ranged from 3–12 years (6.5 ± 2.5). Children having ASD (N = 30) were diagnosed according to the criteria determined by the diagnostic and statistical manual of mental disorders, the fifth edition text revision (DSM 5-TR), in addition to the autism diagnostic interview revised criteria (ADI-R) (American Psychiatric association 2013; Rutter, Le Couteur, and Lord 2003). Confirmation of the DS diagnosis was performed by karyotyping where an extra copy of the chromosome 21 was detected (trisomy 21). All participants were subjected to interviewing for medical history, otorhinolaryngological examination, general examination, neurological examination, and audiological evaluation. Evaluating intellectual abilities was established by a psychologist according to the condition of the child using the fifth edition of Stanford Binet intelligence scale (Farag 2011) or Griffith’s developmental scale (Alin-Åkerman and Norberg 1991). The severity of ASD was measured by a psychiatrist using the second edition of childhood autism rating scale (CARS-2) (Schopler et al. 2010). The language development evaluation was achieved by a phoniatrician using the Arabic preschool language scale (El-Sady et al. 2011).

Children with associated gross motor delay, other psychiatric disorders, metabolic disorder, or currently on medication or phoniatric therapy were excluded. The participants in this study were included when their parents reported delays in communication abilities and/or cognitive development and their IQ was less than 70. The included children were given the same dietary supplement, which contains colostrum, lactoferrin, iron, zinc, magnesium, carnitine, chondroitin, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), lecithin, thioctic acid, methylsulfonylmethane (MSM), benfotiamine (vitamins B1), B2, |B3, B5, B6, B7, and B12, folic acid, and vitamins E and C. It was in the form of sachets which dissolved in about 150 ml of water or juice and ingested orally by the included children once per day after a meal. The ingredients of the formulation used are listed in Table 1. The doses were adjusted according to the child’s age (3–6 years: half sachet, older than 6 years: one sachet).

Table 1.

Components of formulation used for the included children.

Nutritional component	Concentration	%RDA*
Colostrum	200 mg	10$
Lactoferrin	50 mg	50$
Iron ferromate	5 mg	35.7
Magnesium	100 mg	26.7
Folic acid	300 µg	150
Vitamin C	50 mg	62.5
Vitamin B1 (Benfotiamine)	0.5 mg	50
Vitamin B 2	0.7 mg	50
Vitamin B 3	8 mg	50
Vitamin B 5	3 mg	50
Vitamin B 6	0.7 mg	50
Vitamin B12	1.2 µg	50
L-carnitine	300 mg	15$
Lecithin	100mg	10$
Zinc gluconate	2.5 mg	25
Uridine monophosphate	10 mg	6.6$
Glucosamine	20 mg	1.3$
Thioctic acid	50 mg	8.3$
Vitamin E	6 mg	50
Biotin (vitamin B 7)	50 µg	100
Methyl sulphonic methylsulfonylmethane (MSM)	2.5 mg	0.5$
Creatine	10 mg	1$
Chondroitin	1 mg	0.08$

* RDA: Recommended daily allowance.

$ No established recommended daily allowance. Dose is calculated according to research recommendations.

The home-based language stimulating program

A counseling session was given to the parents of participants by a phoniatrician for approximately one hour to encourage the parents to create a rich environment for language stimulation and enhancement of the attention and cognitive abilities of their children (American Speech-language and Hearing Association (ASHA)) 1997). Phone calls with one of the parents (mostly the mother) were weekly performed to ensure commitment with the supplement and the program, to provide new information when required, and to clarify any queries. The counseling session was repeated after 8 wk. The parents were advised to make their usual time spent with their children (e.g. during bathing, dressing, feeding, playing, outdoor activities) rich in activities and responses for improving attention, cognition, receptive language, and expressive language by talking to the child and interacting with the responses of the child accordingly. For example, naming the surroundings or pictures by pointing to them in a book; describing the actions performed while doing them; adding a story time; encouraging the child to play with other peers; giving the child full immediate attention as a positive reinforcement in response to any spontaneous vocalizations; using pretend play and questions in conversations; saying a missing sentence and guiding the child to fill in the missing word. More examples of these instructions are available at the American Speech-Language-Hearing Association website (American Speech-language and Hearing Association (ASHA)) 1997). The advised activities were adjusted in accordance with the preliminary language assessment of each child. The parents were given examples about these activities using materials available at home or in the surrounding environment. Then, they applied these instructions with their children in the session to give the parents immediate feedback by the doctor.

Biochemical analyses

Early morning blood samples were collected from each participant in 5-ml plain tubes for serum isolation. Serum samples were kept in aliquots immediately at −40 °C until further processing. Blood samples were withdrawn from all participants before the supplement intake and after 16 wk of its intake for estimating the levels of the targeted measures. Iron (Fe) and Magnesium (Mg) concentrations were measured using colorimetric method in a spectrophotometer device (JASCO V-730 Spectrophotometer, JASCO Corporation, JAPAN) by using commercial kits (QuantiChrome^TM Iron Assay Kit DIFE-250, BioAssay Systems, USA and Magnesium Phosphonazo III, IVD, SDi, respectively), according to the manufacturer’s instructions. Serotonin (5HT), Vitamin B6 and Vitamin B12 levels were measured using Enzyme Linked Immunosorbent Assay (ELISA) method (Microplate Photometer MULTISKAN FC, Thermoscientific, China) using commercial kits (Serotonin/5-Hydroxytryptamine ELISA Kit, Elabscience, China; Vitamin B6 ELISA Kit, abbexa, USA; AccuDiag^TM Vitamin B12 ELISA Kit, Diagnostic Automation/Cortez Diagnostics, USA, respectively), according to the suppliers’ instructions.

Furthermore, reassessment of their language abilities was achieved by the end of the 16 wk. Children who have ASD were assessed by CARS-2 before and after the supplementation intake. The IQ testing was not repeated as it is advised in the test manual to be repeated at intervals not less than 6 months (Farag 2011).

Written consent was obtained from the parents of the participants. The study was approved by the medical research ethics committee at the National Research Centre.

The statistical package for social sciences was used for statistical analysis after coding, tabulation, and analysis of data using IBM. Data were presented as mean ± standard deviation. The qualitative data were presented as number followed by percentage. For the between-group comparison, Mann-Whitney U test was used. Comparisons were performed using Wilcoxon test for the pre and post supplementation measures. Correlations were investigated between the language ages of the participants and the levels of 5-HT utilizing Spearman correlation coefficient. When p was less than 0.05, it was considered to be significant.

Results

No differences between the groups were detected regarding the age or sex distribution (Table 2).

Table 2.

Demographic data of the participants.

Items	DS group (N = 27)	ASD group (N = 30)	p
Age	6.4 ± 2.5	6.5 ± 2.4	0.8 ^
Male N (%)	19 (70.3)	26 (86.6)	0.1 $
Female N (%)	8 (29.6)	4 (13.3)	0.1 $

ASD: autism spectrum disorder; DS: Down syndrome; N: number; ^: independent t test; $: Chi square test.

Assessment before the supplementation

The intellectual abilities were assessed according to the suitable test for the participant. The scores ranged from 45 to 63 in the group of children having DS and from 41 to 68 in the group with ASD. No sensory neural hearing loss was detected in all participants, but tympanometry revealed that 7 children with DS had type c tympanogram. The range of CARS scores was 32-38.5 in the ASD group.

The receptive language age was higher than the expressive language age in both groups (Table 3). The receptive language age range was 0.7 − 3 years, and expressive language age range was 0.9 − 3 years in the DS group. In the ASD group, receptive language age range was from 1–4.5, whereas the expressive language age range was 1–4 years. The range of the total language age was 0.8-3 years in the DS group, and it was 1–4.25 years in the ASD group. Comparison between the preliminary language ages in both groups revealed non-significant statistical differences.

Table 3.

Comparison between the Down syndrome group, and the ASD group concerning the language age scores and CARS results before and after the supplementation.

Score	Timing	DS group (N = 27)	ASD Group (N = 30)	P
Score of CARS	Preliminary	–	35.7 ± 3.8	–
	Post supplementation	–	31.6 ± 2.7	–
	Change	–	−4.1 ± 1.1	–
	p	–	0.005*	–
Receptive language age	Preliminary	1.9 ± 0.6	2.3 ± 1.2	0.3#
	Post supplementation	2.5 ± 0.9	3.1 ± 1.4	0.04*#
	Change	0.6 ± 0.3	0.8 ± 0.2	0.01*#
	p	0.01*$	0.02*$	–
Expressive language age	Preliminary	1.6 ± 0.5	2.1 ± 1.1	0.05#
	Post supplementation	2.1 ± 0.7	2.8 ± 1.2	0.04*#
	Change	0.5 ± 0.2	0.7 ± 0.1	0.03*#
	p	0.04*$	0.01*$	–
Total language age	Preliminary	2.0 ± 0.6	2.2 ± 1.1	0.3#
	Post supplementation	2.6 ± 0.8	3.1 ± 1.3	0.04*#
	Change	0.6 ± 0.2	0.9 ± 0.2	0.03*#
	p	0.04*$	0.04*$	–

ASD: autism spectrum disorder, CARS: childhood autism rating scale, DS: Down syndrome, *Significant, $: Wilcoxon test, #: Mann-Whitney U test.

The after-supplementation results

Following 16 wk of micronutrients supplementation, the scores of CARS-2 were reduced in the ASD group, with significant statistical differences (p = 0.005). In both groups, the receptive language age showed better improvement than expressive language age. The improvement noticed in the language performance was better in the ASD group (Table 3). The language performance improved in all participants with significant statistical differences (Table 4). The levels of iron, Mg, vitamin B6 and 5-HT were elevated with significant statistical differences. The levels of vitamin B12 were elevated, yet without significant statistical differences (Table 5). No correlations were detected between the language ages and 5-HT levels in the participants.

Table 4.

Comparison between the preliminary values and the after-supplementation values in all participants regarding language ages (in years).

Items	Preliminary values (N = 57)	After supplementation values (N = 57)	Change	p
Receptive language age (years)	2.07 ± 1.04	2.99 ± 1.3	0.92 ± 0.2	0.003*
Expressive language age (year)s	1.78 ± 0.9	2.3 ± 1.1	0.6 ± 0.2	0.01*
Total language age (years)	1.9 ± 0.9	2.5 ± 1.2	0.5 ± 0.3	0.01*

*Significant, Wilcoxon test.

Table 5.

Comparison between before and after-supplementation values in all participants regarding the measured minerals, vitamins and serotonin levels.

Items	Before supplementation values (N = 57)	After supplementation values (N = 57)	Change	P
Iron (mcg/dl)	72.3 ± 0.84	86 ± 11.6	13.7	<0.0001*
Mg (mg/dl)	1.89 ± 0.28	2.09 ± 0.31	0.2	0.01*
B6 (ng/ml)	25.9 ± 8.1	31.1 ± 7.2	5.2	0.01*
B12 (pg/ml)	509.2 ± 168.7	572.5 ± 129.4	63.3	0.1
Serotonin level (ng/ml)	83.9 ± 38.5	160.2 ± 82.8	76.3 ± 44.3	<0.0001*

mcg/dl: microgram/deciliter, mg/dl: milligram/deciliter, ng/ml: nanogram/milliliter, pg/ml: picogram/milliliter, Wilcoxon test.

Discussion

The rehabilitation process of children having DS or ASD can be very challenging for the child and the family. Results of different therapy modalities to improve the language performance of such children differed between various studies (Sandbank et al. 2020). This could be attributed to underlying conditions, which commonly are undiagnosed including micronutrients deficiency, which could respond well to micronutrient supplementation (Indika et al. 2023). Both children having DS (Barišić et al. 2023) and ASD (Nogay and Nahikian-Nelms 2023) are at higher risk for nutritional deficiencies. DS children were reported to exhibit feeding and swallowing problems in the form of chewing difficulties and aspiration, which ranged from 40 to 50% (Serel Arslan 2022). Children with DS have increased prevalence of reduced growth rate (Ravel et al. 2020). Children having ASD were frequently reported to exhibit gastrointestinal problems such as constipation and pica. They are known to show food selectivity, unusual eating patterns and presence of medical comorbidities such as food allergy (Kittana et al. 2023). Moreover, the risk of nutritional deficiency is elevated by the comorbid inflammatory bowel disease or gastrointestinal inflammation with ASD (Kim et al. 2022). All these factors could contribute to inadequate nutrients intake and absorption in DS and autistic children.

These challenges encourage investigating the benefits of supportive supplementation, and family-based intervention aiming at improving language performance in children having DS and ASD, in addition to reducing the severity of ASD symptoms, which was represented by CARS scores. Adding oral supplementation for these children can be employed to improve their health status. Consequently, the effectiveness of intervention and rehabilitation sessions could be maximized when they receive phoniatric therapy sessions (Indika et al. 2023).

In this open - label study, the participants were supplemented by components reported to be essential for proper metabolic function of neural cells, immune modulation, and have neuroprotective effect in individuals diagnosed with DS and ASD (Bjørklund et al. 2019; Antonaros et al. 2021; van der Haar and Zeinstra 2021; Indika et al. 2023). From these given components, we examined the serum levels of iron, magnesium, vitamins B6, and vitamin B12. The concentration levels of iron, magnesium and vitamin B6 showed elevation in their levels after supplementation in the participants with significant statistical differences. On the other hand, an increase in the levels of vitamin B12 was found yet did not show significant difference.

Iron has an important role in many vital functions such as oxygen transport, oxidative stress, DNA and neurotransmitters synthesis. Iron imbalance was found to be associated with neurodevelopmental problems (Ferreira, Neves, and Gozzelino 2019). Studies about prevalence of iron deficiency in DS and ASD are inconsistent. It was mentioned that prevalence did not greatly differ from that in general population. However, it was found that ASD and DS children suffering from iron deficiency anemia could be more susceptible to the hazards of anemia considering the fact that they already exhibit deficits in their cognitive development (van der Haar and Zeinstra 2021; De Giacomo et al. 2022). Furthermore, iron supplementation for iron deficient patients was found to be associated with decreased risk for psychiatric disorders (Lee et al. 2020).

B vitamins are essential for metabolic homeostasis. Each one of them plays a distinctive role in the central nervous system function. Vitamin B6 (pyridoxine) is an essential coenzyme in several reactions involved in lipid, carbohydrates, and amino acid metabolism. It is also involved in the metabolic pathways which produce and break down neurotransmitters in the nervous system such as serotonin (Noah et al. 2021). Its deficiency was reported to lead to social communication deficits. Supplementation with a high-dose of vitamin B6, together with magnesium has been investigated in some placebo-controlled and double-blind studies, which revealed improvements in behavioral problems, communicative and social interaction, in addition to improved sensory processing abnormalities in autistic individuals (Bjørklund et al. 2019).

Cobalamin (vitamin B12) is essential for cognitive development and its deficiency has been suspected to be related to ASD and DS. Supplementation for children with these diagnoses was reported to be beneficial. It was found to improve social communication, reduce stereotypic and repetitive behaviors and enhance oxidative status (Rossignol and Frye 2021; van der Haar and Zeinstra 2021). In the two RCTs by Adams et al. (2018) and Adams et al. (2021) autistic children were given a mixture of multivitamins and minerals. This was accompanied by significant reduction in ASD symptoms as recorded by Autism Treatment Evaluation Checklist (ATEC) and CARS scores. However, in the meta-analysis by Barišić et al. (2023) on micronutrient status in individuals with DS, serum vitamin B12 was found to be higher in DS cases than controls. The authors explained this uncommon finding by the probability of abnormal uptake by tissues or deficiency of vit B12 carrier in blood with emphasis on the need for more future studies on effect of micronutrient status in DS individuals.

The impacts of B vitamins on the nervous system could be attributed to their roles in metabolism of amino acids. The amino acid tryptophan acts as a precursor for a plenty of major neurotransmitters, especially serotonin (Jennings and Basiri 2022). Supplementing ASD patients with magnesium and B vitamins had led to stabilization of tryptophan values in urine of those children versus ASD children who didn’t take the supplement. Thus, it can be speculated that supplementation with vitamins B and magnesium can influence tryptophan level and subsequently its metabolite serotonin by playing a role in its metabolic homeostasis (Kałużna-Czaplińska et al. 2017).

In the present study, serotonin levels were measured and showed elevations with significant statistical difference after the supplementation. Serotonin has been linked to emotion regulation, cognition and motor function, which all were reported to be altered in DS and ASD (Das et al. 2014; Abdulamir, Abdul-Rasheed, and Abdulghani 2018). Deficits in 5-HT homeostasis, either hypo- and hyperserotonemia has been involved in the severity and adaptive behavioral performance of children having DS or ASD (Das et al. 2014; Garbarino et al. 2019).

The delay in language abilities in the participant could be attributed to differences in brain areas involved in language processing in individuals diagnosed with DS or ASD, which was previously reported. Individuals having DS were reported to exhibit reduced overall functional connectivity, in particular left ventromedial frontal cortex and amygdala areas during communication (Cañete-Massé et al. 2022). Individuals with ASD were reported to have different activation patterns in brain areas such as bilateral reduced middle temporal gyrus activation and increased activity in the right superior temporal gyrus and inferior frontal gyrus, which indicated differences in the normal activation pattern between left and right hemispheres (Herringshaw et al. 2016).

In agreement with previous studies which reported that oral mineral and vitamin supplementation were beneficial for improving the metabolic and nutritional status of children having DS and ASD, the results in the present study showed improvement of language performance in children with ASD and DS following supplementation. This could be mediated by improvements in sulfation, methylation status, glutathione level, oxidative stress, energy consumption, and production cycles related to ATP, NADPH, and NADH (Bjørklund et al. 2019; Ergović Ravančić and Obradović 2023).

Despite no correlations were detected between 5-HT and language performance in participants of this study, several previous studies have described the relationship between 5-HT and language abilities. Imaging studies using positron emission tomography have shown reduction in cerebral synthesis of serotonin in children with ASD (Andersson et al. 2021). This abnormal and asymmetric development of the serotonergic system might have affected language development in those children (Chandana et al. 2005; Yoshimura et al. 2020). Additionally, a noticeable increase in language acquisition has been achieved among children with ASD who received fluoxetine in the open-label trial done by DeLong, Teague, and McSwain Kamran (1998). Therefore, it could be suggested that increasing the level of 5-HT in these individuals by dietary supplementation could be beneficial.

The language performance of the participants improved after receiving a family-based intervention combined with the dietary supplementation. The parents of the included participants did not know how to maximize the communication abilities of their children. Consequently, the phoniatric counselling sessions provided them with new information, which they did not apply before with their children. Home-based programs help parents to introduce effective intervention for their children with DS or ASD via improving their skills whenever they lack access to services or are still at a waiting list (Karaaslan and Mahoney 2013; Zhou et al. 2018). Furthermore, the severity of ASD symptoms has been improved in our ASD participants. This was consistent with previously reported results by Shi et al. (2021) and Maksimović et al. (2023). They found that parents’ engagement in the process of intervention helped in developing their children communication skills and reduction in their autistic symptoms. Also, both groups demonstrated better receptive than expressive language age in their baseline assessment, which is consistent with previous studies investigating the language abilities for children having both diagnoses (Meguid et al. 2021; Meguid et al. 2022; Filipe et al. 2022).

However, it has been noticed that improvements in language performance was better in participants with ASD compared to children with DS. This could suggest that gene-environment interaction plays a higher role leading to nutritional deficiencies in children with ASD compared to participants with DS, who have well-established genetic cause. However, this does not underestimate the role of oral supplementation for children having DS considering that these individuals have been reported to exhibit nutritional deficiencies of nutrients essential for brain functioning.

Limitations and future directions

This study includes some limitations. First, the small sample size. This is attributed to the lack of compliance of the parents to the required intervention. The absence of a neurotypical group to compare the preliminary and the post-supplementation levels of the targeted laboratory measures in the participants is also a limitation. However, no adverse effects have been reported by the parents of the participants. Therefore, the study offered and suggested an efficient, safe, and inexpensive method to improve the language performance of children having DS and ASD and to reduce the severity of ASD, especially in developing countries where rehabilitation services are not available in all health care facilities. More studies on larger samples are needed to elucidate how micronutrients supplementation could adjust 5-HT levels and the possible relation between language performance and 5-HT in these children. Moreover, use of supplements should be done with caution with pre-supplementation assessment of given minerals/vitamins as high serum levels of some micronutrients such as iron and vitamin B12 can compass serious adverse effects.

Conclusion

Dietary supplementation of micronutrients, together with home-based language simulation for children with DS and ASD, who are diagnosed with coexisting intellectual disability has benefits concerning their language performance. The response in receptive language was better than expressive language in both groups. The improvement in the severity of ASD has been established. This open-label study has introduced merging dietary supplementation with home-based language and cognitive stimulation under medical supervision as an effective method of management of children with DS and ASD. We have emphasized the possibility of a link between the levels of trace elements, serotonin levels and the presenting behaviors of ASD.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

The study was approved by the medical research ethics committee of the National Research Centre and carried out according to the latest version of the Helsinki Declaration of 1975. All parents of participants signed informed consents.