Dates as a Functional Food for Autism
Condition: Autistic Spectrum Disorder
MeSH terms: Autism Spectrum Disorder
Study type: Interventional

Summary: 
      Autism spectrum disorder (ASD) is a lifelong developmental disability that includes deficits
      in social communication and social interaction and restricted, repetitive patterns of
      behavior, interests, or activities.

      The current treatment approaches for the management of autism are expensive, showing unwanted
      adverse effects; alter the genetic and metabolic pathways. Many studies referred to the
      importance of probiotics, minerals and antioxidant supplementation in the treatment of
      accompanied eating and feeding problems. Meanwhile, there are still controversial results
      about the effectiveness of dietary interventions for ASD like the gluten-free/casein-free
      diet and the ketogenic diet.

      Dates have been documented in the Holy Quran and proved in modern scientific literature to
      act as potent antioxidants and as an anti-inflammatory, provide a suitable alternative
      therapy in various diseases cure.

      The medicinal therapeutic value of date fruits as nutritional probiotic and its implications
      in controlling autism through the anti-oxidant effect will be evaluated. Moreover, at which
      dose Dates fruit can exert its effect and whether this effect is sustained or not will be
      also evaluated. Besides, Dates' effect on cognitive, neurological parameters, eating
      behaviors, and gastrointestinal symptoms and anthropometric measures will be evaluated. A
      non-randomized clinical study on 120 diagnosed autistic children aged 3-12 years in Cairo
      will be conducted. Participants will be randomly assigned to one of three groups (each with
      40 children) receiving one of three regimens; the first group will receive 3 Dates per day
      for 3 months and the second group will receive 5 Dates per day for 3 months and the third
      group will receive nothing. All groups will receive nutrition guidance, behavioral
      modification, and stimulation sessions. Stools and blood samples will be collected before the
      study, after 12 weeks of the intervention and then 12 weeks after completion of the
      intervention. Evaluating Dates' ability to decrease the oxidative stress will be done through
      comparing blood levels of three oxidative markers; Malondialdehyde (MDA), glutathione
      peroxidase (GPX1) and superoxide dismutase (SOD) in children with autism for the three
      proposed regimen. The impact of the Dates fruit consumption on the microbiota of the autistic
      children both the pathogenic bacteria and probiotics will be done through traditional stool
      analysis and Real-time PCR before and after interventions.
    

Detailed description: 
      ASD is progressively increasing; the rate of autism was 3.4 per 1,000 for children aged 3 to
      10 years in the 1990s. Meanwhile, in 2006, the prevalence estimates are in the range of 6.5
      to 6.6 per 1,000 and recently 1 in 160 children have ASD. Though classified as a
      neurodevelopmental condition, ASD is often associated with multiple medical comorbidities and
      gastrointestinal (GI) problems. GI disorders occurred in around 90 % of ASD children with
      suggested possible role of the GI microflora in the severity of symptoms in autistic
      children.

      Children with ASD frequently have food selectivity, which may have an effect on
      gastrointestinal symptoms. The gut flora of autistic children is altered compared to healthy
      children and they have multiple nutritional deficiencies. The microbiota that resides in the
      gut was claimed to be the cause behind the neurodevelopmental disorders occurring among the
      autistic children.

      Due to the frequent occurrence of gastrointestinal dysfunction in patients with ASD, the use
      of probiotics may be an indication for adjuvant therapy. Probiotics ''are living
      nonpathogenic microorganisms, when administered in adequate amounts exert their beneficial
      effects resulting in modulation of the immune and inflammatory response. The supplementation
      of probiotic bacteria to autistic children can lead to changes in the microbiota and it
      considers a useful new therapeutic tool to normalize gut microbiota, restore the function of
      the epithelial barrier resulting in reliving of the gastrointestinal system disorders, reduce
      inflammation, and potentially improve the behavioral symptoms in autistic children.

      Furthermore, children with autism have deficient antioxidant defense Mechanisms. They are
      vulnerable to oxidative stress which is detected by elevated lipid peroxidation, especially
      at younger children. Oxidative stress may play a role in the development and clinical
      manifestations of autism resulting in loss of acquired language skills in autism. Meguid and
      coworkers highlighted that autistic children might benefit from antioxidant supplementation
      coupled with polyunsaturated fatty acids. Early assessment and intervention of antioxidant
      status may decrease the oxidative stress before inducing more irreversible brain damage.

      In Islam, herbs and its constituents have important value in diet and treatment of various
      types of diseases. The Prophet Mohammed (Peace Be Upon Him) used various herbs and
      recommended various medicinal plants for the cure of various diseases.

      Dates and their constituents show a role in disease prevention through anti-oxidant,
      anti-inflammatory, anti-bacterial activity. Dates are considered a staple food item in the
      Middle East and North Africa and are also imported in Europe, the UK, and the USA.

      Dates contain relatively high levels of polyphenols and insoluble fiber. It has shown that
      whole date fruit, and polyphenols extracted from them selectively stimulates Bifidobacterium
      spp. and Bacteroides, along with the total bacterial counts in fecal batch culture models,
      increasing small chain fatty acid (SCFA) production concurrently. In addition, promising
      changes in DNA damage were observed through the anti-proliferative actions of both polyphenol
      extracts and whole date extracts.

      Antioxidant activity of Dates is recognized due to the wide range of phenolic compounds
      present in Dates including p-coumaric, ferulic, and sinapic acids, flavonoids, and
      procyanidins.

      Dates fruit is considered as a rich source of minerals and sugars; its various constituents
      like phytochemicals, carotenoids, steroids, and flavonoids are screened for numerous
      medicine. Rahmani and his colleagues illustrate all the therapeutic functions of the Dates.

      Keeping all information in hands about Dates' therapeutic effect in the management of the
      disease via its anti-oxidant, anti-inflammatory effect and for the sake of autistic children,
      It is worthy to point and essential to evaluate Dates as a good remedy for autistic children
      because it is inexpensive and easy to access.

      Objectives:

      The overall objective is to discover functional food that is effective to control the
      comorbidities accompanied by autism development and to limit its progression. This food
      should be safe, inexpensive and affordable, easy to access without any complications.

      The medicinal therapeutic value of Dates fruit as nutritional prebiotic and its implications
      in controlling autism through anti-oxidant and anti-inflammatory effects will be evaluated.

      Specific Objectives

      The aim of this interventional study is to:

        1. Evaluate Dates' effect on cognitive development

        2. Evaluate Dates' effect on neurological parameters and severity of autism

        3. Evaluate Dates' effect on eating behaviors and diet quality

        4. Evaluate Dates' effect on gastrointestinal symptoms and the microbiota

        5. Evaluate Dates' ability to decrease the oxidative stress before inducing more
           irreversible brain damage (through comparing levels of three oxidative markers;
           Malondialdehyde (MDA), glutathione peroxidase (GPX1) and superoxide dismutase (SOD) in
           children with autism for the three proposed regimen).

        6. Evaluate at which dose Dates fruit can exert its effect as a new therapeutic regimen and
           its persistence over time

      Phases of the study and tools:

      This study will be conducted as three phases that will be done in a simultaneous way:

      The first phase will include patient recruitment and baseline assessment before Dates fruit
      intake:

      1. Applying the confirmatory diagnostic tools for autistic patients aged 3 -12 years.
      (Children with suspected ASD could be then assessed according to either Diagnostic and
      statistical manual of mental disorders, 5th edition. (DSM-V) criteria, and CARS.

      An autism screening tool must meet all three primary areas defined by the DSM-V description
      for the autistic disorder to qualify for a positive rating from First Signs:

      A. A total of six (or more) items from (1), (2), and (3), with at least two from (1), and one
      each from (2) and (3):

        1. Qualitative impairment in social interaction, as manifested by at least two of the
           following:

             1. Marked impairment in the use of multiple nonverbal behaviors, such as eye-to-eye
                gaze, facial expression, body postures, and gestures to regulate social interaction

             2. Failure to develop peer relationships appropriate to the developmental level

             3. A lack of spontaneous seeking to share enjoyment, interests, or achievements with
                other people (e.g., by a lack of showing, bringing, or pointing out objects of
                interest)

             4. Lack of social or emotional reciprocity

        2. Qualitative impairments in communication, as manifested by at least one of the
           following:

             1. Delay in, or total lack of, the development of spoken language (not accompanied by
                an attempt to compensate through alternative modes of communication such as gesture
                or mime)

             2. In individuals with adequate speech, marked impairment in the ability to initiate
                or sustain a conversation with others

             3. Stereotyped and repetitive use of language or idiosyncratic language

             4. Lack of varied, spontaneous make-believe play or social imitative play

        3. Restricted, repetitive, and stereotyped patterns of behavior, interests, and activities
           as manifested by at least one of the following:

             1. Encompassing preoccupation with one or more stereotyped and restricted patterns of
                interest that is abnormal either in intensity or focus

             2. Apparently inflexible adherence to specific, nonfunctional routines or rituals

             3. Stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or
                twisting or complex whole-body movements)

             4. Persistent pre-co-occupation with parts of objects B. Delays or abnormal
                functioning in at least one of the following areas, with onset prior to age 3
                years: (1) social interaction, (2) language as used in social communication, or (3)
                symbolic or imaginative play.

                The Instruments of the investigation will also include socio-demographic assessment
                questionnaire including suggested history of risk factors (Demographics, Medication
                exposure, Medical conditions, Pesticides, Diet, Home environmental exposures,
                Health behaviors/lifestyle, Mental condition/history/symptoms, Vaccine history,
                Personal product use, Anthropometrics, Medical procedures, Occupational history. In
                addition, the questionnaire will focus on socioeconomic indicators as well as
                prenatal and perinatal and neonatal risk factors such as the timing of conception,
                weight gain during pregnancy, parental age, and inter-pregnancy interval.

                2. Assessment of the sociodemographic characteristics through detailed history
                taking, pregnancy history, peri-natal history, and other risk factors

                3. Neurological assessment through thorough clinical examination

                4. Assessing functional gastrointestinal behavior disorders (FGID): Assessing
                changes in the GI symptoms which may be constipation, diarrhea, gaseousness,
                bloating, gastroesophageal reflux, abdominal pain, and vomiting but constipation is
                the more common and the most reported GI symptoms

                5. Detailed nutritional and dietary assessment with anthropometric measurements
                Anthropometric measurements

                  1. Weight (in kg): by Body fat analyzer

                  2. Height (in cm): using Stadiometer

                  3. BMI (weight/Height2 in meter):calculated

                  4. Waist circumference (in cm): measuring tapes

                  5. Hip circumference (in cm): measuring tapes

                  6. Waist / Hip ratio: calculated

                  7. measuring body composition analyzer (Bioelectrical impedance) for autistic
                     children aged seven years and older (measure fat mass, fat-free mass, fat %,
                     water content, Basal metabolic rate (BMR)

                6. Behavioral Assessment; the interview questions will cover eight content areas:

                  1. The subject's background, including family, education, previous diagnoses, and
                     medications

                  2. Overview of the subject's behavior

                  3. Early development and developmental milestones

                  4. Language acquisition and loss of language or other skills

                  5. Current functioning in regard to language and communication

                  6. Social development and play

                  7. Interests and behaviors

                  8. Clinically relevant behaviors, such as aggression, self-injury, and possible
                     epileptic features

                Mental Development, Psychomotor Development and Behavior Rating will be assessed by
                using the "Bailey Scales of Infant and Toddler Development", the cognitive,
                language, and motor abilities will be assessed; as well as social-emotional and
                adaptive behavior. Mental and psychomotor developmental quotients and mental age
                will be scored as well as the behavioral profile. The Bailey Screening Test is an
                Observation Checklist for 5 domains of development (cognitive, language, motor,
                social-emotional, & adaptive behavior).

                The questionnaire will be directed for the mothers of all confirmed cases with ASD
                enrolled in the study

                Second phase Intervention phase

                Special emphasis will be directed towards focusing on treating accompanied
                neurological manifestations Third phase: during this phase, the outcome of the
                intervention on the stool microbiota and on the serum antioxidant markers will be
                evaluated twice; once after completing the intervention and 3 months later.
    

Intervention name(s): Dates fruit as functional Food; behavioral modification and stimulation; nutritional Guidance
Intervention type(s): Other; Behavioral; Other
Intervention description(s): Two groups will receive Dates; The number per group is dependant on the child age. For children aged 3-6 years; they will receive the minimum numbers of dates (3 pieces). For children aged more than 6-12 years will receive 5 pieces of Dates the choice of the minimum numbers of dates (3 pieces) in this current trial is based on a study that was done by Al Jaouni and his colleagues, 2019 which proved the effects of three pieces of Ajwa on infection, hospitalization, and survival among 26 pediatric cancer patients in a university hospital; for which their treatment outcome was improved due to their intake of this amount of Ajwa during their standard treatment; Behavioral modification applied to the autistic children that is based on applied behavior analysis (ABA), a widely accepted approach that tracks a child's progress in improving his or her skills. We use Positive Behavioral and Support (PBS); The nutritional education sessions are based on educating parents on providing their autistic children with a nutritious, balanced diet. Because children with ASD often have restricted diets as well as difficulty sitting through meal times, they may not be getting all the nutrients they need, particularly calcium and protein
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Dates and their constituents show a role in disease prevention through anti-oxidant, anti-inflammatory, anti-bacterial activity. Dates are considered a staple food item in the Middle East and North Africa and are also imported in Europe, the UK, and the USA. (12).
Dates' therapeutic effect in the management of the disease via its anti-oxidant, anti-inflammatory effect and for the sake of autistic children, is worthy to point and essential to evaluate Dates as a good remedy for autistic children because it is inexpensive and easy to access.
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: Dates; Autism; microbiota; antioxidant; anti- inflammatory