The Child Neurology Knowledge Environment
Information
Last updated: 26 June 2024

Metabolic derangements and Autism

Information
Autism, cannabidiol in autism, metabolic interventions in autism, nutritional supplements in autism

Disruption at any of the stages in metabolism could contribute to primary and/or secondary contributions to ASD

Index

  1. Possible Role for Metabolism in the Pathogenesis of ASD
  2. Role of Metabolism in Altered Cognition in ASD
  3. Secondary Contributions of Metabolism to ASD
  4. Effect of Diet and Metabolic Consequences on Behavior and Quality of Life in ASD
  5. Food Intolerances and Nutritional Deficiencies in ASD
  6. Metabolic Interventions and Outcomes in ASD: Special Diets
  7. Gluten-Free, Casein-Free Diets (GFCF)
  8. Ketogenic Diets for ASD (in the Absence of Epilepsy)
  9. Supplements
  10. Vitamins
  11. Folinic Acid
  12. Probiotics
  13. N-Acetylcysteine (NAC)
  14. Omega-3 Fatty Acids
  15. New Treatment Targets
  16. Need for Additional Research and Considerations for Metabolic and Nutritional Interventions in ASD
  17. References

Possible Role for Metabolism in the Pathogenesis of ASD

  • Overview of Metabolism:

    • Metabolism encompasses biochemical processes for:
      • Converting food into energy to power cells
      • Synthesizing cellular components
      • Eliminating waste (López-Otín et al., 2016)
    • Begins with digestion and absorption of nutrients into the bloodstream
    • Continues with cellular and organ-level processes (López-Otín et al., 2016; Shaffer et al., 2017)

  • Disruptions in Metabolism:

    • Disruption at any stage could contribute to ASD through primary and/or secondary pathways (Cheng et al., 2017; Frye, 2015; Schiff et al., 2011).
    • Metabolic disturbances at the cellular level, particularly in neuronal pathways, may cause synaptic dysfunction underlying altered cognitive development in ASD.

  • Mitochondrial Dysfunction as a Candidate:

    • Mitochondrial dysfunction is a potential primary cause of synaptic dysfunction in a subset of ASD cases (Cheng et al., 2017).
    • Risk genes for mitochondrial dysfunction in people with ASD include:
      • SLC25AI2
      • TMLHE
      • IMMP2L
    • Multiple monogenic animal models of ASD (e.g., Mecp2, Ube3a, TSC, Foxg1) show evidence of mitochondrial dysfunction (Cheng et al., 2017).

  • Prevalence and Speculation:

    • Less than 5% of people with ASD meet criteria for classic mitochondrial diseases.
    • There is speculation that more individuals with ASD may have underlying mitochondrial dysfunction (Rossignol and Frye, 2014, 2012).

  • Metabolic Abnormalities and Studies:

    • Blood tests indicate a higher incidence of metabolic abnormalities in people with ASD; however:
      • Many studies are small and not controlled for diet or medication use (Frye, 2015; West et al., 2014).
      • Unclear if metabolic changes contribute to ASD etiology or result from the disorder, given common restricted diets in ASD.

  • Impact of Gut Microbiome:

    • Metabolomic studies in blood plasma are dynamically affected by the gut microbiome, which changes rapidly with dietary alterations (Shaffer et al., 2017).

  • Challenges in Correcting Metabolic Defects:

    • Mixed results have been observed in attempts to correct metabolic defects (Delhey et al., 2018).
    • Unclear if improvements in autistic or gastrointestinal symptoms indicate a direct role for metabolic dysfunction or correction of secondary nutritional deficiencies caused by ASD core features.

  • Ongoing Research:

    • Further research is needed to explore connections between mitochondrial dysfunction and ASD pathophysiology.
    • Unclear to what extent mitochondrial dysfunction contributes to ASD, particularly in animal models.

Role of Metabolism in Altered Cognition in ASD

  • Genetic Mutations and Metabolism:

    • Genetic mutations affecting metabolic function in neurons, such as in mitochondria, may lead to synaptic dysfunction in some individuals with ASD (Cheng et al., 2017).
    • Correcting or modulating mitochondrial function might improve synaptic function and potentially enhance learning and adaptability if technically feasible.

  • Undiagnosed Metabolic Disorders and ASD:

    • Some children with undiagnosed metabolic disorders, potentially missed in regionally variable newborn screening, may be mistakenly diagnosed with ASD.
    • In Crete, investigators found inborn errors of metabolism in 5 out of 187 children previously diagnosed with ASD, including one case of phenylketonuria (PKU) (Spilioti et al., 2013).
    • The incidence of metabolic disorders in the ASD population is likely less than 1%, as evidenced by a French cohort study identifying only 2 people with potential metabolic disorders out of 274 individuals with ASD, similar to the general population's risk (Schiff et al., 2011).

  • Symptom Overlap Between Metabolic Disorders and ASD:

    • Frye (2015) reviewed six categories of metabolic disorders that may overlap phenotypically with ASD, including:
      • Disorders of energy metabolism
      • Cholesterol metabolism
      • Cofactor metabolism (e.g., vitamin deficiencies)
      • GABAergic metabolism
      • Pyrimidine and purine metabolism
      • Amino acid metabolism
    • Anecdotal cases exist of dramatic resolution of ASD symptoms following specific metabolic replacement therapy (Adams et al., 2018).

  • Caution in Diagnosing Metabolic Disorders as ASD:

    • Most metabolic disorders exhibit global developmental delay, a specific exclusion for an ASD diagnosis.
    • These disorders also have many phenotypic features unrelated to ASD, suggesting specific syndromes rather than ASD.
    • Studies linking ASD with high prevalence of co-morbid metabolic disorders should scrutinize the stringency of ASD diagnoses applied (Frye, 2015).

Secondary Contributions of Metabolism to ASD

  • Metabolic Dysfunction and ASD:

    • Metabolic dysfunction may play a secondary role in ASD.
    • People with ASD who are nonverbal or have limited communication may struggle to express discomfort, leading to:
      • Physical pain
      • Frustration
      • Irritability
      • Self-injurious or aggressive behaviors

  • Underlying Medical Conditions and Communication Difficulties:

    • Communication difficulties can mask other underlying medical conditions, particularly gastrointestinal distress, which is common in ASD (Buie et al., 2010).

  • Restricted Food Interests and Gut Microbiome:

    • Many people with ASD have restricted food interests, potentially altering the gut microbiome (Buie, 2015; Mulle et al., 2013).
    • Altered microbiome can lead to gastrointestinal symptoms by:
      • Affecting the breakdown of foods to absorbable metabolites
      • Competing with pathogenic bacteria (Heintz-Buschart and Wilmes, 2018)

  • Microbiome and Systemic Metabolic Dysfunction:

    • The microbiome may contribute to systemic metabolic dysfunction in ASD through:
      • Absorption of different bacterial metabolites into the bloodstream, affecting downstream cellular processes in the body and brain
      • Decreased synthesis of essential vitamins by the microbiome
      • Effects on the immune system (Buie, 2015; Heintz-Buschart and Wilmes, 2018; Mulle et al., 2013)

  • Improving Behavioral Outcomes:

    • Identifying and treating metabolic dysfunction is expected to improve behavioral outcomes in affected individuals.

  • Targeting Metabolism to Modulate Cognitive Function:

    • There is potential for targeting metabolism to modulate cognitive function in people with ASD.
    • Healthy eating is associated with improved cognitive function in neurotypical individuals across the lifespan (Buie, 2015).

Effect of Diet and Metabolic Consequences on Behavior and Quality of Life in ASD

  • Restricted Diets in ASD:

    • Common due to sensory sensitivities to food texture, taste, smell, or color.
    • Meta-analysis including 881 children found children with ASD are five times more likely to have feeding issues than children without ASD (Sharp et al., 2013).

  • Nutritional Supplementation Challenges:

    • People with severe ASD may require additional nutritional supplementation to avoid vitamin deficiencies.
    • Many individuals with ASD have difficulty swallowing pills (Beck et al., 2005; Ghuman et al., 2004).
    • Caregivers often hide supplements in sugary drinks or snacks.

  • Special Diets:

    • Families or caregivers may choose special diets hoping to improve core symptoms of ASD (Sathe et al., 2017).

  • Gastrointestinal (GI) Problems:

    • Common in people with ASD, particularly gastroesophageal reflux disease (GERD) and constipation (Buie et al., 2010; McElhanon et al., 2014).
    • GI distress often missed in individuals with limited verbal abilities, as discomfort may be expressed as self-injurious, repetitive, or aggressive behaviors (Buie et al., 2010).
    • Changes in diet and nutrition may temporarily exacerbate or relieve symptoms.
    • Aggressive treatment of GERD and constipation can reduce harmful behaviors and improve nutrition as the GI system heals (Buie et al., 2010).

  • Impact on Mood, Concentration, Energy, and Social Interaction:

    • Dietary intake affects mood, concentration, energy, and ease of social interaction in people with and without ASD.
    • For non-verbal individuals with ASD, hunger or dietary issues may lead to self-injurious or aggressive behaviors.

Food Intolerances and Nutritional Deficiencies in ASD

  • Undiagnosed Food Intolerances and Nutritional Deficiencies:

    • People with ASD, especially those with limited communication, may have undiagnosed food intolerances and nutritional deficiencies (Buie et al., 2010).
    • Replacing nutritional deficiencies has shown promise in improving autistic symptoms and quality of life (Ranjan and Nasser, 2015).

  • Study on Comprehensive Nutrition Approach:

    • A 12-month, single-blinded study combined:
      • Vitamin/mineral supplements
      • Fatty acids
      • Carnitine
      • Digestive enzymes
      • Gluten-free, casein-free, soy-free diet
    • The study showed modest absolute improvements in autistic symptoms with high variability among participants (Adams et al., 2018).
    • Difficult to pinpoint which components justify a general recommendation due to multiple nutritional changes.

  • Meta-Analyses of Nutritional Replacement Strategies:

    • Meta-analyses show inconclusive results, with studies showing dramatic or no benefits, and varying degrees of bias in study design (Sathe et al., 2017).

  • Case Studies and Clinical Recovery:

    • Case studies revealed previously unrecognized nutritional deficiencies or food intolerances (e.g., carnitine deficiency, lactose intolerance) resulting in dramatic clinical recovery (Adams et al., 2018).
    • Highlights the advantage of evaluating individual nutritional states and specific symptoms needing treatment.

  • General Approach for Primary Care Physicians:

    • Review dietary intake of patients with ASD, potentially with a nutritionist's help, to identify likely nutritional deficiencies (Buie et al., 2010).
    • Common deficiencies in ASD (e.g., calcium, vitamin D) are also prevalent in the general pediatric population (Hyman et al., 2012).

  • Correcting Nutritional Deficiencies:

    • Correct deficiencies one at a time based on likelihood and evaluate over an appropriate timeframe (days to months).
    • Consider family history, especially when the person with ASD cannot answer symptom-related questions (e.g., cramping after eating dairy products).

  • Challenges and Compliance:

    • Specialized regimens can be difficult and expensive for caregivers.
    • Compliance in studies ranges from 60 to 90%, with food exclusion being the most challenging (Sathe et al., 2017).

Metabolic Interventions and Outcomes in ASD: Special Diets

  • Interest in Dietary Interventions:

    • Many families and caregivers are interested in dietary interventions for ASD.

  • Implementation and Challenges:

    • Some diets are easy to implement and unlikely to cause harm.
    • Many diets require significant food restrictions, adding stress and expense for the family and the person with ASD.
    • Maintenance of these diets may provide little or no documented benefit on autistic symptoms or behaviors.

  • Review of Popular Diets:

    • Several popular diets are summarized in Table 1.

 

 RationaleProposed targetProven efficacy in ASD?Risks
SPECIAL DIETS
Gluten- and casein-free diets Possible sensitivity to gluten (wheat) and/or casein (dairy products) Core ASD &/or GI symptoms No Vitamin deficiencies (B, D, and calcium); decrease in food variety
Ketogenic diets High-fat, low carb diet forces brain to use ketones for energy (highly effective for some forms of epilepsy) Core ASD symptoms No Cardiovascular risks of high fat diet from long-term treatment
 
SUPPLEMENTS
Vitamins (e.g., A, C,D,B6,B12, zinc, magnesium) Address vitamin deficiencies due to restricted diets Core ASD; general health Noa Excess supplementation (e.g., vitamin A, C, folate, copper, zinc)
Folinic acid May address folate deficiency Core ASD symptoms Not yetb Few
Probiotics May improve gastrointestinal function Core ASD &/or GI symptoms Not yetb Few
N-acetylcysteine May reduce oxidative stress at cellular level Core ASD symptoms No Diarrhea, vomiting, headache
Omega-3 fatty acids May have anti-inflammatory properties Core ASD; general health Not yetb Few
Sulforaphane Imitates metabolic effects of fever; may also target mitochondria Core ASD symptoms Not yetb Weight gain
Suramin Targets mitochondrial function Core ASD symptoms Not yetb Peripheral neuropathy, liver & kidney toxicity, adrenal insufficiency
Cannabidiol Anxiolytic properties may decrease behavioral problems in autism Core ASD symptoms Not yetb Hypervigilence, sleep disturbances, irritability, loss of appetite, psychosis (rare)
aBenefits might be overall and not specific to autism
bInsufficient evidence available. There are studies ongoing to determine efficacy
source: Mierau SB, Neumeyer AM (2019) Metabolic interventions in Autism Spectrum Disorder. Neurobiol Dis 132 ():104544. DOI: 10.1016/j.nbd.2019.104544 PMID: 31351171.

 

  • Caution with Dietary Interventions:

    • Caution should be taken with any new dietary intervention to avoid:
      • Creating nutritional deficiencies
      • Adding unnecessary stress for the person with ASD and their caregivers

  • Lack of Sufficient Evidence:

    • Systematic reviews of the literature have not found sufficient evidence to recommend any special diet for ASD (Sathe et al., 2017).

Gluten-Free, Casein-Free Diets (GFCF)

  • Popularity and Restrictions:

    • The GFCF diet is popular among people with ASD.
    • It removes most wheat and dairy products, except milk from some exotic animals without casein (e.g., camel milk).

  • Prevalence:

    • 18% of people with ASD were found to be on gluten-free and/or casein-free diets in a study (Hyman et al., 2012).

  • Anti-Gliadin Antibodies and Gluten Sensitivity:

    • Gluten-free diets gained popularity due to a possible higher incidence of anti-gliadin antibodies in ASD.
    • A study comparing IgG antibodies in children with ASD, healthy siblings, and unrelated persons without ASD found no significant difference between children with ASD and their neurotypical siblings (Lau et al., 2013).
    • The higher incidence was only found when comparing children with ASD from the US with unrelated controls mostly from Sweden.
    • No association with increased anti-gliadin antibodies and specific markers for celiac disease was found.
    • Elevated IgG, without a concomitant increase in IgA, may not be related to gluten or come from the gut (Lau et al., 2013).
    • There is no reliable test for gluten sensitivity in the absence of celiac disease (Buie, 2013).

  • Studies on GFCF Diets:

    • Multiple small studies have produced mixed results on the benefits of GFCF diets in ASD.
    • A well-controlled study started the GFCF diet in 3- to 5-year-olds under dietician guidance for 4-6 weeks, followed by 12 weeks of dietary challenges with gluten or casein (Hyman et al., 2016).
    • No association between gluten or casein challenges and behavior, and no overall behavioral benefit of the diet was found (Hyman et al., 2016).
    • Other small randomized-control trials showed improvements on parent-rated scales but lacked monitoring of diet adherence or concurrent ASD treatments (Knivsberg et al., 2002; Whiteley et al., 2010).
    • A small double-blinded study, where food was provided to families to control intake and compliance, showed no improvement in ASD symptoms (Elder et al., 2006).

  • Clinician Guidance and Risks:

    • Clinicians should caution families about the lack of evidence for the GFCF diet's efficacy in ASD.
    • The diet carries risks of deficiencies in B vitamins, calcium, and vitamin D due to wheat and dairy restrictions.
    • Consultation with a dietician is beneficial to ensure good nutrition for those considering restrictive diets (Buie et al., 2010).
    • Vitamin supplementation is common, but vitamins are better absorbed from food than pills.
    • Significant deficiencies in calcium and vitamin D may persist despite supplementation (Stewart et al., 2015).

Ketogenic Diets for ASD (in the Absence of Epilepsy)

  • Overview:

    • Ketogenic diets are high-fat, low-carbohydrate diets known for treating some forms of epilepsy.
    • These diets require strict adherence and are often monitored by specialized dieticians for epilepsy patients.

  • Interest in ASD:

    • There has been interest in using ketogenic diets to improve symptoms in ASD.

  • Limited Trials and Findings:

    • Limited small trials (6–18 children) suggested mild improvement in behavior and cognition for children with ASD who adhered to the diet (Cheng et al., 2017).
    • Implementation is challenging in ASD due to feeding issues.

  • Adherence Challenges:

    • Less than 38% of study participants were able to comply with the ketogenic diet (Spilioti et al., 2013).

  • Risks and Concerns:

    • Unclear how long a person with ASD could stay on the ketogenic diet without experiencing known cardiovascular risks of a high-fat diet.
    • Likely changes in the microbiome add to the concerns (Shaffer et al., 2017).

  • Current Recommendation:

    • Without further elucidation of the risks and potential benefits, a ketogenic diet is not recommended for people with ASD, except when treating epilepsy

Supplements

  • Interest in Nutritional Supplements:

    • In the absence of effective medications for treating the core symptoms of ASD, many families and caregivers have turned to nutritional supplements.
    • A summary of popular supplements among patients is provided in Table 1.

  • Supplement Industry Regulations:

    • The supplement industry is not regulated as strictly as prescription medications (Dodge, 2016).
    • There may be insufficient scientific evidence to support health benefit claims, inadequate investigation or reporting of side effects, and loose regulation over the precise amount of active ingredients in supplements (Marcus, 2016; Pawar and Grundel, 2017).
    • Dosage can vary widely between batches, even from the same manufacturer (Dodge, 2016).

  • Potential Risks and Interactions:

    • Many nutritional supplements are metabolized by the same liver enzymes as prescription medications, particularly antiepileptic or antianxiety medications.
    • This may affect the efficacy and/or toxicity of concurrent drugs (Asher et al., 2017).

  • Recommendations for Caregivers:

    • Caregivers should be encouraged to report all nutritional supplements to any prescribing physicians and their pharmacist to avoid harmful drug-supplement interactions.

Vitamins

  • Prevalence of Vitamin Supplementation:

    • 56%-66% of children with ASD receive vitamin supplements, compared to 31%-37% of the general pediatric population (Hyman et al., 2012; Stewart et al., 2015).

  • Common Micronutrient Deficiencies:

    • Deficiencies in vitamins D, B6, calcium, potassium, and choline are common in children with ASD, similar to neurotypical children.
    • These deficiencies are not always corrected by taking vitamin supplements (Stewart et al., 2015).

  • Nutritional Intake and Bone Health:

    • Adolescent boys with ASD showed lower protein and calcium intake, corresponding with lower bone mineral density scores (Neumeyer et al., 2018b).

  • Excess Supplementation:

    • Evidence of excess supplementation of vitamin A, folate, zinc, and copper in children with ASD was noted.

  • Testing for Deficiencies:

    • It is prudent to test for vitamin deficiencies before recommending supplements.
    • Discussion with a dietician regarding dietary changes may be more effective and reduce the risk of excess supplementation.

  • Studies on Vitamin Supplementation:

    • Studies have examined the effects of supplementation with vitamins D, B6, B12, magnesium, and folic acid, showing mixed results (Li et al., 2018).
    • Vitamin D supplementation, when successful at increasing vitamin D levels, appeared to improve symptoms according to one meta-analysis (Li et al., 2017).
    • Vitamin D deficiency is common in the general population, and supplementation benefits are unlikely to be specific to ASD (Hyman, 2012).

Folinic Acid

  • Overview:

    • Folinic acid is a reduced form of folate (vitamin B9) that is easier for the body to absorb and can cross the blood-brain barrier (Li et al., 2018).

  • Neurologic Symptoms and Cerebral Folate Deficiency:

    • High-dose folinic acid improves neurologic symptoms in cerebral folate deficiency, characterized by neurodevelopmental regression and diagnosed by low folate in cerebrospinal fluid.

  • Folic Acid Receptor Alpha Autoantibodies:

    • Autoantibodies to the folic acid receptor alpha have been identified in some people with ASD (Ramaekers et al., 2005).

  • Open Label Study:

    • An open label study found that high-dose folinic acid improved communication and repetitive behaviors in people with ASD (Frye et al., 2013).

  • Double-Blinded Placebo-Control Study:

    • A small double-blinded placebo control study showed improvement in language and behavioral scoring scales for ASD, particularly for the cohort with folic acid receptor alpha autoantibodies (Frye et al., 2018).

  • Planned Multi-Center Study:

    • A larger, multi-center randomized control study of folinic acid (leucovorin) versus placebo is planned (NCT02839915).
    • The study aims to determine if folinic acid is effective for people with ASD in general or only for a subpopulation with documented folate deficiency and autoantibodies.

  • Potential and Safety:

    • This treatment has few known side effects and holds promise for improving symptoms in a specific subset of people with ASD.

Probiotics

  • Interest in Probiotics:

    • Many families and caregivers are interested in whether probiotics can improve gastrointestinal (GI) symptoms, behavior, and other cognitive symptoms in ASD due to gut-brain interactions (Rose et al., 2018).

  • Gut Permeability and ASD:

    • Recent studies suggest increased gut permeability as a source of GI and potentially cognitive problems in ASD.
    • Zonulin, a biomarker for gut permeability, may be elevated in some people with ASD.
    • Another biomarker, sugar probes, was not elevated, indicating that elevated zonulin could be an epiphenomenon rather than part of the pathogenesis of ASD (Fasano and Hill, 2017).

  • Probiotics and Core Symptoms of ASD:

    • No established benefit of probiotics on the core symptoms of ASD has been found.

  • Probiotics and GI Symptoms:

    • Probiotics may improve GI symptoms in people with ASD (Li et al., 2017).
    • They may decrease constipation and abdominal pain in ASD (Fasano and Hill, 2017).

  • Conclusion:

    • While probiotics may not affect core ASD symptoms, they can offer GI relief, which might indirectly benefit overall well-being in individuals with ASD.

N-Acetylcysteine (NAC)

  • Overview:

    • N-acetylcysteine is a prodrug of the amino acid cysteine and a precursor to glutathione.
    • Glutathione is involved in oxidative stress and scavenging free radicals.

  • Investigation in Psychiatric Disorders:

    • NAC is being investigated for use in multiple psychiatric disorders, including:
      • Depression
      • Obsessive-compulsive disorder
      • Bipolar depression
      • Schizophrenia (Dean et al., 2011)

  • Studies in ASD:

    • Comparison of NAC in children with ASD, with and without concurrent treatment with the antipsychotic risperidone, reported:
      • Mild improvement in irritability
      • No improvement in repetitive behaviors (Ghanizadeh and Moghimi-Sarani, 2013)
    • A small randomized control pilot study with oral NAC in children with ASD found:
      • Improvement in irritability
      • Improvement in repetitive behaviors (Hardan et al., 2012)
    • Other studies failed to show benefit (Williamson et al., 2017)

  • Current Recommendation:

    • Further evidence of efficacy is required before recommending NAC to people with ASD and their caregivers.

Omega-3 Fatty Acids

  • General Benefits:

    • Omega-3 fatty acids supplementation has been tested for:
      • Improving cardiovascular health
      • Enhancing cognitive function in aging populations (Derbyshire, 2018; Jia et al., 2019)

  • Interest in ASD:

    • Due to their proposed anti-inflammatory effects, there has been interest in whether omega-3 fatty acids could improve symptoms in ASD (Sathe et al., 2017).

  • Meta-Analysis Findings:

    • A meta-analysis of 6 randomized controlled studies in people with ASD showed:
      • No benefit in 5 out of 6 trials, all limited by sample size (Li et al., 2018; Williamson et al., 2017)

  • Future Research:

    • As new refinements of the formulation become available, larger trials may be justified to determine if any ASD-specific benefits can be observed from treatment.
    • These trials could assess both potential ASD-specific benefits and overall health benefits.

New Treatment Targets

  • Sulforaphane:

    • Plant derivative thought to interact with heat shock proteins, mimicking the metabolic effects of a fever (Li et al., 2017).
    • In a small study of teenagers with ASD, where parents noted improvement in symptoms during fevers, the drug showed improvement in ASD symptoms compared to placebo.
    • The placebo effect was much lower than expected, suggesting potential efficacy (Li et al., 2017).

  • Intravenous Suramin:

    • Antipurinergic therapy targeting mitochondrial function.
    • A small study compared a single dose of intravenous suramin in 5 boys with ASD to a saline infusion in 5 boys with ASD (Naviaux et al., 2017).
    • Mild improvement was seen on subjective outcomes, with two previously non-verbal children speaking their first sentences.
    • Further investigation is necessary to test efficacy.

  • Cannabidiol (CBD):

    • An anxiolytic component from the cannabis plant being explored for treating behavioral problems in ASD.
    • A whole plant extract with a 20:1 ratio of CBD to tetrahydrocannabinol (THC) was given to 60 children with ASD, most of whom were also on antipsychotics or other psychiatric medications (Aran et al., 2019).
    • Subjective improvement in behavioral problems was reported in 61% of the children.
    • Half of the cohort had to switch to a 6:1 ratio of CBD
       
      due to insufficient response.
    • 27% of the children stopped the trial early due to poor tolerance.
    • Common side effects included hypervigilance, sleep disturbances, irritability, and loss of appetite.
    • One child on the higher THC concentration had a psychotic episode.
    • Current clinical trials are underway to test CBD compounds in placebo-controlled cohorts of 100-150 children with ASD (Aran et al., 2019).

Need for Additional Research and Considerations for Metabolic and Nutritional Interventions in ASD

  • Research Necessity:

    • Additional research is needed to evaluate the effectiveness of metabolic and nutritional interventions in addressing the core symptoms of ASD.

  • Attention to Nutritional Status:

    • Both medical and non-medical providers should pay close attention to the nutritional status of individuals with ASD.
    • Potential comorbid symptoms, such as those arising from poor diet or gastrointestinal issues, should be closely monitored.

  • Impact on ASD Symptoms:

    • Addressing nutritional deficiencies and comorbid symptoms can lead to significant improvements in ASD-related symptoms, particularly self-injurious or aggressive behaviors.
    • Improvements in overall health can boost functionality and quality of life.

  • Promoting Health Strategies:

    • Strategies to enhance overall health hold promise for improving quality of life in individuals with ASD.

  • Current Recommendations:

    • It is crucial to inform families and caregivers that there are currently no evidence-based recommendations for metabolic treatments for individuals with ASD.
    • Emphasis should be placed on monitoring and improving nutritional status through balanced diet and medical guidance.

Key source: Mierau SB, Neumeyer AM (2019) Metabolic interventions in Autism Spectrum Disorder. Neurobiol Dis 132 ():104544. DOI: 10.1016/j.nbd.2019.104544 PMID: 31351171.

Cite this: ICNApedia contributors.Metabolic derangements and Autism. ICNApedia, The Child Neurology Knowledge Environment. 21 November 2024. Available at: https://icnapedia.org/knowledgebase/articles/metabolic-derangements-and-autism Accessed  21 November 2024. 

Information
Keywords: autism, metabolic derangements in autism, nutritional supplements in autism, omega 3 fatty acids, ketogenic diet in autism, N-acetylcysteine in autism, cerebral folate deficiency, folinic acid in autism, vitamins in autism
Details
Hits: 1056

Text is available under the Cc by nc sa iconCC Attribution-Noncommercial-Share Alike 4.0 International; additional terms may apply. 

Recent Articles