NCCIH Clinical Digest

for health professionals

Autism Spectrum Disorder and Complementary Health Approaches: What the Science Says

April 2021

Clinical Guidelines, Scientific Literature, Info for Patients: 
Autism Spectrum Disorder and Complementary Health Approaches

Melatonin

Research findings suggest that melatonin may help with sleep problems in children with ASD.

What Does the Research Show?

  • A 2020 review of the literature concluded that melatonin supplementation is both safe and efficacious in the treatment of sleep disorders for children with ASD.
  • A 2017 randomized controlled trial involving a total of 125 children and adolescents found that a formulation of prolonged-release melatonin was efficacious and safe for treatment of insomnia in children and adolescents with ASD with/without attention-deficit hyperactivity disorder (ADHD) and neurogenetic disorders. After 13 weeks of treatment, participants slept on average 57.5 minutes longer at night with the melatonin intervention compared to 9.14 minutes with placebo. Sleep latency decreased by 39.6 minutes on average in the melatonin treatment group and 12.5 minutes with placebo without causing earlier wakeup time.
  • 2011 systematic review and meta-analysis of 5 randomized, double-blind, placebo-controlled trials involving a total of 57 participants with ASD found that relative to baseline data, melatonin increased total sleep duration by an average of 73 minutes and decreased sleep latency by an average of 66 minutes. Similar beneficial results were observed when melatonin was compared with placebo.

Safety

  • 2014 review of melatonin as an option for managing sleep disorders in children with ASD found no serious safety concerns attributed to melatonin use in this population in the evaluated studies. Some reported adverse effects associated with melatonin use in children with ASD include morning drowsiness, increased enuresis, headache, dizziness, diarrhea, rash, and hypothermia. Melatonin is primarily metabolized by CYP1A2 and CYP2C19, so inhibitors of CYP1A2 may increase melatonin concentrations. Melatonin may decrease blood pressure or serum glucose, so patients who are being treated with agents that affect blood pressure or serum glucose concentrations should be monitored closely.
  • A 2018 prospective, open-label follow-up study evaluated the nightly 2, 5, or 10 mg prolonged-release formulation of melatonin in 95 children and adolescents who completed a 13-week double-blind trial. The study found that this formulation of prolonged-release melatonin was a safe option for long-term treatment (up to 52 weeks reported in the study) of children with ASD and neurogenetic disorders who have insomnia.
  • Most studies of melatonin have examined short-term use; however, there is a lack of long-term safety data.

Omega-3 Fatty Acid Supplementation

At present, there is insufficient evidence that omega-3 fatty acid supplementation is an effective treatment for ASD.

What Does the Research Show?

  • A 2017 systematic review of 19 randomized controlled trials concluded that there is little evidence to support the use of nutritional supplements or dietary therapies for children with ASD.
  • 2011 Cochrane review of two small randomized controlled trials concluded that there is no high-quality evidence that omega-3 fatty acid supplementation is effective for improving core or associated symptoms of ASD.

Safety

  • Omega-3 fatty acid supplements usually do not have negative side effects. When side effects do occur, they typically consist of minor gastrointestinal symptoms.
  • It is uncertain whether people with fish or shellfish allergies can safely consume fish oil supplements.

Probiotics

The current clinical evidence does not support the use of probiotics to modify behavior in people with ASD.

What Does the Research Show?

  • A 2019 systematic review of six clinical trials concluded that overall, there is limited efficacy of probiotics in the management of gastrointestinal or behavioral symptoms in children with ASD.
  • 2015 review of four studies concluded that overall, there is currently no convincing evidence that probiotic supplementation alters behavior in children with ASD.

Safety

  • None of the studies included in the reviews reported adverse effects. However, there have been reports linking probiotics to severe side effects, such as dangerous infections, in people with serious underlying medical problems.

Secretin

Evidence suggests that single or multiple dose intravenous secretin, a gastrointestinal hormone, is not effective as a treatment for ASD.

What Does the Research Show?

  • 2012 Cochrane review of 16 randomized controlled trials of intravenous secretin compared to placebo in a total of more than 900 children found no improvements for core features of ASD. The reviewers concluded that there is strong evidence that single or multiple dose intravenous secretin is not effective, and it should not be recommended or administered as a treatment for ASD.
  • 2011 systematic review of seven randomized controlled trials concluded that there is clear evidence that secretin lacks benefit. The reviewers noted that because of the high strength of evidence for lack of effectiveness, secretin as an intervention for ASD warrants no further study.

Safety

  • The 2012 Cochrane review also analyzed the studies for adverse effect and found that no serious events, such anaphylaxis, were reported. However, several studies reported some adverse events following secretin administration, including tantrums, hyperactivity, aggression, flushing, and other behavioral symptoms.

Vitamin B6 and Magnesium

To date, there is insufficient evidence to support the use of vitamin B6 and magnesium as a treatment option for ASD.

What Does the Research Show?

  • 2005 Cochrane review of one small study concluded that because of the small number of studies, their low methodological quality, and small sample sizes, no recommendation can be advanced regarding the use of vitamin B6 and magnesium as a treatment for ASD.

Safety

  • The studies included in the Cochrane review had no reported clinically significant side effects during administration of high doses of vitamin B6 and magnesium.

Chelation

There is no evidence that indicates the effectiveness of pharmaceutical chelation as an intervention for ASD. Furthermore, there is substantial evidence that there is no link between heavy metals and autism.

What Does the Research Show?

  • 2015 Cochrane review of 1 randomized controlled trial of oral DMSA chelation involving 77 children with ASD found no evidence to suggest that pharmaceutical chelation is an effective intervention for ASD. The reviewers noted that before any more trials on chelation for ASD are conducted, evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed.

Safety

  • There have been previous reports of serious adverse events from intravenous chelation, including hypocalcemia, renal impairment and reported death. The 2015 Cochrane review concluded that given these reports, the risks of chelation for ASD currently outweigh any possible (or potential) benefits.

Music Therapy

There is some evidence that music therapy may help to improve some social and behavioral skills in children with ASD.

What Does the Research Show?

  • A 2018 randomized controlled trial of 51 children (ages 6 to 12) with ASD found that 8 to 12 weeks of individual music intervention improved social communication and functional brain connectivity.
  • 2014 Cochrane review of 10 studies involving a total of 165 children with ASD found that music therapy was superior to “placebo” therapy or standard care for social interaction, non-verbal and verbal communication skills, initiating behavior, and social-emotional reciprocity. The review concluded that music therapy may help children with ASD to improve their skills in areas such as social interaction and communication, and may also contribute to increasing social adaptation skills in children with ASD and to promoting the quality of parent-child relationships.
  • A 2017 randomized controlled trial of 364 children in 9 countries found that improvisational music therapy, when compared with enhanced standard care (i.e., usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD), resulted in no significant difference in severity of symptoms based on the Autism Diagnostic Observation Schedule social affect domain over 5 months.

Safety

  • Music therapy for people with ASD appears to be safe. None of the studies included in the Cochrane review above reported any side effects caused by music therapy.

Acupuncture

Results of clinical trials on the effectiveness of acupuncture for ASD have been mixed, but there is currently no conclusive evidence to support the use of acupuncture for the treatment of ASD.

What Does the Research Show?

  • 2012 systematic review of 11 randomized controlled trials found “mixed” evidence of acupuncture’s effectiveness as a treatment for ASD symptoms.
  • 2011 Cochrane review of 10 randomized controlled trials involving 390 children ages 3 to 18, conducted in China and Egypt, concluded that there is no conclusive evidence that acupuncture is effective for treatment of ASD in children, and no randomized controlled trials have been conducted in adults.
  • A 2019 systematic review and meta-analysis of 14 trials with 968 participants (11 of the trials were included in the meta-analysis) found scalp acupuncture treatment may be an effective treatment for children with ASD. The reviewers noted, however, that given the heterogeneity and number of participants in the reviewed studies, randomized controlled trials of high quality and design are required before widespread application of this therapy.

Safety

  • Relatively few complications from using acupuncture have been reported. Still, complications have resulted from use of nonsterile needles and improper delivery of treatments.
  • A few studies in children with ASD included in the reviews above reported either no adverse events or minor side effects, but relevance between these reported adverse effects and acupuncture was unclear.

References

  • Bieleninik L, Geretsegger M, Mossler K, et al. Effects of improvisational music therapy vs enhanced standard care on symptom severity among children with autism spectrum disorder: The TIME-A Randomized Clinical Trial. JAMA. 2017;318(6):525-535.
  • Cheuk DKL, Wong V, Chen WX. Acupuncture for autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews. 2011;9:CD007849.
  • Damiani JM, Sweet BV, Sohoni P. Melatonin: An option for managing sleep disorders in children with autism spectrum disorder. American Journal of Health-System Pharmacy. 2014;71(2):95-101.
  • Frye RE, Rossignol D, Casanova MF, et al. A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel. Frontiers in Public Health. 2013;1:31.
  • Garstang J, Wallis M. Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child: Care, Health and Development. 2006;32(5):585-589.
  • Geretsegger M, Elefant C, Mössler KA, et al. Music therapy for people with autism spectrum disorder. Cochrane Database of Systematic Reviews. 2014;6:CD004381.
  • Gringas P, Nir T, Breddy J, et al. Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2017;56(11):948-957.
  • James S, Montgomery P, Williams K. Omega-3 fatty acids supplementation for autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews. 2011;11:CD007992.
  • James S, Stevenson SW, Silove N, et. al. Chelation for autism spectrum disorder (ASD). Cochrane Database of Systematic Reviews. 2015;5:CD010766.
  • Krishnaswami S, McPheeters ML, Veenstra-Vanderweele J. A systematic review of secretin for children with autism spectrum disorders. Pediatrics. 2011;127(5):e1322-1325.
  • Lee MS, Choi T-Y, Shin B-C, et al. Acupuncture for children with autism spectrum disorders: a systematic review of randomized clinical trials. Journal of Austism and Developmental Disorders. 2012;42(8):1671-1683.
  • Liu C, Li T, Wang Z, et al. Scalp acupuncture treatment for children’s autism spectrum disorders: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(13):e14880.
  • Malow B, Adkins KW, McGrew SG, et al. Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. Journal of Autism and Developmental Disorders. 2012;42(8):1729-1737.
  • Maras A, Schroder CM, Malow BA, et al. Long-term efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder. Journal of Child and Adolescent Psychopharmacology. 2018;28(10):699-710.
  • Ng QX, Loke W, Venkatanarayanan N, et al. A systematic review of the role of prebiotics and probiotics in autism spectrum disorders. Medicina (Kaunas). 2019;55(5):129.
  • Rzepka-Migut B, Paprocka J. Efficacy and safety of melatonin treatment in children with autism spectrum disorder and attention-deficit/hyperactivity disorder—a review of the literature. Brain Sciences. 2020;10(4):219.
  • Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Developmental Medicine and Child Neurology. 2011;53(9):783-792.
  • Sathe N, Andrews JC, McPheeters ML, et al. Nutritional and dietary interventions for autism spectrum disorder: a systematic review. Pediatrics. 2017;139(6):e20170346.
  • Sharda M, Tuerk C, Chowdhury R, et al. Music improves social communication and auditory-motor connectivity in children with autism. Translational Psychiatry. 2018;8(1):231.
  • Srinivasjois R, Rao S, Patole S. Probiotic supplementation in children with autism spectrum disorder. Archives of Disease in Childhood. 2015;100(5):505-506.
  • Williams K, Wray JA, Wheeler DM. Intravenous secretin for autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews. 2012;4:CD003495.
  • Wirojanan J, Jacquemont S, Diaz R, et al. The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. Journal of Clinical Sleep Medicine. 2009;5(2):145-150.

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