Natural Products and Biologics
There is some limited evidence that suggests melatonin may help with sleep problems in children with ASD.
The Evidence Base
- The evidence base on the efficacy of melatonin on sleep problems in children with ASD consists of several randomized controlled trials limited by the small number of study participants. Melatonin is often used for children with ASD who have sleep disorders, despite the limited published evidence in this population.
- A 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.
- A 2012 controlled trial of 24 children examining dose, tolerability, and outcomes of melatonin for sleep in children with ASD found that supplemental melatonin improved sleep latency in most children at 1 or 3 mg dosages. Findings indicated that melatonin was effective in the first week of administration, maintained effects over several months, and showed improvement in sleep, behavior, and parenting stress.
- A 2006 randomized controlled trial of 7 children, ages 4 to 16 years, with ASD found that melatonin (5 mg per day for 4 weeks) improved sleep latency and total sleep duration, and reduced the number of wakings per night compared to placebo and baseline data.
- A 2009 placebo-controlled trial evaluated the efficacy of melatonin (3 mg per day for 2 weeks) in 12 children, ages 2 to 15 years, with ASD or fragile X syndrome or both. The participants in the melatonin group had improvements in total sleep duration and sleep-onset time compared to placebo. No significant changes were seen in sleep latency or wakings per night between the melatonin and control groups.
- A 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.
- Findings from a 2012 study in 24 children indicated that melatonin in dosages of 1 or 3 mg per day were well tolerated and safe over a 14-week duration.
- 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.
The Evidence Base
- The evidence base on efficacy of omega-3 fatty acid supplementation consists of only a couple of small randomized controlled trials, as well as a Cochrane review on these studies.
- A 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.
- 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.
The current clinical evidence does not support the use of probiotics to modify behavior in people with ASD.
The Evidence Base
- The evidence base on efficacy of probiotic supplementation for ASD consists of several randomized controlled trials and at least one review.
- A 2015 review of four studies concluded that overall, there is currently no convincing evidence that probiotic supplementation alters behavior in children with ASD.
- None of the studies included in the review reported any adverse effects. However, there have been reports linking probiotics to severe side effects, such as dangerous infections, in people with serious underlying medical problems.
Evidence suggests that single or multiple dose intravenous secretin, a gastrointestinal hormone, is not effective as a treatment for ASD.
The Evidence Base
- The evidence base on efficacy of secretin for ASD consists of several randomized controlled trials, which are summarized in two systematic reviews.
- A 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.
- A 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.
- 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.
The Evidence Base
- The evidence base on efficacy of the combination of vitamin B6 and magnesium consists of only a few small studies of poor methodological quality.
- A 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.
- The studies included in the Cochrane review had no reported clinically significant side effects during administration of high doses of vitamin B6 and magnesium.
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.
The Evidence Base
- The evidence base on efficacy of chelation for ASD consists of a Cochrane review of one randomized controlled trial, which had methodological limitations.
- A 2015 Cochrane review of one 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.
- 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.
Gluten-Free and Casein-Free Diet
There is evidence that parents commonly put their children with ASD on exclusion diets. Despite this common practice, there is insufficient evidence to support the use of gluten-free and/or casein free diets as an effective treatment for children with ASD. Nutritionists have raised concerns about potential harms and risks of such diets, but evidence to support these risks is lacking.
The Evidence Base
- The evidence base on efficacy of gluten-free and/or casein-free diets for the treatment of ASD consists of only a few randomized controlled trials and a Cochrane review.
- A 2008 Cochrane review of two studies examined the evidence of gluten-free and casein-free diet as an intervention to improve behavior, and cognitive and social functioning in children with ASD. Findings from the first study indicated that a combined gluten-free and casein-free diet reduced autistic traits, while the second study showed no significant difference in outcome measures between the diet group and the control group.
- None of the studies included in the Cochrane review reported on adverse outcomes or potential adverse effects of gluten-free and/or casein-free diets in this population.
There is limited evidence that the high-fat, very low carbohydrate “ketogenic” diet may help with seizures, which are sometimes associated with autism.
The Evidence Base
- The evidence base on efficacy of a ketogenic diet for children with ASD consists of only a few studies and a case report.
- A 2014 review examining findings from one study and a single case report indicated that children with ASD treated with a ketogenic diet showed a reduction in frequency of seizures and exhibited some behavioral improvements.
- A 2013 systematic review of treatments for seizures in ASD found limited evidence to support the use of traditional non-antiepileptic drugs, such as the ketogenic and modified Atkins diet.
- Ketogenic diets have shown some promising results in children with epilepsy. Because seizures are sometimes associated with ASD, some parents try ketogenic diets for their children with ASD. A 2016 Cochrane review examined the efficacy and tolerability of a ketogenic diet for epilepsy in seven randomized controlled trials involving 427 children and adolescents. It should be noted that none of the studies involved participants with ASD. The authors concluded that, overall, the studies showed promising results for the use of a ketogenic diet for treating epilepsy. Because of the limited number of studies, small sample sizes and a sole pediatric population, however, the overall quality of evidence is poor.
- The mechanism of action of the ketogenic diet is not fully understood, and caution should be taken to avoid deleterious adverse effects or refractory outcomes. Ketogenic diets should be supervised by a nutritionist to ensure that children get the appropriate nutritional requirements for growth. Reported adverse effects include short-term gastrointestinal-related disturbances, to longer-term cardiovascular complications.
Mind and Body Practices
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.
The Evidence Base
- The evidence base on acupuncture for ASD symptoms consists of several randomized controlled trials, most of which were conducted outside of the United States, as well as a systematic review and a Cochrane review.
- A 2012 systematic review of 11 randomized controlled trials found “mixed” evidence of acupuncture’s effectiveness as a treatment for ASD symptoms.
- A 2011 Cochrane review of 10 randomized controlled trials involving 390 children ages 3 to 18, conducted in Hong Kong, 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.
- 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 were unclear.
There is some evidence that music therapy may help to improve some social and behavioral skills in children with ASD.
The Evidence Base
- The evidence base on efficacy of music therapy for children with ASD consists of several studies and a recent Cochrane systematic review.
- A 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.
- 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.
Hyperbaric Oxygen Therapy
Current evidence does not support the use of hyperbaric oxygen therapy as an effective treatment for ASD.
The Evidence Base
- The evidence base on efficacy of hyperbaric oxygen therapy for ASD consists of a few randomized controlled trials, reviews, and a report issued by the Undersea and Hyperbaric Medical Society.
- A 2015 review by the Undersea and Hyperbaric Medical Society found that the evidence is weak for the use of hyperbaric oxygen in ASD, with only one methodologically flawed study showing treatment benefit. The reviewers concluded that hyperbaric oxygen therapy should not be recommended for ASD treatment until more conclusive favorable results and long-term outcomes are demonstrated from well-designed trials.
- A 2009 randomized controlled trial of 62 children with ASD received either hyperbaric oxygen or control (slightly pressurized room air), twice a day, 5 days per week for 4 consecutive weeks. Compared with baseline data, the participants in the hyperbaric oxygen group had improvements in a range of behavioral domains; however, since that study was published, the research has come into question, citing a number of methodological flaws. A subsequent trial replicated the study using the same oxygen and pressure parameter (except for a longer treatment period) and found no differences between hyperbaric oxygen therapy and placebo groups on a wide range of outcomes.
- There are known risks of barotrauma and exacerbation of pulmonary disease at higher atmospheric pressures.
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