New and Emerging Biomedical Treatments for Autism

New and Emerging Biomedical Treatments for Autism
New and Emerging Biomedical Treatments for Autism
Omega-3 fatty acids, melatonin and digestive enzymes are some of the treatments under investigation.

One in 68 U.S. children are believed to have autism or a related disorder, according to the latest CDC estimate. This is a 30% jump from the 2012 federal estimate. Many treatments have been proposed for Autism Spectrum Disorders (ASD) with the most effective being combined treatments involving specialized and supportive educational programming, communication training (e.g., speech/language therapy), social skills support, and behavioral intervention.1,2

Families commonly seek alternative and complementary biomedical treatments for their children who suffer from ASDs. Global studies report rates of biomedical treatment use for ASD range from 32 to 87% in the U.S. 3-6, 52% in Canada7 and 41% in China.8 A potential rationale for biomedical treatments for autism is their potentially beneficial effect on epigenetic processes, which are increasingly demonstrated to have a role in genetic interactions that underlie the development of ASD.

Significant subsets of children with autism have intestinal inflammation, digestive enzyme abnormalities, metabolic impairments, oxidative stress, mitochondrial dysfunction, and immune problems that range from immune deficiency to hypersensitivity to autoimmunity.9 The list of potential biomedical treatments is long and most have inadequate evidence to judge their potential efficacy.10 Some with efficacy and safety data include melatonin, omega-3 fatty acids, and micronutrients. Additional agents with promise include N-acetylcysteine (NAC), methylcobalamin (methyl B12), and digestive enzymes.


Melatonin is synthesized from serotonin through a series of metabolic pathways starting with L-tryptophan, and abnormalities in these pathways have been reported in insomnia as well as noncircadian disorders such as autism.11 Review and meta-analysis report that of 18 treatment studies, there were five randomized trials (N = 61, 2 to 10 mg/day) where sleep duration (44 min, ES = .93) was increased and sleep onset latency was decreased (39 min, ES = 1.28), but nighttime awakenings were unchanged. Adverse effects were minimal to none.

Omega-3 Fatty Acids

Preliminary evidence suggests that omega-3 fatty acids, which may reduce inflammatory processes, may reduce hyperactivity in children with ASD. Two small pilot studies found non-significant trends suggesting that omega-3 fatty acids may reduce hyperactivity in children with ASD12,13 with a favorable safety profile.14

Another study was done at the University of California at San Francisco (UCSF) with 57 subjects recruited online from 28 states. This was the first pediatric autism study conducted entirely online. The research showed the Internet is a viable and cost-effective method of conducting high-quality and rapid clinical trials in ASD population.

The enrolled children were randomly assigned to either receive 1.3 grams of omega-3 fatty acids or an identical placebo daily for six weeks. Once a week, their  parents received an email asking them to complete outcome measures on how their child was doing and report on the child’s level of hyperactivity. The children’s teachers reported changes in hyperactivity as well.

While the researchers found that the omega-3 fatty acids did not lead to a statistically significant reduction in hyperactivity, they concluded an online trial was a promising technique for evaluating treatments for autism.15

N-acetylcysteine (NAC)

NAC is a glutamatergic modulator and an antioxidant. In a12-week randomized, placebo-controlled study, NAC, was initiated at 900 mg daily for four weeks, then 900 mg twice daily for four weeks, and 900 mg three times daily for four weeks. 33 patients (31 male, 2 female; aged 3.2 to 10.7 years) were randomized. Compared with placebo, NAC resulted in significant improvements on ABC-Irritability (F = 6.80; P < .001; d = .96) with few adverse events.16

Methyl B12 Injection

Deficiency of methyl B12 (methylcobalamine) may occur in some people with ASD due to poor dietary intake, poor absorption, or metabolic dysregulation. Methyl B12 is a vital cofactor for the regeneration of methionine from homocysteine. Fifty-three children between the aged between three and seven years old were enrolled in a study at UCSF we conducted. Eligible children were randomly assigned to eight weeks of treatment with methyl B12 at 75 ug/kg given subcutaneously every three days.

Primary outcome measure was the change in Clinical Global Impression-Improvement (CGI-I) score. The mean at eight weeks was significantly better (lower) in the methyl B12 group (2.4) compared to the placebo group (3.1) (95% CI 1.2 to 0.2, P = .005.) Clinical improvement in CGI-I was significantly correlated with methionine (P = .05), decreases in SAH (P = .007), and improvements in S-adenosylmethionine/S-adenosylhomocysteine ratio.(P = .007). The SAM/SAH ratio is a measure of methylation, a chemical process in which genes are “turned on” or turned off,” influencing neurological functions. These results have been submitted for publication.

Digestive Enzymes

Enzyme deficiencies in children with autism result in an inability to digest protein. The inability to digest protein affects the production of amino acids essential for brain function. One study is testing Luminenz CM-AT, a digestive enzyme, to enhance protein digestion and absorption of essential amino acids in children with autism aged between 3 and 8 years old. It is completed, though published results are pending. 


It is necessary for physicians and families to work together to review promising biomedical treatments that are safe and tolerable, have a rationale for use and fit with the family’s values. In terms of talking with families about biomedical treatments for ASD, physicians should recommend agents with more evidence and caution against agents with little evidence and concerns about safety, such as chelation.

Robert L. Hendren, DO, is director of the Autism and Neurodevelopment Program at the UCSF School of Medicine. Felicia Widjaja, MPH, is a senior clinical research coordinator at the school. Hendren will present on this topic at the U.S. Psychiatric and Mental Health Congress in Orlando, Florida, on September 20.


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