Clinical Roundup: Selected Treatment Options for Autism

I generally routinely recommend omega-3 fatty acids (1 or more g), vitamin D3 (2000–5000 international units), a good multinutrient, probiotics, and digestive enzymes if there are gastrointestinal (GI) issues, and melatonin (2–9 mg) if there is sleep difficulty. Of the dose ranges indicated here, the lower dose is for children and the higher dose is for larger adolescents and adults. Is the combination of these three most likely to work? That is the “million-dollar question.” I and my colleagues have been conducting a study at four sites that do that kind of combination treatment. A very large number of patients will be needed for combination treatments to truly show any kind of believable effectiveness. For omega-3, evidence from studies continues to be either equivocal or positive. Omega-3, long-chain fatty-acid supplementation is reasonable to consider because omega-3 fatty acids are essential for brain development,1 being part of optimal neuronal membranes and being a substrate for the production of eicosanoids (e.g., prostaglandins) necessary for cell communication and immune regulation. In addition, low levels of omega-3 fatty acids have been reported in children with autism spectrum disorder (ASD).2–4 The two omega-3 fatty acids of interest are eicosapentaenoic acid and docosahexaenoic acid. Based on data from other disorders, these fatty acids would be expected to improve mood, attention, and activity level as well as possibly reducing autism symptoms. Vitamin D3 is something that people continue to be interested in and seems to have a good rationale for use. There have been case series or case reports that suggest that the vitamin might be helpful. Adams at al. found that oral vitamin/mineral supplementation is beneficial for improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, adenosine triphosphate, the reduced form of nicotine adenine dinucleotide (NAD), and NAD phosphate.5 This finding suggests a possible benefit derived from a comprehensive digestive enzyme supplement with meals to aid digestion of all proteins and peptides, especially for children with ASD who have GI disturbances. My research team has has been conducting a small vitamin D3 study with children with ASD. Because the effect size is small, studies must be conducted over a long period of time. There is not yet a study that truly shows that vitamin D3 is indicated for ASD treatment, although Mostafa and Al-Ayadhi found that 70% of children with autism were below the 30-ng vitamin D3 blood level, which is what most experts consider to be deficient.6 Some say it is 20 ng. If a vitamin D3 blood level of 30 ng were considered to be deficient, this would suggest that a lot of children with autism would need to receive supplementation. Enzyme deficiencies in children with autism result in a reduced ability to digest protein, which affects the availability of amino acids essential for brain function. There is increasing evidence for a gut–brain connection associated with ASD, at least in some cases. N-acetylcysteine (NAC) is an ingestible complementary and alternative treatment that has also shown great potential. NAC is a glutamatergic modulator and antioxidant that was examined in a 12-week, double-blinded, randomized placebocontrolled study in children with ASD.7 It has become fairly accepted in the field to think about recommending melatonin for people with developmental disabilities who have sleep problems. Rossignol and Frye published a very good review and meta-analysis of 35 melatonin studies.8,9 These included 18 treatment studies, of which 13 were uncontrolled and five were randomized, double-blinded, placebo-controlled crossover trials. Six studies of night-time administration led to improvements in daytime behavior. Within the five randomized controlled studies, melatonin was associated with increases in sleep duration and decreases in sleeponset latency, but night-time awakenings were unchanged. Side-effects were minimal to none. Unfortunately, small sample sizes, variability in sleep assessments, and lack of follow-up limit the conclusiveness of these studies, but, overall, melatonin is one of the best-studied complementary and alternative treatments for ASD. Treatment with melatonin has a clear physiologic rationale; use of melatonin is sensible, easy, inexpensive, and safe.10