NAC has a variety of impact on the microbiome, over 800 bacteria impacted. Predicted impact of NAC on the microbiome reported for Autism is that it will increase the shifts overall.

This post looks at reported studies (often these studies are very small samples which makes results unreliable).

• The Use of N-acetylcysteine Supplementation to Decrease Irritability in Four Youths With Autism Spectrum Disorders [2020] Positive subjective response, but ” the authors cannot know whether use of NAC or other medication or behavioral strategies were responsible for such changes because this study was not a controlled trial.”
• Acetylcysteine for Treatment of Autism Spectrum Disorder Symptoms [2015] Subjective improvement in one person “small controlled trials and case reports suggest that acetylcysteine use is associated with improvements in irritability and aggression in prepubertal children with ASD; “
• A Randomized Double Blind Placebo Controlled Clinical Trial of N-Acetylcysteine Added to Risperidone for Treating Autistic Disorders [2013] “The mean score of irritability in the NAC+risperidone and placebo+risperidone groups at baseline was 13.2(5.3) and 16.7(7.8), respectively. The scores after 8 weeks were 9.7(4.1) and 15.1(7.8), respectively. …. The most common adverse effects in the NAC+risperidone group were constipation (16.1%), increased appetite (16.1%), fatigue (12.9%), nervousness (12.9%), and daytime drowsiness (12.9%). There was no fatal adverse effect.”

Bottom Line

There are subjective reports of improvement that looked only at irritability and did not report on changes of other symptoms. The studies tend to focus on high irritability ASD.

Dosage from studies:  NAC (1200 mg/day). NAC has a half life of 6 hrs, so a dosage of 300 mg four times a day, or 400mg three time a day should be considered.

Low levels of Oxytocin has been associated with autism. The impact of administration of Oxytocin is fuzzy.

Animal model research has documented that the administration of OXT and AVP was able to rescue autistic traits and increase social skills [119,120,121]. In humans, there is some evidence that the administration of oxytocin reduces some dysfunctional behaviors associated with autism, especially social skills, repetitive behaviors, anxiety, irritability, and self-injurious behaviors [122,123,124]. However, a recent meta-analysis that reviewed randomized controlled trials on ASD symptomatology did reveal that there was no benefit of oxytocin over placebo and provided further proof to support existing evidence [125].

The Neurochemistry of Autism , 2020

I know from other readings that extracts or refine products often are not as effective as the same chemical “au-natural”. The reason is that the au-natural version have additional chemicals that may work as a catalyst to improve the impact.

In keeping with this approach, I looked for ways of increasing it via the microbiome. This is what I found:

• “Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models [2020]

 It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models. 

Microbial Lysate Upregulates Host Oxytocin, 2016

I could not find studies for any other probiotics increasing oxytocin.

Summary

I checked Novel and Emerging Treatments for Autism Spectrum Disorders: A Systematic Review (2009) and found L. Reuteri was not listed, so this would be a newer suggestion.

• Grade A treatments for ASD include melatonin, acetylcholinesterase inhibitors, naltrexone, and music therapy.

• Grade B treatments include carnitine, tetrahydrobiopterin, vitamin C, alpha-2 adrenergic agonists, hyperbaric oxygen treatment, immunomodulation and anti-inflammatory treatments, oxytocin, and vision therapy.

• Grade C treatments for ASD include carnosine, multivitamin/mineral complex, piracetam, polyunsaturated fatty acids, vitamin B6/magnesium, elimination diets, chelation, cyproheptadine, famotidine, glutamate antagonists, acupuncture, auditory integration training, massage, and neurofeedback.

It would be nice if someone did an update of these based on the last 11 years of research.

A reader passed me a link to an article published on May 23, 2020 which was very interesting.

Dysbiosis of Gut Fungal Microbiota in Children With Autism Spectrum Disorders, J Autism Dev Disorders , 2020 May 23. doi: 10.1007/s10803-020-04543-y. 

” Among the 507 genera identified, Saccharomyces and Aspergillus showed significant differences between ASD (59.07%) and Control (40.36%), indicating that they may be involved in the abnormal gut fungal community structure of ASD. When analyzed at the species level, a decreased abundance in Aspergillus versicolor was observed while Saccharomyces cerevisiae was increased in children with ASD relative to controls. “

The implication are simple:

• Do not supplement with any Saccharomyces probiotics. Check carefully any probiotics that you use to insure there is none

• Supplement with Aspergillus probiotics. There is one that I know of (and use). It is from Japan and called Strong Wakamoto. It consists of:
  • lactobacillus salivarius
  • aspergillus oryzae

I have been in recent discussion with a Ph.D. researching aspergillus oryzae because it frees up a lot of nutrients in food. There are over 3000 studies citing aspergillus, for example:

Production of GABA-enriched idli with ACE inhibitory and antioxidant properties using Aspergillus oryzae: the antihypertensive effects in spontaneously hypertensive rats.

A combination of acid lactase from Aspergillus oryzae and yogurt bacteria improves lactose digestion in lactose maldigesters synergistically: A randomized, controlled, double-blind cross-over trial.

Bottom Line

This is based on a report of a distinctive shift. Conceptually, Wakamoto would complete with Saccharomyces, reducing their numbers and altering the microbiome. There are no clinical studies done. Wakamoto is deemed safe and has been in use for a very long time in Japan.

This is a summary of studies on PubMed. Fecal Matter Transplants (FMT) works well permanently for some conditions, often just for a few months for other conditions, and rarely for other conditions. FMT does have risks to it. It is effectively an organ transplant and we are still learning about “compatible donors”. In a few cases, diseases may be passed; in rare cases deaths have been reported.

• “Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.” 2019
• “An open-label study and a two-year follow-up suggest that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.” 2019

• Microbiota Transfer Therapy (MTT) involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. … clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. 2017
  • “we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. ” [2019]

Bottom Line

• Only a single reported study on 18 participants is in the literature.
• Following the identical procedure is strongly recommended (often FMT is done as a “one shot” process, this extended doses for 8 weeks may be a very significant factor for it’s success)
• Results were good on a subjective basis.
  • Technical issue: There was no control group used
• Suggested donor would be a blood relative (ideally sibling) whose microbiome has been tested and show none of the shifts reported with autism which the target patient has.
• [Speculation] Having the same blood type may contribute to higher success rate.