Stanford Study: NAC Shows Promise as a Treatment for Repetitive Behaviours Associated with Autism

We figured since there are really no negative side effects to taking this and it's simply a nutritional supplement.  We would go ahead and give it a shot, even before the bigger studies are out.  You can follow them on Twitter to get more updates on new studies.

BY ERIN DIGITALE

Antonio Hardan

A specific antioxidant supplement may be an effective therapy for some features of autism, according to a pilot trial from the Stanford University School of Medicine and Lucile Packard Children’s Hospital that involved 31 children with the disorder.

The antioxidant, called N-Acetylcysteine, or NAC, lowered irritability in children with autism as well as reduced the children’s repetitive behaviors. The researchers emphasized that the findings must be confirmed in a larger trial before NAC can be recommended for children with autism.

Irritability affects 60 to 70 percent of children with autism. “We’re not talking about mild things: This is throwing, kicking, hitting, the child needing to be restrained,” said Antonio Hardan, MD, the primary author of the new study. “It can affect learning, vocational activities and the child’s ability to participate in autism therapies.”

The study appears in the June 1 issue of Biological Psychiatry. Hardan is an associate professor of psychiatry and behavioral sciences at Stanford and director of the Autism and Developmental Disabilities Clinic at Packard Children’s. Stanford is filing a patent for the use of NAC in autism, and one of the study authors has a financial stake in a company that makes and sells the NAC used in the trial.

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Finding new medications to treat autism and its symptoms is a high priority for researchers. Currently, irritability, mood swings and aggression, all of which are considered associated features of autism, are treated with second-generation antipsychotics. But these drugs cause significant side effects, including weight gain, involuntary motor movements and metabolic syndrome, which increases diabetes risk. By contrast, side effects of NAC are generally mild, with gastrointestinal problems such as constipation, nausea, diarrhea and decreased appetite being the most common.

The state of drug treatments for autism’s core features, such as social deficits, language impairment and repetitive behaviors, is also a major problem. “Today, in 2012, we have no effective medication to treat repetitive behavior such as hand flapping or any other core features of autism,” Hardan said. NAC could be the first medication available to treat repetitive behavior in autism — if the findings hold up when scrutinized further.

The study tested children with autism ages 3 to 12. They were physically healthy and were not planning any changes in their established autism treatments during the trial. In a double-blind study design, children received NAC or a placebo for 12 weeks. The NAC used was a pharmaceutical-grade preparation donated by the drug manufacturer Bioadvantex Inc. Subjects were evaluated before the trial began and every four weeks during the study using several standardized surveys that measure problem behaviors, social behaviors, autistic preoccupations and drug side effects.

During the 12-week trial, NAC treatment decreased irritability scores from 13.1 to 7.2 on the Aberrant Behavior Checklist, a widely used clinical scale for assessing irritability. The change is not as large as that seen in children taking antipsychotics. “But this is still a potentially valuable tool to have before jumping on these big guns,” Hardan said.

In addition, according to two standardized measures of autism mannerisms and stereotypic behavior, children taking NAC showed a decrease in repetitive and stereotyped behaviors.

“One of the reasons I wanted to do this trial was that NAC is being used by community practitioners who focus on alternative, non-traditional therapies,” Hardan said. “But there is no strong scientific evidence to support these interventions. Somebody needs to look at them.”

Hardan cautioned that the NAC for sale as a dietary supplement at drugstores and grocery stores differs in some important respects from the individually packaged doses of pharmaceutical-grade NAC used in the study, and that the over-the-counter version may not produce the same results. “When you open the bottle from the drugstore and expose the pills to air and sunlight, it gets oxidized and becomes less effective,” he said.

Although the study did not test how NAC works, the researchers speculated on two possible mechanisms of action. NAC increases the capacity of the body’s main antioxidant network, which some previous studies have suggested is deficient in autism. In addition, other research has suggested that autism is related to an imbalance in excitatory and inhibitory neurotransmitters in the brain. NAC can modulate the glutamatergic family of excitatory neurotransmitters, which might be useful in autism.

The scientists are now applying for funding to conduct a large, multicenter trial in which they hope to replicate their findings.

“This was a pilot study,” Hardan said. “Final conclusions cannot be made before we do a larger trial.”

Hardan’s collaborators at Stanford were Lawrence Fung, MD, a psychiatry resident; Robin Libove and Surekha Nair, MD, social science research assistants; postdoctoral scholar Tetyana Obukhanych, PhD; Lenore Herzenberg, DSc, professor of genetics and member of the Stanford Cancer Institute; and Rabindra Tirouvanziam, PhD, a former instructor in pediatric pulmonary medicine at Stanford who is now at the Emory University School of Medicine.

The research was supported by a grant from the Escher Family Fund at the Silicon Valley Community Foundation. Herzenberg and Tirouvanziam are listed as inventors on two patents for NAC used for treating cystic fibrosis that are licensed by Bioadvantex Inc., which supplied NAC for the trial. Herzenberg also has equity in Bioadvantex.

Information about the Stanford Autism Center at Packard Children’s Hospital and the Department of Psychiatry and Behavioral Sciences, which also supported the research, is available online athttp://autism.lpch.org and http://psychiatry.stanford.edu. 

Navigating Autism: Jonathan's Journey to Better Sleep, Gut Health, and Well-being

 By Juan Fermin

As a parent, there's nothing more challenging than seeing your child struggle, especially when they can't articulate their pain. My son, Jonathan, who is non-verbal and autistic, faced immense difficulties from a young age. Born two months premature, his early years were marked by severe sleep disturbances, relentless hyperactivity, and debilitating gastric issues that often led to moodiness and even violent outbursts. These challenges not only impacted Jonathan's quality of life but also cast a shadow over our entire household, particularly during the stressful nighttime hours.

Over the years, I've embarked on a deeply personal journey to understand and alleviate Jonathan's struggles. This journey has been filled with trials, errors, and moments of profound discovery. What I've learned, often through unconventional approaches and persistent observation, has been nothing short of transformative for Jonathan's health and our family's peace of mind. I realized that many other parents are likely grappling with similar issues, and my hope is that by sharing Jonathan's story and the strategies that have worked for us, I can offer a beacon of hope and practical insights to others in the autism community. This article will delve into our experiences with specific interventions, from addressing the oxidation of supplements to understanding the profound impact of diet on gut health and overall well-being. It's a testament to the power of perseverance and the incredible resilience of children like Jonathan.

The NAC Conundrum: Oxidation and Efficacy

One of the first recommendations I frequently encountered for addressing various challenges in children with autism was N-Acetyl Cysteine, or NAC. NAC is a precursor to glutathione, a powerful antioxidant in the body, and has been studied for its potential benefits in reducing irritability, repetitive behaviors, and improving social interaction in individuals with Autism Spectrum Disorder (ASD) [1, 2, 3, 4, 5]. However, I quickly learned that while the potential benefits of NAC were promising, its inherent instability presented a significant hurdle.

NAC is highly susceptible to oxidation, especially when exposed to air and moisture [6, 7, 8]. This means that many commercially available NAC supplements can degrade before they even reach the consumer, rendering them less effective or even inert. I experienced this firsthand; despite trying various brands, I saw little to no improvement in Jonathan's condition. It was a frustrating period, as I was investing in something that, unbekadst to me, was likely losing its potency due to improper manufacturing and packaging.

My breakthrough came when I discovered a brand that manufactured NAC in an oxygen-free environment and individually bubble-wrapped each dose. This meticulous approach to packaging was crucial in preserving the integrity and efficacy of the supplement. Once I started giving Jonathan this specific brand, I began to observe noticeable improvements. This experience underscored a critical lesson: the quality and stability of supplements are paramount, especially for sensitive compounds like NAC. It's not just about what you give, but how it's prepared and protected to ensure its bioavailability and effectiveness.

Melatonin and the Quest for Restful Sleep

Sleep, or the lack thereof, was one of the most debilitating issues we faced with Jonathan. He would often stay awake until 1 or 2 AM, only to wake up after a mere hour or two of sleep, sometimes attempting to go outside completely naked. These nights were incredibly stressful and disruptive for our entire household. Like many parents, I initially turned to melatonin, a hormone that regulates sleep-wake cycles. However, following standard medical advice to administer 0.5 mg or 1 mg yielded no results. This was a common pitfall, as research suggests that children with autism often have significantly lower endogenous melatonin levels, making typical dosages ineffective [9, 10].

Through trial and error, I discovered that Jonathan required a much higher dose. I started with 5 mg, which helped him fall asleep, but he would still wake up around 3 or 4 AM. This partial success led me to refine our nighttime routine. I began giving him a hot bath immediately after his melatonin dose, scrubbing him down with Epsom salts. This combination proved to be a game-changer. Every night we followed this routine, Jonathan would sleep through the entire night, consistently getting a minimum of eight, and often ten, hours of uninterrupted sleep. As an unexpected bonus, the early signs of arthritis I was experiencing at the time completely disappeared, likely due to the magnesium absorption from the Epsom salts.

Currently, Jonathan receives 10 mg of melatonin both in the evening and in the morning. This seemingly high dosage is based on the understanding that melatonin is not just a sleep aid but also a potent antioxidant, even more effective than glutathione in some respects [11]. By supporting glutathione production and acting as a direct antioxidant, melatonin helps reduce inflammation, which in turn contributes to lower stress levels and improved overall well-being. This dual role of melatonin—as a sleep regulator and a powerful antioxidant—has been crucial in managing Jonathan’s symptoms and improving his quality of life.

Unraveling Allergies and the Raw Milk Revelation

Jonathan’s health challenges extended beyond sleep to significant issues with allergies and gastric distress. Initially, we focused solely on gastric problems, but after consulting with several doctors, we realized the necessity of seeing an allergist. The diagnosis was extensive: allergies to soy, eggs, milk, nuts, and several other substances. By the time he was 18 or 19, many of these allergies had subsided, with the egg allergy being the most persistent. However, even seemingly innocuous items like milk consistently posed a problem.

For a while, pea protein milk, specifically a brand called Ripple milk, seemed to be a viable alternative. It worked well initially, but eventually, even that began to cause gastric issues. This continuous struggle led me to explore less conventional avenues, and I stumbled upon an article that profoundly shifted my perspective. The article detailed a study conducted on children living on dairy farms in England. The researchers were initially looking for evidence that these children, who consumed raw milk, would exhibit worse health outcomes compared to those who drank pasteurized milk. What they discovered, however, was astonishing.

Contrary to their initial hypothesis, the study found that children who consumed raw milk were not only significantly less prone to illness but also had far lower levels of allergies than children who drank pasteurized milk [12, 13, 14]. This revelation was a game-changer for me. Given that raw milk is largely illegal for human consumption in South Florida, I sought to create a product that mimicked its beneficial properties as closely as possible. My current formulation, still undergoing refinement, combines probiotics, enzymes, whey, and colostrum. While I’m not yet ready to disclose the precise ingredients, the results have been remarkable. Jonathan, who used to wake up screaming and crying almost daily due to stomach pain, now wakes up happy and ready for school. His teachers, many of whom have known him for years, have observed a fantastic difference in his overall mood and well-being, a testament to the profound impact of addressing his gut health and allergies.

The Gut-Brain Connection: Sugar, Processed Grains, and Inflammation

Jonathan’s journey has consistently highlighted the critical link between diet, gut health, and overall well-being, particularly in the context of autism. Research increasingly points to a significant gut-brain connection, suggesting that imbalances in the gut microbiome and inflammation can profoundly impact neurological function and behavior in individuals with ASD [15, 16, 17]. My experience with Jonathan has strongly validated this scientific understanding.

One of the most crucial dietary interventions we implemented was drastically reducing sugar and processed grains from Jonathan’s diet. These substances are known to contribute to systemic inflammation and can negatively impact gut health, potentially exacerbating symptoms in sensitive individuals [18, 19]. While sugar is detrimental to everyone, children with autism appear to be particularly susceptible and sensitive to its effects. For instance, if rice is given, it should ideally be brown rice, and spaghetti should be whole grain. The bleached, processed junk found in many conventional foods offers little nutritional value and can actively contribute to health issues.

By meticulously removing these 'poisons' from Jonathan’s diet, we’ve seen a dramatic improvement in his behavior and overall health. Beyond just removing harmful elements, I’ve also focused on filling nutritional gaps with essential vitamins, minerals, enzymes, and probiotics. Our modern diets, unfortunately, often fall short in providing these vital components, and for individuals like Jonathan, who may have unique metabolic needs or absorption issues, supplementation becomes even more critical. The positive changes in Jonathan—his improved mood, reduced gastric distress, and enhanced ability to engage with his environment—are a powerful testament to the profound impact of a carefully managed diet and targeted nutritional support. My deepest hope is that by sharing this information, even one family facing similar struggles can find a path toward better health and happiness for their child.

Conclusion

Jonathan's journey is a testament to the power of personalized intervention and the profound impact that a holistic approach can have on the lives of individuals with autism. From battling severe sleep disturbances and gastric issues to thriving in school and waking up with a smile, his progress has been nothing short of miraculous. Our experiences with carefully selected NAC, tailored melatonin dosages, and a diet focused on gut health and natural ingredients have transformed his well-being and, by extension, the peace and happiness of our entire family.

This path has not always been easy, requiring constant vigilance, research, and a willingness to challenge conventional wisdom. However, the rewards—seeing Jonathan flourish and experience a quality of life we once only dreamed of—have been immeasurable. It is my sincere hope that by sharing our story on costifautism.com, other parents navigating the complexities of autism can find inspiration, practical strategies, and a renewed sense of hope. Every child is unique, and what works for one may not work for another, but the principles of diligent observation, informed experimentation, and unwavering dedication to their well-being are universal. If even one child benefits from this information, it will have been worth every effort. Please feel free to reach out and share your own experiences; together, we can build a community of support and knowledge for our extraordinary children.

References

[1] N-acetylcysteine for treatment of autism, a case report. PMC. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC3698662/

[2] NAC: A Promising Aid for Autism Spectrum Disorder and Irritability. Philly Integrative. Available at: https://phillyintegrative.com/blog/nac-in-autism-blog

[3] Antioxidant shows promise as treatment for certain features of autism, study finds. Stanford Medicine. Available at: https://med.stanford.edu/news/all-news/2012/05/antioxidant-shows-promise-as-treatment-for-certain-features-of-autism-study-finds.html

[4] Possible effects of N-acetylcysteine in autism spectrum disorders. Turk J Pediatr. Available at: https://turkjpediatr.org/article/view/93

[5] N-acetylcysteine improves autism-like behavior by recovering. SAGE Journals. Available at: https://journals.sagepub.com/doi/abs/10.1177/15353702231179924

[6] Stability Study of Parenteral N-Acetylcysteine, and Chemical. PMC. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9860916/

[7] Stability of N-Acetylcysteine (NAC) in Standardized Pediatric. PMC. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC7353375/

[8] NAC Stability Explained. Fullscript. Available at: https://fullscript.com/blog/nac-stability

[9] The Relationship between Autism Spectrum Disorder and Melatonin. MDPI. Available at: https://www.mdpi.com/1420-3049/23/1/198

[10] Sleep and autism. National Autistic Society. Available at: https://www.autism.org.uk/advice-and-guidance/topics/physical-health/sleep

[11] Melatonin: from pharmacokinetics to clinical use in autism spectrum disorder. MDPI. Available at: https://www.mdpi.com/1422-0067/22/3/1490

[12] Raw Cow's Milk and Its Protective Effect on Allergies and Asthma. PMC. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6413174/

[13] Allergies and Raw Milk. Raw Milk Institute. Available at: https://www.rawmilkinstitute.org/updates/allergies-and-raw-milk

[14] The Beneficial Effect of Farm Milk Consumption on Asthma, Allergies. ScienceDirect. Available at: https://www.sciencedirect.com/science/article/abs/pii/S2213219819309560

[15] Gut Health and Autism's Important Connection. The Treetop ABA. Available at: https://www.thetreetop.com/aba-therapy/gut-health-and-autism

[16] Nutrition and the Gut-Brain Connection. Autism Research Institute. Available at: https://autism.org/nutrition-gut-brain-connection/

[17] Role of Gut Microbiome in Autism Spectrum Disorder and Its. PMC. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9355470/

[18] 5 Foods That Can Make Autism Worse. Amen Clinics. Available at: https://www.amenclinics.com/blog/5-foods-can-make-autism-worse/

[19] Avoiding Processed Foods. The Autism Community in Action. Available at: https://tacanow.org/family-resources/avoiding-processed-foods/

Following The Routine Isn't Always Routine

It seems we're always giving out advice to special needs parents.  Feeding issues, sleep troubles, allergy  problems.  Not because we're perfect in ANY way or such great experts, but simply because we have a fairly well adjusted and VERY happy little boy, and people are always out for our "secret".  So it just seems kind of funny to me that we've been up since 4AM for not following our own advice, especially when I just finished telling a friend yesterday about how great our routine works for us in keeping him sleeping through the night!  Just what is that routine, read on and we'll tell you everything.

Just to let you know, we didn't come up with this overnight, It took a while and it evolved over a couple of years and will probably be different for every child.

It seems Jonathan had tummy troubles since the day he was born, he was a couple of months "undercooked" and because of that Mommy was having a bit of trouble getting production flowing, so the doc suggested artificial milk as a supplement and gave him a Soy based formula.  That almost immediately put him in distress and required a few more days in the hospital.  Little did we know that his tummy troubles had just begun.

Fast forward a few years later and in addition to the Autism, it turns out he's allergic to Milk Protein, Soy, Egg and Peanuts.  It wasn't until he developed an allergy to horses though, that I started wondering what caused allergies.   (He had been riding for YEARS with no issues)  Turns out it's caused by things like Tylenol!  There's also a link between gut flora imbalances and allergies as well.

Now the routine.
Breakfast was hard, with him being allergic to almost every breakfast item, so we usually give him a combo of Bananas, Pears and Cherries blended with two heaping tablespoons of Organic Oatmeal. After heating this to a boil, I pour it into a bowl and add cold "Oat Milk" (It's actually Pacific Oat Beverage) since it's usually a bit  too thick.  I then put in a capsule of Florajen 4 kids Since we don't want to bore him with the same thing every day, we switch things up with Apple's, Blueberries, Mangos, Strawberries ... the combinations are endless.  The staple is the Oatmeal

since it helps keep him regular, or as I like to say... Premium!

After breakfast I'll give him a blend of Green Pasture Fermented Cod Liver Oil in Licorice Flavor and Scotts Emulsion Cod Liver Oil (Though I'm replacing the Scott's with the better rated Carlson Brand).  The Green Pastures version is superior but the taste is too strong for my son to handle so I mix it with the regular Cod Liver oil.  What's great about the Green Pastures version is that it's produced the same way Cod Liver oil was produced centuries ago, and since it's not pasturized, it still has the CoQ10 along with dozens of other enzymes and beneficial bacteria that are all destroyed with the pasturizing process all other Cod Liver oils go through.

Lunch varies, but we try to always give freshly prepared meals since prepackaged foods don't seem to sit too well with him.  Usually give him NAC after lunch so it doesn't affect his appetite.
Dinner is similar to Lunch, then about an hour later we give him Natrol Melatonin (I think it works better than the Animal based version) with Oat Milk then let him soak in a tub with a cup of regular Epsom Salt, for at least a half hour.  Considering that our kids are usually sensitive to a lot of things out there, I wouldn't go with the ones who add Lavender or other things, keep it simple. To keep the water from getting cold, what I'll do is put him in when the water is about a 1/3rd full, then have hot water just trickling out of the spout, I'll then read a book for the next half hour to an hour or so. Once he's out of the tub, we give him the Cod Liver Oil blend again and usually he'll go to sleep within 15 Min. or so and sleep through the night.

So how did we screw up?  We only put him in the tub for about 10 Min... Not nearly enough time for the Magnesium in the Epsom Salt to absorb into his system, so now we're paying the price for that rush through ... Oh well, Live and Learn.