As a developmental disorder, autism spectrum disorder (ASD) implies a systemic, multidimensional, and interrelated set of symptoms that continuously affect patients throughout their lives. As a result, many patients with ASD require ongoing medical support. However, even strict adherence to conventional treatments often fails to produce complete and durable relief, particularly when it comes to the social withdrawal, deficiencies of communication, and impairment of executive functions that serve as features of ASD. While pharmaceutical and behavioral interventions may reduce the severity of these symptoms, most patients will continue to struggle with them to some degree. This has left many patients and caregivers searching for alternative treatments which might provide the much-needed alleviation of complex symptomatologies.
Unfortunately, many alternative treatments claiming to address ASD symptoms are not supported by scientific evidence, and some—like chelation therapy or hyperbaric therapy—can even cause harm. But there are promising alternative treatments for patients with autism. While some of the most compelling therapeutic agents are still investigational, early evidence suggests that they could provide meaningful benefits for patients who have not responded to conventional therapies. Here, we take a closer look at three alternative treatments for autism spectrum disorder and examine their potential: glutathione, secretin, and immunoglobulin.
GlutathioneGlutathione (GSH) is a powerful antioxidant produced by human cells and an investigation-stage therapeutic for ASD. Glutathione’s potential to treat ASD lies in its ability to mitigate the oxidative stress caused by free radicals. On a molecular level, the glutathione present in cells has two states: oxidized, and reduced. Reduced glutathione (GSSG) attracts free radicals and reacts with them, preventing them from harming cells. After the reduced glutathione has reacted with as many free radicals as it can, it transitions to the oxidized state, and cells can safely decompose the free radicals and recycle the glutathione molecule. After recycling, the glutathione molecule becomes reduced and can return to capture more free radicals.
Using glutathione to treat autism is an exciting therapeutic approach, as studies consistently show that patients with autism exhibit high levels of oxidative stress. That stress is likely a significant cause of inflammation in ASD, especially in the context of the brain, and the cellular damage caused by oxidative stress may contribute to ASD symptoms. This may in part be attributable to the fact that production of glutathione is typically either impaired or otherwise inefficient in patients with ASD. Indeed, a study published in 2012 found that glutathione levels in the cerebellum of patients with ASD were 44.6% lower than in healthy controls.
Researchers strongly suspect that lower levels of glutathione are correlated to higher levels of inflammation and neuronal dysfunction. In samples of brain matter taken from deceased patients, for example, patients with ASD exhibited 72% higher concentrations of biomarker molecules which signify oxidative-stress-based DNA damage. Bolstering glutathione levels via supplementation could be a viable way of supporting the body’s ability to fight oxidative stress and reduce the risk of damage to critical brain tissues. As a result, patients may experience fewer neurological and behavioral symptoms such as executive dysfunction, emotional dysregulation, and social withdrawal. Though no clinical trials investigating glutathione as a treatment for ASD have been completed thus far, fresh research clarifying the link between inflammation and ASD symptoms will continue to spur the development of glutathione supplementation as a prospective therapy.
Historically, glutathione has suffered from notoriously poor absorption in patients, limitings its therapeutic use. Today, however, advanced delivery systems, such as those introduced by Tesseract Medical Research, are enhancing bioavailability and making glutathione supplementation a viable therapeutic option.
Given the link between gastrointestinal dysfunction and autism spectrum disorder, chemicals which impact the gastrointestinal tract are thought to also potentially affect a range of ASD symptoms. The reason behind this lies in the gut-brain axis, the bidirectional connection between the gastrointestinal tract and the central nervous system; evidence suggests that dysfunction of the gut can contribute to neurological and behavioral ASD symptoms while neurological phenomena may affect gastrointestinal health.
Secretin is a hormone that regulates the acidity of the gastrointestinal tract, giving it a critical role in gut health. As a result, researchers long suspected that it could be useful in correcting gastrointestinal deviations associated with ASD. Specifically, secretin therapy inhibits the production of stomach acids, which may reduce some of the gastrointestinal pain and diarrhea which patients with ASD often experience. By acting on the gut-brain axis, this could, in turn, affect a variety of neurological and behavioral ASD symptoms.
However, one early investigation into the efficacy of secretin therapy in the treatment of behavioral ASD symptoms reported contradictory results. In the trial, the language abilities and repetitive behaviors of patients were measured both before and after secretin administration. While objective measurements of patients’ language and social abilities showed that a five-week course of once-weekly secretin therapy had no impact at any point in time, 70% of the patients’ caregivers thought that the therapy had caused moderate to high improvements, and 85% wanted to continue with secretin therapy after the trial had concluded. These results could suggest that secretin provides intangible benefits for patients with ASD which caregivers experience—like higher levels of contentment or improved resilience to behavioral irritant—but are not detected by standard clinical assessment tools. However, they could also simply be confirmation of the power of placebo effect.
Despite positive reports from caregivers, scientific investigations into secretin therapy still haven’t clarified which aspects of ASD secretin may address despite years of study. A systematic review of 16 clinical trials investigating secretin therapy for ASD found that secretin therapy did not consistently improve core ASD behavioral symptoms of social withdrawal, irritability, or communication deficiencies. Additionally, while there is evidence that secretin does address gastrointestinal symptoms in some patients, improvements are not universal. As a result, secretin is not regarded as an effective alternative treatment for autism within the scientific community.
Patients with ASD have a high degree of autoimmunity, meaning that their immune systems are frequently activated by innocuous elements of their bodies. This activation subsequently causes inflammation, which is linked to many dysfunctions like irritability, social withdrawal, deficits in executive function, impaired digestion, and gut pain—all of which may be experienced by patients with ASD. In particular, patients with ASD exhibit excessive quantities of white blood cells in the central nervous system. To control the neural inflammation caused by these white blood cells via errant autoimmune activation, researchers suspect that using one of the body’s own immune modulators—immunoglobulin—could be immensely beneficial.
In the context of autism therapies, immunoglobulins are antibodies which are not intended to tag any specific pathogen. The body produces these immunoglobulins in high volumes at all times, and patients with ASD are no exception. However, patients with ASD typically produce fewer immunoglobulins in their brains than healthy patients do. While the extent of under-production is highly variable, it may be correlated with symptom severity; some research suggests that patients who produce less immunoglobulin also experience worse irritability and social withdrawal. The cause of this correlation remains unknown, but researchers have investigated the possibility of using immunoglobulin to improve symptoms.
A 2018 pilot study of 17 patients sought to examine the impact of intravenous immunoglobulin on social responsiveness, maladaptive behaviors, and stereotyped behaviors. Patients in the study were given immunoglobulin infusions once per day for 21 days for each cycle of treatment. In total, the study performed 10 cycles of treatment over the course of one year. At the end of the study, researchers used a battery of clinical rubrics to assess patients’ symptoms. The broadest of these rubrics, the Clinical Global Impressions scale, found dramatic improvements in comparison to measurements taken at the start of the study. Before immunoglobulin therapy, patients exhibited an average of 4.8 points on the scale’s metric for overall behavioral symptom severity. After therapy, the average was only 3.86 points—nearly a full point of improvement. Other metrics were even more impressive. Before therapy, patients exhibited impairment of social interaction abilities rated at an average of 4.93. After therapy, the average rating was only 3.79. In other words, immunoglobulin therapy had significantly improved the patients’ behavioral symptoms.
More research is needed to determine whether immunoglobulin therapy is safe for all patients with ASD. However, current evidence suggests that it is well-tolerated; while some patients in the pilot study experienced side effects like headaches, gut pain, and nausea, these side effects didn’t cause any patients to withdraw from the study. Nonetheless, researchers know little about how the immune systems of patients with ASD differ from those in healthy individuals, meaning that further investigation will be critical.
New Vectors of ASD TherapyTesseract Medical Research. As a result, patients can integrate cutting-edge alternative therapies in their treatment plans today, potentially allowing them to address complex ASD symptoms and enhance well-being.
Chauhan A, Audhya T, Chauhan V. 2012. Brain region-specific glutathione redox imbalance in autism. Neurochemical Research. (8):1681-1689. https://www.ncbi.nlm.nih.gov/pubmed/22528835
Edmiston E, Ashwood P, Van de Water J. 2017. Autoimmunity, autoantibodies, and autism spectrum disorders. Biological Psychiatry. 81(5):383-390. https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5373490&blobtype=pdf
Heuer LS, Rose M, Ashwood P, and Van de Water J. 2012. Decreased levels of immunoglobulin in children with autism is not a result of B cell dysfunction. Journal of Neuroimmunology. 251(1-2):94-102. https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC3432686&blobtype=pdf
Lightdale JR, Hayer C, Duer A, Lind-White C, Jenkins S, et al. 2001. Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: a single-blinded, open-label pilot study. Pediatrics. 108(5):E90. https://www.ncbi.nlm.nih.gov/pubmed/11694674
Melamed IR, Heffron M, Testoria A, and Lipe K. 2018. A pilot study of high-dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation. Autism Research. 11(3):421-433. https://www.ncbi.nlm.nih.gov/pubmed/29427532
Niederhofer H, Staffen W, and Mair A. 2003. Immunoglobulins as an Alternative Strategy of Psychopharmacological Treatment of Children with Autistic Disorder. Neuropsychopharmacology. 28:1014-1015. https://www.nature.com/articles/1300130.pdf
Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, et al. 2012. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Translational Psychiatry. (2):e134. https://www.nature.com/articles/tp201261.pdf
Williams K, Wray JA, and Wheeler DM. 2012. Intravenous secretin for autism spectrum disorders. Cochrane Database of Systematic Reviews. 4:CD003495. https://www.ncbi.nlm.nih.gov/pubmed/22513913