Updated on April 7, 2023
When parents of autistic children ask what causes the condition, the answers are never satisfying. Although therapy would be far easier if researchers could pinpoint a single causative factor, there is a wide range of genetic and environmental factors that contribute to the characteristic symptoms of autism.
Given autism’s complex etiology, the most promising therapeutic strategies for addressing autism symptoms involve targeting the cellular processes believed to contribute most to the development and exacerbation of the condition. Today, researchers have identified oxidative stress as one of these key cellular processes, which is spurring interest in nutritional supplements that can reduce oxidative stress to, and thus improve quality of life for autistic patients.
Oxidative stress is broadly defined as a state in which the production of reactive oxidative species surpases the cell’s antioxidant defenses. In the brain, this imbalance has the potential to trigger neurotoxic pathways that can fundamentally damage brain cells and might have functional effects ranging from memory loss to the exacerbation of psychiatric symptoms.
There is a strong body of scholarly literature linking high levels of oxidative stress to autism. In a 2012 systematic review, researchers concluded there are multiple oxidative stress-related biomarkers associated with autism, including lower plasma levels of reduced glutathione (GSH), higher levels of oxidized glutathione (GSSG), and lower levels of glutathione peroxidase, methionine, and cysteine.
The data from this comprehensive review supports the concept that oxidative stress plays a significant role in the pathogenesis of autism. Therefore, oxidative stress-related cellular pathways are likely to be ideal targets for innovative therapies.
As a naturally occurring antioxidant in the brain, glutathione is heavily involved in protecting neurons from the damage that can result from oxidative stress.* However, multiple studies have shown that autistic individuals have unusually low levels of glutathione, and the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) is also negatively altered in these individuals.
Specifically, the proportion of the reduced form (GSH) is lower than the proportion of the oxidized form (GSSG), which indicates a chronic state of oxidative stress. This imbalance has led researchers to consider whether restoring GSH levels might help manage symptoms because oxidative stress might be damaging brain cells in ways that have direct clinical impacts.
Although the evidence supporting the benefits of glutathione supplementation for autistic individuals is limited, early results are promising. In 2011, researchers associated with the University of Texas Southwestern Medical Center conducted a small-scale, open-label study in which 13 male autism patients between the ages of three and 13 took oral and transdermal formulations of glutathione.
They observed a significant increase in plasma levels of GSH, as well as other antioxidants like sulfate and cysteine. This suggests that glutathione can be an efficacious nutritional supplement for autistic patients, and the likely reason why the researchers called for more comprehensive future studies with larger sample sizes and greater attention to the behavioral effects of supplementation.
One of the ways in which oxidative stress harms brain cells is by interfering with the function of mitochondria. Mitochondria are key organelles that are involved in essential aspects of cellular function, including energy metabolism and longevity, and some studies suggest that the significant effects of oxidative stress in autistic patients can be mediated by an increase in mitochondrial dysfunction.
One possible way to counteract this phenomenon is to increase cellular exposure to butyrate, a short-chain fatty acid. Although butyrate is normally derived from bacteria in the gut microbiome when they digest fiber, the latest research indicates that the microbiomes of patients with autism are different from those of healthy patients, which might result in a butyrate deficiency; a circumstance that could be resolved through butyrate supplementation.
This hypothesis was recently supported by a cutting-edge 2018 study out of the University of Arkansas, in which researchers conducted an in vitro study using cell lines from the brains of young male autism patients. They found that when the redacted cells were exposed to butyrate during oxidative stress, the exposure enhanced mitochondrial function. These results suggest that butyrate can enhance mitochondrial function during oxidative stress, thus interfering with the oxidative stress-related physiological processes that underpin autism.*
Although further clinical studies on butyrate supplementation are needed to confirm this laboratory evidence and assess the potential real-world implications for patients, this early research provides an exciting opening for researchers and clinicians who are interested in finding ways to benefit patients by reducing the impacts of oxidative stress.
At present, there is not enough conclusive research to definitively determine whether therapeutic strategies to counteract oxidative stress will lead to observable effects in autistic individuals. However, given the strong evidence that oxidative stress does play a role in the pathophysiology of this disorder, it is definitely an avenue worth exploring. Patients, caregivers, and practitioners should know, however, that they can take action now on these connections by supplementing with available glutathione and butyrate nutritional supplements to assess the possible beneficial impacts on individual patients.
The power of Tesseract supplements lies in the proprietary science of proven nutrients and unrivaled smart delivery, making them the most effective for supporting neurological health and gastrointestinal health.*
Bhanizadeh A, Azkhondzadeh S, Hormozi M, et al. 2012. Current Medicinal Chemistry. 19(23): 4000-5.
Burton GJ, Jauniaux E. 2011. Best Practice and Research in Clinical Obstetrics and Gynecology. 25(3): 287-99.
Calabrese V, Lodi R, Tonon C, et al. 2005. Journal of the Neurological Sciences. 2333(1-2): 145-62.
Frustaci A, Neri M, Cesario A, et al. 2012. Free Radical Biology & Medicine. 52(10): 2128-41.
Kern JK, Geier DA, Adams JB, et al. 2011. Medical Science Monitor. 17(12): CR677-82.
Matsuzaki H, Iwata K, Manabe T, Mori N. 2012. Journal of Central Nervous System Disease. 4: 27-36.
Rose S, Bennuri S, Davis J, et al. 2018. Translational Psychiatry. 8:42.
Rossignol DA, Frye RE. 2014. Frontiers in Physiology. 5: 150.
Strati F, Cavelieri D, Albanese D, et al. 2017. Microbiome. 5:24.
Yui K, Kawasaki Y, Yamada H, Ogawa S. 2016. CNS & Neurological Disorders Drug Targets. 15(5): 587-96.