Updated on March 27, 2023
Despite tremendous progress toward developing efficacious therapies targeted at supporting autistic individuals, patients and caregivers continue to struggle with the effects of the condition. Too often, symptoms ranging from behavioral difficulties, like aggression or hyperactivity, to physiological issues, like gastrointestinal distress, are treatment-resistant or seemingly intractable. Due to the incomplete relief provided by conventional therapies and the wide range of unaddressed difficulties associated with autism, practitioners and caregivers are increasingly turning to complementary therapies. For many, these complementary therapies are taking the form of nutritional supplements, an appealing route that can potentially address symptoms without incurring side effects.
Nutritional supplement use is currently increasingly prevalent among autistic patients; one study found that 56 percent of caregivers administer at least one nutritional supplement on a regular basis. Supplementation typically includes vitamins and minerals like vitamin B, vitamin K, magnesium, calcium, and zinc. Unfortunately, the existing research suggests that many supplements are ineffective at addressing symptoms and some, such as caffeine or ashwagandha root extract, might even be harmful. Caregivers seeking to use nutritional supplements will, therefore, need to consider their options carefully to find effective and safe solutions. For caregivers who do find the right nutritional supplement for autism symptoms, the benefits could be substantial for their loved ones—especially if a loved one is unwittingly suffering from a nutrient deficiency.
The benefits of some nutritional supplements for autistic patients often stem from solving an unaddressed deficiency in their diet. Even with the mainstream administration of nutritional supplements, autistic patients often aren’t getting enough of several core vitamins; studies find that nearly one-third of patients are deficient in vitamin D, and over half are deficient in calcium. Often when these dietary needs remain unaddressed, a patient can experience aggravated behavioral symptoms, like social withdrawal or agitation. In addition to deficiencies, some nutrients might be present in excess. Folate, vitamin C, manganese, and copper, for example, are widely found in higher concentrations than necessary to maintain optimal health. The consequences of these excesses vary from diarrhea, which can be caused by too much magnesium, to desiccation, caused by a surplus of vitamin A.
Based on a growing body of literature, researchers are confident these differences in physiological molecules and nutrient concentrations contribute to the severity of autism symptoms. Although the relationship between nutrient levels and symptom severity is complex, it is likely caused by malfunctioning enzymes. The presence of many vitamins and minerals is necessary for enzymes to facilitate chemical reactions in the body. When these nutrients are absent or sparse, these vital reactions can’t occur, and the resulting shortage of the reaction’s product causes diverse and unpredictable symptoms. As such, the right balance of nutrients is necessary for autism patients to experience relief from their symptoms. However, finding this balance is more difficult with an autistic individual than it would be with a healthy person due to the fact that autistic patients have markedly different metabolic profiles.
Physiological molecules like NADH, ATP, tryptophan, and biotin are significantly diminished in autism patients, and the consequence of their scarcity is that the body has a diminished ability to compensate for experiencing stress or recovering from activity. Compensating for physical and mental stress is critical because the molecules that exacerbate stress are a natural byproduct of metabolism. When the stressors generated by normal and healthy metabolic activity are allowed to accumulate rather than be processed by the body, cellular damage can occur, generating inflammation. Inflammation caused by stress damage has a wide variety of detrimental effects depending on the tissue where it occurs. In general terms, inflammation lowers the efficiency of whichever tissue it occurs in. In the brain, inflammation is linked to difficulty concentrating, brain fog, and even depression. Inflammation is also linked to cognitive difficulties like shorter working memory and slower processing speed; autism patients might experience these symptoms either chronically or during acute incidents of inflammation.
Elsewhere, like in the GI tract, inflammation is correlated with lower motility and increased difficulty with bowel movements. These inflammation-based difficulties are prevalent in the autistic population. Likewise, in autism patients, substances like uridine and other biomarkers of stress are significantly more common. The implication is that the body of an autistic patient is routinely heavily stressed far more than normal and is also less capable of dealing with that stress. This means the effect of stress can be exponentially worse than it might be for a normal person.
Addressing the impact of stress is thus an important goal for the caregivers of an autistic child or adolescent. By lowering cellular stress, patients can target their symptoms. This requires providing the nutrition that an autistic patient’s body needs in a format that their body can use. In some cases, the best approach could be to simply circumvent the metabolism of an autistic patient by providing them with the compound that is a product of their metabolism rather than providing the nutritional precursors to that product. With this in mind, there is a small subset of nutritional supplements that can effectively impact the severity of certain symptoms associated with autism. These nutritional supplements don’t necessarily address the same symptoms, however. Thus, it might be necessary for a caregiver to utilize more than one nutritional supplement to achieve broader results.
A multivitamin/mineral supplement is an appealing supplement for addressing autism symptoms because it can provide a swath of essential nutrients in a single serving. This can be particularly beneficial for autism patients because supplement regimen adherence is often challenging for this population. Supplements often smell or taste unappetizing, which, when paired with the sensory integration difficulties experienced by autism patients, can make maintaining a regimen difficult. What might be an unpleasant odor or mediocre taste to a normal person could potentially feel immensely magnified to an autistic individual. If the autistic individual only needs to cope with a difficult sensation once, then there is a much higher likelihood of regimen adherence, which is necessary to derive benefits from any supplement. Significantly, certain formulations of multi-vitamin/mineral supplements have been shown to have a beneficial impact on autism symptoms.
One placebo-controlled clinical trial performed over the course of three months found that a multivitamin/mineral supplement formulated for the purposes of the study lowered hyperactivity, increased receptive language, and lowered the incidence of tantrums as measured by clinical rubrics. On a scale ranging from -3 (indicating much worse symptoms after therapy) to 3 (indicating vast improvement of symptoms), the use of receptive language was 0.4 greater in the supplement group than in the placebo group. Likewise, hyperactivity was 0.37 less severe in the supplement group and tantrums were 0.51 less severe. The supplement tested in the study wasn’t a panacea, however; general sociability and sleep quality were unaffected by the supplement when compared to the placebo.
Overall, the researchers said:
“Since the supplement resulted in many significant improvements in nutritional and metabolic status after three months, we hypothesize that the child’s overall health and learning ability is improved at that point but that more time might be needed for the increase in learning ability to fully translate into greater skills in language, social understanding, and behavior.”
The supplement in the above study contained more than 20 different common vitamins and minerals, making specific attribution of its beneficial effects difficult. However, supplement usage wasn’t associated with any adverse effects. Caregivers seeking information on the supplement’s formulation can consult the methods section of the study, which is open to the public. Notably absent from the supplement’s contents is one popular ingredient in supplements–fish oil.
Fish oil is a widely used nutritional supplement for autism patients owing to its minimal adverse event profile and its potential beneficial impact on behavioral symptoms. A recent study by researchers at the University of Hawaii School of Medicine suggests that fish oil can have a beneficial impact on the frequency and intensity of self-injurious behavior (SIB) in autistic patients. In the study, autistic patients receiving fish oil experienced a 52-percent drop in the intensity of their self-harm episodes compared to patients receiving pharmaceutical therapy. Intensity of self-harm was not the only variable impacted, however. Although the frequency of self-harm episodes remained the same for episodes that were classified as mild in intensity, the episodes that would have been classified as severe intensity were entirely suppressed in the patients receiving the fish oil supplement over the course of the study. Thus, fish oil appeared to be more effective at addressing the frequency of severe-intensity incidents than the frequency of mild-intensity incidents. Importantly, patients in the study who received antipsychotic pharmaceutical medications like risperidone, instead of fish oil, experienced similar results to the group that received fish oil in terms of the incidence and intensity of self-injurious behavior episodes, indicating that fish oil could be as effective as the medications for those patients in some cases. This suggests that fish oil might be a good add-on therapy if medication is failing to lower the incidence of severe-intensity self-harm episodes.
Other studies claim that two-thirds of the patients in their treatment group experienced minor improvements in their behavioral symptoms, like hyperactivity, after consuming fish oil for several months. For patients who struggle with self-injurious behavior or agitation, fish oil might be the missing piece of their therapeutic strategy. For patients who struggle with gastrointestinal issues more than SIB, however, butyrate supplementation might be a better solution.
A growing body of research is finding that using butyrate supplementation for autism might potentially address a variety of autism symptoms, especially gastrointestinal distress. Butyrate is a substance that the body produces to regulate white blood cells in the gastrointestinal tract. By controlling their behavior with butyrate, the white blood cells maintain the health of the gut microbiome, which uses butyrate as an energy source and provides protection from undesirable bacteria in the gut in return.* Autistic patients as a group generally have drastically low levels of butyrate, causing their microbiomes to be populated by different proportions of bacterial populations than those of healthy persons. Because the bacterial populations responsible for warding off detrimental microbiota in the intestinal space are weakened, harmful bacteria can flourish. After becoming established, these harmful bacteria can cause inflammation in the gastrointestinal tract, generating many of the adverse GI symptoms seen in autism, like constipation or difficulty with digestion.
Importantly, inflammation in the gut also has consequences for the rest of the body; thanks to the nerves connecting the gut to the brain, a sickly gut microbiome could cause behavioral symptoms, like social anxiety or anger, in autistic patients. With the help of a high-quality butyrate supplement, it would be possible to restore a healthy microbiome and thus possibly ameliorate these behavioral symptoms.* Although clinical research on butyrate supplementation in autistic individuals is sparse, there is ample in vivo evidence that supports the proposition of regular butyrate consumption.*
A recent study investigating butyrate supplementation using mouse models of autism found that mice that were supplemented with butyrate exhibited less social inhibition and repetitive behavior than the mice which did not. These changes were likely caused by differences in the regulation of certain genes that are linked to excitation and inhibition of the brain. The researchers found that in the mice that received butyrate, the genes associated with excitation were suppressed and the genes associated with inhibition were promoted. Although butyrate hasn’t been tested in this same context in autistic patients, the butyrate supplements that are currently on the market could potentially be a powerful tool for a patient who struggles with agitation, social withdrawal, and compulsive repetitive behaviors. Other benefits might include addressing hyperactivity and gastrointestinal issues, although these symptoms weren’t measured by the researchers who performed the mouse study.
Although a research consensus is still forming, there is reason to believe that glutathione (GSH) can benefit autism symptoms. Glutathione is a tripeptide molecule produced by the body that is used to protect cells from damage caused by stress. Under normal conditions, when those substances associated with causing stress damage in the body are produced by metabolic processes, glutathione removes these substances from the locations where they could cause harm. When there are too many stressors present, however, there might not be enough glutathione to respond to 100 percent of the damage. The damage subsequently causes inflammation.
But how does this relate to autism? Autistic individuals have far lower GSH levels than healthy individuals and far higher levels of those substances associated with stress damage. Although the reason behind this disparity is still unknown, the basis for glutathione supplementation is simple: increasing the level of glutathione in an autistic patient via supplementation can benefit the inflammatory response caused by stress damage.* There are currently no clinical trials that have investigated glutathione supplementation in autism, but the potential benefits for patients would appear to be substantial. Given that autistic patients struggle with both neurological and gastrointestinal symptoms, the currently available glutathione supplements could be an efficacious and safe therapy.
Exciting new research will soon shed more light on the promising early results of dietary supplementation for autism. In the meantime, practitioners and caregivers alike can take advantage of sophisticated nutritional supplements that bring nutrients like butyrate and glutathione to patients in effective formats. Importantly, these supplements are compatible with each other, and there is no evidence that suggests they induce side effects when taken simultaneously. Combining these supplements could be a preferred way to address a broad range of autism symptoms that would enhance the lives of patients and caregivers.
Tesseract Medical Research provides analysis of the most intriguing, impactful, and innovative autism research, including gastrointestinal and behavioral aspects of the condition.
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Durieux AM, Horder J, Mendez MA, et al. 2015. Autism Research. 9:429–435.
Guo M, Zhu J, Yang T, et al. 2018. Nutritional Neuroscience. 1–11.
Kratsman N, Getselter D, Elliott E. 2016. Neuropharmacology. 102:136–145.