Updated on April 13, 2023
Many caregivers know all too well the feeling of helplessness that arises from seeing a loved one with autism spectrum disorder (ASD) suffering from acute anxiousness, particularly if the source of that anxiousness remains elusive. Even in those individuals who are highly independent, episodes of anxiousness can quickly cause functionality to deteriorate, causing the individual to experience a drastic reduction in quality of life.
Unfortunately, anxiousness episodes can be difficult to manage, especially when paired with symptoms like social withdrawal, deficits of speech, and obsessive behaviors that are often present in autistic individuals. Soothing techniques, such as spending time with a therapeutic animal, massage, or talking through fears might not be suitable for some autistic individuals, and caregivers are understandably hesitant to use medications like benzodiazepines and SSRIs due to their potential side effects. In addition, psychotherapeutic approaches like cognitive behavioral therapy can be difficult to implement effectively with individuals with ASD and it can take time to see results.
Now, a growing body of research suggests there might be another way to address anxiousness in autism: by targeting the gut-brain axis. It is widely recognized that acute anxiousness can contribute to the gastrointestinal (GI) disturbances associated with autism, which are notoriously detrimental to well-being and quality of life.
Indeed, most people are familiar to some extent with the influence of anxiousness on the gut, from manifesting merely as “butterflies in the stomach” to severe gastrointestinal distress. However, the gut can also be a source of anxiousness in and of itself due to the complex, bidirectional relationship between the gastrointestinal tract and the central nervous system. This relationship is known as the gut-brain axis.
The major nerve of the gut-brain axis is the vagus nerve, which refers information regarding the position and comfort of the viscera to the brain. Importantly, the gut-brain axis also relates information regarding satiety and immunological threats in the gut via innervation of the vagus nerve. To refer information regarding these immunological threats, the vagus nerve becomes innervated by inflammation in the gut.
This means that an out of balance inflammatory response in the gut can lead to repeated activation of the vagus nerve, leading to a corresponding activation of the recipient regions in the brain. In cases of chronic inflammatory response imbalance, the chronic activation of the vagus nerve might subsequently lead to acute anxiousness because the excessive activation is referred to other areas of the brain. Autistic individuals might be particularly vulnerable to this phenomenon, because the excess propionic acid build-up experienced by many can cause significant disruptions in the gut microbiome.
In individuals with ASD, symptoms deriving from the gut-brain axis can be difficult to recognize, and bouts of acute anxiousness caused by gastrointestinal symptoms might, therefore, seem to be without cause. But research is revealing that participants with gastrointestinal problems are seven percent more likely to experience social problems and 20 percent more likely to experience affective issues like anxiousness. Thus, GI symptoms have the potential to significantly aggravate an autistic individual’s anxiousness and reduce overall quality of life.
As such, controlling the impact of anxiousness on the gut, and vice versa, is critical for individuals and caregivers who want their loved ones to be as comfortable as possible. A growing number of consumers are now turning to nutritional supplements that seek to address anxiousness by supporting gut health.* But although there are several such nutritional supplements on the market, only butyric acid might provide truly comprehensive support.*
The possibility of managing anxiousness in individuals with ASD by manipulating the gut-brain axis via nutritional supplementation opens up exciting new paths to wellness for those who struggle with this symptom. However, the nutritional supplements that are intended for the general public are not always suitable for individuals with ASD, so it is important to recognize the unique challenges this population often faces.
For example, individuals with ASD are often intolerant of the flavors and textures of supplements, and botanical-derived supplements might be particularly unappealing. While caregivers and individuals can sometimes mask unpalatable flavors by including supplements or medications in food, adding food might negatively impact bioavailability and compromise therapeutic efficacy. Selecting a well-tolerated nutritional supplement that is easily integrated into one's diet without compromising efficacy is, therefore, essential.
Furthermore, most nutritional supplements are formulated for users with typical physiology. For individuals with normal metabolisms and normal gastrointestinal tracts, supplements that present absorption challenges can still be therapeutically beneficial provided they take a therapeutic amount. Although most of the supplement might be inactivated by the host’s metabolism before reaching the area in the body where it is bioactive, the excess is often merely excreted.
For individuals with ASD, however, impaired intestinal permeability can lead to excess supplement material accumulating in the gut, causing constipation or, alternatively, diarrhea, as well as other unwanted side-effects. Individuals and caregivers should look for a nutritional supplement that is formulated to optimize bioavailability and support healthy absorption to avoid these complications.*
More importantly, while researchers are confident that ASD leads to impaired intestinal function, they remain uncertain whether ASD is associated with reduced or increased permeability of the intestines. This means that a nutritional supplement might be absorbed faster or slower than in healthy persons, leading to unpredictable onset and uncertain therapeutic impact.
For an autistic individual seeking relief from their anxiousness, this can significantly compromise efficacy; a supplement that takes too long to work might prolong agitation; whereas, a supplement that works too quickly but is poorly persistent within the individual’s system won’t provide an effect long enough for the anxiousness to fully subside. Thus, the most effective supplements for addressing anxiousness in autistic individuals augment the body’s natural anxiolytic systems or use long-acting physiological mechanisms to address the situation.
Among supplements intended to support anxiousness management in ASD by supporting the gut, several are notable for being tried and tested:
Many individuals utilize magnesium as a nutritional supplement due to its mild yet consistent anxiolytic effects. In normal quantities, magnesium carries few side effects and can provide up to 12 hours of efficacy. Although magnesium is typically absorbed in the GI tract over the course of an hour after ingestion, magnesium is processed less efficiently in individuals with ASD, which means they might require higher amounts of magnesium supplementation and its efficacious onset might be slower.
The compromised ability of individuals with ASD to process magnesium has significant consequences for the microbiome and anxiousness levels. Most importantly, a magnesium deficiency can prevent the immune system from regulating the microbiome effectively. One study performed on mice indicates that during a magnesium deficiency the white blood cells of the gut cause a greater inflammatory response than usual.
The increased inflammation activates the gut-brain axis, prompting a mirrored inflammatory response in the brain, to the point where higher concentrations of inflammatory signaling molecules were found in the hippocampi of the mice. Restoring the magnesium satiety of the deficient mice restored their brains and microbiomes to healthy norms. For individuals with ASD, this study has significant implications because of their altered gastrointestinal absorption characteristics.
Because magnesium isn’t processed or absorbed as efficiently, individuals with ASD are at higher risk of being magnesium deficient than neurotypical individuals, which can affect neurological function; because neurons use magnesium to generate electrochemical signals, lower concentrations of magnesium can result in weaker activity by regulatory tracts of neurons. When these regulatory tracts can’t inhibit other areas of the brain with their signals, these other areas remain more excitable than they would otherwise be, causing increased neurological problems.
While magnesium supplementation might seem to be an obvious solution, research suggests it is unlikely to fully manage anxiousness in ASD. A review of 11 high-quality clinical trials found that magnesium supplements are helpful in addressing anxiousness for roughly half of individuals with ASD. Seven additional trials of lower quality documented similar results. All the trials documented reductions in acute anxiousness, aggression, seizure frequency, and constipation concomitant with magnesium supplementation, although the degree of symptom remission varied substantially.
The trials of lower quality tended to document higher magnitudes of symptom relief, with at least one claiming full remission. Higher quality trials are more conservative, indicating that magnesium might be a useful adjunct therapy but unsuitable as a monotherapy for most individuals with ASD.
In terms of tolerability, the body of evidence indicates that palatability of magnesium supplements is rarely a problem, and dosing equivalents specifically for those with ASD are well-characterized. A significant potential contraindication, however, is that magnesium is a potent laxative, potentially threatening more than one problem area for individuals with ASD.
Probiotics might be another way that individuals with ASD can address their anxiousness. Probiotic supplements are composed of living microbiota that can be consumed orally with the intention of seeding the organisms in their gastrointestinal tract. By providing the gut with beneficial bacteria, probiotics can prevent harmful bacteria from settling into the gut while also reducing the harmful effects associated with their presence.
In individuals with ASD, probiotics have the potential to be especially effective because their microbiomes are composed of different proportions of bacteria than in healthy people, leading to an imbalanced inflammatory response. Because an imbalanced inflammatory response in the gut causes excitation of the gut-brain axis via the vagus nerve, reducing this phenomenon in the gut with a probiotic might be a way to diminish the overall level of excitability in the brain and thereby impact anxiousness. This means the therapeutic implications of a healthier microbiome can be potentially substantial for individuals with ASD who struggle with acute anxiousness.
Probiotic supplements could also help reduce gastrointestinal disturbances that might be related to microbiome dysfunction. These disturbances include symptoms like pain, which innervates the vagus nerve directly and subsequently causes anxiousness. Although high-quality human data is lacking, probiotic supplements remain promising due to studies in mice where symptoms of anxiousness caused by an aberrant microbiome were abated by probiotic supplementation.
In one mouse study, ASD-model mice exhibited microbiomes that were on average eight percent deviant from that of healthy mice. The eight percent of their microbiomes that were deviant were dysbiotic, meaning they dislodged beneficial gut bacteria while also harming their hosts by secreting toxins. After administration of a Bacteroides fragilis probiotic—a beneficial bacteria of the human microbiome—the mice exhibited the anxiety levels and socializing behaviors of normal, non-ASD model mice. Although this effect wore off after a couple of days, the researchers had successfully proven that probiotics could affect anxiety levels and socializing symptoms in ASD.
In humans, probiotics tend to be well-tolerated, and few individuals experience side effects other than transient mild nausea after consuming too much at once. Although the proper dosing of probiotics is a subject of much debate, there does not appear to be differences between the way individuals with ASD incorporate the microbiota into their gut and the way that healthy people do. Most probiotics are palatable because they are embedded in foods like yogurts or are encapsulated, although the preferred modality of administration likely varies from person to person.
However, probiotic research is still in its infancy. Individuals seeking symptom management might consider probiotics to be a second-line supplemental therapy or perhaps a useful adjunct to other therapies supporting the health of the microbiome. Significantly, because probiotics contribute relatively small quantities of bacteria when compared to the entire microbiome, they can take several days to become established enough for therapeutic efficacy to begin, although this can vary widely with the species or mixture of bacteria used in the probiotic. As such, probiotics will not provide rapid effects. Once established, however, individuals might experience longer-lasting effects than with magnesium.
Butyric acid is another therapeutic option that supports the health of the microbiome, but it differs substantially from probiotics in several important ways. Researchers have observed that individuals with ASD have lower levels of butyric acid than healthy individuals, which carries significant implications for both their physiological and psychological well-being.
The body naturally produces butyric acid during digestion for the purpose of nourishing the microbiome and regulating the white blood cells that cultivate it. Gut biota consume butyric acid directly as chemical energy and help the gut digest nutrients and absorb water in return. If the microbiota don’t have sufficient butyric acid, then they can’t help the gut with digestion.
Under ideal conditions, these gut biotas have sufficient butyric acid for their needs, and they subsequently exert a beneficial effect on the brain, promoting the synthesis of critical neurotransmitters like serotonin. These neurotransmitters subsequently help regulate anxiousness when they are used by inhibitory tracts of neurons. This is one of the bases of the therapeutic effect that butyric acid exerts: the inhibitory neurotransmitters promoted by butyric acid are associated with reduced anxiousness.* Critically, the fact that butyric acid prompts synthesis of new neurotransmitters contributes to its longer period of therapeutic action,* especially when compared to supplements like magnesium that don’t.
However, the primary benefit of butyric acid might not be derived from its direct impact on the brain or the gut microbiome, but rather its effect on the immune cells of the gut that are responsible for regulating the microbiome.* Individuals with ASD often struggle with imbalanced levels of gastrointestinal inflammatory response.
Although the cause of this is unknown, researchers suspect it is a result of the aberrant microbiomes, including divergent bacterial colonies and proportions, which might be caused in part by excess propionic acid. Because some of these bacteria likely secrete toxins, the immune system attempts to remove them, resulting in a higher level of inflammatory response and subsequent discomfort.
Butyric acid balances excessive propionic acid and attenuates this response, preventing the white blood cells of the gut from causing an excessive inflammatory response except in cases of acutely noxious bacteria.* When white blood cells in the gut encounter butyric acid, the butyric acid behaves as an inhibitory cellular signaling molecule, causing a down-regulated inflammatory response.* But the natural butyric acid deficiency experienced by many individuals with ASD can cause a higher level of inflammatory response in the gut owing to the body’s inability to inhibit the white blood cells there as effectively as it should be able to.
In individuals with ASD, butyric acid deficiency is likely a central cause of an elevated inflammatory response in the gastrointestinal tract, although there might be additional contributing factors. Thus, supplementing the gut with additional butyric acid can help it to make up for any native shortages, while also reducing the inflammatory responses created by other causes associated with ASD.*
More importantly, when the gut has a normal inflammatory response as a result of butyric acid-mediated signaling in ASD, the brain likewise benefits.* In mouse models of ASD, reduced neuroinflammation prompted by butyric acid was correlated to increased sociability and reduced anxiousness.* These results were later replicated by other researchers, indicating that butyric acid supplementation can be an important multimodal therapeutic option. When taken in summary, supplementing butyric acid to the gut could thus have a bevy of beneficial anxiolytic effects in individuals with ASD.*
With the help of advanced butyric acid supplements formulated specifically for use in individuals with ASD, practitioners and their patients now have access to what might be the broadest-acting supplement for autism-related anxiousness thus far.* Unlike older supplements, novel supplements such as ProButyrate and AuRx from Tesseract Medical Research are optimized for bioavailability and have an onset of under an hour, providing assistance in management of anxiousness.*
Whereas other butyric acid supplements are produced using butyrate salts, Tesseract’s supplements deliver butyric acid in its most concentrated form, significantly enhancing efficacy. They are also tasteless, overcoming butyric acid’s notorious palatability issues to enhance user adherence. Most importantly, these supplements have the potential to get to the root—or rather, the gut—of one of the major drivers of anxiousness in individuals with ASD, allowing them to experience safe and effective symptom management without worrying about side effects or invisible damage.*
Although human clinical trials investigating the utility of butyric acid in addressing anxiousness in ASD remain forthcoming, researchers are optimistic that butyric acid supplementation can be a safe and powerful option.*
When a consumer uses a butyric acid supplement, they will be correcting any deficiencies that might have resulted from ASD, while also providing their gut’s immune function with the ability to down-regulate its inflammatory response.* With a normal inflammatory response in the gut and less innervation of the gut-brain axis, individuals will experience better management of their anxiousness, as well as their gastrointestinal symptoms—a uniquely powerful result.*
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your neurological health.*
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