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Updated on February 2, 2023
When it comes to addressing autoimmune digestive disorders, finding an effective solution can be a major challenge. In patients with these disorders—which include inflammatory bowel diseases like Crohn’s disease and ulcerative colitis—the immune system attacks healthy cells in the gastrointestinal tract, which can have a wide range of adverse functional consequences. Common pharmacological therapies include anti-inflammatory drugs, immunosuppressants, and steroids, all of which work by dampening the immune response. Unfortunately, the reported patient response rates to these therapies are less than optimal. Additionally, many standard therapies are associated with debilitating side-effects that compromise quality of life. As a result of the shortcomings of pharmacological therapy, many researchers, clinicians, and patients are turning to dietary interventions to find more satisfactory symptom relief while avoiding unwanted side-effects.
One emerging possibility for patients with inflammatory bowel disease is the Autoimmune Protocol Diet. According to a recently published prospective study, this diet has the potential to help patients with Crohn’s disease and ulcerative colitis achieve remission. More broadly, the researchers’ findings indicate that nutritional intervention, including targeted supplementation, can be an effective approach for dealing with autoimmune digestive disorders.
In 2017, researchers from the Division of Gastroenterology at the Scripps Research Institute in La Jolla, California, published a study in the journal Inflammatory Bowel Diseases on the Autoimmune Protocol Diet as a possible therapy for patients with Crohn’s disease and ulcerative colitis. Although earlier research had implicated diet in the pathogenesis of IBD and served as the impetus for the study, relatively few studies on nutritional interventions had been conducted. The researchers set out to address the gap in the literature by conducting a prospective study on one of the diets they considered to be the most promising: the Autoimmune Protocol Diet. This diet specifically restricts consumption of foods believed to trigger intestinal inflammation and/or symptoms of food intolerance. Essentially, it is an extension of the Paleolithic diet, adding several additional food restrictions that had previously been associated with IBD symptom alleviation, including avoidances of gluten and refined sugar. Due to the comprehensive, combinatorial nature of the diet, the researchers hypothesized it could potentially promote remission in patients with autoimmune digestive disorders.
For their open-labeled, uncontrolled pilot study, the researchers recruited 15 adults (9 with active Crohn’s disease, 6 with active ulcerative colitis) to participate in an 11-week program, which included a 6-week staged elimination phase and a 5-week maintenance phase. Over the course of the first six weeks, the patients were coached to gradually eliminate from their diet dairy, eggs, grains, legumes, nightshades, nuts and seeds, coffee, alcohol, refined and processed sugars, oils, and food additives. Then, during the 5-week maintenance phase, they were instructed not to reintroduce any of these food groups. They were also instructed to avoid non-steroidal anti-inflammatory drugs and other medications as part of the Autoimmune Protocol Diet. At the same time, they were instructed to consume fresh, nutrient-dense foods, bone broth, and fermented foods.
Office visits were conducted at baseline, at week 6, and at week 11. The primary outcome the researchers measured was the achievement of clinical remission, as determined by scores on the established Harvey-Bradshaw Index for active IBD. In addition, the subjects underwent endoscopy, radiology, and biomarker assessment to evaluate the extent of mucosal healing. By the 6-week mark, 11 of the 15 patients in the study had achieved remission, which continued throughout the 5-week maintenance period. The researchers also noticed better scores on the Harvey-Bradshaw Index among all patients, as well as statistically significant improvements on indices measuring damage to gastrointestinal mucosa. Notably, there was no statistically significant difference in the outcomes of patients with Crohn’s disease and those with ulcerative colitis, which suggests the Autoimmune Protocol Diet can be equally effective for addressing both autoimmune digestive disorders.
Of course, it is important to recognize these findings are only preliminary. An open-label, uncontrolled study like this serves only as a basis for future randomized, controlled trials. However, it does offer an option for patients considering dietary interventions, and it offers another piece of strong evidence that diet does play a role in the pathology of autoimmune digestive disorders.
From a broad perspective, the findings of this study suggest that dietary interventions that target the immune system might help patients with Crohn’s disease and ulcerative colitis achieve remission. Therefore, alongside elimination diets like the Autoimmune Protocol Diet, patients might also want to consider nutritional supplements that help maintain a normal inflammatory response in the gut, which could have similar functional effects. For instance, butyric acid induces T regulatory cell differentiation in the gut, and these cells are essential for down-regulating the inflammatory response under conditions when an immune response is unwarranted. Curcumin also plays an important role in immune system regulation and supports the body’s natural inflammatory response, such as the modulation of transcription factors that regulate the production of key proteins involved in the immune response. Adding supplements like these could have similar beneficial effects as the Autoimmune Protocol Diet because they have the same essential goal: targeting dysfunction in the immune system.
Another issue the researchers at Scripps highlighted in their study was the potential for nutrient deficiency in patients with Crohn’s disease and ulcerative colitis. They found that several of the patients were deficient in vitamin D and iron at the start of the study—and without an effective nutritional repletion strategy, these problems are likely to be exacerbated by a highly restrictive diet like the Autoimmune Protocol Diet. This can be a serious problem not only because of the general importance of these nutrients for body functioning, but also because nutrients like vitamin D are associated with positive outcomes in patients with inflammatory bowel disorders. Therefore, for patients who are choosing nutritional supplements to address nutritional deficiencies and/or address symptoms related to autoimmune digestive disorders, choosing a supplement with high bioavailability is essential. This will ensure optimal absorption of the supplement in the gut and maximize its effectiveness.
Overall, a universally effective therapy for autoimmune digestive disorders remains elusive. However, based on the latest research, it is clear that elimination diets like the Autoimmune Protocol Diet offer a promising alternative to traditional pharmacological options. Although more randomized, controlled trials are needed to verify the efficacy of these alternatives, some physicians and patients today are already considering them as possible therapeutic options. At the same time, while elimination diets may be useful, nutritional supplements designed to support gastrointestinal health, such as those from Tesseract Medical Research, can be a less overwhelming option for some individuals and therefore more attractive. As such, they can either replace or complement an elimination diet depending on the response of the patient. Patients and physicians should work closely to find the optimal therapy to meet individual needs.
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 immune health.*
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Updated on February 2, 2023
For thousands of years, the spice turmeric has been renowned for both its culinary uses and for a multitude of potential health benefits, ranging from decongestion to wound healing to addressing chicken pox symptoms. In recent years, as the scientific community has increasingly recognized the therapeutic potential of turmeric, it has led to the development of sophisticated nutritional supplements formulated with curcumin, the active metabolite in turmeric. By combining advanced medical technologies with traditional medicine to create more effective turmeric supplements, new opportunities are opening up for managing a wide range of health conditions.
When it comes to gastrointestinal disorders, biochemical research indicates the benefits of curcumin derive from properties that enhance the body’s natural inflammatory response and promote the optimal functioning of antioxidants.* However, due to the naturally low bioavailability of curcumin, the clinical evidence is still mixed. The most recent research suggests that a relatively new turmeric-based supplement—tetrahydrocurcumin—is effective for addressing gastrointestinal symptoms, particularly when delivered in a highly bioavailable form.* There is already one noted tetrahydrocurcumin therapy on the market and with its promise, we expect to see more over time.
Inflammation in the gastrointestinal tract is associated with many of the functional bowel problems that commonly characterize conditions like ulcerative colitis, irritable bowel syndrome (IBS), and even autism spectrum disorder (ASD). At the biochemical level, the effectiveness of curcumin for helping to maintain a normal inflammatory response in the GI tract is largely the result of its ability to interact with multiple molecular targets and thereby modulate a wide range of inflammation-related signaling pathways.* Specifically, curcumin can benefit the following processes:
In recent years, researchers seeking to understand the mechanistic intricacies of inflammatory bowel disease have identified connections between NF-kappa-B inflammatory cytokines and a specific kinase-associated signaling pathway—and curcumin plays a beneficial role in both pathways. As a result, more researchers and clinicians are suggesting turmeric supplements as possible support options for patients with bowel inflammation.*
Similarly, recent biochemical research highlights the molecular mechanisms through which curcumin acts as an antioxidant.* At the most basic level, reactive oxygen species (ROS) can be generated by various aspects of the immune response, so curcumin can act as an antioxidant.* In addition, curcumin has been shown to beneficially regulate the expression of Nrf2, a protein that turns certain genes on to produce proteins.* These genes code for enzymes that degrade ROS or stop them from being produced unnecessarily. Therefore, when Nrf2 activity is high, the levels of ROS-fighting proteins are also high. In this way, the activity of curcumin indirectly impacts ROS.*
Although there is solid in vitro evidence of biochemistry behind the activities of curcumin, the clinical results are less convincing. For instance, in a 2017 review of clinical studies in which curcumin was used to address functional and gastrointestinal disorders, the results were promising, but not definitive. The authors noted a number of studies indicating potential efficacy:
However, other studies have failed to establish the statistically significant therapeutic effects one would expect based on in vitro findings.
One of the reasons curcumin has proven to be more effective in the lab than in the clinic is its natural low bioavailability, which has long been recognized by researchers. In a 1978 study, researchers found that in rats that took curcumin supplements (1g/kg of body weight), 75 percent was excreted in the feces. More recently, a 2001 study showed that significant quantities of curcumin were also present in the fecal samples of a group of 15 patients who were taking between 36 mg and 180 mg of curcumin per day. This indicates that a considerable proportion of the curcumin the patients took in was being excreted without being absorbed.
Due to these decades-old concerns about bioavailability, researchers are examining the potential efficacy of tetrahyrdocurcumin, an active metabolite of curcumin that can be much more readily metabolized when taken in supplement form than the curcumin in traditional turmeric supplements.* In a 2014 paper out of the Department of Experimental Therapeutics at UT Austin, the authors highlighted both in vitro and animal studies demonstrating that the efficacy of tetrahydrocurcumin as an antioxidant is significantly higher than that of curcumin.* Not only does this metabolite show improved efficacy for quenching free radicals, but it also induces key antioxidant enzymes, including GSH peroxidase, glutathione-S-transferase, quinone reductase, and NADPH.*
It is important to note that the differences in the activity of curcumin and tetrahydrocurcumin are not only derived from their different bioavailability levels but also because they have different molecular targets. While it is true that tetrahydrocurcumin does not bind to some of the targets involved in the body’s natural inflammatory response, it also limits some of the mild pro-inflammatory activities of curcumin, which might contribute to its effectiveness on the clinical level.*
There is also preliminary evidence suggesting that certain delivery systems can better support the bioavailability of different types of curcumin supplements, including both curcumin and tetrahydrocurcumin. In one randomized, double-blind study, researchers at the University of Tampa found that serum levels of curcumin were 45.9 times higher in patients who took a formulation of curcumin that included a hydrophilic carrier, cellulosic derivatives, and natural antioxidants, as compared to those who took an unformulated supplement. In the same study, researchers also reported a 7.9-fold rise in absorption of curcumin in patients who took a phytosome formulation and a 1.3-fold rise in those who took a formulation with volatile oils of turmeric rhizome. These results indicate that the delivery system can make an important difference in the bioavailability of curcumin.
Based on strong biochemical evidence, recommendations for turmeric supplements are becoming increasingly common. Although more research is needed to confirm clinical efficacy on a broad scale, these nutritional supplements present intriguing possibilities for clinicians and patients who want to look beyond conventional gastrointestinal therapies for more additional symptom relief. For those who wish to integrate curcumin or tetrahydrocurcumin into their therapies, TetraCumin from Tesseract Medical Research could be a beneficial place to start.
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 gastrointestinal health.*
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Updated on January 3, 2023
Although gluten intolerance is traditionally associated with celiac disease, this understanding is shifting as the medical community increasingly recognizes both non-celiac gluten sensitivity and the impact of gluten on other health conditions. In particular, the relationship between Crohn’s and gluten has become a critical area of interest, spurring many patients to consider gluten-free diets (GFDs) as potentially effective therapies. By exploring the current literature, clinicians and patients can come to understand both the potential and limits of gluten elimination and why additional dietary support in the form of supplementation might be necessary to obtain symptom management.
Despite the close relationship between celiac disease and gluten intolerance, gluten sensitivity is experienced by individuals without celiac disease. As Chris Kresser, director of the California Center For Functional Medicine, states, “It’s becoming more and more clear that celiac disease is only one manifestation of gluten intolerance, and that ‘non-celiac gluten sensitivity’ (i.e., people who react to gluten but do not have celiac disease) is a legitimate health condition.” As Kresser notes, gluten sensitivity is newly recognized as a pathology in its own right rather than as a symptom of other underlying pathologies, like it is in celiac disease, and such sensitivity can aggravate symptoms of co-occurring Crohn’s disease. Additionally, patients with Crohn’s can be susceptible to gluten-induced gastrointestinal distress due to the impact of gluten on the gut microbiome. In light of the relationship between Crohn’s and gluten, the rationale for using a gluten-free diet is twofold:
Crohn’s disease patients can have gluten intolerance that is separate from their Crohn’s pathology but augments Crohn’s symptoms when triggered. This occurs when B-cells of the immune system are activated by gluten consumption and consistently and incorrectly produce antibodies against it, inducing a minor allergic reaction and subsequent inflammation. While this can occur in non-Crohn’s patients, those with Crohn’s are particularly vulnerable to such a reaction due to abnormally active immune cells in the GI tract, which occurs independently of specific allergens. As a result, Crohn’s patients produce antibodies against many common but harmless antigens present in food, leading to heightened risk of immune activation and inflammation while stopping short of a major allergic reaction. Although wheat gluten antigens are just one set of many other antigens that can trigger Crohn’s disease patients into a flare-up, gluten is a particularly common culprit; one study found that 29.3 percent of Crohn’s patients experience non-celiac gluten sensitivity.
In addition to the inflammation caused by allergic reaction, gluten can cause inflammation of the GI tract by inducing dysbiosis, thereby destabilizing the gut microbiome’s bacterial proportions. Dysbiosis means the immune system is allowing or causing harmful bacteria to out-compete the beneficial bacteria that are characteristic of a healthy microbiome. Once the microbiome is disrupted by an abundance of easy-to-consume fuel in the form of wheat gluten proteins, unhealthy bacteria can rapidly replicate themselves and displace normal microbiomic fauna, causing the immune system to generate more inflammation. Inflammation and de-inflammation cycles can then cause micro-tearing of the intestinal surfaces, causing bleeding and bloody stools.
Additionally, Crohn’s patients often require microbiome-disrupting therapies like antibiotics to control their symptoms. As Kresser notes, “Just a single course of antibiotics can reduce the richness and diversity of the intestinal microbiota, and in many cases, an individual can never completely regain the diversity they lost.” Considering the potential detrimental effects that gluten can have on the microbiome and the generally disrupted state of the microbiome in Crohn’s patients, minimizing gluten consumption might thus make the difference between a destabilized and a balanced microbiome.
Given the link between gluten and Crohn’s symptoms, a growing body of research is highlighting the potential advantages of gluten elimination. One particularly promising investigation found that 65.6 percent of Crohn’s patients experienced better management of one or more of their symptoms while on a GFD. 23.6 percent of these patients used fewer medications to address flare-ups, and 38.3 percent of these patients reported fewer flare-ups overall. This data suggests that a GFD can have a meaningful impact on many Crohn’s patients.
Although the study did not inquire about the specific GFD used by participants, several GFDs have been investigated for their efficacy in addressing Crohn’s disease and other IBDs:
The most heavily-researched GFD used by Crohn’s patients is the specific carbohydrate diet (SCD). Originally intended to address the symptoms of celiac disease before celiac disease itself was characterized, the SCD’s goal is to control the gut microbiome by regulating carbohydrates that are easily broken down by bacteria. In practice, this means eliminating the majority of carbohydrates altogether, with a particular emphasis on removing carbohydrates that produce gas when digested, including all grains. As a result, SCD is incidentally gluten-free.
A study investigating the efficacy of different diets in the context of Crohn’s disease and ulcerative colitis found that the SCD benefitted both sets of patients. The study found that 42 percent of Crohn’s disease and ulcerative colitis patients experienced less inflammation and gastrointestinal disturbances after six months of the SCD. Of this 42 percent, 13 percent reported that remission began within two weeks of starting the SCD. However, the SCD isn’t sufficient to slow down flaring Crohn’s symptoms; once an inflammatory chain reaction begins, it’s too late to switch to a different diet. Additionally, the SCD was not designed with a modern understanding of microbiome health or Crohn’s disease. As such, it is not an optimal strategy for Crohn’s patients, despite being helpful for some.
Originally developed by Drs. Stein and Baldrassano of the Children’s Hospital of Pennsylvania, the Crohn’s Disease Exclusion Diet (CDED) is a new GFD designed specifically to promote microbiome health and to address the symptoms of Crohn’s patients. By excluding those foods to which Crohn’s patients are most likely to experience sensitivity—gluten, milk, beef, pork, and eggs—the diet seeks to address the runaway inflammation that damages the microbiome. As an emerging therapy, the CDED remains under investigation.
The FODMAP (Fermentable Oligo-/Di-/Mono-saccharides And Polyols) exclusion diets are designed to address a wide variety of gastrointestinal disorders, ranging from irritable bowel syndrome (IBS) to inflammatory bowel syndromes like Crohn’s, by reducing the intake of foods that produce large volumes of gas when fermented in the intestinal tract. FODMAP diets are often incidentally gluten-free, although their main focus is the exclusion of certain carbohydrates, referred to as FODMAPs, that are poorly absorbed by the GI tract.
The evidence for FODMAP diets in Crohn’s disease is conflicting. A number of studies have found that FODMAP exclusion diets are linked to reduced GI inflammation and other symptoms in inflammatory bowel diseases. Other studies, however, have not replicated these results. Furthermore, FODMAP diets can lower butyrate production and cause maladaptive changes in the microbiome, which could potentially aggravate GI inflammation. Future research needs to clarify the conflict and determine whether FODMAP diets are useful.
Although diets can provide relief to some patients, the inconsistent evidence finding on the efficacy of GFDs for Crohn’s patients might have an explanation. The group of human leukocyte antigen (HLA) alleles that make up the variable gene complex (haplotype) of the immune system is a large factor. The efficacy of GFDs in Crohn’s patients is likely linked to the HLA-DQ2 and -DQ8 haplotypes, with one study finding that only 12 percent of patients with IBDs and without these haplotypes experienced symptom abatement after six months on a GFD. In contrast, 60 percent of patients with either of the haplotypes experienced symptom abatement. Because 60 percent of Crohn’s patients don’t have either haplotype, these findings suggest that GFDs will not be effective for the majority of patients.
Considering the relationship between Crohn’s and gluten, GFDs might be an important part of the puzzle for some patients. However, the shortcomings of these diets and their restrictive nature leave many clinicians and Crohn’s patients searching for better dietary alternatives for managing symptoms not fully addressed by conventional therapies. Nutritional supplementation designed to promote microbiome health presents new possibilities for symptom management for both those using GFDs and those for whom GFDs are ineffective.
Supplements targeting the microbiome seek to restore a healthy balance of bacterial colonies and support optimal function. As a result, nutritional supplementation could be included along with other therapies, including GFDs, to help correct both natural and therapy-induced microbiome disruption, as well as augment other microbiome-supporting therapies. By integrating multiple therapies designed to support microbiome health, Crohn’s patients can address specific symptoms while building resilience against flare-ups caused by a distorted microbiome.
One of the most promising nutritional supplements for Crohn’s patients is butyric acid, a cellular signaling molecule in the GI tract that is deficient in Crohn’s patients. Providing the GI tract’s immune cells with the butyric acid they’re missing helps normalize the microbiome. Evidence suggests this type of supplementation can have significant beneficial effects; one study found that 69 percent of participants responded to bioavailability-optimized orally administered butyrate supplementation, with 53 percent achieving symptom benefit.
Further research is necessary to more fully understand the potential of butyrate supplementation to address symptoms in Crohn’s disease. However, for now, its use in addition to conventional and non-conventional therapies like GFDs might benefit patients. Other supplements, like fish oil, exist in a similar state, with some evidence in favor of their benefit in Crohn’s, and many questions left to be answered.
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 gastrointestinal health.*
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Updated on January 3, 2023
Butyrate, also known as butyric acid, is an emerging alternative nutritional support therapy for a wide range of health conditions, particularly gastrointestinal disorders and GI-associated neurological conditions like autism spectrum disorder (ASD). Because many of the traditional therapies for these conditions have significant side effects that can interfere with the user’s quality of life, patients, families, and providers are naturally wary of the possible side effects of innovative new supplements that are gaining traction within the research and clinical communities. However, butyrate differs from pharmacological therapies in part because it is natural-based: not only do you eat it every day, but it is directly produced in the body, making it uniquely compatible with human physiology. Understanding how this compound works offers valuable insight into why butyrate supplement side effects are limited, and why this option is widely considered to be safe.
Butyrate is one of the most common short-chain fatty acids found in the gut. Together, butyrate, acetate, and propionate comprise 95 percent of the short-chain fatty acids in the body. The butyrate in the gastrointestinal tract comes from two sources. First, it enters the GI tract when fat-containing animal or plant products are eaten. The other source of butyrate in the body comes from the fermentation of non-digestible fiber by bacteria in the gut. These bacteria ferment insoluble fiber for energy, and butyrate is generated as a byproduct.
Of course, just because butyrate is synthesized by the body does not mean that a butyrate supplement will be free of side effects. However, the way butyrate works in the body suggests that the risk of side effects is minimal. Under normal conditions, the cells of the colon rapidly absorb short-chain fatty acids when they are synthesized by bacteria or introduced with food. In total, about 95 percent of short-chain fatty acids are quickly taken up by colon cells, and any excess butyrate the body doesn’t need is harmlessly excreted in feces—about 5 percent of the butyrate that is synthesized under normal conditions.
Although there are relatively few clinical studies on the safety and effectiveness of butyrate supplements for patients with gastrointestinal and neurological disorders, early studies indicate that side effects are unlikely to occur. In one double-blind, randomized, controlled study that explored the potential for the use of sodium butyrate to address IBS symptoms, none of the 66 trial participants reported adverse side effects. In another preliminary report on the possibility of using sodium butyrate for IBS, the result was the same—none of the participants experienced side effects.
For patients and providers who are concerned about potential butyrate supplement side effects, it can also be helpful to consider the FDA’s insight. The FDA relies on a wide range of data to determine the safety status of different compounds, and the FDA’s status of butyrate is that it is categorized as Generally Recognized As Safe (GRAS).
The safety profile of butyrate makes sense when you consider the way it works in the body. Once butyrate enters a cell, it can play a wide range of essential roles, which suggests that insufficient butyrate is much more likely to produce adverse effects than butyrate supplementation. Patients with autism and/or gastrointestinal disorders are at heightened risk for insufficient butyrate levels due to compromised gut microbiome health, which diminishes the efficiency of butyrate generation. This can have a broad range of detrimental effects, because butyrate plays a range of essential roles, including:
Butyrate supplements make sense for nutritionally supporting patients with gastrointestinal and neurological disorders in part because biochemical evidence suggests that the healthy functioning of the colon is directly linked to some of these activities. For instance, as a gene regulator, butyrate ensures the appropriate expression of the proteins needed to form “tight junctions,” which determine the permeability of the gut. Improper functioning of tight junctions can cause “Leaky Gut” syndrome, which can produce adverse gastrointestinal symptoms and might exacerbate the behavioral symptoms of autism by enabling harmful metabolites to enter the blood and circulate to the brain.
Based on an evaluation of the existing biochemical and clinical literature, the evidence is clear that the risks of having too little butyrate outweigh the risks of butyrate supplementation side effects. So far, reports of side effects in clinical trials are non-existent, and the normal processing of butyrate in the body indicates that extra butyrate not used for essential cell processes is simply excreted. Overall, its appealing safety and functionality profile is one of the main reasons why butyrate is considered to be one of the most promising emerging supplements on the market for providing nutritional support for gastrointestinal and neurological disorders.
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.*
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Updated on January 3, 2023
Autism spectrum disorder (ASD) is a multifaceted neurological condition with a multitude of emotional, cognitive, behavioral, and physical symptoms that vary in presentation among individuals. These symptoms are influenced by a variety of internal and external factors, ranging from genetic characteristics to comorbid conditions to home and school environments. Due to ASD’s complexity, clinicians, parents, and patients often struggle to find alternatives that effectively address the full spectrum of symptoms.
Because conventional therapies, such as pharmacological and behavioral interventions, often fail to produce satisfactory symptom remission, professionals in the research and clinical communities are increasingly considering the potential benefits of diet-based therapies. Owing to a growing body of research, there is now evidence that well-informed, patient-specific dietary decisions and high-quality supplements can address some of the underlying issues that cause or exacerbate autism symptoms. When it comes to autism and diet, here’s what you need to know:
“Gut-brain axis” is a major buzzword in the research and medical communities, especially in the context of autism. This term describes the ongoing bidirectional communication between the Central Nervous System and the components of the enteric nervous system in the gastrointestinal tract. Some of the emotional and cognitive centers in the brain are closely connected to the function of the gastrointestinal system. Communication between the brain and the GI tract is largely facilitated by microbial communities in the gut. Therefore, maintaining a healthy gut microbiome is essential to supporting the normal functioning of the gut-brain axis. In recent years, growing knowledge of how to modulate the microbiome through dietary interventions has opened the door to new approaches that address a range of autism symptoms.
Although supporting the gut microbiome is important for individuals with a wide range of health conditions, microbiome-friendly diets are particularly critical for autism patients due to the fact that the gut microbial communities in autism patients are significantly different from those of their healthy counterparts, thus compromising gut microbiome health. For instance, multiple studies reveal lower levels of bacterial diversity (both within and between phyla) in the GI tracts of autism patients. Other studies show lower levels of “good” bacteria, like species of Bifidobacterium species, as well as higher levels of “bad” bacteria in the Caloramator, Sarcina, and Clostridium genera.
To address these discrepancies, autism patients with autism should be encouraged to choose probiotic-rich foods. Some clinicians are even considering the development of patient-specific probiotic and prebiotic supplementation regimens, which can be tailored to a patient’s needs based on the microbial composition of their GI tract. So far, the evidence on the efficacy of probiotics for improving the gastrointestinal and behavioral symptoms associated with autism is mixed. There is also early biochemical evidence suggesting that vitamin B12 supplements might be able to modulate the gut microbiome in autism patients to support healthy functioning.
One of the reasons it is important for autism patients to support the health of their gut microbiome is that gut bacteria are responsible for generating the bulk of butyric acid in the colon. Patients can get some of this beneficial short-chain fatty acid by eating foods that contain animal fats and plant oils, but in general, patients rely on the bacteria in the gut microbiome to produce the butyric acid they need. Butyric acid plays an important role in the production and function of cells throughout the body, but it is especially important in the colon. By regulating gene expression, mediating signaling protein activity, and serving as an energy substrate, butyric acid supports a healthy GI tract and protects against cellular abnormalities that can trigger debilitating symptoms.
There is also a growing body of research suggesting that butyric acid supplementation can address neurological symptoms in autism patients. According to a 2017 review paper, symptoms of autism are directly associated with problems with gastrointestinal permeability—commonly called Leaky Gut syndrome. This might be associated with defects in intestinal structures like tight junctions. When these protein complexes are not assembled properly by the body, it is easier for metabolites to “leak” out of the GI tract and into the bloodstream, where they have the potential to disrupt chemical balances in the brain and possibly exacerbate autism symptoms. Because butyric acid regulates the genes that code for the proteins in tight junctions, autism patients who have an insufficient butyric acid level can be more vulnerable to Leaky Gut syndrome, which often manifests with gastrointestinal symptoms like diarrhea, in addition to adverse neurological effects.
In addition to supplementation, there are several elimination diets that are increasingly popular for autism patients, the most well-known of which is the gluten-free, casein-free diet. Although there are a variety of hypotheses why this diet works, one of the most popular is that eliminating these two proteins from the diet down-regulates systemic inflammation. Scientists acknowledge this diet is widely acclaimed by parents who say it can “cure” autism, but empirical evidence has yet to offer definitive evidence to support the diet’s efficacy. Although some individual trials have highlighted positive results—such as better scores for the social interaction and communication subdomains on autism symptom measurement scales—the bulk of the evidence remains mixed. Similarly, specific carbohydrate diets—in which certain types of carbohydrates are eliminated—have been proposed as alternatives, although larger research trials are required to assess their effectiveness. So far, there have been only small studies with mixed results on the GI functioning of autism patients.
The mixed outcomes of elimination diets for autism patients might be caused by the complexity of the neurological disorder itself. Autism manifests differently in different patients, and the underlying contributors vary as well. In some patients, the microbial content of the gut might not be sufficient to support the processing of gluten and/or casein, so an elimination diet can make a big difference for both the behavioral and the GI-related symptoms; in other patients, however, an elimination diet might be less effective.
As our understanding of the relationship between autism, the gut microbiome, and diet grows, it is likely that diet-based approaches will be further refined, opening up new possibilities for durable symptom remission. However, even today there are promising options for meaningful intervention, including specialized therapies targeting gut microbiome health.
If you are interested in the connection between autism and diet, then what you need to know is that there is no one-size-fits-all approach. That’s why it is critical for clinicians to work closely with patients and their families to find well-tolerated alternatives that address each individual’s symptomatology.
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.*
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Updated on January 3, 2023
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes patients to experience a higher than normal number of daily stools, bloody or disrupted stools, diarrhea, pain, weight loss, inflammation, and bloating. UC causes damage to intestinal tissues via cycles of inflammation and tissue retraction, and is progressively degenerative, leading it to be potentially fatal if chronically untreated. As a result of modern medicine, however, UC is rarely fatal.
Although clinicians have treated UC pharmacologically for 60 years, and despite drug development over that time, a cure remains elusive. In conventional UC management regimens, clinicians prescribe pharmacotherapies, like specialized anti-inflammatory drugs and immunosuppressants, to control symptoms and vary specific medications within the general categories based on the patient’s maintenance of remission. When symptoms flare up and end remission, clinicians prescribe rescue medications like corticosteroids and, more recently, tumor necrosis factor alpha (TNFa) inhibitors to control inflammation and arrest further tissue damage. If the intestinal tract has areas that are severely damaged, then they can be surgically removed and resected.
Although conventional regimens typically enhance quality of life and allow for a normal lifespan, therapy efficacy varies, and there are many drawbacks that are keeping researchers looking for better options. In an effort to identify the most effective UC therapies for each state of the disease’s progression or remission, researchers are now comparing the efficacy and challenges of UC therapies to identify the best management strategies for creating lasting relief from symptoms. As awareness of the impact of both UC and UC therapy on the gut microbiome grows, these management strategies are increasingly integrating therapies designed to support microbiome health.
In a recent meta-analysis of UC therapies by a research group led by Dr. Fabio Teixeira, the efficacy of conventional UC therapies was examined in the contexts of the disease’s progression, severity, location in the intestinal tract, and therapy resistance. Upon comparison, older therapies were shown to be significantly less effective than newer options. In particular, TNFa inhibitors were found to be the most effective “rescue” (remission-inducing rather than remission-maintaining) therapy, suggesting that many patients who are currently prescribed corticosteroids can benefit from revised therapies. However, all the therapies examined can have a damaging impact on the gut microbiome, potentially causing relapse or the emergence of new symptoms. As a result, clinicians and patients should be cognizant of potential disruptions and seek to support microbiome health for optimal results.
The oldest, most commonly used, and most studied therapy for UC are the 5-ASA class drugs that are administered topically, orally, or as a suppository for both remission maintenance and remission induction. 5-ASA class drugs (like mesalazine) are the first line of therapy in inducing UC remission in mild to moderate cases regardless of the specific area of the intestinal tract. Dr. Texeira’s analysis found that across 38 clinical trials investigating the use of 5-ASAs, there was unanimous consensus regarding their superiority to placebos.
However, patients treated with 5-ASAs often have difficulty tolerating therapy. Although effective enough to induce remission for 52.1 percent of patients in mild to moderate UC cases, 5-ASAs can cause side effects of nausea, weight loss, vomiting, anemia, and potentially organ damage. As a result of these side effects, Dr. Texeira’s analysis states that, “Adherence to [therapy] with salicylates [5-ASAs] is a serious problem that can impact about 40–60 percent of patients.”
In addition to tolerability issues, 5-ASAs also disrupt the microbiome by inhibiting the immune system’s ability to support normal bacterial populations, thus allowing harmful microbiota to flourish and cause delayed onset inflammation. Furthermore, while effective in maintaining remission for many mild to moderate UC cases, 5-ASAs alone often aren’t enough to induce remission during moderate and severe flare-ups. If patients are still symptomatic after the first round of therapy, then 5-ASAs are often administered alongside corticosteroids to control moderate-severity flare-ups, presenting augmented risks to the microbiome.
Corticosteroids are second-line therapy for inflammation during UC flare-ups and are intended for short-term use only, typically in conjunction with 5-ASAs. Unfortunately, corticosteroids operate very slowly. This is the result of a lengthy therapy process that requires initial dosing based on symptom severity, which is then titrated to higher doses if the patient isn’t responding to therapy. Given that corticosteroids must be titrated before therapeutic levels are reached, total therapy time can be close to 8 or 10 weeks, leaving many clinicians and patients looking for a more effective solution. Dr. Texeira’s group points out that the limit of second-line UC therapy is a maximum dosage of corticosteroids, such as prednisone, for as long as 4-6 weeks before tapering off.
The potential adverse effects of corticosteroids on the microbiome also presents concerns. While not known to produce immediately uncomfortable side effects, corticosteroids behave as minor immunosuppressants for immune cells (like neutrophils), arresting their migration from the circulatory system into tissues. This allows unwanted gut microbiota to flourish in gaps of the intestinal epithelia caused by the tissue damage characteristic in UC, which can cause subsequent inflammation and symptom relapse.
Immunosuppressant drugs are the third line of UC therapy and are typically used for maintenance of remission rather than rescue. When used to maintain remission, Dr. Teixeira’s analysis found that two-thirds of patients benefited from the use of one of the examined immunosuppressants, 6-mercaptopurine. However, there are multiple immunosuppressant class drugs, and clinicians can rotate through them to find one that durably maintains remission.
Unfortunately, immunosuppressant drugs have serious side effects like higher risk of infections and anemia. The general state of immune suppression also disrupts the immune system’s ability to support the microbiome, which can become overrun with harmful bacteria and cause inflammation, potentially making future flare-ups more likely.
Although imperfect, immunosuppressants have a place in the future of UC management because they are typically administered to enhance the potency of the newest and most effective therapy: TNFa inhibitors.
When other therapies fail, clinicians turn to TNFa inhibitors to rapidly control UC symptoms. TNFa inhibitors are typically artificial antibodies that bind to the TNFa receptor on T cells, inhibiting pro-inflammatory chemical release. Dr. Teixeira’s team found that TNFa inhibitors are the most effective therapy overall for inducing remission and had an average therapy duration of less than two weeks before remission. This supports the findings of a previous study led by Dr. Siddharth Singh, which suggested that TNFa inhibitors can now be considered a second-line therapy, potentially replacing older therapies like corticosteroids. Significantly, both Dr. Teixeira and Dr. Singh found that TNFa inhibitor therapy led to superior intestinal healing when compared with a placebo, which makes them unique among the UC therapies. The importance of inducing healing is hard to overstate; Dr. Teixeira goes as far as to say that the TNFa inhibitors should make intestinal healing a new therapy objective to be pursued clinically and quantified by future research.
However, TNFa inhibitors come with the potential for a number of side effects, including a higher chance of infection, psoriasis, lymphoma, and nerve disorders. TNFa inhibitors also caused microbiome disruptions in mouse models, which are tentatively documented in a study led by Dr. Yava L. Jones-Hall. Jones-Hall’s team found that TNFa inhibitors cause mouse microbiomes to become less diverse and certain populations of bacteria to be far more abundant than expected. In humans, these disruptions can lead to inflammation and risk of higher relapse.
Although pharmacological interventions are the mainstay of UC therapy, a number of diet-based interventions have shown significant promise for addressing the effects of both UC and UC medications. In particular, Dr. Teixeira’s group underlines the need for solutions to malnutrition and poor nutrient absorption, which can arise both from the illness itself and from pharmacological therapies. As such, regimens should ideally address patient malnutrition through dietary therapies. Iron supplementation, for example, might be useful to slow UC progression or to recover from flare-ups. Likewise, vitamin B supplementation could head off a vitamin B deficiency caused by pharmacological therapies, inhibiting the development of anemia.
Because UC therapies often compromise the immune system’s ability to maintain a healthy gut microbiome, nutritional supplements that promote microbiome health can also be critical. In a weakened immune system, unwanted bacterial colonies can flourish and cause inflammation. The body’s efforts to repair microbiome disruptions caused by UC or UC therapy can be bolstered by short-chain fatty acid supplements, such as butyrate, which has been shown to provide nutritional support in addressing UC symptoms. Butyrate is a necessary cell signaling molecule in the GI tract that ensures the intestinal epithelia get sufficient nutrients and thus have the ability to repair themselves and damage caused by UC while supporting a healthy and resilient microbiome.
As our knowledge of UC expands, clinicians and patients will be able to make more informed therapy choices to achieve durable relief from symptoms. With TNFa inhibitors becoming more established in conventional therapies, the use of corticosteroids will likely fall, changing the way UC is treated in millions of people. Given Dr. Jones-Hall’s analysis of TNFa inhibitors’ impact on the gut microbiome, however, this can cause new disruptions in the microbiome. To protect the microbiome and to promote durable symptom remission, nutritional strategies, including supplementation, should thus be a central component of therapy planning. As Dr. Teixeira points out, taking a multidisciplinary approach to ulcerative colitis management that combines pharmacotherapy with tailored nutritional intervention can help patients ensure the best outcomes.Tesseract Medical Research brings you the latest research and news about gastrointestinal disorders, such as ulcerative colitis, and therapy options.
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 gastrointestinal health.*
Hallert C, Bjorck I, Nyman M, Pousette A, Granno C, et al. 2003. Inflammatory Bowel Diseases. 9:116–121.
Jones-Hall YL, Kozik A, Nakatsu C. 2015. Plos One. 10.
Singh S, Fumery M, Sandborn WJ, Murad MH. 2017. Alimentary Pharmacology & Therapeutics. 47:162–175.
Teixeira FV, Hosne RS, Sobrado CW. 2015. Journal of Coloproctology. 35:230–237.
Updated on January 3, 2023
Crohn’s disease is an inflammatory bowel disease (IBD) in which dietary stimuli cause symptomatic flare-ups that manifest in patients as pain, cramping, and diarrhea. These symptoms can not only cause significant physical discomfort, they can also deeply impact functionality and overall quality of life. Unfortunately, conventional therapies often fail to produce complete and durable relief. As such, there is intense interest from researchers, clinicians, and patients in both a greater understanding of the illness and the development of new protocols to address it.
As a disease of the gastrointestinal tract, the gut microbiome of Crohn’s patients has been the subject of extensive study, and the disease has been found to affect every dimension of the microbiome. In Crohn’s patients, the fungal, bacterial, viral, and archaean populations that make up the microbiome are skewed to contain different species and in different proportions in comparison to healthy patients. In fact, the severity of symptoms has been found to correlate to the degree of divergence from the healthy gut microbiome. However, Crohn’s disease itself is not the only variable impacting the makeup of the microbiome; therapies that seek to alleviate Crohn’s symptoms can also disrupt microbiome composition and behavior.
Until recently, the relationship between the microbiome of Crohn’s patients and the impact of therapies on the microbiome was unclear. Now, however, new research is shedding light on the links between conventional therapies and microbiome health, potentially opening up the door to more effective therapies and strategic nutritional supplementation.
In 2015, a research cohort led by Dr. James D. Lewis published a study examining how the gut microbiome responds to common therapies for Crohn’s disease and whether dietary interventions could be used to correct for imbalances caused by these therapies. The researchers also sought to identify counterproductive therapies for Crohn’s, such as those that offer temporary symptom relief but disrupt the microbiome in a way that ultimately augments symptoms. This study was among the first scientifically rigorous and fully quantitative investigations into the impact of Crohn’s therapies on the microbiome.
In a randomized controlled trial conducted in pediatric Crohn’s patients, the researchers thoroughly examined the microbiome’s response to therapies by periodically taking stool samples and performing extensive microbiome analysis over the 8-week duration of the trial. Upon analysis, the data confirmed that mitigating intestinal inflammation promotes healthy gut microbiome proportions in Crohn’s patients. However, the researchers also found that some conventional therapies for Crohn’s can disrupt an already compromised microbiome, potentially exacerbating existing symptoms or causing the emergence of new ones.
Most significantly, the study proved that Crohn’s therapies targeted toward normalizing the microbiomes of patients can provide meaningful clinical benefits. This marked a new approach to address symptoms of Crohn’s disease, because prior interventions focused primarily on acute symptoms rather than the possibility of balancing the microbiome for long-term relief of symptoms.
To better understand the relationship between the microbiome and therapies for Crohn’s disease, it is valuable to examine each therapy individually.
Antibiotic therapies are frequently used as an adjunctive therapies for Crohn’s disease to control flare-ups of inflammation. The rationale for using antibiotics is that an abnormal microbiome’s bacterial blooms can damage ileal tissue and cause intense discomfort to patients. However, Dr. Lewis’s study found that antibiotics are counterproductive therapies for Crohn’s due to their impact on the microbiome. While initially effective in reducing symptoms, antibiotic use eventually results in rebound symptoms that causes patients’ GI tracts to relapse to an inflamed state.
The reason is that while antibiotic therapies destroy most of the bacterial microbiome when administered, antibiotics have no impact on the fungal members of the microbiome, which readily multiply in the absence of bacteria. The researchers found that when the pediatric patients who experienced the most severe symptoms were administered antibiotics, their fungal populations spiked up to 175 percent of their normal size. This fungal expansion causes a different set of symptoms of Crohn’s than those caused by a microbiome populated by bacteria, including more severe bloating and nausea as the result of microbiotal fungi’s proficiency at fermentation. Fungi also cause inflammation and are more likely to cause loose stools than bacterial blooms. This explains why antibiotic therapies help Crohn’s symptoms temporarily, then cause new symptoms that worsen with time.
Corticosteroids are frequently used in conjunction with antibiotics to combat symptomatic flare-ups of Crohn’s disease because they act as potent immunosuppressors in the ilea, reducing inflammation that might be caused by blooming fungal microbiota. Inflammation disrupts the microbiome by bringing large quantities of leukocytes—like bacteria-destroying phagocytes—to the ileal surfaces. Although essential to control bacteria that can be harmful elsewhere in the body, phagocytes in the microbiome destroy both beneficial and normal bacteria, causing the proportions of the microbiome to shift. Because they address inflammation, steroidal therapies help bring the Crohn’s disease patients closer to normal microbiome proportions.
However, while steroidal therapies can correct some of the drastic changes caused by antibiotic therapies, they cannot address the underlying mechanisms of the microbiome that cause inflammation. Additionally, corticosteroids are not viable for long-term use.
As the newest therapies on the scene, anti-tumor necrosis factor (TNF) therapies are cocktails of antibodies that operate on the GI tract ileal cells’ TNFa receptors, thereby reducing inflammation. By targeting the TNFa receptors, the ileal cells undergo changes that cause a reduction in inflammation. Dr. Lewis’s study found anti-TNF therapies to be the single-most effective therapy at reducing inflammation markers, with 62 percent of the group experiencing reduction of inflammation markers to normal levels.
These results are similar to other studies, including a 2015 study conducted by Drs. Lee and Baldassano, who examined anti-TNF therapies for pediatric Crohn’s disease. They found that pairing anti-TNF therapy with dietary therapy supports quality of life substantially, while reducing inflammation markers for 84 percent of the group within the study cohort. Significantly, they also found that pairing anti-TNF with dietary therapies can restore healthy balance to the gut microbiome: while only about one-third of the patients on anti-TNF therapies alone had microbiomes close to the healthy microbiome profile, 84 percent of patients receiving both dietary therapies and anti-TNF therapies had microbiomes that deviated only slightly from the healthy norm. This means using anti-TNF therapies in combination with dietary therapies is among the most promising therapy options available for Crohn’s patients.
Dietary therapies have long been found to be more effective than steroidal therapies when it comes to healing ileal damage caused by inflammation. Although a variety of such diets exist, they are typically constituted with nutrients that decrease the amount of bacterial fermentation performed in the GI tract, which controls bloating and inflammation.
In Dr. Lewis’s study, dietary therapies were analyzed as adjuncts to the other therapies examined by the research cohort. The most significant finding was that dietary therapies can create meaningful symptom relief, while also causing the least destructive disturbances and most productive changes in the microbiome of all available therapies. Additionally, dietary therapies affected the microbiome more rapidly. Unfortunately, conventional dietary therapies are rarely capable of producing complete remission of symptoms, because baseline levels of inflammation and non-dietary factors can cause flare-ups. As such, further refinement of dietary interventions is necessary to optimize durability of remission.
The microbiomes of Crohn’s patients are exceptionally reactive to stimuli and have a much wider range of fluctuation than healthy patients’ microbiomes. As the study by Dr. Lewis’s group demonstrates, some conventional Crohn’s therapies can have a deleterious effect on the already compromised microbiome, reducing efficacy and ultimately aggravating the condition. As such, it is critical for clinicians to consider the impact of therapies on the microbiome when making therapeutic recommendations.At the same time, the development of therapies designed specifically to restore healthy gut microbiome populations and proportions will be critical to enhancing quality of life for Crohn’s patients. By prioritizing the overall health of the microbiome, rather than focusing solely on alleviation of acute symptoms, researchers can usher in a new era of Crohn’s therapies that both protect the microbiome and create durable remission of symptoms. Dr. Lewis’s finding that dietary strategies—particularly used in conjunction with anti-TNF therapies—can cultivate a more balanced, resilient microbiome is particularly promising. Identifying dietary formulations and nutritional supplements that optimally maintain the microbiome of the Crohn’s patient must thus be a major research goal going forward. However, many patients can benefit from the microbiome-enhancing nutritional supplements already on the market, including advanced butyric acid and curcumin formulations designed to promote gut health.
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 gastrointestinal health.*
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Updated on January 3, 2023
Within both the research and the clinical communities, the relationship between autism spectrum disorder (ASD) and diet has long been a topic of discussion. However, understanding the complex relationship between autism and food continues to be an ongoing challenge. This is largely because food can play a role in each of three distinct areas: the development of autism, the manifestation of symptoms, and addressing the condition. When considering the relationship between autism and food from each of these three perspectives, it is important to examine the existing research and what it can mean for the future of autism therapies.
There is broad consensus within the research community that autism is caused by a wide range of factors, including both genetic characteristics and environmental influences. Most scientists also agree that the pathogenesis of autism begins during prenatal development. This idea has led some researchers to hypothesize that the mother’s nutritional status might be among the environmental causes of autism that interact with genetic factors to cause autism’s development. Indeed, multiple studies have established strong correlations between diet-related health conditions in the mother and a higher risk of autism in the child. For instance, both type 2 diabetes and gestational diabetes are associated with a higher risk of autism. In addition, if the mother meets the standards for obesity, then the risk of autism increases by 21.5 percent, and if the mother has hypertension, then the risk of autism in the child rises by 14.3 percent.
In 2017, a researcher at UC Davis published a paper proposing a mechanism through which a mother’s diet-related health conditions might facilitate the development of autism. Based on a review of the latest research in the field, the researcher suggests that these conditions are associated with a lower intake of several key micronutrients that might be involved in the etiology of autism: zinc, copper, iron, and vitamin B9. In combination with genetic risk factors, an insufficient intake of these nutrients might contribute to disruptions in fetal brain development that lead to autism. Although future research is needed to conclusively establish a causal relationship between maternal nutritional status and autism, it is clear that the mother’s relationship with food before and during pregnancy is associated with the development of autism.
It is important to note that pregnant mothers who have one of these food-related health conditions can still take action — making strategic dietary decisions that target specific micronutrients — to address the risk of autism for the child. Studies in animal models suggest that supplements with certain micronutrients might address autism risk. In the future, clinical trials in humans might make it possible to identify the most effective food and nutritional supplement choices for expectant mothers who are concerned about autism.
Although the discussion of food as a potential cause of autism remains primarily confined to the research community, many patients and families experience a concrete connection between food and autism on a daily basis. Put simply, children with autism are significantly more likely to be “selective” or “picky” eaters. According to one estimate, one-fourth of healthy children are picky eaters, whereas about 80 percent of children with autism demonstrate selective eating tendencies, often refusing to eat (or even try) whole categories of foods. In the most serious cases, an autistic child might limit their diet to as few as five foods.
One of the proposed explanations for selective eating among autistic children is their heightened sensory sensitivity. According to some estimates, about 90 percent of children with autism process tactile, olfactory, visual, and auditory information differently than normally developing children. Based on these statistics, it should come as no surprise that preferences regarding the taste, texture, smell, and even appearance of food are evident in children with autism.
Unsurprisingly, studies also show that selective eating issues in children with autism can lead to deficiencies in important micronutrients—especially among children with the most restrictive diets. Although specific nutritional deficiencies are likely to depend largely on a child’s individual food restrictions, a broad study of more than 250 autistic children from five different U.S. states highlighted insufficient consumption of vitamin A, vitamin C, zinc, phosphorus, fiber, choline, calcium, vitamin D, and potassium. Although the commonness of inadequate intake is just as high among normally-developing children as autistic children for some of these nutrients, the effects on autistic children might be more significant. For instance, evidence suggests that certain nutrients are less readily absorbed by autistic children. As a result, the problem can quickly escalate from inadequate intake to measurable nutrient deficiency.
A possible explanation for why certain nutrients are less readily absorbed in autistic children is the difference between the gut microbiome in children with autism and their healthy counterparts. Bacteria in the gut play a key role in nutrient absorption, and studies in both human and animal models suggest that the bacterial composition of the gut is different for children with autism. Although there are not yet results from clinical trials, modifying the gut microbiome in children with autism to optimize absorption and address gastrointestinal issues is being considered as a potential therapy.
For children with autism, food selectivity can also exacerbate other symptoms. Deficiencies in multiple nutrients, including vitamin B12, vitamin D, and folic acid, have all been associated with autism etiology and the core symptoms of the disorder. Moreover, it is widely recognized within the research and clinical communities that the gut microbiome is impacted by food choices—and the health of the gut microbiome is directly related to both gastrointestinal and neurological symptoms of autism. For instance, disruptions in the gut microbiome can affect gut motility, which is a common symptom of autism. Also, in patients with Leaky Gut syndrome (which is also common among patients with autism), toxins from the microbiome can enter the bloodstream and impact the brain, potentially contributing to the neurological symptoms of autism. Because repetitive behaviors—such as selective eating—are among these neurological symptoms, abnormal food behaviors in autistic children might even be driving a vicious cycle: the more a child restricts nutrients, the more their internal neurological processes will support a tendency toward restriction.
There is also preliminary evidence that consuming certain types of foods directly exacerbate symptoms of autism. For example, some studies indicate that dietary gluten and casein are not properly digested in the gut of individuals with autism. Not only can the resulting peptides interfere with regular bowel motility, they can also directly affect brain functioning. In patients with “leaky gut”—a condition commonly associated with autism—partially-digested peptides can cross the intestinal barrier and build up the brain, where they can have an opioid-like effect associated with some of autism’s core symptoms.
Because of the associations between eating behaviors, nutritional status, and autism, a wide range of food-related therapies have been proposed by both researchers and practitioners. Some of the most popular are elimination diets, like gluten-free, casein-free, and lactose-free diets. Other dietary strategies emphasize the importance of eating more probiotic-rich foods that support the health of the gut microbiome. Although small-scale studies have examined the efficacy of specific diets for individuals with autism, the results are mixed. Given that selective eating patterns vary widely, it is little surprise that no single diet has been identified as the best option.
Still, some clinicians can recommend dietary strategies based on an individualized evaluation of their patient’s symptoms and needs. Improving the health of the gut microbiome can be a major goal of these dietary strategies. As previously mentioned, studies suggest that the bacterial composition of the gut is tied to both gastrointestinal and neurological symptoms, so a physician might recommend nutritional changes that focus specifically on the gut microbiome.
If an autistic child is not getting the nutrition they need from food, then another option is to support micronutrient intake through supplementation. Taking supplements optimized for bioavailability can be helpful for a child who struggles with the sensory processing of a normal, balanced diet. Although research is still in the early stages, studies on supplements like butyric acid, vitamin B12, and folinic acid offer preliminary evidence of addressing behavioral symptoms in children with autism.
Clearly, the relationship between autism and food is complicated. In pregnant mothers, nutritional status can affect a child’s risk for autism. During childhood and beyond, abnormal food behaviors can manifest as a symptom of autism, which can exacerbate other symptoms by affecting the child’s neurological and gastrointestinal functioning. At the same time, the relationship between autism and food presents opportunities for dietary interventions that might help symptoms of autism. This possibility is opening up exciting avenues for research into nutritional supplementation therapies for children with autism.
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.*
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Updated on December 22, 2022
An increasingly detailed and interconnected body of scientific literature is establishing the connection between the pathology of autism spectrum disorder (ASD) and the gut microbiome, leading many to wonder whether manipulation of the gut microbiome can alleviate ASD symptoms. In recent years, a number of studies have clarified the mechanisms behind the gut microbiome’s role in ASD presentation, which has spurred researchers to investigate possible treatment options specifically targeting the gut microbiome. This growing body of research is now opening the door to more effective therapies, potentially allowing individuals with ASD to find relief from symptoms that conventional treatments have not resolved.
Between 2015 and 2016, Drs. Richard Frye, John Slattery, and Derrick MacFabe of the Arkansas Children’s’ Hospital Autism Research Program published a trio of studies that sought to clarify the relationship between ASD and the gut microbiome. A number of researchers had examined this relationship prior to Frye, Slattery, and MacFabe’s experiments, producing promising data indicating that the proportions of bacterial populations within the GI tract of ASD patients could impact ASD symptoms. However, the underlying mechanism of this phenomenon remained unclear. As such, Frye, Slattery, and MacFabe sought to further elucidate the links between bacterial population proportions, mitochondria, and ASD symptoms and examine potential therapeutic avenues based on their findings.
In 2015, the group examined the mitochondria within the GI tracts of children with and without ASD to determine whether there were observable differences in mitochondrial function between them. Their study successfully established several specific metabolic mechanisms by which gut microbiota might cause mitochondrial changes and thus cause physiological changes. Not only were the associations between mitochondrial dysfunction, ASD, and GI pathologies confirmed, the researchers also found these associations are due to an overrepresentation of the Clostridia genus of bacteria in the gut microbiomes of ASD patients.
The Clostridia genus of bacteria produces the fatty acid propanoic acid (PPA) as a result of fermentation, one of the processes by which bacteria metabolize nutrients. GI-tract mitochondria are negatively influenced by high concentrations of PPA, possibly explaining some of the GI issues commonly experienced by ASD patients. This is because PPA acts as a regulator for a wide variety of mitochondrial genes, meaning that exposure to PPA causes mitochondria to function at lower efficiencies, thus causing adverse physiological changes in the GI tract. By connecting Clostridia over-representation and mitochondrial dysfunction, the study clarifies that the microbiome’s proportion of Clostridia is an important clinical factor for ASD symptoms.
Subsequent to these findings in the clinical trial cohort of children with ASD, the researchers then shifted their attention to experiments using animal models of ASD to further investigate the relationship between PPA and ASD symptomatology. Prior to initiation of their investigations, Frye, Slattery, and MacFabe had worked for more than 15 years to develop and validate these animal models so they could follow up on the results of experiments performed using human subjects more invasively. Through their animal model experiments, the researchers found that:
As a result, Frye, Slattery, and MacFabe identified a set of potential PPA producers within the gut microbiota that might be responsible for ASD-related GI issues via their influence on mitochondria.
As a result of their experiments, the research group added further confirmation to what is known in the ASD research community as “the PPA hypothesis.” The PPA hypothesis is a core theory that explains the relationship between gut microbiota and ASD GI symptoms. As described by Frye, Slattery, and MacFabe in their 2016 paper, “the PPA theory of ASD suggests that ASD may be a result of disturbances in the enteric microbiome resulting in the production of elevated levels of PPA in genetically susceptible individuals during a critical neurodevelopmental period.” Although the PPA hypothesis predates the Frye and Slattery experiments, their findings filled critical holes in the hypothesis and contributed invaluable evidence in support of it.
To investigate further, Frye, Slattery, and MacFabe used the PPA hypothesis as an investigational framework to review currently used, but not comprehensively understood, therapies that manipulate the microbiome in ASD patients. These included:
PPA concentrations were used as core metrics indicating whether a therapy might be clinically useful. As a result of their investigation, they suggested several therapies that should be examined further. In particular, FMT and probiotics were singled out as the two most promising—but least investigated—avenues for addressing ASD-related GI issues by altering the gut microbiome to remove PPA-producing colonies.
Frye, Slattery, and MacFabe’s results piqued the interest of the research community, including a clinical trial group led by Dr. D.W. Kang. To further investigate the effects of microbiome manipulation on ASD symptoms, Dr. Kang’s group conducted a study in which the entire gut microbiome of pediatric ASD patients would be removed and then replaced with a probiotic and fecal transplant product. Referred to as Microbiota Transfer Therapy (MTT), the protocol incorporates probiotics into a customized and replicable fecal transplant product with the goal of providing long-lasting relief from ASD symptoms.
Following MTT, ASD patients’ parents reported their children experienced reduction of abdominal pain and other GI symptoms by as much as 82 percent over the course of the treatment protocol, with 89 percent of the study cohort responding positively to the treatment. However, symptom reduction was not confined to GI symptoms; parents also reported improvements in ASD-related behavioral disturbances. Although Dr. Kang’s study wasn’t blinded, controlled, or randomized, it nonetheless suggests that ASD might be treatable via GI interventions designed to manipulate the microbiome and that these interventions can possibly alleviate a broad spectrum of symptoms.
While MTT is a promising treatment, it is also an intensive one. There is, however, evidence that suggests that less invasive means of microbiome manipulation could produce similar results. In 2014, a study by Dr. MacFabe found that certain biologically-produced molecules like butyric acid can act as regulators of critical genes within the cells of the GI tract. This can cause behavioral changes that could mitigate the effects of PPA. However, butyric acid can also have additional benefits. MacFabe found that in vitro butyric acid exposure altered cells’ genetic regulation of a critical protein, tyrosine hydroxylase, an enzyme that is responsible for making many of the precursors to the neurotransmitters implicated in ASD symptomatology, such as dopamine. As such, butyric acid’s impact on cells in vivo in the GI tract might mean that butyric acid supplementation can beneficially impact multiple behavioral ASD symptoms.If butyric acid’s impact on tyrosine hydroxylase can be clarified via future research, then it might be possible to identify which symptoms supplementation can most effectively target. As the research stands, butyric acid supplementation is an intriguing intervention that could provide symptom relief similar to that of the more invasive MTT and FMT, making therapeutic microbiome manipulation far more accessible and comfortable.
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Updated on January 2, 2023
For patients with ulcerative colitis, developing an effective management strategy can be a major challenge. Symptoms vary widely between patients, and many of the most common therapeutics—including aminosalicylates, corticosteroids, antibiotics, and methotrexate—have side effects that can be just as disruptive to the patient’s quality of life as the condition itself. Because ulcerative colitis has no cure, scientists have spent decades searching for therapeutic options that can offer effective assistance in symptom management. Today, a growing body of evidence suggests that short-chain fatty acids are a promising option.
The benefits of short-chain fatty acids for patients with ulcerative colitis are numerous and wide-ranging. After early observations of the effectiveness of topical supplementation of short-chain fatty acids for ulcerative colitis patients, researchers have successfully identified multiple means through which short-chain fatty acids might be able to help manage symptoms in patients with ulcerative colitis. In particular, butyric acid supplementation might serve as an effective, accessible, well-tolerated nutritional support therapy.
Short-chain fatty acids are metabolites produced by the fermentation of dietary fiber by bacteria. These metabolites have a distinctive chemical structure—a carboxylic acid “head” with a saturated hydrocarbon “tail.” There are several different chemicals in this category, and they are distinguished from each other by the number of carbon atoms in their “tails.” The three most common short-chain fatty acids in the human gut are acetic acid (2 carbons in the tail), propionic acid (3 carbons in the tail), and butyric acid (4 carbons in the tail). Together, they make up about 95 percent of the short-chain fatty acids in the GI tract.
Researchers first became interested in the possible benefits of short-chain fatty acids for ulcerative colitis patients when they observed that the concentrations of these compounds in patients’ fecal samples were significantly lower than the concentrations in healthy controls. To examine the clinical relevance of these observations, researchers in the late 1980s and early 1990s conducted studies on the use of topical short-chain fatty acid therapies (such as enemas and rectal irrigation) for patients with distal ulcerative colitis. The results indicated that therapies that directly introduce short-chain fatty acids into the colon could effectively address common symptoms, including rectal bleeding and urgency.
Although the benefits of short-chain fatty acids were clearly observed in ulcerative colitis patients, researchers could only hypothesize as to why patients were experiencing a reduction in symptoms after the introduction of these fatty acids. Only after years of work have researchers been able to formulate a more complete picture of how short-chain fatty acids can support patients with ulcerative colitis.
One of the key benefits of short-chain fatty acids is that they support the structural integrity of the colon. Most patients with ulcerative colitis have a “leaky gut,” which means the intestinal wall is highly permeable to bacteria and other toxins. When these substances enter the bloodstream, they can cause harm throughout the body. However, studies suggest that short-chain fatty acids encourage the proliferation of colonocytes, which helps build a stronger intestinal barrier with a lower level of permeability. The short-chain fatty acid with the most significant role in this process is butyric acid, because it is the major energy substrate for epithelial cells.
Butyric acid also plays a role in the development of the mucosal barrier in the colon, which is also involved in leaky gut. In patients with ulcerative colitis, the thickness of the mucosal barrier is reduced, and its composition (which includes a wide range of proteins, carbohydrates, lipids and antimicrobial compounds) is different from that of healthy patients. In experimental models of ulcerative colitis, butyric acid promotes mucus production and helps restore the optimal level of mucosal permeability.
Another hallmark of ulcerative colitis is the inefficiency with which cells in the colon absorb fluid. Not only can this disrupt electrolyte balances in the body, it can also contribute to debilitating symptoms like diarrhea. Short-chain fatty acids in the colon can directly stimulate sodium and fluid absorption, which can lead, in turn, to a reduction in symptoms.
In addition to the direct impact of short-chain fatty acids on the structure and function of the colon, one particular short-chain fatty acid—butyric acid—has also been shown to directly benefit the inflammatory response in the intestines that is associated with ulcerative colitis. There are several key mechanisms through which butyric acid exerts this effect:
Inducing T regulatory cell differentiation in the colon. T regulatory cells play an important role in the up-regulation of immune function by suppressing the inflammatory response when necessary. By promoting the differentiation of T regulatory cells in the colon, butyric acid helps maintain a normal inflammatory response in patients with ulcerative colitis.
Signaling through G-protein coupled receptors. Butyric acid can interact with a wide range of proteins in the highly diverse signaling protein family of G-protein coupled receptors (GPCRs). In one study, researchers demonstrated that the interaction between butyric acid and a specific type of GPCR addressed the inflammatory response in mouse models of ulcerative colitis.
Acting as an epigenetic regulator. Butyric acid can interact with DNA and DNA storage molecules to determine when and where particular genes are expressed. In this way, butyric acid can influence the expression of multiple pro-inflammatory mediator proteins, such as NF-KB.
Addressing oxidative damage in the colon. Studies suggest that the presence of butyric acid is associated with higher levels of glutathione (GSH), an antioxidant that can beneficially address inflammatory responses by limiting oxidative damage.
Although early research focused on topical short-chain fatty acid therapy for ulcerative colitis patients—that is, through enema or rectal irrigation—more recent studies have suggested that oral supplementation might be effective in animal models. Comprehensive clinical studies on patients with ulcerative colitis are needed to provide more concrete evidence, but the strong biochemical research results have prompted some patients and providers to start considering nutritional support by taking advantage of oral supplementation options. Highly bioavailable butyric acid supplements show the most promise because butyric acid is the short-chain fatty acid with the largest body of evidence indicating potential benefits for ulcerative colitis patients.
One of the most promising nutritional supplements for Crohn’s patients is butyric acid, a cellular signaling molecule in the GI tract that is deficient in Crohn’s patients. Providing the GI tract’s immune cells with the butyric acid they’re missing helps normalize the microbiome. Evidence suggests this type of supplementation can have significant beneficial effects; one study found that 69 percent of participants responded to bioavailability-optimized orally administered butyrate supplementation, with 53 percent achieving symptom benefit.
Further research is necessary to more fully understand the potential of butyrate supplementation to address symptoms in Crohn’s disease. However, for now, its use in addition to conventional and non-conventional therapies like GFDs might benefit patients. Other supplements, like fish oil, exist in a similar state, with some evidence in favor of their benefit in Crohn’s, and many questions left to be answered.
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