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Stimming — short for self-stimulatory behavior — refers to repetitive movements or actions that a person engages in to regulate their sensory input or emotional state is commonly associated with autism spectrum disorder (ASD). Stimming is considered a coping mechanism among affected children to adapt to an unfamiliar environment, to decrease sensory overload, or to calm themselves. Examples of stimming behavior include rocking, flapping, spinning, humming, or repeating the same sets of words over and over.
Stimming behavior can pose challenges in building social relationships for children with ASD, as these behaviors may be misunderstood, stigmatized, and seen as disruptive. While these behaviors aren’t something that needs to be suppressed or eliminated, there are times when frequent or intense stimming can interfere with daily comfort, communication, or social interactions. Traditional approaches, such as medications or behavioral therapies, are sometimes used to support regulation. However, the efficacy of these standard interventions can vary, resulting in many families and individuals exploring additional supportive strategies—such as targeted nutritional supplements—that may help soothe the nervous system and promote overall well-being.
So far, multiple nutritional supplements and medical foods have shown promise, including Korean Red Ginseng, vitamin D, omega-3 fatty acids, sulforaphane, butyric acid, folinic acid, probiotics, and digestive enzymes. This blog post explains some of the popular supplements and medical foods for autism and why you should consider an advanced formulation to help manage ASD symptoms.
The gut-brain axis, a network of nerves connecting the central nervous system and the gastrointestinal tract that sends signals back and forth, is increasingly being recognized as a key factor in influencing the expression of ASD symptoms.
Many children on the autism spectrum experience food selectivity or unique eating patterns, which can sometimes contribute to nutrient gaps. These nutritional imbalances may play a role in intensifying certain symptoms—such as sensory sensitivities or increased stimming—making dietary support and supplementation an important consideration. Supplements and medical foods for autism support are designed to fill the nutritional gaps in the diet of affected children and promote healthy neurological function and gut function.1
| Common Nutritional Supplements for Autism Support | ||||
|---|---|---|---|---|
| Omega-3 fatty acids | Omega-3 fatty acids are critical for healthy brain structure and function. Omega-3’s produce the lipid-based signaling molecules necessary for cellular communication and immune regulation. | |||
| Vitamin B12 | Vitamin B12 plays a significant role in inhibiting the toxicity of nitrous oxide. Nitrous oxide toxicity may cause irreversible inactivation of vitamin B12, which poses a risk factor in ASD. | |||
| Vitamin D3 | Vitamin D plays a crucial role in brain development, especially in early childhood. A vitamin D deficiency may cause adverse neuropathologies2.* | |||
| Butyric acid | Butyric acid is an intracellular signaling molecule and energy substrate for colon cells. Studies indicate that butyric acid benefits gene expression in ASD3.* | |||
| Folinic acid | The reduced form of folate stabilizes cerebrospinal fluid folate concentrations, which can improve the neurological symptoms associated with ASD4. | |||
| Probiotics and digestive enzymes | The current medical literature supports that certain probiotic strains can modulate the gut microbiota, promote the growth of beneficial bacteria, and may help restore microbial diversity after disruptions such as antibiotic or chemotherapy-induced dysbiosis5. Digestive enzymes aid in the breakdown and absorption of macronutrients—fats, proteins, and carbohydrates. Current evidence suggests that some children with autism spectrum disorder and gastrointestinal symptoms may have lower intestinal enzyme activity6. |
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The efficacy of nutritional supplements and medical foods for autism support and the gut-brain axis depends on the bioavailability and absorption of the product’s active nutrients. Before selecting the most suitable supplement or medication for ASD support, it is important to consider the active nutrients and delivery system used in the formulation.
Palatability and bioavailability are the two major challenges when considering a sodium butyrate supplement for autism support. Butyrate is well-known for its unpalatable flavor and odor, and its poor absorption and bioavailability impact its efficacy.
Tesseract Medical Research’s AuRx® is a gold-standard medical food for ASD support. AuRx features a stabilized butyric acid complex delivered as a palatable powder. AuRx can be easily blended with foods, such as applesauce, to ensure user compliance.
This hypoallergenic medical food is designed to help restore key nutrients that support the gut-brain connection. Addressing these imbalances may contribute to easing challenges such as irritability, language delays, and certain behavioral changes sometimes experienced by children on the autism spectrum. AuRx’s proprietary CyLoc® – DexKey® nutrient delivery nanotechnology enables targeted delivery of its butyric acid molecules at the desired point in the intestinal tract for unprecedented absorption. Consult a health-care professional before incorporating dietary changes to an ASD management plan.
AuRx® is butyric acid supplementation reimagined, making it one of the best medical foods for autism support.
The power of Tesseract supplements lies in enhancing palatability, maximizing solubility, bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Shop products on our website and learn more about how they support neurological health.
Reference:
1Adams JB, et al. Journal of Personalized Medicine vol. 11,9 878. 31 Aug 2021, doi:10.3390/jpm11090878
2Li, Maxwell, and Katharine W Lai. The Permanente journal vol. 28,3 (2024): 180-184. doi:10.7812/TPP/24.026
3Nankova, Bistra B et al. PloS one vol. 9,8 e103740. 29 Aug. 2014, doi:10.1371/journal.pone.0103740
4Hoxha, Bianka et al. Cells vol. 10,8 1976. 3 Aug. 2021, doi:10.3390/cells10081976
5Plaza-Diaz J et al. Mechanisms of Action of Probiotics. Adv Nutr. 2019;10(suppl_1):S49-S66. doi:10.1093/advances/nmy063
6Horvath K et al. J Pediatr. 1999;135(5):559-563. doi:10.1016/s0022-3476(99)70052-1
Updated on February 8, 2023
Does glutathione help Parkinson’s disease? That was the question posed by experts from the University of Medicine and Dentistry of New Jersey in a 2008 review paper. By the time of the study, the data supporting a potential role for glutathione supplements as an alternative therapy in Parkinson’s disease had been mounting for almost two decades, piquing the interest of researchers, patients, and practitioners alike. Although the antioxidant activity of glutathione was well-established at the time, the reviewers highlighted more recent evidence of the functional role of glutathione in a variety of additional processes in the central nervous system. These processes include the removal of peroxides and other toxins, the regulation of protein function and synthesis, the modulation of DNA synthesis and repair, the transportation of amino acids, and the cellular communications facilitated by glutamate receptors and hormonal signaling. The authors of the review believe these factors, taken together, might account for the consistent demonstration that the glutathione levels in the substantia nigra (a part of the brain with a role in reward and movement) were 40-50 percent lower in Parkinson’s disease patients. Replenishing and maintaining glutathione levels through supplementation, they suggest, could therefore provide therapeutic benefit in Parkinson’s disease patients.
In the 14 years since that review was published, the in vitro evidence that a glutathione supplement could make a positive difference for Parkinson’s disease patients has only grown stronger. Not only have cell-based studies continued to support the hypothesis that glutathione can play a functional role in opposing the pathophysiological processes associated with Parkinson’s disease, there are also new studies that combine lab-based evidence with measurements of patient outcome measures to solidify the connection between glutathione levels and disease symptoms. As yet, there have only been a few direct clinical trials on glutathione supplements for Parkinson’s disease patients, and they have not produced definitive evidence. However, a 2017 trial highlights some of the opportunities for future exploration and suggests that patients could realize therapeutic benefits.
Over the last decade, researchers have been building a solid case for the potential benefits of glutathione supplements for Parkinson’s disease. One of the most recent contributions came from researchers at Thomas Jefferson University in Philadelphia, who in 2016 published a relevant study in the journal PLoS One. These researchers were focusing on the role of n-acetyl-cysteine (NAC), a precursor to glutathione, in protecting midbrain dopamine neurons. They found that in a tissue culture model of Parkinson’s disease, exposure to NAC led to higher levels of dopamine transmitter binding in two parts of the brain involved in Parkinson’s disease pathophysiology: the caudate and the putamen. Specifically, the glutathione level was 4.4 percent higher in the caudate and 7.8 percent higher in the putamen, both of which are considered to be statistically significant improvements. This suggests that the conversion of NAC to glutathione supports the functioning of the dopamine system in Parkinson’s disease patients, which has been associated with both the physical and the motor effects of the condition.
Another relevant contribution came out of a collaboration by researchers at the University of Washington, Washington State University, and the Bastyr University Research Institute. Building on previous cellular-level research linking oxidative stress to the development of Parkinson’s disease progression, the researchers sought to describe associations between glutathione status, age, and Parkinson’s disease severity, in an attempt to establish a more solid connection between glutathione status and patient symptoms.
In a study of blood samples from 58 Parkinson’s disease patients, they found that glutathione levels not only declined with age, they were also correlated with statistically significant improvements in scores on the Unified PD Rating Scale (UPDRS), which is commonly used to measure Parkinson’s disease severity based on patients’ symptoms, as well as the Patient-Reported Outcomes in PD, another symptom-based scale. This evidence supports their conclusion that serum levels of glutathione can serve as an effective biomarker for Parkinson’s disease. Moreover, the data suggests that glutathione status could be a “modifiable risk factor” for Parkinson’s disease, warranting future clinical trials on glutathione supplementation.
Although there is now three decades’ worth of solid laboratory evidence suggesting that glutathione supplementation can address symptoms in Parkinson’s disease patients, the results from the few clinical studies that have been conducted are somewhat less convincing. So far, only four clinical trials have been published, with the most recent coming in 2017 from the same research group that published the previously-discussed investigation on using glutathione as a biomarker for Parkinson’s disease. This time, they conducted a double-blind, placebo-controlled trial, in which 45 individuals with mild-to-moderate Parkinson’s disease receive intranasal glutathione supplementation.
The participants were assigned to one of three groups: a control group, in which participants received a placebo, or one of two treatment groups, in which participants received intranasal glutathione supplements of either 100 mg or 200 mg, three times daily for three months. To measure the effects, the UPDRS was again used to quantify patient outcomes. In the low-dose treatment group, the researchers reported score improvements, but they were not statistically significant. In the high-dose treatment group, they reported statistically significant improvements in the total score, the motor subscore, and the non-motor subscore. However, it is important to note that their statistical analysis indicated that the statistical significance of the score improvements was stronger in the placebo group than it was in either of the treatment groups. Therefore, although the researchers were able to demonstrate that intranasal glutathione supplementation could have a positive impact on patient symptoms, they failed to demonstrate these effects were distinct from a placebo effect.
The results from the other three clinical trials have been similarly mixed, and because they did not use the rigorous, controlled-trial methodology used in the 2017 study, it is unwise to integrate or compare results. Nevertheless, it is clear that a placebo effect might be impacting the clarity of the results in each of the studies. For instance, in both the 2017 study and an open-label 1996 study, there was a heavy emphasis on the ritual of glutathione administration (which, for the 2017 study, involved tilting the head back and inhaling deeply). These types of administration rituals are well-known to be associated with placebo effects, since regular rituals associated with medication administration can have psychological impacts on patients. For this reason, more researchers are looking to tweak the methodology of future studies to obtain more conclusive, reliable results on the potential effectiveness of glutathione supplementation.
Currently, researchers are looking to preliminary studies on NAC to justify ongoing clinical trials of glutathione supplementation because NAC is converted to glutathione in the body. Alongside their in vitro study, the Thomas Jefferson University-based research group also conducted a randomized trial in which patients were treated with either NAC for three months or received no treatment. This precluded a placebo effect, and it produced promising results. Overall, the researchers found that the intervention led to a rise in dopamine transmitter binding and a 13-percent improvement on UPDRS rating scale scores. Although they could not provide definitive proof these findings were linked, their data offers further support for additional clinical trials on both NAC and glutathione supplementatnio that could prove beneficial for Parkinson’s disease patients.
In the coming years, it will be revealing for researchers to build on lab-based evidence in well-designed, large-scale clinical trials. For patients and practitioners today, it could still be worth considering a glutathione supplement as an alternative therapy for Parkinson’s disease patients. Although the evidence from clinical trials remains inconclusive, the strong evidence from the lab suggests that the effects could be significant for some patients.
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.*
Mischley LK, Lau RC, Shankland EG, et al. 2017. Journal of Parkinson’s Disease. 7(2):289-99.
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Updated on February 2, 2023
For patients with gastrointestinal disorders like inflammatory bowel disease (IBD), ulcerative colitis (UC), and irritable bowel syndrome (IBS), nutritional supplementation can often make an important difference in quality of life. A growing body of evidence is now showing these therapies can address the underlying pathophysiology of these disorders, provide nutritional support for gastrointestinal symptoms, or address the indirect effects of the disorders on other body systems. However, when nutrients are not absorbed as they pass through the digestive system, the opportunity for a supplement to have a therapeutic impact is significantly limited. For clinicians and patients, it is important to understand why this is a concern for individuals who have gastrointestinal disorders and examine the possibilities optimizing bioavailable nutrients.
Due to the nature of inflammatory and functional bowel disorders like IBS, IBD, and UC, the bioavailability of nutrients plays a greater role in the effectiveness of a supplement than for healthy patients. Here are a few key reasons why patients with a gastrointestinal disorder should be concerned about the bioavailability of the supplements they take to better manage their condition, address symptoms, and/or respond to secondary complications:
There are several gastrointestinal conditions that can interfere with nutrient absorption, making it critical to ensure that patients with these disorders take bioavailable forms of nutrients. For instance, inflammation in the gut of patients with IBD and UC can disrupt absorption of a wide range of nutrients, including iron, calcium, vitamin B12, vitamin A, folic acid, magnesium, and zinc. Compounding inflammation-related absorption issues is Small Intestine Bacterial Overgrowth (SIBO), a common contributor to GI symptoms among IBD and IBS patients. Studies suggest that the metabolites produced by “bad” bacteria in the gut of patients with SIBO competitively inhibit the absorption of key nutrients like vitamin B12. Not only can a vitamin B12 deficiency have direct consequences on cellular function, it can also contribute to some of the inflammation-associated malabsorption issues in IBD patients, such as iron-deficiency anemia. Another common nutrient deficiency resulting from malabsorption in IBD patients is vitamin D, which is particularly concerning because a low level of vitamin D can lead to inflammation, which further exacerbates symptoms and leads to higher rates of morbidity.
While nutrient deficiency can have a negative impact on gastrointestinal symptoms and overall health, certain nutritional supplements can also produce undesirable effects due to absorption issues. One of the most well-known culprits is iron. According to one recent study, about 20 percent of IBD patients with iron-deficiency anemia experience constipation, diarrhea, abdominal pain, or other gastrointestinal side-effects when they take iron. This is because gut inflammation can interfere with absorption and the unabsorbed iron remains in the gut, creating gastrointestinal disturbances. Providing iron in a more bioavailable form can prevent a cache of unabsorbed iron from remaining in the gut, reducing the risk of negative gastrointestinal effects. This could be especially beneficial for patients whose malabsorption issues have already led to deficiencies in nutrients that normally support iron absorption, such as vitamin C and vitamin B12.
Although rigorous research studies have produced mixed evidence on the effectiveness of restricted and/or elimination diets for patients with gastrointestinal disorders, anecdotal evidence indicates it is not uncommon for patients with gastrointestinal disorders to find dietary restrictions help with their symptoms, whether via gluten-free diets, low FODMAPs diets, or individualized dietary guidelines that eliminate certain “trigger” foods specific to that patient. The restrictive nature of these diets, however, can often lead to nutritional deficiencies, which makes it more important for bioavailable nutrients to be provided in supplement form.
Moreover, some studies suggest that restrictive diets themselves can limit the absorption of critical nutrients. For example, a study in colon cancer patients indicated that low fiber intake can limit the bioavailability of short-chain fatty acids, such as butyrate. This is a significant concern for patients with gastrointestinal disorders because butyrate can act in multiple capacities to modulate gut inflammation and support normal gastrointestinal function. In fact, the essential role butyrate plays in gut health is a growing area of interest for researchers, clinicians, and patients looking to alleviate gastrointestinal distress. As such, dietary restrictions that limit fiber intake and thereby impede the body’s ability to absorb butyrate might end up effectively alleviating some symptoms while exacerbating others. For patients who wish to continue a low-fiber diet, a highly bioavailable butyrate supplement would be necessary to compensate for diminished absorption and maintain gut health. Formulating an ideal diet-based therapy is thus often a delicate balancing act that must take into account the unique challenges of patients, the broad impact of dietary interventions, and the bioavailability of key nutrients.
As the importance of providing bioavailable nutrients in nutritional supplements becomes increasingly clear, the research community is exploring ways to enhance the bioavailability of formulations. A standout study with particular relevance for patients with gastrointestinal disorders comes from the University of Tampa, where a group of researchers in the Department of Health Sciences and Human Performance examined the bioavailability of several different formulations of curcumin. Curcumin is the bioactive component of turmeric, and it can help address symptoms for patients with gastrointestinal disorders through a variety of mechanisms. However, curcumin is also well-known for its low level of bioavailability, limiting the therapeutic benefit of conventional formulas.
In the study, the researchers developed three different curcumin formulations:
To evaluate the bioavailability of these formulations, the researchers took blood samples from 15 volunteer subjects. Compared to an unformulated curcumin supplement, the researchers found that serum levels of curcumin in the patients were 45.9 times higher when the patients took the first formulation, 7.9 times higher when the patients took the second formulation, and 1.3 times higher when the patients took the third formulation. These data indicate that formulation plays a critical role in harnessing the potential of curcumin supplements that suffer from naturally compromised bioavailability, and developing formulations that enhance absorption is essential to optimizing therapeutic effects.
However, it is important to note there are also downsides to some bioavailability enhancement methods, including those chosen by the researchers who conducted this study. For instance, the first formulation is problematic because soy can trigger allergic reactions in some patients, and phytosomes are rapidly eliminated in the body, rendering them a suboptimal delivery method. Many patients might also shy away from stabilizers like polyvinylpyrrolidone because they are looking for more natural options. The third formulation included turmeric rhizome, which can cause stomach upset in some patients. Finally, although not explored in this particular study, many curcumin products on the market today use piperine, a pepper extract, to enhance absorption, but this can create micro-tears in the lining of the gut that can trigger inflammation and “leaky gut”.
Ultimately, this study did not cover the wide range of possible methods to enhance the bioavailability of dietary supplements of curcumin, but there are researchers exploring exceptional new delivery methods that do not rely on harmful additives or present concerning downsides for patients. For instance, beyond this clinical study, there is evidence from animal and in vitro studies that tetrahydrocurcumin, a biologically active metabolite of curcumin, is a more active antioxidant than curcumin that might be more readily absorbed in the gut. This has sparked interest in delivery systems focusing on tetrahydrocurcumin, as pairing the most promising variants of specific nutrients with specialized delivery formulations will allow patients to realize greater benefits.
Although each type of supplement can each have unique characteristics impacting bioavailability, studies like this provide deeper insight into the formulation strategies emerging in today’s biomedical community. However, greater bioavailability is not just theoretical. Already, cutting-edge delivery systems and bioactive ingredients, such as those offered by Tesseract Medical Research, are unlocking the potential of enhanced absorption for patients with gastrointestinal disorders. Using the most promising molecules and a range of sophisticated technologies—including liposphere-based approaches, colloidal delivery systems, nanodelivery systems, and new encapsulation techniques—these products are giving clinicians and patients opportunities to meaningfully integrate bioavailable nutrients in therapeutic plans. By paying close attention to bioavailability when selecting nutritional supplements, patients are more likely to reap the benefits of these therapies.
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 February 8, 2023
Systemic inflammation is detrimental to many of the body’s tissues and is implicated in countless diseases and health conditions ranging from the common flu to cancer. Emerging research is even linking systemic inflammation to unlikely conditions such as mood disorders and mild anxiety, expanding our understanding of the dangers posed by this circumstance. As more connections are discovered between systemic inflammation and various health conditions, researchers are increasingly seeking to shed light on the mechanisms responsible.
Currently, clinicians often direct patients presenting with inflammation issues to over-the-counter compounds, like non-steroidal anti-inflammatory drugs (NSAIDs), which are proven to address non-chronic inflammation safely. In more serious cases of chronic inflammation that don’t respond to NSAIDs, doctors often prescribe corticosteroids, which can safely address inflammation temporarily. However, these medications are not effective in all applications. Additionally, corticosteroids can cause a number of side effects with significant health implications, making them generally unsuitable for long-term use.
Research is now showing that alternative help is available and powerful. For example, there are currently a number compounds used in nutritional supplements that help maintain the body’s normal inflammatory response that have been proven safe and effective which could augment conventional therapies. Thanks to recent studies that have investigated these therapies, researchers and clinicians now know more about their mechanisms of action and beneficial effects than they ever have before, allowing more patients to benefit from natural alternatives. Because systemic inflammation itself is difficult to fully address with any one compound, it might be prudent to use natural inflammation support in combination with traditional therapies to ensure the problem is being approached from multiple physiological angles.
Systemic inflammation is a complex process, and scientists are striving to more deeply understand its full range of causes and effects. The working understanding of non-systemic inflammation is fairly simple. When local inflammation occurs, such as a cut or injury, small blood vessels in the inflamed area dilate, allowing more blood to rush in. This increased blood flow causes the tissue to become warmer, and external tissues take on a reddened color. Excess plasma from the blood permeates into the inflamed tissues, which then become swollen as a result of their higher-than-normal liquid volume. The body uses the additional blood flow and increased volume to traffick white blood cells, platelets, and other cells responsible for tissue repair to the inflamed area so the damage or external cause of the inflammation can be repaired.
As part of this process, white blood cells release an anti-pathogenic chemical package at the site of inflammation. Unfortunately, this often causes the healthy tissues at the inflamed site to be destroyed along with any pathogens and damaged tissues. The unintended destruction of healthy tissues makes inflammation a dangerous prospect, especially for sensitive organs like the intestines and brain. In these sensitive organs, a normal inflammatory response can evolve into systemic inflammation that can spiral out of control, which means that controlling inflammation must be a priority within medical practice. Additionally, the adverse effects of systemic inflammation are now understood to be implicated in a broad range of adverse health conditions, and clinicians and researchers are reinterpreting many diseases in the context of their inflammatory symptoms in hopes of finding new ways to help patients. As such, anti-inflammatories are an important site of inquiry.
Although drugs that control inflammation include common chemicals like ibuprofen and aspirin, these medications are not always effective and can have undesirable or even dangerous long-term side effects. In particular, members of the most common class of anti-inflammatories, NSAIDs are associated with gastric ulcers, thinned blood, and internal bleeding in the colon. Although most of these side effects only occur with extended periods of NSAID use, some patients might experience them more easily than others. NSAIDs are also associated with slower muscle regrowth following traumatic injury.
One study published in the South African Journal of Medicine found that for patients with acute traumatic hamstring injuries, NSAIDs performed only two percent better than placebo in terms of pain relief, and negligibly better than placebo for inflammation reduction. These two effects were consistent from the day after the injury until a week later. Ultimately, however, NSAIDs slowed the healing process and ultimately left the treatment group with more pain than the placebo group; a week after the initial injury and treatment with NSAIDs, the data showed that patients taking the NSAIDs had a median of 8.8 pain units out of 100 compared to those taking the placebo who experienced a median of 3.9 pain units. Additionally, the two groups exhibited similar reduction of swelling. Other studies have corroborated similar effects.
In contrast to NSAIDs, although corticosteroids have a broader array of side effects, they also have a greater degree of efficacy in reducing inflammation. Unlike NSAIDs, corticosteroids cause veins to constrict, which means they act faster to stop acute inflammatory episodes more effectively. However, vasoconstriction can also produce a number of significant side effects, and corticosteroids are linked to mild anxiety, immunosuppression, hypertension, and slower wound healing as a result of reduced blood access to wound sites. Because of their wider and more serious side effect profile, corticosteroids are typically a second-line therapy that is only used after NSAIDs have failed to control inflammation. After a patient is stabilized and inflammation is suppressed, doctors typically transfer patients back to NSAIDs.
In addition to NSAIDs and corticosteroids, some patients turn to over-the-counter pain relievers such as acetaminophen (Tylenol, for example) to cope with the pain of inflammation. Although acetaminophen can provide temporary pain relief, it does not address the underlying inflammation. Furthermore, acetaminophen can be toxic, causing profound liver damage and, in some cases, acute liver failure when taken in high doses. Overall, acetaminophen is acknowledged as the most common cause of liver injury, and its risk is heightened when taken in concert with alcohol use. It is critical that patients recognize the dangers of acetaminophen and focus their attention on seeking out safe anti-inflammatory remedies that address the root cause of pain rather than potentially damaging pain relievers that simply mask the root cause.
Finding the right compound, however, can be a challenge. Although most local inflammation can be addressed effectively with NSAIDs or corticosteroids, the drugs’ limitations have left a growing number of patients searching for natural remedies that can be used to supplement or replace pharmaceuticals. These natural compounds include substances have long been renowned for their ability to support the body’s natural response to inflammation, as well as innovative new supplements that are emerging to give patients more modern ways of coping with systemic inflammation.
Fish oil is composed of omega-3 fatty acids. As a nutritional supplement, omega-3 fatty acids inhibit the body’s ability to convert fatty acids like arachidonic acid into prostaglandin E2, which is highly proinflammatory. Because fish oil inhibits the metabolic step necessary to generate proinflammatory molecules, the entire body experiences a lower level of inflammation. The ability of omega-3 fatty acids to inhibit inflammation is so marked that some researchers have proposed using the blood concentrations of omega-3s as a diagnostic indicator for the risk of coronary heart disease, which is exacerbated by systemic inflammation. Other researchers have proposed a link between consumption of fish oil and a lower risk of Alzheimer’s disease and stroke, both of which are associated with creating inflammation or being caused by systemic inflammation.
Unlike pharmaceutical anti-inflammatories, fish oil is primarily preventative rather than reactive with regard to reducing inflammation, which means it helps maintain long-term health rather than helping a patient during an acute, local inflammation episode.
Humans have a long relationship with polyphenols, dating back to the prehistoric era of the Indus River Valley civilization. Since then, polyphenols have been renowned for their tissue-shrinking properties, which can help address chronic inflammation safely and effectively. Derived from plants like the green tea leaf, turmeric, and the pine tree, most polyphenols are confirmed to be bioactive, which makes them a natural area for scientists performing drug discovery.
Recently, polyphenols like turmeric have been studied in the context of mitigating systemic inflammation, like in arthritis. A 2006 study found that daily administration of turmeric-derived compounds addressed inflammation caused by subsequent arthritic episodes by as much as 75 percent due to its inhibition of white blood cells’ secretion of damaging chemicals. On average, patients who used turmeric in a preventive capacity experienced a 68-percent reduction in joint inflammation, and scientists who replicated this experiment found an average of 65-percent inflammation reduction. However, the initial study also found that turmeric’s effect on the body’s inflammatory response was heavily impacted and delayed when administered only after injuries. This means that like fish oil, turmeric is best used preventively because it won’t have a therapeutic impact when used to address an acute incident.
Aside from turmeric, other polyphenol-containing plants include green tea extract. Green tea extract contains compounds that inhibit one of the body’s primary pro-inflammatory signaling molecules, the nuclear factor kappa light chain enhancer of activated B cells (NF-kB). Because cells that secrete NF-kB are inhibited by green tea extract from modifying their protein production to generate other inflammatory molecules, systemic inflammation can be addressed. Although these beneficial effects are under active study, researchers state that green tea extract consumed in quantities as high as 400 mg per day is safe and effective.
Botanicals like ginkgo biloba also contain polyphenols that exhibit similar effects. In particular, the polyphenol quercetin is associated with fewer aging-linked inflammatory markers when consumed daily by Japanese adults. Furthermore, quercetin is also associated with lower levels of LDL cholesterol, oxidative stress markers, a slightly longer lifespan, and lower blood pressure in hypertensive patients. These effects are especially pronounced in obese patients, who benefit more than patients of a healthy weight from quercetin supplementation. Like other polyphenols, quercetin is under active investigation by researchers who hope to exploit its medicinal effects.
Butyric acid is perhaps the newest and most promising natural compound. Also known as butyrate, butyric acid is a cellular signaling molecule produced in large volumes in the human gut and subsequently consumed by the gut microbiota for energy. Butyric acid is potent because it inhibits secretion of the critical pro-inflammatory molecules IL-1B, TNF-a, and IL-6. These molecules are secreted by dying cells, creating systemic inflammation that causes circulating white blood cells to clear any pathogens in their vicinity. Because butyric acid inhibits these signals from being secreted and causes proinflammatory t-cells to self-destruct, systemic inflammation is beneficially down-regulated. One study found that administration of butyric acid to cells in vitro reduced their secretion of certain proinflammatory molecules by more than 70 percent.
Historically, butyric acid’s beneficial effects were impossible to access due to the compound’s inability to survive metabolism and produce its systemic physiological effects. As a result, researchers have long sought a way to administer butyric acid in such a way that it could circulate everywhere in the body after oral administration and first pass metabolism. Thanks to recent breakthroughs in high bioavailability delivery systems, patients can now take butyric acid supplements to enjoy its benefits. Rather than losing most of the ingredient’s activity to first-pass metabolism, bioavailability systems like erodible pill coatings or molecule-specific drug release triggers enable the butyric acid to get where it needs to go and remain there longer. Although butyric acid is under active research and many questions remain to be answered, its undeniable efficacy in vitro and safety profile in vivo make it an excellent choice for supporting the body’s natural response to inflammation.
Natural compounds with a beneficial inflammatory response profile are becoming more understood by the day, and evolving knowledge brings new hope and expanded therapy options for patients seeking natural alternatives to conventional pharmaceutical therapies. However, patients who want to take advantage of natural inflammation support must seek out the most appropriate and highest quality supplements to realize optimal benefits; many supplements have been tested in specific disease contexts, and patients should strive to find those that are proven effective for their needs. Natural substances with beneficial inflammatory response characteristics are also often more effective when used in combination with each other and with traditional therapies. With this in mind, clinicians should tailor combination therapies to the specific needs of their patients to achieve the best outcomes, while minimizing side effects and promoting overall wellness.
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
As rates of autism spectrum disorder (ASD) diagnosis continue to rise, the investigation into the potential causes of autism has intensified within the scientific community. As a result of these investigations, autism is currently understood to result from complex interactions between genetic and environmental variables. Now, research indicating that ASD might be caused by propionic acidemia (PA), an uncommon metabolic disorder, might give us even greater etiological insight.
Propionic acidemia (PA), a rare inborn error of metabolism that prevents patients from properly converting amino acids into sugars during digestion, results in a toxic byproduct, propionic acid. As propionic acid builds up in the bloodstream, patients can experience vomiting, seizures, anorexia, and behavioral symptoms similar to ASD. To address this, specialty diets that lower protein intake and avoid the use of the defective enzyme are typically recommended. If these diets are unsuccessful and propionic acid buildup has caused extensive liver damage, then liver transplantation can be necessary as a last resort.
Due to its neurological impact, patients with PA often present with symptoms of autism that might not be sufficiently prevalent for an ASD diagnosis. However, in some newly reported cases, patients experience both PA and a plethora of ASD symptoms. This comorbidity suggests there is a causal relationship between the two, with researchers noting that PA might increase vulnerability to prenatal development of comorbid ASD. However, given the lack of understanding of PA’s prevalence in ASD, researchers have only recently taken the first steps to describe this relationship.
While scientists are still learning about the causes of autism and how PA might play a part, there is reason to believe they are onto a useful hypothesis; the gut-brain axis is implicated in the onset of autism via certain genetic errors of metabolism that cause disruptions of the brain and the intestinal tract. If scientists can discover how to handle diseases that originate in metabolism, then they might be able to more fully address ASD symptoms as well.
The first known foray into PA’s comorbidity in an ASD patient was described in a 2012 paper published in the JIMD Reports journal by Drs M. Al-Owain and N. Kaya of the King Faisal Specialist Hospital and Research Center in Riyadh. This paper examined a young patient from Saudi Arabia who presented with ASD-like symptoms in addition to prenatally diagnosed PA. The potential connection between PA and ASD was tenuous, but not surprising; a link between ASD and GI tract issues fits cleanly under the mainstream theories regarding autism’s pathogenesis.
The potential relationship between PA and ASD was sufficiently compelling for other researchers to undertake more in-depth investigations. Research produced in 2016 by Drs Peter Witters and Eric Debbold corroborates the link between the two conditions in a longitudinal study of 12 patients investigating blood metabolite balance in patients with PA and behavioral disruptions. This investigation was one of the first to document more than a single isolated case of PA and ASD.
Of the 12 patients involved in the study, 8 had features of ASD, and these 8 patients were the focus of the analysis published by the authors after the conclusion of the study. Importantly, only 5 of the patients had enough features of ASD to meet the diagnostic criteria for ASD despite all 8 patients exhibiting abnormal serum levels of common physiological molecules associated with ASD. This result upends the conventional understanding of the molecules implicated in causing autism; the 3 non-ASD patients had symptoms of ASD, but not in sufficient severity or number to fulfill the diagnostic criteria for ASD, which means their symptoms were caused by another pathology.
Regarding the common physiological molecules, Witters and Debbold examined the patients’ blood concentrations of amino acids, ammonia, and lactate, as well as the patients’ urine concentrations of propionic acid to guide their analysis. An abundance of soluble amino acids and ammonia would indicate the patients’ metabolism was insufficiently breaking down proteins and serve as experimental proof of PA or another metabolic disorder. After the patients in the study cohort were established to have PA, the researchers could then draw a quantitative link between the concentration of certain molecules and the incidence or severity of ASD.
The Witters and Debbold study was groundbreaking for its connection of a metabolic disorder to the pathogenesis of ASD and opens up an entirely new subfield of clinical research that has the opportunity to immediately help patients find relief from symptoms. More specifically, if caretakers know that PA and ASD are linked, then they can implement more effective diet-based therapies that control the symptoms of both at the same time.
One of the fundamental objectives of the Witters and Debbold investigation was quantifying and differentiating between ASD and PA symptoms. To facilitate this process, they characterized the symptoms of their patient cohort before proceeding to establish a baseline level of impairment in the study group. Among the patients in the study, all had significant delays in motor development, and all but two had marked intellectual disabilities in keeping with the traditional characterization of PA in isolation. All patients also had delayed or absent speech, and half had central nervous system disorders, like poor muscle tone or difficulty maintaining a normal gait, similar to ASD.
However, while there are significant overlaps between PA and ASD symptoms, PA also causes metabolic crises in which toxic byproducts can reach dangerously high concentrations in the patient’s body, causing liver damage and seizures. Metabolic crises are extremely dangerous for patients with PA and may be life-threatening when combined with malnutrition. This is because in individuals with PA, metabolizing proteins require metabolic processes that result in higher concentrations of propionic acid and worsen the metabolic crisis. Critically, this metabolic dysfunction and resulting concentrations of propionic acid might have a causal relationship with ASD symptoms.
Although propionic acid’s impact on human ASD is just starting to be uncovered, the effects of propionic acid have been investigated much more extensively in animal models of ASD. These experiments in animal models have shown that propionic acidosis can produce ASD-like symptoms that correlate with high concentrations of the acid. In particular, propionic acid has been found to produce symptoms such as social withdrawal and stereotyped behavior.
In an experiment by the widely cited Drs SR Shultz and DF MacFabe, adult rats were injected with propionic acid in their intracerebroventricular space. After injection, the rats rapidly exhibited numerous ASD-like symptoms. Further replications of this experiment by other researchers revealed that the brain lipid concentrations of the rats changed in response to the propionic acid infusion, and these lipid concentrations were directly correlated with ASD-like symptoms. Although the relationship between individual lipids and individual ASD-like symptoms remains unclear, the results suggest that diets that control PA might also help control ASD—a potentially massive breakthrough.
Although propionic acid concentrations in the brain are a potentially causative mechanism for ASD development, it is not the only way PA might induce ASD symptoms. Disruption to the microbiome is also a potential cause of ASD symptomatology resulting from PA, as described in the original study reporting ASD in PA by Drs Al-Owain and Kaya. The study by Al-Owain’s group notes that ASD patients typically suffer from dysbiosis of their intestinal mucosa as a result of impaired carbohydrate metabolism. Dysbiosis is used to refer to situations in which a person’s microbiome has pathological effects on the host, similar to parasitism. Dysbiosis itself is caused by increased production of short-chain fatty acids (SCFAs) in the gut, which allows for maladaptive bacteria to grow while normal and healthy gut microbiota is suppressed. This unhealthy microbiome can adversely affect the gut-brain axis and drive the development of ASD or it might be caused by ASD. Significantly, propionic acid is one of the SCFAs that results from impaired metabolism.
However, even in the absence of ASD, PA patients suffer from dysbiosis. Although intestinal propionic acid concentrations were not measured by the Al-Owain or Witters groups, the two potential mechanisms for dysbiosis—impaired carbohydrate or protein metabolism—both alter those concentrations markedly. It’s feasible that these dual dysbiosis mechanisms could team up to cause even more severe microbiome disruption and GI tract symptoms. Al-Owain’s group suggests that PA acts as one of the drivers of developing ASD under the two-hit model of ASD pathology, which posits that two separate factors must be present before ASD is developed. Under this model, one problem—such as PA in isolation—is insufficient to cause ASD, but when paired with another condition—such as another metabolic disorder affecting the gut-brain axis, like biotinidase deficiency—the combined detrimental effects of the two pathologies can cause ASD. Once developed, ASD likely combines with inborn metabolic disorders to exacerbate negative impacts on the microbiome. This hypothesis is put to the test by Witters’ group’s analysis of the genetic basis for comorbid ASD and PA.
Although a fertile area of interest, the genetic basis for ASD is not yet fully understood. The genetic basis for PA, on the other hand, was believed to be apparent at the time of Debbold and Witters’ study. However, Debbold and Witters’ research calls into question the established genetic understanding of PA in significant ways, which has profound implications for our understanding of both the etiology of PA and the relationship between PA and ASD.
The Debbold and Witter study took DNA samples from each of their 12 research subjects and examined their PCCA and PCCB genes. PCCA and PCCB code for two variations of the propionyl-CoA carboxylase enzyme, which has profound implications for gut health. Everyone has one copy of PCCA and one copy of PCCB, meaning they produce two slightly different variations of an enzyme that both serve the same purpose. However, this enzyme is not correctly produced in patients with PA.
Significantly, all of the patients in the study’s cohort who were diagnosed with comorbid ASD were found to have some kind of loss-of-function mutation in their PCCB gene, resulting in PA—the patients still produced the enzyme, but the enzyme was incapable of performing its job, leading to propionic acid buildup. There are many possible loss-of-function mutations, however, and examining which particular loss-of-function mutation of the PCCB gene individual patients possessed raised more questions than it answered. Critically, two of the ASD patients had only mild PA because, the researchers speculate, they shared a less impairing loss-of-function mutation in their PCCB gene, which shouldn’t be possible; all loss of function mutations should be equally and totally impairing to the enzyme.
This result is inconsistent with what is known about the autosomal recessive inheritance of PA without respect to ASD, which predicts that individuals need two identical copies of the PCCB gene that must both contain the same loss-of-function mutation before PA develops. Under this likely incorrect understanding, if two parents are asymptomatic carriers of PA, then they have a 75 percent chance of producing healthy offspring despite 50 percent of those offspring carrying the loss-of-function mutation. The other 25 percent of their offspring will carry two copies of the loss-of-function mutation, causing them to develop PA. The existence of mild PA means that some loss-of-function mutations are less incapacitating of the enzyme, and thus it might be possible for certain individuals to have both loss-of-function-mutations—indicating that genetically, they have PA—but only experience mild or subclinical symptoms.
Significantly, Debbold and Witter found that the standard inheritance model does not describe the pathological impact of the genetic data that was harvested; when looking at data from siblings of the research subjects, it was discovered that certain individuals did not develop PA despite having both loss-of-function mutations. In other words, the current model for explaining the genetics of PA is wrong. Additionally, not all known loss-of-function PCCB mutations were correlated with ASD symptoms, meaning that PCCB mutations are not universally predictive of ASD. Of particular importance was the finding that the brother of one of the patients in the study did not develop PA, ASD, or any ASD symptoms whatsoever despite the presence of loss-of-function mutations; he defied the genetic model. This means that although PA and ASD are genetically correlated, their exact relationship eludes a comprehensive understanding. However, clinically detectable PA symptoms remain likely to behave as one contributor to developing ASD, supporting the two-hit model of ASD pathogenesis.
In their conclusion, Witters and Debbold make their strongest argument for the connection between propionic acid and ASD by observing that, given the rates of PA and of ASD occurrence in the general population, the probability of there being no link between the two pathologies is 4.34 in 10 trillion. Put differently, comorbid incidences of PA and ASD are far more common than should be expected between two unrelated diseases, meaning there is most likely a link between the two. As such, Witters and Debbold judge their study as supporting a correlation between ASD and PA, although they state that further research is required to elucidate the relationship in detail.If subsequent research does prove a connection between PA and ASD, then ASD pathogenesis will be clearer than ever before. Finding PA to be a causative factor in ASD would be broadly beneficial to ASD research in many other subfields; researchers would be one step closer to having a complete inventory of environment and genetic factors that contribute to the development of ASD. Likewise, if research into the ASD microbiome can solidify the link between certain microbiota and propionic acid concentrations in the gut, then patients will be able to calibrate their diets more effectively and potentially exploit the gut-brain axis for symptom relief. Furthermore, ASD patients without PA might be able to reap the benefits of using a PA-control diet if a definitive link is drawn between PA-negative propionic acid levels and ASD symptoms in humans.
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 February 14, 2023
If you are the parent of a child with autism spectrum disorder (ASD) who displays aggressive behaviors, then you’re not alone: estimates indicate that one in four children diagnosed with autism fall within the clinical range on commonly-used aggressive behavior scales, and this symptom is the primary cause of residential placement for autism patients. Unfortunately, among the widely varying physical and behavioral symptoms associated with autism, aggressive behavior is one of the most challenging to address. This is largely because the etiology of behavioral problems is poorly understood: scientists hypothesize that aggressive behaviors in ASD patients are caused by a complex combination of biological, behavioral, and environmental factors but have yet to develop a fully comprehensive model for understanding the underpinnings of this common symptom.
Currently, the standard recommendation for autism patients who display aggressive behavior is antipsychotic medication. In 2006, risperidone (a second-generation antipsychotic) was approved for patients as young as five years old. Because several controlled studies indicate risperidone can be effective for addressing aggressive behavior in autism patients during childhood, it has become one of the most widely used medications in the field. The other FDA-approved option is aripiprazole, a similar antipsychotic drug. Although these medications have clear safety benefits over clozapine, which was the medication most commonly used in the past, they lack consistent efficacy and can produce unwanted side effects, like weight gain and daytime drowsiness. Therefore, scientists continue to explore pharmacological options that could be considered for future FDA approval, such as haloperidol, olanzapine, lurasidone, quetiapine, and sertraline. Preliminary small-scale, open-label studies suggest these drugs might offer benefits for some ASD patients.
Although lab-based and clinical research has historically focused on pharmacological therapeutics, many parents and practitioners are increasingly interested in alternative therapeutic options. Not only are there concerns about the side effects and overall efficacy of pharmaceutical therapies for addressing aggressive behavior in ASD patients, some parents simply want to avoid starting their child on a prescription medication so early in life. Still, the lack of understanding of the basis of aggressive behavior makes it difficult to address directly, so some researchers are exploring an innovative solution: targeting conditions statistically associated with the symptom. Specifically, scientists have recently observed significant correlations between aggressive behaviors and sleep problems in children with autism. This connection between autism and sleep problems has led to the hypothesis that it might be possible to provide an option for aggressive behavior with butyric acid supplementation.
Multiple studies suggest a relevant clinical connection between aggressive behaviors in autism patients and sleep problems. One particularly persuasive paper from 2015, published by researchers from Oregon Health and Science University, assessed the prevalence and correlation between aggressive behaviors and a variety of other co-varying conditions in a large clinical sample of 400 patients between the ages of 2 and 16 years. Recognizing that the roots of aggressive behavior are poorly understood in autism patients, their goal was to identify better-understood conditions that could be addressed more effectively in the expectation that the therapy would address both the aggressive behavior and the co-morbid condition. Chronic sleep problems was one of the conditions that immediately stood out as a feasible target.
Consistent with previous studies, the Oregon researchers found statistically significant associations between aggressive behavior and scores on a survey that measured eight different sleep domains among autism patients, including:
Based on this data, the researchers concluded that sleep problems were a practicable target in future therapies designed to address aggressive behavior problems in children with ASD.
The next question, of course, is how best to address sleep problems in autism patients. Although traditional over-the-counter sleep aids like diphenhydramine HCl remain an option, drowsiness and dizziness are common side effects—the same side effects, in fact, that many parents are trying to avoid by seeking alternatives to antipsychotics. Also, because sleep problems in autism patients tend to be chronic, an over-the-counter sleep aid is not suitable because they are intended for periodic (not regular) usage, and children can develop a tolerance for them over time.
One promising solution is to address abnormalities in the gut microbiome. According to one recent study in mice, the presence of short-chain fatty acids in the gut has an important role in the regulation of the circadian clock, which influences sleep and wake cycles. In a 2018 study in mouse models, researchers from Waseda University in Tokyo found that the concentrations of short-chain fatty acids in the gut—including butyrate, acetate, and propionate—could directly modulate the functioning of the circadian clock. These short-chain fatty acids are produced by bacteria in the gut when they ferment fibers that humans cannot digest. Therefore, the researchers suggest that increasing the dietary intake of prebiotic fiber, either through whole foods or through supplementation, might enhance outcomes for individuals suffering from sleep problems.
Based on this finding, another option for autism patients would be to introduce short-chain fatty acids directly into the gut with a butyrate supplement. Although the Waseda University researchers who produced this paper did not focus on autism patients, some studies suggest that autism patients lack healthy concentrations of butyrate-producing gut bacteria. For these patients, directly supplementing with butyrate might be more effective for reducing sleep problems than taking prebiotic fiber and assuming the patient’s microbiome is healthy enough to ferment the fiber and produce the circadian-clock-regulating butyrate as expected. Supplementation is also ideal for ASD patients because sensory inputs surrounding food can often trigger symptoms, including aggressive behavior.
Of course, parents and practitioners must recognize that the Waseda University study was conducted in mice, so it is not entirely certain whether supplements like prebiotic fiber and butyrate will have similar effects on the circadian clock in humans. Nevertheless, for parents and practitioners who are looking to indirectly target aggressive behavior in an autism patient through a closely correlated condition—that is, sleep problems—trying a butyrate supplement and/or choosing a diet that is high in prebiotic fiber is a relevant strategy to undertake. Another option to consider is supplementing melatonin, a hormone that has been shown to help resolve sleep problems in children with autism in early studies. In the future, clinical studies can better resolve questions about how best to harness the correlation between sleep problems and aggressive behavior in autism patients for the development of optimal therapies.
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 February 2, 2023
As our population ages, Alzheimer’s disease is becoming increasingly prevalent in the United States and around the world. Unfortunately, the complexity of multifactorial symptoms means that an effective therapy remains elusive; at present, there is no pharmacological therapy that is proven to halt the neurodegenerative effects of Alzheimer’s disease. Nonetheless, there are a number of regimens that support healthy cognition, and researchers are continuously investigating therapeutic combinations.
Although conventional pharmaceuticals have historically been the primary site of inquiry, advancements in alternative and complementary medicine along with the growing integration of such therapies in mainstream practice have led researchers to increasingly turn their attention to the potential benefits of these modalities when paired with conventional therapies. Of particular interest are dietary interventions and nutritional supplements, including brain health supplements that pair nutritional support with pharmaceutical-grade delivery mechanisms and encapsulants. Until recently, however, there were few investigations directly comparing the efficacy of these therapies. Now, that is changing.
In late 2015, Drs. Alessia Giulietti, Arianna Vignini, Laura Nanetti, and Mazzanti Laura of the Universita Politecnica delle Marche in Italy performed an extensive review of randomized controlled trials on nutritional supplements and dietary interventions for Alzheimer’s, seeking to identify those therapies with positive outcomes, particularly when used alongside conventional therapies. Published in DNA Research, their report sifts through the vast amount of contradictory information within the field to identify a number of brain health supplements that might provide benefit for patients when integrated with the current standard of care.
Conventional pharmacological therapy for Alzheimer’s disease focuses on either increasing or decreasing the concentration of certain key neurotransmitters in the brain to compensate for the neurotransmitter abnormalities associated with the condition. The pharmaceuticals currently indicated for addressing Alzheimer’s are acetylcholinesterase inhibitors (AchE inhibitors) and NMDA receptor antagonists (NMDARAs). Although each of these drug classes can be used alone, Giulietti’s group notes that the best outcomes are achieved when they are used in combination:
Within the healthy brain, acetylcholine is a neurotransmitter responsible for triggering neurons to consolidate memories, among many other functions. In patients with Alzheimer’s, however, acetylcholine is either produced in a lower quantity or cleared more rapidly than in healthy individuals, leaving a deficit that compromises memory formation and produces a number of other cognitive impairments. AchE inhibitors seek to enhance cognitive functioning in Alzheimer’s patients by increasing the amount of acetylcholine at the synapses between neurons.
According to Dr. Giulietti and her peers, patients who take AchE inhibitors typically experience better visual memory and cognitive ability. However, these benefits are small. One study found that on a 70-point Alzheimer’s severity scale, introducing AchE inhibitors lowered patient scores by an average of only 2.4 points. Thus, while there is a beneficial effect, AchE inhibitors alone are insufficient for addressing Alzheimer’s symptomatology.
Research also indicates that not all patients experience similar outcomes, and efficacy is highly reliant on the patient’s genotype. If patients have a certain uncommon mutation, then their response to AchE inhibitors will be greater; if they have a different uncommon mutation, then their response will be weaker. Additionally, therapy adherence can be compromised by tolerability issues, because up to 10 percent of patients experience nausea and vomiting while on an AchE inhibitor.
NMDA is a neurotransmitter associated with synaptic plasticity, learning, and memory. In Alzheimer’s patients, NMDA activity is significantly higher than in healthy individuals, interfering with these functions and eventually causing higher concentrations of calcium inside of neurons, producing cellular damage. NMDARA class drugs, which are prescribed for moderate to severe Alzheimer’s, limit the ability of NMDA to cause physiological changes in the brain and avoid this damage. Giuletti et al observe that these drugs likely also have a second mechanism of action affecting neurons’ phosphate metabolism; however, this mechanism is mostly undescribed.
Unfortunately, the efficacy of NMDARAs is comparable to AchE inhibitors in terms of their ability to lower Alzheimer’s severity scale scores—which is to say, they are not very effective. They also don’t slow the progression of the disease.
In addition to prescription pharmaceuticals, the Giulietti et al review investigates studies that examined the use of supplemental metals, like calcium and magnesium, for addressing Alzheimer’s. Giulietti et al finds magnesium supplements to be potentially useful for improving the quality of life of patients as a result of magnesium’s calming effect. However, magnesium is insufficient to reverse the disease’s progression. Magnesium still has a role, however, because it can address malnutrition.
Giulietti et al find that the conditions of malnutrition result in critical shortages of magnesium and calcium, both of which have significantly detrimental effects on the brain’s ability to function in the context of Alzheimer’s. When these minerals are depleted, neurons become incapable of transmitting action potentials to other neurons, and the brain’s activity drops precipitously as a result. In effect, malnutrition multiplies the severity of the symptoms of Alzheimer’s. Malnutrition is more common in mid to late-stage Alzheimer’s, when patients forget to eat or are unable to feed themselves.
Despite the potential to compensate for malnutrition, Giulietti et al finds the research supporting the use of mineral supplementation beyond that required to maintain health scant. Of the studies examined in the review, none could show efficacy alone or in conjunction with other supplements and pharmaceuticals. Nonetheless, there is a study performed in mice that suggests supplementation with magnesium can limit the progression of Alzheimer’s and restore lost functionality, although this study has not yet been replicated. The takeaway message from the Giuletti et al review is that magnesium and calcium supplementation will stave off the detrimental effects of malnutrition, but will do little to slow the progression of Alzheimer’s or address cognitive symptoms.
Due to their role in limiting damage caused by oxidation of neuronal tissues, antioxidants are under active investigation for their potential ability to mitigate impairment in Alzheimer’s, possibly enhancing overall outcomes. As Giulietti et al write, “Since oxidative stress and inflammation appear to be involved in brain aging and in neurodegenerative diseases, it is theorized that higher intake of antioxidants could be effective in […] ameliorating these changes.” Of these antioxidant compounds, the most studied is vitamin E.
Vitamin E is a controversial therapy for Alzheimer’s disease because its effects are proven in the laboratory but inconsistent when used in a clinic with patients. For every methodologically sound study that found a beneficial effect of vitamin E, there is another study that contradicts it. Even in studies with positive results, the effect of vitamin E is typically minor.
One study cited by the Giulietti et al review shows that long-term vitamin E supplementation lowers the chances of developing Alzheimer’s by 56 percent, but a significant number of research subjects who aggressively supplemented with vitamin E still developed Alzheimer’s, which then progressed at normal speed. Giulietti et al also point out that one study on vitamin E unintentionally caused the disease to progress faster in a cohort subset. This suggests that, as with metal supplements, insufficient vitamin E intake will make cognitive symptoms worse, but a glut of vitamin E won’t make symptoms better for individuals who are nourished and might even possibly exacerbate symptoms. This makes the regulatory environment for research into vitamin E difficult, despite the fact that many studies have documented no side effects whatsoever.
Antioxidants derived from fruit could potentially address Alzheimer’s symptoms based on the amount consumed. Figs, blackberries, blueberries, red wines, and black currants have each respectively been studied for their high antioxidant content, and there is some evidence they have positive effects; in a mouse study examined by Giulietti et al, consuming this subset of antioxidants in fruits is associated with restricted cognitive impairment and higher life expectancy. However, correlating the results to human patients is difficult for a disease as complex as Alzheimer’s.
While it isn’t possible to stop the progression of Alzheimer’s disease by eating fruit, dietary supplementation with the antioxidants derived from these fruits is an area of active investigation based on the promise of animal studies. Further experimentation will be necessary to identify the exact compounds responsible for the most effective symptom remission and isolate those compounds to formulate supplements.
Fruit antioxidants aren’t the only ray of hope for Alzheimer’s patients who do not respond to conventional therapies. A number of multi-chemical nutritional supplement therapies have been developed that combine vitamins, fats, and minerals to provide a comprehensive supplement for Alzheimer’s patients that can be used to complement conventional therapies. Patients can take one dose of these compound nutritional supplements daily, which lowers the chance of non-adherence occasioned by multiple supplements. Of the nutritional supplements that claim to be helpful for Alzheimer’s disease, the Giulietti et al review only discusses the most popular one, called Souvenaid.
Souvenaid has been studied extensively in the context of Alzheimer’s therapies and comes in a drinkable formulation that patients take after a meal. Souvenaid contains fatty acids that behave as antioxidants, precursors to acetylcholine, and uridine. By providing the patient with more of the essential building blocks for neuronal repair, the expectation is that the neurons make use of the glut of resources and evidence of efficacy exists in both animal and human studies. According to one study cited by Giulietti et al, Souvenaid enhanced memory function in patients with mild Alzheimer’s by 21 percent based on neuropsychological test battery memory scores. However, these results were short-lived, because Souvenaid failed to slow the disease progression. Additionally, the behavioral symptoms and sleep difficulties associated with Alzheimer’s continued to worsen over time.
The conclusion of the Giulietti et al review crystallizes the multifactorial approach that doctors should take in addressing Alzheimer’s, because multiple therapies are currently necessary to address the multiple symptoms of the disease insufficiently resolved by conventional therapies. Giulietti et al identify a number of potentially promising complementary interventions that can be used to enhance outcomes while steering clinicians and patients away from therapies without empirical backing. However, with the advent of rapidly emerging research, the Giulietti et al review is already incomplete. Supplements like butyric acid, for example, are currently being investigated by a growing number of researchers for their unique approach to potentially achieving cognitive benefits in Alzheimer’s patients.
Although butyric acid is a substance known for its many physiological roles in the gut, it might also offer an innovative approach to addressing Alzheimer’s. This approach is grounded in the ability of butyric acid to inhibit the action of the histone deacetylase enzyme, regardless of where it is in the body. Histone deacetylase blocks memory formation by keeping the DNA responsible for memory formation from being used by neurons, giving it a potentially critical role in the development and progression of Alzheimer’s; a forensic study revealed highly elevated concentrations of neural histone deacetylase in Alzheimer’s patients. By disrupting histone deacetylase activity, butyric acid could thus limit its interference with memory formation.
Much like other nutritional supplements indicated for Alzheimer’s disease, butyric acid needs significant future investigation before researchers can develop exhaustive guidelines for use; in many ways, experimentation with brain health supplements for Alzheimer’s is just beginning. However, due to its potential to enhance memory function, butyric acid will likely have a place in the combination therapies that cutting-edge clinical practices are increasingly using. While butyric acid supplementation is still new, researchers find it promising and are investigating it further, particularly as more advanced delivery systems are developed to enhance bioavailability and augment therapeutic benefit. Thanks to its solid theoretical basis and high tolerability, some patients are already using butyric acid alongside conventional Alzheimer’s therapies in their fight against the disease.
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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Updated on February 8, 2023
Parkinson’s disease, which affects more than 10 million individuals worldwide, extracts a terrible toll on patients and caregivers alike. Throughout the course of the disease, patients’ fundamental motor skills deteriorate in an all-too-familiar march toward incapacitation. Meanwhile, patients experience a debilitating array of cognitive problems that mirror dementia as the central nervous system neurons deteriorate further. This leads to severely compromised functionality, diminished quality of life, and ever-increasing dependence on others for basic needs and safety.
Unfortunately, Parkinson’s disease is currently incurable and conventional pharmacological therapies for Parkinson’s disease primarily attempt to treat the neurochemical deficits that are characteristic of the disease using chemicals like levodopa (L-DOPA), which is deficient in Parkinson’s patients. Although scientists are investigating innovative emerging interventions like gene therapy to help patients, the current standard of care only delays the inevitable. As a result, a growing number of clinicians and patients are turning to alternative therapy in hope of alleviating symptoms. Currently, one such option is proving to be particularly promising: butyric acid.
Butyric acid is a natural molecule produced by the human body and found in high concentrations in the gut. Physiologically, butyric acid has various purposes, ranging from cell signaling to regulating inflammation, which suggests potential therapeutic benefit for Parkinson’s patients. Indeed, several researchers have connected the protective and restorative abilities of substances like butyric acid to a reduction of Parkinson’s symptoms although they have stopped short of a full explanation of mechanisms.
In 2014, a groundbreaking theoretical synthesis by Drs Chandramohan Wakade and Raymond Chong investigated the neuroprotective mechanisms of butyric acid in the context of Parkinson’s disease by analyzing the relationship between the niacin receptor and dopamine levels. Through their synthesis, the researchers propose that butyric acid has the potential to beneficially impact Parkinson’s symptoms and underlying pathology via no fewer than three distinct mechanisms: reducing inflammation, increasing dopamine synthesis, and supporting mitochondrial function to provide cells with more energy. As such, patients seeking to augment their Parkinson’s management strategy would be well advised to carefully examine this emerging therapy to gain a greater understanding of its promise. In particular, Wakade and Chong’s research offers a compelling introduction to the concept of butyric acid as an alternative therapy for Parkinson’s.
Reducing inflammation is the most immediate benefit that butyric acid offers to Parkinson’s patients. In the gut, butyric acid controls inflammation by signaling white blood cells to stand down and refrain from secreting proinflammatory molecules, such as nuclear factor kappa light chain enhancer of activated B cells (known ubiquitously as NF-kB) and tumor necrosis factor alpha (TNFa). Additionally, butyric acid can be used as a substitute for other physiological molecules that support the body’s natural inflammatory response, which means that if these other molecules are in short supply, butyric acid molecules could compensate for this deficit and allow for normal function. Although these effects are known to occur in the gut, it is as of yet unknown if they occur in the brain as well. Nonetheless, researchers are optimistic that the effects do carry over to the brain to produce a therapeutic benefit. Of particular interest to Parkinson’s patients, Wakade and Chong’s analysis argues that butyric acid can stand in for niacin to address the neuroinflammation associated with the disease.
Niacin is a common nutrient with an array of physiological purposes, some of which overlap with butyric acid. Critically, niacin receptors on immune cells act as a brake pedal for inflammation; as long as the niacin receptors are occupied by niacin molecules, the cells don’t secrete inflammatory molecules. Likewise, when niacin is absent, there’s no foot on the brake pedal and inflammation occurs. However, the niacin receptor is highly expressed on immune cells, and butyric acid can bind to the niacin receptor there just as easily as niacin can. Using this logic, Wakade and Chong argue that butyric acid’s impact on these immune cells will be similar to niacin’s; i.e., limiting inflammatory responses.
This has important implications for Parkinson’s patients, because niacin is often depleted as a consequence of conventional Parkinson’s therapy and, some believe, the disease itself; when niacin is depleted, the niacin receptors on white blood cells remain empty, causing inflammation—and inflammation is associated with both the emergence and severity of Parkinson’s symptoms. In fact, one study linked the regular use of drugs that facilitate the body’s natural inflammatory response with a 29-percent lower chance of developing Parkinson’s disease in the first place. Controlling neuroinflammation with butyric acid could thus directly alleviate some of the motor difficulties and diminished concentration that patients experience.
Although treating inflammation is a critical part of Parkinson’s therapy for many, it is only addressing one of the symptoms of Parkinson’s pathology; patients are still ill even when their inflammation is under control. Dopamine synthesis, on the other hand, is independent of inflammation and an even more fundamental aspect of Parkinson’s disease. As such, Wakade and Chong claim the primary benefit of butyric acid is its ability to revitalize dopamine synthesis, thus addressing the underlying pathology of Parkinson’s rather than just its symptoms.
Niacin is a chemical precursor to dopamine, which means it’s a critical nutrient in the context of Parkinson’s disease. Parkinson’s pathology results in heavily depleted dopamine within the brain, which ultimately causes many of the disease’s most visible symptoms, such as motor difficulties. The current approach to treating this dopamine deficiency is administration of L-DOPA, a precursor of dopamine that requires only one metabolic step to turn into dopamine. However, L-DOPA therapy is far from perfect and only a portion of the chemical makes it into the patient’s bloodstream after metabolizing.
According to Wakade and Chong, intervening earlier in the dopamine synthesis pathway is thus potentially beneficial. Niacin’s role in dopamine synthesis occurs prior to L-DOPA and is thus a precursor of other precursors to dopamine. Butyric acid can enhance the amount of free niacin that is available for dopamine synthesis in much the same way it controls inflammation; when butyric acid molecules bind to the niacin receptor instead of niacin, more niacin is free to be incorporated into the dopamine synthesis pathway. Ultimately, the newly freed niacin is used to make dopamine, which means that the symptomology behind Parkinson’s is addressed in multiple dimensions with the same chemical.
The final mechanism of butyric acid that would be beneficial to Parkinson’s patients is the stimulation of the mitochondria, which are dysfunctional in Parkinson’s patients due to niacin deficiency. Niacin is a precursor of the two cellular energy molecules: nicotinamide adenine dinucleotide (NAD) and NAD’s oxygen-reduced format, known as NADH. These two molecules are used by the mitochondria to create chemical sources of energy for the cell. In the event of a NAD and NADH deficiency, the mitochondria can’t perform their functions as effectively, which causes metabolic chemicals like fumarate and excess hydrogen atoms to build up, thus causing significant mitochondrial damage. Over time, this damage becomes debilitating and restricts the mitochondria’s function further, as established by other researchers.
Wakade and Chong suggest that the mitochondrial dysfunction caused by NAD and NADH deficiency is implicated in the negative symptoms of Parkinson’s, such as reduction of fine motor control. Although other pathologies within Parkinson’s disease account for these symptoms more directly than mitochondrial dysfunction does, NAD and NADH are also essential in many metabolic processes, including the synthesis of dopamine. Once again, butyric acid could keep this damage from happening or allow cells to compensate after the fact, potentially reducing Parkinson’s symptoms and protecting patients from further deterioration.
Butyric acid offers exciting possibilities for Parkinson’s patients, making it an attractive option for those seeking effective and well-tolerated alternatives to conventional therapy. However, patients who want to add butyric acid to their management strategy need a supplement that can overcome the body’s natural barriers. Like L-DOPA, butyric acid can cross the blood-brain barrier after it’s soluble in the bloodstream. Unfortunately, butyric acid suffers a large amount of attrition via first pass metabolism prior to that point. As a result, only a fraction of butyric acid ingested makes it to the brain cells where it is needed. Thus, a nutritional supplement that doesn’t enhance butyric acid’s ability to survive first pass metabolism won’t be efficacious.
Although this obstacle is substantial, recent breakthroughs in the generation of high-bioavailability drug delivery mechanisms have opened the door to effective supplementation with butyric acid. These breakthroughs have given patients the opportunity to treat their Parkinson’s with a natural supplement that has few side effects and a substantial amount of evidence indicating its efficacy in addressing multiple dimensions of Parkinson’s disease. A highly bioavailable butyric acid supplement is a promising 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 neurological health.*
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Updated on February 8, 2023
For a growing proportion of Americans, liver damage is a frightening prospect. The liver plays an important role in metabolism and detoxification, and patients with liver damage face debilitating symptoms and a significantly higher risk of death from liver failure. The increasing prevalence of liver damage is driven in part by lifestyle issues; the most common cause of liver damage in the United States is excessive alcohol intake, but a high-fat diet can also contribute to the condition, especially when it leads to obesity. Liver damage is also associated with inflammatory bowel diseases (IBDs) and some of the inflammation-related pathological processes underpinning IBDs, such as ulcerative colitis and Crohn’s disease, are linked to the development of liver disorders. Moreover, recent research indicates that the drugs used to treat IBDs, including immunosuppressants and biologics, can also lead to liver damage.
Regardless of the cause of the liver damage, the health risks are serious, spurring patients to look for ways to support normal functioning and protect against the development of cirrhosis. Unfortunately, depending on the cause of the liver damage, therapeutic options are limited, which has led to growing research interest in the field. Currently, one particular target of research interest is alcohol dehydrogenase, an enzyme found primarily in the liver.
Alcohol dehydrogenase is responsible for catalyzing the oxidation and reduction of various alcohols and aldehydes (organic molecules similar to alcohols, but with a slightly different molecular structure). That makes alcohol dehydrogenase a key player in the detoxifying processes that protect the liver from damage. More specifically, when high levels of toxins like alcohols, “unhealthy” dietary fats, and certain medications reach the liver, they can contribute to the production of free radicals that aggravate inflammation and directly damage hepatic tissue. The activities of alcohol dehydrogenase resist these effects and limit damage.
Emerging research suggests that curcumin, the active compound in turmeric, supports the activity of alcohol dehydrogenase in a way that helps maintain a healthy liver. Although clinical trials have yet to be conducted, there are several early studies in mice that offer key insight into the mechanisms through which all-natural curcumin supplements could provide protective benefits.
The first indication there might be a relationship between alcohol dehydrogenase and curcumin came in 2011 when a group of Japanese scientists published an article in the Proceedings of the Natural Academy of Sciences of the United States (PNAS) describing their discovery of the curcumin metabolic pathway in an intestinal microorganism. Intriguingly, the unique curcumin-metabolizing enzyme they found (which they called NADPH-dependent curcumin/dihydrocurcumin reductase, or CurA), bore a significant sequence similarity to well-known enzymes in the alcohol dehydrogenase family. This finding provided the first indication that it could be possible for curcumin to interact directly with the alcohol dehydrogenase enzymes in the human liver.
The strongest evidence for a direct relationship between curcumin and alcohol dehydrogenase, however, came in 2013, when a group of researchers from several universities in South Korea collaborated on an effort to investigate the protection that low doses of curcumin could provide against liver damage caused by chronic alcohol intake and a high-fat diet. To explore this question, they treated mouse models on high-alcohol, high-fat diets with two different doses of curcumin (0.02 percent and 0.05 percent body weight) for six weeks. At both levels, they observed significant effects. In addition to reducing the activity of the enzymes known to contribute to liver damage, the curcumin supplements restricted the alcohol-induced inhibition of alcohol dehydrogenase activity to a statistically significant degree. Notably, curcumin supplementation also led to significant declines in plasma levels of leptin, free fatty acids, and triglyceride levels, all of which contribute to inflammation and liver damage. These results serve as preliminary evidence that by modulating key enzymes like alcohol dehydrogenase, curcumin supplements can effectively support liver health.
The results of the 2013 study were later supported by a paper out of George Washington University, in which the researchers again reported a connection between supplementary curcumin intake and liver damage in mouse models. Like the Korean researchers, the research team from George Washington set out to explore this connection by treating mice on high-fat, high-alcohol diets with curcumin, this time with supplements of 150 mg/kg/day, daily for eight weeks. At the end of the intervention period, they found that the mice in the treatment group were protected from ethanol-induced hepatic steatosis (that is, the accumulation of fatty tissue in the liver) and displayed lower levels of oxidative stress and liver injury markers (as measured in blood samples) than those that did not take the supplements. Thus, like previous researchers, they concluded that curcumin supplements can offer protection from liver damage.
Like the research community, more patients and practitioners than ever are intrigued by the hepatoprotective benefits that curcumin can provide, partially through its mediation of the alcohol dehydrogenase enzymes in the liver. For patients who are seeking to avoid the health risks of liver damage—whether it is associated with alcohol intake, dietary fats, medications, or inflammatory bowel conditions—a curcumin supplement might offer therapeutic benefits. In the future, clinical research will likely shed more light on the effects in humans, but for now, the animal studies suggest that curcumin supplements are worth exploring.
As patients and practitioners work together to develop a curcumin supplementation strategy to support liver health, it is important to choose a curcumin supplement with high bioavailability. Even though the Korean researchers reported that the mice in the study were treated with “low-dose” curcumin supplements, curcumin is well-known for low bioavailability, meaning it is poorly absorbed in the GI tract. This means its impact on the body can be limited by its formulation, even when it is taken in higher amounts. To maximize the likelihood that a curcumin supplement will be absorbed, metabolized, and provide the desired protective benefits, patients and practitioners should therefore look for curcumin supplements that are specifically designed for optimal bioavailability.
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 hepatic health.*
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Updated on February 2, 2023
Nearly one million U.S. adults suffer from ulcerative colitis (UC) and experience a host of symptoms that can significantly diminish quality of life. In severe cases, UC can even be life-threatening. With no known cure and an unclear etiology, UC presents major challenges, and many patients struggle to find durable relief from symptoms.
Although current ulcerative colitis therapies include traditional small molecule drug therapies, biologics and biosimilars, nutritional supplements, and lifestyle modifications, the relative effectiveness of each option varies depending on the patient. Additionally, most conventional drug therapies for ulcerative colitis are designed to address only the symptoms of UC—and many come along with debilitating side effects—while leaving its root mechanisms unaddressed. However, in recent years, there has been increasing research interest in potential therapies that directly target the underlying causes of UC symptoms to more fully alleviate gastrointestinal distress. As a result of these investigations, in early 2017 a team of Australian researchers introduced multidonor fecal microbiota transplantation (FMT) as a novel therapy. The research team’s paper provides insight into the effectiveness of this intriguing UC supportive therapy, as well as shedding new light on why certain nutritional supplements might also be effective.
In March 2017, a group of researchers from the University of South Wales in Australia published a groundbreaking study in The Lancet on multidonor FMT, in which fecal samples from multiple healthy patients were transplanted into the colon of patients with active ulcerative colitis. The impetus for the study was the growing recognition of the role of microbiome composition in the pathogenesis of ulcerative colitis. The researchers hypothesized that transplanting fecal microbiota from multiple donors might alter the gut microbiota of patients with ulcerative colitis, which would ideally have measurable functional effects. In a randomized, placebo-controlled study of a sample population of 85 patients at three Australian hospitals, the researchers successfully demonstrated that multidonor FMT could accomplish both aims: changing the composition of the gut microbiome and increasing the likelihood of remission.
After the transplantations, the researchers used shotgun metagenomics to analyze the microbial composition of the patients’ gastrointestinal tracts. Not only did they find a significant rise in the diversity of the gut microbiota in the treatment group compared to the control group (who had received a placebo), there were also noticeable shifts in the prevalence of certain bacterial taxa. Significantly, a number of these changes were clearly correlated with clinical outcomes.
One of the study’s key findings was that multidonor FMT results in a shift in the dominant bacteria in the gut microbiome from the genus Bacteroides to Prevotella. These are both genera of bacteria normally present in the gut, although their prevalence can vary. Although the implications of this shift after multidonor FMT are not fully clear, it opened an exciting new avenue for exploration. The authors also observed that the presence of bacteria from the phylum Firmicutes were loosely correlated with symptom remission. This included bacteria from the genus Lachnospiraceae, a genus that other studies have associated with the production of butyrate, a substance that plays a wide range of essential roles in the body. There were also several bacterial genera correlated with a lack of remission. Although it is unclear why these specific genera are not associated with remission, the researchers did note that many are involved in heme biosynthesis.
It is well-understood that the metabolic activities of gut bacteria play a key role in the functioning of the gastrointestinal tract, having both positive and negative impacts. Notably, the researchers found that changes in global bacterial metabolic function after FMT are also correlated with remission or lack thereof. Specifically, the results indicate that a rise in bacterial heme biosynthesis after FMT is associated with a lack of remission, while starch degradation activity and short-chain fatty acid production are correlated with benefits for ulcerative colitis patients.
Multidonor FMT is not among the ulcerative colitis supportive therapy options widely available today. However, the results of the Australian study provide insight into some of the options that are available, including multiple nutritional supplementation options. Of particular interest is the key finding that symptom relief is associated with microbiome changes that facilitate short-chain fatty acid production. Although the breakdown of fibers by bacteria is the main source of short-chain fatty acid production in the gut, they can also be introduced in supplement form. In recent years, anecdotal evidence for the effectiveness of short-chain fatty acid supplements like butyrate has been growing, and they have become increasingly popular among patients. The results of this study provide rigorous evidence that the presence of butyrate in the gut is associated with beneficial impacts on symptoms, which builds a stronger evidence-based case for the effectiveness of butyrate supplements.
Omega-3 fatty acid supplementation is another ulcerative colitis supportive therapy that patients may want to consider. In multiple research studies, omega-3 fatty acid supplements have been associated with some of the same benefits the Australian research team found in patients who achieved remission after multidonor FMT, including an overall rise in microbial diversity and a shift in the prevalence of bacterial genera involved in butyrate production, such as Lachnospiraceae. Additionally, omega-3 fatty acid supplementation is associated with a decline in the prevalence of bacterial species within the genus Faecalibacterium, which are suspected to be involved in the exacerbation of UC symptoms.
In addition to butyrate and omega-3 fatty acids, probiotics and prebiotic supplements also help maintain the health of the gut microbiome. Like multidonor FMT, a probiotic supplement enhances the bacterial composition of the microbiome in UC patients. Meanwhile, prebiotic fiber supplements support the gut microbiome by introducing fibers that feed the “good” bacteria in the gut, giving them fuel to create beneficial metabolites like butyrate.
When considering nutritional supplements as a potential ulcerative colitis supportive therapy, it is essential to recognize the relevance of supplement bioavailability. Recent research indicates there is a wide range of factors that affect the bioavailability of supplements and therefore their efficacy. For individuals taking an omega-3 supplement, for instance, improper dosage and timing of intake might limit bioavailability, whereas bioavailability can be optimized when formulators alter lipid oxidation levels or add omega-3 fatty acids to supplements and functional foods in an emulsified form. For UC patients, finding a highly bioavailable supplement is particularly important because ongoing gut inflammation can interfere with nutrient absorption.
Despite the fact that ulcerative colitis remains poorly understood, it is clear from the latest research breakthroughs that the future is promising. Not only does the Australian study on multidonor FMT present a novel way to support remission in UC patients, it also sheds light on some of the nutritional supplements most commonly used by patients, helping to build on the anecdotal evidence by solidifying the research foundation for supplementation as a viable supportive therapy for UC. As researchers continue to investigate potential future therapies, particularly those aimed at manipulating the gut microbiome, patients and practitioners can take advantage of insights like these when considering the currently available therapies. Already, cutting-edge supplement manufacturers are developing more bioavailable supplements to allow UC patients to explore their potential therapeutic benefits. As a result, patients now have more and better options for creating well-tolerated multidisciplinary therapies and experiencing more relief from symptoms.
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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