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Updated on February 2, 2023
For patients who suffer from allergies, it can often feel like the therapeutic options are severely limited. The most commonly used pharmacological therapies—including antihistamines, corticosteroids, mast cell stabilizers, and decongestants—are not effective for all patients, and they can often result in side effects that disrupt everyday quality of life. After years of frustration with oral antihistamines, nasal sprays, eye drops, inhaled corticosteroids, and other over-the-counter and prescription drugs, many patients are ready to explore alternative therapies to pharmacologics.
Over the last few decades, scientific research into the physiological underpinnings of allergies suggests that inflammatory processes and oxidative stress both mediate the most common symptoms. This has led to increased motivation within the research community to study nutritional supplements as potential therapies. In particular, curcumin has emerged as a non-pharmacological alternative with a strong base of biochemical and early clinical evidence, although there are also several other options, including phytochemicals like quercetin, that have been identified as potential natural therapeutics.
Antioxidants supplements that support the body’s natural inflammatory response have come to the attention of the research community in light of biochemical and clinical evidence suggesting a distinct relationship between allergies, inflammation, and oxidative stress. It is well-known that exposure to allergens leads to systemic inflammation by increasing the circulation of immune cells and by triggering the release of certain proteins and other inflammatory factors. However, scientists have also observed “minimal persistent inflammation” in patients with allergic rhinitis—that is, these patients display chronic, slightly above-average levels of inflammatory markers, even when allergy triggers are not present. Not only can these chronically elevated levels of inflammation make a patient susceptible to the onset of severe allergy symptoms, they can also lead to a rise in oxidative damage—another potential mediator of allergy response.
Both internal inflammation and exposure to external allergy triggers can damage antioxidant enzymes and other key cell factors that play important roles in the cell signaling processes that mediate the manifestation of symptoms. As a result, oxidative stress levels are considerably higher in patients with allergic rhinitis. According to one recent study in children with chronic allergies, blood samples indicated their total oxidant levels were significantly higher than those of their healthy peers. Based on this combination of chemical and clinical research, researchers are increasingly interested in nutritional supplements as alternative allergy remedies.
As an antioxidant supplement, curcumin has emerged as one of the more promising potential therapies to address allergy symptoms. This compound has long been known to support the body’s natural inflammatory response, and there are preliminary laboratory and clinical studies to suggest it can help patients who suffer from allergies. For instance, in 2016, a group of researchers in Turkey conducted a rigorous study on the antioxidant effects of curcumin in rat models of allergic rhinitis. After 28 days of oral curcumin therapy, the researchers measured multiple tissue and serum markers of antioxidant activity (including the levels of seven different enzymes with known antioxidant activity) and observed significantly higher levels in the rats that had been treated with curcumin than in the rats in the control population. Moreover, the researchers noted that serum markers of oxidation were reduced in the curcumin-treated rats, suggesting that curcumin not only supports antioxidant enzyme activity but might also directly limit oxidative stress in patients with allergic rhinitis.
Alongside these findings on the benefits of curcumin as an antioxidant, there is also evidence to suggest that curcumin can have a protective effect in patients with respiratory allergy symptoms. In a 2014 study utilizing mouse models, a group of researchers from China not only demonstrated that curcumin could address inflammatory response in mouse models, they were also able to elucidate the specific molecular mechanism through which the protective benefit is mediated. Through a series of genetic experiments, the researchers showed that the benefits of curcumin in mouse models required the functioning of the Notch1-GATA signaling pathway. When researchers can highlight a specific signaling pathway that directly explains the association between an intervention like curcumin supplementation and its role in supporting the body’s natural inflammatory response, implicating the activity of a particular cell signaling pathway, it strengthens the evidence that the supplement is truly having a beneficial effect—and indicates that human patient studies are warranted.
So far, the clinical evidence for the benefits of curcumin for allergy patients is limited, although a pilot study from 2016 provided the first indication that curcumin can modulate the immune response and help ameliorate nasal and respiratory symptoms in patients. In a randomized, double-blind study of 241 patients with allergic rhinitis, a group of researchers in China found that curcumin led to lower serum levels of multiple inflammatory factors, as well as a drop in the circulation of certain types of immune cells. In addition, the patients who took the curcumin supplement reported direct therapeutic effects, including addressing nasal symptoms and better nasal airflow resistance. For researchers, this study paves the way for more comprehensive human clinical studies in the future. For patients and practitioners, it suggests that a curcumin supplement to alleviate allergy symptoms might be warranted.
Although curcumin is the nutritional supplement with the strongest laboratory and clinical evidentiary support thus far, there is growing evidence that phytochemical nutritional supplements also have positive effects for some patients. These plant-derived compounds inhibit the nuclear transcription factor NF-kappa-B, which is known to mediate the body’s response to inflammation, as well as other transcription factors with similar activity. Some of the phytochemicals that have been highlighted as potential research targets include quercetin, resveratrol, and magnolol.
Indeed, there have been several recent studies highlighting quercetin as a possible natural alternative to antihistamines, including two animal studies in which quercetin supplementation in rat models of rhinitis led to both symptomatic and molecular improvements. There is even growing evidence to suggest there are other ways in which quercetin supplementation supports the allergy-related immune response—that is, beyond the transcription factor inhibition described above. Specifically, quercetin supplementation might also suppress the creation of certain types of immune cells (which can help modulate an unbalanced inflammatory response), limit the release of inflammatory proteins like cytokines, and limit the formation of certain types of antibodies.Clinical evidence on the benefits of phytochemicals for allergy patients is still lacking. However, because these compounds display the same therapeutic properties as curcumin, they are increasingly under consideration as potential alternative allergy remedies. For patients and practitioners who are ready to look beyond prescription and over-the-counter drugs, nutritional supplements like curcumin and quercetin present promising possibilities.
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
What if a stellar therapeutic benefit for Crohn’s disease has been sitting under doctors’ noses for even longer than they’ve known about the disease? What if patients could supplement their diets with a natural compound that could could help maintain a normal inflammatory response in their gut? In light of an abundance of research investigating the therapeutic value of derivatives of the turmeric plant, these hypotheticals are more likely than previously realized.
Derived as a fine orange powder, the turmeric plant has caught the attention of scientists for its potential to support the body’s natural inflammatory response. Longstanding informal research by pastoral healers into the therapeutic value of turmeric, however, has a significant headstart on current scientific efforts; traditional Ayurvedic medicine and Indian cuisine have made use of the rhizome of the turmeric plant for thousands of years, in part due to its medicinal properties. Today, the scientific consensus on turmeric is still evolving because turmeric contains a handful of components, each of which needs to be investigated individually before one of these components can find its niche in addressing Crohn’s disease. The potentially useful compounds in turmeric are called curcuminoids, and these are the compounds on which scientists have primarily focused their inquiry. Curcuminoids are a diverse group, however.
Of the curcuminoids, the most deeply investigated molecule is that which the entire class of chemicals is named after: curcumin. Curcumin has been proven to interact with a plethora of critical physiological molecules, including those associated with the body’s inflammatory response. These interactions with pro-inflammatory molecules serve as the primary basis for the potential of using a turmeric supplement for the nutritional support of Crohn’s disease by down-regulating the inflammatory episodes characteristic of the condition. Patients who are seeking a complementary therapy to their current traditional therapies for more robust symptom relief would therefore do well to learn more about curcumin supplements, in particular, the potentially more effective tetrahydrocurcumin.
Although the evidence supporting the supplemental use of curcumin in Crohn’s is still forming, researchers have already identified how curcumin impacts human cells and limits their ability to down-regulate the inflammatory response. It is believed that curcumin does this by suppressing pro-inflammatory transcription factors, like NF-kB, STATs, and beta-catenin, in the gut. Of these transcription factors, NF-kB is responsible for the self-sustaining chain reaction that occurs during inflammatory response. Inhibiting NF-kB therefore means that inflammatory flare-ups would be beneficially down-regulated, although low levels of inflammation would still occur. Given that inflammation is one of the core symptoms of Crohn’s, curcumin could thus promote a reduction of flare-ups and their accompanying symptoms. The evidence to support its use is mixed, however.
One pilot study found that curcumin supplementation benefited symptom severity scores significantly in four of five study participants with Crohn’s disease. Unfortunately, larger studies have failed to replicate the pilot study’s findings regarding symptom severity. Nonetheless, in a review of several pieces of literature examining curcumin’s impact in Crohn’s, researchers found that patients who were administered curcumin in conjunction with their normal therapeutic regimen experienced an average 55-point reduction of their Crohn’s Disease Activity Index (CDAI). A 55-point reduction in CDAI would have a significant beneficial impact on moderate flare-ups.
Additional investigations suggest that when benefits do occur, they are likely to be significant in duration. A large, placebo-controlled study found that the study’s ulcerative colitis patients who were administered curcumin in addition to traditional therapies achieved better results than patients who were treated with placebo in addition to traditional therapies. The researchers, however, could not propose the mechanism responsible for the medium-term effects of the curcumin supplement, because nearly all other research indicates that curcumin is not biologically active after several hours. The most likely explanation for these beneficial effects is that curcumin alters the regulatory regions of certain genes, inhibiting or activating those genes for periods that extend beyond the presence of curcumin itself.
Due to its rapid metabolism, turmeric supplements for Crohn’s rarely have negative side effects, making it inviting for patients who want to try alternative therapies. Mild diarrhea is the most common side effect reported, which means it would be tolerable for Crohn’s patients in the midst of an inflammatory episode who can’t tolerate more serious side effects. Overall, most patients find curcumin supplementation to be highly tolerable and experience side effects only with doses higher than suggested uses. This makes curcumin a low-risk intervention, especially when patients are concerned about disrupting their compromised gastrointestinal tract. Nonetheless, there are many questions about curcumin which still require answers.
Although there is strong evidence that curcumin is useful in addressing the symptoms of Crohn’s disease, curcumin’s bioavailability is a major obstacle to becoming therapeutically useful. Drs. Kathryn Nelson, Jayme Dahlin, and Jonathan Bisson compiled a review of the literature on curcumin’s bioactivity, finding that:
Curcumin is best typified as a missile that continually blows up on the launch pad, never reaching the atmosphere or its intended target(s). These results have given curcumin the label of pharmacodynamically fierce (hits many targets) yet pharmacokinetically feeble (does not get to its targets).
The ability to reach physiological targets refers to a substance’s absorption and metabolic properties, otherwise known as its bioavailability. Having a low or inconsistent bioavailability is an obstacle for using a given substance to address a patient’s symptoms. With some substances, the workaround is to increase the quantity the patient consumes, although this doesn’t always work in the context of Crohn’s disease; in Crohn’s, intestinal cells can’t absorb chemicals as effectively because of the compromised state of their tissue structure.
Unfortunately, the typically low bioavailability of curcumin hampers researchers’ efforts to examine its efficacy in the body, potentially explaining the inconsistency of research results. However, it is a solvable issue. With the help of advanced drug delivery systems or alternative routes of administration, researchers have overcome low bioavailability of drug molecules in the past. Such experiments with highly bioavailable curcumin have usually centered around formulations that include fat emulsions, plant matter complexes, and cellulose capsules that degrade on contact with specific molecules common to the gastrointestinal tract. More advanced bioavailable formulations include nanospheres that interface with white blood cells to disburse their payload.
According to research, enhanced bioavailability does make a difference. In a study designed to test the efficacy of curcumin in mouse models of inflammatory bowel disease published in Gastroenterology, researchers found that highly bioavailable curcumin supplements were able to support the activities of the T-helper cells in the gut, down-regulating the inflammatory response and promoting healthy microbiota. Attending to the health of the microbiome is critical in Crohn’s disease because patients often have microbiota that are markedly aberrant compared to healthy controls. Although it is unclear whether this is a cause or an effect of Crohn’s disease, unhealthy microbiota make for worse nutrient absorption and likely contribute to inflammation. By formulating curcumin to be highly bioavailable, the researchers were able to observe clear results regarding curcumin’s impact in the gut. However, their unique formulation makes their study nearly impossible to compare with others and so far, such formulations are nearly unrepresented in the literature.
The larger issue with curcumin is that it’s very difficult to work with in the laboratory. Curcumin is unstable, which means it can degrade mid-experiment as a result of environmental conditions. Nelson, Dahlin, and Bisson’s review laments curcumin’s poor stability, noting that “both its in vitro and in vivo stabilities are abysmal relative to commercial drugs.” Even more troublesome than curcumin’s instability is its propensity to react with all biological molecules around it; this is the property the review called “pharmacodynamically fierce.” By reacting promiscuously, scientists are hard-pressed to determine curcumin’s biological impact because their typical tools like antibodies and fluorescent tags can’t be used. Attempts to measure curcumin’s binding to other physiologic molecules result in endless numbers of false positives simply because curcumin disrupts the measuring methodology.
This disruptive effect is likely part of the reason why, despite a number of studies strongly supporting its use, curcumin has not been definitively found to be helpful for any disease despite its investigation in more than 120 different controlled trials. The studies that report positive effects might similarly be mistaken due to curcumin causing false positives in the experiment. Despite these issues, other compounds derived from turmeric are still under active investigation.
As the research community continues to explore the potential of using a turmeric supplement for Crohn’s disease, some are expanding the scope of their investigations beyond curcumin to overcome the barriers presented by the molecule and expand the potential for symptom relief in patients. Of particular interest in the curcuminoid tetrahydrocurcumin, which was highlighted in Nelson, Dahlin, and Bisson’s review as a turmeric-derived compound with a wide number of potential applications.
Tetrahydrocurcumin is a metabolite of curcumin and shares many of the same properties as curcumin, including protecting against certain kinds of DNA damage, scavenging free radicals, and modulating inflammatory response. Tetrahydrocurcumin, however, is naturally more bioavailable, increasing the possibility of therapeutic benefit. Additionally, it provides a higher level of antioxidant activity, which might provide an additional and significant avenue toward creating therapeutic applications for Crohn’s symptoms; because tetrahydrocurcumin is a stronger antioxidant than other curcuminoids, it can be administered to patients in smaller doses while exhibiting superior therapeutic effects.
Antioxidants are potentially beneficial for Crohn’s—as well as a plethora of other conditions—because they capture reactive oxygen species generated as byproducts of normal metabolism. If left to run amok, reactive oxygen species can adversely react with DNA, enzymes, and other cellular components, interfering with their function. In the event that a nearby antioxidant “scavenges” a circulating reactive oxygen species, it can’t hurt important cellular machinery.
While the review finds these antioxidant properties have the most potential for use in addressing issues related to Alzheimer’s disease thanks to the proven relationship between Alzheimer’s and oxidative damage, it’s also possible that tetrahydrocurcumin could help to limit oxidative damage to the intestine resulting from acute inflammatory episodes in patients with Crohn’s disease. By reducing oxidative damage, tetrahydrocurcumin could benefit white blood cells in the GI tract by removing reactive oxygen species that might interfere with their functions by damaging key enzymes. This therapeutic avenue is currently being investigated. While scientists are improving their ability to experiment with tetrahydrocurcumin to ensure the validity of results, tetrahydrocurcumin supplements are already entering the market, giving Crohn’s patients more opportunities to experience the benefits of turmeric.
As turmeric and its associated curcuminoids become better understood, there are many possibilities for their future uses. Turmeric might soon prove useful for addressing health conditions in randomized controlled clinical trials, although it is difficult to predict exactly which health condition will benefit most. Currently, turmeric is under investigation in the contexts of Crohn’s disease, Alzheimer’s disease, HIV, various cancers, and many others. It’s also possible that turmeric may be used in more general research; scientists might find the compounds within turmeric to be advantageous as experimental tools because of the very properties they currently find inconvenient.
No matter the application, researchers are heavily invested in learning more in hope of harnessing turmeric’s power to help a broad spectrum of patients. For patients with Crohn’s disease, turmeric makes for a promising supplemental therapy that carries few risks and significant therapeutic potential. Should a patient with Crohn’s seek to enhance their traditional medication regimen with a safe and efficacious natural alternative turmeric compounds, particularly tetrahydrocurcumin, would be a viable place to start.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your gastrointestinal health.*
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Updated on March 23, 2023
Article Summary:
For parents of autistic children, there are few symptoms that can cause as much day-to-day concern as stimming. Stimming—which is more formally discussed in scientific circles as self-stimulation or stereotypic, repetitive behavior—can be frustrating and concerning for parents who find themselves unable to get through to a child who is rocking, flapping, spinning, or repeating the same sets of words, over and over. Many parents worry that stimming behaviors set their child apart from their peers, who often view stereotypic, repetitive behaviors as “weird,” making it even harder for an autistic child to build strong social relationships.
In clinical settings, stimming is typically addressed with pharmacological drugs, behavioral modification therapy, or a combination of the two. However, because the efficacy of these interventions can vary significantly depending on the child, there is increasing interest within the research and clinical communities in nutritional supplements for addressing stimming. So far, multiple supplements have shown promise in animal models, several of which have also gained preliminary clinical support. Some of these supplements include Korean Red Ginseng, vitamin D, omega-3 fatty acids, and sulforaphane. Together, the similarities between these candidates suggest that supplements with properties that support the body’s natural inflammatory response, including curcumin and quercetin, present the best prospects for future laboratory and clinical research.
One of the ways researchers model stimming in vivo is by administering valproic acid to rats. Administration of valproic acid induces stereotypic, repetitive behaviors that closely parallel stimming behavior in autistic children while also triggering several other autism-related symptoms, such as problems with social interaction and motor activity. In one recent study, researchers used valproic acid-exposed rat models to suggest that Korean Red Ginseng supplements might have therapeutic potential for stimming.
The rat models in the study were treated with Korean Red Ginseng (either 100 mg per kg per day or 200 mg per kg per day, for a total of three weeks). To test the effects of the supplement on stimming behavior, the researchers used a slightly-modified version of the Marble Burying Test, which measures stereotypic and repetitive behaviors. In the rats that received the low dose and the high dose of Korean Red Ginseng, the researchers observed statistically significant positive outcomes. Although the study did not reveal the mechanism of action through which the ginseng mediated this behavior, previous studies have highlighted the potential of Korean Red Ginseng in supporting the body’s natural inflammatory response.* Inflammation is associated with symptoms of autism, suggesting a possible connection.
In a 2017 study, scientists at Jilin University in China utilized a similar valproic acid-exposed rat model to explore the benefits of vitamin D for stimming. They treated rats with 80,000 IU per kg per day and observed significant improvements on repetitive behavior tests. They also measured the levels of vitamin D in the rats’ blood and reported a negative linear relationship between repetitive behavior scores and vitamin D levels. This close correlation strongly suggests the stereotypic behavioral changes in the rat models were linked to the vitamin D supplementation. Although the study does not provide a biochemical mechanism to explain the relationship, the known properties of vitamin D in supporting the body’s natural inflammatory response could be playing a role.
Although clinical studies on the effects of nutritional supplements on stimming are limited, there are several that highlight some of the most promising options. For instance, a 2017 meta-analysis that combined data from six randomized clinical trials identified omega-3 fatty acid supplementation as a potentially viable therapy for stimming, possibly due to the properties of these compounds to support the body’s natural inflammatory response. The pooled data included a total of 109 patients and revealed statistically significant improvements in stereotypic behaviors. Although the six studies were small, the combined results suggest that large-scale, randomized clinical trials on omega-3 fatty acids supplements for providing nutritional support for stimming are warranted in the future.
Another intriguing study by researchers at Massachusetts General Hospital and Harvard Medical School highlights the potential of using sulforaphane supplementation for stimming. Sulforaphane is a phytochemical extract derived from fresh broccoli sprouts and is known to upregulate genes that resist oxidative stress, inflammation, and DNA damage, all of which are believed to be involved in stimming in autistic children. Supplementing with sulforaphane has no known side effects.
In this randomized, double-blind, placebo-controlled study, the authors treated 29 young men (ages 13 to 27) with moderate to severe ASD with 50-150 uL of oral sulforaphane every day for 18 weeks. They then used three behavioral measurement tests to determine the effects. Ultimately, sulforaphane supplementation was associated with improved scores on both the Aberrant Behavior Checklist (34 percent) and the Social Responsiveness Scale (17 percent). On the Clinical Global Impression Improvement Scale, statistically significant improvements were observed for abnormal behaviors (including stimming), as well as social interaction and verbal communication.
Because the evidence is preliminary, it is important to remember that these four supplement options—Korean Red Ginseng, vitamin D, omega-3 fatty acids, and sulforaphane—are not the only possible supplements for managing stimming. Therefore, it is helpful to identify the mechanistic similarities between them when considering future research directions. Most notably, all of them enhance the body’s natural inflammatory response. This suggests that other nutritional supplements with such properties, such as curcumin, could provide similar benefits.* Like Korean Red Ginseng, curcumin has been used in traditional medicine for thousands of years, and scientists are investigating how curcumin’s properties might benefit patients with complex conditions like autism. The promising findings on the benefits of sulforaphane also suggest that other phytochemical supplements, like quercetin, are worthy of further exploration. Quercetin shares structural and functional properties with sulforaphane, and it has known bioactivity in the central nervous system, so it presents another possible therapeutic option for autistic patients.
For the research community, the next steps are clear: build on the existing evidence by conducting well-designed, large-scale clinical trials of the nutritional supplements with the most promise for addressing stimming behavior in autistic patients. For practitioners, it makes sense to consider these supplements today as options for patients who are non-responsive to the current behavioral and pharmacological therapies for stimming. Given the low toxicity of these supplements and the base-level evidence supporting their efficacy, they could prove beneficial for certain patients.
The power of Tesseract supplements lies in the proprietary science of proven nutrients and unrivaled smart delivery, making them the most effective for supporting neurological health and gastrointestinal health.*
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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.*
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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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