Risk FREE. Money Back Guarantee.
Updated on March 27, 2023
Article Summary:
Many patients who struggle with anxiety spend years (or even decades) trying to find an approach that truly works to address their symptoms, often without achieving durable relief. Indeed, studies show that the efficacy of psychotherapy and pharmacotherapy options can vary considerably, depending on both the nature of the therapy and the individual patient’s response. Psychotherapeutic approaches like cognitive behavioral therapy, for example, often only partially alleviate symptoms, and many patients shy away from pharmaceutical drugs that carry side effects and fail to produce the desired outcomes. To develop more reliable therapies for patients with anxiety, scientists have spent decades trying to better understand the biological underpinnings of the condition. Although the question is far from resolved, it is becoming increasingly clear that the gut-brain axis has a role in the mediation of symptoms.
The term “gut-brain axis” refers to the bidirectional connection between the gastrointestinal (GI) tract and the central nervous system (CNS). In recent years, researchers have discovered that the communication between these two systems has a direct impact on mental health, by regulating key physiological processes associated with anxiety. Still remaining to be fully elucidated is an understanding of the biological mechanisms that link the GI tract and CNS to form the connections in the gut-brain axis that mediate symptoms of anxiety. One of the most promising proposals is that the activities of the bacteria in the microbiome play an essential role in the communication process. These findings have important implications for the development of future therapies, suggesting that probiotic, prebiotic, and butyric acid supplementation might be able to address select symptoms of anxiety.
Recent studies suggest there are two important ways in which bacterial activity in the gut facilitates the communication that underpins the gut-brain axis: by interacting directly with peptides in the gut and by producing functional metabolites, like short-chain fatty acids. There is a wide range of peptides present in the gut microbiome, and they communicate with the CNS by binding to immune receptors and the terminal of the vagus nerve, a peripheral nerve with a known connection to both anxiety disorders and inflammatory processes. Signals produced by the bacteria in the microbiome can directly regulate the concentrations of these peptides in the gut, which directly affects their communication with the CNS. According to the latest research, the proportions of the various different bacterial strains residing in the gut microbiome directly determine which peptide-regulating signals are produced, suggesting that supplementation with certain bacterial strains would aid in the modulation of the gut-brain axis in ways that can beneficially address anxiety.
In a healthy gut, the resident bacteria produce a wide range of metabolites, including short-chain fatty acids, which are produced when certain bacterial strains metabolize fiber. These multifaceted short-chain fatty acids have a variety of roles in key body processes, such as energy homeostasis and nutrient absorption. In addition, by acting as epigenetic regulators, short-chain fatty acids are involved in the production and activity of the gut peptides associated with the gut-brain axis, including glucagon-like-peptide and leptin. These findings suggest that an imbalance of the bacteria that produce short-chain fatty acids might lead to disruptions in the gut-brain axis, which in turn contribute to the adverse symptoms of anxiety.
Any individual who has considered taking a probiotic supplement knows that the options on today’s market are practically endless when it comes to the number and combinations of available bacterial strains. This could be one reason the body of literature on the potential benefits of probiotic supplementation for various mental health conditions can only be described as mixed at best; and while some supplements seem to be beneficial for patients, others have no effect. Furthermore, it is unwise to compare studies of probiotic supplements that contain different bacterial strains. To resolve the lack of clarity in this area of study, scientists are now conducting more specific studies on individual strains, a number of which have shown particular promise for addressing anxiety.
For example, in 2014 a group of researchers from University College Cork in Ireland conducted a study that suggested two strains of bacteria—Bifidobacterium longum 1714 and Bifidobacterium breve 1205—could address anxiety symptoms in mouse models, as measured by several different well-established behavioral tests for anxiety. Intriguingly, in a follow-up experiment conducted by researchers at the same university in 2016, these findings were verified in a small group of healthy humans. In the second study, 22 healthy participants were subjected to an anxiety-inducing cold-pressor test, with and without supplementation of B. longum 1714. The researchers used resting encephalography to measure the participants’ output of cortisol (a stress hormone) under both conditions, and they observed lower cortisol levels in the participants who had taken the probiotic supplements. Moreover, in subjective surveys, the participants reported perceiving lower levels of stress after taking the probiotic supplements. Based on these findings, the researchers concluded that Bifidobacterium strains could potentially be used as anti-anxiety therapeutics in the future.
A study from 2011 suggests that the bacterial strain Lactobacillus rhamnosus plays an important role in the mediation of communication via the gut-brain axis in ways that directly impact anxiety levels. The researchers found that taking this strain could alter mRNA expression of GABA receptors in the brains of mouse models. GABA is an inhibitory neurotransmitter in the brain, and receptor levels are associated with anxiety symptoms. According to these researchers, these levels were altered in several different areas of the brain related to anxiety symptoms when the mice were administered L. rhamnosus, including the prefrontal cortex and the hippocampus. Importantly, in mice in which the vagus nerve had been removed, the characteristic symptoms of anxiety were not observed, which offers further evidence the vagus nerve likely plays a mechanistic role in the mediation of anxiety symptoms through the gut-brain axis. Therefore, this study not only suggests L. rhamnosus can be an effective probiotic therapy for anxiety patients, it also highlights the vagus nerve as a target for future research on possible therapeutics.
Probiotic supplementation that supports the health of the microbiome might not be the only way to target the gut-brain axis. There is also growing evidence that certain types of prebiotics offer specific benefits for anxiety patients. Prebiotics are fiber supplements that are indigestible by humans, but that feed certain strains of beneficial bacteria in the GI tract. In a groundbreaking study published in 2017, researchers found that supplementation with two types of prebiotics—fructooligosaccharides (FOS) and galacto-oligosaccharides (GOS)—can modulate the gut microbiome in ways that affect the gut-brain axis. In a study in mouse models of anxiety, researchers found that prebiotic strains containing both FOS and GOS could address anxiety symptoms in mice, based on several well-established behavioral tests. In addition, fiber supplements were associated with lower levels of the pro-inflammatory markers commonly associated with anxiety, as well as lower levels of stress-inducing corticosterone. These findings suggest certain combinations of prebiotic fibers target the bacterial strains that play an essential role in the mediation of anxiety symptoms via the gut-microbiome axis, so they likewise could help alleviate anxiety symptoms, much like direct probiotic supplementation.
Based on the studies described above, it is clear that scientists have a growing sense of which bacterial strains are producing the essential metabolites that mediate the gut-brain axis. However, it is not yet entirely clear exactly which strains need to be replaced or nourished with prebiotics to relieve anxiety symptoms. Therefore, some researchers and clinicians are considering the benefits of direct supplementation with short-chain fatty acids, such as butyric acid. This approach allows a butyric acid supplement to assume the role of the bacteria in the microbiome—that is, short-chain fatty acids are introduced into the gut, thus bypassing the step in which the bacteria metabolize fiber to produce these functional compounds. Instead of relying on bacteria to produce short-chain fatty acids, an oral supplement places them directly where they are needed: in the GI tract. As a result, short-chain fatty acids are readily available to mediate peptide levels and thereby possibly modulate the biological processes that might benefit anxiety patients.
Ultimately, even though the mechanisms through which the gut-brain axis mediates symptoms of anxiety have not been fully elucidated, there is little doubt that the gut microbiome does play an important role. There are already several probiotic strains that have been identified in the connection between the GI tract and the CNS, and supplementation with prebiotics and short-chain fatty acids might also exert beneficial effects in this regard. Although large-scale human studies are still lacking, clinicians and patients dealing with anxiety can harness this evidence to develop unique strategies for individuals who have not found success with traditional anti-anxiety therapies. The research community can also look forward to future studies that offer more mechanistic insight and real-world results related to the microbiome-mediated connection between the gut-brain axis and anxiety.
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.*
Allen AP, Hutch W, Borre YE, et al. 2016. Translational Psychiatry. 6(11):e939.
Bourassa MW, Alim I, Bultman SJ, Ratan RR. 2016. Neuroscience Letters. 625:56-63.
Bravo JA, Forsythe P, Chew MV, et al. 2011. PNAS. 108(38):16050-5.
Breit S, Kupferberg A, Rogler G, Hasler G. 2018. Frontiers in Psychiatry.
Burokas A, Arboleya S, Moloney RD, et al. 2017. Biological Psychiatry. 82(7):472-87.
Clapp M, Aurora N, Herrera L, et al. 2017. Clinics and Practice. 7(4):987.
Cuijpers P, Sijbrandij M, Koole SL, et al. 2013. World Psychiatry. 12(2):137-48.
De Clercq N, Frissen MN, Groen AK, Nieuworp M. 2017. Psychosomatic Medicine. 79(8):874-9.
Foster JA, Rinaman L, Cryan JF. 2017. Neurobiology of Stress. 7:124-36.
Lach G, Schellekens H, Dinan TG, Cryan JF. 2018. Neurotherapeutics. 15(1):36-59.
Savignac HM, Kiely B, Dinan TG, Cryan JF. 2014. Neurogastroenterology and Motility. 26(11):1615-27.
Schnorr SL, Bachner HA. 2016. Yale Journal of Biology and Medicine. 89(3):397-422.
Vinolo MAR, Rodrigues HG, Nachbar RT, Curi R. 2011. Nutrients. 3(10):858-76.
Updated on March 23, 2023
Article Summary:
There’s no denying that the currently available therapies for Alzheimer’s disease are suboptimal. As practitioners, patients, and families grow frustrated with the limited results of pharmacological approaches, researchers have begun exploring all-natural alternatives, including polyphenolic compounds derived from plant extracts.
For years, polyphenolic compounds have been recognized for their antioxidant properties and ability to support the body’s natural inflammatory response.* They also support cardiovascular function, which is important for Alzheimer’s patients because there is evidence suggesting a link between cardiovascular health and Alzheimer’s progression.* Because of the well-known bioactivity of polyphenols, researchers have begun to seriously consider polyphenols as an alternative therapy to utilize with Alzheimer’s patients. In preclinical studies, two of the polyphenols that have shown particular promise are Epigallocatechin-3-gallate (ECGC) and quercetin.
ECGC is a polyphenolic compound best known as the most abundant polyphenolic extract in green tea. Although in vitro studies show that ECGC can play a role in a variety of biological processes, there are three ways it might particularly benefit Alzheimer’s patients:
According to a model based on existing laboratory research, these activities should inhibit enlargement of the ventricles and the atrophy of the cerebral cortex and hippocampus, all of which are key structural changes observed in the brains of Alzheimer’s patients.
A 2017 preclinical animal study provides strong support for this proposed model. Researchers at Xi’an University in China demonstrated that in a mouse model of Alzheimer’s disease, oral supplementation with ECGC inhibited structural changes in the brain. Without supplementation, the mouse model displayed abnormalities in synaptic protein levels in both the frontal cortex and the hippocampus. The study showed that long-term ECGC therapy (15 mg/kg per day) could restore these levels, as measured by the reversal of the decreases in two different synaptic protein biomarkers. Moreover, the structural changes were coupled with notable behavioral effects; the mice treated with ECGC performed significantly better on maze tests that measured memory and spatial learning ability.
There is also pre-clinical evidence that ECGC supplementation can be even more effective when coupled with exercise, an exciting finding for patients interested in activity-based alternative therapies for Alzheimer’s disease. In 2015, researchers at the University of Missouri subjected mouse models to four months of wheel-running exercises combined with daily supplementation of ECGC (50 mg/kg per day). The supplementation led to a significant drop in amyloid beta plaque buildup (a hallmark of Alzheimer’s disease) in the cortex and hippocampus. The combination of ECGC and exercise also had positive behavioral impacts: the mouse models that received the intervention did not demonstrate the same behavioral deficits as the untreated Alzheimer’s mouse models in maze tests (which measured memory) and nest-building tests (which measured anxiety levels).
Not only do these results suggest that ECGC can directly address symptoms of Alzheimer’s disease, it also supports the hypothesis that the cardiovascular effects of ECGC might further contribute to its impacts. Exercise is a known mediator of cardiac function, so its effectiveness for addressing Alzheimer’s disease symptoms suggests that the cardiovascular benefits of ECGC could be indirectly supporting reductions in Alzheimer’s disease progression. This means that ECGC might help Alzheimer’s patients in two ways: through direct effects on the brain and through indirect effects on the cardiovascular system.
Like ECGC, quercetin is a polyphenolic compound that has shown considerable promise as an alternative therapy for Alzheimer’s patients in pre-clinical studies. Again, the potential of quercetin supplementation is underpinned by evidence of structural changes in mouse brains and corresponding behavioral changes. In a study from 2015, researchers treated a mouse model of Alzheimer’s disease with quercetin (25 mg/kg per day for three months). Extensive histological studies (studies of changes in mouse brain tissues) indicated that supplementation led to beneficial impacts on certain brain structures and declines in the presence of certain Alzheimer’s disease-associated proteins.* These effects were observed alongside improvements on behavioral tests of both cognitive and emotional function, which would make quercetin a promising alternative therapy for Alzheimer’s patients and practitioners looking for a more comprehensive treatment regimen.
Although there is broad speculation that antioxidant effects are at the core of quercetin’s effectiveness as a polyphenol, it might also be working through other molecular pathways. A 2016 study suggests that quercetin supplementation modulates levels of Apolipoprotein E (ApoE), a cholesterol carrier protein, and high cholesterol is a known risk factor for Alzheimer’s disease. The researchers propose that improving cholesterol metabolism is a novel mechanism through which quercetin can address an Alzheimer’s risk factor. The findings provide further evidence of a beneficial link between polyphenol supplementation, cardiovascular health, and the cognitive decline observed in Alzheimer’s patients.* In addition, polyphenolic compounds like quercetin could indirectly benefit Alzheimer’s patients by supporting heart health (in addition to their direct actions in the nervous system), thus being more effective than options that only target the brain.*
There are no major clinical studies that support the effectiveness of ECGC or quercetin in Alzheimer’s patients. Although there is one double-blind, placebo-controlled study on resveratrol, a similar polyphenolic compound that has shown promise in preclinical studies, preliminary clinical results are inconclusive. Researchers have determined that both supplements are safe and well-tolerated, but more research is necessary before researchers can confirm their efficacy.
In the future, it will be important to conduct rigorous clinical trials on both ECGC and quercetin while continuing to probe their mechanisms of action. But given the frustrating outcomes of conventional therapies and the promising laboratory evidence of polyphenolic supplements, patients and practitioners might want to consider integrating supplements now.
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.*
Cascella M, Bimonte S, Muzio MR, et al. 2017. Infectious Agents and Cancer. 12(36).
Darvesh AS, Carroll RT, Bishayee A, et al. 2010. Expert Review of Neurotherapeutics. 10(5):729-45.
Guo Y, Zhao Y, Nan W, et al. 2017. Neuroreprots. 28(10):590-7.
Hussain T, Tan B, Yin Y, et al. 2016. Oxidative Medicine and Cellular Longevity.
Sabuncu MR, Desikan RH, Sepulcre J, et al. 2011. Archives of Neurology. 68(8):1040-8.
Sabogal-Guaqueta AM, Munoz-Manco JI, Ramirez-Pineda J, et al. 2015. Neuropharmacology. 93:134-45.
Santos CY, Snyder PJ, Wu WC, et al. 2017. Alzheimer’s Dementia. 7:69-87.
Scarmeas N, Luchsinger JA, Brickman AM, et al. 2011. American Journal of Geriatric Psychiatry. 19(5):471-81.
Syarifah-Noratigah S, Naina-Mohamed I, Zulfarina MS, Qodriyah HM. 2017. Current Drug Targets.
Turner RS, Thomas RG, Craft S, et al. 2015. Neurology. 85(16):1383-91.
Walker JM, Klakostkaia D, Ajit D, et al. 2015. Journal of Alzheimer’s Disease. 44(2):561-72.
Zhang X, Hu J, Zhong L, et al. 2016. Neuropharmacology. 108:179-92.
Updated on March 27, 2023
Article Summary
For parents, it can be heartbreaking to watch an autistic child struggle with one of the most debilitating symptoms of the condition: social anxiety. From early childhood, autistic children often have social problems due to the anxiousness they experience when trying to cope with social situations. As a result, autistic children often struggle to find friends at school, and the severity of this circumstance might not wear off as they get older. The sad reality is that these children often find themselves increasingly isolated in adolescence, as well as later in early adulthood, which can significantly limit their opportunities.
Because social anxiety can have such extensive adverse effects on the life outcomes of autistic children, its pathophysiological underpinnings have long been a subject of study for researchers. The etiology of social anxiety still remains poorly understood, but research over the past several decades suggests the endocannabinoid system plays a role in mediating symptoms that lead to social problems. As a result, some researchers are now considering the endocannabinoid system as a possible target for future therapeutics that address social anxiety in autistic patients while also investigating a number of existing therapies that could address endocannabinoid disruption, including CBD and curcumin.
The endocannabinoid system is considered a major neuromodulatory system, affecting a wide range of cellular processes, including neuroinflammation, energy metabolism, and immune system control. It consists of a complex system of lipid signaling pathways, in which the major players are two arachidonic acid-derived compounds (anandamide and 2-arachidonoyl glycerol) and their cannabinoid receptor targets (CB1 and CB2), along with a variety of associated enzymes and transporters. So far, studies have linked the endocannabinoid system to the regulation of emotional and behavioral responses in social contexts, as well as social interactions, all of which play a role in social anxiety in autistic patients. Although the connections between the endocannabinoid system and the symptoms of autism are indirect, the preliminary findings have contributed to an increasingly well-regarded hypothesis that dysregulation of the endocannabinoid system might be one of the etiological foundations of autism.
One of the strongest early studies providing support for this hypothesis was published in the journal Current Neuropharmacology. In this study, a group of researchers from around the world collaborated on a joint project in which they evaluated the effects of endocannabinoid system disruption in mouse models of autism. Using a combination of behavioral and neurochemical tests, they were able to show that the disruption could enhance stereotypic autism-related behaviors in the mouse models, including those associated with social anxiety.
A more comprehensive systematic review of the evidence, conducted by a group of Stanford University researchers in 2016, provides even more convincing evidence about the broader role of endocannabinoid signaling in social functioning. Recognizing the growing body of evidence that cannabinoid signaling is involved in social functioning, the researchers used a well-established systematic research construct to integrate and analyze the role of endocannabinoid signaling in social functioning across multiple diagnostic categories, including autism. They found that the majority of the evidence supports the hypothesis that primary receptors and effectors in the cannabinoid system—including delta-9-tetrahydrocannabinol, cannabidiol, anandamide, and 2-arachidonoylglycerol—all have relevant effects on measures of social functioning, such as anxiety, chronic stress, attachment, affiliation, and communication. It is important to note that although the authors drew data not only from studies on autism, but also from other psychological and psychiatric disorders (like major depressive disorder, PTSD, and bipolar disorder), their conclusion regarding the role of endocannabinoids on social functioning, in general, has promising implications for autistic patients who are specifically interested in therapeutics that target symptoms of social anxiety.
As yet, there are no major human studies in which researchers have specifically tested therapeutics that target the endocannabinoid system. Nevertheless, related research has produced promising results. For instance, in some animal models of autism, cannabidiol has been shown to impact social deficits, although more research is needed to solidify the results and establish statistical significance. A case report on a young patient with PTSD-related anxiety could also be relevant: when administered cannabidiol (CBD) oil, the patient showed significant improvements in anxiety levels, and there were no major safety concerns associated with targeting the endocannabinoid system. Given the parallels between this patient’s symptoms and those commonly experienced by autistic patients, it is possible that similar therapies targeting the endocannabinoid system might have comparable beneficial effects on social anxiety in such patients.
Additionally, the endocannabinoid system’s role in maintaining healthy neurological status suggests that it might be possible to address endocannabinoid disruption in autistic patients with nutritional supplements, such as curcumin. Studies show that levels of neuroinflammatory cytokines are elevated in autistic patients, and some scientists believe this circumstance could be the result of endocannabinoid disruption. According to a 2015 study published in Life Sciences, it is possible to lower the levels of these same cytokines through curcumin supplementation. In this study, the researchers gave rat models of autism oral doses of curcumin (either 50 mg/kg, 100 mg/kg, or 200 mg/kg), and they found significant improvements in multiple behavioral paradigms associated with social anxiety, including social interaction and repetitive coping behavior. Therefore, addressing the neurological issues associated with endocannabinoid disruption could be another way in which this system can be targeted to address the symptoms of social anxiety in autistic patients.
Although research on the connection between disruption of the endocannabinoid system and social problems in autism is limited, it remains one of the most promising areas of investigation in the field. As the theoretical and in vitro evidence accumulates, more scientists are suggesting the time has come to develop and test targeted therapeutics. However, even now, physicians can consider how the endocannabinoid system might be affected in individual patients and whether supplements like cannabidiol oil and curcumin are appropriate therapy options for individuals who struggle with autism-related social functioning.
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.*
Bhandari R, Khuad A. 2015. Life Sciences. 141:156-69.
Brigida AL, Schultz S, Cascone M, et al. 2017. International Journal of Molecular Sciences. 18(7):1425.
Chakrabarti B, Persico A, Battista N, Maccarrone M. 2015. Neurotherapeutics. 12(4):837-47.
Habib SS, Al-Regaeiey K, Bashir S, Iqbal M. 2017. Journal of Clinical & Diagnostic Research. 11(6):CE01-3.
Hollander E, Uzunova G. 2017. World Psychiatry. 16(1):101-2.
Kharson DS, Hardan AY, Parker KJ. 2016. Translational Psychiatry. 6(9):e905.
Shannon S, Opila-Lehman J. 2016. The Permanente Journal. 20(4):108-11.
Onaivi ES, Benno R, Halpern T, et al. 2011. Current Neuropharmacology. 9(1):209-14.
Xu N, Li X, Zhong Y. 2015. Mediators of Inflammation. 2015:531518.
Zamberletti E, Gabaglio M, Parolaro D. 2017. International Journal of Molecular Sciences. 18(9):1916.
Updated on March 24, 2023
Article Summary:
Autism is popularly considered a disorder of the brain that manifests itself via behavioral and social difficulties. Recently, however, researchers are realizing that profound gastrointestinal and metabolic abnormalities might be inextricably linked to patient behavioral symptoms. In the midst of this new frontier of autism research, scientists like John Slattery are engaging in multi-disciplinary approaches to develop tools for helping patients.
As the founder and CEO of BioROSA Technologies, Inc., and a longtime collaborator with top autism researchers like Dr. Richard Frye, Slattery has a history of making valuable contributions to autism research. By investigating new diagnostic methods and with the hopes of partnering with companies that are developing novel compounds that have the potential to target the microbiome and metabolic pathways of patients, Slattery is pioneering a new diagnostic paradigm. This approach can potentially lead to enhanced understanding and allow practitioners to have novel biomarker tools to assist in therapeutic developments.
Slattery’s company is developing a diagnostic test that, upon successful validation, could complement the autism diagnostic evaluation. BioROSA would do this through biological investigations, in addition to behavioral and clinical evaluations, that would greatly enhance the diagnostic process and decrease the diagnostic bottlenecks and hurdles that currently plague clinicians and parents alike, impeding access to the early interventions known to produce better outcomes. In addition to his role as Founder & CEO of BioROSA Technologies, which aims to create a biologically-based standard of care for ASD, Slattery is also a member of the science advisory board at Tesseract Medical Research, where his extensive experience in conducting clinical trials is invaluable.
In this interview, Slattery discusses the clinical and epidemiological value of his novel testing, as well as his views on the most promising developments in the field and how they might be used to minimize the impact of autism worldwide.
At present, doctors must diagnose autism by observing patient behavior and assessing reports from caregivers. Unfortunately, behavioral diagnosis of autism relies on diagnostic methods that can be inconsistent from clinician to clinician. There is currently no objective biomarker-based methodology to enable clinicians to determine whether they are making the correct diagnosis. For example, if a cardiologist wants to assess cardiac function, then there are many biological tools available to assess how the heart is functioning and which interventions might be needed. This is not possible today with autism. There are no lab-based biomarkers for clinicians to use. Furthermore, doctors can’t assess the risk of developing autism.
Slattery and his colleagues have discovered a compelling method that sidesteps some of the aforementioned complications that accompany subjective assessments and opens up the possibility of better diagnostic methods. “Within the next four years, my company, if successful, will develop a way to diagnose autism through a lab-based test,” he says. By examining biomarkers rather than behavioral symptoms, the test will allow for an easier and more accurate diagnosis. Such a diagnostic test would facilitate earlier and more accurate identification of autism and lead to earlier diagnostic timelines, alleviate diagnostic bottlenecks, and allow for earlier interventions.
However, the value of biomarker testing goes beyond diagnosis. “There are a lot of treatment strategies that are, frankly, ineffective or dangerous,” Slattery explains. “Patients and their families might not need to be practicing these alternative treatment strategies. Hopefully, we can create an objective standard of care which industry and clinicians alike can use to evaluate whether treatments are working.” Currently, much like with diagnosis, practitioners are left to subjectively assess behavioral criteria in response to therapy. These criteria are difficult to sample effectively and efficiently, as doing so requires significant time and cooperation, which within a clinical setting is almost impossible. This is complicated further by the fact that such assessments of behavior are often not a part of the care model because they don’t lead to insurance reimbursement, because there are currently no FDA-approved interventions that have efficacy for ASD. By providing practitioners with a tool to measure the impact of their interventions, it will be possible to create objective rubrics to help the practitioner assess which intervention is appropriate to use for a given patient and track therapeutic efficacy at a physiological level.
To assess a patient’s metabolism and use that assessment for diagnosis, Slattery needed to identify a biochemical property that correlates with developing autism. In Slattery’s Redox Oxidative Stress Analysis (ROSA) test, oxidative stress-related metabolic pathology is that biochemical property. Oxidative stress is the process by which byproducts of metabolism interfere with cellular function, resulting in cellular damage and disrupting proper cell function. This phenomenon is particularly damaging to the mitochondria of cells, which are responsible for producing energy to power other cellular machinery. Patients with autism have been repeatedly shown to exhibit very high levels of oxidative stress compared to their normally developing peers, indicating their body’s cellular machinery is not working properly, which substantially impairs mitochondrial function and leads to other significant physiological concerns.
Using machine learning and laboratory techniques like mass spectrometry, ROSA can determine whether a patient’s cells are experiencing high levels of oxidative stress that impede cellular function. Higher levels of oxidative stress correlate with the more severe behavioral symptoms of autism and might also correlate with more severe gastrointestinal symptoms, as well as other medical symptoms that have been reported in ASD, such as impaired immune function. Importantly, researchers like Slattery have discovered molecules that act as markers for ongoing oxidative stress. In particular, glutathione, a tripeptide, is critical for assessing oxidative stress because glutathione’s primary purpose in the body is to prevent oxidative stress from damaging cells. Malfunctional glutathione utilization in the body is thus a major indicator of autism. As Slattery explains:
“Patients with autism have significant problems with glutathione production and also glutathione utilization. If you look at the metabolic pathways, then you can look at all the biochemical steps above glutathione and find that patients with autism have abnormalities every step along the way. Of course, you’re going to have problems with glutathione when those steps are banged up. Improving glutathione’s metabolism could, therefore, potentially have tremendous implications for correcting the biochemical problems of autism and also enhancing behavior. Investigations into the precursor for glutathione production, N-acetyl-l-cysteine (NAC), have also shown promise in ASD and other neuropsychiatric conditions. I have just published a book chapter on this work with my colleague, Dr. Richard Frye.”
But Slattery’s perspective on how metabolic issues and oxidative stress relate to autism symptoms is broader than abnormal glutathione metabolism alone. Indeed, although oxidative stress impacts many different interconnected physiological systems, all stem from the metabolic action of the mitochondria. “Mitochondrial medicine is a relatively new field in medicine, although, amazingly, the mitochondria were first described as early as the 1840s,” Slattery says. “Mitochondrial medicine has really only been around conceptually as a medical discipline since the 1980s, but it wasn’t until recently that we had the technology to explore it more efficiently and effectively.” This new field of medicine has enormous implications for the future of autism diagnosis and therapy, especially in light of new research that implicates the gastrointestinal tract and microbiome in autism-related dysfunction and how these systems seem to be evolutionarily conserved and interconnected in many complex ways.
Rather than examining autism purely through the lens of neurology and psychology, understanding it in light of the role of mitochondrial dysfunction opens up new possibilities for not only diagnosis, but also for autism therapies. In terms of the possible scope of these new therapies, Slattery doesn’t conceal his excitement:
“Restorative therapies could be possible. All of these metabolic pathways that are interconnected are not performing properly. Can we, in a hypothetical world, identify these pathways and use the right interventions to be leveraged to push those pathways to normal levels to allow more normal physiological function and address patient symptoms to a point where the patient could recover? Potentially. That is the future we think is possible, and that is where we want to go. That’s what we’re going to try to achieve.”
So, what might metabolic-targeted therapies involve? Slattery has a number of ideas on this topic, including therapy with compounds like methyl-B12 and folate. One compound is especially promising to Slattery, however: butyrate.
Slattery emphasizes that butyrate is a compound of great interest within mitochondrial medicine and the field of the microbiome. “Therapies such as butyrate can have a tremendous effect at limiting oxidative stress to the mitochondria,” he explains. Butyrate is particularly appealing to researchers because it is known to be bioactive; it is used by the body to regulate immune cells in the gastrointestinal tract.
Targeting the mitochondria of autism patients with butyrate can be challenging due to its unique characteristics, however. Butyrate is the chemical that gives vomit its characteristic smell, which makes it extremely unpalatable to most patients when given orally and introduces practical barriers to administration. “Butyrate is a gross compound to deal with,” Slattery says. “Trying to get a patient with autism to consume butyrate is no small task unless you can mask the taste and encapsulate it so the patient doesn’t know they’re consuming butyrate.”
Some researchers have addressed this challenge by creating tolerable delivery formulations for butyrate supplements—a major innovation that vastly broadens the landscape of potential therapies. Tesseract Medical Research, which develops cutting-edge therapies for neurological and gastrointestinal conditions, has produced two such nutritional supplements: ProButyrate and AuRx. “The thing that Tesseract has done that sets them apart from everyone else in the field is that they’ve developed a palatable supplement,” Slattery explains. This means that butyrate can be administered in a therapeutic capacity unlike ever before and could be a massive boon to patients. However, taste is not the only challenge to butyrate use; butyrate suffers from significantly poor bioavailability, which means that only specialized delivery mechanisms have a chance at providing a therapeutic benefit.
Butyrate is naturally produced by the body, and the body readily metabolizes any additional butyrate consumed orally as a result. This prevents butyrate from accessing the areas of the body that it needs to act on to produce symptom relief. To eliminate this obstacle, Tesseract has developed highly bioavailable delivery systems that can deliver intact butyrate directly to the physiological target. “You have to deliver butyrate throughout the GI tract, but in particular, to the colon,” says Slattery, “It is not an easy thing to do, but Tesseract has accomplished that.” By delivering butyrate to the colon, the compound can exercise its antioxidant capabilities on the cells that need the most assistance in an autism patient.
Although Dr. Richard Frye and Dr. Shannon Rose’s in vitro research (of which Slattery was a collaborator and co-author) on butyrate showed promising preliminary results, it should be noted that the laboratory findings are far from the goal of clinical utility. A definitive result of butyrate efficacy on ASD symptomatology awaits the completion of clinical studies. “The stage has been set for a clinical trial testing butyrate in autism. That’s the next step. The fact that Tesseract has developed ProButyrate and AuRx is a significant piece of that.” Although Slattery’s company is not involved in ASD therapeutic research, Slattery views the ROSA testing platform as a natural potential companion to any significant ASD therapies. In the future, clinicians could administer the ROSA test and receive a positive result for ASD diagnosis. In turn, hypothetically, they could follow up with alternative therapy (such as butyrate), monitor effects on oxidative stress, determine if the therapy is inhibiting oxidative stress, and correlate the effects with behavioral symptoms. This clinical pairing would be a major asset in the field because it would link therapy to an objective measurement of efficacy.
New testing and therapy paradigms have a massive potential to help patients. But could ROSA or butyrate supplementation be a tool to minimize the prevalence of autism? “Maybe,” Slattery says cautiously before his tone changes to aspirational. “If you can sufficiently reduce the severity of cases by even 1 percent, there’s a significant economic return [from preventing the need for medical services] and you can also potentially change that patient’s life and their family’s life forever.” Slattery contends that although his ROSA technology has potential to open new avenues for diagnosis and monitoring, therapies like butyrate supplementation will have to be tested to assess their ability to improve symptoms. In this framework, Slattery thinks the next 20 years of autism research can address symptoms, but that the road to an autism-free world still extends over the horizon with tremendous amounts of research and validation from diagnostics and therapeutics necessary to achieve that lofty goal.
Nonetheless, Slattery is confident about the future of autism therapeutics research. “We’re optimistic that all is possible if the resources are put into the space and the work that needs to be done can be funded and put to the test through innovative academic-industry collaborative efforts,” Slattery says. “We’re about to be ready for the race. I think we’re still stretching right now … [but] I am optimistic and think things are about to take off like they never have before.”
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.*
Slattery cautions that all mentioned compounds need to be carefully evaluated in clinical trials and that none of his comments have been evaluated by the FDA and that the remarks he makes are strictly research-based without any implied or explicit warranties related to the use of any of these interventions for ASD patients. He stresses that families must consult with a physician before attempting to treat their child with any therapy, irrespective of presumed safety or efficacy.
Updated on March 24, 2023
Article Summary:
This remarkable compound supports the body’s natural inflammatory response and has been used medicinally for thousands of years.* Biologists have investigated curcumin for its numerous bioactive effects. Curcumin supports health naturally and carries few side effects. Thanks to its impact on inflammatory response, immune cells, and the body’s response to stress, using curcumin for brain health sets patients up for success.
Neurodegeneration has many causes, but over the long term, oxidative stress is one of the most significant that curcumin can address. Oxidative stress is a kind of chronic cellular damage that occurs when highly reactive byproducts of normal metabolic processes—or environmental effects which are damaging to cells—are let loose inside of cells. These byproducts, called reactive oxygen species (ROS), cause damage to cellular machinery and DNA by blocking the action of other biological molecules necessary to sustain cellular life.
Curcumin is especially effective at “scavenging” reactive oxygen species, which keeps them from causing damage to cells.*
Molecules like curcumin that are effective at removing ROS from circulation are called anti-oxidants. In a review conducted by Dr. Ramassamy at the University of Laval in Quebec, curcumin was identified as a particularly effective anti-oxidant capable of staving off neuronal death compared to other organic molecules of its type. Furthermore, Dr. Ramassamy states that curcumin’s ability to modulate the gene expression of immune cells—thereby altering their ability to upregulate inflammatory responses—makes it a worthwhile area for future research into alternative therapies for brain health and cognitive function.*
There is a catch when it comes to maintaining a normal inflammatory response in the brain via curcumin’s immune regulatory actions. If curcumin acts on the genes of immune cells, the changes curcumin induces will be delayed. The immune cells will need time to adjust their cellular machinery to reflect the changes that the chemical caused to their genes. In other words, patients won’t get instant relief, and patients who are currently suffering from memory deficits or cognitive issues might have to take curcumin for a sustained period of time before they realize any benefits. But, this delayed and indirect mechanism to address the brain’s inflammatory response is only one of curcumin’s benefits for brain health.
The benefits of curcumin for brain health are promising. Research presents a compelling account of curcumin’s benefits for brain health. Although it isn’t reasonable for patients to expect the exact results experienced by the mice, patients who supplement their diet with curcumin might have an edge when it comes to defending against cognitive decline.
Based on the strength of animal studies, researchers recommend further investigations into curcumin for brain health. In a recently published editorial, a multi-national group of researchers has lauded curcumin as one of the most promising brain health supplements
Duration of supplementation is not the only concern for patients considering curcumin supplementation. Curcumin can be difficult for the body to absorb, and if it isn’t well-absorbed, the body can’t use it. Patients can’t take just any curcumin supplement and expect to derive protective benefits. Instead, patients must find a curcumin supplement designed for high bioavailability, allowing the body to absorb the molecules where and when it can derive the greatest benefit. These supplements should ideally contain variations of curcumin known to be more bioavailable, such as tetrahydrocurcumin. Should patients find the right supplement and use it consistently, they might be able to protect themselves from the onset of aging-related cognitive decline.
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.*
Jiang J, Wang W, Sun YJ, et al. 2007. European Journal of Pharmacology. 561:54–62.
Sun AY, Wang Q, Simonyi A, Sun GY. 2008. NeuroMolecular Medicine. 10:259–274.
Williams RJ, Mohanakumar KP, Beart PM. 2016. Neurochemistry International. 95:1–3.
Updated on February 8, 2023
Despite the best efforts of clinicians, certain diseases are difficult to diagnose. Many conditions share common symptoms like inflammation, diarrhea, nausea, headache, constipation, and more, leaving physicians to make educated guesses based on the probability of a given disease. Under this framework, physicians are more inclined to diagnose common, yet relatively less harmful diseases first, than correct their diagnosis to a more serious disease later if necessary.
Although physicians are generally skilled at separating symptom clusters that occur in different diseases, irritable bowel syndrome (IBS) is a particularly common misdiagnosis due to the breadth of its symptoms and its prevalence as a disease. When added to the fact that IBS is nonfatal and its therapies are typically easy to tolerate, doctors are at high risk of making an incorrect IBS diagnosis; an IBS diagnosis is unlikely to stigmatize the patient, and the diagnosis is unlikely to traumatize the patient when compared to other possible diagnoses. Unfortunately, an incorrect diagnosis of IBS can result in protracted therapy cycling that fails to address the underlying non-IBS pathology, leaving patients to struggle with distressing and potentially dangerous symptoms.
Being an informed patient with an IBS diagnosis or other gastrointestinal pathology means staying abreast of the various conditions that might be mistaken for irritable bowel syndrome. Likewise, being a skilled practitioner means understanding the ways in which other diseases might present similarly to IBS in the clinic. Furthermore, both patient and physician should reassess the IBS diagnostic process such that the right disease is addressed.
IBS can be challenging to diagnose properly because it is not a well-understood or easily identified disease. There are no blood tests for IBS, nor does visual examination or equipment-assisted imaging provide answers. Furthermore, IBS symptoms have no single identifiable trigger, which means they can appear to be transient and without cause or incorrectly associated with a benign stimulus like certain foods. This also leads to confident yet incorrect diagnoses, because corrective action, like refraining from consuming suspected trigger foods, might coincide with a long period without an IBS flare up.
Without objective diagnostic methods, physicians often diagnose IBS using their own judgment, which they are trained to supplement with several clinical diagnostic rubrics. Like elsewhere in medicine, diagnostic rubrics for IBS are pioneered by clinicians, substantiated by research studies, and then refined and eventually replaced by subsequent cooperation between physicians and researchers. The original diagnostic rubric for IBS states there are several core symptoms that always occur:
Since the publication of this rubric, a number of others have emerged, each of which has its own advantages and disadvantages, with some being better at proving IBS specifically and others more effective at ruling out other diseases. Physicians typically use the rubric they were trained with, barring hospital policy to use a specific rubric. Rubrics also place different weights on different symptoms; where mucus and the feeling of incomplete bowel evacuation could be core symptoms to one rubric, they might only be attendant symptoms to another. This inconsistency allows for a wide degree in variation of diagnostic practices.
The tests called for by these diagnostic guidelines are not consistently applied either. According to one study on IBS diagnosis, none of 149 patients were diagnosed using all of the tests required by the most recent guidelines. Even the most common tests—including a basic blood test, a chemistry panel, blood sedimentation rate testing, and a serum thyroxine assay—were inconsistently performed. The researchers found that only 42 percent had a basic blood test, and 41 percent underwent colon imaging. Because IBS is typically diagnosed via exclusion of other similar diseases, insufficient testing leaves a larger area for misdiagnoses to occur. Certain diseases might only show up on a blood test, whereas others might only show up via an imaging study. Other conditions, like mental health disorders or illnesses, that cause a minority of gastrointestinal symptoms might only be correctly diagnosed instead of IBS if a specific questionnaire regarding that condition was administered to the patient, a highly unlikely possibility when the patient is complaining predominantly of gastrointestinal symptoms. Building a basic understanding of these alternative health conditions is necessary for clinicians who want to minimize their misdiagnosis rate and patients who want to ensure their diagnosis is correct.
Because diagnosing IBS correctly is difficult, that difficulty can spill over into making correct diagnoses of other diseases affecting the gastrointestinal tract. In the absence of biopsies or lab results confirming another condition, IBS is an easy go-to diagnosis for a clinician to make because of its transient symptoms, which tend to be of moderate severity. Owing to the inherent ambiguity of the language patients use to describe their issues to their physicians, complaints about gastrointestinal symptoms that aren’t severe enough to be viral and aren’t mild enough to be associated with a non-gastrointestinal disease are at high risk of misdiagnosis as IBS.
Inflammatory bowel diseases (IBDs), like Crohn’s disease and ulcerative colitis, are often initially misdiagnosed as IBS. IBDs are characterized by inflammation, bloating, gas, pain, and often rectal bleeding, all symptoms shared with IBS to some degree. These symptoms are accompanied by disturbances to the microbiome, a propensity for inflammatory episodes, and diminished quality of life. The reasons for misdiagnosis are simple: IBS symptoms often overlap with IBD symptoms, IBS can be comorbid with IBDs, and IBS is a much less serious diagnosis. In the event of a patient with both IBS and an IBD, it might be impossible for a physician to separate the symptoms of IBS from the symptoms of the IBD, especially if the IBD’s onset is relatively recent. Without a history of severe gastrointestinal issues, the diagnosis of IBS is more expedient.
Unfortunately, the differences between IBS and IBDs are often difficult for clinicians to determine even when both are confirmed. However, unlike IBS, IBDs are clinically diagnosable with a variety of blood tests, biopsies, and imaging tests thanks to their telltale inflammation and physical damage to the gastrointestinal tract. Notably, IBDs get better with pharmaceutical therapies targeted at the gut, whereas IBS might not. It’s easy to imagine that a patient could be diagnosed with IBS during the early development of their IBD and fruitlessly spend months or longer trying to address it.
Due to the large degree of overlap between celiac disease and IBS symptoms, physicians diagnosing a patient with both conditions could fail to recognize the presence of celiac, focusing solely on the IBS diagnosis. This problem is widespread and is often complicated by coincidence of other pathologies that more strongly suggest IBS than a diagnosis of celiac disease. One study found that of 200 patients who had IBS, 54 patients of them also had celiac disease that was diagnosable via a blood test. Notably, if these patients were initially diagnosed with IBS using a clinical rubric alone, they might never have received the blood test necessary to detect celiac disease, leaving them to suffer with celiac symptoms without understanding why. Although the diagnostic history of these 54 patients is unknown, it’s likely that at least several of them faced an initial IBS diagnosis before their celiac disease was subsequently diagnosed after their symptoms persisted.
Additionally, patients with celiac disease might not have IBS whatsoever, but could receive a fundamentally incorrect diagnosis as the result of misattributed symptomatology and an absence of testing.
Gluten sensitivity is an increasingly common disorder in which patients experience indigestion, pain, bloating, and gas after consuming gluten-rich foods, such as bread and most starchy vegetables. Although gluten sensitivity is traditionally thought to primarily be a consequence of celiac disease, a new scientific understanding of gluten sensitivity has shown that it can occur independently of other disorders. Today, gluten sensitivity is increasingly associated with IBS, although inconsistently so within the dietary history of a single person. Therefore, a person with gluten sensitivity might or might not have IBS, but a person with IBS is more likely than a healthy control to have some degree of gluten sensitivity. This complicates diagnosis substantially. Because of its seemingly unpredictable gastrointestinal symptoms and transient flare-ups, gluten sensitivity is at high risk of being misdiagnosed as IBS in patients who do not have IBS and missed in patients who have comorbid IBS and gluten sensitivity.
As noted in a study connecting IBS to gluten sensitivity and IBDs, gluten sensitivity is prone to induce symptoms similar to IBS. This is the case whether the gluten sensitivity is associated with another pathology like celiac disease or whether it is in isolation. The consequences of gluten sensitivity misdiagnosed as IBS are clear: an incorrectly diagnosed patient will continue to consume gluten and continue to have flare-ups despite ongoing therapy for IBS. Therapy for IBS will do little to address the gastrointestinal intolerance of gluten, and the patient will suffer.
Physicians have long thought that IBS has a psychiatric component. Indeed, most accounts of IBS consider anxious, depressive, and obsessive symptoms to be features of the condition. However, whether these components cause IBS or are themselves caused by IBS is unclear, which places them at high risk of misdiagnosis. As found in one 2007 study, 46 of 95 patients diagnosed with depression and IBS experienced no IBS symptoms when their depression was in remission, suggesting that IBS symptom presence and severity are closely tied to psychiatric phenomena.
Stress, mood changes, and mild anxiety are very likely to be comorbid with IBS, even though their symptoms are not commonly understood to be as viscerally uncomfortable. Patients with mild anxiety could also have gastrointestinal systems that might either indicate IBS or be subclinical and not severe enough to truly meet the diagnostic criteria for IBS. However, given that patients are more likely to go to their physician and complain about viscerally discomforting pathologies than psychological distress, IBS is an easy diagnosis to make when it’s masking emotional illnesses that are the root cause of symptoms. The growing medical consensus on IBS is thus that it is a predominantly psychosomatic disorder that could be inseparable from these other common psychiatric conditions. The takeaway is that patients diagnosed with IBS who also have low mood, excessive worry, or other symptoms consistent with mild anxiety should seriously consider getting a second opinion.
Of the diagnoses that an IBS diagnosis can mask, perhaps the most serious is that of stomach cancer. Stomach cancer is characterized by heartburn, nausea, blood in stools, indigestion, pain, diarrhea, loss of appetite, and constipation. This condition is difficult to diagnose under ideal conditions and often does not present itself symptomatically until it is in an advanced stage, at which point survival rates are extremely low; less than 10 percent of patients survive more than five years after late-stage diagnosis. Nonetheless, if the cancer is caught early and action is taken quickly, stomach cancer is survivable and even curable with the help of surgery. Under these conditions, however, an incorrect IBS diagnosis could easily be fatal.
Notably, the symptoms that differentiate true IBS from stomach cancer are likely the associated emotional disorders because stomach cancer pre-diagnosis is not associated with emotional disturbances, like mild anxiety, whereas IBS is. If an IBS diagnosis is made without a brief mental health inventory, blood test, or biopsy, then there is a chance it could be hiding a much more pernicious disease.
Colon cancer is yet another serious disease that could be hiding beneath an incorrect IBS diagnosis. Much like with stomach cancer, colon cancer’s symptoms include bloody stools, pain, fatigue, indigestion, and discomfort. Bloody stools are typically the symptom that a physician would use to easily differentiate IBS from a more serious illness like colorectal cancer, which means that a patient going to their physician before experiencing that symptom might be misdiagnosed. Patients with inflammatory bowel diseases are at a much higher risk for colon cancer, which means an initial missed diagnosis or misdiagnosis could cause the physician to miss critical signs of subsequent cancer.
Colon cancer is more treatable than stomach cancer, however. Patients who are misdiagnosed with IBS might have a greater chance of survival thanks to a plethora of surgical and chemotherapy options that are effective enough to rescue a patient with a somewhat late diagnosis. Furthermore, unlike stomach cancer, failure to make a colorectal cancer diagnosis is likely to be addressed in a subsequent screen as part of general adult health maintenance for patients at risk.
Most of the diseases commonly misdiagnosed as IBS are chronic and unlikely to respond to IBS therapies. Likewise, IBS itself is chronic and might not always respond to therapies specifically targeted at it after a correct diagnosis. Patients and their physicians are thus left in a difficult position where they are forced to act on incomplete and potentially incorrect information under the best of circumstances. If an incorrect IBS diagnosis—or missed diagnosis in the presence of comorbid conditions—prevents treatment of another disease that can carry permanent damage, then the chance of long-term consequences is very high. In the case of Crohn’s disease, for example, scarring to the gastrointestinal tract might be impossible to repair even after the diagnosis is rectified, resulting in chronic difficulty with bowel movements, nutrient absorption, and comfortable digestion.
Not all hope is lost, however. Diligence and awareness of IBS’s common position as a first and incorrect diagnosis can address the danger of prolonged misdiagnosis. This means that a patient needs to ensure their physicians has ruled out the most common misdiagnoses after receiving an IBS diagnosis. Patients also need to remain vigilant even after they leave the clinic; if patients receive an IBS diagnosis and their symptoms do not reside quickly, then they must follow up with their physician promptly. Doing so will limit the damage caused by a misdiagnosis and get therapy on the right track. Rather than hoping for a correct initial diagnosis, patients need to take an active role in their care.
For their part, physicians need to use differential diagnostic techniques that take into account the possibility of comorbidities or non-IBS root causes. Following up with the patient regularly will also help to confirm or refute the initial diagnosis. Likewise, physicians must endeavor to be consistent and comprehensive in their diagnostic practices of IBS lest they damage the therapeutic relationship with their patients and tarnish their reputations. With a strong therapeutic alliance and careful application of diagnostic guidelines for a panorama of diseases, moving beyond systemic IBS scapegoating is possible.
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.*
Karling P, Danielsson A, Adolfsson R, Norrback KF. 2007. Neurogastroenterol Motil. 19:896–904.
Manning AP, Thompson WG, Heaton KW, Morris AF. 1978. Br Med J. 2:653–654.
Yawn BP, Lydick E, Locke GR, et al. 2001. BMC Gastroenterol. 1:11.
Zwolińska-Wcisło M, Galicka-Latała D, Rozpondek P, et al. 2009. Przegl Lek. 66:126–129.
Updated on February 14, 2023
Alzheimer’s disease remains a debilitating and tragic disorder despite decades of scientific research attempting to find treatments and cures. Even with the advent of new drugs designed to slow the progression of the disease, patients and doctors alike are still looking for ways to stave off its onset and limit the severity of its cognitive effects. Patients now have reason to be hopeful, however. In the hunt for effective therapy, scientists are exploring a new therapeutic molecule: quercetin.
Quercetin is a molecule produced by a variety of plants, including grains, onions, and leafy greens. It’s also a member of the bioactive flavonoid family of molecules. Like other flavonoids, quercetin is metabolized easily by humans and has a variety of physiological effects ranging from scavenging reactive oxygen species to helping maintain the body’s normal inflammatory response. Importantly, many flavonoids like quercetin have effects that suggest they’re useful in helping maintain cognition in those affected by neurodegenerative diseases.
These effects were first documented in a seminal 2008 paper by Drs. David Vauzour, Katerina Vafeiadou, Ana Rodriguez-Mateos, Catarina Reneiro, and Jeremy Spencer from the University of Reading in England. The researchers’ collation of prior research into flavonoids is directly applicable to quercetin and is one of the few comprehensive summaries of flavonoids’ impact on cognition as portrayed in the scientific literature. The researchers’ analysis cites a handful of other studies on flavonoids sourced from many different plants, finding that the source of the flavonoid doesn’t appear to change their physiological effects. In their research summary, the authors tie together countless pieces of information that, taken together, indicate that if patients obtain the right sources of quercetin and other flavonoids, they can possibly slow down the rate of cognitive decline caused by old age. Significantly, they’ll also promote the ability of their neurons to resist the ravages of dementia that are typical in Alzheimer’s disease.
Flavonoids have a number of beneficial physiological effects; in particular, supporting the body’s natural inflammatory response and neuronal health. In their synthesis of the research on flavonoids, Dr Vauzour’s group approached the neuroprotective properties of flavonoids as their primary point of inquiry. The researchers divided the beneficial properties of flavonoids into three separate but related phenomena, as identified by several other studies examining flavonoid class molecules:
Although functionally discrete, each phenomena is caused by activation of the same physiological mechanisms. This means that flavonoids consumed from any source will be beneficial in all three instances.
The mechanisms of these beneficial effects are the inhibition of cell death and the promotion of blood vessel formation. The former is particularly important, because inhibition of cell death occurs via flavonoids’ interaction with certain enzymes used in cell signaling; when cells are exposed to flavonoids, they don’t send each other chemical signals that trigger cell death, which means that cells destroy themselves less frequently. Additionally, the promotion of new blood vessel formation promotes the resiliency and functionality of tissues by enabling greater oxygenation. Taken together, these effects might have a significant beneficial impact on the symptoms of Alzheimer’s disease.
Of the mechanisms responsible for flavonoids’ neuroprotective effects, the impact on cell death signals is potentially the most useful, because decreasing cell death signaling leads to better neuronal survival. When the glial cells that are responsible for supporting the brain’s neurons are exposed to flavonoids, their production of the cell death signal protein, tumor necrosis factor alpha (TNFa), is inhibited. Because TNFa is linked to up-regulating the brain’s inflammatory response, its inhibition can help maintain the brain’s normal inflammatory response. Increased levels of inflammation are linked to worsening Alzheimer’s symptoms. These combined beneficial effects mean flavonoid supplementation might cause neurons to self-destruct less frequently and perform more efficiently than they would otherwise in an inflamed state.
Neuronal persistence is particularly crucial for Alzheimer’s patients. As part of the main pathology of Alzheimer’s, clumps or “plaques” of a harmful protein called beta-amyloid accumulate inside neurons and inhibit their function, eventually killing them. As increasingly more neurons die, cognitive functions, memory consolidation, and memory recall are hampered. The Vauzour researchers optimistically discussed the ability of flavonoids to limit the cellular death caused by exposure to beta-amyloid plaques, as observed in several validated in vitro studies.
A year after the Vauzour researchers substantiated the connection between the entire class of flavonoid molecules and resistance against beta-amyloid-induced cellular death, another group of researchers from the University of Kentucky published a paper documenting their results examining quercetin. This research cohort performed extensive in vitro investigations of quercetin’s impact on cultured neurons exposed to beta-amyloid. The results were compelling: neurons treated with small quantities of quercetin experienced lower cytotoxicity, lower oxidative stress, and 33 percent less cell death when exposed to beta-amyloid plaques compared to cells that weren’t treated. The samples treated with quercetin also exhibited 75-percent fewer proteins associated with Alzheimer’s-induced cellular damage.
Quercetin was not uniformly helpful, however. When the Kentucky researchers tested the impact of extremely high concentrations of quercetin, they found that its protective effect disappeared. However, reaching these concentrations would not be possible by consuming quercetin from foods alone due to the speed at which quercetin is metabolized, which means that patients would be unlikely to encounter this effect. Although the researchers’ findings were promising, their experiments were limited to cell cultures, which prevented them from speculating about in vivo effects. Their work has subsequently been confirmed by numerous other researchers.
Although Dr. Vauzour’s primary area of interest was Alzheimer’s disease, literature reviews also makes a compelling case for the therapeutic applications of flavonoids for other neurological diseases. Dr. Vauzour’s group discussed several studies that linked flavonoid consumption to better patient outcomes in dementia, Parkinson’s disease, and even depression. Significantly, several of these studies were in vivo investigations with large patient cohorts.
One notable example cited by Dr. Vauzour’s review examined 1,640 subjects who were healthy and without dementia. The study followed the subjects for 10 years, performing cognitive testing and frequently surveying the subjects’ diets. With a very high degree of confidence, the results showed that individuals with higher flavonoid intake exhibited better cognitive performance than those with lower flavonoid intake. This effect was exaggerated when the researchers compared the group with the lowest self-reported flavonoid intake with the group who reported the highest. Earlier research had found the same relationship.
At the conclusion of the study, the researchers found that the difference in cognitive performance between the groups was nearly a full point on the Mini-Mental State Examination. The Mini-Mental State Examination is used as a tool to aid in the diagnosis of dementia and is scored out of 30 points. After controlling for all potential confounding variables, the benefit of flavonoids persisted in the data; the high flavonoid intake group scored on average 0.9 points higher than the low flavonoid intake group. This means that flavonoids might be able to limit the damage caused by Alzheimer’s disease in addition to helping patients maintain a greater degree of cognition in the course of normal aging. Other studies with large patient cohorts have subsequently confirmed this phenomenon. Although Dr. Vauzour’s group was enthusiastic about the safety and potential of flavonoid therapeutics, they did outline one concern: “In order for flavonoids to access the brain, they must first cross the blood-brain barrier, which controls entry of xenobiotics into the brain.” In short, the research group was concerned about flavonoid bioavailability. After examining relevant research, the authors subsequently conclude that, “flavonoids traverse the blood-brain barrier and are able to localize in the brain, suggesting that they are candidates for direct neuroprotective and neuromodulatory actions.”
Flavonoids like quercetin could hold the key to slowing the progression of neurodegenerative diseases. As the researchers note, flavonoids are surprisingly ideal for therapeutic use because, unlike most pharmaceutical molecules, they can easily cross the blood-brain barrier without being modified. However, flavonoids can’t be reliably stored or distributed in the body because they are metabolized by multiple organs at an extremely high rates; although some of the metabolites are also bioactive, they are likewise broken down quickly.
Due to the rapid and comprehensive way the body breaks down quercetin and other flavonoids, their physiological impact is limited. This problem is compounded by the fact that most foods that contain flavonoids have far fewer flavonoid molecules than the quantities necessary to produce the beneficial effects seen in in vitro studies. As such, supplementation will be necessary for patients who want to add quercetin as an alternative therapy, and these supplements must be formulated to compensate for the metabolic barriers of the molecule and ensure bioavailability.
The picture created by Dr. Vauzour’s group is clear: if flavonoids, such as quercetin, can be formulated to be bioavailable, then it will be much easier for patients with Alzheimer’s, dementia, and other neurological conditions to access their benefits. Already, scientists are developing advanced new delivery systems that can survive first-pass metabolism and control the distribution of quercetin to achieve therapeutic concentrations. If patients want a therapeutic edge against Alzheimer’s that spans multiple aspects of the disease’s impact, then finding a highly bioavailable quercetin supplement is an excellent 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.*
Ansari, M. A. et al. 2009. The Journal of Nutritional Biochemistry. 20(4):269–275.
Commenges, D. et al. 2000. European Journal of Epidemiology. 16 (4):357–363.
Dajas, F. et al. 2015. Neurochemistry International. 89140–148.
Ho, L. et al. 2013. The FASEB Journal. 27(2):769–781.
Letenneur, L. et al. 2007. American Journal of Epidemiology. 165(12):1364–1371.
Sabogal-Guaqueta, A. M. et al. 2015. Neuropharmacology. 93134–145
Vauzour, D. et al. 2008. Genes & Nutrition. 3 (3-4):115–126.
Updated on February 8, 2023
Brain fog: whether you’re experiencing it yourself or interacting with someone who is, it can be a frightening symptom. More formally known as mild cognitive dysfunction or mild cognitive impairment, brain fog is characterized by forgetfulness, trouble focusing, mental fatigue, sudden mind blanks, difficulty finding the right words when communicating, and a tendency toward “spacing out.” Additionally, brain fog is associated as a side effect of certain prescription medications.
Although mild cognitive dysfunction itself remains poorly understood within the research community, studies show it is associated with aging, stress, limited metabolic function, declines in neural plasticity, inflammation, and oxidative stress. Due to the latter two associations, some scientists have hypothesized that natural supplements with antioxidant properties, like curcumin, might benefit patients who experience brain fog. So far, although the evidence from the few clinical studies that have been conducted is inconclusive, promising research in animal models suggests that larger, more comprehensive clinical trials are warranted in the future.
When justifying the use of a natural alternative therapy like curcumin for mild cognitive dysfunction, it can be helpful to have mechanistic evidence supporting a relationship through which the supplement might modulate symptoms. In 2017, a breakthrough study in the journal Oxidative Medicine and Cellular Longevity provided just that. Researchers in Romania conducted an experiment in rat models and found that curcumin could reverse mild cognitive dysfunction by reducing oxidative stress in the brain and downregulating a specific cellular signaling pathway: the ERK 1/2 / NF-kB signaling pathway, which is involved in the inflammatory response.
For this study, the researchers simulated cognitive dysfunction by giving the rats diazepam, a drug that is known to have comparable effects on the brain. After 28 days of curcumin administration (150 mg per kg of body weight), they measured the impact on the rat models through a combination of behavioral and biochemical tests. The rats treated with curcumin performed significantly better on a maze test that examines spontaneous alternation behavior, which is commonly used in the field as a measure of spatial learning and working memory. Additionally, biochemical studies showed that biomarkers of oxidative stress were lower in both the blood and the hippocampus (a part of the brain associated with memory) and that the ERK 1/2 / NF-kB signaling pathway was downregulated in both the hippocampus and the frontal lobe of the brain. These findings suggest that curcumin supplementation has anti-oxidation properties that support the body’s natural inflammatory response, and these processes were mediating the observed reductions in behavioral symptoms of mild cognitive dysfunction.
A similar study from 2010 highlighted the potential benefits of curcumin supplementation using rat models. However, this study focused on the potential benefits for patients who experience mild cognitive dysfunction because they use prescription medications that are commonly used to address epilepsy. Research indicates that the brain fog experienced by these patients could be the result of oxidative damage caused by the free radicals generated by these drugs in the brain. Therefore, an antioxidant supplement like curcumin could be a viable intervention option.
For the 21-day study period, the researchers treated half of the rats with two well-known anti-epileptic drug and half of the rats with curcumin and the anti-epileptic drugs. Like the Romanian researchers who conducted the above-described study, these researchers also used a maze test to measure spontaneous alternation behaviors, as well as a passive avoidance paradigm to show that curcumin supplementation had a significant positive effect on learning and memory-related behaviors. At the same time, their biochemical tests showed that while the biomarkers in the blood of the rats increased upon therapy with the anti-epileptic drugs, the increase was significantly smaller in the rats that were simultaneously administered curcumin. Therefore, the researchers conclude that curcumin can be a safe and effective side-by-side therapy for patients who are experiencing mild cognitive dysfunction as the result of pharmacological drug therapy.
Although these in vivo animal studies present exciting evidence supporting the use of curcumin for mild cognitive impairment, the clinical studies on the topic have been characterized as “disappointing” by researchers in the field. According to the most recent systematic review paper, which was conducted by a research group at the University of Rome in 2016, it is not yet possible to draw conclusions from the available evidence. The reviewers acknowledged that both in vitro and in vivo animal studies indicate that curcumin can be effective for patients with mild cognitive impairment, but with only five small-scale clinical studies to analyze—none of which produced particularly strong evidence—their only conclusion is that more research is warranted.
In 2014, a similar systematic review out of the University of Pavia had the same outcome. After examining three published studies and several ongoing clinical trials on using curcumin for mild cognitive dysfunction, the researchers found that the scant data was not enough to draw a conclusion. Importantly, they also suggested that the reasons the data were insufficient was that several of the studies were poorly designed and many involved the use of curcumin formulations with poor bioavailability. Not only do these insights highlight areas for improvement in future research studies, they also indicate that patients and practitioners today should not necessarily take the disappointing results as a sign that solid clinical evidence on the benefits of curcumin supplementation for mild cognitive impairment will never emerge. Rather, their characterization of the data indicates that curcumin supplementation is an appropriate therapy for certain individuals when its effectiveness is assessed through more thorough, rigorous methods. Their conclusions also remind patients who are considering curcumin supplementation that they are likely to see the best results from curcumin supplements that are specifically designed to optimize bioavailability.
Because researchers are still hopeful about the potential for using curcumin supplements to address mild cognitive dysfunction, clinical trials are ongoing. For example, recruitment efforts are currently underway for a clinical study on the potential effects of a curcumin supplement on diagnosed mild cognitive dysfunction in older adults. The premise of this research is that if curcumin has neuroprotective benefits, then it could one day be considered a credible therapeutic option for addressing age-related mild cognitive dysfunction. Patients, practitioners, and researchers alike are looking forward to the results from studies like this one, which could verify the in vitro and in vivo animal studies at the clinical level. It will be exciting to see where the findings lead in the future.
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.*
Brondino N, Re S, Boldrini A, et al. 2014. The Scientific World Journal. 2014:174282.
Frautschy S, Panizzon KL, Mohler NL. 2014. National Institute on Aging.
Mazzanti G, DiGiacomo S. 2016. Molecules. 21(9):E1243.
Reeta KH, Mehla J, Gupta YK. 2010. European Journal of Pharmacology. 644(1-3):106-12.
Ross AJ, Medow MS, Row PC, Stewart JM. 2013. Clinical Autonomic Research. 23(6):305-11.
Sevastre-Berghian AC, Fagarasan V, Toma VA, et al. 2017. Oxidative Medicine and Cellular Longevity. 2017:3037876.
Yelland GW. 2017. Journal of Gastroenterology & Hepatology. 32(Suppl 1):90-3.
Updated on March 24, 2023
Article Summary:
Developing an effective strategy for managing ulcerative colitis (UC) is an ongoing challenge. During flare-ups, patients find themselves desperate for interventions that can dampen debilitating symptoms. During remission, many UC patients constantly worry about the possibility of a relapse. However, for UC patients who are pregnant, dealing with active and/or latent UC symptoms becomes an even greater challenge because therapy options are more limited.
During pregnancy, a surgical intervention is essentially out of the question, even for a woman who has recently been diagnosed with UC, because studies show that surgery raises fetal mortality rate. Although most pharmaceutical therapies are considered safe for pregnant women, there are significant exceptions: methotrexate and thalidomide are contraindicated for pregnant women and designated as Pregnancy Category X medications. There are also several classes of drugs in Pregnancy Category C, including mesalamine and corticosteroids, which means that animal studies suggest possible negative consequences for pregnant mothers. Given the lack of clear, comprehensive evidence on most drugs, both patients and practitioners remain concerned about using these pharmacotherapeutics during pregnancy.
As a result of these limitations, many patients and practitioners are considering nutrition-based management strategies to help manage UC symptoms without putting the health of the mother or the fetus at risk. Effective strategies can include a combination of special diets (such as carrageenan elimination and gluten elimination) and nutritional supplements that can both help maintain the body’s natural inflammatory response and support optimal nutrient levels during pregnancy.
Scientists have recognized for decades that managing UC symptoms is especially important for women during pregnancy. In 1980, a study on more than 250 British women indicated that UC directly affects birth outcomes; women with active UC had a slightly lower chance of producing a live, healthy baby than women who were in remission, and the risk was considerably higher for the patients with the most severe symptoms. These findings were supported by a nationwide Danish study published in 2011. For patients diagnosed with UC in the first six months of pregnancy—and therefore were likely to be experiencing active symptoms—there was a significantly higher risk of preterm birth.
In 2018, researchers at Tokyo Women’s Medical University conducted a retrospective study on the role of UC on pregnancy outcomes in middle-aged women. Once again, abnormal pregnancy—defined as abnormal delivery and/or low birthweight—was more likely in patients with active UC (30.1 percent, as compared with 17 percent for women in the remission group). These results support the hypothesis that UC activity is directly related to pregnancy progression and patient outcomes. Given the concerns about pharmacological therapy for UC during pregnancy, there is great potential value in targeted dietary changes for pregnant UC patients.
Some UC patients worry that specialized diets can make it difficult to get adequate nutrition during pregnancy. This is a particular concern for UC patients because nutrient malabsorption is a common symptom. One solution is to eliminate pro-inflammatory food additives that contribute no significant nutritional value, such as carrageenan. Based on in vitro and animal studies implicating this common food additive in multiple inflammatory processes, researchers at the University of Illinois explored whether lowering carrageenan intake would aid in the management of UC.
In a randomized, double-blind, placebo-controlled study in 2017, patients were instructed to adopt a no-carrageenan diet. Half were then given a carrageenan-containing supplement, while the other half were given a placebo. Patients who took the carrageenan supplement had higher levels of inflammatory biomarkers and a statistically higher risk of remission. The researchers concluded that carrageenan restriction can lower the risk of early relapse—a major goal for UC patients who are in remission at the beginning of their pregnancy. Moreover, cutting out carrageenan can potentially ameliorate symptoms in UC patients when the disease does flare up during pregnancy.
Gluten-free diets might also be a safe way for pregnant patients to address UC symptoms. Because a combination of preliminary research and anecdotal evidence suggests that gluten can trigger inflammation, exacerbating the most common symptoms of UC, elimination can be an effective management strategy. Indeed, in one study of more than 1,600 patients who had been diagnosed with an inflammatory bowel disease (such as UC) and celiac disease, 38.3 percent reported that a gluten-free diet led to fewer or less severe UC flare-ups.
But many gluten-containing foods, like whole wheat bread and whole grain cereal, are fortified with essential B vitamins, including folate, which are particularly important nutrients for women during pregnancy. As a result, removing gluten from a patient’s diet can eliminate important sources of B vitamins. Consistent with this concern, studies on mostly-female patients on gluten-free diets indicate the diet might raise the likelihood of folate deficiency. Therefore, pregnant UC patients who choose a gluten-free diet should make sure that they add a highly bioavailable folate supplement to their diet. A gluten-free pregnancy diet should also emphasize the intake of high-folate fruits and vegetables like leafy greens, lentils, avocado, and papaya.
Another nutritional supplement for pregnant UC patients to consider is quercetin. Quercetin is an all-natural polyphenol derived from plant extracts, and its antioxidant properties have made it a prominent candidate for all patients looking for UC management alternatives. This plant-based nutritional supplement is especially appealing for pregnant women because it poses no major safety concerns. Furthermore, a 2011 study in the journal Toxicology indicates that quercetin has benefits for both the mother and the child beyond helping to maintain a normal inflammatory response in UC patients.* Mouse models show that a quercetin supplement can raise iron levels in the mother, which is important because iron-deficiency anemia is more common among UC patients than the rest of the population.* The study also indicated that exposure to a quercetin supplement can enhance the infant’s future capacity for iron homeostasis (that is, the infant’s ability to maintain healthy iron levels).* These results suggest that quercetin can simultaneously help UC patients manage symptoms, as well as addressing nutrient deficiency-related concerns during pregnancy.
It is essential for UC patients to effectively manage their symptoms during pregnancy, and dietary changes offer a safe, evidence-based option. By eliminating certain dietary components (like food additives and gluten) and raising their intake of others (like B vitamins and quercetin) through supplementation, pregnant UC patients can address their symptoms while ensuring they receive the nutrients they need to support their own health and that of their baby.*
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.*
Bhattacharyya S, Shumard T, Xie H, Dodda A, Varady KA et al. 2017. Nutrition and Healthy Aging. 4(2):181-92.
Habal FM, Ravindran NC. 2008. World Journal of Gastroenterology. 14(9):1326-32.
Hashash JG, Kane S. 2015. Gastroenterology & Hepatology. 11(2).
Herfarth HH, Martin CF, Sandler RS, Kappelman MD, Long, MD. 2014. Inflammatory Bowel Diseases. 20(7):1194-7.
Ito A, Iizuka B, Omori T, Nakamura S, Tokushige K. 2018. Internal Medicine. 57(2):159-64.
Norgard BM. 2011. Danish Medical Bulletin. 58(12):B4630.
Poturoglu S, Ormeci AC, Duman EE. 2016. World Journal of Gastrointestinal Pharmacology and Therapeutics. 7(4):490-502.
Stein J, Dignass AU. 2013. Annals of Gastroenterology. 26(2).
Valente FX, Campos TN, de Sousa Moraes LF, Hermsdorf HHM, Cardoso LM et al. 2015. Nutrition Journal. 14:110.
Vanhees K, Godschalk RW, Sanders A, van Waalwijk van Doorn-Khosrovani SB, van Schooten FJ. 2011. Toxicology. 290(2-3):350-8.
Willoughby CP, Truelove SC. 1980. Gut. 21(6):469-74.
Updated on February 8, 2023
Characterized by pain, diarrhea, bloating, discomfort, and constipation, irritable bowel syndrome (IBS) can produce extreme discomfort that profoundly interferes with functionality and quality of life. Currently, the etiology of IBS remains unknown, and there is no therapy guaranteed to address the underlying pathology of the syndrome. Thus, all therapeutic options for IBS are currently intended to address symptoms rather than cure the condition. Although a variety of conventional therapies exist, their efficacy and tolerability vary, leaving many to seek out alternative and complementary options.
Now, a growing number of patients are exploring the possible relationship between curcumin and IBS. Curcumin has a long history of human use by virtue of its herbal source, turmeric; curcumin is a compound of the turmeric plant, which is commonly utilized as a spice. As a bioactive compound, however, curcumin is being investigated for its potential therapeutic uses. In particular, curcumin is being recognized as a possible therapy for IBS owing to its ability to support the body’s natural inflammatory response. Paired with a reliable high-bioavailability delivery system, patients with IBS might be able to address their symptoms more effectively than is possible with conventional therapy alone.
Understanding the relationship between curcumin and IBS requires a consideration of curcumin’s bioactive properties. According to a 2013 review authored by Drs Pietro Dulbecco and Vincenzo Savarino and published in the World Journal of Gastroenterology, curcumin is a potent inhibitor of proinflammatory cellular signaling molecules in the gut. Maintaining a normal inflammatory response in the gut is critical in the context of IBS, because the disease has an inflammatory component of uncertain origin. In the course of their investigation into curcumin’s usefulness in treating digestive complaints, Drs Dulbecco and Savarino found that curcumin down-regulates the impact of nearly all of the major proinflammatory molecules in the gut via a handful of different mechanisms described by other researchers. These molecules include tumor necrosis factor alpha (TNFa), NF-kB, IL-2, and IL-12—all of which are among the body’s major substances that generate and sustain inflammation.
Each of these proinflammatory molecules is relevant to IBS patients, who experience elevated NF-kB concentrations along with generally elevated levels of other proinflammatory molecules. Elevated levels of NF-kB means that cells are more prone to runaway inflammation incidents. When curcumin is present, however, the proinflammatory molecules bond to curcumin, down-regulating their ability to adversely impact the body. Curcumin might thus provide therapeutic benefit for an IBS flare-up when delivered to patients’ colon cells.
In addition to helping maintain the body’s natural inflammatory response, Dulbecco and Savarino believe that curcumin has another mechanism that is helpful to IBS patients: stabilizing the gut microbiome. Irritable bowel syndrome is partially characterized by a host microbiome that is divergent from the profile of a normal and healthy microbiome. This is caused by certain overstimulated T cells erroneously and transiently secreting chemicals that damage the extracellular matrix responsible for maintaining the integrity of the intestinal tissue. As the extracellular matrix is weakened, healthy gut microbiota have fewer viable habitats and are replaced by harmful bacteria. In IBS, although this phenomenon isn’t sufficiently widespread to cause permanent damage to the intestinal tissue, it does make the intestines more vulnerable to future irritation—and, thus, IBS flare-ups—until the damage is repaired.
Although curcumin can’t restrict the T cells’ ability to secrete these chemicals—which are distinct from the chemicals that cause inflammation—curcumin can down-regulate T cell production. Because curcumin down-regulates the action of one of the signaling molecules that causes T cells to differentiate into the matrix-degrading variant, it can lead to lower concentrations of these cells in the colon. Although there aren’t any studies specifically linking curcumin to better microbiome health in IBS patients, the evidence of their beneficial impact on T cells is undeniable.
In addition to having a remedial benefit for flare-ups, curcumin also has the potential to address the GI discomfort associated with IBS when flare-ups do occur. This is due to the fact that curcumin apparently impacts the gut’s ability to detect discomfort and refer its signals elsewhere in the body. As a result, discomfort-related gastrointestinal symptoms might potentially be alleviated. According to Dulbecco and Savarino’s review, curcumin down-regulates the signals of burning and discomfort in the gut via its inhibition of the TRPV1 sensory transducer protein. This means that patients who supplement their diets with curcumin are likely to experience less microbiome disruption and, most likely, less discomfort. There’s also a likelihood that IBS patients will experience less severe relapses when they supplement with curcumin.
Each of curcumin’s beneficial effects is broadly applicable to not just IBS, but also other bowel conditions, and research on its impact on these conditions provides greater insight into the potential of curcumin to address IBS symptoms. In particular, inflammatory bowel diseases (IBDs) are relevant to IBS patients because many researchers believe the two families of pathologies are deeply related and potentially even identical.
In an open label, pilot study of five patients examining curcumin’s impact on IBDs, Crohn’s disease, and ulcerative colitis, the participants experienced significant benefits from curcumin supplementation. In patients with Crohn’s disease, supplementation with 360 mg of curcumin thrice daily led to a 55-point reduction in Crohn’s disease activity indices. This level of symptom reduction is extremely promising, particularly because the patients did not receive conventional therapy during the period of the study, indicating that curcumin can have a meaningful impact when used in isolation.
In ulcerative colitis patients, on the other hand, when curcumin was administered in concert with regular medication, 100 percent of ulcerative colitis patients experienced significant symptom improvement, and many were able to adjust their level of conventional medication intake accordingly. A large controlled study in 2015 of curcumin for ulcerative colitis further elucidated the efficacy of curcumin supplementation, finding that 20.5 percent of patients who received a placebo relapsed, whereas only 4.65 percent who received curcumin relapsed. Significantly, the researchers who conducted the study found that the patients who received curcumin experienced more positive clinical indicators of ulcerative colitis severity.
These studies on IBD patients indicate that curcumin supplementation helps maintain the gut’s normal inflammatory response, and IBS patients can, therefore, benefit from the same mechanism if they have access to high-quality curcumin supplements.
The potential for curcumin and IBS is profound owing to curcumin’s ability to naturally regulate the gastrointestinal tract and up-regulate the body’s own mechanisms to address IBS symptomatology. However, the path to clinical curcumin use is more difficult than it might seem at first. Curcumin is notorious for being poorly absorbed by body’s cells, as documented by Dulbecco and Savarino. Due to its low bioavailability, curcumin molecules aren’t present in large enough quantities for long enough periods of time to have a therapeutic effect when consumed as part of the turmeric plant. However, new formulations of nutritional supplements designed to optimize curcumin’s bioavailability show great promise in overcoming the compound’s obstacles to clinical application.
Dulbecco and Savarino speak enthusiastically about several new nutrient delivery mechanisms that might be used in creating highly bioavailable curcumin supplements that could enhance the quality of life for IBS patients. With the help of these sophisticated nutrient delivery systems, patients gain access to the natural and highly tolerable curcumin that can give them the natural symptom relief they are seeking. Physicians and patients can thus easily integrate specialized curcumin supplements into their daily IBS regimen to gain greater control over their therapy.
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.*
Bercik, P., Verdu, E. F., & Collins, S. M. 2005. Gastroenterology Clinics of North America, 34(2):235-245.
Dulbecco, P., & Savarino, V. 2013. World Journal of Gastroenterology, 19(48):9256-9270.
Hanai, H., Iida, T., Takeuchi, K., Watanabe, F., & Maruyama, Y. 2006. Clinical Gastroenterology and Hepatology, 4(12):1502-1506.
Holt, P. R., Katz, S., & Kirshoff, R. 2005. Digestive Diseases and Sciences, 50(11):2191-2193.
Patwardhan, R. S., Checker, R., Sharma, D., Kohli, V., & Priyadarsini, K. 2011. Biochemical Pharmacology, 82(6):642-657.
