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Updated on April 10, 2023
Article Summary
Individuals with health issues ranging from autism to epilepsy are increasingly experimenting with dietary supplementation of gamma-amino-butyric acid (GABA), one of the body’s most important neurotransmitters. These individuals, seeking to address symptoms caused by excessive neuronal excitation, have chosen to experiment with an alternative therapy in an attempt to find relief, often after conventional therapies have failed to address symptoms or had undesirable side effects. But although some individuals might indeed find relief using GABA supplements, others are concerned about its potential side effects. Many questions remain to be answered regarding GABA’s efficacy as a supplement, and although GABA’s impact on the body is well understood, far less is known about GABA supplementation’s side effects. Individuals might wish to investigate alternatives for better therapeutic potential and known safety.
Why would a GABA supplement be included in the diet in the first place? The reasoning behind using GABA stems from its physiological purpose as the body’s primary inhibitory neurotransmitter. In the brain, neurons release GABA, which then interfaces with other neurons. When GABA binds to a neuron’s receptors, it triggers a signaling cascade within the neuron that results in the neuron being less prone to activate other neurons. As a result, neurons that have recently been activated by GABA require stronger or more consistent stimuli from other neurons before they will activate and send their electrochemical signal elsewhere in the brain or the body. The applications of inhibitory neurotransmission range from addressing excessive neuronal excitation—like seizures—to supporting sleep. Other conditions, such as Parkinson’s disease, neuralgia, and autism, might also be addressed by the attenuation of excessive neuronal activation.
However, excessive GABA activity can be problematic. Other substances that promote secretion of GABA systemically, like alcoholic beverages, have a side effect profile that is nearly identical to GABA. These side effects include slower cognition, a reduced level of consciousness, sleepiness, slack muscle tone, poor motor coordination, and lowered social inhibitions. Significantly, there is no way to avoid these side effects because they result from GABA’s core function, which makes the prospect of finding the appropriate therapeutic use for a GABA supplement very difficult. In other words, GABA supplementation will cause these side effects if it makes any physiological impact whatsoever; the only question is the degree of these side effects. At the same time, there are a number of technical concerns with GABA supplements that could curtail GABA’s potential for effectively addressing symptoms.
Although side effects are a significant concern for many individuals, GABA supplements also suffer from issues independent of their side effect profile, the most significant of which is GABA’s general lack of bioavailability. In other words, when an individual takes a GABA supplement, only a small portion of the GABA supplement is ready for their body to use. This is because GABA cannot cross the blood-brain-barrier (BBB) in sufficient quantities under normal physiological conditions, which means that it cannot reach the central nervous system unless the supplement is formulated to optimize bioavailability. Presently, prescription pharmaceutical drugs, like Gabapentin, are the only GABA formulations confirmed to reliably cross the BBB in significant concentrations. This is in part because formulating supplements to cross the BBB is expensive, leading many manufacturers to neglect this critical project. As a result, most of the GABA content from these supplements ends up digested by the stomach and rendered useless, with the remainder used by the digestive tract.
Although GABA in the digestive tract is biologically active and available, it does not cause systemic central nervous system inhibition. This means that a person taking a GABA supplement for a seizure disorder is less likely to find it effective than someone taking a GABA supplement for an inflammatory bowel disease. This is because GABA in the digestive tract does operate via the gut-brain axis.
The gut-brain axis includes the vagus nerve, which sends signals regarding the comfort and digestive status of the gut to the brain, among many other functions. If there is an abundance of stimulation of the vagus nerve, then it can result in anxiety and subsequent depression in the central nervous system, although the inverse is not necessarily true; heavy inhibition of the vagus nerve’s transmissions does not heavily inhibit the central nervous system uniformly. However, it can have inhibitory effects in other areas the vagus nerve passes through, like the heart. In fact, stimulation of the vagus nerve is often utilized therapeutically to reduce the heart rate and normalize its pattern of beating. The inhibition of the vagus nerve can thus cause increased heart rate and anxiety—the opposite of what most individuals desiring the effects of GABA would want. As a result, it’s possible that GABA supplementation could be dangerously excitatory for individuals with heart issues.
GABA supplements can also cause issues in unlikely places. For example, GABA acts on the immune cells of the gut in an inhibitory fashion and that inhibition can be excessive. Excessive inhibition of the immune cells in the gut results in weakening the adaptive immune system’s ability to respond to threats. In the context of the gut, the adaptive immune system constantly faces these threats as a result of the microbes incorporated into stool matter. Although there is no research definitively linking GABA supplementation to stool-related gut infections, individuals with a weakened immune system should proceed with caution.
Although the possibilities of an abnormally fast heart rate and a weakened immune system initiated by GABA supplementation have not been confirmed by research, this does raise another important issue: GABA supplements have not been researched sufficiently to build a clinically valid side effect profile, nor have a sufficient number of individuals used GABA supplements to build an anecdotal side effect profile. In fact, there are very few systematic investigations into the effectiveness of GABA supplements and even fewer consistent clinical trials that would have tabulated side effects in a rigorous way. Patient reports are sparse and inconsistent. This means the side effects of GABA supplements might exceed side effects that are hypothesized or be entirely different from what researchers have speculated. For individuals who would choose to be conservative with their health, GABA supplements might be too unproven to experiment with.
Furthermore, GABA supplements are highly non-specific in their effects even if they do make it into the brain. GABA is an inhibitory neurotransmitter in every context. While this makes it well-suited to reduce problems of excessive excitation like seizures, it’s likewise poorly suited for more subtle applications like addressing the behavioral symptoms of autism. This is because, in cases of disorders that are more complicated than uniformly excessive neuronal excitation, GABA supplements have the potential to exacerbate the problem. This is especially true for disorders that contain elements of both over-excitability and under-excitability, such as attention deficit hyperactivity disorder (ADHD); GABA supplements cannot guarantee the GABA molecules will be trafficked only to the anatomical structures where additional inhibition is needed, with side effects of systemic inhibition a likely result.
Given the information that is currently known (and that which remains unknown), the research community has not yet formed a consensus on the merits or risks of GABA supplementation. As stated in the abstract of a recent review on the effects of GABA supplements, “There is some evidence in favor of a calming effect of GABA food supplements, but most of this evidence was reported by researchers with a potential conflict of interest.” Likewise, researchers with potential conflicts of interest have not reported on the side effect profile of their company’s GABA supplements. These gaps in the independent body of research might be addressed with time. For now, however, it is safe to say that because GABA is a biologically active molecule in every tissue that it contacts, there will be some sort of side effect from supplementation—although the nature of those side effects remains unclear.
Depending on the intended purpose, butyric acid can be a suitable alternative to a GABA supplement for individuals with gastrointestinal and neurological health concerns. Similar to GABA, butyric acid is a physiological molecule the body creates in large quantities to serve a variety of purposes. Like GABA, butyric acid behaves as a neurotransmitter when it is present in the central nervous system. However, in contrast to GABA, butyric acid is primarily confined to the gut, where it acts as a nutrient source for the microbiome and behaves as a regulator of immune cells and genes that code for oxidative stress, with neurotransmitter activity occurring as a tertiary function.* And although butyric acid’s effects in the central nervous system are still under active investigation, it appears to lack the uniformly inhibitory effects of GABA. Instead, butyric acid behaves as a modulator of activity, preventing conditions of over- or under-excitability.*
Additionally, increasing the brain’s ability to compensate for oxidative stress means that butyric acid might also have broad applicability to other conditions, like Parkinson’s or Alzheimer’s disease.* These conditions have very high levels of neural oxidative stress, which causes an unbalanced inflammatory response. Although the link between neural inflammatory response and loss of function is complex, researchers agree that a balanced inflammatory response in the brain is generally the preferable condition. Sophisticated butyric acid supplements currently bring the prospect of helping to maintain a balanced inflammatory response to these patient populations,* with more applications being currently explored by research.
These multiple functions of butyric acid have a broad range of potential health implications. For example, with a healthy microbiome, researchers hypothesize that there will be less activation of the gut-brain axis, which would contribute to maintaining mental health.* For example, in autistic individuals, attenuated gut-brain axis activation and reduced neural oxidative stress could address a broad range of characteristic symptoms, including providing a more stable behavioral baseline.* For individuals with inflammatory bowel disease, maintaining the gut’s normal inflammatory response might reduce the frequency and severity of flare-ups, and a healthy microbiome could mean fewer symptoms owing to butyric acid’s support of gut motility.* Meanwhile, increasing the brain’s ability to compensate for oxidative stress means that butyric acid might also have broad applicability to providing nutritional support to other neurological conditions, like Parkinson’s or Alzheimer’s disease, which are associated with high levels of neural oxidative stress and, thus, the likelihood of an unbalanced inflammatory response.*
Significantly, the side effect profile of butyric acid is benign, with users primarily reporting minor stomach discomfort.* Many users find that butyric acid supplementation reduces their levels of gastrointestinal discomfort, such as constipation.* Large clinical trials documenting butyric acid’s efficacy in a handful of health conditions are forthcoming—another notable difference between it and GABA supplements. Importantly, butyric acid does not prevent the immune cells of the gut from responding to threats like GABA supplements might, because there is a finite amount of inhibition that butyric acid can cause in the immune cells.* Significantly, sophisticated supplements designed to optimize butyric acid’s bioavailability are now entering the market, allowing users to experience its full benefits.
Individuals who are willing to experiment with GABA supplements likely are seeking symptom relief they can’t find elsewhere, and accepting the unknowns of GABA supplementation could be worth the potential benefits. However, for those who prefer a more characterized alternative, butyric acid is likely the better choice to address these same symptoms. Like GABA supplementation, butyric acid’s history of use is in its infancy, but forthcoming clinical trials will help clinicians and patients understand the nature of these two therapies and shed light on their strengths and weaknesses. In the meantime, can consider incorporating a butyric acid supplement into their management plans in a safe and highly tolerable manner.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your neurological health.*
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Watanabe M, Maemura K, Kanbara K, et al. 2002. Int Rev Cytol. 213:1-47.
Updated on April 13, 2023
Article Summary
The dreaded tremors and degenerative brain dysfunction of Parkinson’s disease are notoriously emotionally painful for individuals and caretakers alike. Clinically, Parkinson’s disease is marked by highly variable symptoms, like difficulties with voluntary motion and impaired executive functioning, which increase with intensity as the disease progresses.
But individuals might be suffering from Parkinson’s-related depression, anxiety, or cognitive dysfunction for years before a diagnosis is made, significantly diminishing their quality of life before they are even aware of their condition. After being diagnosed, although individuals have an explanation for their symptoms, they often struggle with difficult side effects of treatment that only delays the inevitable; there is no cure for Parkinson’s.
Due to the significant suffering Parkinson’s brings and the lack of curative treatment options, there is widespread interest among practitioners and their patients in combating the condition. At present, there are no pharmaceutical interventions that purport to prevent Parkinson’s.
On the other hand, several nutritional supplements have recently been investigated as potential options for providing nutritional support for Parkinson’s disease. Although these supplements are still being researched, their early promise in helping individuals maintain their health and well-being is undeniable. Individuals who want to take the initiative in responding to Parkinson’s disease rather than reacting to it after it has become established should follow the progress of these supplements closely and understand how they might be beneficial.
Parkinson’s disease is extraordinarily complex in terms of its pathophysiology and also its treatment strategies. This complexity stems from the disease’s protracted progression. The symptoms of Parkinson’s disease have a gradual onset because Parkinson’s slowly damages the individual’s brain, starting with the dopaminergic motor neurons. As dopaminergic motor neurons begin dying, similarly afflicted neighboring neurons are unable to compensate for the absence of the dead cells and symptoms increase in severity.
As the disease progresses, individuals lose voluntary control over many of their body’s movements; voluntary motion becomes more difficult while involuntary tremors and stereotyped motions become harder for the individual to suppress. At the same time, the dearth of dopaminergic neurons can produce significant psychological and cognitive effects, including depression, executive dysfunction, anxiety, apathy, and dementia.
Deaths caused solely by Parkinson’s are rare. Instead, Parkinson’s tends to increase the risk of other health problems, often as the result of diminished motor control. For example, individuals with Parkinson’s are highly vulnerable to falls and often struggle with basic self-care. Nonetheless, with early detection and intervention using the current standard of treatment, individuals who develop Parkinson’s can expect approximately 15 years between initial diagnosis and the need for constant medical aid.
Individuals who don’t receive treatment will experience more rapid progression of the disease, although the speed will vary substantially from individual to individual. Significantly, while Parkinson’s progression can be drastically slowed with the right treatment regimen, no current treatment can cause progression to entirely stop. This underlines the need for adjunctive therapies that help preserve motor neurons.
The difficulty of treating Parkinson’s disease stems not only from the lack of curative therapies, but the fact that several of the most common pharmacological interventions cause lasting disability and an extensive number of intense side effects when they are used over the course of 10 or 15 years.
These side effects range in severity. For example, artificially prompting dopamine secretion to replace the natural dopamine secretion which is lost when dopaminergic neurons die due to Parkinson’s is effective at allaying symptoms for a time, which is why dopamine precursors or dopamine agonists are typically used after initial diagnosis.
After an extended course of these medications, however, the brain adapts to the artificially increased concentrations of dopamine, diminishing their responsiveness. At the same time, the brain has fewer dopaminergic neurons because they have continued to die over the course of treatment. This combination causes Parkinson’s symptoms to worsen and typically heralds the introduction of the next line of treatment.
The second line of treatment is anticholinergic drugs, which antagonize the acetylcholine receptors on neurons, preventing acetylcholine from interacting with the cell. When acetylcholine can’t interact with neurons, the neurons don’t transmit their acetylcholine-prompted signals as frequently or as strongly. This is important because cholinergic neurotransmission tends to also actuate dopaminergic neurotransmission.
In other words, the second line of treatment tries to dampen neurological processes that utilize dopaminergic neurons indirectly. In contrast to the first-line drugs, anticholinergics carry a brutal side effect profile, which includes confusion, hallucination, blurry vision, decreased kidney function, dry mouth, and delirium. As a result, these drugs often incur a large penalty on the individual’s quality of life.
The difficult conditions of treatment for Parkinson’s, in addition to the disease itself, underline the necessity of effective support, but at present, there are only a very limited number of strategies. Studies indicate that getting plentiful exercise during the peak risk years and drinking coffee appear to be associated with a lower risk of developing Parkinson’s.
These methods are not universally effective, though, and data regarding their efficacy is sparse. Thus, for individuals who wish to try to combat Parkinson’s or its progression, the current standard of treatment is woefully insufficient. Thanks to an emerging body of research, however, several supplements to provide nutritional support for Parkinson’s patients might soon offer critical new options.
Addressing Parkinson’s requires novel therapeutic approaches to the disease’s mechanism; in particular, supporting the preservation of dopaminergic motor neurons and dopaminergic activity. The natural substance curcumin, a biologically active compound isolated from turmeric, is one such promising avenue. In recent years, curcumin has been the focus of scientific inquiry owing to its confirmed diverse impact on cells, including its powerful antioxidant activity.* It is this antioxidant activity that might enable curcumin to respond to the rate of dopaminergic neuron death caused by Parkinson’s.*
Neurons are highly sensitive to environmental changes and the body produces many different compounds designed to keep their environment stable. However, a multitude of factors constantly disrupts this stability. One of the most common threats to homeostasis is reactive oxygen species (ROS), the remnants of metabolic reactions that remain circulating within the cell.
As their name implies, ROS react with cellular machinery like enzymes and DNA, preventing those pieces of machinery from doing their job with normal efficiency and causing cellular damage, otherwise known as oxidative stress, as a result.
Researchers believe that high levels of oxidative stress exist in the brains of individuals with Parkinson’s. The neurological level of oxidative stress is considered one of the major contributors to dopaminergic cell death and, thus, the disease’s progression. As such, nutritionally supportive antioxidants like curcumin are promising because they can potentially help healthy cells stay healthy by managing some of the burden of defending against oxidative stress.*
Spending less energy on defending against oxidative stress might also benefit cells suffering from Parkinsonian-related degeneration.* Research into curcumin for the nutritional support of Parkinson’s is still in its nascent stages, but there is early evidence that it might offer these protective benefits.*
In a 2012 experiment conducted in rats, a group of researchers at the Medical College of Qingdao University in China found that a curcumin-based supplement could partially restore neuronal dopamine concentrations after an artificial induction of Parkinsonian symptoms.
The researchers used three groups of rats: one group of rats was set aside as a control, and the other two groups were given 6-OHDA to trigger the development of irreversible Parkinson’s symptoms. 6-OHDA causes damage to dopaminergic motor neurons by creating extreme levels of oxidative stress. Then, one of the groups with Parkinson’s symptoms was given a curcumin-based supplement for 24 days. Measuring the concentrations of dopamine in the rat brains, the researchers found that the rats given the curcumin supplement had an average of one nanogram of dopamine per gram of tissue in their brains. The rats with Parkinson’s that hadn’t received the supplement exhibited an average of zero detectable dopamine. In comparison, healthy control rats had around six nanograms of dopamine per gram of tissue.
In a clinical setting, the difference between one nanogram of dopamine per gram of tissue and none is significant. Even when dopamine concentrations are very low, neurons can adapt to the low level by down-regulating their receptors and can continue to perform dopaminergic neurotransmission, albeit at a reduced rate. If dopamine is entirely absent, then there is no way for neurons to adapt and maintain a semblance of their prior pattern of neurotransmission.
These results indicate that curcumin might be an effective adjunct therapy for providing nutritional support in Parkinson’s disease.*
Curcumin supplements are already widely available to purchase. Most individuals who take a curcumin supplement find that the supplement is easy to tolerate, with transient nausea being the most common side effect reported.
Aside from curcumin, there is another chemical that might also provide nutritional support for Parkinson’s: the antioxidant molecule glutathione. Glutathione (GSH) is naturally produced by cells to help control their level of oxidative stress. Much like with curcumin, glutathione can be thought of as a molecular sponge that absorbs ROS so it can be discharged safely in a controlled environment and thus not cause damage. Because glutathione is already a tool the body uses to manage oxidative stress damage, it has significant potential for providing nutritional support in the context of Parkinson’s.*
In a healthy body, cells constantly recycle glutathione such that there is always some glutathione on hand that is ready to accept ROS. However, in Parkinson’s this might not be the case. A very early (1992) post-mortem study into the role of glutathione in individuals with Parkinson’s found significant differences between Parkinsonian pathology and healthy controls.
The healthy controls had between 92.8 and 12.6 micrograms of glutathione for every gram of brain tissue in the dopaminergic neuronal tracts the researchers examined. Furthermore, only two percent of the detected glutathione molecules were carrying ROS. In contrast, those with Parkinson’s had between 49.3 and 4.6 micrograms of glutathione per gram of tissue, and between 50-to-100-percent of glutathione molecules were laden with ROS.
This finding most likely means that individuals with Parkinson’s exhibit high levels of oxidative stress in their brains. Additionally, the prevalence of ROS-laden glutathione molecules in those with Parkinson’s indicates their neurons might have been incapable of clearing all of the ROS
Although the cause of Parkinson’s and the impact of oxidative stress remains unclear, there is evidence that suggests glutathione might play a role. Significantly, researchers have found that a drop in neuronal glutathione concentrations is an early biochemical sign of Parkinson’s and that glutathione depletion can be partially remedied pharmacologically.
At present, scientists believe that individuals who exhibit naturally high levels of glutathione have vastly improved neuronal survival.*
Clinical data on participants using glutathione supplements for the nutritional support of Parkinson’s remains lacking, but it is an area of active investigation. Preliminary clinical trials have shown that glutathione is well-tolerated in Parkinson’s patients, laying the groundwork for ongoing investigations regarding its efficacy. Those seeking nutritional support for Parkinson’s can do so with the help of a high-quality glutathione supplement.*
Currently available data suggests that glutathione and curcumin are both promising nutritional supplements for individuals interested in optimizing their health, particularly when used in concert. For example, researchers have shown in vitro that curcumin can work in conjunction with glutathione such that neurons are doubly protected.
Curcumin appears to induce glutathione localization, with research indicating that glutathione levels were 64 percent higher in cells that received curcumin than those which did not. Indeed, while human clinical trials of both compounds are still forthcoming, the early evidence indicates that future use will likely operate in combinations to maximize their effectiveness.
If consumers are interested in using curcumin and glutathione supplements to provide nutritional support in Parkinson’s, it is most likely safe to do so.* There is no data that indicates these two supplements are unsafe when used in conjunction than they are individually or that either of the supplements are unsafe when used as indicated.
Both supplements should be safe to use to provide nutritional support in conjunction with the first and second lines of pharmacological treatments for Parkinson’s, although individuals should consult with their clinicians to be certain that no interactions would apply. Notably, it’s very difficult to assess the efficacy of such supportive regimens. Individuals taking curcumin or glutathione or both should remain vigilant regarding changes in their health, and remain in consultation with their physician to achieve the best possible outcome.
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 and healthy aging.*
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Updated on April 10, 2023
Article Summary
Over the last few years, glutathione supplements have been appearing on store shelves and health food websites. So what are the benefits of glutathione supplementation? Does it really help? Whenever a hot new supplement like glutathione hits the market, it is important to consider the research before jumping on the bandwagon.
An abundance of in vitro research supports the use of glutathione. Although there is still a relative lack of large-scale clinical studies on the benefits of glutathione for specific health problems, early research suggests that glutathione might provide nutritional support for a wide variety of health conditions, from neurological health to skin health.*
Glutathione is a low-molecular-weight, water-soluble tripeptide consisting of three amino acids: glycine, cysteine, and glutamic acid. It exists in two forms: the reduced form (GSH) and the oxidized form (GSSG). It is the ratio between these two forms that determines its capacity for antioxidation.
Glutathione is one of the most abundant compounds in cells. Under normal conditions, the concentration of glutathione is comparable to that of glucose, potassium, and cholesterol, a fact that highlights its importance in supporting healthy cell function.*
In vitro research on the benefits of glutathione indicates that it plays a variety of beneficial roles in cellular function, primarily through its activities as an antioxidant.* Glutathione neutralizes several different types of free radicals that can cause cellular and tissue damage, including singlet oxygen radicals, hydroxyl radicals, and superoxide radicals.* Glutathione also plays a detoxifying role by neutralizing the free radicals that are produced during the first phase of liver metabolism.*
These antioxidant activities do not just occur in the cytosol; they are also crucial to the functioning of mitochondria (the organelles involved primarily in cell energy generation) and the protection of mitochondrial DNA from damage.* This beneficial connection between glutathione and mitochondrial function is significant due to the role of the mitochondria in cellular longevity and metabolism—two crucial aspects of health maintenance.
The antioxidant activities of glutathione go beyond its direct function as an antioxidant. Glutathione also serves as an essential cofactor for several antioxidant enzymes, which means that its presence is necessary for these enzymes to carry out their own antioxidant activities.* Additionally, glutathione is a necessary component of the regeneration pathways for two other major antioxidants: ascorbate (vitamin C) and tocopherol (vitamin A).*
Glutathione is also involved in detoxification processes.* For instance, in the second phase of liver metabolism, glutathione is required for the conjugation of toxic intermediates, rendering them sufficiently water-soluble for excretion by the kidneys.* Another detoxifying activity of glutathione is the removal of mercury from cells throughout the body, including neurons in the brain.* In vitro studies also suggest that glutathione aids in detoxification processes after overexposure to toxic chemicals like paraquat, iron, and hydrogen peroxide.*
The Effectiveness of Glutathione Supplementation
The potential benefits of glutathione are impressive. As with any compound, patients and practitioners must recognize that a supplement might not necessarily have clinically relevant benefits. However, the existing evidence suggests that taking glutathione in supplemental form can have a positive effect on overall patient health.*
In 2015, researchers from Penn State University conducted a randomized, double-blinded, placebo-controlled trial to determine whether oral glutathione supplementation increased glutathione stores in participants’ cells. The sample included 54 healthy adults who received either a placebo, a daily supplement of 250 mg of glutathione, or a daily supplement of 1,000 mg of glutathione.
The researchers found statistically significant increases in glutathione stores in both glutathione treatment groups after the 6-month study period. This study was the first-ever demonstration that daily supplementation can lead to higher stores of glutathione in the body.*
Importantly, the researchers also observed multiple improvements in immune function, including a twofold increase in natural killer cell cytotoxicity in patients who took the higher dose of glutathione.* This indicates that supplementation can have clinically significant beneficial effects that directly impact patient health outcomes.*
When it comes to the effectiveness of glutathione supplementation, its naturally low bioavailability is an important concern for both researchers and supplement developers who are interested in the potential health benefits of glutathione supplementation. With recent improvements in delivery technology, researchers have successfully developed innovative systems that enhance the absorption of oral glutathione supplements. By choosing a supplement optimized for bioavailability, patients can maximize the impact of glutathione supplementation.
Thanks to the well-documented antioxidant, detoxifying, and other cell regulatory activities of glutathione, there is growing interest in exploring its impact on specific health conditions and general wellness. Here are several of the most promising findings:
As researchers continue to call for more comprehensive clinical trials on the potential health benefits of glutathione, practitioners and their patients will more fully understand how to harness the wide-ranging activities of this unique compound to support health. Even now, it is possible to take advantage of the existing research and experience the benefits of glutathione supplementation today.
The power of Tesseract supplements lies in the proprietary science of proven nutrients and unrivaled smart delivery, making them the most effective for supporting healthy aging and immune health.*
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Updated on April 7, 2023
Article Summary
Addressing autism is challenging owing to the disease’s diverse symptoms, uncertain causes, and disabling effects. Autistic individuals are commonly affected by a broad array of sensory issues, sociobehavioral difficulties, and gastrointestinal malfunction, all of which can severely diminish quality of life. Although some therapies are helpful, patients often still struggle to reach neurotypical levels of daily functioning. The lack of curative therapies for autism often drives caregivers and the autistic individual to experiment with a plethora of less than satisfactory effective therapies. For a growing number of families, one of those therapies is probiotics.
Probiotics are living bacterial cultures that are intended for oral consumption to confer a number of health benefits. Historically, probiotics have been attributed to long lifespans and good health in certain rural communities with diets that emphasize pickled foods; pickled foods like sauerkraut and kimchi are rich in the same beneficial microbiota that modern probiotic supplements are made from.
In current times, probiotics are being investigated as an autism-targeted therapy that could address behavioral and gastrointestinal symptoms by altering the gut microbiome. The rationale behind using probiotics to address autism symptoms is that rectifying the dysfunctional microbiomes of autistic individuals might modulate complex autistic symptoms via the gut-brain axis. Although it is unknown whether this rationale is clinically sound, it is rapidly gaining popularity within the scientific community, and researchers are currently working to gain greater clarity into the potential of gut microbiome manipulation.
At present, the U.S. Food and Drug Administration has not approved any probiotic supplement to treat any disease. Nonetheless, many autism patients use probiotics due to their purported benefits. To determine if this is the most appropriate approach, it’s critical for caregivers of autistic individuals to understand the potential side effects of probiotics and consider whether there might be superior alternatives.
Recent reviews of probiotic side effects conclude that most individuals, autistic or not, tolerate probiotics extremely well. Mild and transient gastrointestinal disturbances, like nausea, bloating, gas, or diarrhea, can occur but are uncommon and appear to be innocuous. Likewise, these side effects typically are not persistent if a person experiences them at some point. In autistic individuals, however, there might be a greater chance of experiencing these side effects. This is because autistic individuals tend to experience gastrointestinal abnormalities at a higher rate than other people because of genetic and microbiotal factors, so caution is warranted before starting a probiotic therapy course that could aggravate an aggrieved stomach.
According to some reports, there might also be behavioral consequences to probiotic therapy. Anecdotal evidence suggests that autistic individuals are at a risk of experiencing insomnia and aggression resulting from probiotic supplementation. Likewise, sparse and anecdotal reports document behavioral regression after supplementation with probiotics. However, these behavioral side effects appear to be rare, and the gastrointestinal side effects tend to recede with repeated exposure. Gradually phasing in increasing quantities of probiotics might also help to avoid side effects.
Due to the mild nature of the scientifically confirmed side effects of probiotics, many individuals experiment with probiotics on their own without concern. In the overwhelming majority of cases, the biggest risk involved in using a probiotic supplement is that it might not taste very good. To solve this, commercial probiotic products can be easily mixed into other foods or administered as a flavored liquid formulation, making probiotic use more appealing. In the event of food refusal, there are also several probiotics that can be administered enterally, although it is not the preferred route.
The vast majority of individuals do not experience any side effects from using probiotics, whether or not they have autism. There are, however, conditions under which consuming probiotics can have serious side effects. Individuals who are immunocompromised, catheterized, or recovering from invasive surgery, for example, might want to avoid probiotics. The side effects of probiotics for these individuals can range from extreme inflammatory reactions to sepsis, both of which can be life-threatening conditions.
There is some evidence to suggest that individuals in a medically compromised state are at risk of developing complications if they consume probiotics. One study, for example, found that patients who were administered probiotics while experiencing acute pancreatitis were 10 percent more likely to die than those who were administered a placebo. However, this study had no reference to the mechanism by which the probiotics might have caused the increased mortality. Additionally, the evidence regarding probiotic side effects in severe cases is somewhat ambiguous; several pieces of literature claim that probiotics are associated with improved outcomes in the immunocompromised or recovering patient populations, whereas several others have documented the negative side effects. The medical consensus on administering probiotics to weakened patients is still forming, and firm conclusions are impossible to make. As such, practitioners and their patients should proceed with caution. In the case of catheterized patients, probiotics might increase the risk of infection, and other invasive medical devices like insulin pumps and colostomy bags likely carry the same risks. Out of an abundance of caution, patients in these conditions might want to avoid taking probiotics.
There is no evidence to suggest that autistic individuals are at a higher or lower risk of experiencing negative side effects than others either while healthy or in a weakened state. However, an autism patient who is taking a probiotic supplement might need to reconsider their probiotic use should they fall into one of the potential risk groups above.
As discussed, the typical side effect profile of probiotics is very mild, and the more serious side effects appear to be confined to very narrow niches, suggesting that probiotics are generally safe and well-tolerated. But it is important to realize that a comprehensive scientific consensus on probiotic side effects remains elusive.
Several side effects of probiotics are theorized to exist but are not yet confirmed, including runaway immune activation, maladaptive bacterial gene transfer, and lactic acidosis. The implications of these phenomena vary widely; runaway immune activation could potentially be fatal, whereas lactic acidosis would merely be uncomfortable. However, as autistic individuals tend to have sensory integration issues that make being overstimulated extremely unpleasant, lactic acidosis can have a particularly significant impact. Meanwhile, researchers have minimal understanding of what problems patients would face in the event of widespread maladaptive bacterial gene transfer, given that no mechanism has been proposed nor instances of it observed.
It’s valuable to remember that even if these side effects are confirmed to occur only in certain conditions, probiotic supplementation would still remain very safe for the vast majority. At present, there is no evidence to suggest runaway immune activation or bacterial gene transfer has genuinely occurred in any individuals or group consuming probiotics. There are, however, a small number of reports on individual patients with short bowel syndrome who experienced lactic acidosis as a result of probiotic consumption. Although the patients experienced an array of neurological symptoms ranging from agitation to confusion, all improved immediately on cessation of probiotic use. These results will need to be validated in larger clinical trials before clinical advisories against using probiotics can be made with confidence. Other therapeutic options with a similar level of evidentiary backing could be more suitable for patients in the meantime.
For individuals who prefer an alternative to probiotics—whether due to efficacy concerns, tolerability, or potential side effects—butyric acid is a good place to begin. Butyric acid is a short-chain fatty acid produced by the gut and is responsible for regulating the gastrointestinal tract and the immune system, which could have significant implications for behavioral health due to the activities of the gut-brain axis.* Notably, this vital fatty acid has been shown to be deficient in autistic individuals, potentially contributing to autism presentation, including both gastrointestinal and behavioral symptoms. By maintaining a healthy level of butyric acid and supporting the health of the gut microbiome via oral supplementation, it could be possible to beneficially impact these symptoms and enhance overall quality of life.*
Unlike probiotics, butyric acid’s side effect profile is not linked to an increased risk of infection or serious complications in immunocompromised individuals. Anyone with an abnormal intestinal length should consult with their doctor before trying butyric acid, however. For most people, supplementation with butyric acid is likely to have fewer and milder side effects than probiotics, while delivering comparable or superior benefits via the gut-brain axis.
This scenario might change depending on the latest research in probiotics, however; a large clinical trial investigating probiotic therapies for autism is underway. The results of this study will be among the most detailed yet published and will describe the physiological and behavioral changes attributable to several popular probiotic supplements. Side effects will be documented alongside the physiological states which the probiotics caused to generate those effects. Caregivers might want to follow up on the trial to see whether probiotic supplementation is definitively linked to side effects that are specific to its use in autistic individuals.
In the meantime, patients, caregivers, and practitioners evaluating probiotics or butyric should be emboldened by their benign side effect profiles and potential to improve the lives of autistic individuals. When integrated into a comprehensive management plan, these supplements could play a valuable role in providing nutritional support for addressing symptoms, bringing relief and comfort to patients and their families.*
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your gastrointestinal health.*
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Updated on April 10, 2023
Article Summary
As millions of individuals who suffer from it know firsthand, anxiety presents as conditions of unfulfilled opportunities and painful psychological experiences. Although there are cognitive and pharmaceutical interventions that provide symptom relief for many, efficacy is not universal and tolerability can be a hindrance to adherence even when symptoms are alleviated. As such, many patients continue to seek alternatives to standard therapies. In light of a growing body of evidence, physicians and their patients are now increasingly finding success with promising new approach: cannabidiol therapy.
Cannabidiol (CBD) is derived from cannabis, and, like other cannabinoid class chemicals, such as tetrahydrocannabinol (THC), behaves as a potent neurotransmitter in the brain with both excitatory and inhibitory capabilities. In the case of THC, the consequent neurotransmission can cause psychoactive effects and, as a result, THC is most commonly used recreationally.
Some individuals are hesitant to consider CBD as a legitimate anxiety aid due to its association with illicit cannabis use and the mistaken assumption they will experience psychoactive effects, such as those produced by THC. But, although CBD is a major constituent of cannabis, it is widely recognized to not cause psychoactive effects and is therefore of little recreational value.
Furthermore, CBD causes none of the side effects traditionally associated with cannabis use, such as exaggerated appetite, hypersomnia, or spiraling paranoia. On the contrary, CBD’s side effect profile, while mild, includes symptoms like decreased appetite and insomnia. More serious side effects of recreational cannabis use—such as its potential role in the onset of schizophrenia—are also notably absent from tests regarding CBD and anxiety when used therapeutically.
Due largely to its anecdotally-supported efficacy and high tolerability, individuals are already turning to CBD—via their doctors or otherwise—to cope with anxiety. Indeed, a survey of more than 2,400 CBD users conducted in 2017 found that approximately 30 percent of respondents were leveraging the link between CBD and anxiety. Significantly, the survey also found that respondents were using CBD to manage multiple symptoms at once; on average, respondents addressed 2.67 different symptoms with CBD. And the results suggest CBD is highly effective; 36 percent of the respondents reported that CBD manages their condition “very well by itself,” whereas only 4.3 percent reported that CBD was insufficient to manage their symptoms on its own and that additional medications were required.
For individuals desiring to supplement their current anti-anxiety therapies, CBD use in anxiety is a promising new field that could open new avenues for symptom management.
The basis for linking CBD and anxiety is well-established within the scientific literature, despite lagging public perceptions regarding cannabinoid therapeutics. Of particular interest is a research review published in the August 2018 issue of Epidemiology and Psychiatric Sciences, which supports CBD as an effective therapy for anxiety.
Authored by Drs Mandolini and Lazzaretti of the University of Milan’s Department of Neurosciences and Mental Health, the review goes beyond confirming the evidence of efficacy and contends that physicians should begin implementing CBD therapy into their clinical practices sooner rather than later.
To make this point, the authors draw on a plethora of research findings in clinical trials, animal studies, and in vitro experiments published over decades of scientific exploration of CBD. According to the paper, the synthesis of the scientific literature strongly supports using CBD to manage certain forms of anxiety.
Although CBD is effective for managing many types of anxiety, the review cites several studies indicating that CBD might be exceptionally effective at helping with social anxiety via its vasodilatory effect in certain brain regions. By selectively increasing the blood flow to structures of the brain responsible for processing fear and anxiety emotions, like the amygdala, CBD is hypothesized to increase their function and consequently manage anxiety.
CBD might also slightly reduce blood flow in areas responsible for recalling traumatic memories. Mandolini believes this is made possible by CBD’s ability to bind to the 5HT1A serotonin receptor in the brain. The reduction in anxiety caused by CBD therapy supports the cognitive processes that anxiety typically hampers; individuals with this type of anxiety often have racing thoughts, subjective blankness of thought, and difficulty maintaining attention on external stimuli.
These cognitive impairments can significantly interfere with functionality, diminishing quality of life and potentially increasing symptoms of comorbid mood disorders. As such, addressing the cognitive effects of anxiety is necessary for many patients to recover. Unfortunately, anxiety therapies like benzodiazepines might actively weaken or slow cognitive processes owing to their inhibitory effects.
In one of the studies cited by Mandolini on CBD and anxiety, doses of 600 mg of CBD were found to manage or nearly eliminate the cognitive impairment associated with public speaking anxiety, resulting in cognitive function equivalent to healthy controls. In the study, a group of subjects who experienced social anxiety when performing public speaking was split into two groups. One group was administered CBD therapy, whereas the other received a placebo.
Following therapy administration, the subjects performed a public speaking simulation as their anxiety levels and cognitive functioning were measured before, during, and after the simulation. In terms of the overall reduction of anxiety levels in comparison to healthy controls, subjects who took CBD scored nearly 50 percent lower on the Changes In Visual Analogue Mood Scale (VAMS) anxiety assessment instrument than the group with anxiety who received placebo. The VAMS measures both the intensity of the subjective experience of anxiety and the cognitive impairment that accompanies high levels of anxiety. Likewise, the general discomfort score of subjects who took CBD was 10 percent lower than in the placebo group.
Significantly, the CBD therapy group returned to normal levels of arousal as rapidly as healthy controls, while the placebo control group did not return to the lower level of arousal experienced by the other groups in the time points measured by the researchers.
The authors point out this unique therapeutic effect—causing patients to recover more quickly from episodes that cause anxiety even in healthy people—has a plethora of applications for anxiety; post-stimulus anxiety is a major detractor of patient quality of life and is a primary feature in post-traumatic stress disorder. Furthermore, pre-stimulus anxiety—like the anxiety caused by drug withdrawal—might also be effectively managed by CBD.
Studies consistently show the effects of CBD can be extraordinary for individuals who struggle with anxiety. So how does CBD generate such dramatic effects in the brain? Unlike other neurotransmitters responsible for regulating arousal in the brain like GABA (gamma-aminobutyric acid), cannabidiol exhibits both excitatory and inhibitory effects on the neurons it binds to.
The downstream impact of this mixed effect profile is a subtle inhibition of anxiety without the psychoactive effects of cannabis consumption or other anxiolytics like benzodiazepines. Likewise, CBD isn’t fatal in overdoses, meaning that CBD and anxiety might be a safer pairing than addressing anxiety with benzodiazepines, which can cause death via respiratory depression.
Importantly, CBD also lacks the addictive potential of benzodiazepines. Although benzodiazepines present a significant risk for abuse and addiction, CBD has no recognized recreational features nor is it physically habit-forming. This is a critical point because many physicians hesitate to prescribe benzodiazepines to patients and insist on short-term therapy to reduce the possibility of abuse and addiction, which means benzodiazepines can’t be used as a long-term solution for anxiety symptoms.
When benzodiazepines are used on a long-term basis, tolerance and physical dependence can build and patients might experience uncomfortable withdrawal symptoms, including rebound anxiety, when they try to reduce their dose or discontinue the drug. In some cases, withdrawal symptoms are severe and can include seizures, dysphoria, psychosis, and mania. CBD has no such shortcomings.
The side effects of benzodiazepines are also formidable in comparison to CBD. When individuals take benzodiazepines to address their anxiety, they often become transiently cognitively impaired while under the effects of the drug, potentially interfering with social and professional functioning. Users are advised to avoid driving and might find their ability to sustain attention is impaired, along with reaction speed.
Additionally, reduced inhibitions can cause someone taking benzodiazepines at therapeutic doses to engage in risky or undesirable behaviors. Because benzodiazepines also inhibit short-term memory consolidation, a person taking them might also struggle to remember their daily events. In some cases, benzodiazepines can cause depression or excessive emotional numbing, which can be particularly dangerous for those struggling with a comorbid mood disorder. CBD, on the other hand, is not associated with any of these phenomena.
Benzodiazepines aren’t the only class of anxiolytic drugs that CBD outperforms. Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed to address anxiety and used on a long-term basis. These medications, although effective for many, are known for their diverse set of side effects, which include sexual dysfunction, tremors, fatigue, and weight gain. Some individuals even experience additional anxiety when taking SSRIs and many need to try more than one SSRI before finding one to which their symptoms respond.
This often results in a lengthy process of trial and error, as the effects of the medication might not be observed for weeks. In contrast, CBD has no serum concentration build-up period beyond the initial period after dosing, nor does it have the substantial side effect profile of SSRIs. Additionally, although SSRIs are not addictive, some patients build mild physical dependency as the result of their effect on neurotransmitter behavior.
Upon terminating SSRI use, those taking them might experience SSRI discontinuation syndrome for several days or weeks, resulting in symptoms such as malaise, anxiety, nausea, and insomnia. There is no documented discontinuation syndrome associated with CBD and anxiety, nor does its short course of action give reason to suspect there is one that is yet undiscovered.
Dr. Mandolini’s review concludes by stating the present hypotheses regarding CBD’s mechanism of action should offer confidence in its potential to manage anxiety. Large randomly controlled clinical trials will soon be conducted to shed light on the details of how CBD therapy should be implemented to address symptoms. However, clinicians already have an abundance of clues from the extant literature. Likewise, their patients who need a novel anxiety aid today can try CBD therapy on their own using the information compiled by Dr. Mandolini and others. Should those individuals who become early adopters of the CBD and anxiety pairing, they might finally move beyond the limits of anxiety while avoiding the shortcomings of conventional therapies.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your neurological health.*
Bergamaschi MM, Queiroz RHC, Chagas MHN, et al. 2011. Neuropsychopharmacology. 36:1219–1226.
Corroon J, Phillips JA. 2018. Cannabis and Cannabinoid Research. 3:152–161.
Mandolini GM, Lazzaretti M, Pigoni A, et al. 2018. Epidemiology and Psychiatric Sciences. 27:327–335.
Soares VP, Campos AC. 2017. Current Neuropharmacology. 15:291–299.
Updated on April 10, 2023
Article Summary
Glutathione, a tripeptide naturally produced in the liver from three amino acids, is the body’s most essential antioxidant, and its ability to neutralize free radicals in cells and aid in detoxification processes has highlighted it as a promising therapeutic for a wide range of health conditions, including many challenging neurological conditions.* When a practitioner and a patient consider trying a new therapeutic option like glutathione, one of the first things that comes to mind is the question of potential side effects. Regardless of the purported health benefits of a therapeutic option, it might not be worth using if its side effects outweigh its benefits. In the case of glutathione IV therapy side effects, some patients worry that direct injection into the bloodstream could have an off-target impact.
So far, there is no data to indicate this is the case. However, there are lifestyle-related impacts to glutathione IV therapy that makes it less preferable for some patient populations who can benefit most from the compound, which makes it less convenient than alternatives like oral supplementation. Therefore, as supplement delivery technology continues to advance, it makes sense to consider using oral glutathione supplements alongside IV therapy.
No significant side effects of glutathione IV therapy have been reported in the available literature. Researchers first began exploring the intravenous administration of glutathione in the 1990s, and no indications of potentially adverse outcomes were observed. The only serious concern was that glutathione has a relatively short half-life in the bloodstream, which could potentially limit the duration of its efficacy.
These early results regarding glutathione safety and tolerability are supported by more recent clinical studies. For example, in a 2009 pilot evaluation of intravenous glutathione therapy for individuals with Parkinson’s disease at the University of South Florida, researchers reported that glutathione IV therapy that mildly benefited motor symptoms was “well tolerated” and posed “no safety concerns.” A 2017 case report yielded similar results. Although some researchers point out that the overall body of literature on safety is lacking, available studies indicate that with glutathione IV therapy, side effects are unlikely.
Nevertheless, when deciding whether or not to integrate glutathione IV therapy into a nutritional support strategy for a condition like Parkinson’s disease, it is important to recognize other ways that intravenous administration can impact a person’s life. Consider the fact that, in the studies that suggest IV glutathione can be a valuable therapeutic for patients with Parkinson’s disease, it has been administered at least once and sometimes twice a day. On top of the mobility challenges already facing individuals with Parkinson’s disease, the obligation to receive daily glutathione intravenously can make it even more difficult to maintain an independent lifestyle. This makes oral supplementation of glutathione an appealing option.
Similarly, although early studies suggest that glutathione administration can have benefits for autistic individuals,* IV therapy might not be the optimal solution when it comes to the recipient’s lifestyle concerns. For example, one of the most common autism symptoms is a high level of sensory sensitivity, which can make the process of intravenous administration a major challenge, especially for children. Because of the potential drawback of IV administration in these situations, clinicians and parents might want to consider oral glutathione supplement instead.
One of the primary reasons researchers began exploring glutathione IV therapy rather than oral supplementation was concern over the absorption of glutathione from the gastrointestinal (GI) tract. With early versions of supplements, glutathione was not entering the bloodstream sufficiently and being transported to the cells that needed it, such as those in the brain. However, in recent years, that obstacle has been resolved by the development of advanced delivery systems for glutathione. Thus, today’s supplement formulas can reach brain cells, and other cells outside the GI tract, so IV glutathione might not be necessary. Moreover, these new delivery systems address the issue related to glutathione’s short half-life, giving today’s advanced supplement formulas the potential to offer longer-lasting benefits for patients.
Although future studies will likely provide more conclusive data on the side effects of glutathione–whether administered intravenously or orally–today’s clinicians, patients, and parents can be relatively confident that supplemental glutathione is unlikely to lead to adverse effects. And for patient populations for whom daily IV administration is a significant lifestyle disruption, oral supplementation can be a valuable addition to an individual’s daily supplement regimen.
The power of Tesseract supplements lies in the proprietary science of proven nutrients and unrivaled smart delivery, making them the most effective for supporting immune health and hepatic health.*
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Updated on April 10, 2023
Article Summary
Although most individuals understand the link between insulin utilization and diabetes, few recognize the risks and symptoms of insulin resistance. Insulin resistance can lead to having a chronically high blood sugar level, which is a contributing factor to developing type II diabetes. Before it develops into diabetes, insulin resistance is correlated with symptoms like brain fog, confusion, dysexecutive syndrome, sleepiness, excessive hunger, thirst, and weight gain. Once insulin resistance is established, it can be hard to reverse because a variety of lifestyle habits contribute to it, such as poor diet and lack of exercise. Given that the primary therapy for insulin resistance is diet modification and exercise, compliance is often subpar, so a better solution is needed.
Unfortunately, even when an individual does make meaningful lifestyle changes, reversing their insulin resistance can be uncomfortable, and sometimes even debilitating, requiring days or weeks of feeling out-of-sorts while their cells acclimatize to normal insulin levels. Only a few pharmacological therapies for insulin resistance exist, but they suffer from weak long-term efficacy and difficult side effects, like vitamin B deficiency. As clinicians and their patients seek better approaches, a recent flurry of promising investigations into berberine would seem to indicate they might not have to look further.
Practitioners and their patients from Western countries are unlikely to be familiar with berberine and its ability to provide nutritional support for insulin resistance.* Berberine is an alkaloid compound produced by a handful of plants ranging from the barberry bush to the prickly poppy, and its alkaloid structure is partially shared with many mainstream pharmaceuticals. Traditional Chinese medicine has used berberine for thousands of years due to its ability to support the body’s natural inflammatory response.* In the last decade, Western medicine has increasingly recognized the potential of berberine, and researchers have now identified the compound as a viable option for addressing insulin resistance owing to its insulin-sensitizing effects.*
Unlike many folk remedies, berberine’s utility has very rarely been viewed with skepticism, so the barriers to utilizing it as a natural remedy for insulin resistance are fairly low. Berberine, which is readily bioactive, has been confirmed to benefit several different cellular mechanisms reliably and powerfully.* This means that berberine is a solution that is looking for problems to solve rather than a precursor product that needs a substantial amount of engineering toward a specific purpose before it is ready. The chief challenge is finding where it is most effective, rather than finding a single case where it is effective at all. Insulin resistance could be the niche where berberine can shine brightly as a natural remedy.
Berberine provides nutritional support for insulin resistance indirectly by diminishing the intensity of cellular feedback loops that generate resistance in the first place.* These feedback loops are at the center of the cellular energy generation system. Insulin is a hormone, which means the body utilizes it to signal cells to perform a specific action. In the case of insulin, the specific action is to moderate cellular glucose uptake and the cellular breakdown of glucose-derived molecules.
Under normal conditions, insulin prompts cells to uptake glucose and process it for energy that the cells use to perform their somatic functions in the body. Without this energy, the cells die, so insulin levels are closely associated with cellular activity. As with many other hormones, insulin can either promote or inhibit the cellular functions that it regulates depending on the other cellular signals that the cell receives at the same time. However, cells can’t react to any signal involving insulin if their insulin receptors are malfunctional or absent.
Insulin resistance can thus be understood as a condition in which cells’ ability to receive insulin’s signaling is impaired. On a cellular level, insulin resistance manifests as a downregulation in the number of insulin receptors present on external cellular surfaces. The fewer insulin receptors there are on cellular surfaces, the less physiological impact insulin molecules can have on the cell. In other words, more insulin molecules are needed to accomplish the same physiological activity in an insulin resistant individual than in an individual with normal insulin physiology.
What might cause cells to have fewer insulin receptors? The answer lies in the concept of homeostasis. When cells are chronically exposed to high concentrations of insulin—such as when an individual consumes a diet rich in simple sugars—their cells become accustomed to their insulin receptors being activated by insulin very frequently. In this condition, the cells uptake large volumes of glucose and subsequently convert that glucose into lipids when they have more energy than they need to perform their functions in the body. These lipids are secreted from the cell and travel elsewhere in the body. Significantly, some of these lipids are stored for future use in fat cells, which contribute to weight gain. However, the process of storing lipids in fat cells is slow and only utilizes a finite amount of lipids at a time, so the excess lipids continue to circulate, awaiting their turn.
When the concentration of these circulating lipids becomes too high, cellular toxicity can result. To avoid toxicity, physiological feedback mechanisms compensate for the rising lipid levels by prompting cells to reduce their concentration of insulin receptors. Fewer insulin receptors means there are fewer glucose molecules metabolized. Decreased glucose metabolism leads to fewer lipid molecules in circulation, which prevents the toxicity. The body has used its feedback mechanisms to maintain homeostasis in the face of unexpected conditions of toxicity.
But if lipid toxicity continues despite downregulation of glucose metabolism, the cycle repeats itself; downregulation occurs in successive rounds, leaving cells with fewer and fewer insulin receptors. Eventually, a massive amount of insulin is necessary to produce the same physiological outcome, and downregulation stops. Cells can be left with so few insulin receptors that they struggle to get the glucose they need to survive, causing the individual to experience lethargy and other symptoms. The patient has thus become insulin resistant.
Breaking the insulin resistance feedback loop described above requires altering the way cells uptake glucose and turn it into energy, and berberine does exactly that.* Berberine has been shown to mitigate insulin resistance in rats, in mice, and in humans. One particularly significant study, conducted by researchers in the Department of Pharmacology at the Chinese Academy of Medical Sciences, measured the level of RNA transcripts that coded for insulin in type II diabetes subjects. The subjects were weaned off their medications over a 2-week period and split into three groups. Two groups received mainstream pharmacotherapies for insulin resistance, whereas the third group received berberine. Over a period of two months, the three cohorts took their group’s prescribed therapy once daily.
After the two months had elapsed, the participants had their blood compared to samples taken at the start of the trial. The subjects who had taken berberine experienced 25.9 percent reduced blood glucose levels compared to the start of the trial. The two mainstream therapies reduced blood glucose levels by 17.6 percent and 30.3 percent. When the researchers examined cell cultures generated from the participants’ blood samples, they found that the serum insulin levels of the berberine group decreased by 28.2 percent, thus providing a significant benefit for insulin sensitivity.* This means that berberine can act as an attractive natural remedy for providing nutritional support to insulin sensitive individuals, including individuals looking to include a natural product with conventional therapies.*
However, the above researchers didn’t stop after elucidating berberine’s benefits for insulin sensitivity. Because many Chinese people suffer from liver issues caused by viral hepatitis B and C infections, the researchers were also interested in determining if berberine would be effective in benefiting individuals with compromised liver function.* This issue is important because the current pharmacotherapies for insulin resistance tend to be harsh on patients’ livers. In this aspect of the clinical study, berberine was also shown to provide significant benefits to liver function.*
Although researchers are still working to understand how berberine exerts these impressive effects, preliminary evidence suggests it is related to berberine’s benefits exerted within the mitochondria of the cell. Because the mitochondria are responsible for producing chemical energy for the cell, inhibiting mitochondrial energy production would lower the cell’s uptake of glucose and subsequent generation of lipids.* With fewer circulating lipids, the cellular feedback loop that causes insulin resistance would be reduced.*As a result, existing insulin resistance is mitigated at the source, and cells must upregulate their quantity of insulin receptors to continue to maintain the same level of activity and perform their physiological purpose thanks to their lower rate of energy production.*
As practitioners and their patients integrate berberine in their management plans, clinical vigilance is necessary. Although side effects of berberine are not yet comprehensively understood, anecdotal reports indicate that low blood sugar and low blood pressure are the most common issues. Patients with diabetes should be especially careful. Some patients report taking a large dose of berberine can cause cramping or diarrhea; spacing usage over the course of a day would be an effective solution to this issue. Individuals with sensitive gastrointestinal tracts should speak with their healthcare provider regarding strategies for mitigating discomfort.
For individuals wishing to utilize berberine supplementation, careful usage is essential; most clinical trials of berberine for insulin resistance tested usage in the one gram range. Owing to berberine’s interaction with the mitochondria, it is probable that its side effects will be multimodal and increasingly difficult to tolerate at higher amounts, so usage should be adjusted downward if side effects occur. This should not scare patients away however, because the available evidence does indicate that berberine can be a beneficial form of nutritional support for addressing insulin resistance with relatively low amounts and in short-term courses.* Indeed, published clinical reports indicate that berberine is very well tolerated in the short term.
Berberine’s extensive effects require a measure of caution, however. There is evidence that berberine inhibits the critical liver enzyme P450, which would likely mean there is a high potential for drug interactions associated with berberine usage. These interactions could either increase, decrease, prolong, or shorten the effects of other substances processed by the enzyme. To put this into context, however, inhibition of the P450 enzyme is found in a plethora of mainstream therapies that patients use without facing problems. Likewise, individuals with liver issues should use lower amounts of berberine with the expectation that their reduction of blood glucose will be slightly less than in a healthy person. Individuals should discuss berberine supplementation with their doctors before trying it regardless of their liver health.
Ongoing research into berberine will likely elucidate its benefits. In the meantime, patients dealing with insulin resistance should be proactive in learning more about how to use berberine supplementation for their health and wellness.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your endocrine health.*
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Updated on April 7, 2023
Article Summary
When parents of autistic children ask what causes the condition, the answers are never satisfying. Although therapy would be far easier if researchers could pinpoint a single causative factor, there is a wide range of genetic and environmental factors that contribute to the characteristic symptoms of autism.
Given autism’s complex etiology, the most promising therapeutic strategies for addressing autism symptoms involve targeting the cellular processes believed to contribute most to the development and exacerbation of the condition. Today, researchers have identified oxidative stress as one of these key cellular processes, which is spurring interest in nutritional supplements that can reduce oxidative stress to, and thus improve quality of life for autistic patients.
Oxidative stress is broadly defined as a state in which the production of reactive oxidative species surpases the cell’s antioxidant defenses. In the brain, this imbalance has the potential to trigger neurotoxic pathways that can fundamentally damage brain cells and might have functional effects ranging from memory loss to the exacerbation of psychiatric symptoms.
There is a strong body of scholarly literature linking high levels of oxidative stress to autism. In a 2012 systematic review, researchers concluded there are multiple oxidative stress-related biomarkers associated with autism, including lower plasma levels of reduced glutathione (GSH), higher levels of oxidized glutathione (GSSG), and lower levels of glutathione peroxidase, methionine, and cysteine.
The data from this comprehensive review supports the concept that oxidative stress plays a significant role in the pathogenesis of autism. Therefore, oxidative stress-related cellular pathways are likely to be ideal targets for innovative therapies.
As a naturally occurring antioxidant in the brain, glutathione is heavily involved in protecting neurons from the damage that can result from oxidative stress.* However, multiple studies have shown that autistic individuals have unusually low levels of glutathione, and the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) is also negatively altered in these individuals.
Specifically, the proportion of the reduced form (GSH) is lower than the proportion of the oxidized form (GSSG), which indicates a chronic state of oxidative stress. This imbalance has led researchers to consider whether restoring GSH levels might help manage symptoms because oxidative stress might be damaging brain cells in ways that have direct clinical impacts.
Although the evidence supporting the benefits of glutathione supplementation for autistic individuals is limited, early results are promising. In 2011, researchers associated with the University of Texas Southwestern Medical Center conducted a small-scale, open-label study in which 13 male autism patients between the ages of three and 13 took oral and transdermal formulations of glutathione.
They observed a significant increase in plasma levels of GSH, as well as other antioxidants like sulfate and cysteine. This suggests that glutathione can be an efficacious nutritional supplement for autistic patients, and the likely reason why the researchers called for more comprehensive future studies with larger sample sizes and greater attention to the behavioral effects of supplementation.
One of the ways in which oxidative stress harms brain cells is by interfering with the function of mitochondria. Mitochondria are key organelles that are involved in essential aspects of cellular function, including energy metabolism and longevity, and some studies suggest that the significant effects of oxidative stress in autistic patients can be mediated by an increase in mitochondrial dysfunction.
One possible way to counteract this phenomenon is to increase cellular exposure to butyrate, a short-chain fatty acid. Although butyrate is normally derived from bacteria in the gut microbiome when they digest fiber, the latest research indicates that the microbiomes of patients with autism are different from those of healthy patients, which might result in a butyrate deficiency; a circumstance that could be resolved through butyrate supplementation.
This hypothesis was recently supported by a cutting-edge 2018 study out of the University of Arkansas, in which researchers conducted an in vitro study using cell lines from the brains of young male autism patients. They found that when the redacted cells were exposed to butyrate during oxidative stress, the exposure enhanced mitochondrial function. These results suggest that butyrate can enhance mitochondrial function during oxidative stress, thus interfering with the oxidative stress-related physiological processes that underpin autism.*
Although further clinical studies on butyrate supplementation are needed to confirm this laboratory evidence and assess the potential real-world implications for patients, this early research provides an exciting opening for researchers and clinicians who are interested in finding ways to benefit patients by reducing the impacts of oxidative stress.
At present, there is not enough conclusive research to definitively determine whether therapeutic strategies to counteract oxidative stress will lead to observable effects in autistic individuals. However, given the strong evidence that oxidative stress does play a role in the pathophysiology of this disorder, it is definitely an avenue worth exploring. Patients, caregivers, and practitioners should know, however, that they can take action now on these connections by supplementing with available glutathione and butyrate nutritional supplements to assess the possible beneficial impacts on individual patients.
The power of Tesseract supplements lies in the proprietary science of proven nutrients and unrivaled smart delivery, making them the most effective for supporting neurological health and gastrointestinal health.*
Bhanizadeh A, Azkhondzadeh S, Hormozi M, et al. 2012. Current Medicinal Chemistry. 19(23): 4000-5.
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Updated on April 7, 2023
Article Summary
Cannabidiol (CBD) is becoming an increasingly prominent subject in the field of pain management. CBD is the primary non-psychoactive component of the cannabis plant (Cannabis sativa), and there is widespread interest among practitioners and their patients in harnessing CBD’s analgesic effects for both acute and chronic pain. There is significant anecdotal evidence of the benefit of CBD for pain, because it is already being used in the clinical context for this purpose.
Early mechanistic research on CBD for pain has revealed the unique physiological mechanisms through which this compound addresses pain. Researchers have now conducted a series of promising animal studies indicating CBD’s potential for efficacy. Although rigorous human studies on the benefit of CBD for pain have not yet been conducted, the initial evidence indicates it has a strong safety profile, suggesting further investigation will be a worthwhile endeavor.
One of the reasons CBD is considered a particularly promising option for relieving pain is that researchers have a relatively clear understanding of how its analgesic effects work on the cellular level. Specifically, CBD modulates the activity of two G-protein coupled receptors, cannabinoid type 1 (CBD1) and cannabinoid type 2 (CBD2). As a CB1 receptor antagonist, CBD downregulates the protein’s activity in the hippocampus (a region of the brain involved in pain perception, among other functions), thus dampening the level of pain a patient might be experiencing. Interactions between CBD and the CBD1 receptor might also be preventing the release of glutamate, a neurotransmitter that has a role in a variety of pain-related processes. Through the modulation of the CBD2 protein, CBD can help target inflammatory pain.
It is important to note that the mechanistic underpinnings of CBD for pain are not limited to their interactions with cannabinoid receptors. Recent studies indicate the compound can also target non-cannabinoid receptors, including the alpha-3 glycine receptor, another protein with known involvement in pain sensation. In particular, the alpha-3 glycine receptor initiates both inflammatory pain processes and neuropathic pain processes. This is significant because inflammatory pain is different from neuropathic pain in that it can arise from the immune response in any tissue, whereas neuropathic pain comes directly from damaged nerve tissues. Because CBD appears to target both cannabinoid and non-cannabinoid receptor proteins, it could aid in relieving both types of pain.
Most of the existing studies on CBD for pain have been conducted on rodent models of arthritis, and have generally verified the previous mechanistic findings. The first breakthrough came in 2000, when scientists published a study on how CBD has immunosuppressive and anti-inflammatory effects in mouse models of osteoarthritis, which suggested CBD is able to ameliorate the pain from this condition. More recently, in a 2017 study on rat models of osteoarthritis, researchers found that a two-week course of CBD ameliorated early-stage inflammation and nerve damage, highlighting the compound’s promise again, for both inflammatory and neuropathic pain. Similarly, in a 2016 study conducted at the University of Kentucky College of Pharmacy, researchers reported that four-day administration of transdermal CBD alleviated joint swelling in rat models of osteoarthritis. Notably, behavioral experiments also revealed a reduction in the rats’ pain-related behaviors, indicating that the inflammation had a direct adverse impact on the rat’s experience of pain.
While studies on rat models of arthritis indicate that CBD can be a valuable therapy for chronic pain, there is also evidence from animal studies that CBD can help acute pain. In a 2017 study, researchers examined the impacts of CBD on rat models of surgical incision pain. When intraperitoneal injections of CBD were given to the rat models contemporaneous with surgical incisions, it reduced the negative response to the pain of the surgical incision. Because one aspect of the rat model was a conditioned aversion to pain from surgical incision, the results suggest CBD not only blocked the rats’ physical pain response, it might also have affected their emotional reaction to the experience of pain. Based on data that supports the notion CBD has a combination of sensory and affective impacts on pain levels, the researchers tentatively proposed that CBD could have value for other types of pain, such as postoperative pain following surgery.
When considering the potential benefit of CBD for pain, it is also helpful to explore how it compares to other approaches. One recent study offering insight on this subject, used a zebrafish laval model of pain perception to compare three cannabinoid compounds (honokiol, tetrahydrocannabinol, and CBD) with three well-established synthetic pain medications (ibuprofen, acetaminophen, and tramadol). It was found that CBD had properties that address pain more prominently than the other cannabinoids in the study, and on par with the traditional pain medications.
Evidence for the benefit of CBD for pain in humans is currently limited to anecdotes from patients and practitioners. However, there have been several human studies examining the safety and side effects of CBD, and they indicate one of CBD’s benefits is its highly favorable safety profile.
In most early studies, the subjects using CBD rarely reported side effects, and when they did, the adverse impacts were relatively mild. For instance, some subjects reported tiredness, mild gastrointestinal distress, or changes in appetite and/or weight, but it rarely interfered with subject compliance. For practitioners and their patients who are considering the use of CBD for pain, this lack of side effects can be highly attractive, especially considering the fact that traditional prescription and over-the-counter pain medications often come with significant short-term and long-term side effects. As concerns about riskier alternatives like opioids increase, CBD is an increasingly appealing option to consider.
At this point, the way is clear for researchers to build on the animal studies on CBD for pain by conducting large-scale clinical trials in humans. A number of early studies on other cannabinoid compounds have produced promising results, so it will be worth pursuing more comprehensive research in this area. As these studies get underway, interested practitioners and their patients wanting to address pain management should consider how CBD products already on the market might be integrated into such plans.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your neurological health.*
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Updated on April 7, 2023
Article Summary
Irritable bowel syndrome (IBS) is a tricky diagnosis to understand and an even tougher condition to address. Unlike inflammatory bowel diseases (IBD), which are relatively well-characterized based on the physiological processes that underpin their symptoms, IBS is a functional bowel disorder. That means it is diagnosed based on an individual’s specific symptomatic complaints. As a result, IBS can manifest differently in every person, with possible symptoms including constipation, diarrhea, bloating, gas, abdominal pain, and various gastrointestinal (GI) complaints in between.
Moreover, the causes of IBS symptoms can vary considerably between individuals, so even if several persons’ symptoms are similar, there’s no guarantee a single therapy will work for all of them. For instance, one individual with IBS might experience chronic constipation because of a food intolerance, while another might have the same symptom because of a microbiome-related problem. This makes IBS a particularly complicated challenge for those who suffer from it and their healthcare providers.
The good news is that recent research has achieved greater insight into possible causes of functional GI symptoms that don’t fall neatly into the category of an established IBD and are therefore diagnosed as IBS. In some cases, the physiological underpinnings overlap, which indicates that some of the therapies used to treat IBD can be just as effective for IBS. One such promising option is glutathione, an antioxidant supplement that helps combat the oxidative stress that plays a role in some cases of IBS.*
An imbalanced inflammatory response in the GI tract is increasingly being recognized as a potential causative factor in IBS. Although the inflammatory response in the GI tract of a patient with IBS might not be as out of balance as it is in IBD patients, even low-grade imbalance can contribute to intestinal damage in the GI tract that leads to gastrointestinal motor dysfunction.
Like so many other aspects of the condition, the reason the GI tract’s inflammatory response becomes imbalanced in individuals with IBS is not fully understood. Some studies suggest the imbalanced inflammatory response results from immune system dysfunction, while others indicate a possible role for the internal microenvironment, with altered microbial composition contributing to the vulnerability of the intestinal lining to harm caused by free radical species. Whatever the source of the imbalance in a particular IBS patient, it is worth exploring the use of therapeutic options that combat oxidative damage induced by inflammatory processes.
Glutathione plays an important antioxidant role in the body. The compound is a tripeptide consisting of cysteine, glycine, and glutamic acid, and it exists in two states: the reduced state (GSH) and the oxidized state (GSSG). When GSH, the naturally more abundant form, encounters free radicals—including singlet oxygen, hydroxyl radicals, and superoxide radicals, all of which have the potential to damage cells and tissues—it can be oxidized to GSSG. However, it is important to note that glutathione’s antioxidant activities are not limited to its direct oxidation; rather, glutathione also acts as a cofactor for several antioxidant enzymes. Without glutathione’s facilitation, these enzymes would be unable to catalyze essential antioxidant processes.
The primary reason practitioners and their patients should be interested in using glutathione in IBS is that research suggests it is effective for helping maintain a normal inflammatory response in the gut, thus beneficially addressing IBD symptoms.* And in cases where the underlying mechanisms of the condition do overlap, a glutathione supplement could be just as beneficial in IBS as it is in IBD.*
When glutathione facilitates antioxidant processes, it minimizes free radical exposure, which can trigger an inflammatory response imbalance.* If an imbalance in inflammatory response is involved in either IBS or IBD, then a glutathione supplement can be an appropriate choice.* Indeed, as far back as 1998, scientists have recognized that intestinal glutathione synthesis is impaired in patients with IBD, and this dysregulation might play a role in the etiology and progression of the condition. Thus, supplementation with glutathione could address this deficiency.*
Although researchers have not yet conducted studies on glutathione for IBD in either animal models or in humans, there is evidence that other antioxidant therapies can address symptoms—possibly by raising levels of glutathione. For instance, in a 2012 study published in the European Journal of Pharmacology, researchers gave mouse models of IBD N-acetylcysteine, a well-known antioxidant. The therapy had a variety of beneficial physiological effects, including the initiation of a rise in glutathione, which might have further contributed to the positive functional effects of the therapy. Researchers have also found that other natural antioxidants, including multiple dietary polyphenols, can beneficially impact the inflammatory response and combat symptoms in mouse models of IBD. Given that glutathione is the most abundant antioxidant in the body, it stands to reason that it would have similar beneficial effects as other naturally derived antioxidant compounds, like curcumin, quercetin, naringenin, and hesperetin.*
Given the complex nature of IBS, it is necessary to be particularly sensitive to the side effects of supplements and pharmaceuticals used to manage it. Individuals with an IBS diagnosis should be particularly skeptical about novel therapeutics that have a long list of potentially adverse impacts. Since IBS is a functional gastrointestinal disorder, practitioners and their patients should be cognizant about how any potential intervention impacts other functional aspects of a patient’s health.
If an adverse effect, or even the inconvenience, of a particular therapy outweighs the benefits for the patient, then it might not be worthwhile to include it in a management strategy. Therefore, it is promising to note that, in the human studies that have examined the use of glutathione for non-GI conditions, the results indicate a positive safety profile for the supplement.* Few side effects have been reported, and those that have been observed are relatively mild. Thus, for practitioners and their patients considering supplementing glutathione for IBS, side effects are not likely to be a major concern.*
Overall, despite the absence of specific research on glutathione for IBS, the broader scholarly literature on the topic suggests it is a worthwhile option to consider. Underpinned by early research on the role of the inflammatory response in IBS and the possible benefits of antioxidant therapy for IBD patients, the possibility of glutathione as an effective supplement for IBS is becoming increasingly prominent.* Although future research in humans and animals will confirm the value of glutathione for IBS and IBD, patients can already work with their practitioner to explore how glutathione supplementation can become part of their therapeutic strategy.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your gastrointestinal health.*
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