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Updated on April 7, 2023
Article Summary
Being diagnosed with type 2 diabetes means far more than dealing with a single medical condition. Individuals with type 2 diabetes contend with a broad spectrum of health concerns, ranging from blood sugar maintenance to weight management to diabetic neuropathy.
Although there are individual therapies that can help patients address each aspect of the condition, in recent years there have been calls for the development of broad-spectrum solutions that can simultaneously address multiple components of the condition, without subjecting patients to unwanted side effects. Currently, one of the most promising natural management options is berberine.
Berberine is a plant extract that has long been used in traditional Chinese medicine. Following decades of research, researchers have developed a strong understanding of how this natural alkaloid can exert its beneficial activities in individuals with type 2 diabetes.
The success of the in vitro research has driven animal studies that suggest possible ways in which berberine might have positive effects on a wide range of type 2 diabetes symptoms. In the last few years, the first human studies have gotten underway, and although the clinical research is still in its infancy, it has the potential to clarify the specific benefits of berberine supplementation for diabetes.
Berberine stands out because scientists have a solid understanding of the specific cellular pathways through which it works. Specifically, berberine upregulates a protein that plays an important role in a wide range of energy production and utilization pathways.*
According to a 2006 study, berberine stimulates glucose uptake in the cell, which is highly relevant for type 2 diabetes.*
In 2010, researchers at the Chinese Academy of Medical Sciences found that berberine increases the expression of insulin receptors, indicating the potential for a prominent role in providing nutritional support in type 2 diabetes patients.* There is also research to suggest that berberine might help maintain normal cholesterol levels by increasing the degradation of a protein that down-regulates the low-density lipoprotein (LDL) receptor.
As researchers continue to find associations between berberine and a variety of cellular pathways, there is ongoing interest within the research community to elucidate additional mechanisms through which this multifunctional compound might be able to help individuals with type 2 diabetes.
In light of the promising mechanistic research on the role that berberine might play in providing nutritional support for type 2 diabetes, researchers have conducted numerous studies in animal models over the last few decades.
In one rat model of diabetes, administration of berberine led to lower fasting glucose levels, as well as an increase in HDL (good) cholesterol levels and an accompanying decline in total cholesterol, triglycerides, and LDL (bad) cholesterol levels.*
Studies in animal models indicate that berberine might also aid in providing nutritional support for some of the most common issues observed in type 2 diabetes, including the following:
In a 2010 study, researchers at South Dakota State University found that berberine might be effective in a weight management program for individuals with type 2 diabetes.* In their mouse models, berberine supplementation directly inhibited adipogenesis–that is, the generation of fat cells.*
Nerve damage is a debilitating complication of type 2 diabetes. Through multiple pathways, berberine apparently helps maintain the body’s normal inflammatory response, thus helping to maintain normal nerve function.*
A 2010 study published in the Archives of Biochemistry and Biophysics showed that berberine supported kidney health in rat models of diabetes.*
Memory impairment and other signs of cognitive decline are common among type 2 diabetes patients. Through a combination of protein expression studies, brain imaging, and behavioral tests on rat models, researchers at Huazhong University of Science and Technology in China found that administration of berberine helps maintain cognitive function in individuals with type 2 diabetes.*
Although most of the studies on berberine for diabetes have been conducted in vitro and on animal models, the few human studies that have been conducted have produced promising results. For instance, in a pilot study in 2008, researchers gave berberine to newly-diagnosed type 2 diabetes patients.
The berberine group experienced statistically significant benefits in maintaining normal levels of hemoglobin A1c, fasting blood glucose, postprandial blood glucose, and plasma triglycerides, starting only one week after the trial began.*
In a follow-up trial, the researchers recruited 48 adults with type 2 diabetes and found similarly statistically significant benefits.*
This pilot and follow-up studies suggest that berberine supplementation could have significant benefits, warranting larger scale clinical studies on individuals with type 2 diabetes in the future.
Other early studies on berberine for diabetes were conducted over the next few years. According to the authors of a 2012 meta-analytic review of 14 human studies—in which berberine supplementation was compared to lifestyle modification, placebo, and/or alternative oral therapeutics—the compound has considerable promise for providing nutritional support for individuals with type 2 diabetes.*
Based on the research to date, the results thus far indicate there is ample room for researchers to continue to rigorously explore the measurable clinical impacts of berberine for supporting diabetes patients.
Nevertheless, patients and practitioners today can already take advantage of the significant body of existing research. Despite the lack of large-scale clinical trials on berberine’s benefits in type 2 diabetes, the mechanistic evidence for the compound’s efficacy is considerable, and the success of animal studies strongly suggests the biochemical studies are translatable to humans. For patients and practitioners looking for a way to provide nutritional support for individuals with type 2 diabetes, it might be worth considering berberine as an option.
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
Epilepsy often prevents individuals from living a normal life. Even with advanced interventions like vagus nerve stimulation via implanted medical devices, individuals are still liable to be wracked by unpleasant and frightening seizures at any time. If they occur frequently, then these seizures can preclude patients from driving, working, and living independently. Additionally, individuals with epilepsy are often left suffering under the burden of their therapy’s side effects and some side effects—like somnolence and fatigue—can often be just as debilitating as the seizures they are meant to prevent. Nonetheless, even therapies that fail to resolve symptoms to an adequate degree can provide some limited relief, so they continue to be utilized.
Today, however, a growing number of individuals are turning to a powerful therapy that has been proven effective in the context of treatment-resistant epilepsy: cannabidiol. Cannabidiol (CBD) is a chemical derived from the leaves of the hemp plant, which has a history of human use going back thousands of years. CBD has been the subject of intense scientific research owing to relatively recent discoveries that indicate that CBD has the potential to modulate neuronal activity. Significantly, researchers have found that CBD is not overtly psychoactive, unlike other constituents of the cannabis plant, most notably tetrahydrocannabinol (THC). Because CBD isn’t intoxicating or habit-forming, its ability to modulate neuronal activity makes it appealing to many people struggling with epilepsy.
Scientific investigations into CBD’s antiepileptic potential have quickly borne fruitful findings. With a recent systematic review of clinical trials claiming that 48 percent of participants exhibited a 50-percent reduction in the frequency of their seizures after CBD therapy, there is a strong base of evidence in favor of using CBD as an antiepileptic. If an individual is not experiencing remission of their seizures as a result of their current therapeutic regimen, then there is a very real chance they will benefit from trialing CBD therapy.
CBD’s impact on epilepsy is difficult to understand without being familiar with the neural basis of seizures. When neurons in the brain are activated by an electrochemical signal, the neurons transmit their own electrochemical signal to other neurons. The strength of the outgoing signal is dependent on the strength of the signal the neuron receives. Under normal conditions, neurons experience a brief refractory period after they have been activated. This prevents a neuron from repeatedly activating at full strength; subsequent re-activations will not produce as strong of an activation from the recipient neuron until it has recovered from prior activations. And even if a neuron is being over-activated, it is still regulated by other groups of neurons that will detect the over-activation and, subsequently, inhibit it. As a result, neurons normally do not become activated simultaneously, strongly, and repeatedly, even if they are in the same area of the brain and serve the same function.
Under the conditions of extreme over-activation, however, the normal safeguards are overwhelmed. Seizures are caused by the repeated synchronous strong activation of groups of neurons; when the neurons are activated strongly, simultaneously, and repeatedly, this activation cascades to the rest of the brain, temporarily overwhelming the inhibitory circuits. The wave of synchronized over-activation displaces the normal patterns of activation responsible for maintaining homeostasis, disrupting function. Eventually, this cascade arrives at one of the brain’s areas responsible for the visible signs of seizures, typically in the temporal lobes. The activation in these areas can then cause the motions and muscle clenching associated with seizures.
To control seizures, CBD molecules inhibit neuron activation by binding to two of the cannabinoid receptors, CB1 and CB2. Although the mechanism by which binding of CB1 and CB2 inhibit neuronal activation is still under study, researchers believe CBD enables neurons to control their level of calcium, which is necessary for neuronal activation. Rather than simply decreasing the level of intracellular calcium, researchers found that CBD improves the ability of neurons to sequester excess calcium, as well as also their ability to access stored calcium when deficient. Because neurons can’t activate as strongly or as quickly with a modulated calcium balance, the inhibitory neural circuits remain in control, and normal patterns of activation can persist.
CBD’s mode of action differs in significant ways from other therapies. For example, benzodiazepines also inhibit neuron activation but do so via a different mechanism. With benzodiazepines, the level of inhibition is much higher because the drug molecules bind directly to GABA (gamma-aminobutyric acid) receptors rather than CBD receptors. Binding to CBD receptors causes a moderation of the neuron’s ability to activate, but it does not directly engage inhibitory neural mechanisms in the way GABA does. The difference is akin to taking a foot off of the gas (CBD) versus pumping the brakes (benzodiazepines and other GABA-targeted therapies). The consequences of this higher level of neuronal inhibition are sleepiness, reduced motor coordination, slurred speech, sluggish thought, lowered social inhibitions, and amnesia, all of which can significantly compromise quality of life and even personal safety.
Additionally, benzodiazepines are notorious for building both physical and psychological dependency as a result of their anxiolytic properties. Tolerance can build extremely quickly, meaning that patients will often stop experiencing benefits at the dose they were prescribed, causing them to seek stronger doses, potentially resulting in addiction. Furthermore, benzodiazepine class drugs cause neurons to exhibit a rebound effect, wherein neuronal activation is higher than normal following the drug’s clearance from the brain. This rebound effect most often manifests as anxiety, although secondary seizures caused by cessation of antiepileptic therapy and subsequent rebound activation can also occur. Finally, the addictive nature of benzodiazepines makes them unsuitable for long-term seizure therapy in most cases.
Other antiepileptics include carbamazepine and its analogues, phenytoin, phenobarbital, valproate, gabapentin, and lamotrigine. Most of these drugs operate by increasing the concentration of GABA. The impact and side effects of these drugs vary considerably as a result of their differing mechanisms. Some, like phenobarbital, share many overlapping side effects with the benzodiazepines. Others, like valproate, have a different side effect profile altogether; individuals can experience bleeding, anemia, nausea, and depressed mood.
Not all antiepileptic drugs utilize GABA concentrations as their primary mechanism, however. In contrast to the GABA-enabling drugs, carbamazepine and phenytoin block the sodium channels on neurons. This prevents the neurons from initiating the repetitive activation characteristic of seizures but does not result in systemic inhibition in the way that the GABA-enabling drugs do. Persons taking these drugs can struggle with blurred vision and low blood pressure as a consequence. Gabapentin, on the other hand, operates by tuning the calcium channels on neurons, causing transient dizziness, sleepiness, and unexpectedly aggressive behavior. By altering the calcium channels, neurons are less able to rapidly recover the ability to send a strong signal after activation. Thus, the over-activation seizure state is less likely to occur. As powerful and as diverse as these drugs can be, however, some individuals with epilepsy still have seizures even when taking several different medications.
CBD has a distinct advantage over many other epilepsy therapies not only due to the novel mechanism of action, but as a result of its low side effect profile and lack of dependency risk. This makes CBD appealing for a broad range of individuals struggling with epilepsy, giving them the ability to effectively address symptoms in a way other therapies do not, while optimizing quality of life and minimizing the potential of new dangers.
Although the relative safety and tolerability of CBD make it highly attractive to many, CBD therapy is also exciting because it has been shown to ameliorate epilepsy symptoms even when other interventions have failed. For the 74 patients from a study of five Israeli pediatric epilepsy clinics, CBD therapy might have been life-changing. In the study, the patients selected for analysis experienced daily seizures despite trials of eight or more antiepileptic drugs. If CBD therapy was successful within this cohort, then researchers posited it would make for an effective adjunct therapy that might give patients relief before last resort therapies were necessary. The majority of the patients were under age 12, and all were under age 18. In each of the five clinics, patients received varying doses of CBD over different intervals of time. Because each clinic had its own methods, there was no unified study protocol, but rather a handful of different clinical practices being implemented piecemeal in an attempt to help patients after other interventions had failed.
Nonetheless, CBD succeeded where the other therapies had failed. In fact, 89 percent of patients with treatment-resistant epilepsy experienced a lower frequency of seizures after they began CBD therapy. Of these patients, 18 percent claimed their seizures nearly or totally disappeared as a result of CBD therapy. Another 34 percent experienced a 50 percent reduction in the frequency of their seizures, and an additional 12 percent reported lesser but still significant reductions. These impressive results suggest that most people with epilepsy will experience a substantial improvement in their symptoms with the help of CBD therapy. Although larger clinical trials with adults are needed to characterize the most effective therapeutic regimen, the results of the Israeli study are extremely promising and have been replicated in a slightly older cohort by other researchers.
Of course, CBD—like other therapies—does have the potential for side effects. Patients who take CBD sometimes experience daytime sleepiness, excessive fatigue, or gastrointestinal disturbances, which sometimes make patients discontinue CBD therapy. According to the summary of the Israeli trials, as many as seven percent of the study participants experienced a worsening of their seizures after starting CBD therapy, although no causal relationship was established. For most individuals, however, there will be few side effects of CBD therapy. Nonetheless, experimentation with CBD should be performed with the help of a medical professional and begun gradually.
As a result of the overwhelmingly positive evidence in favor of using CBD therapeutically, the antiepileptic therapy landscape today is drastically more favorable than that in prior years. And there is reason to believe this landscape will continue to improve; scientific interest in CBD therapeutics for epilepsy of all types is growing at a rapid pace, and new studies are increasing the understanding clinicians have regarding what CBD therapy can do. Although there is strong evidence that CBD can be highly beneficial for individuals with treatment-resistant epilepsy, research indicates that CBD has the potential to be an excellent first-line therapy for epilepsy as well. Given the extensive side effect profile of traditional antiepileptics, CBD is likely to soon become a mainstream therapy, helping individuals with epilepsy improve their quality of life and potentially allowing them to replace their current regimen of antiepileptics.
Individuals with epilepsy need not wait for the forthcoming clinical trials regarding CBD therapy to begin to address their symptoms. A plethora of CBD products intended for therapeutic use are already on the market, and more are soon to arrive. Although clinical protocols for CBD therapy are still forming, the abundance of evidence suggests patients can benefit from 10-20 mg/kg of 99 percent CBD oil and 1 percent propylene glycol administered daily. As a result of the recent publications and positive press coverage of CBD therapeutics, individuals struggling with epilepsy will likely find that their health-care providers are amenable to helping them with a trial of CBD therapy.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your neurological health.*
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Updated on April 7, 2023
Article Summary
Although curcumin has been used for medicinal purposes for more than four thousand years, it has only recently gained attention as a nutritional supplement. This polyphenol, which is the active component in the spice turmeric (Curcuma longa), stands out among supplements because of its versatility. Over the last few decades, researchers have conducted both laboratory and clinical studies indicating that curcumin can offer health benefits to a broad spectrum of health conditions because it can play so many different roles in the body. The benefits of curcumin stem primarily from its antioxidant activities, but it also has other beneficial properties that further expand its potential.*
Despite these promising findings, it is important to note that curcumin is not a miracle compound. Specifically, there are concerns about the compound’s bioavailability, which could limit its usefulness as a nutritional supplement. Therefore, when considering how curcumin might be integrated into a health and wellness strategy, it is important to understand both the limitations of curcumin and the innovative delivery systems that have been developed to overcome them.
Curcumin has long been a staple of traditional medicine. Although its historical uses vary somewhat between cultures, the health conditions that it has been used to address have certain things in common, and these similarities have directed scientists’ research on curcumin, and the subsequent studies have borne out the anecdotal evidence.
For instance, multiple comprehensive review studies highlight curcumin’s effectiveness, which can help explain why it has been used historically. For example, recent studies suggest that curcumin plays a modulatory role in the activation of key components of the immune system—including T cells, B cells, macrophages, neutrophils, natural killer cells, dendritic cells, and a wide range of cytokines—which suggests that it can beneficially modulate immune function.*
The effects of curcumin on immune health are also facilitated by its role as an antioxidant. This can help explain the traditional use of curcumin for various common health conditions.
Thousands of years of anecdotal evidence suggests that patients can benefit from supplementation, and the latest clinical research indicates the same. For instance, in a 2016 systematic review and meta-analysis published in the Journal of Medicinal Food, researchers combined the data from eight randomized controlled trials—which together included more than 800 patients—to analyze the efficacy of curcumin for benefiting joint health. Based on the statistical significance of the results, the authors reported that taking a curcumin supplement of 1,000 mg daily is likely to have observable beneficial results. Although they also expressed concerns about the methodologies and the sample sizes of the studies they reviewed, the early evidence supports the efficacy of curcumin for supporting joint health.*
In addition to offering benefits for joint health, recent research also suggests that curcumin may support neurological health. Studies show that the compound can provide nutritional support for various neurological conditions. Although the mechanisms through which curcumin provides these benefits are not entirely clear, research suggests its effects stem from its ability to support the body’s inflammatory response.
One piece of evidence for this hypothesis comes from a 2015 study, in which a group of researchers from Punjab University in India explored how the active properties of curcumin might provide nutritional support benefits for individuals with autism. In this study, the researchers gave their rat models of autism either 50, 100, or 200 mg/kg of curcumin per day. Then, the rats were tested for behavioral paradigms of the disorder, including social problems, locomotor issues, spatial learning deficits, and repetitive behaviors. On the behavioral tests, the researchers noted statistically significant improvements, and their subsequent biochemical tests revealed a decline in the activity of metalloproteinases and their associated impacts on the inflammatory response.*
Another study examining the potential of curcumin for providing nutritional support for neurological disorders was published in the journal Metabolic Brain Disease in 2017. In this study, the researchers gave a rat model of Parkinson’s disease 200 mg/kg of curcumin and examined the effects using a combination of electrophysiological and behavioral experiments. The data indicated that supplementation could benefit motor impairments, so it may be beneficial in providing nutritional support for Parkinson’s patients.*
In both of these studies, researchers expressed hope about the future of curcumin as an effective supplement in providing benefits for neurological disorders.* Although it will be necessary to verify these animal studies with more comprehensive clinical studies in the future, they strongly suggest curcumin’s beneficial effects on brain health.*
Because the majority of the research on curcumin’s health benefits has been conducted in the lab and clinical trials have remained small, there are still questions about whether or not the studies in cells and animals will be able to translate to human patients. This is particularly true because curcumin has an unusually low level of bioavailability—that is, when taken directly as an oral supplement, only a limited amount of the compound can be absorbed by the body. Although this has been one of the major barriers to the use of curcumin as a nutritional supplement, scientists have found ways to overcome this limitation.
To address the problem of bioavailability, researchers have developed innovative delivery systems that can increase the absorption rate of curcumin, ensuring that a person’s cells will be exposed to the same levels as the cells and the animals in the lab. Therefore in contrast to the mixed results of earlier studies, future research is more likely to reveal real-world benefits of curcumin. Thanks to these new delivery systems, practitioners and their patients now have the opportunity to explore how curcumin’s traditional benefits have truly been enhanced by the latest technology.
The power of Tesseract supplements lies in the proprietary science of proven nutrients and unrivaled smart delivery, making them the most effective for supporting musculoskeletal health and immune health.*
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Darbinyan LV, Hambardzumyan LE, Simonyan KV, et al. 2017. Metabolic Brain Disease. 32(6):1791-1803.
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Prasad S, Aggarwal BB. 2011. Herbal Medicine: Biomolecular and Clinical Aspects.
Updated on March 27, 2023
Article Summary:
Working day and night to metabolize substances of all sorts, the liver is constantly in action. Yet the liver is not infallible, nor is it invulnerable. As a person ages, their liver can accumulate damage that prevents them from operating at full capacity. Consumption of alcohol and ingesting other toxins exacerbate the rate at which this damage occurs, leaving the body with a slower metabolism and a liver with a compromised ability to detoxify. With a weaker liver, the body is exposed to toxins for longer and in a wider array of tissues, causing dysfunctions that can range from jaundice to cancer. Therefore, maintaining the health of the liver should be near the top of every individual’s healthcare priorities.
To maintain good liver health, many people turn to detoxification regimens. A detox regimen aims to purge the liver of toxins that ostensibly accumulate there, thereby enhancing its function. Although the scientific basis behind most detox regimens is more fable than fact, there are a number of practices that individuals can use in specific situations to support their liver’s ability to combat toxins.
The most effective detox regimens contain compounds that behave synergistically with the liver’s normal functioning. In other words, these detox regimens have compounds that are more effective when administered together. Individuals seeking an especially effective regimen have recently discovered a powerful new combination: glutathione and milk thistle extract. Milk thistle is a bioactive botanical that has long been associated with liver health; in contrast, glutathione is a compound naturally created by the body that is highly concentrated in liver cells. Both substances are safe, natural, and effective means of supporting the liver. Although a natural liver detox using glutathione and milk thistle will not reverse accumulated damage that occurred prior, individuals who opt to try the regimen will reliably experience its liver-enhancing effects.
Glutathione (GSH) is a tripeptide created by the body to address oxidative stress. As a natural antioxidant, glutathione “scavenges” harmful free radicals, which are byproducts of metabolism, that cause damaging oxidative stress when left unaddressed. In damaging a cell, free radicals will react with a cell’s enzymes, blocking the ability of the enzymes to perform their physiological functions. Rather than allowing the free radicals to react with intricate cellular machinery in a damaging way, glutathione reacts with the radicals instead. After the glutathione has reacted with as many free radicals as possible, the glutathione molecules are trafficked to the bile where they are safely degraded. In the liver, glutathione molecules are normally present in high concentrations. However, there are many free radicals and other dangerous chemicals being generated in the liver under normal conditions and if there aren’t enough glutathione molecules in the liver to offload the free radicals being generated, damage to the liver can accumulate quickly.
Using this rationale, researchers were able to prove that mice with chronically low glutathione levels in their livers experience a cascade of damage starting with the mitochondria in their liver cells and ending with total liver failure a month later. Conversely, it is believed that a higher level of glutathione can address ongoing damage caused by residual toxins or free radicals. This is why some healthcare providers offer intravenous glutathione in an aqueous format for rapid replenishment of depleted reserves. Typically, however, glutathione is taken orally in a powder or capsule format. When administered in supplement form, the side effects of glutathione are mild or absent, making it highly tolerable.
Glutathione is a potent antioxidant to include in a detox regimen, but it’s even more effective when paired with milk thistle, which enhanced glutathione’s activity. Milk thistle is a common botanical found worldwide, easily recognizable by its spiky purple flower and bright green stem. Significantly, the milk thistle plant contains a number of bioactive chemicals, including silybin and silymarin, both of which offer detoxifying benefits. Although the other constituents of milk thistle might also benefit liver cells, silybin and silymarin are the most studied because they are the most abundant ones in the plant.
Milk thistle can be consumed as a liquid extract or in dehydrated form in nutritional supplements. Although there is no consensus on the quantity that should be consumed to derive benefits, research has shown that milk thistle is safe to consume at quantities far beyond the amounts generally offered in supplements. The side effects of milk thistle are mild and include transient nausea, headaches, and dizziness. At high doses, milk thistle can cause diarrhea, although at lower doses the effect is merely to precipitate a bowel movement. And milk thistle appears to be safe for the liver when taken over a long period of time in individuals with a compromised liver.
Why is milk thistle beneficial for liver detoxing? In the context of liver health, milk thistle, like glutathione, behaves as an antioxidant. More importantly, milk thistle synergistically causes the liver to use glutathione more efficiently and in higher concentrations than normal.
The antioxidant properties of milk thistle make it effective in detoxing the liver when the liver is experiencing oxidative stress. Although milk thistle scavenges free radicals, it is not a particularly outstanding scavenger compared to glutathione. However, milk thistle does possess several unique properties that make up for its relatively weaker scavenging ability. These properties tie in directly with glutathione, making the two compounds natural complements.
Unique among common antioxidants, milk thistle inhibits free radical formation. This effect is especially pronounced in the inhibition of free radicals generated by alcohol consumption. Alcohol consumption is an egregious producer of free radicals, so the health-supportive effects of limiting alcohol’s oxidative impact are hard to overstate. Although milk thistle won’t prevent the negative systemic effects of alcohol—like a hangover—it might help to purge the leftover aldehydes and other metabolic byproducts of alcohol that are toxic. Because milk thistle can prevent free radicals from forming, its efficacy as an antioxidant is higher than it would seem based on its ability to scavenge free radicals alone. When used in combination with glutathione, its impact on the concentration of free radicals in the liver might be exponentially more beneficial. Lowering the rate at which free radicals are formed would free up more glutathione than would otherwise be available, leading to superior degradation of the remaining free radicals. Lowering the rate of free radical formation would also provide individuals with impaired glutathione synthesis or systemically high oxidative stress—as is commonly experienced in people with a variety of health conditions, including autism spectrum disorder—more time between experiencing oxidative stress and damage to their tissues.
Furthermore, milk thistle could ostensibly be used to preventively recruit extra glutathione to the liver in situations where an individual expects to be placing high than normal oxidative stress on their system. Although milk thistle hasn’t been explored in this context in humans, rats that received a mixture of constituents derived from milk thistle experienced 40% fewer instances of enzyme degradation when later exposed to a chemical cocktail designed to induce high levels of oxidative stress than did the control group. Although this activity is not “detoxification” per se, preventing damage from accumulating in the first place serves the same purpose.
Milk thistle’s active constituents also enhance the efficacy of glutathione by preventing its breakdown by liver enzymes in addition to recruiting glutathione molecules to the site of oxidative stress. This can lead to a higher concentration of glutathione than would otherwise be present. To accomplish this, milk thistle inhibits certain enzymes that degrade glutathione, like glutathione reductase and glutathione peroxidase. Although these enzymes are necessary for glutathione to offload its free radical cargo outside the liver, their presence inside the liver is detrimental for the purpose of detoxing. When these enzymes aren’t impacting glutathione, glutathione can remain in a high oxidative stress area longer, thus inhibiting damage. This effect makes milk thistle an excellent complement to glutathione for individuals expecting to confront oxidative stress in the near future.
In addition to recruiting antioxidants and supporting their function, milk thistle also supports mitochondrial function. As the “powerhouse” of the cell, the mitochondria is an organelle that transforms nutrients, like glucose, into a format that cells can use for energy. Although this process would normally increase the rate of free radical generation, this effect is mitigated owing to milk thistle’s attraction of glutathione.
When liver cells have a higher supply of chemical energy than usual, they can perform more cycles of toxin removal than usual. As such, liver cells with overpowered mitochondria operate can more effectively when there is sufficient milk thistle present. The end effect is that blood exiting the liver has fewer toxins than it would otherwise. Likewise, a higher energy supply allows liver cells to traffic glutathione to problem areas more expediently. Later, cells with more energy can quickly remove and recycle the saturated glutathione molecules, closing the loop much more rapidly. For healthy individuals, the difference is likely negligible, but for individuals with lowered liver function, or high levels of oxidative stress, or a heavy toxin load, the impact could be significant.
Even for healthy individuals, boosting the amount of chemical energy generated by the mitochondria has other beneficial effects on liver cells. Research shows that, when exposed to a high concentration of toxic chemicals that would typically kill liver cells, cells that received supplemental milk thistle experienced lower mortality than those that did not. This phenomenon can most likely be attributed to the increased glutathione concentrations resulting from the administration of milk thistle.
These effects carry over into living patients with dramatic results. In a human trial investigating the impact of milk thistle extract on patients with liver damage caused by hepatitis B or C, those who received milk thistle extract experienced a 50% lower risk of mortality caused by liver pathologies. Although this was only the case in patients also receiving standard pharmaceutical therapies to support liver function—milk thistle alone did not lower mortality—the picture is clear: patients with weakened livers have better outcomes with milk thistle than without. This is due to the fact that cells with extra chemical energy are more resilient when faced with extreme conditions because they can export toxins using glutathione more efficiently. They’re also more resilient when toxins are degraded before they can cause permanent damage.
In terms of direct detoxification of the liver, both glutathione and milk thistle are effective at degrading some of the most potent toxins that can be present in the liver. For example, milk thistle lowers the cellular concentration of a toxic chemical called malondialdehyde by degrading it into harmless components. Many other aldehyde class chemicals are created by the metabolic breakdown of alcohol and are similarly degraded by milk thistle before they can do significant damage. Unlike the aldehydes generated by alcohol metabolism, malonaldehyde is itself a product of reactive oxygen species reacting with other physiological compounds like phospholipids, which means that its synthesis has already caused damage to occur. Although most individuals might not know about malonaldehyde, it’s doubtlessly something their livers have encountered; whenever a reactive oxygen species gains access to a polyunsaturated lipid molecule, the ensuing chemical reaction will generate a molecule of malonaldehyde.
Like its precursors, malonaldehyde is highly reactive, although it reacts with a different set of targets than its precursors; rather than reacting with enzymes, malonaldehyde reacts with DNA. After this reaction, the section of DNA with which the malonaldehyde reacted is no longer “readable” by cellular machinery. In isolation, rendering a section of DNA unreadable would mean the cell could not implement whichever instructions were coded in that region—problematic, but not catastrophic because there are multiple redundant copies of DNA within the cell. The damage to the DNA is not so manageable when caused by malonaldehyde, however. This is because malonaldehyde persists long after the initial reaction period as a mutagen embedded with the DNA. These embedded mutagens are called DNA adducts, and they are highly correlated with developing cancers in whichever cell type they are found. The fact that milk thistle appears to degrade malonaldehyde, therefore, means that it might prevent damage to DNA that might lead to cancer. Although milk thistle’s cancer-preventing effects have been subject to a handful of clinical trials, the results of its efficacy remain inconclusive. Nonetheless, milk thistle’s beneficial impact on liver cells is proven, as is its extensive antioxidant capability.
Glutathione, on the other hand, is proficient at helping the liver to purge some of its most dangerous contaminants that don’t bind to DNA. For example, in one study, researchers found that when glutathione was depleted in liver cells, the cells died much faster when exposed to cadmium. Cadmium is a metal found in a variety of products, including certain paints, toys, alloys, and plastics, as well as tobacco smoke, batteries, solar panels, and older steel products. Cadmium is toxic to cells and difficult to remove from the liver without expensive and time-consuming metal chelation therapy. Even though the toxic nature of cadmium is well-known, many products still contain cadmium because it is not acutely toxic in commercial concentrations. But despite a lack of acute toxicity, chronic cadmium exposure can cause cellular dysfunction in the liver, which can have a detrimental impact on health. Glutathione can resist such dysfunction; the study demonstrated that when glutathione was boosted to greater than normal levels, liver cells recovered from cadmium exposure and maintained normal functioning. This beneficial effect of glutathione has been documented with other metals, ranging from iron to lead.
Given that metal chelation therapy is typically the only other option that a patient might have to address the toxicity caused by these metals, glutathione supplementation as part of a detox regimen could make a meaningful difference. Especially for patients who have chronic conditions that cause oxidative stress from other sources, addressing the stress caused by metal toxicity could provide significant benefits.
Ongoing research is attempting to shed more light on the scope and breadth of the combination of milk thistle and glutathione and their potential for purging the liver and the next few years will likely be replete with new findings. However, individuals seeking a more effective detoxification therapy for their liver can already benefit from therapeutic glutathione and milk thistle use, particularly as sophisticated new supplements enter the market.* These supplements can be used both routinely and preemptively when an individual expects to be drinking alcohol or being exposed to other sources of oxidative stress, like tobacco smoke.* For individuals who already have a weakened liver and seek to boost their liver’s ability to process toxins in the face of greater-than-usual oxidative stress, a milk thistle and glutathione detox regimen could also be a valuable addition to conventional therapies.* Taken together, these supplements offer a natural, highly tolerable, and potent combination to support health and well-being, potentially enhancing both longevity and quality of life.*
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your hepatic health.*
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Updated on March 27, 2023
Article Summary:
After watching someone you know struggle with dementia, the prospect of developing the condition yourself can be terrifying, especially given the fact that effective therapies continue to elude researchers. That’s especially true for those with a family history of Alzheimer’s and other genetic risk factors. Widespread public concern about dementia and Alzheimer’s risk have sparked decades of research on how to support brain health, including strategies that focus on food and nutritional supplements. Although this remains a broad area of research exploration, the strongest published data suggests that special diets (like the Mediterranean diet), specific foods (such as olive oil and coffee), and certain nutritional supplements (including phenolic compounds like curcumin and quercetin) can make a difference. If you are concerned about Alzheimer’s and dementia, then food support could be the best place to start.
The Mediterranean Diet was first identified as a possible strategy for Alzheimer’s disease based on observations of longer life expectancies and lower incidence of Alzheimer’s disease in the Mediterranean region, particularly around Naples, Italy. Unlike other specialized diets, the Mediterranean Diet is not strictly defined but generally understood to include high consumption of fruits, vegetables, whole grains, beans, nuts, and seeds, combined with moderate consumption of fish, poultry, and dairy products. The diet is also characterized by a low level of red meat consumption.
During the last several decades, a combination of laboratory, clinical, and epidemiological studies highlight the Mediterranean diet as a possible measure for combating Alzheimer’s disease. For instance, a community-wide study was conducted on 2,200 individuals in New York between 1992 and 1999. The participants’ diets were monitored every 1.5 years, and the researchers reported a statistically significant association between adherence to the general principles of the Mediterranean Diet and Alzheimer’s disease risk.
More recently, researchers have taken advantage of advanced technology to provide more solid evidence for a connection between the Mediterranean Diet and Alzheimer’s disease. In 2018, researchers at the University of Florence published a breakthrough study in which they used brain imaging to examine the neurological biomarkers of Alzheimer’s disease in individuals who adhered closely to a traditional Mediterranean Diet, as opposed to those who did not. The participants ranged in age from 30 to 70 years old, and the study lasted three years. Based on a combination of clinical and neuropsychological measures, the researchers estimated that adherence to a Mediterranean Diet could provide between 1.5 to 3.5 years of protection against Alzheimer’s disease. Although they caution that further investigations are necessary, the results indicate the Mediterranean Diet has clear potential as food support for Alzheimer’s disease.
Some critics of the research on the Mediterranean Diet warn that the diet is too general to produce reliable research results. Although the researchers who have studied the effects of the Mediterranean Diet developed rigorous methods for measuring patients’ adherence to the diet, these intricate scoring schemes can be hard for patients (and even clinicians) to understand and implement. Put more simply: it’s too hard for a person to know if their Mediterranean Diet is similar enough to those of the study participants for whom improvements were observed. Therefore, some researchers have begun to look at the specific benefits of individual components of the Mediterranean Diet, which can be more easily integrated into a patient’s daily meal plan. One of the most promising foods is extra-virgin olive oil—a characteristic element of the Mediterranean diet.
In the past few years, several animal studies offer strong evidence that extra virgin olive oil provides support against Alzheimer’s disease. For instance, in a 2015 study at the University of Louisiana, researchers observed that exposure to extra virgin olive oil reduced amyloid beta and tau buildup—both of which are hallmarks of Alzheimer’s disease onset and progression—in the brains of mouse models of Alzheimer’s. In 2017, another study confirmed these findings in mouse models, indicating that extra virgin olive oil could inhibit the amount of amyloid beta deposition and overall buildup in mouse models while lowering the amount of phosphorylated tau protein. The researchers also propose the activation of cell autophagy as a potential mechanism through which these anti-Alzheimer’s activities might be mediated.
The most recent studies in the field are providing increasing insight into the specific mechanisms through which the compounds in extra virgin olive oil could be supporting neurons during the onset and progression of Alzheimer’s disease. For instance, one study in the journal Advances in Experimental Medicine and Biology highlighted the role of olive oil-derived phenolic compounds—especially oleuropein aglycone and oleocanthal—in several key processes related to Alzheimer’s disease onset: amyloid-beta peptide and tau aggregation, the impairment of autophagy, and neuroinflammation. These multifunctional phenolic compounds not only have antioxidant activities that help reduce inflammation in the brain, but they are also associated with the activation of autophagy and the regulation of other pathways that are relevant to the disease development process, such as the phosphorylation of tau protein. Because it appears that olive oil-derived phenolic compounds target Alzheimer’s disease from multiple directions, it is a particularly appealing form of Alzheimer’s and dementia food support.
Although the increased consumption of certain foods is one possible way to modulate dementia and Alzheimer’s disease risk, some clinicians and patients prefer more targeted strategies. This has sparked research on which nutritional supplements can best support cognitive health. The nutritional supplements that show the most potential are plant-based, multifunctional phenolic compounds well-known for their antioxidant activities.* Considering that the Mediterranean Diet contains many foods that are high in these compounds, this should come as no surprise.
One of the most promising polyphenolic compounds is curcumin, which is derived from turmeric. Curcumin could provide support for maintaining cognitive health in many of the same ways as the phenolic compounds in olive oil. According to a 2017 review of in vitro and in vivo research, studies indicate that curcumin can resist the formation of amyloid plaques, promote the disaggregation of existing plaques, modify microglial activity to improve neuroprotection, disrupt the oxidative processes that contribute to inflammation, and regulate other pathways with known relevance to diminished cognition.* Because the data indicate that curcumin can have broad beneficial impacts on the brain when it comes to neural health, the authors conclude that it has “the potential to be . . . efficacious . . . .”
However, the researchers acknowledge that curcumin has a naturally low level of bioavailability. That’s why it’s better for curcumin to be taken in supplement form rather than in the form of food; i.e., because curcumin is so poorly absorbed in the gut, it is nearly impossible to add enough of it to food to make a clinical difference. Therefore, choosing a curcumin supplement that is scientifically formulated for bioavailability is the best way to take advantage of the multiple benefits of this phenolic compound for maintaining long-term cognitive health.*
Another phenolic compound that has shown promise for maintaining long-term cognitive health is quercetin. Quercetin is naturally found in some of the foods that characterize the Mediterranean diet, including leafy greens, red wine, citrus fruit, and garlic. Quercetin is also the key phenolic component in coffee, another food known to have potent neuroprotective effects. In fact, in a study conducted by researchers at the University of British Columbia in 2016, it was quercetin—not caffeine, as others had previously proposed—that was found to be the major neuroprotective component in coffee.* Like curcumin and the phenolic compounds in olive oil, quercetin helps maintain long-term cognitive health through multiple mechanisms, including the attenuation of the release of several key inflammatory proteins and the regulation of key proteins in several cell signaling pathways associated with cognitive dysfunction, such as the MAPK pathway and the NFkB pathway.
Another study out of the University of Kentucky indicates that the exposure of primary neurons to quercetin can inhibit the accumulation of amyloid beta, similar to curcumin and the phenolic compounds in olive oil.* The researchers measured free radical production in neurons in cell culture, and their findings suggest that the effects of quercetin are partially mediated by the compound’s antioxidant activities. After exposure to quercetin, the researchers observed lower levels of amyloid beta-related cytotoxicity, protein oxidation, lipid peroxidation, and apoptosis. When considered in the context of the other studies on phenolic compounds, these data further support the notion that phenolic compounds help maintain long-term cognitive health through multiple mechanisms.*
When it comes to maintaining long-term cognitive health, especially in the context of healthy aging, there is no clear consensus on which foods are best, although strong evidence points to the benefits of the Mediterranean Diet, especially phenolic-compound-containing elements like olive oil. Because food is not always the best way for patients to consume the compounds that support neural health, researchers are also exploring supplement options, with phenolic compounds like curcumin and quercetin showing particular promise. More comprehensive studies in the future will help clarify the clinical benefits of different dietary options, but clinicians and patients can already make health choices based on the strongest studies, using what is known to take action today.
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
Patients and families have long known about the connection between Parkinson’s disease and the GI tract. That’s because gastrointestinal dysfunction is one of the most common non-motor symptoms of Parkinson’s disease, and like so many of these symptoms, it often goes unaddressed.
However, as research in the field is advancing, there is a growing awareness of the importance of gastrointestinal function in the etiology of Parkinson’s disease. Many researchers now recognize the role of the brain-gut-microbiota axis in the onset and development of the condition.
Not only might changes in the microbiome be responsible for gastrointestinal dysfunction in Parkinson’s disease patients, they might also be linked to some of the characteristic neurological symptoms of the condition, including tremors, visual problems, and dementia.
This has led to calls for the development of a microbiome diet for Parkinson’s disease that might help ameliorate symptoms and slow the progress of the condition.
Multiple studies suggest the microbiome in individuals with Parkinson’s disease is compositionally different from that of healthy patients. For instance, in 2018, researchers from the University of Luxembourg reported statistically significant differences in the type and abundance of the bacterial species in the GI tracts of individuals with Parkinson’s disease, as compared to healthy controls. This association was also true for individuals with idiopathic rapid eye movement sleep behavior disorder, a condition seen as a red flag for the future development of Parkinson’s disease. This further suggests the composition of the microbiome plays a role in both the onset of the disease and its progress over time.
When considering the possibility of a microbiome diet for Parkinson’s disease, it is important to look at which types of bacteria are different in the GI tracts of individuals with the condition, as well as the functional impacts of these changes.
A particularly insightful study addressing these topics was conducted in 2015 by researchers at Rush University Medical Center in Chicago. The researchers collected fecal samples from 38 individuals with Parkinson’s disease and 34 healthy controls and found that the abundance of butyrate-producing bacteria from the genera Blautia, Coprococcus, and Roseburia was far lower in patients with Parkinson’s disease than their healthy counterparts.
Moreover, the Parkinson’s cohort was found to have higher levels of bacteria known to promote inflammation, including bacteria from the genus Ralstonia. These distinctions were associated with higher levels of colonic inflammation in the Parkinson’s cohort. This suggests that dietary strategies designed to maintain a normal inflammatory response in the gut, possibly including butyrate supplementation, might be a component of a future microbiome diet for Parkinson’s disease patients.*
Another study out of Saarland University in Germany supports this notion. Like the researchers who conducted the first study, they compared the gut microbial composition of 34 individuals with Parkinson’s disease with 34 healthy controls. Once again, they found the abundance of bacteria that produce short-chain fatty acids like butyrate was far lower in the gut microbiota of the Parkinson’s cohort.
They also extended the study to include measurements of the actual levels of short-chain fatty acids produced by the bacteria remaining in the gut to evaluate whether the lack of these bacteria was actually having an impact on short-chain fatty acid levels. Indeed, the lack of bacteria ultimately meant lower concentrations of short-chain fatty acids in the GI tracts of the Parkinson’s cohort. This deficiency might be playing a role in the dysfunction of the gut-brain axis and the exacerbation of debilitating symptoms.
Given the potential connections between gastrointestinal dysfunction and the motor and non-motor symptoms of Parkinson’s disease, a microbiome diet for Parkinson’s disease might prove to be an effective management option. However, scientific studies on this possibility are still in their infancy. One of the interventions that has been proposed involves increasing the intake of probiotics, either through supplementation or the consumption of fermented foods, because this strategy directly introduces beneficial bacteria in the gut microbiome.
In 2011, researchers at the Parkinson Institute in Milan, Italy, explored this idea by testing the efficacy of milk fermented with the probiotic strain Lactobacillus casei Shirota for managing patients with Parkinson’s who were also experiencing constipation. There was a statistically significant decrease in constipation symptoms among the 40 Parkinson’s patients who took part in the study. The researchers did not extend the study to include an evaluation of how the dietary therapy might have impacted the patients’ neurological symptoms via the gut-brain axis; therefore, additional research in this area is warranted.
Another relevant study from 2012 examined the potential neuroprotective benefits of curcumin, the active compound in turmeric, a spice that is commonly used in Indian food.* As a polyphenol, it makes sense that curcumin might ameliorate some of the symptoms associated with dysfunction of the gut-brain axis, given its well-established role in helping to maintain a normal inflammatory response throughout the body.*
As previously mentioned, colonic and neuronal inflammation have both been observed in Parkinson’s disease, and multiple studies suggest that curcumin intake (either in the diet or in bioavailable supplements) might have potential as a nutritional support therapy.*
In 2017, researchers from Bastyr University Research Institute in Washington adopted a much broader approach to early research on the development of a microbiome diet for Parkinson’s disease patients. Instead of evaluating the impacts of a specific type of food, the researchers conducted a survey of more than a thousand individuals with Parkinson’s disease to determine which foods were associated with slower progression of the condition and which foods were associated with faster progression.
They found that the foods that were significantly associated with slower progression of the disease included fresh vegetables, fresh fruit, nuts, seeds, non-fried fish, olive oil, coconut oil, wine, fresh herbs, and spices. There were also two nutritional supplements that provided benefits: coenzyme Q10 and fish oil.*
At the same time, the researchers found statistically significant associations between faster Parkinson’s disease progression and canned fruit, canned vegetables, soda (diet and non-diet), fried foods, beef, ice cream, yogurt, cheese, and iron supplementation. Although it is not clear how clinically relevant these associations might be, the findings provide a basic foundation for a microbiome diet for Parkinson’s disease in the future.
Given the relative lack of clinical studies on specific dietary interventions, there is not yet a single microbiome diet for Parkinson’s disease that can be recommended for all individuals.
However, anti-inflammatory foods and supplements like butyrate and curcumin that help maintain the body’s normal inflammatory response might play a role, so it could be worth considering how they could support symptom management through their mechanisms of action and their beneficial impact on the gut-brain axis.* Nutrient-dense fruits and vegetables, as well as probiotic foods, also appear to have positive effects, as they do for so many health conditions.
However, the field is still wide open for researchers, and it will be exciting to see where the data leads in the future. As the research progresses, patients and practitioners will be able to gain a better understanding of the connections between nutrition and Parkinson’s disease, which can ultimately lead to the development of a more specific microbiome diet for Parkinson’s disease patients.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your neurological health and gastrointestinal health.*
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Updated on April 7, 2023
Article Summary
In the United States, millions of patients and caregivers struggle endlessly with the multidimensional impact of autism. With diverse symptoms like social withdrawal, repetitive behavior, self-injury, stereotyped gestures, and gastrointestinal distress, therapies for autism must impact multiple neurobiological mechanisms to provide benefit to patients. Therapies that purport to address multiple symptoms simultaneously are attractive to researchers, patients, and caregivers alike. For many, gamma-aminobutyric acid (GABA) is one such therapy.
GABA is one of the brain’s core neurotransmitters responsible for inhibiting neuronal transmissions. When neurons are inhibited, they can’t transmit their electrochemical signals to other neurons as readily as they typically would.
Most people are familiar with the subjective effects of GABA in their brains owing to the sedating effect of alcohol consumption; alcohol molecules bind to GABA receptors, precipitating an inhibitory effect across the brain. As more GABA receptors are bound, this inhibitory effect increases, leading to sluggishness, sedation, relaxed muscles, uncoordinated movements, and weakening of impulse inhibition – the hallmark symptoms of being “drunk.” Cognitive ability drops, and memory consolidation is hampered. Although normal levels of GABA don’t cause these effects, they’re still responsible for helping the brain to regulate its level of arousal in multiple ways.
The relaxing effect of GABA inhibition is only half of the story, however. Individuals who are deficient in GABA are prone to the following neurological issues of over-excitability: seizures, agitation, irritability, and anxiety. These are issues that are common in autistic individuals. The rationale for using GABA supplements for autism is simple: because autism presents the same symptoms as systemically overly-excitable neurons, some believe that autistic patients don’t produce enough GABA to regulate neuronal activity.
However, autistic individuals don’t necessarily have insufficient GABA. Instead, they might not have sufficient cellular machinery necessary to utilize GABA normally. Caregivers who are looking for a new therapy to address the agitated or anxious behavior associated with autism must thus be careful when evaluating GABA as a therapeutic option and might want to explore butyric acid as a more promising alternative.
At first glance, GABA would seem to make for an effective autism therapy. Symptoms of acute agitation, anxiety, and self-harm in individuals without autism are often addressed with anxiolytic drugs like benzodiazepines, which increase the concentration of GABA in the synaptic cleft of neurons. The subsequent inhibition of neurotransmission transiently calms the patient.
This suggests that supplementation with GABA might provide a similar but lesser effect, potentially addressing the same symptoms of excitation in autism without the risks inherent with benzodiazepines. Unfortunately, GABA might not be an effective therapy for autism because autistic individuals might have neuronal defects that prevent them from effectively using additional GABA.
Autistic individuals are known to have fewer of several GABA receptor subtypes on the neurons in the prefrontal cortex. Similar aberrations are likely present in other parts of the brain. Although the cause of this phenomenon is unclear, the effect is that the neurons of autistic individuals are less inhibited by GABA than those of a neurotypical person.
This means that even if autistic individuals have sufficient GABA, their neurons would have a much lower limit on the amount of inhibition they could bring to bear when they encounter GABA. The downstream result is that some regions of the brain, like the prefrontal cortex, are habitually overstimulated, causing effects ranging from depression to stereotyped behavior. Adding GABA won’t make up for having fewer GABA receptors.
Furthermore, researchers believe that autistic individuals have malformations in the neuronal pathways that utilize GABA to inhibit other tracts of neurons. As such, even if there is a sufficient quantity of GABA ready for use and a sufficient number of receptors ready to accept the molecules, autistic individuals might not have the neurotypical neuronal connections that allow GABA to be used effectively. This would lead to a weaker than expected effect of GABA. Adding more GABA won’t change the structure of neuronal tracts, but it might cause systemic inhibition and cause intense sedation as a side effect.
There are also other issues with GABA supplements. It is generally accepted that GABA cannot cross the blood-brain-barrier. This means GABA would not be capable of addressing neurological issues by operating directly on neurons. Even when delivered to the brain directly via injection (something not done outside experimental contexts), neuronal mechanisms like the GABA reuptake protein ensure it is rapidly eliminated. Nutritional supplements claiming to offer therapeutic benefits owing to their GABA content have nonetheless shown minor beneficial effects. In a small pilot study, patients who took a GABA supplement experienced reduced levels of anxiety. As noted by the authors, this finding indicates that GABA might be able to cross the blood-brain-barrier in small quantities, although further research is needed to draw firm conclusions.
At present, there are no studies examining the efficacy of GABA supplements on autism symptoms; the above study, like others investigating GABA supplementation, was limited to neurotypical participants examined during performance of anxiogenic tasks, like mental arithmetic. The above study also found that the participants’ immune systems showed signs of suppression in the form of reduced immunoglobulin secretion—a problematic side effect that would lead to a higher risk of illness.
The gaps in the research and lingering engineering challenges regarding bioavailability mean that GABA supplements must be studied further before it can be concluded that they can help autistic patients. However, this conclusion shouldn’t dissuade patients, caregivers, and practitioners from investigating an alternative compound that might seem superficially similar. Indeed, those who are interested in a natural yet more promising therapeutic option for autism might be better served by butyric acid, a compound that has the potential to address multiple dimensions of autism at the same time, but which lacks the major drawbacks of GABA.
Although GABA is an organic acid, other organic acids might be more effective therapeutic options for autism. Butyric acid is one such option. Although laymen might believe that butyric acid is similar to gamma-aminobutyric acid owing to its name, butyric acid is distinctly different from GABA, as is its physiological role. Produced in the gut, butyric acid is used by the body to feed helpful gut microbiota and signal white blood cells.*
Butyric acid might also be considered a neurotransmitter, although its capacity in this role requires further research. Interestingly, in the capacity of immune cell signaling, GABA and butyric acid share similar purposes; both inhibit the ability of white blood cells to up-regulate inflammatory response by reducing the ability of white blood cells to secrete proinflammatory molecules.* Butyric acid has more to offer autistic individuals than only the down-regulation of inflammatory response, however.
Researchers have determined that autistic individuals typically have markedly lower concentrations of butyric acid in their intestines than is found in healthy patients. This might be a contributing factor to autistic patients’ consistent symptoms of gastrointestinal distress. But the benefits of butyric acid aren’t limited to gastrointestinal health; researchers believe butyric acid could be effective at simultaneously addressing the GI tract’s inflammatory response and addressing behavioral symptoms in autism patients.* The rationale is that by down-regulating the activity of gastrointestinal white blood cells, which are causing an excessive inflammatory response, the patient’s gut-brain axis will be less overstimulated, resulting in a concomitant drop in overstimulation of the patient’s brain.*
Modulating the level of stimulation in the gut-brain axis is critical. The gut-brain axis is the primary conduit of nerves connecting the gut to the brain’s sensory cortices. In short, when patients experience nausea or distress in their intestines, it’s the gut-brain axis that relays that information to the brain and links it to initiating compensatory behavior.
Too much actuation of the gut-brain axis leads to over-stimulation of the areas of the brain that process the sensory input. Patients could thus experience agitation, self-injurious behavior, and overanxiousness. Butyric acid therapy thus holds promise for keeping the gut-brain axis from causing problems elsewhere.*
There is another major reason butyric acid is an appealing therapeutic option: unlike GABA, butyric acid can reliably cross the blood-brain-barrier.* Although butyric acid administered orally would initially act on the gastrointestinal tract, after the butyric acid is distributed through the patient’s bloodstream it would eventually reach the brain. After reaching the brain, butyric acid’s beneficial effects could include better orientation of attention, inhibition of motor tics, and improved emotional regulation—areas in which autistic individuals often struggle.* *These benefits are the result of butyric acid reducing the propensity of the white blood cells to up-regulate the inflammatory response.
Autistic individuals are thought to have high levels of inflammation in their brains, which contributes to cognitive and behavioral symptoms. When inflammation in the brain increases, general brain function decreases. The deficits of brain function that are the most noticeable in terms of patient symptoms occur in the frontal lobe and include symptoms like difficulty concentrating and regulating emotions.
Maintaining the brain’s normal inflammatory response is therefore a pathway to addressing a handful of different autism symptoms. Butyric acid weakens the ability of white blood cells to up-regulate the brain’s inflammatory response by inhibiting their ability to retransmit chemical signals that tell them to secrete proinflammatory molecules.* The systemic impact is that the brain’s normal level of inflammatory response is maintained.* For the moment, measuring the concentration of proinflammatory molecules in the brain isn’t possible with living patients.
Exciting new research is in the process of establishing a definitive account of butyric acid’s benefits for autistic individuals, and the initial evidence is more than sufficient to make a comparison with GABA. Although GABA suffers from a number of immutable physiological barriers to being an effective therapeutic option for addressing autism symptoms, butyric acid takes advantage of a variety of different mechanisms to aid autistic patients more effectively.* Furthermore, whereas the GABA supplements on the market are unproven in the scientific literature, butyric acid is already produced to a high standard of quality and is supported by a growing body of literature.
Butyric acid is known to be effective in aiding the GI tract’s inflammatory response in multiple contexts.* As shown by a 2011 study published in the Cellular Metabolism journal, butyric acid inhibits an autoimmune response in the event of compromised colon cells.* When colon cells are compromised by excessive inflammatory response or malnutrition—both of which are likely to occur in autistic individuals—they begin a process known as autophagy, in which the cells on the inside of the colon wall are broken down and consumed for energy.
As shown in the 2011 study, adding butyric acid to the colonocytes inhibits this destructive behavior.* The inflammatory response is suppressed as a result, and negative externalities like intestinal discomfort or constipation are ameliorated.* These benefits carry over directly to autistic patients who struggle with these symptoms.*
Mouse studies have also reliably linked the beneficial effects of butyric acid to behavioral autism symptoms. In one such mouse study, a group of mice was artificially induced to have symptoms that mimicked autism. Then, the mice were split into several groups and given either placebo or compounds containing butyric acid and similar chemicals. The researchers subsequently introduced the mice to neurotypical mice they had not associated with before.
The neurotypical mice in the control group interacted with the new neurotypical mice for an average of 300 seconds, whereas the autism model mice who had received the placebo interacted with the neurotypical mice for 20 percent less time. When the researchers tested the autism model mice that had received the butyric acid-containing compound, the mice socialized with the others for just under 290 seconds—an improvement of roughly 50 seconds compared to the mice that didn’t receive the therapy. With the addition of butyric acid, the mice were able to socialize 95 percent as long as neurotypical mice.Although the results in the mouse models don’t imply similar results will occur in human patients, the results do show that the implications of there being similar successful therapy in humans are substantial. Clinical trials in humans are ongoing, and soon researchers should be able to determine if similar results occur in human patients. If patients and caregivers are eager to utilize this therapeutic option before the clinical data is available, then they can easily and safely do so.
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 gastrointestinal health.*
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Updated on April 7, 2023
Article Summary
As people become more health-conscious and increasingly seek natural alternatives to pharmaceutical drugs, those with a wide variety of health conditions are expressing interest in the benefits of antioxidant supplementation. There is good reason for this; in the body, antioxidant molecules scavenge the free radicals that are produced by oxidative processes, which otherwise have the potential to cause significant cell and tissue damage.
Indeed, a growing body of research indicates that in both foods and in nutritional supplements, antioxidant-containing compounds can provide nutritional support for a broad range of physical and mental health conditions, from cardiovascular disease to autism spectrum disorder (ASD).* For many patients, families, and practitioners looking to manage conditions like these, antioxidants pose an appealing alternative to traditional pharmacotherapy, given that they are often derived from all-natural sources.
The appeal of antioxidants also hinges on the notion they are generally less likely to have side effects than standard pharmaceutical treatments. However, this view has been called into question over the years, and many are increasingly expressing concerns about the safety of antioxidant use. Upon consideration of the reported side effects of dietary supplementation, there is no clear connection between a compound’s antioxidants and its potential side effects.
In fact, most side effects are relatively mild, and they have been reported in only a minority of users. Therefore, it’s best to approach the use of antioxidant-containing compounds for health purposes on a case-by-case basis. By examining the evidence more closely, you can determine whether antioxidant supplementation is right for you.
One of the first instances in which the safety of antioxidants was called into question was that of beta-carotene, a carotenoid found in many fruits and vegetables. In the late 1990s and early 2000s, there were several clinical studies in which higher mortality rates were observed in patients who were taking beta-carotene supplements. Although these studies naturally raised concerns in the research community, follow-up studies were unable to confirm a direct connection between beta-carotene and disease or mortality risk.
As early as 1999, scientists pointed out that the concerns about the side effects of antioxidants like carotenoids were limited to highly specific clinical circumstances. Indeed, according to a review in the Journal of the American College of Nutrition, the antioxidant activities of carotenoids “promote health when taken at dietary levels,” and adverse health effects are only observed when the compounds are “taken in a high dose by subjects who have smoked or who have been exposed to asbestos.”
More recently, comprehensive studies on beta-carotene have also failed to demonstrate an association between this antioxidant-containing nutrient and potential long-term side effects. In 2013, the data from a meta-analysis of six randomized controlled trials (which included more than 40,500 patients) indicated the link between beta-carotene and cancer risk was tenuous at best, even in high-risk populations; the authors of the study found the incidence of cancer was not significantly higher among healthy patients who took beta-carotene supplements, and the risk was only “marginally increased” among cancer patients.
This lack of long-term side effects of beta-carotene was verified in a broader 2016 meta-analysis. In this review, the researchers probed seven studies for evidence of a link between beta-carotene and all-cause mortality—not just deaths from cancer. Not only was beta-carotene not associated with a higher risk of mortality, the data indicated that supplementation with beta-carotene actually led to a significantly lower risk of all-cause mortality, directly contradicting what had been found in the earlier studies.
As more evidence accumulates, it now appears the potential long-term side effects of beta-carotene are outweighed by its beneficial antioxidant activities and other likely health benefits.
Beta-carotene is not the only compound with significant antioxidant activity. In recent years, researchers have explored a wide range of all-natural, plant-based phytochemicals with antioxidant effects. Most of the human and animal studies on the efficacy of these compounds for various health issues have included evaluations of potential side effects. On the whole, the side effects of antioxidants tend to be minimal or nonexistent. Consider the following findings for several of the antioxidant-containing compounds that have recently shown particular promise for various physical and mental health conditions:
Within the clinical and research communities, curcumin has a well-established safety record. Both the Joint United Nations and World Health Organization Expert Committee on Food Additives (JECFA) and the European Food Safety Authority (EFSA) have established an allowable daily intake of curcumin at 0-3 mg/kg of body weight. While the participants in some studies reported minor side effects—such as nausea, diarrhea, headache, and rash—these were most often observed when curcumin was being taken at an unusually high dosage of 500 to 12,000 mg per day. Considering that curcumin supplements are now provided in highly bioavailable forms, individuals usually do not need to take such high doses to see therapeutic results.
Like curcumin, resveratrol is generally considered to be safe and well-tolerated by almost all users. In a 2017 review in the journal Oxidative Medicine and Cellular Longevity, researchers examined clinical studies in which resveratrol supplements were taken in doses ranging from 20 mg per day to 2 g per day, and they found that almost all subjects reported no side effects.
Only when healthy subjects were taking 2 mg to 5 mg per day did side effects become more frequent, and they were still limited to mild gastrointestinal complaints: flatulence, nausea, stomach pain, and/or diarrhea. Similarly, studies in animal models have reported no adverse short-term or long-term side effects of resveratrol supplementation.
A 2018 review in the journal Molecular Nutrition and Food Research examined the safety profile of quercetin, another phytochemical with beneficial antioxidant activity.* According to the researchers, in human research studies, negative side effects “have rarely been reported, and any such effects were mild in nature.” Indeed, since the late 1990s and early 2000s, studies have consistently shown that quercetin has “very small side effects,” even at dosages as high as four grams per day. Although the authors did report on animal studies suggesting possible interactions between quercetin and common pharmaceutical drugs, this issue must be considered when trying any nutritional supplement, not just an antioxidant.
Another antioxidant-containing compound that has recently risen to prominence for addressing various health conditions is glutathione (GSH). As the most abundant endogenous antioxidant in the body, glutathione’s activity is considered essential to a wide range of cellular processes.
In a recent randomized, placedbo-controlled trial, research showed, for the first time, that daily supplementation with glutathione can significantly increase how the body’s stores of GSH, which otherwise declines with age.* Moreover, no serious side effects were reported by participants in the study, which further adds to glutathione’s promise as a nutritional supplement.
This result mirrors earlier findings. In a 2011 clinical study involving GSH supplementation, only eight of the 40 participants reported adverse effects: Five noted increased flatulence and loose stools, two said they experienced flushing, and one said they had gained weight. Therefore, in regard to safety, the researchers concluded that, “it is not an apparent barrier to continued clinical trials” on GSH supplementation. This conclusion was further verified in a 2015 study comparing oral and sublingual glutathione supplementation.
Although the 2015 study was relatively small in scale—only 20 participants—no adverse events were reported by any participants, regardless of the GSH supplementation method. Considered in the context of the other research on the topic, these findings suggest it is unlikely for patients to experience adverse symptoms from using GSH. Even if they do, the side effects of this antioxidant-containing compound are likely to be far more mild than those often reported for the most common pharmaceutical drugs on the market.
Ultimately, when considering the existing body of scholarly literature, it appears unwise to draw a broad conclusion about the side effects of antioxidants because they vary so widely. Based on the results of studies on beta-carotene, other common phytochemicals, and glutathione, there are three major factors that affect the potential for an antioxidant-containing compound to produce side effects: the dosage, the user’s unique physiology, and the nature of the compound itself. Because there are no clear connections between the side effects observed for different antioxidants, it does not seem like the antioxidant activity of these compounds is directly responsible for any adverse effects.
That’s good news for consumers and practitioners both, because it leaves lots of room for experimentation. For instance, if a consumer experiences mild gastrointestinal discomfort when they increase their intake of a particular antioxidant (either through nutritional supplementation or dietary changes), they might still be able to reap the health benefits of antioxidant intake by trying a different dosage or a different antioxidant compound that has been shown to exert a similar physiological effect.
Further research into the efficacy of these compounds will likely shed more light on the reasons some individuals experience adverse effects and others do not. For now, consumers and practitioners can take comfort in the knowledge that most antioxidants are generally considered safe and pose a low risk of side effects, especially compared to the pharmaceutical drugs that might otherwise be used to address important health concerns. Individuals who want to optimize potential benefits while reducing the possibility of side effects further should consider supplements formulated with advanced delivery methods, such as those produced by Tesseract Medical Research.
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 healthy aging.*
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Updated on March 27, 2023
Article Summary
From major operations to minor outpatient procedures, surgery is ubiquitous in modern medicine. Unfortunately, even the least invasive surgeries are hard on the body. Even surgeries with local anesthesia leave behind wounds that take time to heal. For more serious surgeries, patients are heavily medicated with sedative and analgesic drugs and experience substantial tissue damage. Without any complications, a major surgery still causes blood loss, trauma, and a prolonged period of chemical washout after the procedure ends.
For most patients, the surgery itself is the easy part; the challenges usually begin when they enter the postoperative recovery period, particularly if they struggle with the therapeutic coverage and side effects of postoperative medications. But they don’t have to. For many patients, these struggles can be eased by post-op recovery supplements that can help normalize the body’s inflammatory response.
Inflammation commonly crops up in the postoperative environment with symptoms like painful swelling, redness, and heat at the site of wounds. Recently, researchers have started to consider inflammation as a systemic phenomenon that can cause wide-ranging problems. Even when far from a surgical site, inflammation can hamper the operation of the brain, and, when paired with the toll that anesthesia takes on the brain, might even be temporarily debilitating. For example, patients often experience a variety of mood issues after surgery, which might in part be caused by excess inflammation. Thus, normalizing the body’s inflammatory response is a major factor influencing the rate at which patients recover from surgery.
Many surgeons recommend commercially available non-steroidal anti-inflammatories (NSAIDs) for use after discharge. Although these medications are effective at reducing inflammation to safe levels, patients who still have residual pain might end up taking more than is safe, potentially compromising their health. NSAIDs are known to cause ulcers when used in excess, and in severe cases could even degrade the integrity of the colon. Additionally, even when taken in therapeutic quantities, NSAIDs can slow wound healing and thin the blood, which makes them an imperfect solution at a time when healing is paramount. Therefore, although these medications are ubiquitous among postoperative therapies, many patients are still searching for complementary therapies that don’t cause uncomfortable or counterproductive side effects.
Aside from the medications suggested by doctors, patients also commonly turn to ice packs to calm inflammation and provide pain relief. Application of ice shrinks blood vessels, which inhibits swelling. When used for too long, however, ice packs can cause damage of their own or inhibit wound healing. Furthermore, the packs can’t be kept on the patient 24/7; there’s a large amount of therapeutic “downtime” during which patients aren’t able to use the therapy. As such, ice packs are often insufficient to relieve patient discomfort.
Due to the shortcomings of standard inflammation control, both patients and practitioners are increasingly looking toward achieving postoperative symptom relief from the nutritional support provided by supplements.
Evidence suggests that restoring the body’s normal inflammatory response postoperatively can be achieved by a natural compound.* That compound is butyrate, also known as butyric acid, a physiological molecule produced by the cells of the large intestine. In the large intestine, butyrate is responsible for regulating cellular behavior, maintaining normal inflammatory responses in the gut, and helping immune cells manage the gut microbiome. Butyric acid has also been identified in a research review as helping to prevent the translocation of harmful bacteria from the intestines to the bloodstream.
In the review, researchers noted that daily supplementation with a small quantity of butyric acid peaked the proliferation of cells responsible for maintaining a normal inflammatory response in the gastrointestinal tract by 60 percent.* This means that more of those cells were present in the GI tract, increasing the overall beneficial response to inflammation.* When recovering from surgery, these additional cells could help the gastrointestinal tract return to its normal function much faster than it otherwise would. According to the authors, this means that approximately 66 percent of elderly people with gastrointestinal issues would benefit from butyrate supplementation.
The applications of butyrate in the postoperative environment are likely beneficial to patients struggling with recovery issues, and large clinical trials demonstrating this impact are forthcoming. Investigations into the tolerability of butyrate are promising, with several studies reporting no adverse effects among participants. Additionally, butyrate is, in principle, compatible with other supplements that can be used in a postoperative environment; supplements like fish oil are natural companions to butyrate when it comes to achieving postoperative symptom relief*.
Fish oil is widely recognized as having proven applications in postoperative inflammation. A 2012 study examining the impact of fish oil administration on postoperative outcomes found that patients who received fish oil experienced 33.3 percent reduced liver dysfunction caused by inflammation and 27.8 percent fewer infections. Furthermore, the patients who were supplemented with fish oil exhibited lower levels of a wide swath of proinflammatory molecules. These effects are due to the presence of compounds called eicosanoids that behave as cellular signaling molecules. Although the study wasn’t blinded or controlled, the data are unambiguous: fish oil is effective in reducing postoperative inflammation.
In normal therapeutic quantities, fish oil results in no side effects. However, when taken in excess, the vitamin A present in fish oil can cause vitamin A toxicity. Although this toxicity can cause brittle bones and liver malfunction, it is very rarely a result of fish oil consumption. As such, fish oil is considered to be a safe and well-tolerated supplement with broad appeal. But it has newer challenges, including tetrahydrocurcumin, a particularly promising solution returning the body’s inflammatory response back to post-surgery normalcy.*
Tetrahydrocurcumin is a member of the curcuminoid class of compounds that are derived from the turmeric root. Curcuminoids have a history of medicinal use going back thousands of years, and modern research has found them to be a compelling avenue of investigation owing to their ability to support the body’s natural inflammatory response.*
This ability to support a healthy response to inflammation is especially pronounced in the case of tetrahydrocurcumin because it more efficiently down-regulates proinflammatory genes than other curcuminoid types.* One in vitro study found that a mix of curcuminoid compounds containing predominantly tetrahydrocurcumin down-regulated the activity of a gene coding for a critical proinflammatory molecule by 85 percent. The gene, NF-kB, is one of the core molecules the body uses to signal cells to initiate inflammation. Importantly, in 2018, an in vivo study found that tetrahydrocurcumin limited the production of NF-kB molecules by as much as 90 percent depending on the amount of tetrahydrocurcumin consumed. Furthermore, tetrahydrocurcumin can down-regulate the production of another proinflammatory molecule known as COX2.* As a result, tetrahydrocurcumin holds significant potential for reducing patient discomfort in a postoperative environment.*
Providing nutritional support from safe and effective nutritional supplements that help restore the body’s normal processes for responding to inflammation would be very useful for postoperative patients, potentially addressing an array of postoperative challenges.
Many medications administered during surgery conducted under general anesthesia have an array of side effects, including constipation. These medications include antibiotics, analgesics, sedatives, anxiolytics, and muscle relaxants.
Of these drugs, all but anxiolytics have the potential to negatively impact the gastrointestinal system in the short term by slowing it down or stopping its activity altogether. Doctors compensate for the impact of these drugs by limiting patients to certain kinds of foods before and after surgery, but by the time patients are discharged, there are still traces of the drugs impacting their systems. When paired with postoperative pain management, gastrointestinal issues are some of the hardest to resolve and are highly unpleasant to patients.
Gastrointestinal tract issues often persist well after the patient leaves the hospital; constipation is all but assured from the surgical medicine regimen and the tools that patients receive to control pain at home can make the problem worse. In particular, nearly all but the most minor surgical procedures can involve operative and postoperative administration of opioid painkillers. Opioids are notorious for reducing intestinal motility, diminishing intestinal energy usage, and subsequently inhibiting normal bowel movements. To make matters worse, the typical nutritional aids to help patients with bowel movements might not be accessible while recovering from surgery. Coffee or green tea, for example, might be prohibited after surgery due to their stimulating properties. Likewise, fiber-rich foods, like lentils, might be restricted until the patient’s gastrointestinal tract has recovered. This is where butyrate can again play a significant role.
Today, a growing number of patients are using butyrate as a powerful tool in the face of postoperative constipation owing to its ability to promote a healthy gut microbiome.* According to Polish researchers, butyrate effectively addresses constipation.* In the study, the researchers administered small quantities of butyrate to patients with constipation during a 12-week period. After four weeks, stools in the patients who received butyrate were consistently textured twice as much than the control patients, and patients who took butyrate reported 69 percent less discomfort.* Furthermore, the patients who received butyrate supplements experienced constipation half as frequently and reported a 42.1 percent reduction in discomfort during bowel movements compared to the patients who didn’t.* These effects were durable for the remainder of the 12-week period and beyond. Importantly, the results corroborate the group’s prior research.
The group’s prior clinical review also suggests a broader role for butyrate in addressing a wide variety of other gastrointestinal diseases. In the context of postoperative care, patients might be inclined to take a butyrate supplement to address more than one of their health challenges. Because butyrate can address both constipation and inflammatory response, it’s uniquely disposed to help patients recover after surgery.
With nutritional supplements that contain tetrahydrocurcumin and butyrate, post-op patients have access to better resources than ever before. Although robust clinical trials supporting the use of these compounds in the postoperative niche are still forthcoming, an abundance of evidence suggests that the buzz generated by impressive in vitro results will carry over to patients. Researchers already have enough confidence in these two compounds to formulate specialized delivery systems to enable patients to take advantage of them to the fullest extent possible. Thanks to these compounds, patients can better deal with the side effects of surgery and postoperative medications.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your immune health.*
Banasiewicz T, Borycka-Kiciak K, Dobrowolska-Zachwieja A, et al. (2010). Gastroenterology Review, 6, 329-334.
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Updated on March 24, 2023
Article Summary:
There’s nothing wrong with having a glass of wine to relax after dinner or occasionally letting loose on a Saturday night. For some individuals, however, the consequences of even a small amount of alcohol consumption can be intense. A hangover can leave you feeling terrible whether it’s the result of one too many bellinis or a night of heavy partying. Regardless of your drinking habits, the reality is that alcohol plays an essential role in our culture today—and that can present a major challenge for individuals who struggle with hangover symptoms. As a result, there is growing interest in the science behind hangover symptoms, including the effects of the byproducts of the body’s metabolism of alcohol, like acetaldehyde.
Acetaldehyde’s role in causing the characteristic pharmacological and behavioral effects of alcohol consumption has long been controversial. Acetaldehyde is the first breakdown product in the multi-step process of alcohol metabolism, and the buildup of this toxic compound in the liver is associated with some of the most common hangover symptoms, including headache and nausea. Although the evidence remains mixed, a number of studies have highlighted statistically significant correlations between acetaldehyde levels in the blood and hangover severity. Based on the available data, some researchers hypothesize that therapies targeting acetaldehyde-related pathways could be effective in improving symptoms. In particular, preliminary studies suggest that supplements derived from phenolic compounds, such as resveratrol, quercetin, curcumin, and other antioxidants are effective therapeutics for reducing hangover symptoms.*
To understand why acetaldehyde buildup worsens a hangover, it is essential to consider the initial steps of alcohol metabolism in the liver. The first step is the breakdown of ethanol to acetaldehyde, a toxic compound that promotes cell and tissue damage. From there, acetaldehyde is metabolized by the enzyme alcohol dehydrogenase, leading to the production of glutathione, an antioxidant. However, when ethanol intake is excessive, the normal activity of alcohol dehydrogenase is insufficient to process the amount of acetaldehyde that is accumulating, which can lead to acetaldehyde buildup in the liver. It is the subsequent acetaldehyde accumulation that is believed to account for hangover symptoms like headache and nausea.
As the level of acetaldehyde rises, the level of glutathione falls. This is partially because less acetaldehyde is being broken down by the acetaldehyde dehydrogenase enzyme. Additionally, glutathione is further depleted in the presence of excessive acetaldehyde because it conjugates with acetaldehyde. The rise in these glutathione-acetaldehyde conjugates has the potential to lower glutathione antioxidant activity, which can further contribute to oxidative stress that produces more severe hangover symptoms.
Although questions remain within the scientific community regarding the connections between hangover symptoms, acetaldehyde levels, and glutathione levels, their intertwined relationships are supported by recent genetic data on acetaldehyde dehydrogenase enzyme activity in ethnic Asian populations. There are three genes that encode acetaldehyde dehydrogenase, and several variants are associated with a higher risk of alcohol dependence among certain ethnic populations, suggesting that gene-based reductions in acetaldehyde dehydrogenase activity might be the source of problems with alcohol metabolism, leading to more severe hangover symptoms. Indeed, the populations studied reveal that certain gene variants are associated with limited acetaldehyde dehydrogenase activity, increased acetaldehyde buildup, and more severe reactions to alcohol consumption. Therefore, this study has served as a foundation for research on therapeutic strategies for hangover relief that seeks to target the chemical pathways involved in acetaldehyde buildup during the alcohol metabolism process.
Preliminary research suggests that dietary supplementation with phenolic compounds can effectively address acetaldehyde-mediated symptoms of hangovers.* One of the most enlightening studies was conducted by researchers from Kyungpook National University in South Korea. Recognizing the connection between acetaldehyde buildup and inhibited antioxidant activity, the researchers conducted a study to determine whether supplementation with sprouted peanut extract could mediate ethanol-induced hangover symptoms in rat models. Sprouted peanut extract is high in resveratrol, a phenolic compound with known antioxidant properties and the ability to support the body’s natural inflammatory response. Upon treatment with 100 mg, 200 mg, or 400 mg of sprouted peanut extract, the rat models exhibited higher levels of alcohol dehydrogenase activities. Based on their findings, the researchers propose that phenolic compounds, such as resveratrol, quercetin, and curcumin can effectively limit acetaldehyde accumulation by improving alcohol metabolism, making supplementation a possible option for addressing symptoms.*
Another relevant study by researchers at Sun Yat-Sen University in China produced mixed evidence, although the overall implications are consistent with those of the above-described study. These researchers simultaneously treated mouse models with ethanol and various non-alcoholic beverages, including two types of tea that are high in phenolic compounds: green tea and honey chrysanthemum tea. Although intake of these beverages did not lower acetaldehyde levels to a statistically significant degree, they did significantly increase acetaldehyde dehydrogenase activity in the liver, suggesting they might still enhance the alcohol metabolism process. The researchers also suggest that the antioxidant activity of the phenolic compounds in these teas further contributes to reductions in hangover symptoms by reversing the toxic oxidative effects of acetaldehyde buildup. Therefore, they propose the development of nutritional supplements formulated with the active phenolic compounds in green tea and honey chrysanthemum tea for minimizing hangover symptoms, as well as other harmful impacts of alcohol consumption.
A related preliminary study out of Suwon Women’s University in South Korea generated similar results and recommendations. This 2016 study stands out because it was conducted on humans. Again, the research was premised on the notion that these compounds can enhance alcohol metabolism and lower oxidative stress, thereby reducing hangover symptoms. For this study, 20 healthy adult males were recruited to participate. The treatment group was directed to ingest a supplement containing three botanical extracts with antioxidant activity that have traditionally been used to address hangover symptoms—Viscum album L. (40 percent), Lycium chinesense L. (30 percent), Inonotus obliquus (20 percent), and Acathopanax senticosus H. (10 percent)—contemporaneous with consuming a bottle of commercially available liquor. The control group ingested a placebo along with the liquor. In the participants in the treatment group, although the researchers observed a non-significant decline in acetaldehyde levels, they also noted a significant rise in antioxidant activity levels two hours after drinking. Not only does the study provide additional evidence that acetaldehyde levels are directly related to hangover symptoms, but the results also suggest that supplements with antioxidant activity help resist the oxidative stress that leads to hangover symptoms.
Research on acetaldehyde and hangovers is still in its preliminary stages. The scientific community has yet to come to a consensus on the mechanisms of action by which hangovers can be mediated and the roles that acetaldehyde and other reaction products play in the process. Although early animal studies suggest that polyphenolic compounds and other antioxidants are promising candidates for the development of nutritional supplements in the future, the evidence is not definitive. Similarly, the results in small-scale human studies suggest that reducing acetaldehyde levels can address hangover symptoms, but an ideal strategy is not yet clear.What is clear is that researchers need to build on the existing research, through a combination of in vitro and in vivo studies, to establish stronger connections between acetaldehyde levels and hangovers, as well as to explore the efficacy of various nutritional supplements—especially polyphenolic compounds that have antioxidant properties. However, practitioners and consumers can consider trying polyphenol-based nutritional supplements to address the usual headaches and nausea caused by a hangover, before such large-scale research gets underway.* Because anecdotal evidence often serves as a driver of comprehensive, randomized controlled trials, the research community can benefit from input from the clinical community. Plant-derived compounds like resveratrol, quercetin, and curcumin are considered to be safe for otherwise healthy individuals, so they are worthy of consideration by those who are seeking hangover relief.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your hepatic health.*
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