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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.*
Bhandari R, Kuhad A. 2015. Life Sciences. 141:156-69.
Darbinyan LV, Hambardzumyan LE, Simonyan KV, et al. 2017. Metabolic Brain Disease. 32(6):1791-1803.
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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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Hyllested M, Jones S, Pedersen J, Kehlet H. (2002). British Journal of Anaesthesia, 88(2), 199-214.
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Trads M, Deutch SR, Pedersen PU. (2017). Scandinavian Journal of Caring Sciences.
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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Updated on March 27, 2023
Article Summary:
Many patients who struggle with anxiety spend years (or even decades) trying to find an approach that truly works to address their symptoms, often without achieving durable relief. Indeed, studies show that the efficacy of psychotherapy and pharmacotherapy options can vary considerably, depending on both the nature of the therapy and the individual patient’s response. Psychotherapeutic approaches like cognitive behavioral therapy, for example, often only partially alleviate symptoms, and many patients shy away from pharmaceutical drugs that carry side effects and fail to produce the desired outcomes. To develop more reliable therapies for patients with anxiety, scientists have spent decades trying to better understand the biological underpinnings of the condition. Although the question is far from resolved, it is becoming increasingly clear that the gut-brain axis has a role in the mediation of symptoms.
The term “gut-brain axis” refers to the bidirectional connection between the gastrointestinal (GI) tract and the central nervous system (CNS). In recent years, researchers have discovered that the communication between these two systems has a direct impact on mental health, by regulating key physiological processes associated with anxiety. Still remaining to be fully elucidated is an understanding of the biological mechanisms that link the GI tract and CNS to form the connections in the gut-brain axis that mediate symptoms of anxiety. One of the most promising proposals is that the activities of the bacteria in the microbiome play an essential role in the communication process. These findings have important implications for the development of future therapies, suggesting that probiotic, prebiotic, and butyric acid supplementation might be able to address select symptoms of anxiety.
Recent studies suggest there are two important ways in which bacterial activity in the gut facilitates the communication that underpins the gut-brain axis: by interacting directly with peptides in the gut and by producing functional metabolites, like short-chain fatty acids. There is a wide range of peptides present in the gut microbiome, and they communicate with the CNS by binding to immune receptors and the terminal of the vagus nerve, a peripheral nerve with a known connection to both anxiety disorders and inflammatory processes. Signals produced by the bacteria in the microbiome can directly regulate the concentrations of these peptides in the gut, which directly affects their communication with the CNS. According to the latest research, the proportions of the various different bacterial strains residing in the gut microbiome directly determine which peptide-regulating signals are produced, suggesting that supplementation with certain bacterial strains would aid in the modulation of the gut-brain axis in ways that can beneficially address anxiety.
In a healthy gut, the resident bacteria produce a wide range of metabolites, including short-chain fatty acids, which are produced when certain bacterial strains metabolize fiber. These multifaceted short-chain fatty acids have a variety of roles in key body processes, such as energy homeostasis and nutrient absorption. In addition, by acting as epigenetic regulators, short-chain fatty acids are involved in the production and activity of the gut peptides associated with the gut-brain axis, including glucagon-like-peptide and leptin. These findings suggest that an imbalance of the bacteria that produce short-chain fatty acids might lead to disruptions in the gut-brain axis, which in turn contribute to the adverse symptoms of anxiety.
Any individual who has considered taking a probiotic supplement knows that the options on today’s market are practically endless when it comes to the number and combinations of available bacterial strains. This could be one reason the body of literature on the potential benefits of probiotic supplementation for various mental health conditions can only be described as mixed at best; and while some supplements seem to be beneficial for patients, others have no effect. Furthermore, it is unwise to compare studies of probiotic supplements that contain different bacterial strains. To resolve the lack of clarity in this area of study, scientists are now conducting more specific studies on individual strains, a number of which have shown particular promise for addressing anxiety.
For example, in 2014 a group of researchers from University College Cork in Ireland conducted a study that suggested two strains of bacteria—Bifidobacterium longum 1714 and Bifidobacterium breve 1205—could address anxiety symptoms in mouse models, as measured by several different well-established behavioral tests for anxiety. Intriguingly, in a follow-up experiment conducted by researchers at the same university in 2016, these findings were verified in a small group of healthy humans. In the second study, 22 healthy participants were subjected to an anxiety-inducing cold-pressor test, with and without supplementation of B. longum 1714. The researchers used resting encephalography to measure the participants’ output of cortisol (a stress hormone) under both conditions, and they observed lower cortisol levels in the participants who had taken the probiotic supplements. Moreover, in subjective surveys, the participants reported perceiving lower levels of stress after taking the probiotic supplements. Based on these findings, the researchers concluded that Bifidobacterium strains could potentially be used as anti-anxiety therapeutics in the future.
A study from 2011 suggests that the bacterial strain Lactobacillus rhamnosus plays an important role in the mediation of communication via the gut-brain axis in ways that directly impact anxiety levels. The researchers found that taking this strain could alter mRNA expression of GABA receptors in the brains of mouse models. GABA is an inhibitory neurotransmitter in the brain, and receptor levels are associated with anxiety symptoms. According to these researchers, these levels were altered in several different areas of the brain related to anxiety symptoms when the mice were administered L. rhamnosus, including the prefrontal cortex and the hippocampus. Importantly, in mice in which the vagus nerve had been removed, the characteristic symptoms of anxiety were not observed, which offers further evidence the vagus nerve likely plays a mechanistic role in the mediation of anxiety symptoms through the gut-brain axis. Therefore, this study not only suggests L. rhamnosus can be an effective probiotic therapy for anxiety patients, it also highlights the vagus nerve as a target for future research on possible therapeutics.
Probiotic supplementation that supports the health of the microbiome might not be the only way to target the gut-brain axis. There is also growing evidence that certain types of prebiotics offer specific benefits for anxiety patients. Prebiotics are fiber supplements that are indigestible by humans, but that feed certain strains of beneficial bacteria in the GI tract. In a groundbreaking study published in 2017, researchers found that supplementation with two types of prebiotics—fructooligosaccharides (FOS) and galacto-oligosaccharides (GOS)—can modulate the gut microbiome in ways that affect the gut-brain axis. In a study in mouse models of anxiety, researchers found that prebiotic strains containing both FOS and GOS could address anxiety symptoms in mice, based on several well-established behavioral tests. In addition, fiber supplements were associated with lower levels of the pro-inflammatory markers commonly associated with anxiety, as well as lower levels of stress-inducing corticosterone. These findings suggest certain combinations of prebiotic fibers target the bacterial strains that play an essential role in the mediation of anxiety symptoms via the gut-microbiome axis, so they likewise could help alleviate anxiety symptoms, much like direct probiotic supplementation.
Based on the studies described above, it is clear that scientists have a growing sense of which bacterial strains are producing the essential metabolites that mediate the gut-brain axis. However, it is not yet entirely clear exactly which strains need to be replaced or nourished with prebiotics to relieve anxiety symptoms. Therefore, some researchers and clinicians are considering the benefits of direct supplementation with short-chain fatty acids, such as butyric acid. This approach allows a butyric acid supplement to assume the role of the bacteria in the microbiome—that is, short-chain fatty acids are introduced into the gut, thus bypassing the step in which the bacteria metabolize fiber to produce these functional compounds. Instead of relying on bacteria to produce short-chain fatty acids, an oral supplement places them directly where they are needed: in the GI tract. As a result, short-chain fatty acids are readily available to mediate peptide levels and thereby possibly modulate the biological processes that might benefit anxiety patients.
Ultimately, even though the mechanisms through which the gut-brain axis mediates symptoms of anxiety have not been fully elucidated, there is little doubt that the gut microbiome does play an important role. There are already several probiotic strains that have been identified in the connection between the GI tract and the CNS, and supplementation with prebiotics and short-chain fatty acids might also exert beneficial effects in this regard. Although large-scale human studies are still lacking, clinicians and patients dealing with anxiety can harness this evidence to develop unique strategies for individuals who have not found success with traditional anti-anxiety therapies. The research community can also look forward to future studies that offer more mechanistic insight and real-world results related to the microbiome-mediated connection between the gut-brain axis and anxiety.
The power of Tesseract supplements lies in the proprietary science of proven nutrients and unrivaled smart delivery, making them the most effective for supporting neurological health and gastrointestinal health.*
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Updated on March 23, 2023
Article Summary:
There’s no denying that the currently available therapies for Alzheimer’s disease are suboptimal. As practitioners, patients, and families grow frustrated with the limited results of pharmacological approaches, researchers have begun exploring all-natural alternatives, including polyphenolic compounds derived from plant extracts.
For years, polyphenolic compounds have been recognized for their antioxidant properties and ability to support the body’s natural inflammatory response.* They also support cardiovascular function, which is important for Alzheimer’s patients because there is evidence suggesting a link between cardiovascular health and Alzheimer’s progression.* Because of the well-known bioactivity of polyphenols, researchers have begun to seriously consider polyphenols as an alternative therapy to utilize with Alzheimer’s patients. In preclinical studies, two of the polyphenols that have shown particular promise are Epigallocatechin-3-gallate (ECGC) and quercetin.
ECGC is a polyphenolic compound best known as the most abundant polyphenolic extract in green tea. Although in vitro studies show that ECGC can play a role in a variety of biological processes, there are three ways it might particularly benefit Alzheimer’s patients:
According to a model based on existing laboratory research, these activities should inhibit enlargement of the ventricles and the atrophy of the cerebral cortex and hippocampus, all of which are key structural changes observed in the brains of Alzheimer’s patients.
A 2017 preclinical animal study provides strong support for this proposed model. Researchers at Xi’an University in China demonstrated that in a mouse model of Alzheimer’s disease, oral supplementation with ECGC inhibited structural changes in the brain. Without supplementation, the mouse model displayed abnormalities in synaptic protein levels in both the frontal cortex and the hippocampus. The study showed that long-term ECGC therapy (15 mg/kg per day) could restore these levels, as measured by the reversal of the decreases in two different synaptic protein biomarkers. Moreover, the structural changes were coupled with notable behavioral effects; the mice treated with ECGC performed significantly better on maze tests that measured memory and spatial learning ability.
There is also pre-clinical evidence that ECGC supplementation can be even more effective when coupled with exercise, an exciting finding for patients interested in activity-based alternative therapies for Alzheimer’s disease. In 2015, researchers at the University of Missouri subjected mouse models to four months of wheel-running exercises combined with daily supplementation of ECGC (50 mg/kg per day). The supplementation led to a significant drop in amyloid beta plaque buildup (a hallmark of Alzheimer’s disease) in the cortex and hippocampus. The combination of ECGC and exercise also had positive behavioral impacts: the mouse models that received the intervention did not demonstrate the same behavioral deficits as the untreated Alzheimer’s mouse models in maze tests (which measured memory) and nest-building tests (which measured anxiety levels).
Not only do these results suggest that ECGC can directly address symptoms of Alzheimer’s disease, it also supports the hypothesis that the cardiovascular effects of ECGC might further contribute to its impacts. Exercise is a known mediator of cardiac function, so its effectiveness for addressing Alzheimer’s disease symptoms suggests that the cardiovascular benefits of ECGC could be indirectly supporting reductions in Alzheimer’s disease progression. This means that ECGC might help Alzheimer’s patients in two ways: through direct effects on the brain and through indirect effects on the cardiovascular system.
Like ECGC, quercetin is a polyphenolic compound that has shown considerable promise as an alternative therapy for Alzheimer’s patients in pre-clinical studies. Again, the potential of quercetin supplementation is underpinned by evidence of structural changes in mouse brains and corresponding behavioral changes. In a study from 2015, researchers treated a mouse model of Alzheimer’s disease with quercetin (25 mg/kg per day for three months). Extensive histological studies (studies of changes in mouse brain tissues) indicated that supplementation led to beneficial impacts on certain brain structures and declines in the presence of certain Alzheimer’s disease-associated proteins.* These effects were observed alongside improvements on behavioral tests of both cognitive and emotional function, which would make quercetin a promising alternative therapy for Alzheimer’s patients and practitioners looking for a more comprehensive treatment regimen.
Although there is broad speculation that antioxidant effects are at the core of quercetin’s effectiveness as a polyphenol, it might also be working through other molecular pathways. A 2016 study suggests that quercetin supplementation modulates levels of Apolipoprotein E (ApoE), a cholesterol carrier protein, and high cholesterol is a known risk factor for Alzheimer’s disease. The researchers propose that improving cholesterol metabolism is a novel mechanism through which quercetin can address an Alzheimer’s risk factor. The findings provide further evidence of a beneficial link between polyphenol supplementation, cardiovascular health, and the cognitive decline observed in Alzheimer’s patients.* In addition, polyphenolic compounds like quercetin could indirectly benefit Alzheimer’s patients by supporting heart health (in addition to their direct actions in the nervous system), thus being more effective than options that only target the brain.*
There are no major clinical studies that support the effectiveness of ECGC or quercetin in Alzheimer’s patients. Although there is one double-blind, placebo-controlled study on resveratrol, a similar polyphenolic compound that has shown promise in preclinical studies, preliminary clinical results are inconclusive. Researchers have determined that both supplements are safe and well-tolerated, but more research is necessary before researchers can confirm their efficacy.
In the future, it will be important to conduct rigorous clinical trials on both ECGC and quercetin while continuing to probe their mechanisms of action. But given the frustrating outcomes of conventional therapies and the promising laboratory evidence of polyphenolic supplements, patients and practitioners might want to consider integrating supplements now.
The power of Tesseract supplements lies in enhancing palatability, maximizing bioavailability and absorption, and micro-dosing of multiple nutrients in a single, highly effective capsule. Visit our website for more information about how Tesseract’s products can help support your neurological health.*
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