Updated on April 13, 2023
Article Summary
- Although loss of cognitive function is affecting more people than ever before, the efficacy of standard therapy options is limited.
- Research suggests that quercetin, butyrate, and glutathione can provide nutritional support for addressing neurocognitive decline.*
- Although research into the efficacy of these compounds is ongoing, patients can safely integrate high-quality supplements in their natural therapy regimens now.
As the world population ages, more people than ever before are struggling with significant loss of cognitive function or endeavoring to prevent it. Recognized as cognitive decline beyond that which is normal in the course of aging, the toll of significant cognitive decline weighs heavily on those affected and their loved ones; from its starting point as mild cognitive impairment, significant loss of cognitive function slowly and unstoppably progresses until patients have only minimal cognitive capability.
Declining cognitive function as an aspect of aging has been known to medical science for more than two thousand years. Although there are several therapies intended to address loss of cognitive function, these are of limited efficacy. While researchers try to develop new therapies, those affected are often left to fend for themselves using questionably effective tools that address neurocognitive symptoms temporarily but don’t slow the progression of loss of cognitive function. For patients and caregivers who are not content to accept only the current standard of care, however, a number of natural compounds might address this situation. Of these, the compounds quercetin, butyrate, and glutathione are especially promising natural remedies for addressing the loss of cognitive function.
Quercetin
Quercetin is a phenolic compound that is a constituent of many vegetables and red wine. As with many other phenols, quercetin is an antioxidant, although this property is negligible in the quantities typically consumed in food. More significantly, quercetin in a nutritional supplement format might be helpful in providing nutritional support for helping to maintain cognitive function owing to its numerous interactions with critical proteins responsible for initiating cellular signaling pathways. Currently, the strongest evidence comes in the form of in vivo animal research.
In a particularly intriguing study published in 2009, researchers induced vascular dementia in rats, then administered quercetin to the treatment group. All the rats were then introduced to the Morris water maze. The rats who received quercetin exhibited the same ability to complete the maze task as healthy control rats, while the rats who didn’t receive quercetin were incapable of completing the task.
There are reasons to believe the effects of quercetin supplements wouldn’t be as profound in humans as in rats. First, although quercetin was shown to be effective at mitigating vascular dementia in the rats, the dementia was caused by the researchers externally. Outside the laboratory, loss of cognitive function occurs gradually and can’t be measured consistently in the same person across short time periods. This means that quercetin is likely more effective at mitigating “acute” cognitive loss caused by experimentation than it is at warding off the natural loss of cognitive function experienced by human patients. Likewise, if the loss of cognitive function is caused by a chronic condition, for example, diabetes, quercetin might be able to offer more to patients than to those with loss of another origin. The assumed basis for this difference is that vascular damage to the brain caused by diabetes is assumed to be easier to repair than chronic degeneration.
Furthermore, rats are not sound experimental models to derive the magnitude of therapeutic efficacy. Although rats are effective at modeling very basic indications of cognitive function, like the ability to navigate through their environment, human behavior is substantially more complex. In other words, restoring the ability of a rat to navigate a maze doesn’t translate to restoring the ability of an individual with lost cognitive function to remember how to perform important daily tasks. However, the results of this in vivo study are promising and justify future research in humans.
Part of the reason quercetin is a compelling potential therapy for addressing loss of cognitive function is that it is proven to be bioactive via a handful of mechanisms.* These mechanisms include binding to critical transcriptional regulators—the mediators of gene function—and other essential biological signaling molecules like phosphatidylinositol-3-kinase (PI-3K).* The exact impact of what these mechanisms might be on loss of cognitive function is difficult to speculate on. Indeed, binding to a signaling molecule as fundamental as the PI-3 kinase would likely have systemic effects completely distinct from the other therapies on the market. Although the experimental PI-3 kinase pharmaceutical therapies are too toxic to be used in patients, quercetin is not similarly destructive. Because loss of cognitive function entails a number of physiological deficits ranging from weaker axonal myelination to neuroinflammation and protein plaque formation, leveraging genetic and metabolic mechanisms increase the chances of beneficially affecting multiple pathologies. Addressing neuroinflammation via a genetic regulator, for example, could lead to improved short-term memory functionality, while improved metabolic control of myelination could lead to improved motor control and arousal. As research in this area progresses, we will gain greater insight into how quercetin affects these critical variables to support brain function.*
Butyrate
Although quercetin is a promising natural remedy for addressing loss of cognitive function, it is not the only molecule capable of doing so. Butyrate is now widely regarded as another possible approach to maintaining cognitive health.* Butyrate, also known as butyric acid, is an intracellular signaling chemical produced by the body that has mechanisms of action that are likely to be beneficial to cognitive health. These beneficial effects are substantiated in the scientific literature, although, like with quercetin, large clinical trials are still forthcoming. Nonetheless, butyrate’s diverse physiological roles mean that it can potentially play a role in providing nutritional support for maintaining cognitive function during aging.*
Butyrate is naturally produced in the gut, where it is used to nourish beneficial gut microbiota and upregulate the activity of white blood cells.* Because it’s common to the digestive system, butyrate is generally well-tolerated and produces few side effects. Butyrate can cross the blood-brain-barrier and exhibit similar beneficial effects on white blood cells in the brain as well. This means that patients whose loss of cognitive function might be caused in part by neuroinflammation could benefit from a well-formulated, highly bioavailable butyrate supplement that promotes healthy brain tissue.*
Although trials in human dementia models are lacking, there are several studies in animal models that support the idea of using butyrate to address loss of cognitive function. In one study with rats, rats with artificial diabetically-induced loss of cognitive function experienced substantial improvement in a short-term memory consolidation task when administered butyrate. This experiment was similar in setup to the earlier experiments investigating quercetin’s ability to mitigate loss of cognitive function. The promising results of the butyrate study were later substantiated by a similar experiment examining rats performed by a separate research group.
Unlike quercetin, butyrate has been shown to be associated with faster learning of operant conditioning responses in rats. In one study, rats that received a butyrate supplement learned to associate a stimulus with an action that they could take to receive food as a reward with less than a third as many trials as the non-supplemented rats. This means that butyrate might have the potential to support the cognitive abilities that are affected negatively by aging.* Whether or not these results could carry over to human patients remains to be seen, but researchers are currently investigating if and how butyrate could be used in that role. With further research, physicians and patients will soon better understand the extent of butyrate’s benefits for maintaining cognitive function during aging.
Glutathione
Butyrate, for all its potential benefits, hasn’t been studied for its benefits for brain health as extensively as another physiological molecule: glutathione (GSH). Glutathione is a molecule produced by the body to use as an antioxidant, especially in the liver and the brain. Dietary glutathione intake does little to improve health because it is readily destroyed by metabolism. This means that cells must synthesize their own glutathione supply from precursor molecules, or, alternatively, receive glutathione that has been formatted such that it survives digestion and liver enzymes. Due to the difficulty with delivering glutathione to patients intact, research on glutathione has only recently taken off with the advent of sophisticated new delivery systems designed to optimize bioavailability. In light of these new advancements, researchers believe that boosting glutathione’s antioxidant activity can be a critical boon to brain health; unlike butyrate and quercetin, glutathione is a powerful antioxidant.
Under normal circumstances, most individuals have a high concentration of glutathione in their bodies and in their brains. This glutathione protects cells from damage caused by oxidative stress.* Oxidative stress occurs when molecular byproducts of metabolism—like reactive oxygen species—clutter cellular machinery and prevent cells from performing their task. When cellular machinery can’t perform its purpose, the cell can’t perform basic self-maintenance and gradually takes on more and more wear and tear. Eventually, this wear and tear can kill the cell. In most cases, however, the wear and tear is only extensive enough to make the cell less efficient at performing its physiological purposes. In the case of a neuron, a cell suffering from a high amount of oxidative stress might be incapable of signaling other neurons with the same strength or frequency that is necessary to maintain normal cognition.
Glutathione has been studied in the context of supporting brain health a number of times, with consistent results.* One study, for example, linked the concentration of an enzyme responsible for trafficking glutathione to problem areas in cells with the risk of developing cognitive deficits. The researchers found that when levels of the trafficking enzyme glutathione s-transferase omega-1 were low, patients had 2.2 times the normal risk of developing cognitive deficits for any given age. Likewise, patients with high levels of this enzyme typically had low levels of biomarkers indicating oxidative stress, meaning they were healthier than those with lower levels. Notably, the researchers didn’t explicitly examine glutathione, only the cellular machinery responsible for moving glutathione to problem areas. Nonetheless, the study was one out of many linking increased levels of glutathione to better outcomes for maintaining healthy cognitive function.*
Another study explicitly examined glutathione levels in relation to deficits in cognitive function. Healthy control patients had an average of 5.1 micromoles of glutathione per milliliter of blood. Patients of the same age with cognitive deficits had an average of 3.4 micromoles per milliliter of blood—only 66 percent as much. The authors of the study summarized the meaning of their findings succinctly: “Our results suggest that there is a defect in the antioxidant defense system [in cognitively deficient patients] that is incapable of responding to increased free radical production, which may lead to oxidative damage and the development of the pathological alterations that characterize the neurodegenerative disorder of patients.” Interestingly, the researchers found that this effect varied depending on whether the patient was male or female; men without loss of cognitive function had higher glutathione levels than women without loss of cognitive function, but this was reversed in the case of patients who had cognitive function loss. The significance of this difference might indicate that men would benefit more from glutathione therapy than women, but further research is necessary. Glutathione therapy for maintaining cognitive function is under active investigation, and future findings will determine the precise symptoms of cognitive function that glutathione could benefit most.
The Future of Natural Remedies for Preventing Loss of Cognitive Function
For patients seeking natural remedies that can provide nutritional support for maintaining neurocognitive function, quercetin, butyrate, and glutathione are exciting options that will be fleshed out further by researchers. Clinical trials with butyrate in a number of different neurocognitive applications are ongoing. Likewise, researchers are examining whether quercetin might be more useful in being supportive in instances of vascular issues caused by diabetes rather than other forms of cognition loss with less certain causes. If patients wish to incorporate these compounds into their natural therapy regimens now, then there are already a number of state-of-the-art supplements on the market. Although researchers will continue to endeavor to answer the many questions regarding the way that these supplements might be beneficial for maintaining and supporting cognitive health, including how these natural substances can be used to forestall the loss of cognitive function, those individuals who try using them early will have the advantage of better maintaining their cognitive health before those who wait for the final research verdict. Given that there is no current medical consensus, the potential benefits of acting early are difficult to overstate.
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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