Polyphenols and their immunotherapeutic benefit have been clinically validated in recent years
Polyphenols, a diverse class of bioactive compounds found in plant-based foods, have gained significant attention for their immunomodulatory and therapeutic effects. These naturally occurring molecules play a crucial role in maintaining immune homeostasis, reducing chronic inflammation, and mitigating the progression of diseases such as cancer, neurodegenerative disorders, metabolic syndrome, and autoimmune conditions.
The therapeutic potential of polyphenols lies in their ability to interact with key immune cells, modulate inflammatory pathways, and influence the gut microbiome, all of which contribute to their disease-preventive and health-promoting effects. In this brief article, we explore and touch on the immunomodulatory properties of polyphenols, their mechanisms of action, and their role in disease management, with an emphasis on their relevance to chronic inflammation and immune regulation.
Polyphenols exert a profound influence on the immune system by modulating cytokine production. Chronic inflammation, driven by an overproduction of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, contributes to the development of various chronic diseases.
Polyphenols like quercetin, luteolin, epicatechin, and curcumin are known to inhibit the activation of nuclear factor-kappa B (NF-κB), a transcription factor that upregulates pro-inflammatory cytokines. At the same time, polyphenols enhance the production of anti-inflammatory cytokines such as IL-10, thereby restoring immune balance and preventing excessive inflammatory responses.
The immune system comprises innate and adaptive immunity, both of which are influenced by polyphenols.
The gut microbiome is a key mediator of immune responses, and polyphenols interact with gut bacteria to shape immune function. Proanthocyanidins, epicatechins, and thymoquinone are prebiotic-like polyphenols that enhance the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium while inhibiting pathogenic bacteria.
Through microbial fermentation, polyphenols are metabolized into smaller bioactive compounds, such as dihydroxyphenylacetic acid and phenylpropionic acids, which exhibit strong anti-inflammatory and immunoregulatory effects. This interaction between polyphenols and the gut microbiome strengthens the gut barrier, prevents endotoxemia, and reduces systemic inflammation.
Polyphenols show promise in mitigating autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease (IBD) by modulating immune tolerance and reducing autoantigen-driven inflammation.
Chronic neuroinflammation is a hallmark of Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Polyphenols play a neuroprotective role by:
Polyphenols combat metabolic syndrome by modulating lipid metabolism, improving insulin sensitivity, and reducing oxidative stress.
Polyphenols contribute to cancer prevention through:
ACEND, a clinically formulated medical food, integrates key polyphenols to support immune modulation and combat chronic inflammation. The formulation includes:
By leveraging a combination of these polyphenols, ACEND provides a comprehensive, drug-free therapeutic approach to preventing and managing immune-related conditions.
Polyphenols represent a powerful class of bioactive compounds with extensive immunomodulatory and therapeutic implications. Their ability to regulate inflammation, support gut microbiota, and modulate immune cell function makes them vital in preventing and managing chronic diseases.
ACEND integrates these polyphenols into a scientifically backed formulation, offering a targeted approach to immune resilience, chronic inflammation reduction, and overall health optimization. As research continues to expand, the role of polyphenols in immune health will only become more significant, further cementing their place in functional medicine and food-as-medicine strategies.
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.
Polyphenols are GLP-1 boosters due to their ability to inhibit DPP-4. Read on to understand…
January 20, 2025
Contributing Authors: Team TRILITY / ACEND
In recent years, glucagon-like peptide-1 (GLP-1) has gained significant attention for its role in regulating blood sugar levels and supporting metabolic health. GLP-1 is an incretin hormone produced in the intestines in response to food intake, stimulating insulin secretion while suppressing glucagon release. However, its effects are short-lived due to rapid degradation by the enzyme dipeptidyl peptidase-4 (DPP-4), limiting its ability to help regulate blood sugar effectively (Gulati & Singh, 2017).
A growing body of research suggests that certain polyphenols—bioactive compounds found in plants—naturally inhibit DPP-4, extending the half-life of GLP-1 and improving insulin response. This article explores how polyphenols function as natural DPP-4 inhibitors and their potential impact on metabolic health.
DPP-4 is an enzyme responsible for degrading GLP-1 and another key incretin hormone, glucose-dependent insulinotropic polypeptide (GIP). By cleaving these hormones, DPP-4 significantly reduces their ability to stimulate insulin release, which can lead to impaired glucose metabolism (Kawser et al., 2019).
DPP-4 inhibitors are commonly prescribed for individuals with type 2 diabetes to prevent the degradation of GLP-1, allowing it to remain active for longer periods. However, certain naturally occurring polyphenols found in food may have similar inhibitory effects on DPP-4, offering a diet-based approach to supporting GLP-1 activity.
Polyphenols are naturally occurring compounds with strong antioxidant and anti-inflammatory properties found in fruits, vegetables, tea, coffee, and wine. Several studies have demonstrated their potential in inhibiting DPP-4 activity, which enhances GLP-1 secretion and insulin sensitivity (Zhu et al., 2020).
Research suggests that polyphenols can bind to the active site of DPP-4, preventing it from interacting with and degrading GLP-1. This mechanism effectively prolongs the half-life of GLP-1, allowing for sustained insulin secretion and better glucose control (Bruckbauer & Zemel, 2018).
Including polyphenol-rich foods in the diet can naturally enhance GLP-1 levels and improve metabolic function. Some of the most well-researched polyphenol-rich foods that have shown potential DPP-4 inhibitory properties include:
By regularly consuming these foods, individuals may naturally support their GLP-1 activity and improve overall blood sugar control.
Given their ability to inhibit DPP-4, polyphenols offer several metabolic health benefits, particularly for individuals managing type 2 diabetes or prediabetes:
To take advantage of polyphenols’ DPP-4 inhibitory properties, consider adding more of the following foods into your daily routine:
Scientific research continues to uncover the power of polyphenols as natural DPP-4 inhibitors, highlighting their potential to support GLP-1 activity and improve metabolic health. While pharmaceutical DPP-4 inhibitors are widely used for diabetes management, incorporating polyphenol-rich foods into the diet presents a natural, food-based approach to enhancing GLP-1 levels and blood sugar control.
For those looking to support healthy glucose metabolism naturally, increasing the intake of polyphenol-rich foods may be a beneficial strategy—one that aligns with the growing food-as-medicine movement.
Sugar sweetened beverages are defined as beverages with 6 grams or more of sugar per 8oz serving
Sugar-sweetened beverages (SSBs) are drinks that contain added sugars or sweeteners to enhance flavor and appeal. These beverages range from sodas, sports drinks, and energy drinks to fruit juices, flavored waters, and even some enteral nutrition formulas. SSBs are a significant source of added sugar in the modern diet, contributing to calorie overconsumption, poor nutritional intake, and an increased risk of chronic diseases. This article explores the diverse landscape of SSB products, their role in modern health crises, and their links to conditions such as obesity, type 2 diabetes, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD).
SSBs include any beverage containing caloric sweeteners such as high-fructose corn syrup, sucrose, or other forms of sugar. The generally agreed upon rule of thumb is a SSB contains 6 grams or more of sugar per 8oz serving.
Common examples include:
The sugar content of SSBs varies widely, making it important to highlight actual examples to understand their impact on health:
The excessive consumption of SSBs is a well-documented contributor to the global obesity epidemic. These beverages are calorically dense yet provide little to no nutritional value. Research shows that liquid calories from SSBs do not induce the same level of satiety as solid foods, leading to higher overall calorie intake.
A study published in The New England Journal of Medicine found a direct correlation between SSB consumption and weight gain, particularly among adolescents. Regular consumption of just one 12-ounce soda daily can lead to an average weight gain of 15 pounds per year if the excess calories are not offset by physical activity.
SSBs are a leading dietary source of rapidly absorbed sugars, contributing to insulin resistance and beta-cell dysfunction. These effects significantly increase the risk of developing type 2 diabetes. A meta-analysis published in Diabetes Carereported that consuming one or more servings of SSBs daily increases the risk of type 2 diabetes by 26%.
The glycemic load of SSBs leads to frequent spikes in blood glucose levels, creating a chronic state of metabolic stress. Over time, this can result in impaired glucose tolerance and full-blown diabetes, particularly in individuals with sedentary lifestyles.
Excessive sugar intake from SSBs is associated with dyslipidemia, hypertension, and systemic inflammation, all of which are risk factors for cardiovascular disease (CVD). The Journal of the American Medical Association (JAMA) published findings showing that individuals who consume 17–21% of their calories from added sugars have a 38% higher risk of dying from CVD compared to those who limit their sugar intake to less than 10%.
The high fructose content in many SSBs is particularly harmful to liver health. Unlike glucose, fructose is metabolized almost exclusively in the liver, where it is converted into fat. Over time, this can lead to NAFLD, a condition now affecting 25% of the global population.
SSBs have been implicated in the development of NAFLD due to their high fructose content. A study in Hepatologyhighlighted that children consuming more than 3 SSBs daily had a significantly higher prevalence of liver fat compared to non-consumers.
Enteral nutrition formulas, while critical for patients with specific medical needs, are an overlooked category of SSBs. Products like Ensure and Boost often contain high levels of sugar to improve taste and ensure compliance. However, these formulas are increasingly consumed by healthy individuals seeking weight management or added nutrition, inadvertently increasing their sugar intake.
For example, Ensure Original contains 15 grams of sugar per 8-ounce serving, with some variants exceeding 20 grams. While these products are essential for patients requiring rapid caloric intake, their misuse can contribute to the same health issues associated with other SSBs.
The harmful effects of SSBs are driven by several biological mechanisms:
Addressing the health crisis caused by SSBs requires a multi-faceted approach involving education, policy, and innovation:
Replacing SSBs with healthier alternatives can significantly reduce sugar intake and associated health risks:
SSBs are a ubiquitous part of the modern diet, but their health consequences are far-reaching. From obesity and diabetes to cardiovascular disease and NAFLD, the evidence linking SSBs to chronic illness is overwhelming. Recognizing the diversity of SSB products, including enteral formulas, is essential to addressing their role in the current health crisis.
Consumers, healthcare providers, and policymakers must collaborate to reduce SSB consumption and promote healthier alternatives. Public education, policy interventions, and innovation in medical foods offer pathways to mitigate the harmful impact of SSBs on global health.
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.
Disease Related Malnutrition effects patients under clinical supervision. Why?
Disease-related malnutrition (DRM) is a critical yet underrecognized condition that significantly impacts health outcomes in patients suffering from chronic or acute illnesses. Despite its prevalence and role in exacerbating disease progression, DRM remains inadequately addressed in healthcare. This article explores the prevalence of DRM in the United States, its influence on disease progression, reasons for its limited recognition, and the potential role of ACEND, a medical food, in addressing this widespread issue.
DRM affects millions of Americans annually, particularly those hospitalized or living with chronic illnesses. According to estimates, approximately 30-50% of hospitalized patients are malnourished or at risk of malnutrition, with higher prevalence observed in those with cancer, chronic obstructive pulmonary disease (COPD), heart failure, and gastrointestinal diseases. Older adults, who are more likely to have multiple comorbidities, are especially vulnerable.
The economic burden of DRM is equally concerning. Malnutrition-related healthcare costs in the United States are estimated to exceed $15 billion annually, largely due to prolonged hospital stays, increased readmission rates, and the need for more intensive medical care.
Malnutrition contributes to disease progression through several mechanisms:
Despite its profound implications, DRM remains underdiagnosed and underreported for several reasons:
ACEND, a medical food designed to combat chronic inflammation and support recovery, is uniquely positioned to address DRM. By incorporating a blend of bioavailable nutrients, polyphenols, and probiotics, ACEND provides targeted nutritional support for patients at risk of malnutrition.
Integrating nutrition as a core component of disease management requires a paradigm shift in healthcare. Policymakers, healthcare providers, and researchers must work collaboratively to:
DRM is a pervasive but underacknowledged factor in disease progression. Addressing it requires a holistic approach to patient care, emphasizing the role of targeted nutrition. ACEND offers a promising solution, providing evidence-based, drug-free therapeutic support to patients at risk of malnutrition. By prioritizing nutrition in clinical practice, we can improve health outcomes, reduce healthcare costs, and enhance the quality of life for millions of patients.
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.
Polyphenols and Gut Health
Polyphenols, a diverse group of naturally occurring compounds found in plants, are rapidly gaining recognition as a powerful tool for enhancing gut health. Beyond their well-documented antioxidant and anti-inflammatory properties, emerging research suggests that polyphenols play a pivotal role as prebiotics, substances that selectively promote the growth of beneficial gut microbiota. By fostering a healthy gut microbiome, polyphenols not only prevent and reverse conditions like leaky gut syndrome but also fortify the immune system.
The human gut is home to trillions of microorganisms, collectively known as the gut microbiome. These microorganisms regulate a wide range of physiological functions, including digestion, metabolism, and immune defense. A balanced microbiome, rich in beneficial bacteria such as Lactobacillus and Bifidobacterium, is essential for maintaining gut integrity and preventing dysbiosis, a state of microbial imbalance linked to chronic inflammation and various diseases.
Traditionally, prebiotics were defined as non-digestible fibers that feed beneficial bacteria. However, polyphenols, despite being metabolized differently, are now recognized as potent prebiotics. While polyphenols themselves are poorly absorbed in the small intestine, they are metabolized by gut bacteria into bioactive compounds, which enhance the growth and activity of beneficial microbial populations.
Leaky gut syndrome, characterized by increased intestinal permeability, occurs when the tight junctions in the intestinal lining become compromised. This allows toxins, pathogens, and partially digested food particles to enter the bloodstream, triggering inflammation and immune dysfunction. Polyphenols play a vital role in reinforcing gut barrier integrity and preventing the onset of leaky gut syndrome.
The gut and immune system are intricately linked, with approximately 70% of the immune system residing in the gut-associated lymphoid tissue (GALT). A robust microbiome is essential for training and regulating the immune response, and polyphenols contribute significantly to this process.
Numerous clinical studies underline the transformative potential of polyphenols for gut health and immune support:
ACEND, a clinically formulated medical food, incorporates potent polyphenols such as quercetin, curcumin, grape seed extract, and green tea extract. These ingredients are carefully selected for their synergistic effects on gut health, targeting key mechanisms such as:
Additionally, the polyphenols in ACEND are paired with prebiotic fibers and other bioactive compounds to maximize their efficacy in preventing and reversing gut-related disorders.
Polyphenols represent a transformative approach to gut health, offering unique prebiotic benefits that extend beyond traditional fibers. By promoting beneficial microbiota, repairing the gut barrier, and supporting immune function, polyphenols provide a comprehensive solution to modern gut health challenges, including leaky gut syndrome.
For individuals seeking a science-backed approach to gut health, incorporating polyphenol-rich foods or clinically-formulated medical foods like ACEND may offer unparalleled benefits. As research continues to unravel the complexities of the gut microbiome, polyphenols are poised to become a cornerstone of gut and overall health.
References:
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.
Angiogenesis, the process by which new blood vessels form from pre-existing ones, is a cornerstone of human biology. Essential for growth, healing, and tissue regeneration, angiogenesis can also drive disease when it becomes dysregulated. As research evolves, medical foods like ACEND offer novel solutions to promote healthy angiogenesis while mitigating its pathological effects.
Angiogenesis is the body’s natural response to increased demands for oxygen and nutrients. It is regulated by a delicate balance of pro-angiogenic and anti-angiogenic factors. Key growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), stimulate blood vessel formation, while inhibitors like angiostatin and endostatin prevent excessive vascular growth.
Physiological angiogenesis is crucial for:
While angiogenesis is vital for health, its dysregulation is linked to various diseases. Excessive or insufficient blood vessel growth can disrupt tissue homeostasis and fuel pathological processes.
Chronic inflammation is a key driver of angiogenic imbalances. Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), can upregulate VEGF, exacerbating angiogenesis in diseases like cancer and AMD. Conversely, persistent inflammation may impair angiogenic signaling, as seen in chronic wounds and ischemic heart disease.
ACEND, a medical food, leverages evidence-based ingredients to regulate angiogenesis by targeting inflammation and restoring vascular balance.
By targeting chronic inflammation and oxidative stress, ACEND helps restore the balance between pro-angiogenic and anti-angiogenic factors. This dual action ensures that angiogenesis supports healing and growth without fueling pathological processes.
Angiogenesis is a double-edged sword, essential for tissue repair and regeneration but potentially harmful when dysregulated. By addressing the root causes of angiogenic imbalances, such as chronic inflammation, ACEND offers a targeted, drug-free therapeutic solution. With its synergistic blend of bioactive compounds, ACEND promotes healthy angiogenesis while minimizing the risks associated with excessive or impaired blood vessel growth.
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.
Metabolic syndrome isn’t simply a collection of risk factors – it’s a complex interplay of physiological disturbances.
Metabolic syndrome is a complex cluster of conditions that affects approximately 34% of adult Americans, yet its management through dietary intervention remains underappreciated, particularly regarding the powerful role of flavonoids – natural compounds found abundantly in fruits, vegetables, and other plant-based foods.
Recent studies have provided strong evidence for the role of flavonoids in managing metabolic syndrome:
Painkillers play a vital role in modern medicine, providing relief from acute and chronic pain.
Painkillers, or analgesics, are among the most commonly used medications worldwide. From mild headaches to chronic pain, these drugs provide relief to millions. However, despite their widespread use, many people are unaware of the unintended effects that common painkillers can have on the body. These effects, ranging from subtle biochemical changes to severe long-term health implications, underscore the importance of understanding these medications beyond their pain-relieving properties.
Recent research has revealed surprising mechanisms and outcomes associated with these medications, including the discovery that some nonsteroidal anti-inflammatory drugs (NSAIDs) act through mechanisms beyond their traditional enzyme inhibition. These discoveries could help explain the varied effects of NSAIDs on health, including their links to heart disease, cancer, and other inflammatory conditions. This article explores the unexpected effects of common painkillers, focusing on their impact on the gastrointestinal system, cardiovascular health, mental well-being, and overall body physiology, incorporating the latest findings on how these drugs operate.
NSAIDs such as ibuprofen, naproxen, and aspirin are widely used for their anti-inflammatory and analgesic properties. However, their use is closely linked to gastrointestinal (GI) complications, which can range from mild irritation to severe ulcers and bleeding. This effect stems from their inhibition of cyclooxygenase (COX) enzymes, particularly COX-1. While this inhibition reduces inflammation, it also decreases the production of protective prostaglandins in the stomach lining, making it more susceptible to damage. Long-term NSAID use is a leading cause of peptic ulcer disease and GI bleeding.
Acetaminophen (paracetamol), while not an NSAID and generally gentler on the stomach, poses a significant risk of liver toxicity in high doses. Its metabolism in the liver produces a toxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI). Normally detoxified by glutathione, excessive acetaminophen overwhelms this system, leading to liver cell damage and even acute liver failure in extreme cases.
NSAIDs have been linked to an increased risk of cardiovascular events such as heart attacks and strokes. Selective COX-2 inhibitors like celecoxib were initially developed to minimize GI side effects but were later found to heighten cardiovascular risks. The imbalance caused by COX-2 inhibition affects prostacyclin and thromboxane levels, tipping the scales toward increased platelet aggregation and vasoconstriction, which can contribute to cardiovascular events.
Aspirin, uniquely, is a double-edged sword for cardiovascular health. While low-dose aspirin is widely prescribed for its antiplatelet effect in preventing heart attacks and strokes, higher doses or prolonged use can exacerbate bleeding risks, especially in the brain or GI tract. Additionally, some NSAIDs may activate nuclear factor erythroid 2-related factor 2 (NRF2), a protein that triggers anti-inflammatory processes in the body. This mechanism, uncovered in recent research, adds complexity to our understanding of NSAIDs and their diverse effects on cardiovascular and overall health.
Acetaminophen has been shown to have surprising psychological effects, potentially blunting not only physical pain but also emotional responses. Research suggests it may reduce emotional sensitivity to both positive and negative stimuli, raising questions about its long-term effects on mood and emotional well-being during prolonged use.
Prescription opioids such as oxycodone and hydrocodone pose significant risks to mental health. While effective for severe pain, they carry a high risk of addiction due to their activation of the brain’s reward system. Prolonged opioid use can lead to dependency, withdrawal symptoms, and a range of psychological issues, including depression and anxiety.
NSAIDs can pose risks to kidney function, particularly in individuals with pre-existing kidney conditions or dehydration. These drugs reduce blood flow to the kidneys by inhibiting prostaglandins, which play a crucial role in maintaining renal perfusion. Chronic NSAID use has been associated with acute kidney injury and chronic kidney disease.
Acetaminophen, while generally safer for the kidneys than NSAIDs, has also been implicated in kidney damage with excessive or prolonged use, particularly when taken alongside alcohol or other nephrotoxic substances.
Emerging research indicates that painkillers may modulate immune responses. Acetaminophen’s fever-reducing properties, for example, can interfere with an essential immune response to infection. Similarly, NSAIDs’ anti-inflammatory effects can sometimes dampen the body’s natural immune reactions, such as impairing the migration of white blood cells to sites of infection, potentially delaying recovery. Additionally, NRF2 activation by certain NSAIDs could influence immune response, metabolism, and inflammation in ways not yet fully understood.
Gut health has emerged as a critical factor in overall well-being, and painkillers can significantly impact gut microbiota. NSAIDs, in particular, can disrupt the balance of beneficial gut bacteria, contributing to dysbiosis. This alteration in the gut environment has been linked to conditions such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Aspirin, despite its widespread use, has also been shown to alter gut microbiota composition. These findings underscore the importance of further research into how these medications affect gut health, particularly for chronic users.
Prolonged opioid use can paradoxically lead to opioid-induced hyperalgesia (OIH), a condition where patients become more sensitive to pain. This phenomenon, thought to result from changes in the central nervous system, complicates pain management and underscores the risks of long-term opioid therapy.
Recent studies have raised concerns about NSAID use and fertility. These drugs may interfere with ovulation by inhibiting prostaglandin production, which plays a crucial role in the release of eggs from the ovaries. Men may also experience reduced testosterone levels and sperm motility with prolonged NSAID use.
There is emerging evidence that prolonged use of some painkillers may have neurological implications. For instance, chronic NSAID use has been associated with an increased risk of Alzheimer’s disease, although the exact mechanism remains unclear. Conversely, some studies suggest that aspirin’s anti-inflammatory effects might protect against neurodegenerative diseases, highlighting the complex relationship between painkillers and brain health.
The unintended effects of painkillers extend beyond individual health, posing significant challenges to public health systems. The opioid epidemic, fueled in part by the over-prescription of painkillers, has resulted in economic burdens and societal costs, including lost productivity, increased healthcare expenses, and the devastating toll on families and communities.
Understanding the unintended effects of painkillers is crucial for their safe use. Strategies to minimize risks include following dosing recommendations, monitoring for side effects, considering non-drug pain management options, and collaborating with healthcare providers to prevent potential interactions and adverse effects.
Painkillers play a vital role in modern medicine, providing relief from acute and chronic pain. However, their unintended effects—ranging from gastrointestinal and cardiovascular risks to impacts on mental health, kidney function, and gut microbiota—underscore the importance of their judicious use. Recent discoveries, such as the activation of NRF2 by some NSAIDs, add to the complexity of their effects and open avenues for more targeted therapies. As research continues to unravel the multifaceted impacts of these medications, a balanced approach that weighs their benefits and risks is essential for safeguarding public health.
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.
Polyphenols and Advanced Therapeutics in Chronic Inflammation and Pain
Emerging research highlights the significant role of diet quality in managing chronic pain, particularly in reducing inflammation. A study published in Nutrition Research found that women who followed nutrient-dense dietary patterns reported lower levels of pain, independent of body fat percentages. This correlation suggests that the anti-inflammatory properties of high-quality diets, particularly those rich in antioxidants and omega-3 fatty acids, may directly influence pain perception.
Foods like berries, dark leafy greens, fatty fish, nuts, and seeds contain compounds that mitigate pain pathways. Among these are polyphenols and flavonoids, plant-based bioactives known for their anti-inflammatory and antioxidant effects. These compounds may reduce pain by targeting specific biochemical pathways, such as inhibiting the cyclooxygenase-2 (COX-2) enzyme. COX-2 plays a critical role in producing prostaglandins, which trigger inflammation and pain. Polyphenols like curcumin and epicatechins work similarly to nonsteroidal anti-inflammatory drugs (NSAIDs) by naturally suppressing COX-2 activity, without the side effects associated with pharmaceuticals.
Polyphenols also reduce pain by suppressing nuclear factor-kappa B (NF-κB), a key regulator of inflammatory signaling, and by neutralizing oxidative stress, which exacerbates chronic pain. Flavonoids, a subclass of polyphenols, further enhance pain relief by desensitizing pain receptors like TRPV1 and supporting the body’s natural pain-modulating mechanisms.
ACEND, a drug-free therapeutic, incorporates clinically validated polyphenols such as curcumin, luteolin, quercetin, and green tea extract, offering targeted relief for chronic inflammation and pain. Its carefully selected ingredients address inflammatory pathways, enhance gut microbiota metabolism, and support antioxidant defenses, providing a comprehensive approach to pain management.
Adopting a nutrient-rich diet and incorporating polyphenol-rich medical foods like ACEND can be powerful strategies for alleviating chronic pain while enhancing overall health.
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.
Cyclophilin A (CypA) is a pivotal protein involved in cellular processes like protein folding and immune regulation. However, elevated levels of CypA contribute to chronic inflammation, vascular dysfunction, and neurodegenerative diseases, making it a critical target for therapeutic intervention. Recent research highlights the potential of natural compounds, including polyphenols and other bioactive substances, in inhibiting CypA and supporting overall health.
This article explores the importance of CypA inhibition, discusses natural compounds with proven or potential inhibitory effects, and explains how they may benefit health and cognitive function.
Cyclophilin A (CypA) is an enzyme that catalyzes the cis-trans isomerization of proline residues in proteins, facilitating protein folding and stability. It also acts as a secreted pro-inflammatory mediator, attracting immune cells to sites of inflammation. While essential for normal cellular functions, dysregulated CypA activity is implicated in several diseases:
Inhibiting CypA can restore tight junctions, maintaining the integrity of blood vessels and the BBB. It can also improve vascular function by reducing oxidative stress and inflammation, mitigate neurodegeneration by preserving BBB integrity, and control inflammation by targeting pathways linked to chronic inflammatory diseases.
Polyphenols are plant-based compounds known for their anti-inflammatory and antioxidant properties. Several polyphenols have been shown to directly or indirectly inhibit Cyclophilin A:
Epigallocatechin Gallate (EGCG) is a major component of green tea that inhibits CypA’s enzymatic activity, reducing inflammation and supporting vascular and brain health. It is known for its anti-cancer, anti-inflammatory, and neuroprotective properties.
Quercetin, found in apples, onions, and berries, binds to CypA and inhibits its activity, reducing vascular inflammation while enhancing immune health and combating oxidative stress.
Resveratrol, present in grapes and red wine, modulates CypA activity, improving endothelial function and protecting against BBB breakdown. Its benefits include cardiovascular health, anti-aging, and neuroprotection.
Sanglifehrin A, derived from the bacterium Streptomyces species, potently binds to cyclophilins, including CypA, and exhibits anti-inflammatory effects with potential applications in immunosuppression and cancer therapy.
Curcumin, a bioactive compound in turmeric, indirectly modulates CypA-related inflammatory pathways, offering anti-inflammatory effects and supporting vascular and brain health.
23-Demethyl 8,13-Deoxynargenicin (C9) is a natural derivative of nargenicin A1. It targets CypA and disrupts its interactions with CD147 and EGFR, reducing cancer stem cell growth, particularly in non-small-cell lung cancer.
Dihydromyricetin, found in Ampelopsis grossedentata (a traditional Chinese herb), exhibits anti-inflammatory and neuroprotective effects with potential regulation of CypA.
Proanthocyanidins, derived from grape seeds and cocoa, have anti-inflammatory effects that may modulate CypA pathways, supporting vascular health and cognitive function.
Luteolin, present in parsley and celery, has potent anti-inflammatory effects that may indirectly regulate CypA activity, offering protection against oxidative stress and chronic inflammation.
Improved cognitive function is a significant benefit, as CypA inhibition prevents BBB disruption and neuroinflammation, protecting against cognitive decline in neurodegenerative diseases. Enhanced vascular health is another benefit, as inhibition reduces endothelial dysfunction and vascular inflammation, supporting heart health and blood flow. Reduced chronic inflammation is also achievable by targeting pathways driving autoimmune and metabolic disorders, enhancing resilience against chronic disease progression.
Green tea is a rich source of EGCG, a potent natural CypA inhibitor. Colorful fruits and vegetables, such as apples, onions, berries, parsley, and celery, provide quercetin, luteolin, and other bioactives. Grape-based products, including red wine and grape seed extract, are excellent sources of resveratrol and proanthocyanidins. Spices like turmeric offer curcumin, and supplements with polyphenol extracts can also be considered under professional guidance.
Cyclophilin A is a critical protein involved in various diseases, including cardiovascular conditions, neurodegeneration, and cancer. Inhibiting its activity through natural compounds like polyphenols and other bioactives offers a promising, drug-free therapeutic approach. By integrating CypA-inhibiting foods into your diet, you can support vascular health, cognitive function, and overall well-being.
Note: Always consult with a healthcare professional before considering any treatment options or significant dietary changes.