Immunity-Building Effects of Dietary Polyphenols in Humans & Animals
By Winston A. Samuels, Ph.D, founder, president, and chief executive officer of Maxx Performance Inc.
The great range of health-promoting activities of dietary polyphenols has been widely investigated. Dietary polyphenols have been shown to increase gut health across different species and, potentially, can be used to decrease medicated feed additives in animal production (26).
Recently, consumers have driven awareness on issues related to medicated growth promotants in animal production. This heightened awareness has resulted in the animal industry looking closely at alternatives considered more “natural.” Phytogenic compounds (polyphenols) are among the alternatives that are being investigated.
Phytogenic compounds can be made from herbs, essential oils, spices, and other plant parts. Dietary polyphenols are natural compounds occurring in plants, including fruits, vegetables, cereals, tea, coffee, and wine (resveratrol). Phytogenic products feature a combination of plant-based ingredients that show a synergistic effect when successfully formulated together. Phytogenics are commonly used as feed additives; the effects can range from focused support for the microbiome, to overall support helping animals live up to their genetic potential and production performance (10).
Overall, phytogenic products with their well-documented evidence in improving human gut health (4, 14) response have increased the focus on phytogenic products and their benefits in animal health. Phytogenics represent a cost-effective, natural source of microbial suppression for poultry producers and other livestock producers facing pressures to cut back on or eliminate antibiotics in their barns.
How Do Polyphenols Work?
The biological properties of dietary polyphenols are dependent on their bioavailability, which is greatly influenced by their degree of polymerization (2). The gut microbiota plays a key role in modulating the production, bioavailability, and therefore, the biological activities of phenolic metabolites, particularly after the intake of diets containing high-molecular-weight polyphenols (11). In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. Studies have suggested that both the phenolic substrates supplied to the gut bacteria through different dietary intake patterns and the aromatic metabolites produced, may, in turn, modulate, and cause fluctuations in the composition of the microflora populations through selective prebiotic effects and antimicrobial activities against gut pathogenic bacteria (23). The formation of bioactive polyphenol-derived metabolites and the modulation of colonic microbiota may both contribute to host health benefits, although the mechanisms of how this occurs have not been explained (6). The health properties attributed to beneficial bacteria for human hosts include protection against gastrointestinal disorders and pathogens, nutrient processing, reduction of serum cholesterol, reinforcement of intestinal epithelial cell-tight junctions (overcoming leaky gut syndrome), and increased mucus secretion and modulation of the intestinal immune response through cytokine stimulus.
The health-promoting activities of dietary polyphenols in humans include their anti-inflammatory, antioxidant, anti-carcinogenic, anti-adipogenic, anti-diabetic, and neuroprotective potentials, suggesting an association between the consumption of polyphenol-rich foods and a reduced risk of several chronic diseases (8, 9). Polyphenols are believed to reduce morbidity and/or slow down the development of cardiovascular and neurodegenerative diseases as well as cancer (12). Biological activity of polyphenols is strongly related to their antioxidant properties. They tend to reduce the pool of reactive oxygen species (25) as well as to neutralize potentially carcinogenic metabolites. A broad spectrum of health-promoting properties of plant polyphenols comprises antioxidant, anti-inflammatory, anti-allergic, anti-atherogenic, anti-thrombotic, and anti-mutagenic effects (13, 17). Scientific studies present the ability of polyphenols to modulate the human immune system by affecting the proliferation of white blood cells, and also the production of cytokines or other factors that participate in the immunological defense (16). Overall, consumption of polyphenols rich diets has been shown to boost immunity. A strong immune system is a prerequisite for good health. Currently, with COVID-19, there is a greater recognition of the importance of maintaining a balanced immune system. However, even after the world becomes COVID-free, consumers will keep on seeking products that support a resilient immune system. Also, the traction of this trend is further elevated by the world’s aging population, as elderly people are typically more vulnerable to infections than younger generations. Moreover, as the pandemic may lead to a surge in older patient hospital admissions, the use of nutritional solutions to help support their immune system and recovery is likely to rise.
Microencapsulation Improves Stability and Bioavailability of Resveratrol
Once ingested, polyphenols are recognized by the human body as xenobiotics, and their bioavailability is therefore relatively low in comparison to micro and macronutrients (6). Furthermore, depending on their degree of structural complexity and polymerization, these compounds may be readily absorbed in the small intestine. Only about 5-10% of the total dietary polyphenol intake may be directly absorbed in the small intestine (18), the remaining 95% are acted upon by colonic bacteria (3) to produce a series of microbial phenolic derivative compounds all of which may be absorbed, or excreted in the feces (6). Resveratrol is a polyphenol that has been reported to have benefits for human health, including antioxidant, anti-inflammatory, anti-carcinogenic, anti-obesity, and heart/brain-protective effects. However, resveratrol as a nutraceutical in the food industry is limited due to its high chemical instability and low oral bioavailability. Maxx Performance has used microencapsulation technology to improve stability and bioavailability of resveratrol for use in a wide application of human and companion animal preparations. Dogs fed diets with slow-released microencapsulated resveratrol demonstrate improved mobility and soundness, a healthy inflammatory response, and healthy free radical levels.
Microencapsulation Also Masks the Bitter Taste of Polyphenols Like Green Tea
Green tea is rich in polyphenols, including catechins, gallic acid, theaflavins, tannins, and flavonoids. It also includes epigallocatechin gallate (EGCG), epigallocatechin, epicatechin gallate, and epicatechin that work as antioxidants and offer a number of health benefits (27, 21). They lower inflammation in the body and prevent early signs of aging, cancer, diabetes, promote weight management, arthritis, heart disease, and neurodegenerative diseases (5, 22). Because of its anti-inflammatory effect the EGCG in Green Tea Extract should be repurposed in COVID-19 patients with the aim to revert the hyper-inflammatory status (19). Taking into account that a timely administration of EGCG to COVID-19 patients is most likely crucial, Menegazzi and co-workers (19) suggested administering EGCG, orally, at the dosage of 600–900 mg/day, once the symptoms aggravate and/or the blood C-reactive protein, or other markers of inflammation increase. They further stated that they expect that EGCG administration can prevent the further aggravation leading to inflammatory markers decline. While the benefits are clear, oral consumption of powdered green tea has been compromised due to the bitter taste of its polyphenols, such as catechins, and the potential, for the polyphenols in green tea to seep into membranes and become unstable in the gut due to their reactive nature (7). Because these polyphenols are highly soluble and reactive, they are not well absorbed by the body. Even the bacteria in the gut tend to degrade the polyphenols. In spite of their strong antioxidant activity green tea polyphenols are limited in bioavailability (15)
One challenge has always been how to mask the bitter taste of this beneficial ingredient so that it can be used in everyday items such as chocolate, baked goods, and beverages such as malts, or sprinkled on salads, cereals, and more. Another challenge is stabilizing powdered green tea for slow release so that it can be delivered in the lower gut, thereby preventing degradation of polyphenols by gut bacteria. In both cases, microencapsulation has been used to cost-effectively mask the bitter taste of green tea extract and deliver stabilized, sustained released of preparations of this polyphenol. Each particle of green tea extract is coated with a thin, tasteless film of vegetable food-grade material. The resulting material is a very fine, free-flowing brownish powder that can be used in powdered mixes, bakery products, nutrient bars, chocolate, soft chews, and stick packs. Previous attempts by the industry to mask the bitter taste of polyphenols, such as green tea extract, were focused on using expensive dairy products, high-priced flavors, sweeteners, and other bulking agents.
The Case for Using Microencapsulation to Enhance the Bioavailability of Turmeric
Turmeric has many beneficial health effects. However, a major drawback for widespread use of turmeric is its poor bioavailability. In fact, some researchers have argued that given its unstable, reactive, and low bioavailability, further clinical trials on turmeric are not needed (1). Turmeric has been confirmed to exhibit very poor bioavailability, with many studies showing very low, or even undetectable, concentrations in blood and extra intestinal tissue. Major reasons postulated are due to its poor absorption, rapid metabolism, chemical instability, and rapid systemic elimination (1). About 90% of oral turmeric is excreted in the feces (20). Several methods have been implemented to increase the bioavailability of turmeric. These include the use of adjuvants such as piperine, formulating liposomal turmeric, turmeric nanoparticles, turmeric phospholipid complexes, and the use of structural analogs of turmeric such as turmeric oil (1, 24). Such efforts have met with some success, as increased blood concentrations have been shown. Advances in microencapsulation, as a delivery system, now makes it possible to increase bioavailability of turmeric. By coating each particle of turmeric with a lipid layer the active turmeric is released in the small intestine and presented as a lipid moiety at the site of absorption. Our Maxx Performance lab has microencapsulated turmeric, with enhanced bioavailability, that is being used in different formulations.
The Effect of Stabilized, Slow-Released Microencapsulated Polyphenols on Animal Performance
On a recent commercial farm trial, eight hundred and sixty-four beef cattle were fed a typical standard feed yard diet consisting of a name brand medicated feed additive, while a similar number of cattle were fed a diet consisting of stabilized, slow-released microencapsulated polyphenol supplement, early and late in the finishing period. At the end of the study, there was a 58% higher death loss for animals fed diets supplemented with the name brand medicated feed additive compared to animals fed diets containing the microencapsulated stabilized polyphenol. Animals supplemented with the stabilized, slow-released polyphenol were 20 lbs. heavier, representing an increase of $19,711, a 0.14 lb./head/day higher average daily gain, and a lower number of liver abscesses than animals fed the name brand medicated feed additive. The results of this on-farm trial demonstrate that stabilized, slow-release polyphenol fed to finishing beef cattle can improve rumen pH and function while helping support the animal through systemic stress and inflammation caused by subclinical or clinical ruminal acidosis. Stabilized polyphenols have the potential to decrease the use of medicated feed additives in animal production. Phytogenics represent a cost-effective, natural source of microbial suppression for producers facing pressures to cut back on or eliminate antibiotics in their production systems.
It is clear that dietary polyphenols and their metabolites contribute to the maintenance of gut health by modulating microbial balance—stimulating the growth of beneficial bacteria and inhibiting the presence of pathogenic bacteria. By exerting prebiotic-like effects, these compounds have the potential to increase overall immunity and well-being, and lessen the dependency on medicated feed additives. In this way, microencapsulation can be used to enhance the bioavailability of polyphenolic compounds, and thereby increase their nutritive value in humans and animals.
- Anand, P., A. B. Kunnumakkara, R. A. Newman and B. B. Aggarwal. 2007. Bioavailability of curcumin: problems and promises. Mol. Pharm. 4: 807-18.
- Appeldoom, M. M., J. P. Vincken, H. Gruppen and P. C. Hollman. 2009. Procyanidin dimers A1, A2, and B2 are absorbed without conjugation or methylation from the small intestine of rats. J. Nutr. 139: 1469-1473.
- Bowey, E. H., H. Adelercreutz and I. Rowland. 2003. Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats. Food Chem. Toxicol. 41: 631-636.
- Brennes, A., A. Viveros, S. Chamorro and I. Anija. 2016. Use of polyphenol-rich grape by-products in monogastric nutrition. A review. Anim. Feed. Sci. Tech. 211: 1-17.
- Butt, M. S. and M. T. Sultan. 2009. Green tea: nature’s defense against malignancies. Crit. Rev. Food Sci. Nutr. 49: 463-473.
- Cardona, F., C. Andres-Lacueva, S. Tulipani, F. J. Tinahones, M. I. Queipo-Ortuno. 2013. Benefits of polyphenols on gut microbiota and implications in human health. J. Nutr. Biochem. 24: 1415-1422.
- Chung, E., S. Campise, H. Joiner, M. Tomison, G. Kaur, J. Dufour, L. Cole and L. Ramalingam. 2019. Effects of annatto-extracted tocotrienols and green tea polyphenols on glucose homeostasis and sketal muscle metabolism in obese male mice. J. Nutr. Biochem. 67: 36-43.
- Debicka-Gorzynik, M. P. Przchodzen, F. Capello, Alicja Kuban-Jankowska, A, Marino Gammazza, N. Knap, M. Wozniak and M. Gorska-Ponikowska. 2018. Potential health benefits of olive oil and plant polyphenols. Int. J. Mol. Sci. 686.
- Del Rio, D., A. Rodriquez-Matos, J. P. Spencer, M. Tognolini, G. Borges and A. Grozier. 2013. Dietary (poly) phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid. Redox Signal. 18: 1812-1892.
- Dhama, K., S. Latheef, S. Mani, H. Samad, K. Kartik, R. Tiwari, R. Khan, M. Al-agawany, M. Frarag, G. Alam, V. Laudadio and V. Tufarelli. 2015. Multiple beneficial applications and modes of action of herbs in poultry health and production. A review. Int. J. Pharmacol. 11: 152-176.
- Duggan, C., J. Gannon and W. A. Walker. 2002. Protective nutrients and functional foods for the gastrointestinal tract. Am. J. Clin. Nutr. 75: 789-808.
- Duthie, G. G. and K. M. Brown. 1994. Reducing the risk of cardiovascular disease. In: Goldberg 1. Functional Foods. Designer Foods, Pharmafoods. Nutraceuticals. Chapman & Hall; New York, NY, USA: 1994. pp 19-38.
- Ellis, L. Z., W. Liu, Y. Luo, M. Okamoto, D. Qu, J. H. Dunn and M. Fujita. 2011. Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion. Biochem. Biophys. Res. Commun. 414: 551-556.
- Etxeberria, U., A. Fernadez-Quintela, F. Milagro, L. Aguirre, J. Martinez and M. Portillo. 2013. Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. J. Agr. Food. Chem. 61: 9517-9533.
- Henning, S., Y. Niu, Y. Liu. N. Lee, Y. Hara, G. Thames, R. Minutti, C. Carpenter, H. Wangad and D. Heber. 2004. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement. Am. J. Clin. Nutr. 80: 1558-1564.
- John, C. M., P. Sandrasaizaran, C. K. Tong, R. Adam and R. Ramasamy. 2011. Immunodulatory activity of polyphenols derived from Casia auriculta flowers in aged rats. Cell. Imminol. 271: 474-479.
- Kunnumakkara, A. B., D. Bordolo, G. Padmavathi, J. Monisha, N. K. Roy, S. Prassad and B. B. Aggarwal. 2017. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. Br. J. Pharmacol. 174: 1325-1328.
- Manach, C. G. Williamson, C. Morand, A. Scalbert and C. Remesy. 2005. Bioavailability and bioefficiency of polyphenols in humans. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 81: 2305
- Menegazzi, M., R. Campagnari, M. Bertoldi, R. Crupi, R. Di Paola and S. Cuzzocrea. 2020. Protective effect of epigallocatechin-3 gallate (EGCG) in diseases with uncontrolled immune activation: Could such a scenario be helpful to counteract COVID-19? Int. J. Mol. Sci. 21: 5171.
- Metzler, M., E. Pfeiffer, S. I Shultz and J. S. Dempe. 2013. Curcumin uptake and metabolism. Biofactors 39: 14-20.
- Pae, M. and D. Wu. 2013. Immunodulating effects of epigallocatechin-3-gallate from green tea: Mechanisms and applications. Food Funct. 4:1287-1303.
- Rastmanesh, R. 2011. High polyphenol, low probiotic diet for weight loss because of intestinal microbiota interaction. Chem. Biol. Interact. 189 (1-2): pp. 1-8.
- Selma, M., J. Espin and F. Tomas-Barberan. 2009. Interaction between phenolics and gut microbiota: Role in human health. J. Agric. Food Chem. 57: 6485-6501.
- Siviero, A. E. Gallo, V. Maggini, L. Gori, A. Mugelli, F. Firenzuoli and A. Vannacci. 2015. Curcumin, a golden spice with a low bioavailability. J. Herb. Med. 5: 57-70.
- Tsao, R. 2010. Chemistry and Biochemistry of Dietary Polyphenols. Nutrients. 2:1231-1246.
- Wallace, R., W. Oleszek, C. Franz, I. Hahn, K. Baser, A. Mathe and K. Teichmann. 2010. Dietary plant bioactives for poultry health and productivity. Brit. Poultry Sci. 51:461-487.
- Xing, L., H. Zhang, R. Qi, R. Tsao and Y. Mine. 2019. Recent advances in the understanding of the health benefits and molecular mechanisms associated with green tea polyphenols. J. Agric. Food Chem. 67: 1029-1043.