Wednesday, November 27, 2019

The Role of Polyphenols in Human Health and Food Systemsls and i mechanisms hold true in humans (37–40). Furthermore, recent evidence has elucidated the effect of absorption pharmacokinetics on efficacy of polyphenols as antioxidants and other potentially health-promoting mechanisms; these physiochemical properties of the molecules may explain the variable effects observed in human and animal models, as well as conflicting data in the literature (41–45). Some harmful effects have been reported from polyphenol intake. Adverse outcomes have been documented from polyphenolic botanical extracts in beverages, especially for individuals with degenerative disease, high blood pressure, thyroid disease, epilepsy, or heart disease (46). Due to pre-absorptive interactions during digestion, dietary polyphenols have also been shown to reduce the transport of thiamin and folic acid, and to alter the activity of drugs through interactions that affect drug transporters or enzymes involved in reactions, resulting in both inhibition and increasing bioavailability depending on the case (14). For example, the iron-chelating and inhibitory effects on absorption of iron associated with polyphenols may lead to poor iron status (47). This could be harmful for populations consuming crops rich in phytates that also inhibit iron absorption, such as sorghum, beans, and millet, especially for populations that already have marginal iron stores. Isoflavones may impact the long-term growth and pubertal development of children fed soy-based formulas in infancy (48, 49). Previous research suggested that isoflavones, found in soy products, may adversely affect women with or at-risk for estrogen-sensitive breast cancer and endometrial cancer as a result of the endocrine-disrupting properties of these compounds (50, 51); however, recent epidemiological reviews suggest either a null or protective effect of isoflavones on these cancer types (52, 53). A recent report by the European Food Safety Authority found no risk of taking isoflavone-containing food supplements for peri- and post-menopausal women (54). Non-communicable diseases Evidence suggests that polyphenols inhibit pro-inflammatory transcription factors by interacting with proteins involved in gene expression and cell signaling, leading to protective effects against many inflammation-mediated chronic diseases (55). Polyphenols hypothesized to be anti-carcinogenic are thought to arrest cellular growth by inducing cell senescence or apoptotic cell death, and their differential redox status may selectively affect tumor cells (14). Resveratrol, found in red wine, is reported to prevent platelet aggregation and relax the arterial blood vessels, disrupting the oxidation of low density lipoprotein (LDL) cholesterol (20, 21, 24–26). However, a systematic review and meta-analysis of 282 human studies found that resveratrol supplementation had no impact on blood lipid levels. This may be because resveratrol is usually consumed in small quantities, and thus any protective effect is marginal (27). Anthocyanins have been associated with both the prevention and management of type 2 diabetes in animal, human, and epidemiological studies (28). The mechanisms of these benefits vary based on the polyphenolic compound, but include protection of pancreatic beta cells from oxidation, anti-inflammatory and antioxidant action, decreased starch digestion due to the suppression of enzyme activity, and the inhibition of advanced glycation end product formation (28). A number of studies have shown improved fasting glucose levels, and improved glucose tolerance and insulin sensitivity, with the consumption of foods containing anthocyanins (56). Neurodegenerative diseases Some polyphenols may also protect against neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases. A population-based prospective study in the Bordeaux region found that consuming three to four glasses of wine per day, which contains resveratrol, was associated with an 80% lower incidence of dementia and Alzheimer's disease compared to non-drinkers (6). Other epidemiologic evidence from the Copenhagen City Heart Study has shown that monthly or weekly red wine was associated with a reduced risk of neurodegenerative diseases, while the other alcoholic beverages studied, beer and spirits, were not (7). Animals studies have shown that a class of polyphenols, epigallocatechin gallate (EGCG), competitively inhibited a neurotoxin known to induce Parkinson's-like disease (8). EGCG may also protect neurons by activating cell survival signaling pathways (9). Turmeric, which is found in curry and contains the polyphenol curcumin, has been hypothesized to contribute to the low incidence of Alzheimer's disease in India due to its high rate of consumption. Improved cognitive function have been found in a study of elderly South Asian participants who frequently consumed curry compared to those who rarely did (10). A prospective cohort study found that Japanese elderly adults who drank green tea had a lower incidence of cognitive decline compared to non-tea drinkers and compared to coffee and black tea drinkers, after adjusting for other factors like alcohol consumption and physical activity (11). Obesity Numerous cellular and animal, and some human studies, have examined the impact of polyphenols on weight status. In the cases of population-based studies, the reduced risk of obesity associated with polyphenol intake from foods may be confounded by the fact that polyphenolic-rich foods are nutrient-dense rather than energy-dense, resulting in a lower calorie intake overall. Evidence from in-vitro and randomized-controlled trials suggest that certain polyphenolic compounds promote a reduction in the genesis, differentiation, and proliferation of adipocytes, in addition to the prevention of inflammation and promotion of lipolysis (18). Catechin polyphenols, including EGCG, have been associated with antioxidant, anti-inflammatory and anti-mutagenic effects (57–59). Catechins are thought to prevent weight gain by promoting greater energy expenditure and fat oxidation (60), though evidence suggests that the effects of green tea on fat oxidation may be due to an interaction with caffeine consumption (59). A meta-analysis of 11 randomized trials found that participants randomized to green tea consumption were better able to maintain their weight loss compared to non-green tea drinkers (61). Blueberries, a rich source of anthocyanins, reduce weight gain in animal studies by protecting against inflammation and modulating obesity pathways (62). Yet, animal trials have demonstrated mixed effects for mitigating weight gain depending on the form in which anthocyanins were consumed (63). Findings from studies investigating the anti-obesogenic properties of resveratrol in animal and human studies have been mixed. Resveratrol has been shown to inhibit lipogenesis and adipocyte differentiation in rats (64). A systematic review and meta-analysis of 282 human subjects found that resveratrol supplementation had no impact on blood triglyceride levels (65). Because resveratrol is consumed in small quantities, its protective effects are unlikely with standard levels of intake (56). Lastly, curcumin has been hypothesized to reduce adiposity through increased energy metabolism, reduced inflammation, and suppressed angiogenesis (66). Animal studies have shown that supplementation with dietary curcumin led to reductions in adiposity and liver fatty acid synthesis, and higher fatty acid oxidation levels (67). Interaction with gut microbiota A growing area of interest in the field of polyphenols is their potential interactions with gut microbiota. Though the mechanisms are not entirely understood, it is hypothesized that polyphenol metabolites may promote beneficial gut bacteria, while inhibiting invasive species (68, 69). Trials have found that blueberry extract drink can promote presence of beneficial bifidobacteria (70), while green tea extract has been found to modulate bacteria like Clostridium difficile, Escherichia coli, and Salmonella typhimurium (71, 72). Evidence suggests that these interactions may also modulate potential impacts on chronic disease risk, such as improved insulin sensitivity and the atheroprotective and hepatoprotective effects of polyphenols (73–77). There is growing evidence that the presence of phenolic compounds may promote beneficial actions of probiotics (78). Further research is needed to characterize the bioavailability of polyphenols and how related metabolites, either phase II metabolites or those generated from gut microbiota, may interact with systemic tissues, in both in vitro and in vivo models (79–81). Go to: Implications for food systems and policy Food processing Food processing and storage strongly influences the polyphenol content of foods. Certain compounds are prone to oxidation, and the addition of polyphenols to foods may compromise shelf stability (82, 83) Methods to prevent this are currently being researched (84). In other cases, antioxidants derived from fruits, vegetables, mushrooms, and herbs have been used to inhibit lipid and protein oxidation and prevent microbial activity in meats (84, 85). Food manufacturers and processors take advantage of the antioxidant properties of polyphenols by adding them to foods and drinks, such as meats and beer, so that they can be sacrificed to prevent the oxidation of other compounds in the food, like lipids, to increase shelf stability (86–91). As use of these extracts potentially broadens, the antioxidant polyphenols they contain could lead to meats becoming a source of dietary polyphenols (92, 93). Culinary preparation plays a significant role in polyphenol content. The quercetin content of tomatoes and onions can be reduced by up to 80% from boiling, 65% from microwaving, and 30% from frying (24). Other types of antioxidants have shown the opposite trend; carotenoids were most depleted in frying methods and most retained from boiling methods in carrots, zucchini, and broccoli, although polyphenolic content was highest when these vegetables were raw and depleted with any cooking (94). Overall, the relationship between cooking method and polyphenol availability is complex and depends on the food, polyphenolic compound, cooking method, and other factors, often exhibiting a U-shaped relationship. Food processing also impacts the bioavailability of polyphenols. Removal of peels and hulls can strip foods of their polyphenol content, while maceration can facilitate the diffusion of polyphenols. For example, red wine is produced through maceration with polyphenol-rich grape skins, resulting in a polyphenol content 10-times greater than white wine (95). Processing methods of foods, like fermentation and drying, can promote the production of toxic substances, including biogenic amines, which has been shown to be counteracted by some polyphenols (91, 96–99). Marketing and regulation Due to the many findings of health benefits, many strategies have emerged to market polyphenols to consumers. Polyphenol-containing products are being promoted as functional foods, which are “foods that have a potentially positive effect on health beyond basic nutrition” (4). The global polyphenols market, which includes applications in food and beverages, pharmaceuticals, and cosmetics, was estimated to exceed 700 million USD in 2015 and is projected to reach 1.1 billion USD by 2022 (99, 100). Some research has shown improvements in biomarkers—including glycemic response (82)—from polyphenols consumed in these forms, but their long-term effects have not been fully assessed. The ability to evaluate and market polyphenol products is also growing, with new methods and procedures currently being developed for assessing bioavailability and bioaccessibility in different foods (101, 102). While it is unlikely to be able to catalog all of the effects of polyphenols per dose due to the myriad of compounds, their interactions with other compounds during consumption, and our incomplete understanding of their effects on health, these methods are important to begin to understand safe levels of consumption. No regulatory recommendations currently exist for the consumption of polyphenols in functional foods (5). Creating such regulations is challenging due to the multitude of compounds, the limited evidence from human studies, and variability in the polyphenol content of foods. Furthermore, the lack of standardized methods, cost of analysis, shelf instability, and lack of intake references make it difficult to add information on food polyphenol content to labels (103). The United States Food and Drug Administration allows health claims for antioxidant nutrients with an established Recommended Daily Intake (RDI), for example, vitamins A and C. Because polyphenols are neither a vitamin nor have an RDI, they cannot be marketed with health claims (104). Polyphenols are often sold as nutritional supplements, which are minimally regulated in the United States, meaning a greater number of functional claims can be made (104). A danger of under-regulated supplementation is the risk of creating mega-doses of polyphenols. The risks of polyphenol intake are difficult to quantify, as the majority of studies investigating risk have been in vitro. Despite myriad studies highlighting potential benefits, unambiguous links between polyphenols and human health have been few and far between. This gap exists largely due to the difficulty of mimicking in vivo conditions effectively in in vitro models. At this time, the European Food Safety Authority only permits health claims for olive oil hydroxytyrosol and cocoa flavanols (81, 105, 106). The health effects of mega-doses of polyphenolic compounds are unlikely to be feasibly characterized by research and as such, alternative approaches must be developed to understand the efficacy of compound-containing foods and supplements and guide regulation efforts. A 2014 report found that 20% of drug-related liver injuries were due to herbal and dietary supplements, many of which contain polyphenols (107). Green tea extract supplements are commonly marketed for weight loss; however, high doses of catechins found in green tea have been found to cause hepatotoxicity, possibly due to oxidative stress caused by EGCG and its metabolites (108, 109). The current lack of regulation in the United States may contribute to overhyped claims, potentially resulting in misuse and overconsumption at potentially harmful levels by consumers (110). Concerns regarding polyphenol fortification and supplementation There are some concerns regarding polyphenol fortification and supplementation. First, their consumption may replace intake of healthy whole foods, like fruits and vegetables. Moreover, polyphenol extracts used in supplementation and fortification may lack the synergistic effects and health benefits of a diet naturally rich in polyphenols (111). These additional benefits include consumption of a high-fiber diet, intake of other and potentially interacting nutrients and non-nutrients, and satiation. In polyphenol research, it is challenging to understand the complex interactions underlying the functional benefits observed with consumption of whole foods containing polyphenols (4). Consumption of the isolated polyphenolic compounds alone may not produce the same benefits observed in epidemiological studies, or the benefits may be overstated by food marketing companies. Fortified foods may also be more energy-dense, rather than nutrient-dense, which could offset any potential anti-obesogenic effects of polyphenols and potentially lead to weight gain (5). Cellular and animal trials test for benefits of polyphenols at amounts much higher than those commonly found in human diets, thus the level at which they can be safely and beneficially added to foods for human consumption remains unclear. The potential for the consumption of deleterious levels of polyphenols is especially of concern with supplements. Some manufacturers recommend intakes over 100-times higher than those currently associated with a Western diet (110). In some cases, supplementation trials of antioxidants have been associated with adverse effects, including increased mortality or stroke in some studies (112–115). Concerns regarding heterogeneous effects in subpopulations and interactions with medications also arise with the promotion of polyphenol consumption at levels far above natural occurrence (114). Without a complete understanding of the safe and beneficial levels of polyphenol intake, their fortification in foods cannot be adequately informed. Researchers should be extremely cautious before undertaking supplementation trials of polyphenolic compounds in humans to ensure that mechanisms and effects in vivo are well-understood. Go to: Conclusions This narrative mini-review provides an overview of the role of polyphenols in relation to topics highly that are relevant to nutrition research and practice, including obesity, type 2 diabetes, neurodegenerative diseases, and gut microbiota. There is substantial evidence that specific polyphenols benefit health status, especially for the prevention and management of certain chronic diseases. The ability to harness these benefits is limited by the current understanding of mechanisms, dosage requirements, and potential unintended effects. Potential negative outcomes for some subgroups should be investigated, and additional human studies are needed to confirm biological mechanisms and public health implications of polyphenols. Studies in vitro and in animals have used levels much higher than those commonly found in human diets, and so the level at which polyphenols can be safely and beneficially consumed remains unclear. Further research is needed to understand whether and how the same benefits from polyphenols consumed in whole foods can be derived from isolated forms. The multitude of polyphenols with different structures, pathways, and physiological roles makes it challenging to fully elucidate their short and long term health effects. As scientific understanding of polyphenols grows, consumers' awareness of proposed benefits and potential risks will increase, as will marketing efforts and the need for understanding efficacy to guide regulation. Regulatory bodies should consider staying abreast of the scientific evidence to provide guidelines for polyphenol consumption and supplementation, including the regulation of their health and functional claims, and the establishment of Dietary Reference Intakes (DRIs) for common and/or potentially harmful polyphenols. Because polyphenols are most commonly found in healthful, plant-based foods like fruits and vegetables, recommendations for consumption should be tied into existing nutrition education efforts and guidelines to promote healthy diets. Although much remains unknown in this burgeoning field, public health measures should be taken early to ensure that consumers are safe and informed. Go to: Author contributions HC and SP conceptualized the topic, researched and analyzed the literature, and wrote the manuscript, including interpretations. JS analyzed background literature and drafted portions of the manuscript. MT and JM provided substantial scholarly guidance on the conception of the topic, manuscript draft and interpretation, and revised the manuscript critically for intellectual content. All authors approve the final version of the manuscript, ensure the accuracy and integrity of the work, and agree to be accountable for all aspects of the work. Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Go to: Acknowledgments The authors thank Suna Park for contributing to this review. We appreciate the comments from our colleagues from the 2016 Principles of Nutrition course at Harvard TH Chan School of Public Health. Go to: Footnotes Funding. HC was supported by the Robert Wood Johnson Foundation Health Policy Research Scholars Award. MT was supported by the National Council of Science and Technology (CONACyT, Mexico). JM was supported by a NIH-NHLBI Mentored Career Development Award to Promote Faculty Diversity in Biomedical Research (grant number K01-HL120951). Go to: References 1. Lecour S, Lamont KT. Natural polyphenols and cardioprotection. Mini Rev Med Chem. (2011) 11:1191–9. 10.2174/13895575111091191 [PubMed] [CrossRef] [Google Scholar] 2. Pérez-Jiménez J, Neveu V, Vos F, Scalber A. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur J Clin Nutr. (2010) 64:S112–20. 10.1038/ejcn.2010.221 [PubMed] [CrossRef] [Google Scholar] 3. Singh A, Holvoet S, Mercenier A. Dietary polyphenols in the prevention and treatment of allergic diseases. Clin Exp Allergy (2011) 41:1346–59. 10.1111/j.1365-2222.2011.03773.x [PubMed] [CrossRef] [Google Scholar] 4. Crowe KM, Francis C. Position of the academy of nutrition and dietetics: functional foods. J Acad Nutr Diet. (2013) 113:1096–103. 10.1016/j.jand.2013.06.002 [PubMed] [CrossRef] [Google Scholar] 5. Williamson G, Holst B. Dietary reference intake (DRI) value for dietary polyphenols: are we heading in the right direction? Brit J Nutr. (2008) 99:S55–8. 10.1017/S0007114508006867 [PubMed] [CrossRef] [Google Scholar] 6. Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, et al. . Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area. Rev Neurol. (1997) 153:185–92. [PubMed] [Google Scholar] 7. Truelsen T, Thudium D, Grønbæk M. Amount and type of alcohol and risk of dementia: the copenhagen city heart study. Neurology (2002) 59:1313–9. 10.1212/01.WNL.0000031421.50369.E7 [PubMed] [CrossRef] [Google Scholar] 8. Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. Role of nitric oxide synthases in Parkinson's disease: a review on the antioxidant and anti-inflammatory activity of polyphenols. Neurochem Res. (2008) 33:2416–26. 10.1007/s11064-008-9697-6 [PubMed] [CrossRef] [Google Scholar] 9. Rossi L, Mazzitelli S, Arciello M, Capo CR, Rotilio G. Benefits from dietary polyphenols for brain aging and Alzheimer's disease. Neurochem Res. (2008) 33:2390–400. 10.1007/s11064-008-9696-7 [PubMed] [CrossRef] [Google Scholar] 10. Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol. (2006) 164: 898–906. 10.1093/aje/kwj267 [PubMed] [CrossRef] [Google Scholar] 11. Noguchi-Shinohara M, Yuki S, Dohmoto C, Ikeda Y, Samuraki M, Iwasa K, et al. . Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS ONE (2014) 9:e96013. 10.1371/journal.pone.0096013 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 12. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. J Am Med Assoc. (2007) 297:842–57. 10.1001/jama.297.8.842 [PubMed] [CrossRef] [Google Scholar] 13. Ogle WO, Speisman RB, Ormerod BK. Potential of treating age-related depression and cognitive decline with nutraceutical approaches: a mini-review. Gerontology (2012) 59:23–31. 10.1159/000342208 [PubMed] [CrossRef] [Google Scholar] 14. Zhang H, Tsao R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Curr Opin Food Sci. (2016) 8:33–42. 10.1016/j.cofs.2016.02.002 [CrossRef] [Google Scholar] 15. Zhou Y, Zheng J, Li Y, Xu DP, Li S, Chen YM, et al. . Natural polyphenols for prevention and treatment of cancer. Nutrients (2016) 8:515. 10.3390/nu8080515 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 16. Khurana S, Venkataraman K, Hollingsworth A, Piche M, Tai TC. Polyphenols: benefits to the cardiovascular system in health and in aging. Nutrients (2013) 5:3779–827. 10.3390/nu5103779 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 17. Jiang H, Wang J, Rogers J, Xie J. Brain iron metabolism dysfunction in Parkinson's disease. Mol Neurobiol. (2017) 54:3078–101. 10.1007/s12035-016-9879-1 [PubMed] [CrossRef] [Google Scholar] 18. Wang S, Moustaid-Moussa N, Chen L, Mo H, Shastri A, Su R. Novel insights of dietary polyphenols and obesity. J Nutr Biochem. (2014) 25:1–18. 10.1016/j.jnutbio.2013.09.001 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 19. Fujiki H, Sueoka E, Watanabe T, Suganuma M. Primary cancer prevention by green tea, and tertiary cancer prevention by the combination of green tea catechins and anticancer compounds. J Cancer Prev. (2015) 20:1–4. 10.15430/JCP.2015.20.1.1 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 20. Guo R, Li W, Liu B, Li S, Zhang B, Xu Y. Resveratrol protects vascular smooth muscle cells against high glucose-induced oxidative stress and cell proliferation in vitro. Med Sci Monit Basic Res. (2014) 20:82–92. 10.12659/MSMBR.890858 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 21. Zhang H, Liu Q, Lin J, Wang Y, Chen S, Hou J. GW27-e0657 resveratrol protects against oxidized LDL-induced foam cells formation and apoptosis through inhibition of ER stress and downregulation of CD36. J Am Coll Cardiol. (2016) 16:C26 10.1016/j.jacc.2016.07.097 [CrossRef] [Google Scholar] 22. Boullata JI, Hudson LM. Drug–nutrient interactions: a broad view with implications for practice. J Acad Nutr Diet (2012) 112:506–17. 10.1016/j.jada.2011.09.002 [PubMed] [CrossRef] [Google Scholar] 23. Wang S, Sun Z, Dong S, Liu Y, Liu Y. Molecular interactions between (–)-epigallocatechin gallate analogs and pancreatic lipase. PLoS ONE (2014) 9:e111143. 10.1371/journal.pone.0111143 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 24. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. (2009) 2:270–8. 10.4161/oxim.2.5.9498 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 25. Berman AY, Motechin RA, Wiesenfeld MY, Holz MK. The therapeutic potential of resveratrol: a review of clinical trials. NPJ Prec Oncol. (2017) 1:35. 10.1038/s41698-017-0038-6 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 26. Guo H, Chen Y, Liao L, Wu W. Resveratrol protects HUVECs from oxidized-LDL induced oxidative damage by autophagy upregulation via the AMPK/SIRT1 pathway. Cardiovasc Drugs Ther. (2013) 27:189–98. 10.1007/s10557-013-6442-4 [PubMed] [CrossRef] [Google Scholar] 27. Weiskirchen S, Weiskirchen R. Resveratrol: how much wine do you have to drink to stay healthy? Adv Nutr. (2016) 7:706–18. 10.3945/an.115.011627 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 28. Xiao JB, Hogger P. Dietary polyphenols and type 2 diabetes: current insights and future perspectives. Curr Med Chem. (2015) 22:23–38. 10.2174/0929867321666140706130807 [PubMed] [CrossRef] [Google Scholar] 29. Jakobek L. Interactions of polyphenols with carbohydrates, lipids and proteins. Food Chem. (2015) 175:556–67. 10.1016/j.foodchem.2014.12.013 [PubMed] [CrossRef] [Google Scholar] 30. Zhang B, Deng Z, Ramdath DD, Tang Y, Chen PX, Liu R. Phenolic profiles of 20 Canadian lentil cultivars and their contribution to antioxidant activity and inhibitory effects on α-glucosidase and pancreatic lipase. Food Chem. (2015) 172:862–72. 10.1016/j.foodchem.2014.09.144 [PubMed] [CrossRef] [Google Scholar] 31. Barrett A, Farhadi NF, Smith TJ. Slowing starch digestion and inhibiting digestive enzyme activity using plant flavanols/tannins—a review of efficacy and mechanisms. LWT Food Sci Technol. (2017) 87:394–9. 10.1016/j.lwt.2017.09.002 [CrossRef] [Google Scholar] 32. Yamagata K, Tagami M, Yamori Y. Dietary polyphenols regulate endothelial function and prevent cardiovascular disease. Nutrition (2015) 31:28–37. 10.1016/j.nut.2014.04.011 [PubMed] [CrossRef] [Google Scholar] 33. Martin-Pelaez S, Covas M, Fito M, Kusar A, Pravst I. Health effects of olive oil polyphenols: recent advances and possibilities for the use of health claims. Mol Nutr Food Res. (2013) 57:760–71. 10.1002/mnfr.201200421 [PubMed] [CrossRef] [Google Scholar] 34. Fraga CG, Galleano M, Verstraeten SV, Oteiza I. Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Aspects Med. (2010) 31:435–45. 10.1016/j.mam.2010.09.006 [PubMed] [CrossRef] [Google Scholar] 35. Sroka Z, Cisowski W. Hydrogen peroxide scavenging, antioxidant and anti-radical activity of some phenolic acids. Food Cheml Toxicol. (2003) 41:753–8. 10.1016/S0278-6915(02)00329-0 [PubMed] [CrossRef] [Google Scholar] 36. Saeidnia S, Abdollahi M. Antioxidants: friends or foe in prevention or treatment of cancer: the debate of the century. Toxicol Appl Pharmacol. (2013) 271:49–63. 10.1016/j.taap.2013.05.004 [PubMed] [CrossRef] [Google Scholar] 37. Habas K, Brinkworth MH, Anderson D. Diethylstilbestrol induces oxidative DNA damage, resulting in apoptosis of spermatogonial stem cells in vitro. Toxicology (2017) 382:117–21. 10.1016/j.tox.2017.03.013 [PubMed] [CrossRef] [Google Scholar] 38. Magrone T, Jirillo E. Influence of polyphenols on allergic immune reactions: mechanisms of action. Proc Nutr Soc. (2012) 71:316–21. 10.1017/S0029665112000109 [PubMed] [CrossRef] [Google Scholar] 39. Anderson AL, Harris TB, Tylavsky FA, Perr SE, Housto DK, Le JS. Dietary patterns, insulin sensitivity and inflammation in older adults. Eur J Clin Nutr. (2012) 66:18–24. 10.1038/ejcn.2011.162 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 40. Auclair S, Chironi G, Milenkovic D, Hollman PCH, Renard CMGC, Mégnien J-L. The regular consumption of a polyphenol-rich apple does not influence endothelial function: a randomised double-blind trial in hypercholesterolemic adults. Eur J Clin Nutr. (2010) 64:1158–65. 10.1038/ejcn.2010.135 [PubMed] [CrossRef] [Google Scholar] 41. Selby-Pham SNB, Howell KS, Dunshea FR, Ludbey J, Lutz A, Bennett L. Statistical modelling coupled with LC-MS analysis to predict human upper intestinal absorption of phytochemical mixtures. Food Chem. (2018) 245:353–63. 10.1016/j.foodchem.2017.10.102. [PubMed] [CrossRef] [Google Scholar] 42. Jaiswal AK, Abu-Ghannam N. Degradation kinetic modelling of color, texture, polyphenols and antioxidant capacity of York cabbage after microwave processing. Food Res Int. (2013) 53:125–33. 10.1016/j.foodres.2013.04.007 [CrossRef] [Google Scholar] 43. Selby-Pham SNB, Osborne SA, Howell KS, Dunshea FR, Bennett LE. Transport rates of dietary phytochemicals in cell monolayers is inversely correlated with absorption kinetics in humans. J Funct Foods (2017) 39:206–14. 10.1016/j.jff.2017.10.016. [CrossRef] [Google Scholar] 44. Selby-Pham SNB, Cottrell JJ, Dunshea FR, Ng K, Bennett LE, Howell KS. Dietary phytochemicals promote health by enhancing antioxidant defence in a pig model. Nutrients (2017) 29:758. 10.3390/nu9070758. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 45. Selby-Pham SNB, Miller RB, Howell K, Dunshea FR, Bennett LE. Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine. Sci Rep. (2017) 7:1931. 10.1038/s41598-017-01888-w. [PMC free article] [PubMed] [CrossRef] [Google Scholar] 46. Jackson C-JC, Paliyath G. Functional foods and nutraceuticals. In: Paliyath G, Bakovic M, Shetty K, editors. Functional Foods, Nutraceuticals, and Degenerative Disease Prevention. New York, NY: John Wiley & Sons; (2011). 11–43. [Google Scholar] 47. Hurrell R, Egli I. Iron bioavailability and dietary reference values. Am J Clin Nutr. (2010) 91:1461S−7S. 10.3945/ajcn.2010.28674F [PubMed] [CrossRef] [Google Scholar] 48. Nguyen RH, Umbach DM, Parad RB, Stroehla B, Rogan WJ, Estroff JA. US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity. Pediatr Radiol. (2011) 41:633–42. 10.1007/s00247-010-1895-0 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 49. Kim J, Kim S, Huh K, Kim Y, Joun H, Park M. High serum isoflavone concentrations are associated with the risk of precocious puberty in Korean girls. Clin Endocr (Oxf). (2011) 75:831–5. 10.1111/j.1365-2265.2011.04127.x [PubMed] [CrossRef] [Google Scholar] 50. Yang X, Belosay A, Hartman JA. Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors. Clin Exp Metastasis. (2015) 32:323–33. 10.1007/s10585-015-9709-2 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 51. Carbonel AF, Calió ML, Santos MA, Bertoncini CA, Sasso GDS, Simões RS. Soybean isoflavones attenuate the expression of genes related to endometrial cancer risk. Climacteric (2015) 18:389–98. 10.3109/13697137.2014.964671 [PubMed] [CrossRef] [Google Scholar] 52. Zhong XS, Ge J, Chen SW, Xiong YQ, Ma SJ, Chen Q. Association between dietary isoflavones in soy and legumes and endometrial cancer: a systematic review and meta-analysis. J Acad Nutr Diet (2016) 118:637–51. 10.1016/j.jand.2016.09.036 [PubMed] [CrossRef] [Google Scholar] 53. Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Tr. (2011) 125:315–23. 10.1007/s10549-010-1270-8 [PubMed] [CrossRef] [Google Scholar] 54. Dai J, Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules (2010) 15:7313–52. 10.3390/molecules15107313 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 55. EFSA Panel on Food Additives and Nutrient Sources Added to Food. Risk assessment for peri- and postmenopausal women taking food supplements containing isolated isoflavones. EFSA J. (2015) 13:4246 10.2903/j.efsa.2015.4246 [CrossRef] [Google Scholar] 56. Azzini E, Giacometti J, Russo GL. Antiobesity effects of anthocyanins in preclinical and clinical studies. Oxid Med Cell Longev. (2017) 2017:2740364. 10.1155/2017/2740364 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 57. Meydani M, Hasan ST. Dietary polyphenols and obesity. Nutrients (2010) 2:737–51. 10.3390/nu2070737 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 58. Rains TM, Agarwal S, Maki KC. Antiobesity effects of green tea catechins: a mechanistic review. J Nutr Biochem. (2011) 22:1–7. 10.1016/j.jnutbio.2010.06.006 [PubMed] [CrossRef] [Google Scholar] 59. Miyatake N, Sakano N, Numata T. Comparison of coffee, tea and green tea consumption between Japanese with and without metabolic syndrome in a cross-sectional study. Open J Epidemiol. (2012) 2:4–49. 10.4236/ojepi.2012.22007 [CrossRef] [Google Scholar] 60. Hursel R, Viechtbauer W, Dulloo AG, Tremblay A, Tappy L, Rumpler W, et al. . The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis. Obes Rev. (2011) 12:e573–81. 10.1111/j.1467-789X.2011.00862.x [PubMed] [CrossRef] [Google Scholar] 61. Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysis. Int J Obes. (2009) 33:956–61. 10.1038/ijo.2009.135 [PubMed] [CrossRef] [Google Scholar] 62. Pojer E, Mattivi F, Johnson D, Stockley CS. The case for anthocyanin consumption to promote human health: a review. Comp Rev Food Sci Food Safety (2013) 12:483–508. 10.1111/1541-4337.12024 [CrossRef] [Google Scholar] 63. Papandreou MA, Dimakopoulou A, Linardaki ZI, Cordopatis P, Klimis-Zacas D, Margarity M, et al. . Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity. Behav Brain Res. (2009) 198:352–8. 10.1016/j.bbr.2008.11.013 [PubMed] [CrossRef] [Google Scholar] 64. Szkudelska K, Nogowski L, Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol. (2009) 113:17–24. 10.1016/j.jsbmb.2008.11.001 [PubMed] [CrossRef] [Google Scholar] 65. Sahebkar A. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. (2013) 71:822–35. 10.1111/nure.12081 [PubMed] [CrossRef] [Google Scholar] 66. Ejaz A, Wu D, Kwan P, Meydani M. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr. (2009) 139:919–25. 10.3945/jn.108.100966 [PubMed] [CrossRef] [Google Scholar] 67. Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, et al. . Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytes. PLoS ONE (2012) 7:e28784. 10.1371/journal.pone.0028784 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 68. Laparra JM, Sanz Y. Interactions of gut microbiota with functional food components and nutraceuticals, Pharmacol Res. (2010) 61:219–25. 10.1016/j.phrs.2009.11.001 [PubMed] [CrossRef] [Google Scholar] 69. Marín L, Miguélez EM, Villar CJ, Lombó F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties. BioMed Res Int. (2015) 2015:905215. 10.1155/2015/905215 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 70. Vendrame S, Guglielmetti S, Riso P, Arioli S, Klimis-Zacas D, Porrini M. Six-week consumption of a wild blueberry powder drink increases bifidobacteria in the human gut. J Agric Food Chem. (2011) 59:12815–20. 10.1021/jf2028686 [PubMed] [CrossRef] [Google Scholar] 71. Lee HC, Jenner AM, Lowand CS, Lee YK. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Res Microbiol. (2006) 157:876–84. 10.1016/j.resmic.2006.07.004 [PubMed] [CrossRef] [Google Scholar] 72. Pacheco-Ordaz R, Wall-Medrano A, Goñi MG, Ramos-Clamont-Montfort G, Ayala-Zavala JF, González-Aguilar GA. Effect of phenolic compounds on the growth of selected probiotic and pathogenic bacteria. Lett Appl Microbiol. (2018) 66:25–31. 10.1111/lam.12814 [PubMed] [CrossRef] [Google Scholar] 73. Bagarolli RA, Tobar N, Oliveira AG, Araújo TG, Carvalho BM, Rocha GZ. Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice. J Nutr Biochem. (2017) 50:16–25. 10.1016/j.jnutbio.2017.08.006 [PubMed] [CrossRef] [Google Scholar] 74. Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly) phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal. (2013) 18:1818–92. 10.1089/ars.2012.4581 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 75. Zanotti I, Dall'Asta M, Mena P, Mele L, Bruni R, Ray S, et al. . Atheroprotective effects of (poly) phenols: a focus on cell cholesterol metabolism. Food Funct. (2015) 6:13–31. 10.1039/c4fo00670d [PubMed] [CrossRef] [Google Scholar] 76. Santhakumar AB, Battino M, Alvarez-Suarez JM. Dietary polyphenols: structures, bioavailability and protective effects against atherosclerosis. Food Chem Toxicol. (2018) 113:49–65. 10.1016/j.fct.2018.01.022 [PubMed] [CrossRef] [Google Scholar] 77. Porras D, Nistal E, Martínez-Flórez S, Pisonero-Vaquero S, Olcoz JL, Jover R. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radic Biol Med. (2017) 102:188–202. 10.1016/j.freeradbiomed.2016.11.037 [PubMed] [CrossRef] [Google Scholar] 78. De Souza EL, de Albuquerque TM, dos Santos AS, Massa NM, de Brito Alves JL. Potential interactions among phenolic compounds and probiotics for mutual boosting of their health-promoting properties and food functionalities–a review. Crit Rev Food Sci Nutr. (2018) 23:1–5. 10.1080/10408398.2018.1425285 [PubMed] [CrossRef] [Google Scholar] 79. González-Sarrías A, Espín JC, Tomás-Barberán FA. Non-extractable polyphenols produce gut microbiota metabolites that persist in circulation and show anti-inflammatory and free radical-scavenging effects. Trends Food Sci Technol. (2017) 69, 281–288. 10.1016/j.tifs.2017.07.010 [CrossRef] [Google Scholar] 80. Espín JC, González-Sarrías A, Tomás-Barberán FA. The gut microbiota: a key factor in the therapeutic effects of (poly)phenols. Biochem Pharmacol. (2017) 139:82–93. 10.1016/j.bcp.2017.04.033 [PubMed] [CrossRef] [Google Scholar] 81. Ávila-Gálvez MA, González-Sarrías A, Espín JC. In vitro research on dietary polyphenols and health: a call of caution and a guide on how to proceed. J Agric Food Chem. (2018) 66:7857–8. 10.1021/acs.jafc.8b03377 [PubMed] [CrossRef] [Google Scholar] 82. Törrönen R, McDougall GJ, Dobson G, Stewart D, Hellström J, Mattila P, et al. Fortification of blackcurrant juice with crowberry: impact on polyphenol composition, urinary phenolic metabolites, and postprandial glycemic response in healthy subjects. J Funct Foods (2012) 4:746–56. 10.1016/j.jff.2012.05.001 [CrossRef] [Google Scholar] 83. Ofori JA, Hsieh Y-HP. Novel technologies for the production of functional foods. In: Bagchi D, Bagchi M, Moriyama H, Shahidi F, editors. , editors. Bio-Nanotechnology: A Revolution in Food, Biomedical and Health Sciences. New York, NY: John Wiley & Sons; (2013). p. 143–62. [Google Scholar] 84. Falowo AB, Fayemi PO, Muchenje V. Natural antioxidants against lipid–protein oxidative deterioration in meat and meat products: a review. Food Res Int. (2014) 64:171–81. 10.1016/j.foodres.2014.06.022 [PubMed] [CrossRef] [Google Scholar] 85. Bao HN, Ushio H, Ohshima T. Antioxidative activity and antidiscoloration efficacy of ergothioneine in mushroom (Flammulina velutipes) extract added to beef and fish meats. J Agric Food Chem. (2008) 56:10032–40. 10.1021/jf8017063 [PubMed] [CrossRef] [Google Scholar] 86. Taranto F, Pasqualone A, Mangini G, Tripodi P, Miazzi MM, Pavan S, et al. . Polyphenol oxidases in crops: biochemical, physiological and genetic aspects. Int J Mol Sci. (2017) 10:18:377. 10.3390/ijms18020377 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 87. Papuc C, Goran G, Durdun C, Nicorescu V, Stefan G. Plant polyphenols as antioxidant and antibacterial agents for shelf-life extension of meat and meat products: classification, structures, sources, and action mechanisms. Comp Rev Food Sci Food Safety (2017) 16:1243–68. 10.1111/1541-4337.12298 [CrossRef] [Google Scholar] 88. Aron PM, Shellhammer TH. A discussion of polyphenols in beer physical and flavour stability. J Inst Brew. (2010) 116:369–80. 10.1002/j.2050-0416.2010.tb00788.x [CrossRef] [Google Scholar] 89. Schneider M, Esposito D, Lila MA, Foegeding EA. Formation of whey protein–polyphenol meso-structures as a natural means of creating functional particles. Food Funct. (2016) 7:1306–18. 10.1039/C5FO01499A [PubMed] [CrossRef] [Google Scholar] 90. Li T, Li J, Hu W, Zhang X, Li X, Zhao J. Shelf-life extension of crucian carp (Carassius auratus) using natural preservatives during chilled storage. Food Chem. (2012) 135:140–5. 10.1016/j.foodchem.2012.04.115 [CrossRef] [Google Scholar] 91. Wenjiao F, Yunchuan C, Junxiu S, Yongkui Z. Effects of tea polyphenol on quality and shelf life of pork sausages. J Food Sci Technol. (2014) 51:191–5. 10.1007/s13197-013-1076-x [PMC free article] [PubMed] [CrossRef] [Google Scholar] 92. Carpenter R, O'Grady MN, O'Callaghan YC, O'Brien NM, Kerry JP. Evaluation of the antioxidant potential of grape seed and bearberry extracts in raw and cooked pork. Meat Sci. (2007) 76:604–10. 10.1016/j.meatsci.2007.01.021 [PubMed] [CrossRef] [Google Scholar] 93. Wootton-Beard PC, Moran A, Ryan L. Stability of the total antioxidant capacity and total polyphenol content of 23 commercially available vegetable juices before and after in vitro digestion measured by FRAP, DPPH, ABTS and Folin–Ciocalteu methods. Food Res Int. (2011) 44:217–24. 10.1016/j.foodres.2010.10.033 [CrossRef] [Google Scholar] 94. Miglio C, Chiavaro E, Visconti A, Fogliano V, Pellegrini N. Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetables. J Agric Food Chem. (2007) 56:139–47. 10.1021/jf072304b [PubMed] [CrossRef] [Google Scholar] 95. Arranz S, Chiva-Blanch G, Lamuela-Raventos RM, Estruch R. Wine Polyphenols in the Management of Cardiovascular Risk Factors. In: Watson RR, Preedy VR, Zibadi S, editors. , editors Polyphenols in Human Health and Disease. London; Waltham, MA; San Diego, CA: Academic Press; (2014). p. 993–1006. [Google Scholar] 96. Bozkurt H. Utilization of natural antioxidants: green tea extract and Thymbra spicata oil in Turkish dry-fermented sausage. Meat Sci. (2006) 73:442–50. 10.1016/j.meatsci.2006.01.005 [PubMed] [CrossRef] [Google Scholar] 97. Naila A, Flint S, Fletcher G, Bremer P, Meerdink G. Control of biogenic amines in food—existing and emerging approaches. J Food Sci. (2010) 75:R139–50. 10.1111/j.1750-3841.2010.01774.x [PMC free article] [PubMed] [CrossRef] [Google Scholar] 98. Wang Y, Li F, Zhuang H, Chen X, Li L, Qiao W, et al. Effects of plant polyphenols and α-tocopherol on lipid oxidation, residual nitrites, biogenic amines, and N-nitrosamines formation during ripening and storage of dry-cured bacon. LWT Food Sci Technol. (2015) 60:199–206. 10.1016/j.lwt.2014.09.022 [CrossRef] [Google Scholar] 99. Zhang QQ, Jiang M, Rui X, Li W, Chen XH, Dong MS. Effect of rose polyphenols on oxidation, biogenic amines and microbial diversity in naturally dry fermented sausages. Food Control. (2017) 78:324–30. 10.1016/j.foodcont.2017.02.054 [CrossRef] [Google Scholar] 100. Grand View Research Polyphenols Market Analysis by Product (Grape Seed, Green Tea, Apple), by Application (Functional Food, Functional Beverages, Dietary Supplements) and Segment Forecasts to 2024 (2016). Available online at: https://www.grandviewresearch.com/industry-analysis/polyphenols-market-analysis?utmsource=pressrelease&utmmedium=referral&utmcampaign=PRNFeb27DietarySupplementsRL3&utmcontent=Content 101. Rothwell JA, Perez-Jimenez J, Neveu V, Medina-Remon A, M'Hiri N, García-Lobato P, et al. . Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content. Database (2013) 1:bat070. 10.1093/database/bat070 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 102. Carbonell-Capella JM, Buniowska M, Barba FJ, Esteve MJ, Frígola A. Analytical methods for determining bioavailability and bioaccessibility of bioactive compounds from fruits and vegetables: a review. Comp Rev Food Sci Food Safety (2014)13:155–71. 10.1111/1541-4337.12049 [CrossRef] [Google Scholar] 103. Li J, He X, Li M, Zhao W, Liu L, Kong X. Chemical fingerprint and quantitative analysis for quality control of polyphenols extracted from pomegranate peel by HPLC. Food Chem. (2015) 176:7–11. 10.1016/j.foodchem.2014.12.040 [PubMed] [CrossRef] [Google Scholar] 104. Vinson JA, Motisi MJ. Polyphenol antioxidants in commercial chocolate bars: is the label accurate? J Funct Food (2015) 12:526–9. 10.1016/j.jff.2014.12.022 [CrossRef] [Google Scholar] 105. Guidance for Industry Food Labeling; Nutrient Content Claims; Definition for “High Potency” and Definition for “Antioxidant” for Use in Nutrient Content Claims for Dietary Supplements and Conventional Foods; Small Entity Compliance Guide. U.S. Food and Drug Administration (2008). Available online at: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocuments/RegulatoryInformation/LabelingNutrition/ucm063064.htm 106. European Food Safety Authority (EFSA) Scientific Opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles from oxidative damage (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL-cholesterol concentrations (ID 1639), maintenance of normal blood pressure (ID 3781), “anti-inflammatory properties” (ID 1882), “contributes to the upper respiratory tract health” (ID 3468), “can help to maintain a normal function of gastrointestinal tract” (3779), and “contributes to body defences against external agents” (ID 3467) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J (2011) 9:2033 10.2903/j.efsa.2011.2033 [CrossRef] [Google Scholar] 107. European Food Safety Authority (EFSA) Scientific Opinion on the modification of the authorisation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/ 2006 following a request in accordance with Article 19 of Regulation (EC) No 1924/2006. EFSA J (2014) 12:3654 10.2903/j.efsa.2014.3654 [CrossRef] [Google Scholar] 108. Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. . Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology (2014) 60:1399–408. 10.1002/hep.27317 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 109. Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R, Santuccio C, et al. . Hepatotoxicity from green tea: a review of the literature and two unpublished cases. Eur J Clin Pharmacol. (2009) 65:331–41. 10.1007/s00228-008-0610-7 [PubMed] [CrossRef] [Google Scholar] 110. Garcia-Cortes M, Robles-Diaz M, Ortega-Alonso A, Medina-Caliz I, Andrade RJ. Hepatotoxicity by dietary supplements: a tabular listing and clinical characteristics. Int J Mol Sci. (2016) 17:537. 10.3390/ijms17040537 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 111. Mazzanti G, Di Sotto A, Vitalone A. Hepatotoxicity of green tea: an update. Arch Toxicol. (2015) 89:1175–91. 10.1007/s00204-015-1521-x [PubMed] [CrossRef] [Google Scholar] 112. Whitsett M, Marzio DH, Rossi S. SlimQuick-associated hepatotoxicity resulting in fulminant liver failure and orthotopic liver transplantation. ACG Case Rep J. (2014) 1:220–2. 10.14309/crj.2014.59 [PMC free article] [PubMed] [CrossRef] [Google Scholar] 113. Martin KR, Appel CL. Polyphenols as dietary supplements: a double-edged sword. Nutr Diet Suppl. (2010) 2:1–12. 10.2147/NDS.S6422 [CrossRef] [Google Scholar] 114. Hooper B, Frazier R. Polyphenols in the diet: friend or foe? Nutr Bull. (2012) 37:297–308. 10.1111/j.1467-3010.2012.02001.x [CrossRef] [Google Scholar] 115. Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements and mortality. Curr Opin Clin Nutr Metabolic Care (2014) 17:40–4. 10.1097/MCO.0000000000000009 [PubMed] [CrossRef] [Google Scholar] Articles from Frontiers in Nutrition are provided here courtesy of Frontiers MA

The Role of Polyphenols in Human Health and Food Systems: A Mini-Review

Introduction

Polyphenols, organic compounds found abundantly in plants, have become an emerging field of interest in nutrition in recent decades. A growing body of research indicates that polyphenol consumption may play a vital role in health through the regulation of metabolism, weight, chronic disease, and cell proliferation. Over 8,000 polyphenols have thus far been identified, though their short- and long-term health effects have not been fully characterized (). Animal, human and epidemiologic studies show that various polyphenols have antioxidant and anti-inflammatory properties that could have preventive and/or therapeutic effects for cardiovascular disease, neurodegenerative disorders, cancer, and obesity (). However, some have cautioned that there may be harmful effects of overconsumption, especially in cases where compounds are isolated rather than consumed in a food matrix (). This narrative mini-review explores the current evidence relating polyphenols to general health and non-communicable diseases (NCDs), describes the implications of this evidence for public health, and discusses potential future directions for practice, policy, and research.

Scientific background

General evidence on health

Recent polyphenol research is primarily composed of epidemiologic cohort and case-control studies that focus on disease endpoints, in addition to mouse-model and human feeding experiments that explore mechanistic interactions. Evidence generated by animal and human studies shows that the antioxidant and anti-inflammatory properties of polyphenols may potentially prevent or serve as treatment against many non-communicable diseases (Table (Table1)1) ().

Table 1

Summary of Reviewed Potential Health Effects of Polyphenols.
Type of diseaseEvidence of effects
Neurodegenerative diseases
  • Curcumin, resveratrol, and catechins (like epigallocatechin gallate (EGCG)) may protect against Alzheimer's-like diseases and dementia through antioxidant and immunomodulatory and scavenging properties that protect neurons and inhibition of the neurotoxic effects of the beta-amyloid protein, the accumulation of which is linked to Alzheimer's disease ().
  • The iron-chelating effects of EGCG, curcumin, myricetin, ginsenosides, and ginkgetin are thought to be an underlying mechanism through which polyphenols prevent neurotoxicity, leading to a neuroprotective effect against neurodegenerative diseases like Parkinson's Disease, Alzheimer's Disease, and Huntington's Disease ().
Inflammation
  • Phenolic compounds may prevent systemic and/or localized inflammation by restoring the redox balance to reduce oxidative stress, and by modulating inflammatory responses through mitigation of cytokine pathways ().
Cancer
  • Flavanoids such as anthocyanins, catechins, flavanols, flavones, flavanones, and isoflavones, may neutralize free radicals and decrease cancer risk by arresting cellular growth in tumors ().
  • Specific types of cancers with evidence of beneficial effects from polyphenols include colon, prostate, epithelial, endometrial, and breast cancer ().
Cardiovascular health
  • Flavonoid-rich foods have been associated with improved ventricular health, reduced platelet activity, enzymatic modulation, anti-inflammatory effects, and lower blood pressure, to increase overall vascular health ().
  • Flavonoids and resveratrol may block cholesterol oxidation to reduce LDL and lower risk of cardiovascular disease ().
Type 2 diabetes
  • Several polyphenolic compounds, anthocyanins being the most substantiated, are associated with both the prevention and management of type 2 diabetes through protection of beta cells from glucose toxicity, anti-inflammatory and antioxidant effects, slowing of starch digestion, and regulation and altered transport of glucose, leading to better glycemic control ().
Obesity
  • Polyphenols like catechins, resveratrol, and curcumin are associated with anti-obesogenic effects, potentially through adipocyte oxidation, inhibition of lipogenesis, reduction in inflammation, and increases in energy expenditure, leading to improved weight loss and maintenance ().
  • A number of polyphenols have been shown to have protein-binding properties that can inhibit starch, lipid, and protein digestion in the gastrointestinal tract by interacting with and inhibiting digestive enzymes ().
Current literature suggests that the long-term consumption of diets rich in polyphenols protects against certain cancers, cardiovascular diseases, type 2 diabetes, osteoporosis, pancreatitis, gastrointestinal problems, lung damage, and neurodegenerative diseases (). The dominant explanation for these benefits is the “biochemical scavenger theory,” which posits that polyphenolic compounds negate free radicals by forming stabilized chemical complexes, thus preventing further reactions (). There is also evidence of an additional mechanism by which polyphenols protect against oxidative stress by producing hydrogen peroxide (H202), which can then help to regulate immune response actions, like cellular growth (). Yet, the majority of evidence comes from in vitro models and it is unclear if these mechanisms hold true in humans (). Furthermore, recent evidence has elucidated the effect of absorption pharmacokinetics on efficacy of polyphenols as antioxidants and other potentially health-promoting mechanisms; these physiochemical properties of the molecules may explain the variable effects observed in human and animal models, as well as conflicting data in the literature ().
Some harmful effects have been reported from polyphenol intake. Adverse outcomes have been documented from polyphenolic botanical extracts in beverages, especially for individuals with degenerative disease, high blood pressure, thyroid disease, epilepsy, or heart disease (). Due to pre-absorptive interactions during digestion, dietary polyphenols have also been shown to reduce the transport of thiamin and folic acid, and to alter the activity of drugs through interactions that affect drug transporters or enzymes involved in reactions, resulting in both inhibition and increasing bioavailability depending on the case (). For example, the iron-chelating and inhibitory effects on absorption of iron associated with polyphenols may lead to poor iron status (). This could be harmful for populations consuming crops rich in phytates that also inhibit iron absorption, such as sorghum, beans, and millet, especially for populations that already have marginal iron stores. Isoflavones may impact the long-term growth and pubertal development of children fed soy-based formulas in infancy (). Previous research suggested that isoflavones, found in soy products, may adversely affect women with or at-risk for estrogen-sensitive breast cancer and endometrial cancer as a result of the endocrine-disrupting properties of these compounds (); however, recent epidemiological reviews suggest either a null or protective effect of isoflavones on these cancer types (). A recent report by the European Food Safety Authority found no risk of taking isoflavone-containing food supplements for peri- and post-menopausal women ().

Non-communicable diseases

Evidence suggests that polyphenols inhibit pro-inflammatory transcription factors by interacting with proteins involved in gene expression and cell signaling, leading to protective effects against many inflammation-mediated chronic diseases (). Polyphenols hypothesized to be anti-carcinogenic are thought to arrest cellular growth by inducing cell senescence or apoptotic cell death, and their differential redox status may selectively affect tumor cells (). Resveratrol, found in red wine, is reported to prevent platelet aggregation and relax the arterial blood vessels, disrupting the oxidation of low density lipoprotein (LDL) cholesterol (). However, a systematic review and meta-analysis of 282 human studies found that resveratrol supplementation had no impact on blood lipid levels. This may be because resveratrol is usually consumed in small quantities, and thus any protective effect is marginal ().
Anthocyanins have been associated with both the prevention and management of type 2 diabetes in animal, human, and epidemiological studies (). The mechanisms of these benefits vary based on the polyphenolic compound, but include protection of pancreatic beta cells from oxidation, anti-inflammatory and antioxidant action, decreased starch digestion due to the suppression of enzyme activity, and the inhibition of advanced glycation end product formation (). A number of studies have shown improved fasting glucose levels, and improved glucose tolerance and insulin sensitivity, with the consumption of foods containing anthocyanins ().

Neurodegenerative diseases

Some polyphenols may also protect against neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases. A population-based prospective study in the Bordeaux region found that consuming three to four glasses of wine per day, which contains resveratrol, was associated with an 80% lower incidence of dementia and Alzheimer's disease compared to non-drinkers (). Other epidemiologic evidence from the Copenhagen City Heart Study has shown that monthly or weekly red wine was associated with a reduced risk of neurodegenerative diseases, while the other alcoholic beverages studied, beer and spirits, were not (). Animals studies have shown that a class of polyphenols, epigallocatechin gallate (EGCG), competitively inhibited a neurotoxin known to induce Parkinson's-like disease (). EGCG may also protect neurons by activating cell survival signaling pathways (). Turmeric, which is found in curry and contains the polyphenol curcumin, has been hypothesized to contribute to the low incidence of Alzheimer's disease in India due to its high rate of consumption. Improved cognitive function have been found in a study of elderly South Asian participants who frequently consumed curry compared to those who rarely did (). A prospective cohort study found that Japanese elderly adults who drank green tea had a lower incidence of cognitive decline compared to non-tea drinkers and compared to coffee and black tea drinkers, after adjusting for other factors like alcohol consumption and physical activity ().

Obesity

Numerous cellular and animal, and some human studies, have examined the impact of polyphenols on weight status. In the cases of population-based studies, the reduced risk of obesity associated with polyphenol intake from foods may be confounded by the fact that polyphenolic-rich foods are nutrient-dense rather than energy-dense, resulting in a lower calorie intake overall. Evidence from in-vitro and randomized-controlled trials suggest that certain polyphenolic compounds promote a reduction in the genesis, differentiation, and proliferation of adipocytes, in addition to the prevention of inflammation and promotion of lipolysis ().
Catechin polyphenols, including EGCG, have been associated with antioxidant, anti-inflammatory and anti-mutagenic effects (). Catechins are thought to prevent weight gain by promoting greater energy expenditure and fat oxidation (), though evidence suggests that the effects of green tea on fat oxidation may be due to an interaction with caffeine consumption (). A meta-analysis of 11 randomized trials found that participants randomized to green tea consumption were better able to maintain their weight loss compared to non-green tea drinkers ().
Blueberries, a rich source of anthocyanins, reduce weight gain in animal studies by protecting against inflammation and modulating obesity pathways (). Yet, animal trials have demonstrated mixed effects for mitigating weight gain depending on the form in which anthocyanins were consumed ().
Findings from studies investigating the anti-obesogenic properties of resveratrol in animal and human studies have been mixed. Resveratrol has been shown to inhibit lipogenesis and adipocyte differentiation in rats (). A systematic review and meta-analysis of 282 human subjects found that resveratrol supplementation had no impact on blood triglyceride levels (). Because resveratrol is consumed in small quantities, its protective effects are unlikely with standard levels of intake ().
Lastly, curcumin has been hypothesized to reduce adiposity through increased energy metabolism, reduced inflammation, and suppressed angiogenesis (). Animal studies have shown that supplementation with dietary curcumin led to reductions in adiposity and liver fatty acid synthesis, and higher fatty acid oxidation levels ().

Interaction with gut microbiota

A growing area of interest in the field of polyphenols is their potential interactions with gut microbiota. Though the mechanisms are not entirely understood, it is hypothesized that polyphenol metabolites may promote beneficial gut bacteria, while inhibiting invasive species (). Trials have found that blueberry extract drink can promote presence of beneficial bifidobacteria (), while green tea extract has been found to modulate bacteria like Clostridium difficile, Escherichia coli, and Salmonella typhimurium (). Evidence suggests that these interactions may also modulate potential impacts on chronic disease risk, such as improved insulin sensitivity and the atheroprotective and hepatoprotective effects of polyphenols (). There is growing evidence that the presence of phenolic compounds may promote beneficial actions of probiotics (). Further research is needed to characterize the bioavailability of polyphenols and how related metabolites, either phase II metabolites or those generated from gut microbiota, may interact with systemic tissues, in both in vitro and in vivo models ().

Implications for food systems and policy

Food processing

Food processing and storage strongly influences the polyphenol content of foods. Certain compounds are prone to oxidation, and the addition of polyphenols to foods may compromise shelf stability () Methods to prevent this are currently being researched (). In other cases, antioxidants derived from fruits, vegetables, mushrooms, and herbs have been used to inhibit lipid and protein oxidation and prevent microbial activity in meats (). Food manufacturers and processors take advantage of the antioxidant properties of polyphenols by adding them to foods and drinks, such as meats and beer, so that they can be sacrificed to prevent the oxidation of other compounds in the food, like lipids, to increase shelf stability (). As use of these extracts potentially broadens, the antioxidant polyphenols they contain could lead to meats becoming a source of dietary polyphenols ().
Culinary preparation plays a significant role in polyphenol content. The quercetin content of tomatoes and onions can be reduced by up to 80% from boiling, 65% from microwaving, and 30% from frying (). Other types of antioxidants have shown the opposite trend; carotenoids were most depleted in frying methods and most retained from boiling methods in carrots, zucchini, and broccoli, although polyphenolic content was highest when these vegetables were raw and depleted with any cooking (). Overall, the relationship between cooking method and polyphenol availability is complex and depends on the food, polyphenolic compound, cooking method, and other factors, often exhibiting a U-shaped relationship.
Food processing also impacts the bioavailability of polyphenols. Removal of peels and hulls can strip foods of their polyphenol content, while maceration can facilitate the diffusion of polyphenols. For example, red wine is produced through maceration with polyphenol-rich grape skins, resulting in a polyphenol content 10-times greater than white wine (). Processing methods of foods, like fermentation and drying, can promote the production of toxic substances, including biogenic amines, which has been shown to be counteracted by some polyphenols ().

Marketing and regulation

Due to the many findings of health benefits, many strategies have emerged to market polyphenols to consumers. Polyphenol-containing products are being promoted as functional foods, which are “foods that have a potentially positive effect on health beyond basic nutrition” (). The global polyphenols market, which includes applications in food and beverages, pharmaceuticals, and cosmetics, was estimated to exceed 700 million USD in 2015 and is projected to reach 1.1 billion USD by 2022 (). Some research has shown improvements in biomarkers—including glycemic response ()—from polyphenols consumed in these forms, but their long-term effects have not been fully assessed. The ability to evaluate and market polyphenol products is also growing, with new methods and procedures currently being developed for assessing bioavailability and bioaccessibility in different foods (). While it is unlikely to be able to catalog all of the effects of polyphenols per dose due to the myriad of compounds, their interactions with other compounds during consumption, and our incomplete understanding of their effects on health, these methods are important to begin to understand safe levels of consumption.
No regulatory recommendations currently exist for the consumption of polyphenols in functional foods (). Creating such regulations is challenging due to the multitude of compounds, the limited evidence from human studies, and variability in the polyphenol content of foods. Furthermore, the lack of standardized methods, cost of analysis, shelf instability, and lack of intake references make it difficult to add information on food polyphenol content to labels (). The United States Food and Drug Administration allows health claims for antioxidant nutrients with an established Recommended Daily Intake (RDI), for example, vitamins A and C. Because polyphenols are neither a vitamin nor have an RDI, they cannot be marketed with health claims (). Polyphenols are often sold as nutritional supplements, which are minimally regulated in the United States, meaning a greater number of functional claims can be made ().
A danger of under-regulated supplementation is the risk of creating mega-doses of polyphenols. The risks of polyphenol intake are difficult to quantify, as the majority of studies investigating risk have been in vitro. Despite myriad studies highlighting potential benefits, unambiguous links between polyphenols and human health have been few and far between. This gap exists largely due to the difficulty of mimicking in vivo conditions effectively in in vitro models. At this time, the European Food Safety Authority only permits health claims for olive oil hydroxytyrosol and cocoa flavanols (). The health effects of mega-doses of polyphenolic compounds are unlikely to be feasibly characterized by research and as such, alternative approaches must be developed to understand the efficacy of compound-containing foods and supplements and guide regulation efforts. A 2014 report found that 20% of drug-related liver injuries were due to herbal and dietary supplements, many of which contain polyphenols (). Green tea extract supplements are commonly marketed for weight loss; however, high doses of catechins found in green tea have been found to cause hepatotoxicity, possibly due to oxidative stress caused by EGCG and its metabolites (). The current lack of regulation in the United States may contribute to overhyped claims, potentially resulting in misuse and overconsumption at potentially harmful levels by consumers ().

Concerns regarding polyphenol fortification and supplementation

There are some concerns regarding polyphenol fortification and supplementation. First, their consumption may replace intake of healthy whole foods, like fruits and vegetables. Moreover, polyphenol extracts used in supplementation and fortification may lack the synergistic effects and health benefits of a diet naturally rich in polyphenols (). These additional benefits include consumption of a high-fiber diet, intake of other and potentially interacting nutrients and non-nutrients, and satiation. In polyphenol research, it is challenging to understand the complex interactions underlying the functional benefits observed with consumption of whole foods containing polyphenols (). Consumption of the isolated polyphenolic compounds alone may not produce the same benefits observed in epidemiological studies, or the benefits may be overstated by food marketing companies.
Fortified foods may also be more energy-dense, rather than nutrient-dense, which could offset any potential anti-obesogenic effects of polyphenols and potentially lead to weight gain (). Cellular and animal trials test for benefits of polyphenols at amounts much higher than those commonly found in human diets, thus the level at which they can be safely and beneficially added to foods for human consumption remains unclear.
The potential for the consumption of deleterious levels of polyphenols is especially of concern with supplements. Some manufacturers recommend intakes over 100-times higher than those currently associated with a Western diet (). In some cases, supplementation trials of antioxidants have been associated with adverse effects, including increased mortality or stroke in some studies (). Concerns regarding heterogeneous effects in subpopulations and interactions with medications also arise with the promotion of polyphenol consumption at levels far above natural occurrence ().
Without a complete understanding of the safe and beneficial levels of polyphenol intake, their fortification in foods cannot be adequately informed. Researchers should be extremely cautious before undertaking supplementation trials of polyphenolic compounds in humans to ensure that mechanisms and effects in vivo are well-understood.

Conclusions

This narrative mini-review provides an overview of the role of polyphenols in relation to topics highly that are relevant to nutrition research and practice, including obesity, type 2 diabetes, neurodegenerative diseases, and gut microbiota. There is substantial evidence that specific polyphenols benefit health status, especially for the prevention and management of certain chronic diseases. The ability to harness these benefits is limited by the current understanding of mechanisms, dosage requirements, and potential unintended effects. Potential negative outcomes for some subgroups should be investigated, and additional human studies are needed to confirm biological mechanisms and public health implications of polyphenols. Studies in vitro and in animals have used levels much higher than those commonly found in human diets, and so the level at which polyphenols can be safely and beneficially consumed remains unclear. Further research is needed to understand whether and how the same benefits from polyphenols consumed in whole foods can be derived from isolated forms.
The multitude of polyphenols with different structures, pathways, and physiological roles makes it challenging to fully elucidate their short and long term health effects. As scientific understanding of polyphenols grows, consumers' awareness of proposed benefits and potential risks will increase, as will marketing efforts and the need for understanding efficacy to guide regulation. Regulatory bodies should consider staying abreast of the scientific evidence to provide guidelines for polyphenol consumption and supplementation, including the regulation of their health and functional claims, and the establishment of Dietary Reference Intakes (DRIs) for common and/or potentially harmful polyphenols. Because polyphenols are most commonly found in healthful, plant-based foods like fruits and vegetables, recommendations for consumption should be tied into existing nutrition education efforts and guidelines to promote healthy diets. Although much remains unknown in this burgeoning field, public health measures should be taken early to ensure that consumers are safe and informed.

Author contributions

HC and SP conceptualized the topic, researched and analyzed the literature, and wrote the manuscript, including interpretations. JS analyzed background literature and drafted portions of the manuscript. MT and JM provided substantial scholarly guidance on the conception of the topic, manuscript draft and interpretation, and revised the manuscript critically for intellectual content. All authors approve the final version of the manuscript, ensure the accuracy and integrity of the work, and agree to be accountable for all aspects of the work.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

The authors thank Suna Park for contributing to this review. We appreciate the comments from our colleagues from the 2016 Principles of Nutrition course at Harvard TH Chan School of Public Health.

Footnotes

Funding. HC was supported by the Robert Wood Johnson Foundation Health Policy Research Scholars Award. MT was supported by the National Council of Science and Technology (CONACyT, Mexico). JM was supported by a NIH-NHLBI Mentored Career Development Award to Promote Faculty Diversity in Biomedical Research (grant number K01-HL120951).

References

1. Lecour S, Lamont KT. Natural polyphenols and cardioprotectionMini Rev Med Chem. (2011) 11:1191–9. 10.2174/13895575111091191 [PubMed] [CrossRef[]
2. Pérez-Jiménez J, Neveu V, Vos F, Scalber A. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer databaseEur J Clin Nutr. (2010) 64:S112–20. 10.1038/ejcn.2010.221 [PubMed] [CrossRef[]
3. Singh A, Holvoet S, Mercenier A. Dietary polyphenols in the prevention and treatment of allergic diseasesClin Exp Allergy (2011) 41:1346–59. 10.1111/j.1365-2222.2011.03773.x [PubMed] [CrossRef[]
4. Crowe KM, Francis C. Position of the academy of nutrition and dietetics: functional foodsJ Acad Nutr Diet. (2013) 113:1096–103. 10.1016/j.jand.2013.06.002 [PubMed] [CrossRef[]
5. Williamson G, Holst B. Dietary reference intake (DRI) value for dietary polyphenols: are we heading in the right direction? Brit J Nutr. (2008) 99:S55–8. 10.1017/S0007114508006867 [PubMed] [CrossRef[]
6. Orgogozo JM, Dartigues JF, Lafont S, Letenneur L, Commenges D, Salamon R, et al. . Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux areaRev Neurol. (1997) 153:185–92. [PubMed[]
7. Truelsen T, Thudium D, Grønbæk M. Amount and type of alcohol and risk of dementia: the copenhagen city heart studyNeurology (2002) 59:1313–9. 10.1212/01.WNL.0000031421.50369.E7 [PubMed] [CrossRef[]
8. Aquilano K, Baldelli S, Rotilio G, Ciriolo MR. Role of nitric oxide synthases in Parkinson's disease: a review on the antioxidant and anti-inflammatory activity of polyphenolsNeurochem Res. (2008) 33:2416–26. 10.1007/s11064-008-9697-6 [PubMed] [CrossRef[]
9. Rossi L, Mazzitelli S, Arciello M, Capo CR, Rotilio G. Benefits from dietary polyphenols for brain aging and Alzheimer's diseaseNeurochem Res. (2008) 33:2390–400. 10.1007/s11064-008-9696-7 [PubMed] [CrossRef[]
10. Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderlyAm J Epidemiol. (2006) 164: 898–906. 10.1093/aje/kwj267 [PubMed] [CrossRef[]
11. Noguchi-Shinohara M, Yuki S, Dohmoto C, Ikeda Y, Samuraki M, Iwasa K, et al. . Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive declinePLoS ONE (2014) 9:e96013. 10.1371/journal.pone.0096013 [PMC free article] [PubMed] [CrossRef[]
12. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysisJ Am Med Assoc. (2007) 297:842–57. 10.1001/jama.297.8.842 [PubMed] [CrossRef[]
13. Ogle WO, Speisman RB, Ormerod BK. Potential of treating age-related depression and cognitive decline with nutraceutical approaches: a mini-reviewGerontology (2012) 59:23–31. 10.1159/000342208 [PubMed] [CrossRef[]
14. Zhang H, Tsao R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effectsCurr Opin Food Sci. (2016) 8:33–42. 10.1016/j.cofs.2016.02.002 [CrossRef[]
15. Zhou Y, Zheng J, Li Y, Xu DP, Li S, Chen YM, et al. . Natural polyphenols for prevention and treatment of cancerNutrients (2016) 8:515. 10.3390/nu8080515 [PMC free article] [PubMed] [CrossRef[]
16. Khurana S, Venkataraman K, Hollingsworth A, Piche M, Tai TC. Polyphenols: benefits to the cardiovascular system in health and in agingNutrients (2013) 5:3779–827. 10.3390/nu5103779 [PMC free article] [PubMed] [CrossRef[]
17. Jiang H, Wang J, Rogers J, Xie J. Brain iron metabolism dysfunction in Parkinson's diseaseMol Neurobiol. (2017) 54:3078–101. 10.1007/s12035-016-9879-1 [PubMed] [CrossRef[]
18. Wang S, Moustaid-Moussa N, Chen L, Mo H, Shastri A, Su R. Novel insights of dietary polyphenols and obesityJ Nutr Biochem. (2014) 25:1–18. 10.1016/j.jnutbio.2013.09.001 [PMC free article] [PubMed] [CrossRef[]
19. Fujiki H, Sueoka E, Watanabe T, Suganuma M. Primary cancer prevention by green tea, and tertiary cancer prevention by the combination of green tea catechins and anticancer compoundsJ Cancer Prev. (2015) 20:1–4. 10.15430/JCP.2015.20.1.1 [PMC free article] [PubMed] [CrossRef[]
20. Guo R, Li W, Liu B, Li S, Zhang B, Xu Y. Resveratrol protects vascular smooth muscle cells against high glucose-induced oxidative stress and cell proliferation in vitroMed Sci Monit Basic Res. (2014) 20:82–92. 10.12659/MSMBR.890858 [PMC free article] [PubMed] [CrossRef[]
21. Zhang H, Liu Q, Lin J, Wang Y, Chen S, Hou J. GW27-e0657 resveratrol protects against oxidized LDL-induced foam cells formation and apoptosis through inhibition of ER stress and downregulation of CD36J Am Coll Cardiol. (2016) 16:C26 10.1016/j.jacc.2016.07.097 [CrossRef[]
22. Boullata JI, Hudson LM. Drug–nutrient interactions: a broad view with implications for practiceJ Acad Nutr Diet (2012) 112:506–17. 10.1016/j.jada.2011.09.002 [PubMed] [CrossRef[]
23. Wang S, Sun Z, Dong S, Liu Y, Liu Y. Molecular interactions between (–)-epigallocatechin gallate analogs and pancreatic lipasePLoS ONE (2014) 9:e111143. 10.1371/journal.pone.0111143 [PMC free article] [PubMed] [CrossRef[]
24. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and diseaseOxid Med Cell Longev. (2009) 2:270–8. 10.4161/oxim.2.5.9498 [PMC free article] [PubMed] [CrossRef[]
25. Berman AY, Motechin RA, Wiesenfeld MY, Holz MK. The therapeutic potential of resveratrol: a review of clinical trialsNPJ Prec Oncol. (2017) 1:35. 10.1038/s41698-017-0038-6 [PMC free article] [PubMed] [CrossRef[]
26. Guo H, Chen Y, Liao L, Wu W. Resveratrol protects HUVECs from oxidized-LDL induced oxidative damage by autophagy upregulation via the AMPK/SIRT1 pathwayCardiovasc Drugs Ther. (2013) 27:189–98. 10.1007/s10557-013-6442-4 [PubMed] [CrossRef[]
27. Weiskirchen S, Weiskirchen R. Resveratrol: how much wine do you have to drink to stay healthy? Adv Nutr. (2016) 7:706–18. 10.3945/an.115.011627 [PMC free article] [PubMed] [CrossRef[]
28. Xiao JB, Hogger P. Dietary polyphenols and type 2 diabetes: current insights and future perspectivesCurr Med Chem. (2015) 22:23–38. 10.2174/0929867321666140706130807 [PubMed] [CrossRef[]
29. Jakobek L. Interactions of polyphenols with carbohydrates, lipids and proteinsFood Chem. (2015) 175:556–67. 10.1016/j.foodchem.2014.12.013 [PubMed] [CrossRef[]
30. Zhang B, Deng Z, Ramdath DD, Tang Y, Chen PX, Liu R. Phenolic profiles of 20 Canadian lentil cultivars and their contribution to antioxidant activity and inhibitory effects on α-glucosidase and pancreatic lipaseFood Chem. (2015) 172:862–72. 10.1016/j.foodchem.2014.09.144 [PubMed] [CrossRef[]
31. Barrett A, Farhadi NF, Smith TJ. Slowing starch digestion and inhibiting digestive enzyme activity using plant flavanols/tannins—a review of efficacy and mechanismsLWT Food Sci Technol. (2017) 87:394–9. 10.1016/j.lwt.2017.09.002 [CrossRef[]
32. Yamagata K, Tagami M, Yamori Y. Dietary polyphenols regulate endothelial function and prevent cardiovascular diseaseNutrition (2015) 31:28–37. 10.1016/j.nut.2014.04.011 [PubMed] [CrossRef[]
33. Martin-Pelaez S, Covas M, Fito M, Kusar A, Pravst I. Health effects of olive oil polyphenols: recent advances and possibilities for the use of health claimsMol Nutr Food Res. (2013) 57:760–71. 10.1002/mnfr.201200421 [PubMed] [CrossRef[]
34. Fraga CG, Galleano M, Verstraeten SV, Oteiza I. Basic biochemical mechanisms behind the health benefits of polyphenolsMol Aspects Med. (2010) 31:435–45. 10.1016/j.mam.2010.09.006 [PubMed] [CrossRef[]
35. Sroka Z, Cisowski W. Hydrogen peroxide scavenging, antioxidant and anti-radical activity of some phenolic acidsFood Cheml Toxicol. (2003) 41:753–8. 10.1016/S0278-6915(02)00329-0 [PubMed] [CrossRef[]
36. Saeidnia S, Abdollahi M. Antioxidants: friends or foe in prevention or treatment of cancer: the debate of the centuryToxicol Appl Pharmacol. (2013) 271:49–63. 10.1016/j.taap.2013.05.004 [PubMed] [CrossRef[]
37. Habas K, Brinkworth MH, Anderson D. Diethylstilbestrol induces oxidative DNA damage, resulting in apoptosis of spermatogonial stem cells in vitroToxicology (2017) 382:117–21. 10.1016/j.tox.2017.03.013 [PubMed] [CrossRef[]
38. Magrone T, Jirillo E. Influence of polyphenols on allergic immune reactions: mechanisms of actionProc Nutr Soc. (2012) 71:316–21. 10.1017/S0029665112000109 [PubMed] [CrossRef[]
39. Anderson AL, Harris TB, Tylavsky FA, Perr SE, Housto DK, Le JS. Dietary patterns, insulin sensitivity and inflammation in older adultsEur J Clin Nutr. (2012) 66:18–24. 10.1038/ejcn.2011.162 [PMC free article] [PubMed] [CrossRef[]
40. Auclair S, Chironi G, Milenkovic D, Hollman PCH, Renard CMGC, Mégnien J-L. The regular consumption of a polyphenol-rich apple does not influence endothelial function: a randomised double-blind trial in hypercholesterolemic adultsEur J Clin Nutr. (2010) 64:1158–65. 10.1038/ejcn.2010.135 [PubMed] [CrossRef[]
41. Selby-Pham SNB, Howell KS, Dunshea FR, Ludbey J, Lutz A, Bennett L. Statistical modelling coupled with LC-MS analysis to predict human upper intestinal absorption of phytochemical mixturesFood Chem. (2018) 245:353–63. 10.1016/j.foodchem.2017.10.102. [PubMed] [CrossRef[]
42. Jaiswal AK, Abu-Ghannam N. Degradation kinetic modelling of color, texture, polyphenols and antioxidant capacity of York cabbage after microwave processingFood Res Int. (2013) 53:125–33. 10.1016/j.foodres.2013.04.007 [CrossRef[]
43. Selby-Pham SNB, Osborne SA, Howell KS, Dunshea FR, Bennett LE. Transport rates of dietary phytochemicals in cell monolayers is inversely correlated with absorption kinetics in humansJ Funct Foods (2017) 39:206–14. 10.1016/j.jff.2017.10.016. [CrossRef[]
44. Selby-Pham SNB, Cottrell JJ, Dunshea FR, Ng K, Bennett LE, Howell KS. Dietary phytochemicals promote health by enhancing antioxidant defence in a pig modelNutrients (2017) 29:758. 10.3390/nu9070758. [PMC free article] [PubMed] [CrossRef[]
45. Selby-Pham SNB, Miller RB, Howell K, Dunshea FR, Bennett LE. Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestineSci Rep. (2017) 7:1931. 10.1038/s41598-017-01888-w. [PMC free article] [PubMed] [CrossRef[]
46. Jackson C-JC, Paliyath G. Functional foods and nutraceuticals. In: Paliyath G, Bakovic M, Shetty K, editors. Functional Foods, Nutraceuticals, and Degenerative Disease Prevention. New York, NY: John Wiley & Sons; (2011). 11–43. []
47. Hurrell R, Egli I. Iron bioavailability and dietary reference valuesAm J Clin Nutr. (2010) 91:1461S−7S. 10.3945/ajcn.2010.28674F [PubMed] [CrossRef[]
48. Nguyen RH, Umbach DM, Parad RB, Stroehla B, Rogan WJ, Estroff JA. US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activityPediatr Radiol. (2011) 41:633–42. 10.1007/s00247-010-1895-0 [PMC free article] [PubMed] [CrossRef[]
49. Kim J, Kim S, Huh K, Kim Y, Joun H, Park M. High serum isoflavone concentrations are associated with the risk of precocious puberty in Korean girlsClin Endocr (Oxf). (2011) 75:831–5. 10.1111/j.1365-2265.2011.04127.x [PubMed] [CrossRef[]
50. Yang X, Belosay A, Hartman JA. Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumorsClin Exp Metastasis. (2015) 32:323–33. 10.1007/s10585-015-9709-2 [PMC free article] [PubMed] [CrossRef[]
51. Carbonel AF, Calió ML, Santos MA, Bertoncini CA, Sasso GDS, Simões RS. Soybean isoflavones attenuate the expression of genes related to endometrial cancer riskClimacteric (2015) 18:389–98. 10.3109/13697137.2014.964671 [PubMed] [CrossRef[]
52. Zhong XS, Ge J, Chen SW, Xiong YQ, Ma SJ, Chen Q. Association between dietary isoflavones in soy and legumes and endometrial cancer: a systematic review and meta-analysisJ Acad Nutr Diet (2016) 118:637–51. 10.1016/j.jand.2016.09.036 [PubMed] [CrossRef[]
53. Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studiesBreast Cancer Res Tr. (2011) 125:315–23. 10.1007/s10549-010-1270-8 [PubMed] [CrossRef[]
54. Dai J, Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer propertiesMolecules (2010) 15:7313–52. 10.3390/molecules15107313 [PMC free article] [PubMed] [CrossRef[]
55. EFSA Panel on Food Additives and Nutrient Sources Added to Food. Risk assessment for peri- and postmenopausal women taking food supplements containing isolated isoflavonesEFSA J. (2015) 13:4246 10.2903/j.efsa.2015.4246 [CrossRef[]
56. Azzini E, Giacometti J, Russo GL. Antiobesity effects of anthocyanins in preclinical and clinical studiesOxid Med Cell Longev. (2017) 2017:2740364. 10.1155/2017/2740364 [PMC free article] [PubMed] [CrossRef[]
57. Meydani M, Hasan ST. Dietary polyphenols and obesityNutrients (2010) 2:737–51. 10.3390/nu2070737 [PMC free article] [PubMed] [CrossRef[]
58. Rains TM, Agarwal S, Maki KC. Antiobesity effects of green tea catechins: a mechanistic reviewJ Nutr Biochem. (2011) 22:1–7. 10.1016/j.jnutbio.2010.06.006 [PubMed] [CrossRef[]
59. Miyatake N, Sakano N, Numata T. Comparison of coffee, tea and green tea consumption between Japanese with and without metabolic syndrome in a cross-sectional studyOpen J Epidemiol. (2012) 2:4–49. 10.4236/ojepi.2012.22007 [CrossRef[]
60. Hursel R, Viechtbauer W, Dulloo AG, Tremblay A, Tappy L, Rumpler W, et al. . The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysisObes Rev. (2011) 12:e573–81. 10.1111/j.1467-789X.2011.00862.x [PubMed] [CrossRef[]
61. Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysisInt J Obes. (2009) 33:956–61. 10.1038/ijo.2009.135 [PubMed] [CrossRef[]
62. Pojer E, Mattivi F, Johnson D, Stockley CS. The case for anthocyanin consumption to promote human health: a reviewComp Rev Food Sci Food Safety (2013) 12:483–508. 10.1111/1541-4337.12024 [CrossRef[]
63. Papandreou MA, Dimakopoulou A, Linardaki ZI, Cordopatis P, Klimis-Zacas D, Margarity M, et al. . Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activityBehav Brain Res. (2009) 198:352–8. 10.1016/j.bbr.2008.11.013 [PubMed] [CrossRef[]
64. Szkudelska K, Nogowski L, Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytesJ Steroid Biochem Mol Biol. (2009) 113:17–24. 10.1016/j.jsbmb.2008.11.001 [PubMed] [CrossRef[]
65. Sahebkar A. Effects of resveratrol supplementation on plasma lipids: a systematic review and meta-analysis of randomized controlled trialsNutr Rev. (2013) 71:822–35. 10.1111/nure.12081 [PubMed] [CrossRef[]
66. Ejaz A, Wu D, Kwan P, Meydani M. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL miceJ Nutr. (2009) 139:919–25. 10.3945/jn.108.100966 [PubMed] [CrossRef[]
67. Shao W, Yu Z, Chiang Y, Yang Y, Chai T, Foltz W, et al. . Curcumin prevents high fat diet induced insulin resistance and obesity via attenuating lipogenesis in liver and inflammatory pathway in adipocytesPLoS ONE (2012) 7:e28784. 10.1371/journal.pone.0028784 [PMC free article] [PubMed] [CrossRef[]
68. Laparra JM, Sanz Y. Interactions of gut microbiota with functional food components and nutraceuticalsPharmacol Res. (2010) 61:219–25. 10.1016/j.phrs.2009.11.001 [PubMed] [CrossRef[]
69. Marín L, Miguélez EM, Villar CJ, Lombó F. Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial propertiesBioMed Res Int. (2015) 2015:905215. 10.1155/2015/905215 [PMC free article] [PubMed] [CrossRef[]
70. Vendrame S, Guglielmetti S, Riso P, Arioli S, Klimis-Zacas D, Porrini M. Six-week consumption of a wild blueberry powder drink increases bifidobacteria in the human gutJ Agric Food Chem. (2011) 59:12815–20. 10.1021/jf2028686 [PubMed] [CrossRef[]
71. Lee HC, Jenner AM, Lowand CS, Lee YK. Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiotaRes Microbiol. (2006) 157:876–84. 10.1016/j.resmic.2006.07.004 [PubMed] [CrossRef[]
72. Pacheco-Ordaz R, Wall-Medrano A, Goñi MG, Ramos-Clamont-Montfort G, Ayala-Zavala JF, González-Aguilar GA. Effect of phenolic compounds on the growth of selected probiotic and pathogenic bacteriaLett Appl Microbiol. (2018) 66:25–31. 10.1111/lam.12814 [PubMed] [CrossRef[]
73. Bagarolli RA, Tobar N, Oliveira AG, Araújo TG, Carvalho BM, Rocha GZ. Probiotics modulate gut microbiota and improve insulin sensitivity in DIO miceJ Nutr Biochem. (2017) 50:16–25. 10.1016/j.jnutbio.2017.08.006 [PubMed] [CrossRef[]
74. Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly) phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseasesAntioxid Redox Signal. (2013) 18:1818–92. 10.1089/ars.2012.4581 [PMC free article] [PubMed] [CrossRef[]
75. Zanotti I, Dall'Asta M, Mena P, Mele L, Bruni R, Ray S, et al. . Atheroprotective effects of (poly) phenols: a focus on cell cholesterol metabolismFood Funct. (2015) 6:13–31. 10.1039/c4fo00670d [PubMed] [CrossRef[]
76. Santhakumar AB, Battino M, Alvarez-Suarez JM. Dietary polyphenols: structures, bioavailability and protective effects against atherosclerosisFood Chem Toxicol. (2018) 113:49–65. 10.1016/j.fct.2018.01.022 [PubMed] [CrossRef[]
77. Porras D, Nistal E, Martínez-Flórez S, Pisonero-Vaquero S, Olcoz JL, Jover R. Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activationFree Radic Biol Med. (2017) 102:188–202. 10.1016/j.freeradbiomed.2016.11.037 [PubMed] [CrossRef[]
78. De Souza EL, de Albuquerque TM, dos Santos AS, Massa NM, de Brito Alves JL. Potential interactions among phenolic compounds and probiotics for mutual boosting of their health-promoting properties and food functionalities–a reviewCrit Rev Food Sci Nutr. (2018) 23:1–5. 10.1080/10408398.2018.1425285 [PubMed] [CrossRef[]
79. González-Sarrías A, Espín JC, Tomás-Barberán FA. Non-extractable polyphenols produce gut microbiota metabolites that persist in circulation and show anti-inflammatory and free radical-scavenging effectsTrends Food Sci Technol. (2017) 69, 281–288. 10.1016/j.tifs.2017.07.010 [CrossRef[]
80. Espín JC, González-Sarrías A, Tomás-Barberán FA. The gut microbiota: a key factor in the therapeutic effects of (poly)phenolsBiochem Pharmacol. (2017) 139:82–93. 10.1016/j.bcp.2017.04.033 [PubMed] [CrossRef[]
81. Ávila-Gálvez MA, González-Sarrías A, Espín JC. In vitro research on dietary polyphenols and health: a call of caution and a guide on how to proceedJ Agric Food Chem. (2018) 66:7857–8. 10.1021/acs.jafc.8b03377 [PubMed] [CrossRef[]
82. Törrönen R, McDougall GJ, Dobson G, Stewart D, Hellström J, Mattila P, et al. Fortification of blackcurrant juice with crowberry: impact on polyphenol composition, urinary phenolic metabolites, and postprandial glycemic response in healthy subjectsJ Funct Foods (2012) 4:746–56. 10.1016/j.jff.2012.05.001 [CrossRef[]
83. Ofori JA, Hsieh Y-HP. Novel technologies for the production of functional foods. In: Bagchi D, Bagchi M, Moriyama H, Shahidi F, editors. , editors. Bio-Nanotechnology: A Revolution in Food, Biomedical and Health Sciences. New York, NY: John Wiley & Sons; (2013). p. 143–62. []
84. Falowo AB, Fayemi PO, Muchenje V. Natural antioxidants against lipid–protein oxidative deterioration in meat and meat products: a reviewFood Res Int. (2014) 64:171–81. 10.1016/j.foodres.2014.06.022 [PubMed] [CrossRef[]
85. Bao HN, Ushio H, Ohshima T. Antioxidative activity and antidiscoloration efficacy of ergothioneine in mushroom (Flammulina velutipes) extract added to beef and fish meatsJ Agric Food Chem. (2008) 56:10032–40. 10.1021/jf8017063 [PubMed] [CrossRef[]
86. Taranto F, Pasqualone A, Mangini G, Tripodi P, Miazzi MM, Pavan S, et al. . Polyphenol oxidases in crops: biochemical, physiological and genetic aspectsInt J Mol Sci. (2017) 10:18:377. 10.3390/ijms18020377 [PMC free article] [PubMed] [CrossRef[]
87. Papuc C, Goran G, Durdun C, Nicorescu V, Stefan G. Plant polyphenols as antioxidant and antibacterial agents for shelf-life extension of meat and meat products: classification, structures, sources, and action mechanismsComp Rev Food Sci Food Safety (2017) 16:1243–68. 10.1111/1541-4337.12298 [CrossRef[]
88. Aron PM, Shellhammer TH. A discussion of polyphenols in beer physical and flavour stabilityJ Inst Brew. (2010) 116:369–80. 10.1002/j.2050-0416.2010.tb00788.x [CrossRef[]
89. Schneider M, Esposito D, Lila MA, Foegeding EA. Formation of whey protein–polyphenol meso-structures as a natural means of creating functional particlesFood Funct. (2016) 7:1306–18. 10.1039/C5FO01499A [PubMed] [CrossRef[]
90. Li T, Li J, Hu W, Zhang X, Li X, Zhao J. Shelf-life extension of crucian carp (Carassius auratus) using natural preservatives during chilled storageFood Chem. (2012) 135:140–5. 10.1016/j.foodchem.2012.04.115 [CrossRef[]
91. Wenjiao F, Yunchuan C, Junxiu S, Yongkui Z. Effects of tea polyphenol on quality and shelf life of pork sausagesJ Food Sci Technol. (2014) 51:191–5. 10.1007/s13197-013-1076-x [PMC free article] [PubMed] [CrossRef[]
92. Carpenter R, O'Grady MN, O'Callaghan YC, O'Brien NM, Kerry JP. Evaluation of the antioxidant potential of grape seed and bearberry extracts in raw and cooked porkMeat Sci. (2007) 76:604–10. 10.1016/j.meatsci.2007.01.021 [PubMed] [CrossRef[]
93. Wootton-Beard PC, Moran A, Ryan L. Stability of the total antioxidant capacity and total polyphenol content of 23 commercially available vegetable juices before and after in vitro digestion measured by FRAP, DPPH, ABTS and Folin–Ciocalteu methodsFood Res Int. (2011) 44:217–24. 10.1016/j.foodres.2010.10.033 [CrossRef[]
94. Miglio C, Chiavaro E, Visconti A, Fogliano V, Pellegrini N. Effects of different cooking methods on nutritional and physicochemical characteristics of selected vegetablesJ Agric Food Chem. (2007) 56:139–47. 10.1021/jf072304b [PubMed] [CrossRef[]
95. Arranz S, Chiva-Blanch G, Lamuela-Raventos RM, Estruch R. Wine Polyphenols in the Management of Cardiovascular Risk Factors. In: Watson RR, Preedy VR, Zibadi S, editors. , editors Polyphenols in Human Health and Disease. London; Waltham, MA; San Diego, CA: Academic Press; (2014). p. 993–1006. []
96. Bozkurt H. Utilization of natural antioxidants: green tea extract and Thymbra spicata oil in Turkish dry-fermented sausageMeat Sci. (2006) 73:442–50. 10.1016/j.meatsci.2006.01.005 [PubMed] [CrossRef[]
97. Naila A, Flint S, Fletcher G, Bremer P, Meerdink G. Control of biogenic amines in food—existing and emerging approachesJ Food Sci. (2010) 75:R139–50. 10.1111/j.1750-3841.2010.01774.x [PMC free article] [PubMed] [CrossRef[]
98. Wang Y, Li F, Zhuang H, Chen X, Li L, Qiao W, et al. Effects of plant polyphenols and α-tocopherol on lipid oxidation, residual nitrites, biogenic amines, and N-nitrosamines formation during ripening and storage of dry-cured baconLWT Food Sci Technol. (2015) 60:199–206. 10.1016/j.lwt.2014.09.022 [CrossRef[]
99. Zhang QQ, Jiang M, Rui X, Li W, Chen XH, Dong MS. Effect of rose polyphenols on oxidation, biogenic amines and microbial diversity in naturally dry fermented sausagesFood Control. (2017) 78:324–30. 10.1016/j.foodcont.2017.02.054 [CrossRef[]
100. Grand View Research Polyphenols Market Analysis by Product (Grape Seed, Green Tea, Apple), by Application (Functional Food, Functional Beverages, Dietary Supplements) and Segment Forecasts to 2024 (2016). Available online at: https://www.grandviewresearch.com/industry-analysis/polyphenols-market-analysis?utmsource=pressrelease&utmmedium=referral&utmcampaign=PRNFeb27DietarySupplementsRL3&utmcontent=Content
101. Rothwell JA, Perez-Jimenez J, Neveu V, Medina-Remon A, M'Hiri N, García-Lobato P, et al. . Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol contentDatabase (2013) 1:bat070. 10.1093/database/bat070 [PMC free article] [PubMed] [CrossRef[]
102. Carbonell-Capella JM, Buniowska M, Barba FJ, Esteve MJ, Frígola A. Analytical methods for determining bioavailability and bioaccessibility of bioactive compounds from fruits and vegetables: a reviewComp Rev Food Sci Food Safety (2014)13:155–71. 10.1111/1541-4337.12049 [CrossRef[]
103. Li J, He X, Li M, Zhao W, Liu L, Kong X. Chemical fingerprint and quantitative analysis for quality control of polyphenols extracted from pomegranate peel by HPLCFood Chem. (2015) 176:7–11. 10.1016/j.foodchem.2014.12.040 [PubMed] [CrossRef[]
104. Vinson JA, Motisi MJ. Polyphenol antioxidants in commercial chocolate bars: is the label accurate? J Funct Food (2015) 12:526–9. 10.1016/j.jff.2014.12.022 [CrossRef[]
105. Guidance for Industry Food Labeling; Nutrient Content Claims; Definition for “High Potency” and Definition for “Antioxidant” for Use in Nutrient Content Claims for Dietary Supplements and Conventional Foods; Small Entity Compliance Guide. U.S. Food and Drug Administration (2008). Available online at: http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocuments/RegulatoryInformation/LabelingNutrition/ucm063064.htm
106. European Food Safety Authority (EFSA) Scientific Opinion on the substantiation of health claims related to polyphenols in olive and protection of LDL particles from oxidative damage (ID 1333, 1638, 1639, 1696, 2865), maintenance of normal blood HDL-cholesterol concentrations (ID 1639), maintenance of normal blood pressure (ID 3781), “anti-inflammatory properties” (ID 1882), “contributes to the upper respiratory tract health” (ID 3468), “can help to maintain a normal function of gastrointestinal tract” (3779), and “contributes to body defences against external agents” (ID 3467) pursuant to Article 13(1) of Regulation (EC) No 1924/2006EFSA J (2011) 9:2033 10.2903/j.efsa.2011.2033 [CrossRef[]
107. European Food Safety Authority (EFSA) Scientific Opinion on the modification of the authorisation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/ 2006 following a request in accordance with Article 19 of Regulation (EC) No 1924/2006EFSA J (2014) 12:3654 10.2903/j.efsa.2014.3654 [CrossRef[]
108. Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. . Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology (2014) 60:1399–408. 10.1002/hep.27317 [PMC free article] [PubMed] [CrossRef[]
109. Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R, Santuccio C, et al. . Hepatotoxicity from green tea: a review of the literature and two unpublished casesEur J Clin Pharmacol. (2009) 65:331–41. 10.1007/s00228-008-0610-7 [PubMed] [CrossRef[]
110. Garcia-Cortes M, Robles-Diaz M, Ortega-Alonso A, Medina-Caliz I, Andrade RJ. Hepatotoxicity by dietary supplements: a tabular listing and clinical characteristicsInt J Mol Sci. (2016) 17:537. 10.3390/ijms17040537 [PMC free article] [PubMed] [CrossRef[]
111. Mazzanti G, Di Sotto A, Vitalone A. Hepatotoxicity of green tea: an updateArch Toxicol. (2015) 89:1175–91. 10.1007/s00204-015-1521-x [PubMed] [CrossRef[]
112. Whitsett M, Marzio DH, Rossi S. SlimQuick-associated hepatotoxicity resulting in fulminant liver failure and orthotopic liver transplantationACG Case Rep J. (2014) 1:220–2. 10.14309/crj.2014.59 [PMC free article] [PubMed] [CrossRef[]
113. Martin KR, Appel CL. Polyphenols as dietary supplements: a double-edged swordNutr Diet Suppl. (2010) 2:1–12. 10.2147/NDS.S6422 [CrossRef[]
114. Hooper B, Frazier R. Polyphenols in the diet: friend or foe? Nutr Bull. (2012) 37:297–308. 10.1111/j.1467-3010.2012.02001.x [CrossRef[]
115. Bjelakovic G, Nikolova D, Gluud C. Antioxidant supplements and mortalityCurr Opin Clin Nutr Metabolic Care (2014) 17:40–4. 10.1097/MCO.0000000000000009 [PubMed] [CrossRef[]

Articles from Frontiers in Nutrition are provided here courtesy of Frontiers Media SA

No comments: