Cited by 4,219Phytochemicals and Antioxidant ActivitiesNutritional Studies and DietPomegranate: compositions and health benefits

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Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies

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Manach, Claudine, Williamson, Gary, Morand, Christine, Scalbert, Augustin, Rémésy, Christian·2005·The American Journal of Clinical Nutrition

DOI 10.1093/ajcn/81.1.230s

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Abstract

Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.

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Gut Microbial Metabolism of Polyphenols from Black Tea and Red Wine/Grape Juice Is Source-Specific and Colon-Region Dependent
van Dorsten, F. A., Peters, S., Gross, G., Roldán, M. V. G., Klinkenberg, M., de Vos, R. C., Vaughan, E. E., van Duynhoven, J., Possemiers, S., de Wiele, T. V., et al. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf303165w · Cited by 96
Lactic acid bacterial fermentation modified phenolic composition in tea extracts and enhanced their antioxidant activity and cellular uptake of phenolic compounds following in vitro digestion
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Molecular and Therapeutic Targets of Genistein in Alzheimer’s Disease
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Dietary Flavonoids for Immunoregulation and Cancer: Food Design for Targeting Disease
Ahn‐Jarvis, J. H., Parihar, A., & Doseff, A. I. (2019) · Antioxidants · doi:10.3390/antiox8070202 · Cited by 101
“These conjugates can be mobilized to systemic circulation where they will eventually be excreted in urine or back to the intestine with biliary secretion [177,208].”
Background
Pelargonidin-3‑ O ‑glucoside Derived from Wild Raspberry Exerts Antihyperglycemic Effect by Inducing Autophagy and Modulating Gut Microbiota
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Flavonoids in Baby Spinach (Spinacia oleracea L.): Changes during Plant Growth and Storage
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Influence of food polyphenols on aryl hydrocarbon receptor-signaling pathway estimated by in vitro bioassay
Amakura, Y., Tsutsumi, T., Sasaki, K., Nakamura, M., Yoshida, T., & Maitani, T. (2007) · Phytochemistry · doi:10.1016/j.phytochem.2007.07.022 · Cited by 97
Catechin Glucosides: Occurrence, Synthesis, and Stability
Raab, T., Barron, D., Vera, F. A., Crespy, V., Oliveira, M., & Williamson, G. (2010) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf9034095 · Cited by 95
Quercetin enhances adiponectin secretion by a PPAR-γ independent mechanism
Wein, S., Behm, N., Petersen, R. K., Kristiansen, K., & Wolffram, S. (2010) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2010.05.004 · Cited by 95
Evaluation of antioxidant activity of phenolic fractions from the leaves and petals of dandelion in human plasma treated with H2O2 and H2O2/Fe
Jędrejek, D., Kontek, B., Lis, B., Stochmal, A., & Olas, B. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.12.003 · Cited by 94
Dietary Application of Tannins as a Potential Mitigation Strategy for Current Challenges in Poultry Production: A Review
Choi, J., & Kim, W. K. (2020) · Animals · doi:10.3390/ani10122389 · Cited by 118
Sensory Nutrition and Bitterness and Astringency of Polyphenols
Osakabe, N., Shimizu, T., Fujii, Y., Fushimi, T., & Calabrese, V. (2024) · Biomolecules · doi:10.3390/biom14020234 · Cited by 102
Tyrosol, a main phenol present in extra virgin olive oil, increases lifespan and stress resistance in Caenorhabditis elegans
Cañuelo, A., Gilbert‐López, B., Pacheco-Liñán, P. J., Martínez‐Lara, E., Siles, E., & Miranda‐Vizuete, A. (2012) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2012.07.004 · Cited by 95
Anthocyanin and Flavonol Variation in Bog Bilberries (Vaccinium uliginosum L.) in Finland
Primetta, A. K., Jaakola, L., Riihinen, K., & Kainulainen, P. S. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf903033m · Cited by 93
Cocoa Phytochemicals: Recent Advances in Molecular Mechanisms on Health
Kim, J., Kim, J., Shim, J., Lee, C. Y., Lee, K. W., & Lee, H. J. (2013) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2011.641041 · Cited by 93
“are not necessarily those leading to the highest concentrations of active metabolites in target tissues (Manach et al., 2005).”
Background
Effect of Food Structure and Processing on (Poly)phenol–Gut Microbiota Interactions and the Effects on Human Health
Tomás-Barberán, F. A., & Espı́n, J. C. (2019) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-032818-121615 · Cited by 94
Evaluation of the Bioactive Compounds Found in Tomato Seed Oil and Tomato Peels Influenced by Industrial Heat Treatments
Szabo, K., Dulf, F. V., Teleky, B., Eleni, P. N., Boukouvalas, C. J., Krokida, M. K., Kapsalis, N., Alexandru Vasile, R. U. S. U., Socol, C. T., & Vodnar, D. C. (2021) · Foods · doi:10.3390/foods10010110 · Cited by 93
“They occur naturally in plants like grapes, green tea, olives, blueberries, nuts, cocoa and others, with the highest concentrations found in the fruit’s skins and many of them show strong antioxidant effect [26,27].”
Background
Synergistic neuroprotection by epicatechin and quercetin: Activation of convergent mitochondrial signaling pathways
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Inhibition of Proinflammatory Biomarkers in THP1 Macrophages by Polyphenols Derived From Chamomile, Meadowsweet and Willow bark
Drummond, E. M., Harbourne, N., Marete, E. N., Martyn, D. M., Jacquier, J., O’Riordan, D., & Gibney, E. R. (2012) · Phytotherapy Research · doi:10.1002/ptr.4753 · Cited by 93
Antibacterial Potential of Northeastern Portugal Wild Plant Extracts and Respective Phenolic Compounds
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“Both phenolic compounds have been described as potent antioxidant, and as consequence they exert some chemopreventive effects on animal cells [39, 40].”
Background
Urinary excretions of 34 dietary polyphenols and their associations with lifestyle factors in the EPIC cohort study
Zamora‐Ros, R., Achaintre, D., Rothwell, J. A., Rinaldi, S., Assi, N., Ferrari, P., Leitzmann, M. F., Boutron‐Ruault, M., Fagherazzi, G., Auffret, A., et al. (2016) · Scientific Reports · doi:10.1038/srep26905 · Cited by 93
“chemical structures 7 .”
Host: Microbiome co-metabolic processing of dietary polyphenols – An acute, single blinded, cross-over study with different doses of apple polyphenols in healthy subjects
Trôst, K., Ulaszewska, M., Stanstrup, J., Albanese, D., Filippo, C. D., Tuohy, K. M., Natella, F., Scaccini, C., & Mattivi, F. (2018) · Food Research International · doi:10.1016/j.foodres.2018.06.016 · Cited by 93
Stirred-type yoghurt incorporated with sour cherry extract in chitosan-coated liposomes
Akgün, D., Gültekin-Özgüven, M., Yücetepe, A., Altin, G., Gibis, M., Weiss, J., & Özçelik, B. (2020) · Food Hydrocolloids · doi:10.1016/j.foodhyd.2019.105532 · Cited by 81
Polyphenols: Bioavailability, Microbiome Interactions and Cellular Effects on Health in Humans and Animals
Scott, M. B., Styring, A., & McCullagh, J. (2022) · Pathogens · doi:10.3390/pathogens11070770 · Cited by 98
Bioavailability of the phenolic compounds of the fruits (drupes) of Olea europaea (olives): Impact on plasma antioxidant status in humans
Kountouri, A. M., Mylona, A., Kaliora, A. C., & Andrikopoulos, N. K. (2007) · Phytomedicine · doi:10.1016/j.phymed.2007.06.001 · Cited by 94
“, 2006) activities, measurement of plasma concentrations and urinary excretion among subjects provided with pure PP, plant extracts or whole food/beverages rich in PP is increasingly a component of studies (Manach et al., 2005).”
Background
Cocoa procyanidins with different degrees of polymerization possess distinct activities in models of colonic inflammation
Bitzer, Z. T., Glisan, S. L., Dorenkott, M. R., Goodrich, K. M., Ye, L., O’Keefe, S. F., Lambert, J. D., & Neilson, A. P. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.02.007 · Cited by 98
“Reported oral bioavailability is generally <10% for monomers (although up to 55% has been reported for cocoa catechins) [16, 17], much lower for small procyanidins, and essentially 0% for large procyanidins [17–20].”
Background
Cardioprotective effects of cocoa: Clinical evidence from randomized clinical intervention trials in humans
Arranz, S., Valderas-Martínez, P., Chiva‐Blanch, G., Casas, R. M., Urpí-Sardà, M., Lamuela-Raventós, R. M., & Estruch, R. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201200595 · Cited by 91
“The beneficial effects of cocoa polyphenols depend on the amount consumed and their bioavailability (absorption, distribution, metabolism, and elimination) and are also influenced by their chemical structure and the biological activities of the metabolites formed [20].”
Molecular mechanisms underlying the potential antiobesity‐related diseases effect of cocoa polyphenols
Ali, F., Ismail, A., & Kersten, S. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300277 · Cited by 95
“There are possible explanations behind the low concentrations of CPs in plasma (i) there is experimental evidence that more than 90% of absorbed CPs are converted into conjugates with glucoronic acid and sulphate [18], or (ii) polyphenols may be rapidly metabolized by cells and, therefore, difficult to detect within t…”
Mechanisms by which cocoa flavanols improve metabolic syndrome and related disorders
Strat, K. M., Rowley, T. J., Smithson, A. T., Tessem, J. S., Hulver, M. W., Liu, D., Davy, B. M., Davy, K. P., & Neilson, A. P. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.12.008 · Cited by 93
“Reported oral bioavailability of flavanols is generally b10% for monomeric catechins [206,207] (when Phase-II metabolites are accounted for, bioavailability of monomers from catechins has been reported as high as 55%), much lower for small PCs (dimers-, trimers) and essentially 0% for larger PCs [29,39,207,208].”
Background
Some Anthocyanins Could Be Efficiently Absorbed across the Gastrointestinal Mucosa: Extensive Presystemic Metabolism Reduces Apparent Bioavailability
Fang, J. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf405356b · Cited by 93
Berries and anthocyanins: promising functional food ingredients with postprandial glycaemia-lowering effects
Castro-Acosta, M. L., Lenihan-Geels, G. N., Corpe, C. P., & Hall, W. L. (2016) · Proceedings of The Nutrition Society · doi:10.1017/s0029665116000240 · Cited by 92
Comparison of the in vitro gastrointestinal bioavailability of acylated and non-acylated anthocyanins: Purple-fleshed sweet potato vs red wine
Oliveira, H., Pérez-Gregório, R., de Freitas, V. A. P., Mateus, N. F. D. C. B., & Fernandes, I. (2018) · Food Chemistry · doi:10.1016/j.foodchem.2018.09.159 · Cited by 94
Anthocyanins, Vibrant Color Pigments, and Their Role in Skin Cancer Prevention
Diaconeasa, Z. M., Ştirbu, I., Xiao, J., Leopold, N., Ayvaz, Z., Danciu, C., Ayvaz, H., Stănilă, A., Nistor, M., & Socaciu, C. (2020) · Biomedicines · doi:10.3390/biomedicines8090336 · Cited by 91
Flavonoids as RTK inhibitors and potential anticancer agents
Teillet, F., Boumendjel, A., Boutonnât, J., & Ronot, X. (2007) · Medicinal Research Reviews · doi:10.1002/med.20122 · Cited by 91
Gargling with Tea Catechin Extracts for the Prevention of Influenza Infection in Elderly Nursing Home Residents: A Prospective Clinical Study
Yamada, H., Takuma, N., Daimon, T., & Hara, Y. (2006) · The Journal of Alternative and Complementary Medicine · doi:10.1089/acm.2006.12.669 · Cited by 91
Bioavailability of silymarin flavonolignans: drug formulations and biotransformation
Theodosiou, E., Purchartová, K., Stamatis, H., Kolisis, F. N., & Vladimír Křen, A. (2013) · Phytochemistry Reviews · doi:10.1007/s11101-013-9285-5 · Cited by 91
“However, the in vivo effectiveness of silymarin is governed by the bioavailability and the achieved therapeutic concentrations of the flavonolignans that reach the organs of interest (Manach et al. 2005; Silberberg et al. 2006).”
Background
Indicaxanthin from Cactus Pear Fruit Exerts Anti-Inflammatory Effects in Carrageenin-Induced Rat Pleurisy
Allegra, M., Ianaro, A., Tersigni, M., Panza, E., Tesoriere, L., & Livrea, M. A. (2013) · Journal of Nutrition · doi:10.3945/jn.113.183657 · Cited by 92
Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore
Yuan, J., Koh, W., Sun, C., Lee, H.-P., & Yu, M. C. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi080 · Cited by 91
High-Molecular-Weight Proanthocyanidins in Foods: Overcoming Analytical Challenges in Pursuit of Novel Dietary Bioactive Components
Neilson, A. P., O’Keefe, S. F., & Bolling, B. W. (2016) · Annual Review of Food Science and Technology · doi:10.1146/annurev-food-022814-015604 · Cited by 90
“PACs are considered one of themost abundant classes of dietary polyphenols (Manach et al. 2005).”
Background
Flavanols and Methylxanthines in Commercially Available Dark Chocolate: A Study of the Correlation with Nonfat Cocoa Solids
Langer, S., Marshall, L. J., Day, A. J., & Morgan, M. R. A. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf201398t · Cited by 90
Protocatechuic Acid: Inhibition of Fibril Formation, Destabilization of Preformed Fibrils of Amyloid-β and α-Synuclein, and Neuroprotection
Ortega, R. H., Álvarez‐Fernández, M. A., Cerezo, A. B., Richard, T., Troncoso, A. M., & García-Parrilla, M. C. (2016) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b03217 · Cited by 92
The protective effects of polyphenols on Alzheimer's disease: A systematic review
Colizzi, C. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.09.002 · Cited by 97
Alcohol and Head and Neck Cancer: Updates on the Role of Oxidative Stress, Genetic, Epigenetics, Oral Microbiota, Antioxidants, and Alkylating Agents
Ferraguti, G., Terracina, S. A., Petrella, C., Greco, A., Minni, A., Lucarelli, M., Agostinelli, E., Ralli, M., VINCENTIIS, M. D., Raponi, G., et al. (2022) · Antioxidants · doi:10.3390/antiox11010145 · Cited by 95
“They can be divided into four main groups: phenolic acids, flavonoids, stilbenes, and lignans [274,280,281].”
Background
Bioavailability of wine-derived phenolic compounds in humans: a review
Stockley, C. S., Teissèdre, P., Boban, M., Lorenzo, C. D., & Restani, P. (2012) · Food & Function · doi:10.1039/c2fo10208k · Cited by 90

Authors: Manach, C., Williamson, G., Morand, C., Scalbert, A., & Rémésy, C.
Affiliations: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
Institut National de la Recherche Agronomique (FR)
Corresponding author: Manach, Claudine
ORCID: Manach, Claudine
Williamson, Gary
Morand, Christine
Scalbert, Augustin
Venue: The American Journal of Clinical Nutrition
Publisher: Elsevier BV
Published: 2005-01
Volume: 81
Issue: 1
Pages: 230S-242S
ISSN: 0002-9165 (ISSN-L)
DOI: 10.1093/ajcn/81.1.230s
OpenAlex: W2119331100
Cited by: 4,219
References: 162
Citations by year: 2026: 201 · 2025: 170 · 2024: 170 · 2023: 170 · 2022: 189 · 2021: 215 · 2020: 241 · 2019: 216 · 2018: 224 · 2017: 242 · 2016: 235 · 2015: 211 · 2014: 246 · 2013: 257 · 2012: 266
FWCI: 78.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 6628 d)
Locations: American Journal of Clinical Nutrition (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Topics: Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
Health Sciences › Nursing › Nutrition and Dietetics › Pomegranate: compositions and health benefits
Keywords: polyphenols, bioavailability, bioefficacy, plasma concentration, urinary excretion, polyphenol metabolism, absorption kinetics, gallic acid, isoflavones, catechins, flavanones, quercetin glucosides, proanthocyanidins, anthocyanins, hydroxycinnamic acids, degenerative disease prevention
MeSH terms: Adult, Anthocyanins, Biological Availability, Female, Flavonoids, Food Analysis, Half-Life, Humans, Intestinal Absorption, Isoflavones, Male, Phenols, Area Under Curve, Polyphenols

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Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies

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