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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Pharmacological Applications of Quercetin and its Derivatives: A Short Review
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“Quercetin is a plant pigment, abundantly occurs in many ethnic plants, especially onion and tea, therefore, a sufficient amount may be consumed daily [1].”
Background
Identification and quantification of novel cranberry-derived plasma and urinary (poly)phenols
Feliciano, R. P., Boeres, A., Massacessi, L., Istas, G., Ventura, M. R., dos Santos, C. N., Heiß, C., & Rodriguez‐Mateos, A. (2016) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2016.01.014 · Cited by 165
Lactic Fermentation as a Strategy to Improve the Nutritional and Functional Values of Pseudocereals
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“The covalent interactions between these two components increase their individual anti-inflammatory effects and their positive impact on the gut microbiome (67, 69, 110).”
Background
Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes
Maher, P. A., Dargusch, R., Ehren, J. L., Okada, S., Sharma, K., & Schubert, D. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021226 · Cited by 165
“Flavonoids are extensively metabolized following oral consumption resulting in glucuronidated, sulfated and methylated metabolites (for reviews see [48], [49]).”
Background
Bioavailability and Metabolism of Orange Juice Flavanones in Humans: Impact of a Full-Fat Yogurt
Mullen, W., Archeveque, M.-A., Edwards, C. A., Matsumoto, H., & Crozier, A. (2008) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf801974v · Cited by 161
Wheat Bran Phenolic Acids: Bioavailability and Stability in Whole Wheat-Based Foods
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“Also, evidence is emerging on how dietary polyphenols can modulate the colonic microbial population composition or activity [63,75].”
Background
Quercetin mediated lifespan extension in Caenorhabditis elegans is modulated by age-1, daf-2, sek-1 and unc-43
Pietsch, K., Saul, N., Menzel, R., Stürzenbaum, S. R., & Steinberg, C. E. W. (2008) · Biogerontology · doi:10.1007/s10522-008-9199-6 · Cited by 164
“Indeed, the bioavailability and bioefficacy of certain polyphenols have been demonstrated in humans (Manach et al. 2004, 2005; Nielsen et al. 2003; Rechner et al. 2002).”
Background
Urinary metabolites as biomarkers of polyphenol intake in humans—a systematic review
Pérez-Jiménez, J., Hubert, J., Hooper, L., Cassidy, A., Manach, C., Williamson, G., & Scalbert, A. (2010) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.29924 · Cited by 159
“Urinewas selected because of the short half-life of polyphenols in plasma and the stronger expected dependence of polyphenol concentrations on sampling time (20).”
Influential
Effects of cooking methods on polyphenols, pigments and antioxidant activity in potato tubers
Perla, V., Holm, D. G., & Jayanty, S. S. (2011) · LWT · doi:10.1016/j.lwt.2011.08.005 · Cited by 168
Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation
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“Some classes of polyphenols include anthocyanins, lignans, flavonols, flavanones, flavanol monomers, proanthocyanidins, isoflavones, hydroxycinnamic acids, and hydroxybenzoic acids [126, 132].”
Background
Fucaceae: A Source of Bioactive Phlorotannins
Catarino, M. D., Silva, A. M. S., & Cardoso, S. M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061327 · Cited by 166
Proanthocyanidins against Oxidative Stress: From Molecular Mechanisms to Clinical Applications
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“Small-molecule PCs, such as catechin monomers, tend to be easily absorbed, whereas PCs with large (−)-epigallocatechin-3-gallate molecules are poorly absorbed through the gut barrier [32, 33].”
Background
Safety and pharmacokinetics of naringenin: A randomized, controlled, single‐ascending‐dose clinical trial
Rebello, C. J., Beyl, R. A., Lertora, J. J. L., Greenway, F. L., Ravussin, É., Ribnicky, D., Poulev, A., Kennedy, B. J., Castro, H. F., Campagna, S. R., et al. (2019) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13868 · Cited by 170
“In humans, the maximum plasma concentrations achieved from food sources of naringenin has only reached <1 μM.(15,16,19,20) In the only other clinical trial of naringenin in the aglycone form,(26) ingestion of a single 135-mg dose of the pure compound delivered in a solid dispersion capsule produced a Cmax of 7.”
Background
Bioavailability of Phenolic Antioxidants Associated with Dietary Fiber: Plasma Antioxidant Capacity After Acute and Long-Term Intake in Humans
Pérez‐Jiménez, J., Serrano, J. C. E., Tabernero, M., Arranz, S., Diaz-Rubio, M. E., García‐Diz, L., Goñi, I., & Saura-Calixto, F. D. (2009) · Plant Foods for Human Nutrition · doi:10.1007/s11130-009-0110-7 · Cited by 159
“Since the bioavailability of quercetin from onion and apple was firstly described [4], several studies have proven that a fraction of the PA present in different foods and beverages such as wine, onion, tea, berries or chocolate are bioavailable in the human gastrointestinal tract [2, 3, 5].”
Background
Wine Polyphenols: Potential Agents in Neuroprotection
Basli, A., Soulet, S., Chaher, N., Mérillon, J., Chibane, M., Monti, J., & Richard, T. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/805762 · Cited by 162
“Polyphenols are extensively metabolized in different tissues such as colon, small intestine, and liver [119].”
Background
Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment
Afrin, S., Giampieri, F., Gasparrini, M., Forbes-Hernández, T. Y., Varela‐López, A., Quiles, J. L., Mezzetti, B., & Battino, M. A. (2016) · Molecules · doi:10.3390/molecules21020169 · Cited by 162
Natural polyphenol disposition via coupled metabolic pathways
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Gene expression, cell cycle arrest and MAPK signalling regulation in Caco‐2 cells exposed to ellagic acid and its metabolites, urolithins
González‐Sarrías, A., Espı́n, J. C., Tomás-Barberán, F. A., & García‐Conesa, M. (2009) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200800150 · Cited by 158
Enhancing the therapeutic effects of polyphenols with macromolecules
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Does Quercetin Improve Cardiovascular Risk factors and Inflammatory Biomarkers in Women with Type 2 Diabetes: A Double-blind Randomized Controlled Clinical Trial.
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Metabolic syndrome and the role of dietary lifestyles in Alzheimer’s disease
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“Over 35 thousand plant species currently used for medicinal purposes around the world possess more than 4 thousand polyphenolic structures (Macheix et al. 1990; Maclennan et al. 2002; Manach et al. 2005; Williamson and Manach 2005).”
Background
Non-Digestible Food Ingredients, Colonic Microbiota and the Impact on Gut Health and Immunity: A Role for Metabolomics
Jacobs, D. M., Gaudier, E. A., van Duynhoven, J., & Vaughan, E. E. (2009) · Current Drug Metabolism · doi:10.2174/138920009787048383 · Cited by 168
“Alternatively, non-absorbed polyphenols reach the colon by directly passing through the small intestine [55-57].”
Background
Anthocyanins. Plant Pigments and Beyond
Santos‐Buelga, C., Mateus, N. F. D. C. B., & de Freitas, V. A. P. (2014) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf501950s · Cited by 157
Immunomodulatory; Anti-inflammatory/antioxidant Effects of Polyphenols: A Comparative Review on the Parental Compounds and Their Metabolites
Sobhani, M., Farzaei, M. H., Kiani, S., & Khodarahmi‬, R. (2020) · Food Reviews International · doi:10.1080/87559129.2020.1717523 · Cited by 162
Supplemental Naringenin Prevents Intestinal Barrier Defects and Inflammation in Colitic Mice
Azuma, T., Shigeshiro, M., Kodama, M., Tanabe, S., & Suzuki, T. (2013) · Journal of Nutrition · doi:10.3945/jn.113.174508 · Cited by 159
Atheroprotective effects of (poly)phenols: a focus on cell cholesterol metabolism
Zanotti, I., Dall’Asta, M., Mena, P. R., Mele, L., Bruni, R., Ray, S., & Rio, D. D. (2014) · Food & Function · doi:10.1039/c4fo00670d · Cited by 160
Acute Effects of Chlorogenic Acid on Nitric Oxide Status, Endothelial Function, and Blood Pressure in Healthy Volunteers: A Randomized Trial
Mubarak, A., Bondonno, C. P., Liu, A. H., Considine, M. J., Rich, L., Mas, E., Croft, K. D., & Hodgson, J. M. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf303440j · Cited by 157
Recent trends in nano-based drug delivery systems for efficient delivery of phytochemicals in chemotherapy
Subramanian, A. P., Jaganathan, S. K., Manikandan, A., Pandiaraj, K. N., Gomathi, N., & Supriyanto, E. (2016) · RSC Advances · doi:10.1039/c6ra07802h · Cited by 156
Rutin as Neuroprotective Agent: From Bench to Bedside
Budzyńska, B., Faggio, C., Kruk-Słomka, M., Šamec, D., Nabavi, S. F., Sureda, A., Devi, K. P., & Nabavi, S. M. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666171003114154 · Cited by 157
Complementary effects of cereal and pulse polyphenols and dietary fiber on chronic inflammation and gut health
Awika, J. M., Rose, D. J., & Şimşek, Ş. (2018) · Food & Function · doi:10.1039/c7fo02011b · Cited by 161
Crosstalk between obesity, diabetes, and alzheimer’s disease: Introducing quercetin as an effective triple herbal medicine
Ebrahimpour, S., Zakeri, M., & Esmaeili, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101095 · Cited by 163
Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension
Muniyappa, R., Hall, G., Kolodziej, T. L., Karne, R. J., Crandon, S. K., & Quon, M. J. (2008) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26457 · Cited by 161
“6 h consistent with previous studies in humans (37, 69).”
Result
Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells
Monagas, M., Khan, N., Andrés‐Lacueva, C., Urpí-Sardà, M., Vázquez-Agell, M., Lamuela-Raventós, R. M., & Estruch, R. (2009) · British Journal Of Nutrition · doi:10.1017/s0007114508162110 · Cited by 155
“Among polyphenols, the oligomers and polymers of flavan-3-ols, also called proanthocyanidins, are not absorbed or degraded into monomers during their transit through the stomach((2,3)).”
Background
Polyphenols as Potential Attenuators of Heat Stress in Poultry Production
Hu, R., He, Y., Arowolo, M. A., Wu, S., & He, J. (2019) · Antioxidants · doi:10.3390/antiox8030067 · Cited by 155
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The Quest for Phenolic Compounds from Macroalgae: A Review of Extraction and Identification Methodologies
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Nutraceuticals and Cancer: Potential for Natural Polyphenols
Maiuolo, J., Gliozzi, M., Carresi, C., Musolino, V., Oppedisano, F., Scarano, F., Nucera, S., Scicchitano, M., Bosco, F., Macrì, R., et al. (2021) · Nutrients · doi:10.3390/nu13113834 · Cited by 164
Effect of grape antioxidant dietary fibre on the prevention of lipid oxidation in minced fish: Evaluation by different methodologies
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Intestinal Absorption and First-Pass Metabolism of Polyphenol Compounds in Rat and Their Transport Dynamics in Caco-2 Cells
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Apoptotic Effect of Quercetin on HT-29 Colon Cancer Cells via the AMPK Signaling Pathway
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Enhancement of the solubility, stability and bioaccessibility of quercetin using protein-based excipient emulsions
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“b10 [35,36] Anthocyanins b1 [37] Quercetin ~5 [37] Naringenin b6 [37] Catechins (green tea) b2 [37] Ascorbate (at 60 mg/daily uptake) ~23 [38] Ascorbate (at 150 mg/daily uptake) ~57 [38]”
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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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