CoChat
Sign Up
Cited by 410Phytochemicals and Antioxidant ActivitiesNutritional Studies and DietAntioxidant Activity and Oxidative Stress

The DOI matches its Crossref record; 151 of the 159 references it cites were found in a registry or an index.

Diet-Derived Phenols in Plasma and Tissues and their Implications for Health

Open access
Clifford, M. N.·2004·Planta Medica
DOI 10.1055/s-2004-835835
Open this paper in CoChat — free accountOpen PDF

Abstract

This paper seeks to catalyse a reappraisal of the nature, fate and biological significance in humans of phenols, polyphenols and tannins (PPT) consumed in normal diets, and in particular questions the primacy of PPT radical-scavenging mechanisms for the supposed health benefits of diets rich in fruits and vegetables. PPT are classified by structure and function. Arguments are presented to show that cinnamates and derived polyphenols make significantly larger contributions to the total PPT intake than the flavonols and flavones upon which the vast majority of attention has been focussed previously. Daily intakes of total PPT may range from less than 100 mg to in excess of 2 g, and the critical importance of coffee and black tea as the major dietary sources is shown. Only some 5% of the dietary PPT is absorbed in the duodenum, and of this only some 5%, mainly flavanols, reaches the plasma unchanged, the balance being mammalian conjugates. Over 95% of the intake passes to the colon and is fermented by the gut microflora. A fraction of the resulting microbial metabolites is absorbed and appears in the plasma primarily as mammalian conjugates. Even following high intakes of PPT, the plasma metabolites collectively make a very small (less than 5%) and transient contribution to the total concentration of redox active substances in plasma. This explains the failure of most studies that sought to detect an increase in plasma antioxidant power after consuming a PPT-rich meal or supplement. The powerfully antioxidant PPT aglycones, much used in in vitro studies, do not reach the plasma. The redox potential of those unchanged PPT and PPT metabolites that reach the plasma enables them to scavenge damaging radicals, but the endogenous plasma antioxidants, especially ascorbate, are required for disposal of the resultant phenoxyl radicals. Black tea and coffee, the major sources of PPT, are poor sources of ascorbate. It is suggested that if diets rich in fruits and vegetables are health-promoting, and if these effects are due to PPT, then alternatives to radical-scavenging mechanisms must be sought. Evidence is presented to show that some mammalian metabolites of PPT may indeed be able to protect the vascular endothelium and that diets rich in PPT may in humans at normal dietary levels have the ability to protect against Type II diabetes and the metabolic syndrome through effects on glucose absorption and associated hormones. Such effects are recommended for further investigation.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1055/s-2004-835835

Cites

151 of 151 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 159 references

Research works printed but not linked: 63

  1. Parr AJ, Bolwell GP. Phenols in the plant and in man. The potential for possible nutritional enhancement of the diet by modifying phenolic content or composition. J Sci Food Agric 2000; 80: 985 ± 1012
  2. Clifford MN. The health effects of tea and tea components. Appendix 1. A nomenclature for phenols with special reference to tea. CRC Crit Rev Food Sci Nutr 2001; 41: 393 ± 7
  3. Lindsay DG, Clifford MN. Special issue devoted to critical reviews pro- duced within the EU Concerted Action ªNutritional Enhancement of Plant-based Food in European Tradeº (NEODIET). J Sci Food Agric 2000; 80: 793 ± 1137
  4. Clifford MN. Chlorogenic acids and other cinnamates ± nature, occur- rence and dietary burden. J Sci Food Agric 1999; 79: 362 ± 72
  5. Clifford MN. Chlorogenic acids and other cinnamates -nature, occur- rence, dietary burden, absorption and metabolism. J Sci Food Agric 2000; 80: 1033 ± 42
  6. Clifford MN. Miscellaneous phenols in foods and beverages ± nature, occurrence and dietary burden. J Sci Food Agric 2000; 80: 1126 ± 37
  7. Soler-Rivas C, Espin JC, Wichers HJ. Oleuropein and related com- pounds. J Sci Food Agric 2000; 80: 1013 ± 23
  8. Tomµs-Barberµn FA, Clifford MN. Dietary hydroxybenzoic acid deri- vatives ± nature, occurrence and dietary burden. J Sci Food Agric 2000; 80: 1024 ± 32
  9. Hertog MGL, Hollman PCH, Katan MB. Content of potentially anticar- cinogenic flavonoids of 28 vegetables and 9 fruits consumed in The Netherlands. J Agr Food Chem 1992; 40: 2379 ± 83
  10. Santos-Buelga C, Scalbert A. Proanthocyanidins and tannin-like com- pounds ± nature, occurrence, dietary intake and effects on nutrition and health. J Sci Food Agric 2000; 80: 1094 ± 1117
  11. Clifford MN, Scalbert A. Ellagitannins ± nature, occurrence and dietary burden. J Sci Food Agric 2000; 80: 1118 ± 25
  12. Cassidy A, Hanley B, Lamuela-Raventós RM. Isoflavones, lignans and stilbenes ± origins, metabolism and potential importance to human health. J Sci Food Agric 2000; 80: 1044 ± 62
  13. Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C, Wil- liamson G. COMMENTARY: How should we assess the effects of expo- sure to dietary polyphenols in vitro. Am J Clin Nutr 2004; 80: 15 ± 21
  14. Cameira-dos-Santos P-J, Brillouet J-M, Cheynier V, Moutounet M. De- tection and partial characterisation of new anthocyanin-derived pig- ments in wine. J Sci Food Agric 1996; 70: 204 ± 8
  15. Fulcrand H, Benabdeljalil C, Rigaud J, Cheynier V, Moutounet M. A new class of wine pigments yielded by reaction between pyruvic acid and the grape anthocyanins. Phytochemistry 1998; 47: 1401 ± 7
  16. Sang S, Tian W, Meng X, Stark RE, Rosen RT, Yang CS, Ho C-T. Theadi- benztropolone A, a new type pigment from enzymatic oxidation of (±)-epicatechin and (±)-epigallocatechin gallate and characterized from black tea using LC/MS/MS. Tetrahedron Lett 2002; 43: 7129 ± 33
  17. Linseisen J, Radtke J, Wolfram G. Flavonoid intake of adults in a Bavar- ian subgroup of the National Food Consumption survey. Z Ernäh- rungswiss 1997; 36: 403 ± 12
  18. Radtke J, Linseisen J, Wolfram G. Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey. Z Ernäh- rungswiss 1998; 37: 190 ± 7
  19. Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P. Flavonol and flavone intake and the risk of cancer in male smokers (Finland). Cancer Causes Control 2001; 12: 789 ± 96
  20. Gosnay SL, Bishop JA, New SA, Catterick J, Clifford MN. Estimation of the mean intakes of fourteen classes of dietary phenolics in a popula- tion of young British women aged 20 ± 30 years. Proc Nutr Soc 2002; 61: 125A
  21. Woods E, Clifford MN, Gibbs M, Hampton S, Arendt J, Morgan L. Esti- mation of mean intakes of 14 classes of dietary phenols in a popula- tion of male shift workers. Proc Nutr Soc 2003; 62: 60A 51
  22. Hertog MGL, Sweetman PM, Fehily AM, Elwood PC, Kromhout D. An- tioxidant flavonols and ischaemic heart disease in a Welsh popula- tion of men: the Caerphilly Study. Am J Clin Nutr 1997; 65: 1489 ± 94
  23. Tomµs-Barberµn FA, Clifford MN. Flavanones, chalcones and dihydro- chalcones ± nature, occurrence and dietary burden. J Sci Food Agric 2000; 80: 1073 ± 80
  24. Price KR, Bacon JR, Rhodes MJC. Effect of storage and domestic pro- cessing on the content and composition of flavonol glucosides in onion (Allium cepa). J Agr Food Chem 1997; 45: 938 ± 42
  25. Chuda Y, Suzuki M, Nagata T, Tsushida T. Contents and cooking loss of three quinic acid derivatives from Garland (Chrysanthemum coronarium L.). J Agr Food Chem 1998; 46: 1437 ± 9
  26. Price KR, Casuscelli F, Colquhoun IJ, Rhodes MJC. Composition and content of flavonol glycosides in broccoli floreets (Brassica oleracea) and their fate during cooking. J Sci Food Agric 1998; 77: 468 ± 72
  27. Bond TA, Lewis JR, Davis A, Davies AP. Analysis and purification of ca- techins and their transformation products. In: Santos-Buelga C, Wil- liamson G, editors. Methods in Polyphenol Analysis Cambridge: Roy- al Society of Chemistry, 2003: pp 229 ± 66
  28. Garcia-Closas R, Gonzalez CA, Agudo A, Riboli E. Intake of specific car- otenoids and flavonoids and the risk of gastric cancer in Spain. Cancer Causes Control 1999; 10: 71 ± 5
  29. Arts ICW, Hollman PCH, Feskens EJM, de Mesquita BB, Kromhout D. Catechin intake is inversely associated with coronary heart disease mortality; Results from the Zutphen Elderly Study. Circulation 2000; 101: 4
  30. Crozier A, Burns J, Aziz AA, Stewart AJ, Rabiasz HS, Jenkins G, Edwards CA, Lean MEJ. Antioxidant flavonols from fruits, vegetables and bev- erages: measurement and bioavailability. Biol Res 2000; 33: 79 ± 88
  31. Porteous L. Nutritional and dietary risk factors for osteoporosis: An investigation of association between diet and indices of bone health in young British women aged 25 ± 30 years. B.Sc. Thesis. University of Surrey, 2001
  32. Bennett G. Food choices, dietary patterns and circulation adaptation in shift workers: an investigation into the possible impact on coron- ary heart disease risk. B.Sc. Thesis. University of Surrey, 2001
  33. Paul N. Do eating patterns and post-prandial hormonal and metabol- ic markers vary significantly according to shift type and circadian sta- tus in swing shift workers in the offshore oil industry. B.Sc. Thesis. University of Surrey, 2001 79
  34. Clifford MN. Tea. In: Ranken MD, Kill RC and Baker CJG, editors. Food Industries Manual; 24th edition London: Blackie, 1997: pp 379 ± 95
  35. Harbowy ME, Balentine DA. Tea Chemistry. CRC Crit Rev Plant Sci 1997; 16: 415 ± 80
  36. Hollman PCH, van Trijp JM, Buysman MN, van der Gaag MS, Menge- lers MJ, de Vries JHM, Katan MB. Relative bioavailability of the antiox- idant quercetin from various foods in man. FEBS Lett 1997; 418: 152 ± 6
  37. Krishnamurty HG, Cheng KJ, Jones GA, Simpson FJ, Watkin JE. Identi- fication of products produced by the anaerobic degradation of rutin and related flavonoids by Butyrivibrio sp. C3. Can J Microbiol 1970; 16: 759 ± 67
  38. Scheline RR. Mammalian Metabolism of Plant Xenobiotics. London: Academic Press, 1978: pp 1 ± 502
  39. Groenewoud G, Hundt HKL. The microbial metabolism of (+)-cate- chins to two novel diarylpropan-2-ol metabolites in vitro. Xenobioti- ca 1984; 14: 711 ± 7
  40. Coldham NG, King LJ, Macpherson DD, Sauer MJ. Biotransformation of genistein in the rat: elucidation of metabolite structure by product ion mass fragmentology. J Steroid Biochem Mol Biol 1999; 70: 169 ± 84
  41. Simmering R, Kleessen B, Blaut M. Quantification of the flavonoid-de- grading bacterium Eubacterium ramulus in human fecal samples with a species-specific oligonucleotide hybridization probe. Appl Environ Microbiol 1999; 65: 3705 ± 9 101
  42. Clifford MN, Copeland EL, Bloxsidge JP, Mitchell LA. Hippuric acid is a major excretion product associated with black tea consumption. Xe- nobiotica 2000; 30: 317 ± 26 104
  43. Jenkins DI, Wolever TM, Taylor RH. Glycaemic index of foods: a phys- iological basis for carbohydrate exchange. Am J Clin Nutr 1981; 34: 362 ± 6 108
  44. Olthof MR. Bioavailability of flavonoids and cinnamic acids and their effect on plasma homocysteine in humans. PhD Thesis. Wageningen University, 2001: pp 136 110
  45. Braune A, Gutschow M, Engst W, Blaut M. Degradation of quercetin and luteolin by Eubacterium ramulus. Appl Environ Microbiol 2001; 67: 5558 ± 67 114
  46. Tsuji A, Takanaga H, Tamai I, Terasaki T. Transcellular transport of benzoic acid across Caco-2 cells by a pH-dependent and carrier- mediated transport mechanism. Pharm Res 1994; 11: 30 ± 7 120
  47. Konishi Y, Kobayashi S, Shimizu M. Transepithelial transport of p- coumaric acid and gallic acid in Caco-2 cell monolayers. Biosci Bio- technol Biochem 2003; 67: 2317 ± 24 123
  48. Holt RR, Lazarus SA, Sullards MC, Zhu QY, Schramm DD, Hammer- stone JF, Fraga CG, Schmitz HH, Keen CL. Procyanidin dimer B2 [epica- techin-(4beta-8)-epicatechin] in human plasma after the consump- tion of a flavanol-rich cocoa. Am J Clin Nutr 2002; 76: 798 ± 804 127
  49. O'Byrne DJ, Devaraj S, Grundy SM, Jialal I. Comparison of the antioxi- dant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults. Am J Clin Nutr 2002; 76: 1367 ± 74 149
  50. Simonetti P, Ciappellano S, Gardana C, Bramati L, Pietta P. Procyani- dins from Vitis vinifera seeds: in vivo effects on oxidative stress. J Agr Food Chem 2002; 50: 6217 ± 21 154
  51. Jovanovic SV, Steenken S, Tosic M, Marjanovic B, Simic MG. Flavo- noids as antioxidants. J Am Chem Soc 1994; 116: 4846 ± 51 163
  52. Ayrton AD, Lewis DFV, Walker R, Ioannides C. Antimutagenicity of el- lagic acid toward the food mutagen IQ: investigations into the possi- ble mechanisms of action. Food Chem Toxicol 1992; 30: 289 ± 95 166
  53. Shirai M, Moon JH, Tsushida T, Terao J. Inhibitory effect of a quercetin metabolite, quercetin 3-O-b-D-glucuronide, on lipid peroxidation in liposomal membranes. J Agr Food Chem 2001; 49: 5602 ± 8 168
  54. Sauberlich HE. Human requirements and needs. Vitamin C status: methods and findings. Ann NY Acad Sci 1975; 258: 438 ± 50 172
  55. Terao J, Yamaguchi S, Shirai M, Miyoshi M, Moon JH, Oshima S, Inaku- ma T, Tsushida T, Kato Y. Protection by quercetin and quercetin 3-O-b- d-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein. Free Radic Res 2001; 35: 925 ± 31 175
  56. Matsui T, Ebuchi S, Kobayashi M, Fukui K, Sugita K, Terahara N, Mat- sumoto K. Anti-hyperglycemic effect of diacylated anthocyanin de- rived from Ipomoea batatas cultivar Ayamurasaki can be achieved through the a-glucosidase inhibitory action. J Agr Food Chem 2002; 50: 7244 ± 8 186
  57. Kawabata J, Mizuhata K, Sato E, Nishioka T, Aoyama Y, Kasai T. 6-hydro- xyflavonoids as a-glucosidase inhibitors from marjoram (Origanum majorana) leaves. Biosci Biotechnol Biochem 2003; 67: 445± 7 187
  58. Hilt P, Schieber A, Yildirim C, Arnold G, Klaiber I, Conrad J, Beifuss U, Carle R. Detection of phloridzin in strawberries (Fragaria x ananassa Duch.) by HPLC-PDA-MS/MS and NMR spectroscopy. J Agr Food Chem 2003; 51: 2896 ± 9 188
  59. Nakazawa F. Influence of phloridzin on intestinal absorption. Tohoku J Exptl Med 1922; 3: 288 ± 94 189
  60. Gee JM, DuPont MS, Rhodes MJC, Johnson IT. Quercetin glucosides in- teract with the intestinal glucose transport pathway. Free Radic Biol Med 1998; 25: 19 ± 25 197
  61. Walgren RA, Lin JT, Kinne RK, Walle T. Cellular uptake of dietary fla- vonoid quercetin 4¢-b-glucoside by sodium-dependent glucose trans- porter SGLT1. J Pharmacol Exp Ther 2000; 294: 837 ± 43 198
  62. Steenken S, Neta P. Electron transfer rates and equilibria between substituted phenoxide ions and phenoxyl radicals. J Phys Chem 1979; 83: 1134 ± 7 211
  63. Jovanovic SV, Tosic M, Simic MG. Use of Hammett correlation and s + for calculation of one-electron redox potentials of antioxidants. J Phys Chem 1991; 95: 10 824 ± 7 212 Koppenol WH. Oxyradical reactions: from bond-dissociation ener- gies to reduction potentials. FEBS Lett 1990; 264: 165 ± 7 213

Cited by

Sorted by citations

Items 201–300 of 410

Related

See all

Metadata

Authors
Clifford, M. N.
Affiliations
University of Surrey (GB)
Corresponding author
Clifford, M. N.
ORCID
Clifford, M. N.
Venue
Planta Medica
Publisher
Georg Thieme Verlag KG
Published
2004-12
Volume
70
Issue
12
Pages
1103-1114
ISSN
  • 0032-0943 (ISSN-L)
  • 1439-0221
DOI
10.1055/s-2004-835835
OpenAlex
W1975642738
Cited by
410
References
159
Citations by year
2026: 7 · 2025: 13 · 2024: 10 · 2023: 18 · 2022: 29 · 2021: 27 · 2020: 22 · 2019: 25 · 2018: 21 · 2017: 25 · 2016: 20 · 2015: 19 · 2014: 26 · 2013: 19 · 2012: 21
FWCI
1.39
Type
journal article
Language
de
Open access
Locations
  • Planta Medica (publishedVersion)
  • PubMed (publishedVersion)
  • Open Research (University of Surrey) (submittedVersion)
  • Surrey Research Insight Open Access (The University of Surrey) (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 › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords
dietary polyphenols, phenols, tannins, cinnamic acid derivatives, flavonols, flavan-3-ols, gut microbiota fermentation, free radical scavenging, antioxidant capacity, vitamin C, black tea, coffee, dietary intake, vascular endothelium protection, type 2 diabetes, metabolic syndrome, glucose absorption
MeSH terms
Antioxidants, Diet, Flavonoids, Fruit, Humans, Phytotherapy, Phenols, Tannins, Vegetables, Polyphenols

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review