Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans
Open accessAbstract
Background In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d. Objective We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples. Design In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing approximately 4.3 mmol polyphenols and comparable to approximately 2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order. Results Total homocysteine in plasma collected 4-5 h after supplement intake was 12% (1.2 micromol/L; 95% CI: 0.6, 1.7) higher after chlorogenic acid and 11% (1.1 micromol/L; 95% CI: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4% (0.4 micromol/L; 95% CI: 0.0, 0.8) higher after chlorogenic acid and 5% (0.5 micromol/L; 95% CI: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations. Conclusions Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established.
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Long-term heavy coffee consumption has been associated with a slightly elevated risk of hypertension and a higher level of plasma homocysteine.
“Long-term heavy coffee consumption has been associated with a slightly elevated risk of hypertension,40 and a higher level of plasma homocysteine.41, 42”
From Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose–Response Meta-Analysis of Prospective Cohort Studies (2014) · cites this paper as [42]
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Cites
Homocysteine and Cardiovascular Disease
Refsum, H., Ueland, P. M., Nygård, O., & Vollset, S. E. (1998) · Annual Review of Medicine · doi:10.1146/annurev.med.49.1.31 · Cited by 2,180 · see citing works
Vitamin Status and Intake as Primary Determinants of Homocysteinemia in an Elderly Population
Selhub, J. (1993) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1993.03510220049033 · Cited by 1,972 · see citing works
Methionine metabolism in mammals
Finkelstein, J. D. (1990) · The Journal of Nutritional Biochemistry · doi:10.1016/0955-2863(90)90070-2 · Cited by 1,495 · see citing works
Hertog, M. G. L., Hollman, P. C. H., & Katan, M. (1992) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf00024a011 · Cited by 1,381 · see citing works
Self-citationHertog, M. G. L., Hollman, P. C. H., Katan, M. B., & Kromhout, D. (1993) · Nutrition and Cancer · doi:10.1080/01635589309514267 · Cited by 1,216 · see citing works
Self-citationThe chemistry of tea flavonoids
Balentine, D. A., Wiseman, S. A., & Bouwens, L. C. M. (1997) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408399709527797 · Cited by 1,130 · see citing works
Total Plasma Homocysteine and Cardiovascular Risk Profile
Nygard, O. K., Vollset, S. E., Refsum, H., Stensvold, I., Tverdal, A., Nordrehaug, J. E., Ueland, P. M., & Kvåle, G. (1995) · JAMA · doi:10.1001/jama.1995.03530190040032 · Cited by 1,043 · see citing works
Total homocysteine in plasma or serum: methods and clinical applications
Ueland, P. M., Refsum, H., Stabler, S. P., Malinow, M. R., Andersson, A. D. R., & Allen, R. H. (1993) · Clinical Chemistry · doi:10.1093/clinchem/39.9.1764 · Cited by 984 · see citing works
Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices
Hertog, M. G. L., Hollman, P. C. H., & van de Putte, B. (1993) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf00032a015 · Cited by 900 · see citing works
Self-citationRapid high-performance liquid chromatographic assay for total homocysteine levels in human serum
Ubbink, J., Vermaak, W. J. H., & Bissbort, S. (1991) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/0378-4347(91)80407-4 · Cited by 684 · see citing works
Flavonols and flavones in food plants: a review
HERRMANN, K. (1976) · International Journal of Food Science & Technology · doi:10.1111/j.1365-2621.1976.tb00743.x · Cited by 581 · see citing works
The Hordaland Homocysteine Studies
Ueland, P. M., Nygard, O. K., Vollset, S. E., & Refsum, H. (2001) · Lipids · doi:10.1007/s11745-001-0679-7 · Cited by 327 · see citing works
Zhu, B. T., Ezell, E. L., & Liehr, J. G. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42348-9 · Cited by 237 · see citing works
Coffee consumption and plasma total homocysteine: The Hordaland Homocysteine Study
Nygard, O. K., Refsum, H., Ueland, P. M., Stensvold, I., Je, N., Kvåle, G., & Vollset, S. (1997) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/65.1.136 · Cited by 220 · see citing works
Levels of the Cholesterol-Elevating Diterpenes Cafestol and Kahweol in Various Coffee Brews
Rob Urgert, B., van der Weg, G., Kosmeijer‐Schuil, T. G., van de Bovenkamp, P., Hovenier, R., & Katan, M. (1995) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf00056a039 · Cited by 217 · see citing works
Self-citationPlasma Homocysteine and Cardiovascular Disease
Ueland, P. M., & Refsum, H. (2000) · Cited by 191 · see citing works
Metabolism of chlorogenic acid by human plasma, liver, intestine and gut microflora
Plumb, G. W., García‐Conesa, M., Kroon, P. A., Rhodes, M. J. C., Ridley, S., & Williamson, G. (1999) · Journal of the Science of Food and Agriculture · doi:10.1002/(sici)1097-0010(19990301)79:3 · Cited by 189 · see citing works
Atherosclerotic Cardiovascular Disease, Hemostasis and Endothelial Function
Machin, S. J. (1993) · Blood Coagulation & Fibrinolysis · doi:10.1097/00001721-199306000-00021 · Cited by 181 · see citing works
Elevated Plasma Levels of Homocysteine inParkinson’s Disease
Kuhn, W., Roebroek, R., Blom, H. J., van Oppenraaij, D., Przuntek, H., Kretschmer, A., Büttner, T., Woitalla, D., & Müller, T. H. (1998) · European Neurology · doi:10.1159/000007984 · Cited by 171 · see citing works
Ubbink, J., Serfontein, W. J., & VILLIERS, L. S. D. (1985) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)84518-1 · Cited by 161 · see citing works
Atherosclerotic cardiovascular disease, hemostasis, and endothelial function
Francis, R. B. (1992) · M. Dekker eBooks · Cited by 150 · see citing works
Grubben, M. J. A. L., Boers, G. H. J., Blom, H. J., Broekhuizen, R., de Jong, R. D. J., van Rijt, L. S., de Ruijter, E., Swinkels, D. W., Nagengast, F. M., & Katan, M. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.480 · Cited by 147 · see citing works
Self-citationRob Urgert, B., van Vliet, T., Zock, P. L., & Katan, M. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/72.5.1107 · Cited by 136 · see citing works
Self-citationStolzenberg‐Solomon, R. Z., Miller, E. R., Maguire, M. G., Selhub, J., & Appel, L. J. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.3.467 · Cited by 134 · see citing works
Nigral endothelial dysfunction, homocysteine, and Parkinson's disease
Müller, T. H., Weme, B., Fowler, B., & Kuhn, W. (1999) · The Lancet · doi:10.1016/s0140-6736(99)01660-8 · Cited by 132 · see citing works
Sulfate and cysteine levels in the plasma of patients with Parkinson's disease.
Allain, P., Le Bouil, A., Cordillet, E., Le Quay, L., Bagheri, H., & Montastruc, J. (1995) · PubMed · Cited by 106 · see citing works
Schrijver, J., Speek, A. J., & Schreurs, W. H. P. (1981) · PubMed · Cited by 78 · see citing works
Kinetics of plasma homocysteine in healthy subjects after peroral homocysteine loading
Guttormsen, A. B., Mansoor, A. M., Fiskerstrand, T., Ueland, P. M., & Refsum, H. (1993) · Clinical Chemistry · doi:10.1093/clinchem/39.7.1390 · Cited by 70 · see citing works
Hyperhomocysteinaemia in Parkinson's disease
Kuhn, W., Roebroek, R., Blom, H. J., van Oppenraaij, D., & Müller, T. H. (1998) · Journal of Neurology · doi:10.1007/s004150050292 · Cited by 61 · see citing works
Oshaug, A., Bugge, K. H., & Refsum, H. (1998) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1600505 · Cited by 50 · see citing works
Andersson, A. D. R., Brattström, L. E., Israelsson, B., Isaksson, A., & Hultberg, B. L. (1990) · Clinica Chimica Acta · doi:10.1016/0009-8981(90)90273-u · Cited by 29 · see citing works
Daly, D., Miller, J. W., Nadeau, M., & Selhub, J. (1997) · The Journal of Nutritional Biochemistry · doi:10.1016/s0955-2863(97)00110-1 · Cited by 26 · see citing works
Ion capture assay for folate with the Abbott IMx analyzer
Wilson, D. H., Herrmann, R., Hsu, S. C., Biegalski, T. T., Sohn, L., Forsythe, C. M., Novotny, M., Beggs, M., & Manderino, G. L. (1995) · Clinical Chemistry · doi:10.1093/clinchem/41.12.1780 · Cited by 25 · see citing works
Automated Assay of Vitamin B-12 by the Abbott IMx® Analyzer
Kuemmerle, S. C., Boltinghouse, G. L., Delby, S. M., Lane, T. L., & Simondsen, R. P. (1992) · Clinical Chemistry · doi:10.1093/clinchem/38.10.2073 · Cited by 23 · see citing works
Flagged first, then by citations
5 of the 39 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Dietary polyphenols and the prevention of diseases
Scalbert, A., Manach, C., Morand, C., Rémésy, C., & Jiménez, L. (2005) · Critical Reviews in Food Science and Nutrition · doi:10.1080/1040869059096 · Cited by 2,999 · see citing works
“[297] Olthof, M.”
Biomarkers of Nutrition for Development—Folate Review
Bailey, L. B., Stover, P. J., McNulty, H., Fenech, M. F., Gregory, J. F., Mills, J. L., Pfeiffer, C. M., Fazili, Z., Zhang, M., Ueland, P. M., et al. (2015) · Journal of Nutrition · doi:10.3945/jn.114.206599 · Cited by 1,147 · see citing works
Coffee and Health: A Review of Recent Human Research
Higdon, J. V., & Frei, B. (2006) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408390500400009 · Cited by 1,090 · see citing works
Tajik, N., Tajik, M., Mack, I., & Enck, P. (2017) · European Journal of Nutrition · doi:10.1007/s00394-017-1379-1 · Cited by 730 · see citing works
The Role of Tea in Human Health: An Update
McKay, D. L., & Blumberg, J. B. (2002) · Journal of the American College of Nutrition · doi:10.1080/07315724.2002.10719187 · Cited by 772 · see citing works
“[47] recently tested the consumption of 4 g/day of black tea solids (equivalent to 1 L of strong black tea) for seven days in 20 healthy, young adults, 24 8 years of age and found their mean plasma total homocysteine increased 11% (1.”
BackgroundDing, M., Bhupathiraju, S. N., Satija, A., van Dam, R. M., & Hu, F. B. (2014) · Circulation · doi:10.1161/circulationaha.113.005925 · Cited by 565 · see citing works
“Long-term heavy coffee consumption has been associated with a slightly elevated risk of hypertension(40) and a higher level of plasma homocysteine.(41,42) In addition, cafestol in unfiltered coffee increases serum total cholesterol concentrations.”
The role of polyphenols in modern nutrition
Williamson, G. (2017) · Nutrition Bulletin · doi:10.1111/nbu.12278 · Cited by 551 · see citing works
“Coffee consumption over 1 week has been reported to increase (Olthof et al. 2001) or not affect (Esposito et al.”
BackgroundRefsum, H., Nurk, E., Smith, A. D., Ueland, P. M., Gjesdal, C. G., Bjelland, I., Tverdal, A., Tell, G. S., Nygard, O. K., & Vollset, S. E. (2006) · Journal of Nutrition · doi:10.1093/jn/136.6.1731s · Cited by 493 · see citing works
“However, other observational studies confirmed the association (36,37,44), and intervention studies have now demonstrated that coffee raises tHcy levels (45,46), an effect that is probably mediated by chlorogenic acid (47) and caffeine (48), which are coffee constituents.”
ResultDietary Polyphenols May Affect DNA Methylation
Fang, M., Chen, D., & Yang, C. S. (2007) · Journal of Nutrition · doi:10.1093/jn/137.1.223s · Cited by 465 · see citing works
“Alteration of levels of SAM, SAH, and homocysteine after the administration of EGCG to mice Consumption of polyphenols was reported to reduce SAM levels and increase homocysteine levels in humans (34).”
BackgroundNguyen, V., Taine, E. G., Meng, D., Cui, T., & Tan, W. (2024) · Nutrients · doi:10.3390/nu16070924 · Cited by 385 · see citing works
“Cautiously, a high-dosage consumption of CGA (2 g/day) or black tea (4 g/4 L/day) four times in 7 days can moderately increase plasma homocysteine levels by 12% or 11% in humans, respectively [17].”
BackgroundFarah, A. (2012) · Coffee · doi:10.1002/9781119949893.ch2 · Cited by 330 · see citing works
Coffee Drinking Influences Plasma Antioxidant Capacity in Humans
Natella, F., Nardini, M., Giannetti, I., Dattilo, C., & Scaccini, C. (2002) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf025768c · Cited by 324 · see citing works
de Bree, A., Verschuren, W. M. M., Kromhout, D., Kluijtmans, L. A. J., & Blom, H. J. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.4.599 · Cited by 283 · see citing works
Thom, E. (2007) · Journal of International Medical Research · doi:10.1177/147323000703500620 · Cited by 280 · see citing works
Complexity and health functionality of plant cell wall fibers from fruits and vegetables
Padayachee, A., Day, L., Howell, K. S., & Gidley, M. J. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.850652 · Cited by 284 · see citing works
“Although these processes are applied in order to create food products with increased shelf life by eliminating enzymes and microorganisms that can cause spoilage, textural changes due to cell wall denaturation inevitably occur (Ormerod et al., 2004).”
MethodBellik, Y., Boukraâ, L., Alzahrani, H. A., Bakhotmah, B. A., Abdellah, F., Hammoudi, S. M., & Iguer‐Ouada, M. (2012) · Molecules · doi:10.3390/molecules18010322 · Cited by 280 · see citing works
Tea flavonoids and cardiovascular health
Hodgson, J. M., & Croft, K. D. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.09.004 · Cited by 275 · see citing works
“A controlled intervention study using high doses of tea solids found that tea solids increased tHcy (Olthof et al., 2001), but a dose more representative of a usual tea intake did not alter tHcy (Hodgson et al., 2003).”
BackgroundHaplotype-phased genome and evolution of phytonutrient pathways of tetraploid blueberry
Colle, M., Leisner, C. P., Wai, C. M., Ou, S., Bird, K. A., Wang, J., Wisecaver, J. H., Yocca, A. E., Alger, E. I., Tang, H., et al. (2019) · GigaScience · doi:10.1093/gigascience/giz012 · Cited by 265 · see citing works
Polyphenols as dietary supplements: A double-edged sword
Martin, K. R. (2009) · Nutrition and Dietary Supplements · doi:10.2147/nds.s6422 · Cited by 265 · see citing works
“High polyphenol intake could also increase the risk of CVD through alterations in homocysteine processing, a well-accepted biomarker for CVD. 76,77 Lastly, polyphenols, specifically naringenin in grapefruit, can inhibit drug-metabolizing enzymes such as CYP3A4, among others, involved in xenobiotic metabolism and, thus…”
BackgroundJacobo‐Velázquez, D. A., Martínez–Hernández, G. B., Rodríguez, S., Cao, C.-M., & Cisneros‐Zevallos, L. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf2006529 · Cited by 257 · see citing works
Impact on DNA Methylation in Cancer Prevention and Therapy by Bioactive Dietary Components
Li, Y.-C., & Tollefsbol, T. O. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710791299966 · Cited by 256 · see citing works
Watanabe, T., Arai, Y., Mitsui, Y., Kusaura, T., Okawa, W., Kajihara, Y., & Saito, I. (2006) · Clinical and Experimental Hypertension · doi:10.1080/10641960600798655 · Cited by 242 · see citing works
Suzuki, A., Yamamoto, N., Jokura, H., Yamamoto, M., Fujii, A., Tokimitsu, I., & Saito, I. (2006) · Journal of Hypertension · doi:10.1097/01.hjh.0000226196.67052.c0 · Cited by 231 · see citing works
Sánchez-González, I., Jiménez‐Escrig, A., & Saura-Calixto, F. D. (2004) · Food Chemistry · doi:10.1016/j.foodchem.2004.03.037 · Cited by 227 · see citing works
Anti-hypertensive Nutraceuticals and Functional Foods
Chen, Z., Peng, C., Jiao, R., Wong, Y. M., Yang, N., & Huang, Y. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf900803r · Cited by 218 · see citing works
Prior, R. L., Gu, L., Wu, X., Jacob, R. A., Sotoudeh, G., Kader, A. A., & Cook, R. A. (2007) · Journal of the American College of Nutrition · doi:10.1080/07315724.2007.10719599 · Cited by 219 · see citing works
“Chlorogenic acid is also found in coffee and black tea [32].”
BackgroundIn vitro transformation of chlorogenic acid by human gut microbiota
Tomás-Barberán, F. A., Garcı́a-Villalba, R., Quartieri, A., Raimondi, S., Amaretti, A., Leonardi, A., & Rossi, M. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300441 · Cited by 202 · see citing works
Stefanska, B., Karlic, H., Varga, F., Fabianowska‐Majewska, K., & Haslberger, A. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02002.x · Cited by 200 · see citing works
“Moreover, consumers of high doses of chlorogenic acid had an increased plasma concentration of total homocysteine, which is an inhibitor of methylation reactions (Olthof et al., 2001).”
BackgroundDeveloping a metagenomic view of xenobiotic metabolism
Haiser, H. J., & Turnbaugh, P. J. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2012.07.009 · Cited by 186 · see citing works
“For example, the conjugated hydroxycinnamate chlorogenic acid is one of the most abundant polyphenols in the human diet, found in coffee, fruits, and vegetables [74].”
BackgroundCoffee consumption and disease correlations
Gökcen, B. B., & Şanlıer, N. (2017) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2017.1369391 · Cited by 188 · see citing works
“Firstly, Olthof et al. (2001) found that chlorogenic acids, which are compounds of coffee, increase the total homocysteine levels in plasma (Olthof, et al., 2001).”
BackgroundBioavailability and metabolism of chlorogenic acids (acyl‐quinic acids) in humans
Clifford, M. N., Kerimi, A., & Williamson, G. (2020) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12518 · Cited by 183 · see citing works
“In the earliest “modern” study, Olthof et al. (2001) gave volunteers 2.8 mmol of 5-CQA 3 and detected ca 9 µmol caffeic acid 7 and ca 8 µmol 5-CQA 3 in 24-hr urine after enzymic deconjugation.”
BackgroundInfluentialDietary recommendations for prevention of atherosclerosis
Riccardi, G., Giosuè, A., Calabrese, I., & Vaccaro, O. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab173 · Cited by 186 · see citing works
“Conversely, heavy coffee consumption is associated with a slightly elevated risk of hypertension(59) and higher levels of plasma homocysteine in the long term.(60,61)”
BackgroundDigestion and bioavailability of bioactive phytochemicals
Karaś, M., Jakubczyk, A., Szymanowska, U., Złotek, U., & Zielińska, E. (2016) · International Journal of Food Science & Technology · doi:10.1111/ijfs.13323 · Cited by 182 · see citing works
Acute and long-term cardiovascular effects of coffee: Implications for coronary heart disease
Riksen, N. P., Rongen, G. A. P. J. M., & Smits, P. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.10.006 · Cited by 166 · see citing works
“Indeed, Olthof et al. demonstrated that a 7 day treatment with chlorogenic acid, one of the other components of coffee, also increased plasma homocysteine levels (Olthof et al., 2001).”
BackgroundChlorogenic acid‐mediated chemical defence of plants against insect herbivores
Kundu, A., & Vadassery, J. (2018) · Plant Biology · doi:10.1111/plb.12947 · Cited by 163 · see citing works
Niseteo, T., Komes, D., Belščak‐Cvitanović, A., Horžić, D., & Budeč, M. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.03.095 · Cited by 161 · see citing works
Coffee consumption and risk of type 2 diabetes, cardiovascular diseases, and cancer
van Dam, R. M. (2008) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h08-120 · Cited by 161 · see citing works
Verhoef, P., Pasman, W. J., van Vliet, T., Urgert, R., & Katan, M. B. (2002) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.6.1244 · Cited by 158 · see citing works
“We previously reported (19) that chlorogenic acid raises homocysteine: consumption of 2 g chlorogenic acid/d for 7 d—an amount equivalent to 1.”
BackgroundSelf-citationOnakpoya, I., Spencer, E. A., Thompson, M., & Heneghan, C. J. (2014) · Journal of Human Hypertension · doi:10.1038/jhh.2014.46 · Cited by 146 · see citing works
Jin, S.-S., Chang, C., Zhang, L., Liu, Y., Huang, X.-R., & Chen, Z. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120842 · Cited by 141 · see citing works
“Prabhakar et al. showed that CGA stimulates glucose transport in myotubes by increasing the expression of GLTU4 [40].”
BackgroundInfluentialvan Dam, R. M., Dekker, J. M., Nijpels, G., Stehouwer, C. D. A., Bouter, L. M., & Heine, R. J. (2004) · Diabetologia · doi:10.1007/s00125-004-1573-6 · Cited by 133 · see citing works
Biotransformations and biological activities of hop flavonoids
Karabín, M., Hudcová, T., Jelínek, L., & Dostálek, P. (2015) · Biotechnology Advances · doi:10.1016/j.biotechadv.2015.02.009 · Cited by 133 · see citing works
Tomé‐Carneiro, J., & Visioli, F. (2015) · Phytomedicine · doi:10.1016/j.phymed.2015.10.018 · Cited by 132 · see citing works
Pharmacologic Overview of Chlorogenic Acid and its Metabolites in Chronic Pain and Inflammation
Bağdaş, D., Gül, Z., Meade, J. A., Çam, B., Çinkılıç, N., & Gurun, M. S. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666191021111809 · Cited by 126 · see citing works
Li, L., Su, C., Chen, X., Wang, Q., Jiao, W., Luo, H., Tang, J., Wang, W., Li, S., & Guo, S. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c01554 · Cited by 124 · see citing works
Ștefănescu, B. E., Szabo, K., Mocan, A., & Crișan, G. (2019) · Molecules · doi:10.3390/molecules24112046 · Cited by 123 · see citing works
Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation
Fuentes, E., Caballero, J., Alarcón, M., Rojas, A., & Palomo, I. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090699 · Cited by 115 · see citing works
“chlorogenic acid from foods (apples, pears, berries, artichokes and aubergines, among others) will enter the blood circulation and thus can induce biological effects [45].”
BackgroundCoffee, caffeine, and coronary heart disease
Cornelis, M. C., & El‐Sohemy, A. (2007) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e3282f05d81 · Cited by 113 · see citing works
Coffee, caffeine, and coronary heart disease
Cornelis, M. C., & El‐Sohemy, A. (2007) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3280127b04 · Cited by 110 · see citing works
Epigenetic Effects of Green Tea Polyphenols in Cancer
Henning, S. M., Wang, P., Carpenter, C. L., & Heber, D. (2013) · Epigenomics · doi:10.2217/epi.13.57 · Cited by 105 · see citing works
Moderate coffee consumption increases plasma glutathione but not homocysteine in healthy subjects
Esposito, F., Morisco, F., Verde, V., Ritieni, A., Alezio, A., Caporaso, N., & Fogliano, V. (2003) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2003.01429.x · Cited by 105 · see citing works
Mennen, L. I., de Courcy, G. P., Guilland, J.-C., Ducros, V., Bertrais, S., Nicolas, J., Maurel, M., Zarebska, M., Favier, A. E., Franchisseur, C., et al. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.6.1279 · Cited by 104 · see citing works
“A recent intervention study showed that consumption of a high dose of chlorogenic acid, a major polyphenol in coffee, or consumption of black tea increases tHcy 4–5 h after intake (23).”
BackgroundAlmoosawi, S., Fyfe, L., Ho, C. K. M., & Al‐Dujaili, E. A. S. (2009) · British Journal Of Nutrition · doi:10.1017/s0007114509992431 · Cited by 101 · see citing works
Martínez‐López, S., Sarriá, B., Mateos, R., & Bravo, L. (2018) · European Journal of Nutrition · doi:10.1007/s00394-018-1726-x · Cited by 101 · see citing works
Pasquale, L. R., Wiggs, J. L., Willett, W. C., & Kang, J. H. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.12-10085 · Cited by 97 · see citing works
“After acute ingestion of filtered caffeinated coffee, there is an increase in plasma Hcy, and polyphenols such as chlorogenic acid, a compound abundant in coffee but not found in other foods, may contribute to this effect.(33,34) The Hordaland homocysteine study,(53) a population-based study of 11,940 healthy subjects…”
BackgroundPlant phenolic compounds for food, pharmaceutical and cosmetiсs production
Sytar, O. (2012) · Journal of Medicinal Plants Research · doi:10.5897/jmpr11.1695 · Cited by 94 · see citing works
The Cardiovascular Effects of Methylxanthines
Riksen, N. P., Smits, P., & Rongen, G. A. P. J. M. (2010) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-13443-2_16 · Cited by 89 · see citing works
Important medicinal herbs in Parkinson’s disease pharmacotherapy
Srivastav, S., Fatima, M., & Mondal, A. C. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.05.137 · Cited by 87 · see citing works
Tagliazucchi, D., Helal, A., Verzelloni, E., & Conte, A. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf302694a · Cited by 83 · see citing works
Alcohol, smoking, coffee and risk of non-fatal acute myocardial infarction in Italy
Tavani, A., Bertuzzi, M., Negri, E., Sorbara, L., & Vecchia, C. L. (2001) · European Journal of Epidemiology · doi:10.1023/a:1021276932160 · Cited by 83 · see citing works
“Among the proposed biological mechanisms through which coffee may increase CHD risk there are the coffee-dependent rise in blood pressure [33] and in low density lipoprotein cholesterol [34], and plasma total homocysteine concentrations [35].”
Therapeutic Promises of Chlorogenic Acid with Special Emphasis on its Anti-Obesity Property
Kumar, R., Sharma, A., Iqbal, M. S., & Srivastava, J. K. (2019) · Current Molecular Pharmacology · doi:10.2174/1874467212666190716145210 · Cited by 82 · see citing works
Environment, diet and CpG island methylation: Epigenetic signals in gastrointestinal neoplasia
Johnson, I. T., & Belshaw, N. J. (2007) · Food and Chemical Toxicology · doi:10.1016/j.fct.2007.09.101 · Cited by 87 · see citing works
Coffee Consumption and Cardiovascular Health: Getting to the Heart of the Matter
Rebello, S. A., & van Dam, R. M. (2013) · Current Cardiology Reports · doi:10.1007/s11886-013-0403-1 · Cited by 78 · see citing works
“These effects occur for both filtered [57] and unfiltered [58] coffee, are likely to be mediated by both caffeine [59] and CGA [60] and are probably persistent [57, 61].”
InfluentialFlavoring and Coloring Agents: Health Risks and Potential Problems
Ramesh, M., & Muthuraman, A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-811518-3.00001-6 · Cited by 77 · see citing works
Carman, A. J., Dacks, P. A., Lane, R. F., Shineman, D. W., & Fillit, H. M. (2014) · The journal of nutrition health & aging · doi:10.1007/s12603-014-0021-7 · Cited by 68 · see citing works
Miranda, A. M., Steluti, J., Fisberg, R. M., & Marchioni, D. M. L. (2017) · Nutrients · doi:10.3390/nu9030276 · Cited by 67 · see citing works
“Additionally, chlorogenic acid, a polyphenol that is present in coffee, may also be partly responsible for the increase of the homocysteine production through increased methylation reactions [47].”
BackgroundMursu, J., Voutilainen, S., Nurmi, T., Alfthan, G., Virtanen, J. K., Rissanen, T., Happonen, P., Nyyssönen, K., Kaikkonen, J., Salonen, R. M., et al. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.11.025 · Cited by 65 · see citing works
“Chlorogenic acid and caffeine have been identified to be mainly responsible for the increase of tHcy after coffee consumption [11,12].”
BackgroundThe Contribution of Buckwheat Genetic Resources to Health and Dietary Diversity
Sytar, O., Brestič, M., Živčák, M., & Tran, L. P. (2016) · Current Genomics · doi:10.2174/1389202917666160202215425 · Cited by 65 · see citing works
“Other nutritional sources of chlorogenic acid include berries, aubergines, apples, pears and artichokes [94].”
Green coffee infusion as a source of caffeine and chlorogenic acid
Macheiner, L., Schmidt, A., Schreiner, M., & Mayer, H. K. (2019) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2019.103307 · Cited by 64 · see citing works
Association of coffee drinking with all-cause mortality: a systematic review and meta-analysis
Zhao, Y., Wu, K., Zheng, J., Zuo, R., & Li, D. (2014) · Public Health Nutrition · doi:10.1017/s1368980014001438 · Cited by 61 · see citing works
“(41) assumed that the homocysteine-elevating effect was possibly caused by the chlorogenic acid in coffee.”
Characterization of nutraceutical components in tomato pulp, skin and locular gel
Tamasi, G., Pardini, A., Bonechi, C., Donati, A., Pessina, F., Marcolongo, P., Gamberucci, A., Leone, G., Consumi, M., Magnani, A., et al. (2019) · European Food Research and Technology · doi:10.1007/s00217-019-03235-x · Cited by 60 · see citing works
Chlorogenic acid attenuates adhesion molecules upregulation in IL-1β-treated endothelial cells
Chang, W., Chen, C., Lee, M., Chang, T., & Yu, Y. (2009) · European Journal of Nutrition · doi:10.1007/s00394-009-0083-1 · Cited by 58 · see citing works
Wakeling, L. A., Ions, L. J., & Ford, D. (2009) · AGE · doi:10.1007/s11357-009-9104-5 · Cited by 58 · see citing works
Chlorogenic Acid: The Conceivable Chemosensitizer Leading to Cancer Growth Suppression
Lukitasari, M., Nugroho, D. A., & Widodo, N. (2018) · Journal of Evidence-Based Integrative Medicine · doi:10.1177/2515690x18789628 · Cited by 57 · see citing works
“This substance is mostly found in green coffee bean.(30) Moreover, this substance is an ester that consist of cinnamic acid and quinic acid.”
BackgroundPhytochemistry, Bioaccessibility, and Bioactivities of Sesame Seeds: An Overview
Li, M., Luo, J., Nawaz, M. A., Stockmann, R., Buckow, R., Barrow, C. J., Dunshea, F. R., & Suleria, H. A. R. (2023) · Food Reviews International · doi:10.1080/87559129.2023.2168280 · Cited by 56 · see citing works
“[109 ,112] Olthof, et al. [113] showed that the colon would be the digestion site for the esterified hydroxycinnamic acids.”
BackgroundHerbal Medicines in Pregnancy and Lactation: An Evidence-Based Approach
Mills, E. J., Duguoa, J.-J., Perri, D., & Koren, G. (2006) · Cited by 50 · see citing works
Cardiovascular protection effect of chlorogenic acid: focus on the molecular mechanism
Lukitasari, M., Rohman, M. S., Nugroho, D. A., Widodo, N., & Nugrahini, N. I. P. (2020) · F1000Research · doi:10.12688/f1000research.26236.1 · Cited by 49 · see citing works
Pereira, J. A. M., Berenguer, C. V., Andrade, C. F. P., & Câmara, J. S. (2022) · Applied Sciences · doi:10.3390/app12052747 · Cited by 53 · see citing works
“, caffeic, ferulic, synaptic, or p-coumaric acids) often occur in their esterified form with quinic and tartaric acids or carbohydrate derivatives, being absorbed in the colon [61,63].”
BackgroundMethylation demand and homocysteine metabolism
Stead, L. M., Jacobs, R. L., Brosnan, M. E., & Brosnan, J. T. (2004) · Advances in Enzyme Regulation · doi:10.1016/j.advenzreg.2003.11.012 · Cited by 49 · see citing works
Apple polyphenols and cardiovascular disease - a review of the evidence
Weichselbaum, E., Wyness, L., & Stanner, S. A. (2010) · Nutrition Bulletin · doi:10.1111/j.1467-3010.2010.01822.x · Cited by 48 · see citing works
Coffee as a speciality and functional beverage
Farah, A. (2009) · Elsevier eBooks · doi:10.1533/9781845695569.3.370 · Cited by 47 · see citing works
Chlorogenic Acid Attenuates Ventricular Remodeling After Myocardial Infarction in Mice
Kanno, Y., Watanabe, R., Zempo, H., Ogawa, M., Suzuki, J., & Isobe, M. (2013) · International Heart Journal · doi:10.1536/ihj.54.176 · Cited by 47 · see citing works
Dietary Patterns Are Associated with Hyperhomocysteinemia in an Urban Pakistani Population
Yakub, M., Iqbal, M. P., & Iqbal, R. (2010) · Journal of Nutrition · doi:10.3945/jn.109.120477 · Cited by 46 · see citing works
“Although we think that the effect of tea in terms of polyphenol concentration may not be very significant (45), it could be adding to the homocysteine concentrations by decreasing the bioavailability of folate and, hence, affect the homocysteine remethylation cycle (46).”
BackgroundHealthy components of coffee processing by-products
Dorsey, B. M., & Jones, M. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-811290-8.00002-5 · Cited by 51 · see citing works
Enas, E. A., Senthilkumar, A., Chennikkara, H., & Bjurlin, M. A. (2003) · PubMed · Cited by 46 · see citing works
Rajan, R. K., Hussein, M. Z., Fakurazi, S., Yusoff, K., & Masarudin, M. J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194667 · Cited by 45 · see citing works
“Hence to confront these limitations, administration of a high dosage was used [1] but in which led to observable events of severe side effects such as DNA damage [32], cardiovascular complications [33], inflammatory and oxidative stress injuries [34], disruption in natural oxidant and antioxidant balance mechanisms [3…”
BackgroundInfluentialEffects of Dietary Nutrients on Epigenetic Changes in Cancer
Andreescu, N. I., Puiu, M., & Niculescu, M. D. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8751-1_7 · Cited by 45 · see citing works
A 6-month randomized pilot study of black tea and cardiovascular risk factors
Mukamal, K. J., MacDermott, K., Vinson, J. A., Oyama, N., Manning, W. J., & Mittleman, M. A. (2007) · American Heart Journal · doi:10.1016/j.ahj.2007.07.008 · Cited by 44 · see citing works
Husemoen, L. L. N., Thomsen, T. F., Fenger, M., & Jørgensen, T. (2004) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1601942 · Cited by 44 · see citing works
“Chlorogenic acid, a polyphenol, also present in coffee may also be partly responsible for the increase in tHcy (Olthof et al, 2001).”
BackgroundResultvan der Hoeven, T., Browne, J. L., Uiterwaal, C. S. P. M., van der Ent, C. K., Grobbee, D. E., & Dalmeijer, G. W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177619 · Cited by 43 · see citing works
Consumption of green coffee and the risk of chronic diseases
Şanlıer, N., Atik, A., & Atik, İ. (2018) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2018.1461061 · Cited by 43 · see citing works
“Total homocysteine in the postprandial plasma of individuals consuming chlorogenic acid compared to placebo was 12 % higher; total homocysteine was increased by 4 % in fasting plasma, and fasting plasma folate concentration was decreased by 8 % (Olthof et al. 2001).”
BackgroundCoffee Consumption and Coronary Calcification
Woudenbergh, G. J. G.-V., Vliegenthart, R., van Rooij, F. J. A., Albert Hofman, D., Oudkerk, M., Witteman, J. C. M., & Geleijnse, J. M. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.160457 · Cited by 42 · see citing works
The potential role of epigenetic responses to diet in ageing
Ford, D., Ions, L. J., Alatawi, F. S., & Wakeling, L. A. (2011) · Proceedings of The Nutrition Society · doi:10.1017/s0029665111000851 · Cited by 41 · see citing works
Chlorogenic Acid’s Role in Metabolic Health: Mechanisms and Therapeutic Potential
Zalewska, K., Kulawik, M., Gierszewska, J., Gramala, Z., Kalus, O., Karpiński, M., Maćkowiak, J., Staniewski, A., Szymańska, Z., Zalewska, B., et al. (2025) · Nutrients · doi:10.3390/nu17203303 · Cited by 39 · see citing works
“In recent years, there has been growing interest in CGA in both basic and clinical research, owing to its promising pharmacological properties and safety [4,8,18].”
The Effect of Caffeine on Tear Secretion
Osei, K. A., Ovenseri-Ogbomo, G. O., Kyei, S., & Ntodie, M. (2013) · Optometry and Vision Science · doi:10.1097/opx.0000000000000129 · Cited by 39 · see citing works
Choi, S.-W., & Friso, S. (2009) · CRC Press eBooks · doi:10.1201/9781420063561 · Cited by 39 · see citing works
Coffee Consumption and Circulating B-Vitamins in Healthy Middle-Aged Men and Women
Ulvik, A., Vollset, S. E., Hoff, G. S., & Ueland, P. M. (2008) · Clinical Chemistry · doi:10.1373/clinchem.2008.103465 · Cited by 39 · see citing works
Can black tea influence plasma total homocysteine concentrations?
Hodgson, J. M., Burke, V., Beilin, L. J., Croft, K. D., & Puddey, I. B. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.4.907 · Cited by 37 · see citing works
Green coffee: economic relevance and a systematic review of the effects on human health
Bosso, H., Barbalho, S. M., Goulart, R. D. Á., & Otoboni, A. M. M. B. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1948817 · Cited by 36 · see citing works
“The subsequent studies did not report whether or not there were any adverse effects: Suzuki et al. (2019); Mart ınez-L opez et al. (2019); Bobillo et al. (2018); Sarri a et al. (2018); (Haidari et al. (2017); Beam et al. (2015); Camfield et al. (2013); Lecoultre et al. (2014); ReyesIzquierdo et al. (2013); Olthof et a…”
BackgroundInfluentialAsbaghi, O., Sadeghian, M., Nasiri, M., Khodadost, M., Shokri, A., Panahande, S. B., Pirouzi, A., & Sadeghi, O. (2020) · Nutrition Journal · doi:10.1186/s12937-020-00587-z · Cited by 35 · see citing works
- Authors
- Olthof, M. R., Hollman, P. C., Zock, P. L., & Katan, M. B.
- Affiliations
- Wageningen University & Research (NL)
- Corresponding author
- Olthof, Margreet R
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2001-03
- Volume
- 73
- Issue
- 3
- Pages
- 532-538
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2137832364
- Cited by
- 222
- References
- 39
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 11 · 2019: 16 · 2018: 11 · 2017: 13 · 2016: 5 · 2015: 9 · 2014: 9 · 2013: 12 · 2012: 13
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- chlorogenic acid, coffee, black tea, homocysteine, plasma homocysteine, polyphenols, rutin, cardiovascular risk, dietary supplementation, flavonols
- MeSH terms
- Adult, Cardiovascular Diseases, Chlorogenic Acid, Coffee, Fasting, Female, Flavonoids, Folic Acid, Glucosides, Homocysteine, Humans, Male, Phenols, Polymers, Pyridoxine, Quercetin, Risk Factors, Tea, Vitamin B 12, Cross-Over Studies, Postprandial Period
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