DOCSLIB.ORG

Cafestol and Kahweol: a Review on Their Bioactivities and Pharmacological Properties

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cafestol and Kahweol: a Review on Their Bioactivities and Pharmacological Properties International Journal of Molecular Sciences Review Cafestol and Kahweol: A Review on Their Bioactivities and Pharmacological Properties Yaqi Ren 1, Chunlan Wang 2, Jiakun Xu 2,* and Shuaiyu Wang 1,* 1 College of Veterinary Medicine, China Agricultural University, Beijing 100193, China 2 Key Laboratory of Sustainable Development of Polar Fisheries, Ministry of Agriculture and Rural Affairs, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences; Laboratory for Marine Drugs and Byproducts of Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266071, China * Correspondence: [email protected] (J.X.); [email protected] (S.W.); Tel.: +86-138-6982-8530 (J.X.); +86-136-1100-7081 (S.W.) Received: 17 July 2019; Accepted: 18 August 2019; Published: 30 August 2019 Abstract: Cafestol and kahweol are natural diterpenes extracted from coffee beans. In addition to the effect of raising serum lipid, in vitro and in vivo experimental results have revealed that the two diterpenes demonstrate multiple potential pharmacological actions such as anti-inflammation, hepatoprotective, anti-cancer, anti-diabetic, and anti-osteoclastogenesis activities. The most relevant mechanisms involved are down-regulating inflammation mediators, increasing glutathione (GSH), inducing apoptosis of tumor cells and anti-angiogenesis. Cafestol and kahweol show similar biological activities but not exactly the same, which might due to the presence of one conjugated double bond on the furan ring of the latter. This review aims to summarize the pharmacological properties and the underlying mechanisms of cafestol-type diterpenoids, which show their potential as functional food and multi-target alternative medicine. Keywords: cafestol; kahweol; serum lipid; anti-inflammation; anti-tumor; anti-diabetes 1. Introduction Coffee is one of the most wildly consumed beverages in the world. Extensive experiments and meta-analysis of studies show that coffee consumption is associated with the risk of some human diseases [1]. Statistics show that moderate consumption of coffee (3 to 5 cups/day) reduces the risk of cardiovascular disease [2]. There is growing evidence that coffee can prevent some chronic diseases such as cancer, cardiovascular disease, metabolic disease, and cirrhosis [1–5]. The main active compounds in coffee that play these roles include caffeine, chlorogenic acid, cafestol and kahweol [6,7]. Cafestol and kahweol are natural diterpenes extracted from coffee beans, which mainly present as fatty esters in unfiltered coffee like Turkish coffee [8]. Unfiltered coffee contains 3–6 mg of these diterpenes per cup [9]. The only difference of their structures is that kahweol has an extra double bond [10] (Figure1). In vivo, About 70% of the consumption of cafestol and kahweol can be absorbed in small intestine [11]. In theory, glucuronidation and sulphation are the major pathways of xenobiotic biotransformation in mammalian species, which occurs largely in the liver, to produce water-soluble products that can be excreted by urine [11]. However, only about 1% or less of the consumption was detected to be excreted as conjugate of glucuronic or sulphuric acid in urine in previous studies [11,12]. It indicates that the major part of the absorbed cafestol and kahweol must be subject to more extensive metabolism, not just by glucuronidation or sulphation. There is evidence that cafestol and/or its metabolites largely accumulate in liver and gastrointestinal tract through the enterohepatic cycle [13]; triggering a variety of biological effects, including secondary changes in liver metabolism. Int. J. Mol. Sci. 2019, 20, 4238; doi:10.3390/ijms20174238 www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2019, 20, 4238 2 of 15 Int. J. Mol. Sci. 2019, 20, x FOR PEER REVIEW 2 of 14 1 Early studies confirmedconfirmed that cocoffeeffee diterpenesditerpenes (especially(especially cafestol), eeffectivelyffectively increase humanhuman 2 plasma triacylglycerol and low-density lipoprotein (LDL), may be a potential risk of inducing some 3 cardiovascular diseasesdiseases [7 ,[7,14].14]. However, However, from from a more a more comprehensive comprehensive perspective, perspective, cafestol andcafestol kahweol and 4 showkahweol a remarkable show a remarkable two-faced etwo-facedffect. In addition effect. toIn theaddition deleterious to the eff deleteriousects on serum effects lipid on levels serum and lipid liver 5 enzymeslevels and in someliver enzymes cases, extensive in some studies cases, have extens demonstratedive studies that have cafestol demonstrated and kahweol that exhibit cafestol awide and 6 varietykahweol of pharmacologicalexhibit a wide variety activities, of includingpharmacological anti-inflammatory,anti-angiogenic activities, including anti-inflammatory, and anti-tumorigenic anti- 7 properties.angiogenic Withand multipleanti-tumorigenic bioactivities properties. of cafestol With and multiple kahweol reported,bioactivities the of development cafestol and of potentialkahweol 8 multi-targetreported, the drugs development with diterpenes of potential should multi-target be encouraged. drugs with Therefore, diterpenes it is ofshould great be significance encouraged. to 9 summarizeTherefore, it the is pharmacologicalof great significance and to biological summarize studies the onpharmacological the two compounds, and biological review the studies mechanisms on the 10 behindtwo compounds, the effects, review and get the a comprehensivemechanisms behind picture the of effects, their miscellaneousand get a comprehensive functions. picture of their 11 miscellaneous functions. 12 13 Figure 1.1. Structure and chemicalchemical characteristicscharacteristics of cafestolcafestol andand kaweol.kaweol. They are naturalnatural diterpenesditerpenes 14 extracted from cocoffeeffee beans.beans. 2. Biological and Pharmacological Activities of Cafestol and Kahweol 15 2. Biological and Pharmacological Activities of Cafestol and Kahweol 2.1. Raising Serum Lipid 16 2.1. Raising Serum Lipid Since Thelle et al. first found a positive correlation between coffee consumption and serum 17 concentrationSince Thelle of total et al. cholesterol first found and a triglycerides positive correlation in 1983, many between studies coffee have consumption supported their and findings serum 18 overconcentration the years [15of ].total It is confirmedcholesterol that and long-term triglyceri consumptiondes in 1983, of many unfiltered studies coff eehave will supported effectively causetheir 19 thefindings increase over of the plasma years triacylglycerol [15]. It is confirmed and low-density that long-term lipoprotein consumption (LDL) cholesterol of unfiltered in humans coffee [will14]. 20 Theeffectively two diterpenoids, cause the increase cafestol of plasma and kahweol, triacylglycerol are mainly and responsiblelow-density forlipoprotein this effect. (LDL) Plasma cholesterol lipids, 21 especiallyin humans LDL [14]. cholesterol, The two diterpenoids, are important cafestol factors in and promoting kahweol, the are occurrence mainly responsible of cardiovascular for this diseases. effect. 22 PlasmaIn humans,lipids, especially cafestol LDL appears cholesterol, to be more are important effective on factors elevating in promoting serum lipid the thanoccurrence kahweol. of 23 Meta-analysescardiovascular ofdiseases. observational researches showed that after daily treatment with 10 mg of cafestol for 24 4 weeks,In humans, serum cholesterol cafestol appears increased to be by more 0.13 mmoleffectiveL 1on, while elevating kahweol serum raised lipid that than by kahweol. 0.02 mmol Meta- L 1. 25 · − − LDLanalyses cholesterol of observational accounts researches for about 80% showed of elevated that after serum daily cholesterol. treatment with Similarly, 10 mg the of samecafestol dose for of 4 26 cafestolweeks, serum is more cholesterol effective than increased kahweol by to0.13 increase mmol∙ serumL-1, while triglyceride kahweol levels. raised In that the by test 0.02 of volunteers,mmol L-1. 27 cafestolLDL cholesterol increased accounts serum triglycerides for about 80% by 86%,of elevated but the serum combination cholesterol. of cafestol Similarly, and kahweol the same increased dose of 28 thecafestol response is more only effective 7% higher than than kahweol that of to cafestol increase alone. serum With triglyceride the long-term levels. intake In the of test coff ofee volunteers, diterpenes, 29 mostcafestol of theincreased rising serum triglycerides willby 86%, subside but the [16 ,combination17]. of cafestol and kahweol increased 30 the responseThe metabolism only 7% of LDLhigher is primarily than that mediated of cafe bystol the alone. LDL receptor With the pathway. long-term LDL receptorsintake of locatedcoffee 31 onditerpenes, the cell membranes most of the are rising involved serum in triglycerides the endocytic will process subside of lipoproteins[16,17]. containing apolipoprotein 32 B andThe apolipoprotein metabolism of E, LDL thereby is primarily inducing mediated LDL cholesterol by the toLDL be eliminatedreceptor pathway. from the LDL bloodstream. receptors 33 Somelocated studies on the indicate cell membranes that the LDLare involved receptor mayin the be endocytic the active process site for of cafestol lipoproteins and kahweol containing on 34 apolipoprotein B and apolipoprotein E, thereby inducing LDL cholesterol to be eliminated from the cholesterol-raising effect. In vitro studies suggested that cafestol elevated plasma LDL-cholesterol 35 bloodstream. Some studies indicate that the LDL receptor
Load more

Recommended publications
  • Coffee and Its Effect on Digestion
    Expert report Coffee and its effect on digestion By Dr. Carlo La Vecchia, Professor of Medical Statistics and Epidemiology, Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy. Contents 1 Overview 2 2 Coffee, a diet staple for millions 3 3 What effect can coffee have on the stomach? 4 4 Can coffee trigger heartburn or GORD? 5 5 Is coffee associated with the development of gastric or duodenal ulcers? 6 6 Can coffee help gallbladder or pancreatic function? 7 7 Does coffee consumption have an impact on the lower digestive tract? 8 8 Coffee and gut microbiota — an emerging area of research 9 9 About ISIC 10 10 References 11 www.coffeeandhealth.org May 2020 1 Expert report Coffee and its effect on digestion Overview There have been a number of studies published on coffee and its effect on different areas of digestion; some reporting favourable effects, while other studies report fewer positive effects. This report provides an overview of this body of research, highlighting a number of interesting findings that have emerged to date. Digestion is the breakdown of food and drink, which occurs through the synchronised function of several organs. It is coordinated by the nervous system and a number of different hormones, and can be impacted by a number of external factors. Coffee has been suggested as a trigger for some common digestive complaints from stomach ache and heartburn, through to bowel problems. Research suggests that coffee consumption can stimulate gastric, bile and pancreatic secretions, all of which play important roles in the overall process of digestion1–6.
    [Show full text]
  • Coffee and Liver Diseases
    Fitoterapia 81 (2010) 297–305 Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote Review Coffee and liver diseases Pablo Muriel ⁎, Jonathan Arauz Departamento de Farmacología, Cinvestav-IPN., Apdo. Postal 14-740, México 07000, D.F., Mexico article info abstract Article history: Coffee consumption is worldwide spread with few side effects. Interestingly, coffee intake has Received 26 August 2009 been inversely related to the serum enzyme activities gamma-glutamyltransferase, and alanine Accepted in revised form 25 September 2009 aminotransferase in studies performed in various countries. In addition, epidemiological Available online 13 October 2009 results, taken together, indicate that coffee consumption is inversely related with hepatic cirrhosis; however, they cannot demonstrate a causative role of coffee with prevention of liver Keywords: injury. Animal models and cell culture studies indicate that kahweol, diterpenes and cafestol Coffee (some coffee compounds) can function as blocking agents by modulating multiple enzymes Hepatic injury involved in carcinogenic detoxification; these molecules also alter the xenotoxic metabolism by Fibrosis Cirrhosis inducing the enzymes glutathione-S-transferase and inhibiting N-acetyltransferase. Drinking Cancer coffee has been associated with reduced risk of hepatic injury and cirrhosis, a major pathogenic step in the process of hepatocarcinogenesis, thus, the benefit that produces coffee consumption on hepatic cancer may be attributed to its inverse relation with cirrhosis, although allowance for clinical history of cirrhosis did not completely account for the inverse association. Therefore, it seems to be a continuum of the beneficial effect of coffee consumption on liver enzymes, cirrhosis and hepatocellular carcinoma. At present, it seems reasonable to propose experiments with animal models of liver damage and to test the effect of coffee, and/or isolated compounds of this beverage, not only to evaluate the possible causative role of coffee but also its action mechanism.
    [Show full text]
  • Cafestol That Raises Serum Cholesterol in Humans
    Human Nutrition and Metabolism Coffee Oil Consumption Increases Plasma Levels of 7␣-Hydroxy-4- cholesten-3-one in Humans1 Mark V. Boekschoten,*†2 Maaike K. Hofman,*,** Rien Buytenhek,** Evert G. Schouten,* Hans M. G. Princen,** and Martijn B. Katan*† *Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; †Wageningen Centre for Food Sciences, Wageningen, The Netherlands; and **TNO Prevention & Health, Gaubius Laboratory, Leiden, The Netherlands ABSTRACT Unfiltered coffee brews such as French press and espresso contain a lipid from coffee beans named cafestol that raises serum cholesterol in humans. Cafestol decreases the expression and activity of cholesterol 7␣-hydroxylase, the rate-limiting enzyme in the classical pathway of bile acid synthesis, in cultured rat hepatocytes and livers of APOE3Leiden mice. Inhibition of bile acid synthesis has been suggested to be responsible for the cholesterol-raising effect of cafestol. Therefore, we assessed whether cafestol decreases the activity of cholesterol ␣ ␣ 7 -hydroxylase in humans. Because liver biopsies were not feasible, we measured plasma levels of 7 -hydroxy- Downloaded from 4-cholesten-3-one, a marker for the activity of cholesterol 7␣-hydroxylase in the liver. Plasma 7␣-hydroxy-4- cholesten-3-one was measured in 2 separate periods in which healthy volunteers consumed coffee oil containing cafestol (69 mg/d) for 5 wk. Plasma levels of 7␣-hydroxy-4-cholesten-3-one increased by 47 Ϯ 13% (mean Ϯ SEM, n ϭ 38, P ϭ 0.001) in the first period and by 23 Ϯ 10% (n ϭ 31, P ϭ 0.03) in the second treatment period. Serum cholesterol was raised by 23 Ϯ 2% (P Ͻ 0.001) in the first period and by 18 Ϯ 2% (P Ͻ 0.001) in the second period.
    [Show full text]
  • Roles of Xenobiotic Receptors in Vascular Pathophysiology Lei Xiao, Phd; Zihui Zhang, Bsc; Xiaoqin Luo, Phd
    1520 XIAO L et al. Circulation Journal REVIEW Official Journal of the Japanese Circulation Society http://www.j-circ.or.jp Roles of Xenobiotic Receptors in Vascular Pathophysiology Lei Xiao, PhD; Zihui Zhang, BSc; Xiaoqin Luo, PhD The pregnane X receptor (PXR) and constitutive androstane receptor (CAR), 2 closely related and liver-enriched members of the nuclear receptor superfamily, and aryl hydrocarbon receptor (AhR), a nonnuclear receptor transcrip- tion factor (TF), are major receptors/TFs regulating the expression of genes for the clearance and detoxification of xenobiotics. They are hence defined as “xenobiotic receptors”. Recent studies have demonstrated that PXR, CAR and AhR also regulate the expression of key proteins involved in endobiotic responses such as the metabolic ho- meostasis of lipids, glucose, and bile acid, and inflammatory processes. It is suggested that the functions of PXR, CAR and AhR may be closely implicated in the pathogeneses of metabolic vascular diseases, such as hyperlipid- emia, atherogenesis, and hypertension. Therefore, manipulation of the activities of these receptors may provide novel strategies for the treatment of vascular diseases. Here, we review the pathophysiological roles of PXR, CAR and AhR in the vascular system. (Circ J 2014; 78: 1520 – 1530) Key Words: Aryl hydrocarbon receptor; Constitutive androstane receptor; Pregnane X receptor; Vascular diseases he circulation system is the major organ exposed to for- ly expressed in liver and intestine and mainly function to cata- eign substances, or “xenobiotics”, as well as endog- lyze the first step of detoxification.9,10 Phase II conjugation T enous chemicals, or endobiotics, during metabolic ho- reactions are catalyzed by a large group of transferases, such meostasis.
    [Show full text]
  • Clinical Correlates in Drug-Herbal Interactions Mediated Via Nuclear Receptor PXR Activation and Cytochrome P450 Induction
    J Endocrinol Reprod 12 (2008) 1: 1-12 Review Article Clinical correlates in drug-herbal interactions mediated via nuclear receptor PXR activation and cytochrome P450 induction Seema Negi1, Mohammad A. Akbarsha2 and Rakesh K. Tyagi1 1Special Centre for Molecular Medicine, Jawaharlal Nehru University New Delhi – 110067, India 2Department of Animal Science, School of Life Sciences, Bharathidasan University Tiruchirappalli - 620 024, India This article is dedicated to the memory of Late Prof. Ben M.J. Pereira of Indian Institute of Technology, Roorkee, who had been actively associated with SRBCE and the Journal of Endocrinology and Reproduction Summary Pregnane and Xenobiotic Receptor (PXR), a vital xenosensor, acts as master regulator of phase-I (cytochrome P450) and phase-II enzymes (glutathione S-transferases, sulfotransferases, and uridine 5’-diphosphate glucuronosyltransferases) as well as several drug transporters (multi-drug resistance protein, and multi- drug resistance-associated protein). PXR can bind to a variety of chemically distinct endobiotics (steroids, bile acids and their derivatives, vitamins, etc.) and xenobiotics (prescription drugs, herbal medicines, endocrine disruptors, etc.). Activation of PXR by various compounds leads to trans-activation of PXR- target genes involved in detoxification system (phase-I and phase-II enzymes, and efflux proteins). Herbal medicines are readily used without prescription under the belief that anything natural is safe. These medicines contain active chemical constituents which execute distinctly different or similar pharmacological response(s). But, like prescription drugs, herbal drugs also have both therapeutic and, sometimes, adverse effects. Some of the herbal drugs induce drug metabolizing enzymes (especially CYP3A4) and drug efflux proteins via activation of PXR. Phase-I enzyme CYP3A4 is involved in the metabolism of 50-60% of clinical drugs as well as the chemical ingredients in herbal medicines.
    [Show full text]
  • Physiological Effects of Caffeine and Its Congeners Present in Tea And
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 2 August 2018 doi:10.20944/preprints201808.0032.v1 1 Type of the paper: Review 2 3 Physiological effects of caffeine and its congeners 4 present in tea and coffee beverages 5 6 I. Iqbal1, M. N. Aftab2, M. A. Safer3, M. Menon4, M. Afzal5⌘ 7 1Department of Life Sciences, Lahore College for Women, Lahore, Pakistan 8 2Institute of Biochemistry and Biotechnology, Government College University, 9 Lahore 54000, Pakistan 10 3Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait 11 4Plamer University (West Campus) San Jose, CA 12 5Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait 13 ⌘ Correspondence: [email protected], Tel. +1 352 681 7347 14 15 16 Running title: Caffeine 17 18 19 20 21 22 23 Corresponding author: 24 M. Afzal, 25 10547 NW 14th PL. 26 Gainesville, FL. USA 27 email: [email protected] 28 Tel. +1 352 681 7347 29 30 1 © 2018 by the author(s). Distributed under a Creative Commons CC BY license. Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 2 August 2018 doi:10.20944/preprints201808.0032.v1 31 Abstract: Tea and coffee are the most commonly used beverages throughout the 32 world. Both decoctions are rich in small organic molecules such as 33 phenolics/polyphenolics, purine alkaloids, many methylxanthines, substituted 34 benzoic and cinnamic acids. Many of these molecules are physiologically 35 chemopreventive and chemoprotective agents against many severe conditions such 36 as cancer, Alzheimer, Parkinsonism, inflammation, sleep apnea, cardiovascular 37 disorders, bradycardia, fatigue, muscular relaxation, and oxidative stress.
    [Show full text]
  • Enrichment of Diterpenes in Green Coffee Oil Using Supercritical fluid
    J. of Supercritical Fluids 95 (2014) 137–145 Contents lists available at ScienceDirect The Journal of Supercritical Fluids j ournal homepage: www.elsevier.com/locate/supflu Enrichment of diterpenes in green coffee oil using supercritical fluid extraction – Characterization and comparison with green coffee oil from pressing a a Paola Maressa Aparecida de Oliveira , Rafael Henrique de Almeida , a b a Naila Albertina de Oliveira , Stephane Bostyn , Cintia Bernardo Gonc¸ alves , a,∗ Alessandra Lopes de Oliveira a Departamento de Engenharia de Alimentos, Universidade de São Paulo, Av Duaue de Caxias Norte 225, Caixa Postal 23, CEP 13635-900 Pirassununga, Sao Paulo, Brazil b Institut de Combustion, Aérothermique, Réactivité, et Environnement (ICARE) 1C, Avenue de la recherche scientifique, 45071 Orléans cedex 2, France a r t a b i c l e i n f o s t r a c t Article history: Supercritical fluid extraction (SFE) was used to obtain green coffee oil (Coffea arabica, cv. Yellow Catuaí) Received 1 May 2014 enriched in the diterpenes, cafestol and kahweol. To obtain diterpenes-enriched green coffee oil relevant Received in revised form 12 August 2014 for pharmaceuticals, a central composite rotational design (CCRD) was used to optimize the extraction Accepted 15 August 2014 process. In this study, pressure and temperature did not have influences on cafestol and kahweol con- Available online 23 August 2014 centrations, but did affect the total phenolic content (TPC), which ranged from 0.62 to 2.62 mg GAE/g of the oil. The analysis and quantification of diterpenes according to gas chromatography indicated that Keywords: green coffee oil from SFE presented a cafestol content of 50.2 and a kahweol content of 63.8 g/kg green Cafestol Kahweol coffee oil under optimal conditions.
    [Show full text]
  • Cafestol [CASRN 469-83-0] and Kahweol [CASRN 6894-43-5]
    Cafestol [CASRN 469-83-0] and Kahweol [CASRN 6894-43-5] Review of Toxicological Literature Prepared for Scott Masten, Ph.D. National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, North Carolina 27709 Contract No. N01-ES-65402 Submitted by Raymond Tice, Ph.D. Integrated Laboratory Systems P.O. Box 13501 Research Triangle Park, North Carolina 27709 October 1999 TOXICOLOGICAL SUMMARY FOR CAFESTOL AND KAHWEOL 10/99 EXECUTIVE SUMMARY Cafestol was nominated by a private individual for toxicity and carcinogenicity testing based on an association between exposure and elevated cholesterol levels in humans coupled with the potential to activate the nuclear receptor FXR. Significant exposure to the substance occurs through consumption of coffee. Kahweol, a structurally similar compound also in coffee and found to cause a rise in cholesterol concentrations, has been included in the nomination for testing. Global coffee production comes from mainly two species, Coffea arabica and Coffea robusta. Cafestol and kahweol, which are naturally occurring diterpenes found only in coffee, are present in the unsaponifiable lipid fraction. Their content in a coffee drink is influenced by the brew method; brewing releases oil droplets containing cafestol and kahweol from the ground coffee beans. Boiled coffee, such as Scandinavian-style and Turkish-style, contains the highest concentrations, while instant, drip-filtered, and percolated coffee brews contain negligible amounts. Many uses have been patented for cafestol and kahweol. Coffee bean oil, which contains both compounds, has been reported useful as a sun filter. In combination with a cosmetically or pharmaceutically acceptable carrier, topical compositions containing an effective amount of cafestol have been patented for the prevention or treatment of various skin conditions.
    [Show full text]
  • Open Rodrigues Dissertation 10 28 05.Pdf
    The Pennsylvania State University The Graduate School College of Health and Human Development EFFECTS OF CAFFEINE, STRESS, AND FAMILY HISTORY OF HYPERTENSION ON BLOOD PRESSURE AND BLOOD MARKERS OF CARDIOVASCULAR DISEASE RISK A Thesis in Biobehavioral Health by Isabella M. Rodrigues © 2005 Isabella M. Rodrigues Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December 2005 ii The thesis of Isabella M. Rodrigues was reviewed and approved* by the following: Laura Cousino Klein Associate Professor of Biobehavioral Health Thesis Advisor Chair of Committee Frank M. Ahern Senior Research Associate Department of Biobehavioral Health Lynn T. Kozlowski Professor of Biobehavioral Health Head of the Department of Biobehavioral Health Robert M. Stern Distinguished Professor of Psychology *Signatures are on file in the Graduate School iii ABSTRACT Cardiovascular disease has been the leading cause of death in the United States since 1918. A number of studies have investigated the connection between caffeine, primarily through coffee, and its potentially detrimental effects on cardiovascular health. The vast majority of such investigations have been focused on blood cholesterol, while other blood markers of cardiovascular disease such as fibrinogen and C-reactive protein and their relationship with caffeine has been vastly understudied. A large number of studies have reported that both fibrinogen and C-reactive protein can be useful predictors of future cardiovascular disease, but their relationship with caffeine remains unknown. Furthermore, to this date, no published studies have reported on the effects of psychological stress on these blood markers, either alone, or in combination with caffeine, and no gender differences have been reported.
    [Show full text]
  • Drinking Coffee, Mate, and Very Hot Beverages Volume 116
    DRINKING COFFEE, MATE, AND VERY HOT BEVERAGES VOLUME 116 This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 24–31 May 2016 LYON, FRANCE - 2018 IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC RISKS TO HUMANS 4. MECHANISTIC AND OTHER RELEVANT DATA 4.1 Toxicokinetic data in a randomized, double-blind, single-dose, placebo-controlled, study of caffeine pharmaco- 4.1.1 Humans kinetics in 8 men and 5 women characterized (a) Absorption as regular coffee and cola consumers (1 smoker) (Liguori et al., 1997). (i) Caffeine Studies in humans given caffeine added to Table 4.1 (web only; available at: http:// decaffeinated instant coffeeGelal ( et al., 2003) publications.iarc.fr/566) summarizes pharmaco- or caffeine as a capsule or gum Kaplan( et al., kinetics parameters maximum plasma concen- 1997; Kamimori et al., 2002; Skinner et al., 2014) tration (Cmax), time to peak concentration (Tmax), reported rapid, dose-dependent absorption. and the area under the curve (AUC) of caffeine An in vitro study using human skin from studies in humans. membrane [of less relevance to pharmacokinetics Several studies in humans have shown rapid of caffeine from coffee] demonstrated absorption and dose-dependent absorption of caffeine in of caffeine (100 µg/m2) with time to maximum subjects administered coffee. Coffee consump- rate of 1.2 ± 0.2 hour to 5.2 ± 1.2 hour (van de tion significantly increased caffeine in plasma Sandt et al., 2004). in a single-blind, three-stage clinical trial of 11 (ii) Phenolic acids men and 36 women, all regular coffee consumers (4.0 ± 1.7 cups/day) who had abstained from coffee Table 4.2 (web only; available at: http:// consumption for 1 month (Kempf et al., 2010).
    [Show full text]
  • WO 2010/067327 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 17 June 2010 (17.06.2010) WO 2010/067327 Al (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, C08B 37/00 (2006.01) A61K 8/73 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/IB2009/055663 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 10 December 2009 (10.12.2009) NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (25) Filing Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 0858501 11 December 2008 ( 11.12.2008) FR GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, (71) Applicant (for all designated States except US): SEDER- TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, MA [FR/FR]; 29 rue du Chemin Vert, F-78610 Le Perray ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, en Yvelines (FR).
    [Show full text]
  • Elucidating the Mechanism Behind the Lipid-Raising Effect of Cafestol Boekschoten, Mark, Vincent
    Elucidating the mechanism behind the lipid-raising effect of cafestol Mark Boekschoten Promotor: Prof. Dr. M.B. Katan Persoonlijk hoogleraar bij de afdeling Humane Voeding, Wageningen Universiteit Co-promotor: Dr. Ir. G.J.E.J. Hooiveld Wetenschappelijk medewerker bij de afdeling Humane Voeding, Wageningen Universiteit Promotiecommissie: Prof. Dr. M.H. Hofker Universiteit Maastricht Prof. Dr. R.P. Mensink Universiteit Maastricht Prof. Dr. R.P.J. Oude Elferink Universiteit van Amsterdam Prof. Dr. E.G. Schouten Wageningen Universiteit Prof. Dr. S.C. de Vries Wageningen Universiteit Dit onderzoek is uitgevoerd binnen de onderzoekschool VLAG. Elucidating the mechanism behind the lipid-raising effect of cafestol Mark Boekschoten Proefschrift ter verkrijging van de graad van doctor op gezag van de rector magnificus van Wageningen Universiteit, Prof. Dr. Ir. L. Speelman, in het openbaar te verdedigen op woensdag 10 november 2004 des namiddags te vier uur in de Aula. Elucidating the mechanism behind the lipid-raising effect of cafestol Boekschoten, Mark, Vincent. Thesis Wageningen University. –With ref. –With summary in Dutch. ISBN 90-8504-113-9 2004 Boekschoten Abstract Elucidating the mechanism behind the lipid-raising effect of cafestol PhD thesis by Mark Boekschoten, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands The objective of this thesis was to identify genes that control the response of serum lipid levels to diet. To this end we used cafestol as model substance for a food component that affects serum lipids and therefore health. Cafestol is a cholesterol-raising diterpene present in coffee beans and unfiltered coffee types. A possible explanation for the cholesterol-raising effect of cafestol is inhibition of bile acid synthesis.
    [Show full text]