Coffee Components Research Articles

Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Benefits in Alzheimer's Mice

Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.

Finite element simulation for coffee (Coffea arabica) drying

This paper describes moisture diffusivity, shrinkage, equilibrium moisture content and finite element simulated drying of coffee. The moisture diffusivities in different components of parchment coffee were determined by minimizing the sum of square of deviations between the predicted and the experimental values of moisture contents during thin layer drying under controlled conditions of drying air temperature and relative humidity. The drying of coffee bean and parchment was conducted in thin layers at a temperature of 40, 50 and 60°C with relative humidity in the range of 14–25%. The mean diffusivity values of coffee bean and parchment are related to the temperatures and are expressed by Arrhenius-type equations. The moisture diffusivities of parchment are lower than those of the coffee bean. The shrinkage of coffee bean derived from experiments is expressed as a function of moisture reduction. GAB model is sufficient for the prediction for sorption isotherm of parchment coffee and the parameters of the GAB model are a function of temperature and it is expressed by Arrhenius-type equations. Sensory evaluation of the coffee dried at 40, 50 and 60°C shows that the overall acceptance by coffee cupping test and the concentration of caffeine is within the acceptable limit. A two-dimensional finite element model was developed for simulate moisture diffusion during drying process of parchment coffee. The finite element model was programmed in Compaq Visual FORTRAN version 6.5. The model simulates the moisture contents in different components of parchment coffee well and it provides a better understanding of the transport processes in the different components of the parchment coffee.

Coffee Consumption and Prostate Cancer Risk and Progression in the Health Professionals Follow-up Study

Coffee contains many biologically active compounds, including caffeine and phenolic acids, that have potent antioxidant activity and can affect glucose metabolism and sex hormone levels. Because of these biological activities, coffee may be associated with a reduced risk of prostate cancer. We conducted a prospective analysis of 47,911 men in the Health Professionals Follow-up Study who reported intake of regular and decaffeinated coffee in 1986 and every 4 years thereafter. From 1986 to 2006, 5035 patients with prostate cancer were identified, including 642 patients with lethal prostate cancers, defined as fatal or metastatic. We used Cox proportional hazards models to assess the association between coffee and prostate cancer, adjusting for potential confounding by smoking, obesity, and other variables. All P values were from two-sided tests. The average intake of coffee in 1986 was 1.9 cups per day. Men who consumed six or more cups per day had a lower adjusted relative risk for overall prostate cancer compared with nondrinkers (RR = 0.82, 95% confidence interval [CI] = 0.68 to 0.98, P(trend) = .10). The association was stronger for lethal prostate cancer (consumers of more than six cups of coffee per day: RR = 0.40, 95% CI = 0.22 to 0.75, P(trend) = .03). Coffee consumption was not associated with the risk of nonadvanced or low-grade cancers and was only weakly inversely associated with high-grade cancer. The inverse association with lethal cancer was similar for regular and decaffeinated coffee (each one cup per day increment: RR = 0.94, 95% CI = 0.88 to 1.01, P = .08 for regular coffee and RR = 0.91, 95% CI = 0.83 to 1.00, P = .05 for decaffeinated coffee). The age-adjusted incidence rates for men who had the highest (≥6 cups per day) and lowest (no coffee) coffee consumption were 425 and 519 total prostate cancers, respectively, per 100 000 person-years and 34 and 79 lethal prostate cancers, respectively, per 100 000 person-years. We observed a strong inverse association between coffee consumption and risk of lethal prostate cancer. The association appears to be related to non-caffeine components of coffee.

C8H10O2H4섭취량에 의한 조음기관의 변화 요소 분석 연구

현대사회에서 일에 대한 스트레스, 여가 생활, 기호 식품에 대한 매력 등이 증가되면서 커피를 즐겨 마시는 사람들이 늘고 있다. 커피는 품종, 가공방법, 원두의 혼합여부 및 인위적인 향의 첨가여부 등에 따라 다양한 종류로 현대인의 입맛을 사로잡고 있다. 그러나 대부분의 커피에는 <TEX>$C_8H_{10}O_2N_4$</TEX> 함유되어 있고 이로 인해 인체의 여러부위에 영향을 미치고 있다. 이러한 <TEX>$C_8H_{10}O_2N_4$</TEX>이 커피의 주성분인 카페인이다. 따라서 본 논문에서는 블랙커피 한 잔에 함유되어 있는 <TEX>$C_8H_{10}O_2N_4$</TEX> 250mg에 대해 섭취량이 증가할 때마다 조음기관에 미치는 영향을 분석하였다. 이를 위해 20대 남성 30명을 대상으로 <TEX>$C_8H_{10}O_2N_4$</TEX> 섭취량을 점차 늘라면서 이에 대해 반응하는 조음기관의 변화를 음성 분석 요소인 Jitter, Formant 및 Spectrum을 적용하여 결과값을 추출하고 이를 분석하는 연구를 수행하였다. The people frequently drink coffee under stress at work, according to increase attractive of leisure activities, favourite food in modern society. The coffee taste which we are catching the taste of modern people is depending on various kinds processing methods such as a mixture of beans. However, the most coffee contains <TEX>$C_8H_{10}O_2N_4$</TEX> which affected various parts of the body. These <TEX>$C_8H_{10}O_2N_4$</TEX>, is that the main component of coffee is caffeine. Therefore, in this paper, we are analyzed influence about articulator according to increase in <TEX>$C_8H_{10}O_2N_4$</TEX> 250mg contains a cup of coffee. From this, we gradually increased the amount of <TEX>$C_8H_{10}O_2N_4$</TEX> intake about thirty persons of men in his 20's in experiments. Then we performed a study about Jitter, Formant, Spectrum in voice analysis parameter by applying the results having an affect articulator.

Identification of H2O2 as a major antimicrobial component in coffee

Coffee shows distinct antimicrobial activity against several bacterial genera. The present study investigated molecular mechanisms and active ingredients mediating the antimicrobial effect of coffee. Depending on concentration, roasted, but not raw coffee brew inhibited the growth of Escherichia coli and Listeria innocua. Several coffee ingredients with known antibacterial properties were tested for their contribution to the observed effect. In natural concentration, caffeine, ferulic acid and a mixture of all test compounds showed very weak, but significant activity, whereas trigonelline, 5-(hydroxymethyl)furfural, chlorogenic acid, nicotinic acid, caffeic acid, and methylglyoxal were not active. Antimicrobial activity, however, was completely abolished by addition of catalase indicating that H(2)O(2) is a major antimicrobial coffee component. In accordance with this assumption, bacterial counts during 16 h of incubation were inversely related to the H(2)O(2) concentration in the incubation solution. Pure H(2)O(2) showed slightly weaker activity. The H(2)O(2) dependent antimicrobial activity of coffee could be mimicked by a reaction mixture of d-ribose and l-lysine (30 min 120 °C) indicating that H(2)O(2) is generated in the coffee brew by Maillard reaction products. Identification of H(2)O(2) as major antimicrobial coffee component is important to evaluate the application of coffee or coffee extracts as natural preservatives.

Influence of Coffee Intake on Urinary Hippuric Acid Concentration

Intake of foods and drinks containing benzoic acid influences the urinary hippuric acid (HA) concentration, which is used to monitor toluene exposure in Japan. Therefore, it is necessary to control the intake of benzoic acid before urine collection. Recently, some reports have suggested that components of coffee, such as chlorogenic, caffeic, and quinic acids are metabolized to HA. In this study, we evaluated the influence of coffee intake on the urinary HA concentration in toluene-nonexposed workers who had controlled their benzoic acid intake, and investigated which components of coffee influenced the urinary HA concentration. We collected urine from 15 healthy men who did not handle toluene during working hours, after they had consumed coffee, and we measured their urinary HA concentrations; the benzoic acid intake was controlled in these participants during the study period. The levels of chlorogenic, caffeic, and quinic acids in coffee were analyzed by LC-MS/MS. Urinary HA concentration increased significantly with increasing coffee consumption. Spectrophotometric LC-MS/MS analysis of coffee indicated that it contained chlorogenic and quinic acids at relatively high concentrations but did not contain benzoic acid. Our findings suggest that toluene exposure in coffee-consuming workers may be overestimated.

Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on incretin hormones

Coffee consumption is associated with a lower risk of type 2 diabetes. We tested the hypothesis that this is mediated by incretin hormones by measuring the acute effects of decaffeinated coffee and coffee components on GLP-1 and GIP concentrations. A randomized cross-over trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo on total and intact GLP-1 and GIP concentrations during an oral glucose tolerance test took place in fifteen overweight men. No treatment significantly affected the overall GLP-1 or GIP secretion pattern following an OGTT relative to placebo. Decaffeinated coffee slightly increased total GLP-1 concentration 30 minutes after ingestion (before the OGTT) relative to placebo (2.7 pmol/L, p = 0.03), but this change did not correspond with changes in glucose or insulin secretion. These findings do not support the hypothesis that coffee acutely improves glucose tolerance through effects on the secretion of incretin hormones. Chronic effects of coffee and its major components still need to be investigated.

Analysis of Iodine-like (Chlorine) Flavor-causing Components in Brazilian Coffee with Rio Flavor

Green beans and roasted beans of coffee with Rio flavor were analyzed by gas chromatography-olfactometry to clarify the causal substances of Rio flavor in Brazilian coffee. In addition to 2,4,6-trichloroanisole (TCA) and 2,4,6-trichlorophenol (TCP), which are known as the main causal substances of Rio flavor, a new iodine-like flavor-causing compound, 2,6-dichlorophenol (DCP), was detected. The detected amounts of 2,6-DCP and 2,4,6-TCA were less than 0.1 and 0.1 ppb in Rio flavor-free coffee beans, 0.8 and 1.2 ppb in weak Rio flavored beans, and 3.0 and 2.6 ppb in strong Rio flavored beans, respectively. Musty and chlorine flavors were sensed more strongly in model coffee containing both 2,4,6-TCA and 2,6-DCP than in the coffee containing them individually. In the present study, 2,6-DCP was identified as a new causal substance of Rio flavor, and it was found that the presence of 2,4,6-TCA intensifies Rio flavor, as a synergy effect.

Influences of pH and temperature on infrared spectroscopic features of brewed coffee

We developed an infrared spectroscopic evaluation method of brewed coffee, whose quality and taste highly depend on the chemical contents, the interactions between the components, the pH value and the temperature, using a Fourier transform infrared (FT-IR) spectrometer equipped with an attenuated total reflection (ATR) accessory. The objective of this study is to understand the influences of the pH values and temperature on the spectral features of brewed coffee and the main components, since the component balances of the organic acids originating from coffee beans and being produced during processes such as roasting and extraction could closely relate to the brewed coffee characteristics. The absorption peak sifts of the ATR spectra of brewed coffee were observed as the influences of the pH and temperatures. Therefore, by analyzing the spectra of the coffee components under the various pH and temperature conditions based on the ionic dissociation equilibrium theory, the spectral behavior of the brewed coffee model due to the pH and temperature changes could mainly result from those of the organic acids as the main components. Consequently, the infrared spectral information analysis would be acceptable as a new method to evaluate a profile of brewed coffee for the quality evaluation relating to the taste and the non-intensive on-line monitoring of the coffee process.

First identification of dimethoxycinnamic acids in human plasma after coffee intake by liquid chromatography–mass spectrometry

There is a substantial amount of published literature on the bioavailability of various coffee components including the most abundant metabolites, caffeic and ferulic acids. Surprisingly, to date, the appearance of dimethoxycinnamic acid derivatives in humans has not been reported despite the fact that methylated form of catechol-type polyphenols could help maintain, modify or even improve their biological activities. This study reports an LC–MS method for the detection of dimethoxycinnamic acid in human plasma after treatment with an esterase. Liquid chromatography, including the combination of methanol and acetonitrile as organic eluent, was optimized to resolve all interferences and enable reliable detection and identification of 3,4-dimethoxycinnamic and 3,4-dimethoxy-dihydrocinnamic acids. In addition to the good mass accuracy achieved (better than 5ppm), tandem mass spectrometric and co-chromatography experiments further confirmed the identity of the compounds. The optimized method was applied to analyze samples obtained immediately, 1 and 10h after coffee ingestion. The results show that in particular 3,4-dimethoxycinnamic acid appears in high abundance (∼380nM at 60min) in plasma upon coffee intake, indicating that it is important to consider these derivatives in future bioavailability and bioefficacy studies.

Kaffee und Diabetes

Lack of physical activity and high caloric diet are main causes for increasing diabetes prevalence. Thus, it is possible to influence blood glucose levels by lifestyle modifications. Coffee is an important lifestyle factor in Germany with a mean consumption of about 150 litres per inhabitant. It is important to know that coffee cannot be equated with caffeine. Scientific investigations have shown that caffeine can temporarily have a negative impact on cardiovascular risk factors but does not promote development of cardiovascular events. On the other hand, several international prospective studies demonstrate a protective effect of coffee on the development of type 2 diabetes as coffee consumption can reduce glucose uptake. Coffee components, e.g. chlorogenic acid, play a central role, as they can inhibit oxidative stress and inflammation in addition. In the context of lifestyle tasks coffee consumption therefore is an additional option for modifying diabetes risk.

Coffee Reduces Liver Damage in a Rat Model of Steatohepatitis: The Underlying Mechanisms and the Role of Polyphenols and Melanoidins

Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70-kg person) were added for 8 weeks to the drinking water of rats who were being fed a high-fat, high-calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two-fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF-α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF-α and interferon-γ and increased anti-inflammatory interleukin-4 and interleukin-10. Our data demonstrate that coffee consumption protects the liver from damage caused by a high-fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β-oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation.

Coffee consumption but not green tea consumption is associated with adiponectin levels in Japanese males

Coffee is among the most widely consumed beverages in the world. Numerous epidemiological studies have reported a significant inverse association between coffee consumption and risk of type 2 diabetes mellitus, but the underlying mechanisms are still not fully understood. Therefore, we conducted an epidemiological study to clarify the relationship between coffee consumption and adiponectin levels in Japanese males. We also evaluated whether green tea consumption affected adiponectin levels. We carried out a cross-sectional study. The subjects were 665 male employees in Japan. Coffee consumption was assessed, using a self-administered questionnaire, as the number of times per week and cups per day respondents drank, and subjects were grouped into four levels (non, 1-5times/week, 1-2cups/day and ≥3cups/day). The means of adiponectin levels were positively associated with coffee consumption. A dose-response relationship was found between coffee consumption and circulating adiponectin levels. The relationship remained significant after adjustment for potential confounding factors (P for trend <0.05). However, green tea consumption was not significantly associated with adiponectin levels (P for trend=0.90). We not only revealed that habitual coffee consumption is associated with higher adiponectin levels in Japanese males but also found a dose-dependent association between coffee consumption and adiponectin levels. Therefore, our study suggested that coffee components might play an important role in the elevation of adiponectin level.

Formation of Volatile Chemicals from Thermal Degradation of Less Volatile Coffee Components: Quinic Acid, Caffeic Acid, and Chlorogenic Acid

The less volatile constituents of coffee beans (quinic acid, caffeic acid, and chlorogenic acid) were roasted under a stream of nitrogen, air, or helium. The volatile degradation compounds formed were analyzed by gas chromatography and gas chromatography-mass spectrometry. Caffeic acid produced the greatest amount of total volatiles. Quinic acid and chlorogenic acid produced a greater number of volatiles under the nitrogen stream than under the air stream. These results suggest that the presence of oxygen does not play an important role in the formation of volatile compounds by the heat degradation of these chemicals. 2,5-Dimethylfuran formed in relatively large amounts (59.8-2231.0 microg/g) in the samples obtained from quinic acid and chlorogenic acid but was not found in the samples from caffeic acid. Furfuryl alcohol was found in the quinic acid (259.9 microg/g) and caffeic acid (174.4 microg/g) samples roasted under a nitrogen stream but not in the chlorogenic sample. The three acids used in the present study do not contain a nitrogen atom, yet nitrogen-containing heterocyclic compounds, pyridine, pyrrole, and pyrazines, were recovered. Phenol and its derivatives were identified in the largest quantities. The amounts of total phenols ranged from 60.6 microg/g (quinic acid under helium) to 89893.7 microg/g (caffeic acid under helium). It was proposed that phenol was formed mainly from quinic acid and that catechols were formed from caffeic acid. Formation of catechol from caffeic acid under anaerobic condition indicates that the reaction participating in catechol formation was not oxidative degradation.

In vitro effect of coffee on oral malodor-related parameters

In the present investigation we examined the effect of three brands of coffee on microbial volatile sulfur compound (VSC) production using a decarboxylase incubation assay. Stimulated whole saliva was added to decarboxylase medium supplemented with 0.005% hemin. Incubation was carried out anaerobically for 72 h in the presence of powdered coffee at concentrations ranging from 0.5 to 2.0% (w/v), as compared with appropriate controls. VSC levels were determined using OralChroma™ and Halimeter™ and malodor was scored by an experienced odor judge. Experimental biofilm was grown with or without coffee and examined for VSC-producing bacteria using confocal laser scanning microscopy. Results showed that VSC and malodor levels were decreased by 85% in the presence of 2% coffee. The data suggest that coffee components reduce malodor production, VSC levels and experimental biofilm VSC-producing bacteria in vitro.

Activity-Guided Fractionation to Characterize a Coffee Beverage that Effectively Down-Regulates Mechanisms of Gastric Acid Secretion as Compared to Regular Coffee

In some individuals, the consumption of coffee beverages is related to symptoms of gastric irritation. Hot water steam-treatment of raw coffee beans is hypothesized to reduce the contents of stomach irritating compounds, and products to which this technology is applied are launched as stomach-friendly coffee. However, data on the effect of steam-treated coffee on gastric acid secretion are conflicting and it has not been proven yet as to which coffee components act as pro- or antisecretory stimulants. The work presented here aimed at the characterization of a coffee beverage that effectively down-regulates mechanisms of proton secretion in human gastric cells (HGT-1). At first, a regular coffee beverage was fractionated by using solvents of different polarity: water, ethylacetate, dichloromethane, and pentane. Functional assays on the proton secretory activity (PSA) of these solvent fractions revealed the least pronounced effect for the water fraction, for which quantitative analyses demonstrated the highest distribution of chlorogenic acid (95%), (beta)N-alkanoyl-5-hydroxytryptamides (55%), and N-methylpyridinium (N-MP, >99%) among all fractions. Following experiments demonstrated that HGT-1 cells treated with regular coffee fortified with N-MP at a concentration of about 20 mg/mL N-MP showed a significantly decreased PSA as compared to cells which were exposed to coffee beverages containing higher (32-34 mg/L) or lower (5 mg/L) N-MP concentrations. Results from cellular pathway analyses of transcription (ATF-1 and Akt1) and signaling (cAMP and EGFr) factors and kinases (ERK1/2), and experiments on the gene expression of pro (histamine-HRH2 and acetylcholine-CHRM3)- and anti (somatostatin-SSTR1)-secretory receptors and H(+),K(+)-ATPase verified this antisecretory activity of N-MP in coffee beverages.

Determination of coffee origins by integrated metabolomic approach of combining multiple analytical data

The flavor and taste of coffee are the most important criteria for evaluating its quality and they are influenced by environmental as well as genetic factors. Because of these factors, including soil, climate and species, diverse components of coffee have been developed. To observe the variation of coffee components by region, a metabolomic approach was applied. In this study, 21 coffee samples of different origin were analyzed by various measuring devices. The acquired data was then integrated and processed by principal component analysis (PCA) using SAS 9.1 software. We found that we could successfully identify the origins of the coffee, dividing the samples in the regions of Asia, South America, and Africa, using the integrated metabolomic approach of combining diverse analytical data with multivariate analysis. In particular, the enhancement of subtle differences by combining data from several instruments resulted in the accurate discrimination of coffee origins.

Measurement of the Intracellular pH in Human Stomach Cells: A Novel Approach To Evaluate the Gastric Acid Secretory Potential of Coffee Beverages

As the consumption of coffee beverages sometimes is reported to cause gastric irritation, for which an increased stomach acid secretion is one of the promoting factors, different processing technologies such as steam-treatment have been developed to reduce putative stomach irritating compounds. There is evidence-based data neither on the effect of detailed processing variations nor on individual coffee components affecting the proton secretory activity (PSA). This work aimed at developing a screening model suitable for investigating the effects of commercial coffee beverages and components thereof on human parietal cells. Human gastric cancer cells (HGT-1) were treated with reconstituted freeze-dried coffee beverages prepared from customary coffee products such as regular coffee (RC, n = 4), mild bean coffee (MBC, n = 5), stomach friendly coffee (SFC, n = 4), and SFC decaffeinated (SFCD, n = 3). PSA was analyzed by flow cytometry using the pH-sensitive dye SNARF-AM. Treatment of the cells with MBC did not result in a PSA different from RC treatment (p <or= 0.07), whereas cells treated with SFC (p <or= 0.04) or SFCD (p <or= 0.03) showed a significantly lower PSA than those treated with RC. Quantitative and principle component analysis of putative stomach irritating compounds revealed significantly reduced contents of (beta)N-alkanoyl-5-hydroxytryptamides, caffeine, N-methylpyridinium, and catechol in SFCD compared to RC. However, none of these compounds seem to act as the sole key bioactive reducing the PSA of SFCD, since their contents in MBC and SFC samples were not different from those in RC samples, although the PSA of these beverages was significantly lower than that of reconstituted freeze-dried RC beverage.

Abstract A106: Coffee consumption and risk of lethal and advanced prostate cancer

Abstract Background: Coffee is a commonly consumed beverage which contains many biologically active compounds. It is a major source of caffeine and antioxidants, and it has effects on insulin and glucose metabolism as well as sex hormone levels. This suggests that coffee may have a beneficial effect on risk of prostate cancer; however, this association has not been studied in depth. Methods: We prospectively investigated the association between coffee intake and prostate cancer risk in the Health Professionals' Follow-Up Study. From 1986 to 2006, 4975 cases of prostate cancer were identified. Intake of regular and decaffeinated coffee was assessed in 1986 and every four years thereafter. We used Cox proportional hazards models to assess the association between coffee intake and risk of prostate cancer. To investigate possible mechanisms, we used linear regression to examine the cross-sectional association between coffee intake and levels of circulating hormones in blood samples collected between 1993 and 1995 from a subset of men in the cohort. Results: There was a weak inverse association between total coffee intake and overall prostate cancer risk, with an adjusted relative risk of 0.81 (95% CI: 0.67–0.97, p-value for linear trend=0.08) for men consuming six or more cups of coffee (regular or decaf) per day compared to non-drinkers. The association was stronger for lethal and advanced (fatal, T3b or T4, or N1 or M1) prostate cancers. Compared to non-drinkers, the highest consumers had a relative risk of 0.41 (CI: 0.22–0.77, p-trend=0.02) for lethal cancer and 0.41 (CI: 0.24–0.71, p-trend=0.002) for advanced cancer. The association with lethal and advanced cancers was more pronounced in never smoking men (RR=0.11; CI: 0.02–0.83, p-trend=0.001 for advanced cancer). The inverse association was seen in both the pre-PSA and PSA screening eras. Results were similar for regular and decaffeinated coffee. For the highest versus lowest groups of intake, the relative risk of advanced cancer was 0.67 (CI: 0.34–1.33, p-trend=0.03) for regular coffee and 0.72 (CI: 0.46–1.13, p-trend=0.03) for decaffeinated coffee. There was an inverse association between caffeine intake and risk of lethal and advanced disease, but this association was weaker than that seen for coffee, and it became non-significant when total coffee intake was also included in the model. Coffee intake was inversely associated with plasma levels of C-peptide (p-trend=0.003) and positively associated with testosterone (p-trend=0.03) and SHBG (p-trend=0.04). Coffee intake was not related to circulating levels of IGF-1, IGFBP3, free testosterone, or estradiol. Conclusion: The strong inverse association between coffee consumption and risk of lethal and advanced prostate cancers is potentially important and should be confirmed in other populations. The association appears to be related to non-caffeine components of coffee and may be mediated through effects on insulin metabolism and/or sex hormone levels. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A106.

Nuclear Factor-.KAPPA.B/Signal Transducers and Activators of Transcription-1-Mediated Inflammatory Responses in Lipopolysaccharide-Activated Macrophages Are a Major Inhibitory Target of Kahweol, a Coffee Diterpene

Diterpene kahweol, one of the major components in coffee, has anti-cancer, anti-oxidative, and anti-inflammatory activity. In this study, we explored the molecular mechanism of the anti-inflammatory activity of kahweol. Lipopolysaccharide (LPS)-activated RAW264.7 cells were used to explore the modulatory role of kahweol on nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production and the activation of signaling proteins and transcription factors using immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). Kahweol diminished both the production of NO and PGE(2) and the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2. Interestingly, this compound suppressed the phospho-signal transducers and activators of transcription (STAT)-1 and p65/nuclear factor (NF)-kappaB levels in the nucleus but not c-Jun and c-fos. In conjunction, the phosphorylation of Akt and Janus kinase (JAK)2 also decreased. Therefore, our data suggest that kahweol in coffee may be an anti-inflammatory modulator with NF-kappaB/STAT-1-targeted inhibitory properties in LPS-activated RAW264.7 cells.