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This cross-sectional study aimed to investigate the association between hyperuricemia and the frequency of coffee, tea, and soft drink consumption, based on data from the Korean Genome and Epidemiology Study (KoGES) (2004-2016). We used the KoGES health examinee data, obtained from urban residents aged ≥ 40 years. Information on the participants' medical history, nutrition (total calorie, protein, fat, and carbohydrate intake), frequency of alcohol consumption, smoking status, household income, and frequency of coffee/green tea/soft drink intake was collected. A logistic regression model was used to analyze the data. Subgroup analyses were performed according to the participant's age and sex. Among 173,209 participants, there were 11,750 and 156,002 individuals with hyperuricemia and non-hyperuricemia controls, respectively. In an adjusted model, frequent coffee and green tea consumption did not increase the risk of hyperuricemia, compared to the "no intake" reference group. However, an adjusted odds ratio of hyperuricemia was 1.23 (95% confidence interval, 1.11-1.35, p < 0.001) for participants who reported consuming soft drinks ≥ 3 times per day, compared to the respective "no drink" reference group. Even after adjusting for nutritional and sociodemographic factors, frequent soft drink intake was associated with an increased risk of hyperuricemia. Meanwhile, neither coffee nor green tea intake was associated with an increased risk of hyperuricemia.

The aim of this study was to examine the association between coffee and prostate cancer. Firstly, we conducted an observational study using data from National Health and Nutrition Examination Survey (NHANES) 1999-2010. Coffee intake was derived from 24 h dietary recalls. Weighted multivariable-adjusted logistic regression was applied to evaluate the association. Then, we performed Mendelian randomization (MR) to explore the possible causal effect of coffee on prostate cancer risk. Primary and secondary genetic instruments were obtained from genome-wide association studies among 375,833 and 91,462 individuals separately. Prostate cancer summary statistics were extracted from Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) (79,194 cases and 61,112 controls) and FinnGen project (4754 cases and 63,465 controls). Inverse variance weighted (IVW) was the primary analytical method. Through selection, we enrolled 8336 individuals (weighted number = 58,796,070) for our observational study in NHANES. Results suggested that there was no association between coffee and prostate cancer. MR analyses with primary genetic instruments also did not support a causal association between coffee intake and prostate cancer risk, whether using summary data from PRACTICAL (IVW: OR 1.001, 95% CI 0.997-1.005) or FinnGen (IVW: OR 1.005, 95% CI 0.998-1.012). Similar results were observed when using secondary genetic instruments. Therefore, our study did not support a causal association between coffee intake and prostate cancer risk. Further studies with a larger sample size are needed to examine if an association exists by different coffee bean types, roasting procedures, and brewing methods.

Military personnel rely on caffeinated products such as coffee or energy drinks (ED) to maintain a maximal level of vigilance and performance under sleep-deprived and combat situations. While chronic caffeine intake is associated with decreased sleep duration and non-restful sleep in the general population, these relationships are relatively unclear in the military personnel. We conducted a focused review of the effects of caffeinated products on sleep and the functioning of military personnel. We used a pre-specified search algorithm and identified 28 peer-reviewed articles published between January 1967 and July 2019 involving military personnel. We classified the findings from these studies into three categories. These categories included descriptive studies of caffeine use, studies evaluating the association between caffeinated products and sleep or functioning measures, and clinical trials assessing the effects of caffeinated products on functioning in sleep-deprived conditions. Most of the studies showed that military personnel used at least one caffeine-containing product per day during active duty and coffee was their primary source of caffeine. Their mean caffeine consumption varied from 212 to 285 mg/day, depending on the type of personnel and their deployment status. Those who were younger than 30 years of age preferred ED use. Caffeine use in increasing amounts was associated with decreased sleep duration and increased psychiatric symptoms. The consumption of caffeinated products during sleep deprivation improved their cognitive and behavioral outcomes and physical performance. Caffeine and energy drink consumption may maintain some aspects of performance stemming from insufficient sleep in deployed personnel, but excessive use may have adverse consequences., (Published by Elsevier Inc.)

Aims: The association between caffeinated coffee consumption and atrial fibrillation remains unclear. Recent studies suggest an inverse association only between a moderate caffeinated coffee consumption and atrial fibrillation, but others have reported no association. The aim of our study was to prospectively assess the association between caffeinated coffee consumption and atrial fibrillation in two Spanish cohorts, one of adults from a general population and another of elderly participants at high cardiovascular risk., Methods and Results: We included 18,983 and 6479 participants from the 'Seguimiento Universidad de Navarra' (SUN) and 'Prevención con Dieta Mediterránea' (PREDIMED) cohorts, respectively. Participants were classified according to their caffeinated coffee consumption in three groups: ≤3 cups/month, 1-7 cups/week, and >1 cup/day. We identified 97 atrial fibrillation cases after a median follow-up of 10.3 years (interquartile range 6.5-13.5), in the SUN cohort and 250 cases after 4.4 years median follow-up (interquartile range 2.8-5.8) in the PREDIMED study. No significant associations were observed in the SUN cohort although a J-shaped association was suggested. A significant inverse association between the intermediate category of caffeinated coffee consumption (1-7 cups/week) and atrial fibrillation was observed in PREDIMED participants with a multivariable-adjusted hazard ratio = 0.53 (95% confidence interval 0.36-0.79) when compared with participants who did not consume caffeinated coffee or did it only occasionally. No association was found for higher levels of caffeinated coffee consumption (>1 cup per day), hazard ratio = 0.79 (95% confidence interval 0.49-1.28). In the meta-analysis of both PREDIMED and SUN studies, the hazard ratio for intermediate consumption of caffeinated coffee was 0.60 (95% confidence interval 0.44-0.82) without evidence of heterogeneity. Similar findings were found for the association between caffeine intake and atrial fibrillation risk., Conclusion: Intermediate levels of caffeinated coffee consumption (1-7 cups/week) were associated with a reduction in atrial fibrillation risk in two prospective Mediterranean cohorts., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10 -7 ), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10 -6 ). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.

Objective: Clinical studies suggest increasing prevalence of cardiovascular disease (CVD) risk factors and diabetes among the elderly. Meanwhile, some food compounds, such as coffee, can also have beneficial effects on CVD risk factors. The aim of the present study was to examine the relationship between coffee consumption and CVD risk factors in the elderly with type 2 diabetes mellitus (T2DM)., Methods: This cross-sectional study was performed during 2017 on 300 elderly people above 60 years of age with T2DM in Isfahan, Iran. Dietary assessment was performed using a food frequency questionnaire. Coffee consumption was classified into three groups including < 1, 1-3, and > 3 cups/day. Partial correlation test was used to investigate the relationship between CVD risk factors and usual coffee consumption., Results: The mean age and body mass index of participants were 70.04 ± 4.87 years and 24.74 ± 3.34 kg/m 2 respectively. Coffee consumption had a significant inverse relationship with fasting plasma glucose (FPG) and diastolic blood pressure (DBP) in the elderly with T2DM (r: - 0.117, 0.134; p: 0.046, 0.022). Triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) had a significant positive relationship with coffee consumption levels (r: 0.636, 0.128; p: 0.028, 0.029). These results were obtained after controlling for potential confounders., Conclusion: Increasing coffee consumption was linked to improved status of some CVD risk factors including FPG, HDL-C, and DBP in the elderly with T2DM. Nevertheless, increasing coffee consumption was also associated with higher TG level and had no significant effect on other risk factors. Further studies are required to confirm these results.

Purpose: To evaluate the association between daily coffee consumption and intraocular pressure (IOP) in healthy persons without glaucoma and the association between daily coffee consumption and history of glaucoma., Design: Cross-sectional study., Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016., Methods: All participants underwent a standardized ophthalmic examination. Self-reporting questionnaires were completed by all participants. First, the association between habitual coffee consumption and IOP among nonglaucoma individuals was evaluated by a multivariate linear regression analysis, adjusting for possible confounders. Second, the association between habitual coffee consumption and history of glaucoma also was evaluated using a multivariate logistic regression analysis., Main Outcome Measures: The association between habitual coffee consumption and IOP among nonglaucoma individuals., Results: Of 9850 participants, 9418 did not have history of glaucoma. Among these participants, the mean ± standard deviation IOP of both eyes was 14.7 ± 2.9 mmHg. The multivariate regression analysis revealed that habitual coffee consumption was associated significantly with IOP (P < 0.001): the higher the consumption of coffee, the lower the IOP of an individual. The IOP of the group who consumed coffee most frequently (3 times daily or more) was 0.4 mmHg lower (95% confidence interval, 0.2-0.5 mmHg lower) than that of the group that consumed coffee least frequently (less than once daily). However, the logistic regression analysis showed that habitual coffee consumption was not associated significantly with history of glaucoma (P = 0.53)., Conclusions: Frequent coffee consumption was associated with a slightly lower IOP in people without glaucoma but was not associated with a decreased risk of glaucoma developing. Additional experimental studies are needed to examine the effects of coffee on IOP and glaucoma risk., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent., Aim: To provide further information on the risk of colorectal cancer in relation to coffee consumption., Methods: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates., Results: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95-1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72-1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75-1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87-1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites., Conclusion: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This paper reviews provenance, chemical composition and properties of tea (Camelia sinensis L.) and coffee (Coffee arabica, L. and Coffeacaniphora, L.), their general health effects, as well as the currently available knowledge concerning their action on fat storage, physiological mechanisms of their effects, as well as their safety and recommended dosage for treatment of obesity. Both tea and coffee possess the ability to promote health and to prevent, to mitigate and to treat numerous disorders. This ability can be partially due to presence of caffeine in both plants. Further physiological and medicinal effects could be explained by other molecules (theaflavins, catechins, their metabolites and polyphenols in tea and polyphenol chlorogenic acid in coffee). These plants and plant molecules can be efficient for prevention and treatment of numerous metabolic disorders including metabolic syndrome, cardiovascular diseases, type 2 diabetes and obesity. Both plants and their constituents can reduce fat storage through suppression of adipocyte functions, and support of gut microbiota. In addition, tea can prevent obesity via reduction of appetite, food consumption and food absorption in gastrointestinal system and through the changes in fat metabolism.

Background: To assess the association between coffee intake and breast cancer risk using data from studies published during the past 15 years., Methods: Articles published between January 2005 and May 2020 were collected from PubMed, Embase, and Web of Science databases, and the Cochrane library. Coffee consumption was set as the exposure factor of breast cancer risk, and relative risk (RR) was set as the assessment indicator. Random-effects or fixed-effects models were used for the meta-analysis, depending on the level of heterogeneity. The linear and non-linear dose-response relationship was assessed using the generalized least-squares method and restricted cubic spline model. Articles were evaluated by sensitivity analysis, and Begg's and Egger's tests and funnel plots were used to evaluate publication bias. The process of meta-analysis referred to Meta-analyses of Observational Studies in Epidemiology (MOOSE)., Results: We retrieved 26 relevant studies in the dose-response analysis and meta-analysis. A negative correlation was found between coffee consumption and breast cancer risk (RR: 0.95; 95% CI: 0.92-0.99). A linear and marginal dose-response relationship was found for six case-control studies (RR: 0.98; 95% CI: 0.95-1.00) and 10 cohort studies (RR: 0.98; 95% CI: 0.97-1.00). Subgroup analysis showed that the relationship between coffee consumption and breast cancer risk was moderated by menstrual status and geographic region., Conclusions: Overall, the meta-analysis found a negative correlation between coffee intake and breast cancer risk, especially in postmenopausal and European women.

A few studies to date have examined the association between prenatal exposure to alcohol, tobacco, and coffee, and congenital complications/adverse birth outcomes among South Korean populations. Thus, this study analyzed the data of 1675 Korean women with birth experience within the last 3 years for pregnancy-related health and nutritional behaviors and relative outcomes. During their pregnancies, 11.58% of the study population consumed alcohol at least once, 1.43% drank throughout all three trimesters, 1.13% smoked, 25.43% were exposed to secondhand smoking, and 28.18% consumed 3 coffees or more every day. Prenatal alcohol exposure was associated with 11.24 times increased risk of birth defects/disabilities [Odds Ratio (OR): 11.24, 95% Confidence Interval (CI) 1.07-117.86] and 10.66 times increased risk of inherited metabolic diseases (OR: 10.66, 95% CI: 1.08-104.82). Prenatal secondhand smoke exposure (OR: 1.62, 95% CI: 1.01-2.62) and coffee consumption (OR: 1.92, 95% CI: 1.22-3.03) was associated with increased risk of low birth weight. Such results were in alignment with that of previous studies and confirmed that prenatal alcohol, tobacco, and coffee exposure can have detrimental neonatal and maternal consequences.

It was hypothesized that periodontal diseases could be influenced by nutrition and food types. However, the role of nutritional factors in the risk of periodontal disease has not been clearly elucidated. This study was aimed at investigating the relationship between coffee, green tea, or soft drink intake and periodontitis. This prospective cohort study used epidemiological data from 2004 to 2016 from the Korean Genome and Epidemiology Study. Among 173,209 participants, 9,933 with periodontitis and 124,922 controls were selected. The frequency histories of coffee/green tea/soft drink intake among the participants were analyzed, and intake was categorized as no drink, mild drink (one time a month through six times a week), and heavy drink (one or more times a day). Variable factors were adjusted using logistic regression analysis (adjusted model). The chi-square test and independent t -test were used for statistical analysis. Adjusted odds ratio (aOR) for coffee or green tea intake and periodontitis were not statistically significant. The aOR was 1.16 (95% confidence interval (CI) = 1.11-1.21, P < 0.001) for mild soft drink intake and 1.02 (95%CI = 0.96-1.09, P = 0.518) for heavy soft drink intake. Subgroup analysis showed that mild soft drink intake was significant across all groups ( P < 0.05), whereas coffee and green tea intakes were not significant in any subgroup. Overall, the study elucidated an association between mild soft drink intake and periodontitis., Competing Interests: The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2021 Seok Jin Hong et al.)

Coffee is widely consumed worldwide, and numerous studies indicate that coffee consumption may potentially affect the development of chronic diseases. Metabolic syndrome (MetS) may constitute a risk factor for chronic diseases. We aimed to prospectively evaluate the association between coffee consumption and MetS incidence. All participants were selected from the Health Examinees study. MetS was defined by the Adult Treatment Panel III criteria of the National Cholesterol Education Program. A multivariate Cox proportional hazards regression model was used to assess the relationship between coffee consumption and MetS incidence. In comparison with non-consumers, male moderate consumers (≤3 cups/day) showed a lower risk for low high-density lipoprotein cholesterol (HDL-C) (≤1 cup/day, hazard ratio (HR): 0.445, 95% confidence interval (CI): 0.254-0.780; 1-3 cups/day, HR: 0.507, 95% CI: 0.299-0.859) and high fasting blood glucose (FPG) (≤1 cup/day, HR: 0.694, 95% CI: 0.538-0.895; 1-3 cups/day, HR: 0.763, 95% CI: 0.598-0.972). Male 3-in-1 coffee (coffee with sugar and creamer) consumers also showed a lower risk for low HDL-C (HR: 0.423, 95% CI: 0.218-0.824) and high FPG (HR: 0.659, 95% CI: 0.497-0.874). These findings indicate a negative association between moderate coffee consumption and low HDL-C and high FPG among Korean male adults.

Objective: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown., Methods: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon's epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with ≥1 focal seizure (FS), valid pulse oximetry (SpO 2 ) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (≤3 cups/week), moderate (4 cups/week to 3 cups/day), and high (≥4 cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO 2 < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both., Results: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07-.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04-.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042)., Significance: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect., (© 2021 International League Against Epilepsy.)

Aims: Lifestyle interventions are an important and viable approach for preventing cognitive deficits. However, the results of studies on alcohol, coffee and tea consumption in relation to cognitive decline have been divergent, likely due to confounds from dose-response effects. This meta-analysis aimed to find the dose-response relationship between alcohol, coffee or tea consumption and cognitive deficits., Methods: Prospective cohort studies or nested case-control studies in a cohort investigating the risk factors of cognitive deficits were searched in PubMed, Embase, the Cochrane and Web of Science up to 4th June 2020. Two authors searched the databases and extracted the data independently. We also assessed the quality of the studies with the Newcastle-Ottawa scale. Stata 15.0 software was used to perform model estimation and plot the linear or nonlinear dose-response relationship graphs., Results: The search identified 29 prospective studies from America, Japan, China and some European countries. The dose-response relationships showed that compared to non-drinkers, low consumption (<11 g/day) of alcohol could reduce the risk of cognitive deficits or only dementias, but there was no significant effect of heavier drinking (>11 g/day). Low consumption of coffee reduced the risk of any cognitive deficit (<2.8 cups/day) or dementia (<2.3 cups/day). Green tea consumption was a significant protective factor for cognitive health (relative risk, 0.94; 95% confidence intervals, 0.92-0.97), with one cup of tea per day brings a 6% reduction in risk of cognitive deficits., Conclusions: Light consumption of alcohol (<11 g/day) and coffee (<2.8 cups/day) was associated with reduced risk of cognitive deficits. Cognitive benefits of green tea consumption increased with the daily consumption.

Background: Coffee is one of the most widely consumed beverages around the world. Dietary habits, specifically, coffee consumption has long been a suspected cause of hypertension. However, previous findings on coffee consumption and its association with the incidence of hypertension are not homogeneous and still inconsistent., Purpose: To examine the association of habitual coffee consumption with the risk of developing hypertension in a middle-aged Brazilian cohort., Methods: Data were from the multicenter prospective cohort "Brazilian Longitudinal Study for Adult Health - ELSA-Brasil". The cohort comprises 15,105 civil servants, aged 35-74 years at baseline, who were sampled from universities located in six Brazilian cities. For the present study, we analyzed data from 8780 participants initially free of hypertension during a mean follow-up of 3.9 years. The consumption of coffee was obtained at baseline using a previously validated semi-quantitative food frequency questionnaire (FFQ). Subsequently coffee intake was categorized into four categories (cups/day): never/almost never, ≤1, 1-3, and >3. Hypertension status was defined as a systolic blood pressure ≥140 mmHg or a diastolic blood pressure ≥90 mmHg, use of antihypertensive drug treatment, or both. Poisson regression model with a robust variance was performed to estimate relative risk (RR) and confidence interval (95% CI) for hypertension according to baseline coffee consumption. The effect of interaction between coffee consumption and smoking status was assessed., Results: Most participants (90%) drank coffee, and the median total coffee intake was 150 mL/day. A total of 1285 participants developed hypertension. Compared to participants who never or almost never drink coffee, the risk of hypertension was lower for individuals consuming 1-3 cups/day (RR 0.82, 95% CI: 0.68-0.97) (P for interaction=0.018). After stratification by smoking status the analysis revealed a decreased risk of hypertension in never smokers drinking 1-3 cups of coffee per day (RR 0.79, 95% CI: 0.64-0.98), whereas the hypertension risk among former and current smokers was not associated with coffee consumption significantly. Moreover, upper category of coffee drinking (>3 cups/day) the association was not significant for risk of hypertension., Conclusion: The association between coffee consumption and incidence of hypertension was related to smoking status. The beneficial effect of moderate coffee intake (1-3 cups/day) on risk of hypertension was observed only in never smokers., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Coffee consumption can be expected to reduce mortality due to cardiovascular diseases and cancer. This study tested the hypothesis of an inverse association between coffee intake and all-cause mortality and mortality due to cancer, coronary heart disease, or stroke., Study Design: Prospective cohort study., Methods: We analyzed data from the Jichi Medical School Cohort Study, Japan, enrolling 9946 subjects (men/women: 3870/6,076, age: 19-93 years) from 12 communities. A food frequency questionnaire assessing the subjects' daily coffee consumption was used., Results: During an average follow-up of 18.4 years, the total number of deaths was 2024, including 677 for cancer, 238 for coronary heart disease, and 244 for stroke. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality and cause-specific mortality due to cancer, coronary heart disease, and stroke. Overall, no significant association was shown between coffee consumption and all-cause mortality. In the cause-specific mortality analyses, stroke mortality was significantly lower in those who consumed 1-2 cups of coffee daily (HR [95% CI]: 0.63 [0.42-0.95]) than in those who do not consume coffee, and this association occurred only in men., Conclusion: This study showed no significant association between coffee consumption and all-cause mortality. A U-shaped association between coffee consumption and stroke mortality with a 37% lower stroke mortality, only significant in men who consume 1-2 cups of coffee daily was observed. It is necessary to examine the possibility of intervention studies to reduce stroke mortality through coffee consumption., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Crohn's disease (CD) and ulcerative colitis (UC) are widely associated with smoking in epidemiological studies, whereas there are conflicting results for the association between CD and UC for both coffee and alcohol consumption. Herein, we aimed to investigate whether cigarette smoking and alcohol and coffee consumption are causally associated with either CD or UC., Methods: We utilized 540 genome-wide significant single-nucleotide polymorphisms for 3 potentially addictive substances-nicotine, alcohol, and caffeine-to assess the association of smoking, coffee, and alcohol consumption with CD and UC (12,194 CD cases, 12,366 UC cases, and 25,042 controls of European ancestry), using Mendelian randomization analysis. Mendelian randomization estimates were used to evaluate the effect of the exposure factors on CD and UC risk. Sensitivity analysis was employed to test for any directional pleiotropy., Results: We found evidence for a positive causal association between the age of smoking initiation and UC risk and between alcohol consumption and CD risk, which disappeared after sensitivity analysis for both associations (P > 0.05). No evidence for a causal association between cigarettes per day, smoking initiation, smoking cessation, and coffee consumption variables and UC or CD was found., Conclusions: We found no clear evidence that either genetically predicted smoking, coffee consumption, or alcohol consumption are causally associated with the risk for CD or UC, although our findings indicate a potential positive association between the age of smoking and UC and between alcohol consumption and CD., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer., Methods: We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations., Results: One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07)., Conclusions: The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association., Competing Interests: The authors have declared that no competing interests exist.

Background: Results of stroke risk and coffee consumption are inconclusive. This study aimed to provide an updated systematic review and meta-analysis of the association between coffee consumption and stroke risk., Method: Random-effects models were used to pool relative risk estimates (RRs) with 95% confidence intervals (CIs). The highest versus the lowest categories of coffee consumption as well as dose-response analysis with a one-stage robust error meta-regression model (REMR) were assessed for stroke risk., Results: In total, 21 studies including 30 independent cohorts that comprised more than 2.4 million participants were included. The pooled RR with 95% CI for the highest versus the lowest categories of coffee consumption was 0.87 (0.80-0.94) with moderate heterogeneity (I 2  = 32.0%). Sensitivity analysis suggested that the influence of each individual data set to an overall result was not significant. As suggested by Begg's funnel plots and Egger tests (p=0.006), some evidence for publication bias was observed. Further analysis with the trim-and-fill method indicated no noticeable harm to our results was generated by any potential bias. Dose-response analysis suggested a nonlinear relationship (U-shape) between stroke risk and coffee (p = 0.0002). The strongest association for stroke (21% lower risk) was found for coffee consumption of 3-4 cups/day and no further reduction in stroke risk was observed with increasing levels of coffee consumption beyond this amount., Conclusion: Our study provided evidence of a significant inverse association between coffee consumption and risk of stroke. Future large prospective studies with excellent design are warranted to confirm our findings and provide a more definitive conclusion., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The consumption of caffeinated drinks and soft drinks is widespread in society, including by pregnant women. Data regarding the association of caffeine intake and stillbirth are varied. We aimed to investigate the degree of consumption of caffeinated drinks or soft drinks in the last four weeks of pregnancy in women who experienced a late stillbirth compared to women with ongoing live pregnancies at similar gestation. Influences on maternal caffeine intake and soft drink consumption during pregnancy were also investigated., Study Design: A case-control study undertaken in 41 maternity units in the United Kingdom. Cases were women who had a singleton non-anomalous stillbirth ≥28 weeks' gestation (n = 290) and controls were women with an ongoing pregnancy at the time of interview (n = 729). Data were collected using an interviewer-administered questionnaire which included questions regarding consumption of a variety of caffeinated drinks and soft drinks in the last four weeks of pregnancy as well as other behaviours (e.g. cigarette smoking)., Results: Multivariable analysis adjusting for co-existing demographic and behavioural factors found the consumption of instant coffee, energy drinks and cola were associated with increased risk of stillbirth. There was an independent association between caffeine intake and late stillbirth (adjusted Odds Ratio 1.27, 95 % Confidence Interval (95 %CI) 1.14, 1.43 for each 100 mg increment/day). 15 % of cases and 8% of controls consumed more than the World Health Organisation (WHO) recommendation (>300 mg of caffeine/day; aOR 2.30, 95 % CI 1.40, 4.24). The population attributable risk for stillbirth associated with >300 mg of caffeine/day was 7.4 %. The majority of respondents reduced caffeine consumption in pregnancy. Midwives and internet resources were the most frequently used sources of information which influenced maternal behaviour with regard to soft drinks and caffeine, and this did not differ between cases and controls., Conclusions: Women should be informed that consumption of caffeine during pregnancy is associated with increased risk of stillbirth, particularly at levels greater than recommended by the WHO (>300 mg/day). Recommendations from midwives and internet-based resources are likely to be the most effective means to influence maternal behaviour., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, whether these associations are causal remains unknown. This study aimed to identify genetic variants associated with caffeine intake, and to investigate evidence for causal links with CAD or T2DM. In addition, we aimed to replicate previous observational findings. Methods and Results Observational associations were tested within UK Biobank using Cox regression analyses. Moderate observational caffeine intakes from coffee or tea were associated with lower risks of CAD or T2DM, with the lowest risks at intakes of 121 to 180 mg/day from coffee for CAD (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82; P <1×10 -16 ]), and 301 to 360 mg/day for T2DM (HR, 0.76 [95% CI, 0.67-0.86]; P =1.57×10 -5 ). Next, genome-wide association studies were performed on self-reported caffeine intake from coffee, tea, or both in 407 072 UK Biobank participants. These analyses identified 51 novel genetic variants associated with caffeine intake at P <1.67×10 -8 . These loci were enriched for central nervous system genes. However, in contrast to the observational analyses, 2-sample Mendelian randomization analyses using the identified loci in independent disease-specific cohorts yielded no evidence for causal links between genetically determined caffeine intake and the development of CAD or T2DM. Conclusions Mendelian randomization analyses indicate genetically determined higher caffeine intake might not protect against CAD or T2DM, despite protective associations in observational analyses.

Aim: The aim of this study was to investigate whether the coffee brewing method is associated with any death and cardiovascular mortality, beyond the contribution from major cardiovascular risk factors., Methods and Results: Altogether, 508,747 men and women aged 20-79 participating in Norwegian cardiovascular surveys were followed for an average of 20 years with respect to cause-specific death. The number of deaths was 46,341 for any cause, 12,621 for cardiovascular disease (CVD), 6202 for ischemic heart disease (IHD), and 2894 for stroke. The multivariate adjusted hazard ratios (HRs) for any death for men with no coffee consumption as reference were 0.85 (082-0.90) for filtered brew, 0.84 (0.79-0.89) for both brews, and 0.96 (0.91-1.01) for unfiltered brew. For women, the corresponding figures were 0.85 (0.81-0.90), 0.79 (0.73-0.85), and 0.91 (0.86-0.96) for filtered, both brews, and unfiltered brew, respectively. For CVD, the figures were 0.88 (0.81-0.96), 0.93 (0.83-1.04), and 0.97 (0.89-1.07) in men, and 0.80 (0.71-0.89), 0.72 (0.61-0.85), and 0.83 (0.74-0.93) in women. Stratification by age raised the HRs for ages ≥60 years. The HR for CVD between unfiltered brew and no coffee was 1.19 (1.00-1.41) for men and 0.98 (0.82-1.15) for women in this age group. The HRs for CVD and IHD were raised when omitting total cholesterol from the model, and most pronounced in those drinking ≥9 of unfiltered coffee, per day where they were raised by 9% for IHD mortality., Conclusion: Unfiltered brew was associated with higher mortality than filtered brew, and filtered brew was associated with lower mortality than no coffee consumption.

Morning coffee is a common remedy following disrupted sleep, yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated. In a randomised crossover design, twenty-nine adults (mean age: 21 (sd 1) years, BMI: 24·4 (sd 3·3) kg/m2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep approximately 23.00-07.00 hours), the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), with and without morning coffee approximately 1 h after waking (approximately 300 mg caffeine as black coffee 30 min prior to OGTT). Individualised peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (mean (normalised CI) for Control, Fragmented and Fragmented + Coffee, respectively; glucose: 8·20 (normalised CI 7·93, 8·47) mmol/l v. 8·23 (normalised CI 7·96, 8·50) mmol/l v. 8·96 (normalised CI 8·70, 9·22) mmol/l; insulin: 265 (normalised CI 247, 283) pmol/l; and 235 (normalised CI 218, 253) pmol/l; and 310 (normalised CI 284, 337) pmol/l). Likewise, incremental AUC for plasma glucose was higher in the Fragmented + Coffee trial compared with Fragmented. Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed, then a reduction in glucose tolerance can be expected.

Background and Aim: Dyslipidemia is a common metabolic disease worldwide and also an important predisposing factor for cardiovascular diseases (CVDs). Coffee is loved by people all over the world; however, the association between coffee consumption and blood lipids has yielded inconsistent results. So we carried this meta-analysis to explore the effects of coffee consumption on blood lipids., Methods and Results: Medline, PubMed, Web of science, Embase, and Cochrane Library databases were systematically searched until April 2020. Combined weighted mean differences (WMD) with their 95% confidence interval (CI) were calculated using random-effects models, and between-study heterogeneity was assessed by Cochran's Q test and I 2 statistics. Subgroup analysis and meta-regression analysis were also conducted to explore the potential heterogeneity. A total of 12 RCT studies involving the association between coffee consumption and blood lipid levels were included in the meta-analysis. The pooled results showed that coffee consumption significantly increased total cholesterol (TC) (WMD: 0.21 mmol/L, 95% CI: 0.04; 0.39, P = 0.017), triglyceride (TG) (WMD: 0.12 mmol/L, 95% CI: 0.03; 0.20, P = 0.006) and low-density lipoprotein (LDL-C) (WMD: 0.14 mmol/L, 95% CI: 0.05; 0.24, P = 0.003) while had no significant effect on high-density lipoprotein (HDL-C) (WMD: -0.01 mmol/L, 95% CI: -0.06; 0.04, P = 0.707). Dose-response analysis results revealed significant positive nonlinear associations between coffee consumption and the increase in TC, LDL-C, and TG levels., Conclusions: Evidence from this meta-analysis suggested that coffee consumption may be associated with an elevated risk for dyslipidemia and CVDs. So a reasonable habit of coffee consumption (<3 cups/d) is essential for the prevention of dyslipidemia., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: This systematic review aims to evaluate the impact of coffee consumption in patients with previous myocardial infarction (MI), in relation to all-cause and cardiovascular mortality, as well as other major cardiovascular events (MACE) such as stroke, heart failure, recurrent MI and sudden death., Methods and Results: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection, SciELO Citation Database, Current Contents Connect®, KCI Korean Journal Database, African Index Medicus, and LILACS were searched for longitudinal studies evaluating the impact of coffee consumption in patients with previous myocardial infarction. We performed a random-effects meta-analysis to estimate the pooled hazard ratios (HR) with 95% confidence intervals (CI). The statistical heterogeneity was measured by I 2 . A dose-response analysis was also conducted. Six prospective cohort studies were included in the primary meta-analysis. Consumption of coffee was associated with lower risk of cardiovascular mortality (HR = 0.70; 95% CI 0.54-0.91, I 2  = 0%; 2 studies) and was not associated with an increased risk of all-cause mortality (HR = 0.85; 95% CI 0.63-1.13; I 2  = 50%; 3 studies), recurrent MI (HR = 0.99; 95% CI 0.80-1.22; I 2  = 0%; 3 studies), stroke (HR = 0.97; 95% CI 0.63-1.49; I 2  = 39%; 2 studies) and MACE (HR = 0.96; 95% CI 0.86-1.07; I 2  = 0%; 2 studies). A significant non-linear inverse dose-response association was found for coffee consumption and all-cause mortality., Conclusions: Consumption of coffee was not associated with an increased risk of all-cause mortality and cardiovascular events in patients with previous myocardial infarction., Competing Interests: Declaration of competing interest DC has participated in educational meetings and/or attended a conferences or symposia (including travel, accommodation and/or hospitality) with Roche, Daiichi-Sankyo, and Menarini, Merck-Serono, in the last 3 years. MA reported participation in conferences with Boehringer-Ingelheim, AstraZeneca, Bayer, Bristol-Myers-Squibb, Grünenthal, Tecnimede, Merck Sharp & Dohme. JJF had speaker and consultant fees with Grünenthal, Fundação MSD (Portugal), TEVA, MSD, Allergan, Medtronic, GlaxoSmithKline, Novartis, Lundbeck, Solvay, BIAL, Merck-Serono, Merz, Ipsen, Biogen, Acadia, Allergan, Abbvie, Sunovion-Pharmaceuticals. FJP had consultant and speaker fees with AstraZeneca, Bayer, BMS, Boehringer Ingelheim and Daiichi Sankyo., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

DNA methylation represents an important epigenetic regulation of the genome. Earlier studies have suggested that dietary phenolic compounds including those contained in coffee, tea and soy products may modulate the level of DNA methylation. In this study, we first characterize the effect of caffeic acid phenethyl ester (CAPE) and other dietary phenolic compounds on DNA methylation in vitro. The IC 50 values of CAPE, daidzein, isorhamnetin and genistein are 7.6, 6.9, 6.2, and 4.3 μM, respectively, in an in-vitro enzymatic assay system. Computational analysis indicates that CAPE, daidzein, isorhamnetin and genistein can bind inside the DNA substrate-binding site in human DNMT1 with a favorable binding energy. In an animal study, we find that maternal CAPE treatment shifts the coat color distribution of the 21-day-old A vy /a offspring towards the yellow phenotype, indicating that CAPE inhibits the methylation of the agouti gene promoter sequence in vivo. The results from this study may shed light on the potential epigenetic effect in the offspring resulting from maternal intake of certain coffee phenolics during pregnancy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A 59-year-old woman presented with pharyngeal discomfort and dysphagia starting the previous day. Esophagogastroduodenoscopy revealed a longitudinal reddish area and hematoma mainly on the left wall of the esophagus. On the previous day, she had felt a piece of meat sticking in her throat while eating; she therefore rapidly gulped down some hot coffee to hasten the passage of the meat. Based on the history, we diagnosed her endoscopic findings as esophageal hematoma and thermal injury associated with hot coffee. We herein describe a case of an acute esophageal hematoma and thermal injury and the clinical course following endoscopy.

Background: There is limited evidence of a potential inverse association between coffee, particularly caffeinated coffee, consumption and postmenopausal breast cancer risk, and few studies have examined this association by tumor hormone receptor status. To provide further evidence, we examined total, caffeinated, and decaffeinated coffee consumption in relation to postmenopausal invasive breast cancer incidence overall, and by tumor estrogen receptor (ER) and/or progesterone receptor (PR) subtype., Methods: Among 57,075 postmenopausal women in the Cancer Prevention Study-II Nutrition Cohort who were cancer free and reported coffee intake in 1999, we identified 2,980 women diagnosed with invasive breast cancer during follow-up through June 2015. Multivariable-adjusted Cox proportional hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI)., Results: Neither total, caffeinated, nor decaffeinated coffee consumption was associated with invasive breast cancer risk; HRs (95% CIs) comparing consumption of ≥2 cups per day with <1 cup per month were 0.99 (0.89-1.11), 0.96 (0.87-1.06), and 1.06 (0.95-1.19), respectively. Similarly, coffee consumption was not associated with risk of hormone receptor-positive (ER + or PR + ) or hormone receptor-negative (ER - and PR - ) breast tumors., Conclusions: These findings do not support an association between coffee consumption and invasive breast cancer risk among postmenopausal women., Impact: This large prospective study contributes to the limited evidence on coffee consumption and breast cancer risk, finding no association overall or by tumor receptor subtype., (©2020 American Association for Cancer Research.)

Importance: Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown., Objective: To evaluate the association of coffee consumption with disease progression and death in patients with advanced or metastatic colorectal cancer., Design, Setting, and Participants: This prospective observational cohort study included 1171 patients with previously untreated locally advanced or metastatic colorectal cancer who were enrolled in Cancer and Leukemia Group B (Alliance)/SWOG 80405, a completed phase 3 clinical trial comparing the addition of cetuximab and/or bevacizumab to standard chemotherapy. Patients reported dietary intake using a semiquantitative food frequency questionnaire at the time of enrollment. Data were collected from October 27, 2005, to January 18, 2018, and analyzed from May 1 to August 31, 2018., Exposures: Consumption of total, decaffeinated, and caffeinated coffee measured in cups per day., Main Outcomes and Measures: Overall survival (OS) and progression-free survival (PFS)., Results: Among the 1171 patients included in the analysis (694 men [59%]; median age, 59 [interquartile range, 51-67] years). The median follow-up time among living patients was 5.4 years (10th percentile, 1.3 years; IQR, 3.2-6.3 years). A total of 1092 patients (93%) had died or had disease progression. Increased consumption of coffee was associated with decreased risk of cancer progression (hazard ratio [HR] for 1-cup/d increment, 0.95; 95% CI, 0.91-1.00; P = .04 for trend) and death (HR for 1-cup/d increment, 0.93; 95% CI, 0.89-0.98; P = .004 for trend). Participants who consumed 2 to 3 cups of coffee per day had a multivariable HR for OS of 0.82 (95% CI, 0.67-1.00) and for PFS of 0.82 (95% CI, 0.68-0.99), compared with those who did not drink coffee. Participants who consumed at least 4 cups of coffee per day had a multivariable HR for OS of 0.64 (95% CI, 0.46-0.87) and for PFS of 0.78 (95% CI, 0.59-1.05). Significant associations were noted for both caffeinated and decaffeinated coffee., Conclusions and Relevance: Coffee consumption may be associated with reduced risk of disease progression and death in patients with advanced or metastatic colorectal cancer. Further research is warranted to elucidate underlying biological mechanisms.

Coffee consumption has been associated with the risk of cancer at several anatomical sites, but the findings, mostly from studies of non-Hispanic whites and Asians, are inconsistent. The association between coffee consumption and the incidence of cancer has not been thoroughly examined in African Americans. We conducted a nested case-control study including 1801 cancer cases and 3337 controls among African Americans from the Southern Community Cohort Study (SCCS) to examine the association between coffee drinking, as assessed by a semi-quantitative food frequency questionnaire, and the risk of four common cancers (lung, prostate, breast, colorectal). We used logistic regression adjusted for age, sex and cancer-specific risk factors. Overall, only ≤ 9.5% of African American cases and controls from the SCCS drank regular or decaffeinated coffee ≥ 2 times/day. After adjustment for major cancer-specific risk factors, coffee consumption was not statistically significantly associated with the risk of lung, breast, colorectal, or prostate cancers (OR range 0.78-1.10; P ≥ 0.27 for ≥ 2 versus < 1 times/day) or overall cancer risk (OR 0.93; 95% CI 0.75-1.16; P = 0.52 for ≥ 2 versus < 1 times/day). Coffee consumption was not associated with the risk of cancer among African Americans in our study.

Coffee consumption has previously been reported to reduce overall and cause-specific mortality. We aimed to further investigate this association by coffee brewing methods and in a population with heavy coffee consumers. The information on total, filtered, instant, and boiled coffee consumption from self-administered questionnaires was available from 117,228 women in the Norwegian Women and Cancer (NOWAC) Study. We used flexible parametric survival models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause, cardiovascular, and cancer mortality by total coffee consumption and brewing methods, and adjusted for smoking status, number of pack-years, age at smoking initiation, alcohol consumption, body mass index, physical activity, and duration of education. During 3.2 million person-years of follow-up, a total of 16,106 deaths occurred. Compared to light coffee consumers (≤ 1 cup/day), we found a statistically significant inverse association with high-moderate total coffee consumption (more than 4 and up to 6 cups/day, HR 0.89; 95% CI 0.83-0.94) and all-cause mortality. The adverse association between heavy filtered coffee consumption (> 6 cups/day) and all-cause mortality observed in the entire sample (HR 1.09; 95% CI 1.01-1.17) was not found in never smokers (HR 0.85; 95% CI 0.70-1.05). During the follow-up, both high-moderate total and filtered coffee consumption were inversely associated with the risk of cardiovascular mortality (HR 0.79; 95% CI 0.67-0.94; HR 0.80; 95% CI 0.67-0.94, respectively). The association was stronger in the analyses of never smokers (> 6 cups of filtered coffee/day HR 0.20; 95% CI 0.08-0.56). The consumption of more than 6 cups/day of filtered, instant, and coffee overall was found to increase the risk of cancer deaths during the follow-up. However, these associations were not statistically significant in the subgroup analyses of never smokers. The data from the NOWAC study indicate that the consumption of filtered coffee reduces the risk of cardiovascular deaths. The observed adverse association between coffee consumption and cancer mortality is most likely due to residual confounding by smoking.

Roasted coffee and many coffee flavorings emit volatile organic compounds (VOCs) including diacetyl and 2,3-pentanedione. Exposures to VOCs during roasting, packaging, grinding, and flavoring coffee can negatively impact the respiratory health of workers. Inhalational exposures to diacetyl and 2,3-pentanedione can cause obliterative bronchiolitis. This study summarizes exposures to and emissions of VOCs in 17 coffee roasting and packaging facilities that included 10 cafés. We collected 415 personal and 760 area full-shift, and 606 personal task-based air samples for diacetyl, 2,3-pentanedione, 2,3-hexanedione, and acetoin using silica gel tubes. We also collected 296 instantaneous activity and 312 instantaneous source air measurements for 18 VOCs using evacuated canisters. The highest personal full-shift exposure in part per billion (ppb) to diacetyl [geometric mean (GM) 21 ppb; 95th percentile (P95) 79 ppb] and 2,3-pentanedione (GM 15 ppb; P95 52 ppb) were measured for production workers in flavored coffee production areas. These workers also had the highest percentage of measurements above the NIOSH Recommended Exposure Limit (REL) for diacetyl (95%) and 2,3-pentanedione (77%). Personal exposures to diacetyl (GM 0.9 ppb; P95 6.0 ppb) and 2,3-pentanedione (GM 0.7 ppb; P95 4.4 ppb) were the lowest for non-production workers of facilities that did not flavor coffee. Job groups with the highest personal full-shift exposures to diacetyl and 2,3-pentanedione were flavoring workers (GM 34 and 38 ppb), packaging workers (GM 27 and 19 ppb) and grinder operator (GM 26 and 22 ppb), respectively, in flavored coffee facilities, and packaging workers (GM 8.0 and 4.4 ppb) and production workers (GM 6.3 and 4.6 ppb) in non-flavored coffee facilities. Baristas in cafés had mean full-shift exposures below the RELs (GM 4.1 ppb diacetyl; GM 4.6 ppb 2,3-pentanedione). The tasks, activities, and sources associated with flavoring in flavored coffee facilities and grinding in non-flavored coffee facilities, had some of the highest GM and P95 estimates for both diacetyl and 2,3-pentanedione. Controlling emissions at grinding machines and flavoring areas and isolating higher exposure areas (e.g., flavoring, grinding, and packaging areas) from the main production space and from administrative or non-production spaces is essential for maintaining exposure control., (Copyright © 2020 LeBouf, Blackley, Fortner, Stanton, Martin, Groth, McClelland, Duling, Burns, Ranpara, Edwards, Fedan, Bailey, Cummings, Nett, Cox-Ganser and Virji.)

Background: As the self-administration of coffee enema is being used as a mean of self-care for detoxication in various indications, it is important that evidence-based public health information is provided for effective and safe use. However, the evidence is so far rare. This systematic review was conducted to investigate the safety and effectiveness of self-administered coffee enema in a wide range of use, and to provide evidence about its benefits and risks., Methods: Relevant studies were retrieved from Ovid MEDLINE, Ovid Embase, the Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature; and also from oriental databases, KoreaMed, Korean Medical Database, Korean Studies Information Service System, National Discovery for Science Leaders, and Korea Institute of Science and Technology Information, Oriental Medicine Advanced Searching Integrated System, China National Knowledge Infrastructure, and Japan Science and Technology Information Aggregator. Considering self-administered coffee enema being used in a various indication, study population was not restricted. Any types of published studies that included outcomes of effectiveness and safety of self-administered coffee enema with or without comparators were eligible for this systematic review. Data on biomedical indications, patient-reported outcomes, and adverse events were collected. Descriptive analyses were planned because diverse health conditions and outcome variables did not allow for quantitative synthesis., Results: Nine case reports that describe adverse events were identified and included in the analysis. Of these, 7 recent ones reported colitis after self-administration, mentioning that the most plausible cause assumed was the coffee fluid itself, which contained numerous chemical substances. Two others reported more critical adverse events. All 9 case reports with acceptable quality of evidence warned against the self-administration of the procedure. No study that reports the effectiveness of coffee enema was found., Conclusions: Based on the evidences reviewed, this systematic review does not recommend coffee enema self-administration as a complementary and alternative medicine modality that can be adopted as a mean of self-care, given the unsolved issues on its safety and insufficient evidence with regard to the effectiveness.

Objective: Previous systematic reviews evaluating the association between coffee consumption and pancreatic cancer showed inconsistent results. The aim was to conduct a meta-epidemiological study to explore further the association between coffee consumption and the incidence of pancreatic cancer., Methods: The selection criteria were defined as a population-based prospective cohort study reporting adjusted relative risk (RR) and their 95% confidence interval (95%CI) of pancreatic cancer occurrence according to coffee consumption. Adjusted RR for the highest versus the lowest level of coffee consumption in each study was extracted. A fixed-effect model was applied to calculate a summary RR (sRR) and its 95%CI. Two-stage random-effects dose-response meta-analysis (DRMA) was performed to estimate the incidence risk per unit dose (cup per day)., Results: Twelve cohort studies were selected for meta-analysis. The total number of cohort participants was 3,230,053, and pancreatic cancer incidents were 10,587. The sRR of pancreatic cancer risk for the highest versus the lowest level of coffee consumption indicated no statistical significance (sRR=0.98, 95% CI: 0.88-1.10; I-squared=0.0%). Two-stage random-effect DRMA showed the non-linear relationship between the amount of coffee consumption and pancreatic cancer risk. And the RR for an increment of one cup per day of coffee consumption was 0.97 (95%CI: 0.91-1.04, P=0.42), without statistically significant., Conclusion: There was no association between coffee consumption habits and pancreatic cancer risk. And there was no statistical significance in the dose-response relationship between the amount of coffee consumption and pancreatic cancer risk. Finding the turning point would be important because it can be critical information for the prevention of pancreatic cancer. , .

Background: Depression in elderly people is a major global concern around the world. Epidemiological evidence of the association of beverages with depressive symptoms has received research attention; however, epidemiological studies on the association of coffee and green tea consumption with depressive symptoms among the elderly population are limited. The objective of this study is to cross-sectionally examine the association of depressive symptoms with the intake of coffee, green tea, and caffeine and to verify the antidepressant effect of caffeine., Methods: The subjects were 1,992 women aged 65-94 years. Intakes of coffee, green tea, and caffeine, as well as depressive symptoms, were assessed with a validated brief dietary history questionnaire (BDHQ) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Multiple logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for depressive symptoms with adjustments for potential confounders., Results: Coffee intake was associated with a lower prevalence of depressive symptoms, the ORs of which for the 4th versus the 1st quartiles of intake was 0.64 (95% CI, 0.46-0.88, P for trend = 0.01) in a fully adjusted model. Caffeine intake was marginally associated with depressive symptoms, but the association was not statistically significant (OR 0.75; 95% CI, 0.55-1.02, P for trend = 0.058)., Conclusion: The result suggests that the inverse association of coffee intake with depressive symptoms might be associated with not only caffeine intake but also some other substances in coffee or factors related to coffee intake. Because of the cross-sectional design of the present study, longitudinal studies are required to confirm the present finding.

Background:   Lung cancer is a major cause of cancer death worldwide. The incidence of lung cancer in Thailand increasing, but risk factors are rarely reported., Objective: To investigate the effect of coffee consumption on lung cancer in Thai population., Methods: Between 1990 and 2001, lifestyle and demographic data were collected from 24,528 participants in the Khon Kaen Cohort Study (KKCS), who were followed through 2016, by linking to the Khon Kaen Population-based Cancer Registry. A total of 12,668 eligible participants (68.8% females, mean age 51.0 years at baseline) having complete datasets (239,488 person-years of follow up with 138 incident cases of lung cancer observed) were analyzed using a multi-variable adjusted Cox proportional hazard models., Results: Coffee consumption was associated with reduced risk for lung cancer (adj. HR = 0.54; 95% CI: 0.35-0.84) after adjusting for age and gender.  Cigarette smoking (adj. HR = 2.76; 95% CI: 1.32-5.78) and family history of cancer (adj. HR = 1.65; 95% CI: 1.10-2.48) were associated with higher risk., Conclusion: This study suggests coffee consumption may be a protective factor for lung cancer in among this cohort., .

Objectives: To estimate a possible association between coffee intake during pregnancy and risk of childhood acute leukemia by using a cohort design., Methods: We included data from two birth cohorts; the Danish National Birth Cohort and the Aarhus Birth Cohort. Recruitment of 141,216 eligible pregnancies occurred from 1 August 1989 to 31 December 2012. Information on maternal prenatal coffee intake and covariates was collected in early second trimester of pregnancy. Information on childhood AL diagnosed in offspring was obtained from the Danish National Patient Register. We used competing risk time-to-event regression analysis, using the pseudo-observation method to estimate risk ratio (RR) with no coffee intake during pregnancy considered the reference group., Results: In total 96 children were diagnosed with AL, hereof 73 with acute lymphoblastic leukemia (ALL). Coffee intake of 0.5-3 cups/day during pregnancy was not associated with a higher risk of childhood AL; aRR = 0.89, 95 % confidence interval (CI): 0.48, 1.65, however, an intake of >3 cups/day resulted in aRR = 1.37, 95 % CI: 0.56, 3.32. Only including ALL as outcome we found similar results; aRR = 0.80, 95 % CI: 0.37-1.74 and aRR = 1.46 95 % CI: 0.52-4.09, respectively., Conclusion: We found no significant association between maternal coffee intake and risk of childhood AL but the number of cases was limited. The confidence limits does not exclude that a high prenatal coffee intake may increase the risk of childhood AL and larger studies based on prospective data are needed., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The association between coffee consumption and colorectal cancer risk generally appears null, but recent evidence suggests that risk may vary by coffee type. We examined associations of caffeinated and decaffeinated coffee intake with colorectal cancer risk overall and with colon and rectum separately, among older U.S. men and women., Methods: In 1999, 47,010 men and 60,051 women with no previous diagnosis of cancer, aged 47-96 years, in the Cancer Prevention Study-II Nutrition Cohort completed a food frequency questionnaire that assessed caffeinated and decaffeinated coffee intake; consumption was updated in 2003. A total of 1829 colorectal cancer cases were verified through June 2015. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard rate ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking history, alcohol, caffeinated/decaffeinated coffee intake (depending on the model), and other colorectal cancer risk factors., Results: Consumption of ≥2 cups/day of decaffeinated coffee, compared to no decaffeinated coffee, was associated with lower risk of overall colorectal cancer (HR = 0.82, 95% CI: 0.69-0.96, P-trend = 0.04), colon cancer (HR = 0.82, 95% CI: 0.69-0.99, P-trend = 0.05) and rectal cancer (HR = 0.63, 95% CI: 0.40-0.99, P-trend = 0.17). Consumption of ≥2 cups/day of caffeinated coffee was associated with higher risk of rectal cancer (HR = 1.37, 95% CI: 0.99-1.89, P-trend = 0.04), but not with colorectal or colon cancer., Conclusion: In this prospective study, higher intake of decaffeinated coffee was associated with lower risk of colorectal, colon, and rectal cancers. Further study on associations of caffeinated and decaffeinated coffee with colorectal cancer risk by subsite is needed., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To examine differences in the frequency and severity of federally reported adverse events between caffeine-containing and non-caffeine-containing products while also identifying the category of caffeine-containing products associated with the highest frequency and severity of adverse events., Patients and Methods: All adverse event reports that met specified eligibility criteria and were submitted to the Center for Food Safety and Applied Nutrition Adverse Event Reporting System between January 1, 2014, and June 29, 2018, were extracted. In this retrospective observational study, the most severe adverse event experienced, an ordinal variable, was categorized into death, life-threatening, hospitalization/disability, and emergency department visit. A nonproportional odds model was used to compare the odds of caffeine-containing products being associated with more severe adverse events relative to a noncaffeine group. The analysis is of data only from those reporting adverse events and may or may not be representative of the entire population exposed to these products, which is not known from the examined data., Results: Energy and preworkout products saw a significant increase in the odds of the adverse event experienced being death rather than the other less severe outcomes relative to the noncaffeinated group. Those products, along with weight loss products, had greater odds of the adverse event being death or life-threatening vs the less severe outcomes relative to the noncaffeinated group., Conclusion: Caffeine-containing products have a greater association with severe adverse events compared with non-caffeine-containing products. Exposure to preworkout and weight loss products had greater odds of being associated with a more serious adverse event relative to noncaffeinated products. Health care practitioners should use these outcomes to better inform and educate patients about the many factors related to caffeine intake and adverse outcomes., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The association between coffee consumption and the risk of type 2 diabetes may vary by genetic variants. Our study addresses the question of whether the incidence of type 2 diabetes is related to the consumption of coffee and whether this relationship is modified by polymorphisms related to type 2 diabetes. We performed a pooled analysis of four Korean prospective studies that included 71,527 participants; median follow-up periods ranged between 2 and 13 years. All participants had completed a validated food-frequency questionnaire (FFQ) at baseline. The odds ratios (ORs) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using logistic regression models. The ORs were combined using a fixed or random effects model depending on the heterogeneity across the studies. Compared with 0 to <0.5 cups/day of coffee consumption, the OR for type 2 diabetes was 0.89 (95% CI: 0.80-0.98, p for trend = 0.01) for ≥3 cups/day of coffee consumption. We did not observe significant interactions by five single nucleotide polymorphisms (SNPs) related to type 2 diabetes ( CDKAL1 rs7756992, CDKN2A /B rs10811661, KCNJ11 rs5215, KCNQ1 rs163184, and PEPD rs3786897) in the association between coffee and the risk of type 2 diabetes. We found that coffee consumption was inversely associated with the risk of type 2 diabetes.

Habitual coffee consumption and its association with health outcomes may be modified by genetic variation. Adults aged 40 to 69 years who participated in the Korea Association Resource (KARE) study were included in this study. We conducted a genome-wide association study (GWAS) on coffee consumption in 7868 Korean adults, and examined whether the association between coffee consumption and the risk of prediabetes and type 2 diabetes combined was modified by the genetic variations in 4054 adults. In the GWAS for coffee consumption, a total of five single nucleotide polymorphisms (SNPs) located in 12q24.11-13 (rs2074356, rs11066015, rs12229654, rs11065828, and rs79105258) were selected and used to calculate weighted genetic risk scores. Individuals who had a larger number of minor alleles for these five SNPs had higher genetic risk scores. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) to examine the association. During the 12 years of follow-up, a total of 2468 (60.9%) and 480 (11.8%) participants were diagnosed as prediabetes or type 2 diabetes, respectively. Compared with non-black-coffee consumers, the OR (95% CI) for ≥2 cups/day by black-coffee consumers was 0.61 (0.38-0.95; p for trend = 0.023). Similarly, sugared coffee showed an inverse association. We found a potential interaction by the genetic variations related to black-coffee consumption, suggesting a stronger association among individuals with higher genetic risk scores compared to those with lower scores; the ORs (95% CIs) were 0.36 (0.15-0.88) for individuals with 5 to 10 points and 0.87 (0.46-1.66) for those with 0 points. Our study suggests that habitual coffee consumption was related to genetic polymorphisms and modified the risk of prediabetes and type 2 diabetes combined in a sample of the Korean population. The mechanisms between coffee-related genetic variation and the risk of prediabetes and type 2 diabetes combined warrant further investigation.

Aim: We studied the influence of coffee consumption on the therapeutic effect of methotrexate (MTX) in patients with rheumatoid arthritis (RA) sorted according to ADORA2A genotypes. Patients & methods: 82 RA patients were dichotomized according to caffeine intake with a threshold of 700 mg/week. Disease activity score 28 (DAS28) was applied (>3.2: high; <3.2: low or remission). Patients were genotyped using quantitative PCR allelic discrimination. Results: We found significantly higher risk of RA in patients with higher caffeine intake and the CT genotype of ADOARA2A rs2298383, rs3761422 and rs2267076 SNPs. The CC genotype of ADORA2A rs2236624 SNP in patients with lower caffeine intake treated with MTX is significantly protective. Conclusion: ADORA2A genotypes and coffee intake influence risk of RA and efficacy of it MTX treatment.

Background: Anecdotal evidence suggests consumers of caffeine self-administer strategies to reduce consumption, but little is known of what these strategies are or how they are implemented. This study aimed to understand the lived experience of reducing caffeine consumption including specific techniques (what) and implementation strategies (how), harm and withdrawal symptoms (why)., Methods: We developed a classification system through an inductive and deductive approach and applied it to a large dataset derived from online sources., Results: A total of 112 internet sources were identified, containing 2,682 different strategies. The classification system identified 22 categories of Behaviour Change Techniques (BCT): 10 categories were directly aligned with a BCT, one was split into two categories (substance and behavioural substitution), six represented a cluster of BCT's (e.g., withdrawal management and maintaining momentum) and four appeared to uniquely represent a consumer perspective (e.g., realisation of a problem). The most common techniques were substance substitution, seek knowledge and information, avoidance of caffeine and identify prompts for change. The most frequently perceived benefit was the stimulating effects of caffeine and a feeling of mental alertness. The most frequently cited harms were sleep problems including insomnia and concerns about dependence (or addiction) to caffeine. We found 16 categories of withdrawal symptoms. The most frequently endorsed symptom was headaches, followed by fatigue, exhaustion and low energy., Conclusions: Consumers use a wide range of techniques when attempting to reduce caffeine consumption. Treatment approaches are focused on fading, but the current study found consumers most frequently focus on substance and behavioural substitution., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest, (Copyright © 2020 Elsevier B.V. All rights reserved.)

BACKGROUND The purpose of this study is to evaluate and compare color stability of 3 resin based restorative materials when immersed into staining media at 0, 3, 30, 45, 60, and 75 days, and to assess the efficacy of surface polishing in reducing possible discoloration. MATERIAL AND METHODS Ninety composite discs were prepared in a custom-made mold (5 mm diameter and 2 mm thick) from 3 different light cured composites (Filtek™ Z250, Harmonize™, and G-aenial). Color differences of all specimens were measured by a spectrophotometer according to the CIE L*a*b* system. After baseline color measurements, 30 discs from each composite group were randomly divided into 3 subgroups of 10 specimens each. Subgroups (n=10) were immersed for 75 days into different staining solutions: coffee, tomato sauce, and distilled water (control). Solutions were changed every week and color measurements were repeated every 15 days. At day 75, color measurements of the specimens were performed before and after surface polishing with aluminum oxide discs. The experimental data were statistically evaluated using repeated measures one-way ANOVA test followed by Tukey's multiple pairwise comparison with a significance level of 5%. RESULTS Of the 3 composites, G-aenial reported the highest color change deviation when immersed into coffee (ΔE=8.674), and tomato sauce (ΔE=7.737) at day 75, followed by Harmonize that also exhibited a significant difference for coffee (ΔE=4.7) and tomato sauce (ΔE=3.8) when compared to distilled water. While Filtek™ Z250 did not show any significant difference between the 3 storage solutions (P>0.05). Only G-aenial had significant color change (P<0.05) after polishing with aluminum oxide discs for all tested samples, whereas Filtek™ Z250 and Harmonize presented no significant difference after surface polishing (P>0.05). CONCLUSIONS Under the tested experimental conditions, Filtek™ Z250, among the 3 resin-based composites, exhibited the highest color stability when subjected to coffee and tomato sauce as well. Whereas, G-aenial presented the highest color deviation when immersed in both staining media. Surface polishing effectively reduced coffee and tomato sauce discolorations for G-aenial's specimens and had no significant effect regarding Filtek™ Z250 and Harmonize.

Recent epidemiological studies have shown varying associations between coffee consumption and bladder cancer (BC). This research aims to elucidate the association between coffee consumption and BC risk by bringing together worldwide cohort studies on this topic. Coffee consumption in relation to BC risk was examined by pooling individual data from 12 cohort studies, comprising of 2601 cases out of 501,604 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel Weibull regression models. Furthermore, dose-response relationships were examined using generalized least squares regression models. The association between coffee consumption and BC risk showed interaction with sex (P-interaction < 0.001) and smoking (P-interaction = 0.001). Therefore, analyses were stratified by sex and smoking. After adjustment for potential confounders, an increased BC risk was shown for high (> 500 ml/day, equivalent to > 4 cups/day) coffee consumption compared to never consumers among male smokers (current smokers: HR = 1.75, 95% CI 1.27-2.42, P-trend = 0.002; former smokers: HR = 1.44, 95% CI 1.12-1.85, P-trend = 0.001). In addition, dose-response analyses, in male smokers also showed an increased BC risk for coffee consumption of more than 500 ml/day (4 cups/day), with the risk of one cup (125 ml) increment as 1.07 (95% CI 1.06-1.08). This research suggests that positive associations between coffee consumption and BC among male smokers but not never smokers and females. The inconsistent results between sexes and the absence of an association in never smokers indicate that the associations found among male smokers is unlikely to be causal and is possibly caused by residual confounding of smoking.