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Thermal injuries of the esophagus are rare causes of benign esophageal stricture, and all published cases were successfully treated with conservative management. A 28-year-old Japanese man with a thermal esophageal injury caused by drinking a cup of hot coffee six months earlier was referred to our hospital. The hot coffee was consumed in a single gulp at a party. Although the patient had been treated conservatively at another hospital, his symptoms of dysphagia gradually worsened after discharge. An upper gastrointestinal endoscopy and computed tomography revealed a pin-hole like area of stricture located 19 cm distally from the incisors to the esophagogastric junction, as well as circumferential stenosis with notable wall thickness at the same site. The patient underwent a thoracoscopic esophageal resection with reconstruction using ileocolon interposition. The pathological findings revealed wall thickening along the entire length of the esophagus, with massive fibrosis extending to the muscularis propria and adventitia at almost all levels. Treatment with balloon dilation for long areas of stricture is generally difficult, and stent placement in patients with benign esophageal stricture, particularly young patients, is not yet widely accepted due to the incidence of late adverse events. Considering the curability and quality-of-life associated with a long expected prognosis, we determined that surgery was the best treatment option for this young patient. In this case, we decided to perform an esophagectomy and reconstruction with ileocolon interposition in order to preserve the reservoir function of the stomach and to avoid any problems related to the reflux of gastric contents. In conclusion, resection of the esophagus is a treatment option in patients with benign esophageal injury, especially in cases involving young patients with refractory esophageal stricture. In addition, ileocolon interposition may help to improve the quality-of-life of patients.

Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.7 ± 8.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC., (© 2013 UICC.)

The impact of coffee and green tea consumption on upper aerodigestive tract (UADT) cancer risk has not been established. Evaluation of the possible anticarcinogenic properties of their ingredients is confounded by the potential increase in risk owing to the high temperatures at which these beverages are generally consumed. We conducted a case-control study to evaluate the association between coffee and tea consumption and the risk of UADT cancer. The study enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who visited Aichi Cancer Center between 2001 and 2005. Information on coffee and green tea consumption and other lifestyle factors was collected via a self-administered questionnaire. Consumption of three or more cups of coffee per day had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55-0.96]. In contrast, consumption of three or more cups of green tea per day had a significant positive association with UADT cancer (OR 1.39, 95% CI 1.13-1.70). These associations were evident for head and neck cancer but not for esophageal cancer. The association of coffee consumption with head and neck cancer was observed only among never smokers and alcohol drinkers. Similarly, the association of green tea consumption was observed among never smokers and never alcohol drinkers. No change in these associations was seen on stratification by each confounding factors. These findings suggest that consumption of coffee might be associated with a decreased risk of UADT cancer, whereas that of green tea might be associated with an increased risk., (© 2013 UICC.)

Introduction: Antiepileptic drugs (AEDs) are widely used for the treatment of epilepsy. However, ∼ 30% of patients do not remain seizure free. It is possible that methylxanthine derivatives (e.g., caffeine and theophylline) may partially account for this outcome., Areas Covered: Data on the convulsive activity of methylxanthines are reviewed. The negative impact of caffeine and theophylline (or aminophylline) on the protective activity of classic and newer AEDs is also considered. Case report studies indicate that ingestion of caffeine may increase seizure frequency, which returns to baseline when the consumption of coffee or caffeine-rich drinks is terminated. However, the existing data also provide clinical evidence that caffeine may not be a trigger for precipitation of seizure activity and this discrepancy is evaluated., Expert Opinion: Experimental data indicate that caffeine and aminophylline both significantly reduce the anticonvulsant activity of a number of AEDs. Clinical data are controversial. Patients with epilepsy should be advised not to take methylxanthine-containing medications. Caffeine consumption, especially accidental and in huge quantities, should be avoided in patients with epilepsy.

Aims: Coffee consumption is associated with a reduced risk of Type 2 diabetes. Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults, an autoimmune form of diabetes with features of Type 2 diabetes., Methods: We used data from a population-based case-control study with incident cases of adult onset (≥ 35 years) diabetes, including 245 cases of latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody positive), 759 cases of Type 2 diabetes (glutamic acid decarboxylase antibody negative), together with 990 control subjects without diabetes, randomly selected from the population. Using questionnaire information on coffee consumption, we estimated the odds ratio of latent autoimmune diabetes in adults and Type 2 diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol, education and family history of diabetes., Results: Coffee intake was inversely associated with Type 2 diabetes (odds ratio 0.92, 95% CI 0.87-0.98 per cup/day). With regard to latent autoimmune diabetes in adults, the general trend was weak (odds ratio 1.04, 95% CI 0.96-1.13), but stratification by degree of autoimmunity (median glutamic acid decarboxylase antibody levels) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults (odds ratio 1.11, 95% CI 1.00-1.23 per cup/day). Furthermore, for every additional cup of coffee consumed per day, there was a 15.2% (P = 0.0268) increase in glutamic acid decarboxylase antibody levels., Conclusions: Our findings confirm that coffee consumption is associated with a reduced risk of Type 2 diabetes. Interestingly, the findings suggest that coffee may be associated with development of autoimmunity and possibly an increased risk of more Type 1-like latent autoimmune diabetes in adults., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Caffeine is considered the world's most popular psychoactive substance. Its actions on the central nervous system, mainly mediated by antagonism of adenosine receptors and subsequent modulation of dopaminergic activity, would be particularly sought by depressed patients, as an attempt of self-medication. However, published data suggested that coffee consumption may worsen psychopathological conditions in mood disorders. Thus, we reviewed available evidence in the literature that investigated the effects of coffee consumption on clinical development of underlying psychopathology. Literature research was done by typing on Medline/PubMed and PsychINFO the key words "coffee AND major depression", "coffee AND dysthymia". The research was limited to English language publications and to studies conducted exclusively on humans. Although literature data are conflicting, extensive follow-up studies indicate a significant caffeine effect on risk reduction of developing clinical depression symptoms. Clinical worsening was observed mainly in cases of postpartum depression and comorbid panic disorder. Taking in account the study limitations, we observed a biphasic profile in caffeine psychostimulant effect: low to moderate doses may correlate with a reduction in depressive risk in healthy subjects and an improvement of many clinical symptoms (attention, arousal, psychomotor performance) in depressed patients, whereas the assumption of high doses may result in thymic dysregulation, favor mixed affective states and worsen circadian profiles and anxiety symptoms.

Purpose: The data on the association between coffee consumption and the risk of fractures are inconclusive. We performed a comprehensive literature review and meta-analysis to better quantify this association., Methods: We identified all potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, and CINAHL (until February 2013). The keywords "coffee," "caffeine," "drink," and "beverage" were used as the exposure factors, and the keyword "fracture" was used as the outcome factor. We determined the overall relative risk (RR) and confidence interval (CI) for the highest and lowest levels of coffee consumption. A dose-response analysis was performed to assess the risk of fractures based on the level of coffee consumption., Results: We included 253,514 participants with 12,939 fracture cases from 9 cohort and 6 case-control studies. The estimated RR of fractures at the highest level of coffee consumption was 1.14 (95% CI: 1.05-1.24; I(2)=0.0%) in women and 0.76 (95% CI: 0.62-0.94; I(2)=7.3%) in men. In the dose-response analysis, the pooled RRs of fractures in women who consumed 2 and 8 cups of coffee per day were 1.02 (95% CI: 1.01-1.04) and 1.54 (95% CI: 1.19-1.99), respectively., Conclusions: Our meta-analysis suggests that daily consumption of coffee is associated with an increased risk of fractures in women and a contrasting decreased risk in men. However, future well-designed studies should be performed to confirm these findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Recent research in a large cohort of women showed that coffee consumption is not associated with increased risk of fracture. Whether this is the case also among men is less clear., Methods: In the Cohort of Swedish Men (COSM) study, 42,978 men aged 45-79 years old at baseline in 1997 answered a self-administered food frequency questionnaire covering coffee consumption and a medical and lifestyle questionnaire covering potential confounders. Our main outcomes first fracture at any site and first hip fracture were collected from the National Patient Registry in Sweden. The association between coffee consumption and fracture risk was investigated using Cox's proportional hazards regression., Results: During a mean follow-up of 11.2 years, 5,066 men had a first fracture at any site and of these, 1,186 (23%) were hip fractures. There was no association between increasing coffee consumption (per 200 ml) and rate of any fracture (hazard ratio [HR] 1.00; 95% confidence interval [CI] 0.99-1.02) or hip fracture (HR 1.02; 95% CI 0.99-1.06) after adjustment for potential confounders. For men consuming ≥ 4 cups of coffee/day compared to those consuming <1 cup of coffee/day, HR for any type of fracture was 0.91 (95% CI 0.80-1.02) and for hip fracture: 0.89 (95% CI 0.70-1.14)., Conclusions: High coffee consumption was not associated with an increased risk of fractures in this large cohort of Swedish men.

Although early studies suggested that coffee consumption might increase risk of some cancers, more comprehensive epidemiological and experimental data now generally indicate either neutral or beneficial effects. In this review, we summarize the current evidence for associations between breast, prostate, colorectal, and liver cancers and the consumption of coffee, and discuss the experimental evidence for potential chemopreventive mechanisms of coffee and coffee constituents. The epidemiological evidence consistently indicates that coffee protects against liver cancer, and also point toward protective effects for risk of colorectal cancers (with relative risks of 0.50 (95% CI: 0.42-0.59) and 0.83 (95% CI: 0.75-0.92), respectively, in the most recent meta-analyses). There seems to be no association between the overall risk of breast and prostate cancer and coffee intake. However, for subgroups such as postmenopausal breast cancers, advanced prostate cancers, and breast and prostate cancer survivors, an inverse association with coffee intake is indicated. Potential mechanisms for chemopreventive effects of coffee phytochemicals includes inhibition of oxidative stress and oxidative damage, regulation of DNA repair, phase II enzymatic activity, apoptosis, inflammation, as well as having antiproliferative, antiangiogenetic effects and antimetastatic effects. The experimental evidence for effects of coffee and coffee constituents on each of these processes is discussed., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Coffee consumption has been shown to be associated with various health outcomes, but no comprehensive review and meta-analysis of the association between coffee consumption and total mortality has been conducted. To quantitatively assess this association, we conducted a meta-analysis of prospective cohort studies. Eligible studies were identified by searching the PubMed and EMBASE databases for all articles published through June 2013 and reviewing the reference lists of the retrieved articles. Pooled relative risks (RR) with 95% CI were calculated using a random-effects model. We identified twenty studies of coffee consumption and total mortality, including 129,538 cases of deaths among the 973,904 participants. The RR of total mortality for the high v. low category of coffee consumption was 0.86 (95% CI 0.80, 0.92). The pooled RR for studies using ≥ 2-4 cups/d as a cut-off for the high category was similar to that for studies using ≥ 5-9 cups/d as the cut-off. By geographical region, the inverse association tended to be stronger for the eight studies conducted in Europe (RR 0.78, 95% CI 0.70, 0.88) and three studies carried out in Japan (RR 0.82, 95% CI 0.73, 0.92) than for the nine studies conducted in the USA (RR 0.92, 95% CI 0.84, 1.00). The inverse association was similar for men (RR 0.81, 95% CI 0.73, 0.90) and women (RR 0.84, 95% CI 0.79, 0.89). A weak, but significant, inverse association was found with moderate coffee consumption (1-2 cups/d; RR 0.92, 95% CI 0.87, 0.98). High decaffeinated coffee consumption was also found to be associated with a lower risk of death, but the data are limited. Our findings indicate that coffee consumption is associated with a reduced risk of total mortality.

DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC) risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM) analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028), whereas XRCC1 Arg 399 (p<0.006) was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001), coffee (p<0.001), cumulative AAs exposure (p = 0.041) and MnSOD (p = 0.009) and a decreased risk by MPO (p<0.008) were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different critical life stages.

Aims: A dose-response meta-analysis was carried out between Parkinson's disease (PD) risk, and coffee, tea and caffeine consumption., Methods: A comprehensive search was carried out to identify eligible studies. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline., Results: A total of 13 articles involving 901 764 participants for coffee, eight articles involving 344 895 participants for tea and seven articles involving 492 724 participants for caffeine were included. A non-linear relationship was found between coffee consumption and PD risk overall, and the strength of protection reached the maximum at approximately 3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65-0.81). A linear relationship was found between tea and caffeine consumption, and PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for every two cups/day and 200 mg/day increments, respectively. The association of coffee and tea consumption with PD risk was stronger for men than that for women, and the association of caffeine consumption with PD risk was stronger for ever users of hormones than that for never users of hormones among postmenopausal women. The aforementioned associations were weaker for USA relative to Europe or Asia., Conclusions: A linear dose-relationship for decreased PD risk with tea and caffeine consumption was found, whereas the strength of protection reached a maximum at approximately 3 cups/day for coffee consumption overall. Further studies are required to confirm the findings., (© 2013 Japan Geriatrics Society.)

Background/objectives: Epidemiologic findings concerning the association between coffee consumption and prostate cancer risk yielded mixed results. We aimed to investigate the association by performing a meta-analysis of all available studies., Subjects/methods: We searched PubMed, Web of Science and EMBASE for studies published up to July 2013. We calculated the summary relative risk (RR) and 95% confidence intervals (CIs) for ever, moderate and highest consumption of coffee vs non/lowest consumption. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression., Results: A total of 12 case-control studies and 12 cohort studies with 42,179 cases were selected for final meta-analysis. No significant associations were found among overall analysis. A borderline positive association was found for highest drinkers in five small hospital-based case-control (HCC) studies involving 2278 cases. However, compared with non/lowest drinkers, the summary RRs were 0.92 (95% CI=0.85-0.99) for ever drinkers, 0.92 (95% CI=0.85-1.00) for moderate drinkers and 0.83 (95% CI=0.72-0.96) for highest drinkers from 12 cohort studies, comprising a total of 34,424 cases. An increase in coffee intake of two cups/day was associated with a 7% decreased risk of prostate cancer according to cohort studies. A significant inverse relationship was also found for fatal prostate cancers and high-grade prostate cancers., Conclusions: Case-control studies especially HCC ones might be prone to selection bias and recall bias that might have contributed to the conflicting results. Therefore, the present meta-analysis suggests a borderline significant inverse association between coffee consumption and prostate cancer risk based on cohort studies.

Background: Existing epidemiological evidence is controversial regarding the possible associations between coffee consumption and risk of prostate cancer (PCa) by aggressiveness of the disease., Materials and Methods: We conducted a random-effects dose-response meta-analysis to assess the relationships between coffee consumption and nonaggressive, aggressive and fatal PCa risk. Studies were identified by a search of Medline and Embase databases to 15 July 2013. We carried out separate analyses by grade (Gleason score: low-grade, high-grade) and stage (TNM staging system: localized, advanced) of the tumors. Nonaggressive tumors were defined as low-grade or localized, while aggressive tumors were defined as high-grade or advanced., Results: Eight studies (three case-control and five cohort) were included in this meta-analysis. Gleason 7 tumors were classified as high-grade in one study, while in another study, Gleason 7(4 + 3) tumors were classified as high-grade and Gleason 7(3 + 4) as low-grade. In the remaining four studies, Gleason 7 tumors were excluded from the analyses or analyzed separately. The pooled relative risk (RR) for a consumption increment of 3 cups/day was 0.97 [95% confidence interval (CI) 0.92-1.03] for low-grade PCa (n = 6), 0.97 (95% CI 0.94-0.99) for localized PCa (n = 6), 0.89 (95% CI 0.78-1.00) for high-grade PCa (n = 6), 0.95 (95% CI 0.85-1.06) for advanced PCa (n = 6) and 0.89 (95% CI 0.82-0.97) for fatal PCa (n = 4). No evidence of publication bias was observed. Heterogeneity was absent or marginal (I(2) range = 0-26%), with the only exception of the analysis on advanced PCa, where moderate heterogeneity was observed (I(2) = 60%). When restricting the analyses only to those studies that defined high-grade tumors as Gleason 8-10, the inverse association became slightly stronger [RR: 0.84 (95% CI 0.72-0.98); n = 4]., Conclusions: Results from this dose-response meta-analysis suggest that coffee consumption may be inversely associated with the risk of fatal PCa. No clear evidence of an association with PCa incidence was observed.

Background: Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose-response relationship of long-term coffee consumption with CVD risk., Methods and Results: PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified (P for heterogeneity=0.09, P for trend <0.001, P for nonlinearity <0.001). Compared with the lowest category of coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87-1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80-0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84-0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease (P for heterogeneity=0.001, P for trend <0.001, P for nonlinearity <0.001) and stroke (P for heterogeneity=0.07, P for trend <0.001, P for nonlinearity <0.001; P for trend differences >0.05) risks., Conclusions: A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.

Observational studies and animal evidence suggest an association between coffee consumption and the risk of prostate cancer. However, the results are inconsistent. We evaluated the association by conducting a meta-analysis of prospective cohort studies. PubMed and Embase were searched through June 2013 to identify studies that met predetermined inclusion criterion. A random-effects model was used to calculate the pooled risk estimates. Ten prospective cohort studies involving 8973 patients with prostate cancer and 206 096 participants were included in this systematic review. Compared with individuals who seldom or never drink coffee, the pooled relative risk of prostate cancer was 0.88 (95% confidence interval: 0.82-0.95) for regular coffee drinkers. Exclusion of any single study did not materially alter the combined risk estimate. Visual inspection of a funnel plot and Begg's and Egger's tests did not indicate evidence of publication bias. In summary, integrated evidence from prospective cohort studies supports the hypothesis that coffee consumption may decrease the risk of prostate cancer.

Background and Aims: Understanding the effect of coffee on health-related quality of life (HRQL) would contribute to explain the mechanisms of the long-term effect of coffee on health. The aim of this study was to examine the association between coffee consumption and HRQL., Methods: Cross-sectional study conducted in 2008-2010 among 11,423 individuals representative of the Spanish population aged ≥18 years. Habitual coffee and food consumption was assessed with a validated diet history. HRQL was measured using the Spanish version of the SF-12 questionnaire. The analyses were performed using linear regression and adjusted for the main confounders., Results: Among men, no association was found between coffee consumption and the physical and mental composite summaries (PCS and MCS) of the SF-12. Among women, compared to those who did not consume coffee, habitual coffee drinkers showed similar scores on the PCS [beta coefficients (p value) for 1, 2, 3, and ≥4 cups/day: 0.49 (0.20), 0.62 (0.21), 0.50 (0.45), and 0.36 (0.59)]; but slightly better scores on the MCS [beta (p value): 1.58 (<0.001), 1.58 (0.004), 0.80 (0.31), and 1.22 (0.10)]. These results reflect mostly the consumption of non-filtered caffeinated coffee. Tea consumption and total caffeine intake did not show an association with HRQL., Conclusion: We found no evidence of an adverse effect of coffee on HRQL. These results are consistent with the null association between this beverage and several chronic diseases and all-cause mortality reported in many studies. The weak positive association of coffee with the MCS found among women needs further confirmation., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: This study was undertaken to explore the association between maternal coffee consumption during pregnancy and childhood acute leukemia (AL)., Study Design: The PubMed database was used to search studies up to May 5, 2013, and the lists of references of retrieved articles were also screened to identify additional relevant studies. Studies were included if they reported the odds ratio and corresponding 95% confidence interval (CI) of childhood AL, including childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), with respect to maternal coffee consumption during pregnancy., Results: Compared with non/lowest drinkers, the combined odds ratio regarding the relationship of maternal coffee consumption during pregnancy and childhood AL was 1.22 (95% CI, 1.04-1.43) for ever drinkers, 1.16 (95% CI, 1.00-1.34) for low to moderate-level drinkers, and 1.72 (95% CI, 1.37-2.16) for high-level drinkers. When analysis was conducted by subtypes of childhood AL, maternal coffee consumption (high-level drinkers vs non/lowest drinkers) was statistically significantly associated with childhood ALL (1.65; 95% CI, 1.28-2.12) and childhood AML (1.58; 95% CI, 1.20-2.08). We observed the linear dose-response relationship of coffee consumption and childhood AL (P for nonlinearity = .68), including childhood ALL and childhood AML; with increased coffee consumption, the risk of childhood AL increased., Conclusion: The findings of the metaanalysis suggest that maternal coffee consumption during pregnancy may increase the risk of childhood AL. Because of limited studies, further prospective studies are urgently needed to explore the adverse effect of coffee consumption on childhood AL., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Current evidence from experimental studies in animals and humans along with findings from prospective studies indicates beneficial effects of green and black tea as well as chocolate on cardiovascular health, and that tea and chocolate consumption may reduce the risk of stroke. The strongest evidence exists for beneficial effects of tea and cocoa on endothelial function, total and LDL cholesterol (tea only), and insulin sensitivity (cocoa only). The majority of prospective studies have reported a weak inverse association between moderate consumption of coffee and risk of stroke. However, there are yet no clear biological mechanisms whereby coffee might provide cardiovascular health benefits. Awaiting the results from further long-term RCTs and prospective studies, moderate consumption of filtered coffee, tea, and dark chocolate seems prudent.

Objective: The purpose of this clinical investigation was to evaluate the effectiveness of a marketed whitening chewing gum compared to a no-gum control in preventing the formation of extrinsic stains on the teeth of stain-forming subjects when chewed over a 12-week period of regular unsupervised use in conjunction with daily tooth brushing., Methods: This was a single-center, examiner-blind, randomized, 12-week crossover clinical trial. Stain-forming (after smoking or drinking coffee or tea) adults, starting with a stain-free baseline, either chewed the test gum (Orbit White) unsupervised four times per day, 15 minutes/chew, or used no gum along with daily brushing with a commercially available toothbrush and dentifrice for 12 weeks. At the crossover, all procedures were repeated with subjects assigned the opposite treatment. Extrinsic stain was measured at six and 12 weeks by both the Lobene Stain Index (LSI) and the Modified Lobene Stain Index (MLSI) using separate experienced examiners., Results: After 12 weeks, LSI stain scores showed a significant 25% reduction (p = 0.0008) in new stain formation for subjects using the test chewing gum along with tooth brushing versus tooth brushing alone (no-gum control). The corresponding MLSI stain scores demonstrated a 36% reduction (p < 0.0001) in the formation of extrinsic stain on the teeth., Conclusion: The overall findings of this clinical study demonstrated that regular use of Orbit White chewing gum, soon after smoking or drinking coffee or tea, will supplement daily tooth brushing in preventing unsightly stains from forming on the anterior teeth compared to brushing alone.

Objective: Epidemiologic studies have reported various results relating coffee to urolithiasis. A meta-analysis of cohort and case-control studies was conducted to pool the relative risk (RR) estimates of the association between coffee and urolithiasis., Methods: Eligible studies were retrieved via both computer searches and review of references. We analyzed abstracted data with random effects models to obtain the summary RR estimates. A dose-response meta-analysis was performed for studies reporting categorical RR estimates for a series of exposure levels., Results: A total of 6 studies (2 cohort and 4 case-control studies) on coffee intake were included in the meta-analysis. The pooled odds ratio (OR) showed a significant influence of the highest coffee consumption (OR = 0.70, 95% confidence interval 0.60-0.82) on the risk of urolithiasis. Coffee exhibited an inverse dose-response relationship with urolithiasis. In stratified analysis, a significant inverse association between coffee and urolithiasis was observed in study design, geographical region and gender subgroup., Conclusions: The overall current literature suggests that coffee intake is associated with a decreased risk of urolithiasis. Further efforts should be made to clarify the underlying biological mechanisms., (2014 S. Karger AG, Basel.)

Unlabelled: The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1-4 cups of tea daily was associated with a lower risk of hip fracture., Introduction: Prospective cohort and case-control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture., Methods: We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95% confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose-response, heterogeneity, publication bias, and subgroup analyses., Results: Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case-control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95% CI 0.71-1.17) and 0.84 (95% CI 0.66-1.02), respectively. For the dose-response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p(nonlinearity) < 0.01). Compared to no tea consumption, 1-4 cups of tea per day may reduce the risk of hip fracture by 28% (0.72; 95% CI 0.56-0.88 for 1-2 cups/day), 37% (0.63; 95% CI 0.32-0.94 for 2-3 cups/day), and 21% (0.79; 95% CI 0.62-0.96 for 3-4 cups/day)., Conclusions: We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1-4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.

Background: Epidemiologic studies have reported coffee consumption to be associated with various health conditions. The purpose of this study was to examine the relationship of coffee consumption with colorectal cancer incidence in a large-scale prospective cohort study in Japan., Methods: We used data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). Here, we analyzed a total of 58 221 persons (23 607 men, 34 614 women) followed from 1988 to the end of 2009. During 738 669 person-years of follow-up for the analysis of colorectal cancer risk with coffee consumption at baseline, we identified 687 cases of colon cancer (355 males and 332 females) and 314 cases of rectal cancer (202 males and 112 females). We used the Cox proportional-hazard regression model to estimate hazard ratio (HR)., Results: Compared to those who consumed less than 1 cup of coffee per day, men who consumed 2-3 cups of coffee per day had an HR of 1.26 (95% confidence interval [CI] 0.93-1.70), and men who consumed more than 4 cups of coffee per day had an HR of 1.79 (95% CI 1.01-3.18). A statistically significant increase in the risk of colon cancer was associated with increasing coffee consumption among men (P for trend = 0.03). On the other hand, coffee consumption in women was not associated with incident risk of colon cancer. Coffee consumption was also not associated with rectal cancer incidence in men or women., Conclusions: This large-scale population-based cohort study showed that coffee consumption increases the risk of colon cancer among Japanese men.

Background: Data regarding the effects of tea, coffee, and milk on the risk of colorectal cancer are inconsistent. We investigated associations of tea, coffee, and milk consumption with colorectal cancer risk and attempted to determine if these exposures were differentially associated with the risks of proximal colon, distal colon, and rectal cancers., Methods: Data from 854 incident cases and 948 controls were analyzed in a case-control study of colorectal cancer in Western Australia during 2005-07. Multivariable logistic regression was used to analyze the associations of black tea (with and without milk), green tea, herbal tea, hot coffee, iced coffee, and milk with colorectal cancer., Results: Consumption of 1 or more cups of herbal tea per week was associated with a significantly decreased risk of distal colon cancer (adjusted odds ratio, 0.37; 95% CI, 0.16-0.82; PTrend = 0.044), and consumption of 1 or more cups of iced coffee per week was associated with increased risk of rectal cancer (adjusted odds ratio, 1.52; 95% CI, 0.91-2.54; PTrend = 0.004). Neither herbal tea nor iced coffee was associated with the risk of proximal colon cancer. Hot coffee was associated with a possible increased risk of distal colon cancer. Black tea (with or without milk), green tea, decaffeinated coffee, and milk were not significantly associated with colorectal cancer risk., Conclusions: Consumption of herbal tea was associated with reduced risk of distal colon cancer, and consumption of iced coffee was associated with increased rectal cancer risk.

Background: Intake of caffeinated beverages, such as coffee and tea, has been related to improvements in components of metabolic syndrome (MetS), but studies conducted in the Mediterranean region are scarce. The aim of this study was to evaluate whether or not consumption of a variety of beverages containing caffeine was associated with components of MetS in an Italian population., Methods: From May 2009 to December 2010, a cross-sectional survey was conducted on 1889 inhabitants living in Sicily, southern Italy. Data regarding demographic characteristics, habitual beverage intake, and adherence to the Mediterranean diet were collected, and clinical information was retrieved from the general practitioners' computer records., Results: After adjusting for all covariates, coffee (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.27-0.70) and tea (OR 0.51, 95% CI 0.34-0.78) were associated with MetS, whereas no association was observed between caffeine intake and MetS. Among other factors, age, body mass index, physical activity, current smoking, and adherence to Mediterranean diet were associated with having MetS. Triglycerides were inversely associated with consumption of both espresso coffee and tea. The healthy effects of such beverages were more evident in individuals with unhealthy dietary habits., Conclusions: Although no direct association between caffeine intake and MetS or its components was observed, coffee and tea consumption was significantly related to reduced odds of MetS.

This study aimed to add to prospective data on the possible inverse association between coffee consumption and endometrial cancer risk, already supported by several case-control studies. Coffee and tea consumption and possible confounding factors were assessed among 42,270 women aged 30-49 years at enrollment in 1991-1992 in the Swedish Women's Lifestyle and Health cohort study, with complete follow-up through 2009. We calculated caffeine intake per day; Cox proportional hazard models were used to estimate multivariable relative risks (mRR) for endometrial cancer with 95% confidence intervals (CIs). One hundred forty-four endometrial cancers were diagnosed during follow-up. Women with and without endometrial cancer had a similar mean daily coffee consumption (549 vs. 547 g), tea consumption (104 vs. 115 g), and caffeine intake (405 vs. 406 mg). Compared to those consuming <2 cups of coffee per day, women consuming >3 cups had a mRR of 1.56 (95% CI: 0.94-2.59; P for trend = 0.17). Compared with the lowest tertile of caffeine intake, the highest tertile had a mRR of 1.32 (95% CI: 0.87-1.99; P for trend = 0.27). Our study provides no convincing evidence of an association between coffee consumption, tea consumption, or caffeine intake and endometrial cancer risk among middle-aged women.

Objective: Taking levothyroxine (L-T₄) with coffee or with water followed by coffee intake within a few minutes results in poor TSH response in many patients. T₄ is available in tablet form worldwide, but novel formulations in soft gel capsule or liquid form are now available., Design: We fortuitously identified a euthyroid patient who wrongly consumed liquid L-T₄ with coffee at breakfast; after changing the time of consumption to 30 min before breakfast, no change in TSH, free T₄ (fT₄), and free tri-iodothyronine (fT₃) concentrations was observed. Once the first patient was identified, additional stable euthyroid patients who consumed liquid L-T₄ with coffee were identified., Methods: Patients were recruited by searching our 'thyroid patients' database. All the patients on liquid L-T₄ treatment were contacted by phone to ask them whether they took L-T₄ at breakfast. We identified 54 patients who were submitted to TSH, fT₄, and fT₃ evaluation, with the indication that the same dosage of L-T₄ be consumed 30 min before breakfast. We determined their TSH, fT₄, and fT₃ concentrations after 3 and 6 months again., Results: no significant difference in thyroid hormone concentrations was observed in patients when they consumed L-T₄ at breakfast or when they consumed it 30 min before breakfast for 3 and 6 months (TSH: 2.5±1.1 vs 2.5±1.1 and 2.4±1.1 mIU/l respectively, fT₄: 12.4±2.4 vs 12.5±2.4 and 12.3±2.1 pg/ml respectively, and fT₃: 3.4±0.6 vs 3.4±0.6 and 3.3±0.5 pg/ml respectively)., Conclusion: Oral liquid L-T₄ formulations could diminish the problem of L-T₄ malabsorption caused by coffee when using traditional tablet formulations.

Background & Aims: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer., Methods: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression., Results: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers., Conclusions: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Tea and coffee, after water, are the most commonly consumed beverages in the world and are the top sources of caffeine and antioxidant polyphenols in the American diet. The purpose of this review is to assess the health effects of chronic tea and/or coffee consumption., Recent Findings: Tea consumption, especially green tea, is associated with significantly reduced risks for stroke, diabetes and depression, and improved levels of glucose, cholesterol, abdominal obesity and blood pressure. Habitual coffee consumption in large epidemiological studies is associated with reduced mortality, both for all-cause and cardiovascular deaths. In addition, coffee intake is associated with risks of heart failure, stroke, diabetes mellitus and some cancers in an inverse dose-dependent fashion. Surprisingly, coffee is associated with neutral to reduced risks for both atrial and ventricular arrhythmias. However, caffeine at high doses can increase anxiety, insomnia, calcium loss and possibly the risk of fractures., Summary: Coffee and tea can generally be recommended as health-promoting additions to an adult diet. Adequate dietary calcium intake may be particularly important for tea and coffee drinkers.

The purpose of the present study was to evaluate whether exposure to coffee during bleaching treatment with 16% carbamide peroxide (CP) affects the degree of whitening and tooth sensitivity. Forty patients with central incisors darker than A2 were selected. Participants who did not drink coffee were assigned to the control group (CG), while participants who drink coffee at least twice a day were assigned to the experimental group (EG). For CG, foods with dyes were restricted. For EG there was no restriction on food and patients were asked to make coffee rinses for 30 seconds, four times daily. For both groups 16% CP was used for a period of three hours daily for three weeks. Shade evaluation was assessed visually by Vita classical shade guide and by the Easyshade spectrophotometer at baseline, during bleaching (first, second, and third weeks), and postbleaching (one week and one month). Patients recorded their sensitivity perceptions by means of the numerical rating scale and 0-10 visual analog scales. Variation in shade guide units and the two colors (ΔE) were evaluated by two-way analysis of variance and Tukey tests (α=0.05). Absolute risk of tooth sensitivity and intensity of tooth sensitivity was evaluated by Fisher exact and Mann-Whitney tests (α=0.05). Effective bleaching was observed for both groups after three weeks, without statistical difference. No difference in terms of risk of tooth sensitivity and intensity of tooth sensitivity was detected between groups. Approximately 57% of the participants experienced tooth sensitivity, which was recorded mainly as "mild." Exposure to coffee during bleaching treatment does not seem to affect the degree of bleaching and tooth sensitivity.

As coffee-consumption is a widespread tradition, its possible impact on health has been of considerable interest. This review examines the effects of coffee on cardiovascular risk, outlines underlying biological mechanisms, and discusses implications for public health. In the past, coffee was often viewed as a cardiovascular risk-factor. However, in meta-analyses of recent well-controlled prospective epidemiologic studies, coffee-consumption was not associated with risk of coronary heart disease and weakly associated with a lower risk of stroke and heart failure. Also, available evidence largely suggests that coffee-consumption is not associated with a higher risk of fatal cardiovascular events. In randomized trials coffee-consumption resulted in small increases in blood pressure. Unfiltered coffee increased circulating LDL cholesterol and triglycerides concentrations, but filtered coffee had no substantial effects on blood lipids. In summary, for most healthy people, moderate coffee consumption is unlikely to adversely affect cardiovascular health. Future work should prioritize understanding the effects of coffee in at-risk populations.

Background: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, and risk factors are well established. Caffeine exposure has been associated with increased risk of AF, but heterogeneous data exist in the literature., Objective: To evaluate the association between chronic exposure to caffeine and AF., Design: Systematic review and meta-analysis of observational studies., Data Sources: PubMed, CENTRAL, ISI Web of Knowledge and LILACS to December 2012. Reviews and references of retrieved articles were comprehensively searched., Study Selection: Two reviewers independently searched for studies and retrieved their characteristics and data estimates., Data Synthesis: Random-effects meta-analysis was performed, and pooled estimates were expressed as OR and 95% CI. Heterogeneity was assessed with the I(2) test. Subgroup analyses were conducted according to caffeine dose and source (coffee)., Results: Seven observational studies evaluating 115 993 individuals were included: six cohorts and one case-control study. Caffeine exposure was not associated with an increased risk of AF (OR 0.92, 95% CI 0.82 to 1.04, I(2)=72%). Pooled results from high-quality studies showed a 13% odds reduction in AF risk with lower heterogeneity (OR 0.87; 95% CI 0.80 to 0.94; I(2)=39%). Low-dose caffeine exposure showed OR 0.85 (95% CI 0.78 to 92, I(2)=0%) without significant differences in other dosage strata. Caffeine exposure based solely on coffee consumption also did not influence AF risk., Conclusions: Caffeine exposure is not associated with increased AF risk. Low-dose caffeine may have a protective effect.

Objective: To evaluate the association between coffee consumption and mortality from all causes and from cardiovascular disease., Patients and Methods: Data from the Aerobics Center Longitudinal Study representing 43,727 participants with 699,632 person-years of follow-up were included. Baseline data were collected by an in-person interview on the basis of standardized questionnaires and a medical examination, including fasting blood chemistry analysis, anthropometry, blood pressure, electrocardiography, and a maximal graded exercise test, between February 3, 1971, and December 30, 2002. Cox regression analysis was used to quantify the association between coffee consumption and all-cause and cause-specific mortality., Results: During the 17-year median follow-up, 2512 deaths occurred (804 [32%] due to cardiovascular disease). In multivariate analyses, coffee intake was positively associated with all-cause mortality in men. Men who drank more than 28 cups of coffee per week had higher all-cause mortality (hazard ratio [HR], 1.21; 95% CI, 1.04-1.40). However, after stratification based on age, younger (<55 years old) men and women showed a significant association between high coffee consumption (>28 cups per week) and all-cause mortality after adjusting for potential confounders and fitness level (HR, 1.56; 95% CI, 1.30-1.87 for men; and HR, 2.13; 95% CI, 1.26-3.59 for women)., Conclusion: In this large cohort, a positive association between coffee consumption and all-cause mortality was observed in men and in men and women younger than 55 years. On the basis of these findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups per day). However, this finding should be assessed in future studies of other populations., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

High consumption of coffee has been suggested to reduce the risk of some late-onset diseases and death but also to contribute to the development of osteoporotic fractures. Results of previous fracture studies have been inconsistent, and a comprehensive study is needed. The longitudinal population-based Swedish Mammography Cohort, including 61,433 women born in 1914-1948, was followed up from 1987 through 2008. Coffee consumption was assessed with repeated food frequency questionnaires. During follow-up, 14,738 women experienced fracture of any type, and 3,871 had a hip fracture. In a subcohort (n = 5,022), bone density was measured and osteoporosis determined (n = 1,012). After multivariable adjustment, there was no evidence of a higher rate of any fracture (hazard ratio per 200 mL coffee = 0.99; 95% confidence interval: 0.98, 1.00) or hip fracture (hazard ratio per 200 mL coffee = 0.97, 95% confidence interval: 0.95, 1.00) with increasing coffee consumption. A high coffee intake (≥4 cups daily) versus a low intake (<1 cup daily) was associated with a 2%-4% lower bone density, depending on site (P < 0.001), but the odds ratio for osteoporosis was only 1.28 (95% confidence interval: 0.88, 1.87). Thus, high coffee consumption was associated with a small reduction in bone density that did not translate into an increased risk of fracture.

Background: Coffee and tea are commonly consumed and carry potential anticancer components that could reduce the risk of colorectal cancer; however, their relationships with colorectal cancer risk remain inconsistent., Methods: A prospective analysis was carried out to examine the relationships of coffee and tea intake with colorectal cancer risk in 57,398 men and women in the intervention arm of the National Cancer Institute-Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, a national screening study that limits differential detection biases. Coffee and tea intakes were assessed by food frequency questionnaire., Results: Six hundred and eighty-one incident colorectal cancer cases were ascertained during a median follow-up of 11.4 years. Greater coffee intake was not associated with risk of colorectal cancer (relative risk (RR)=1.08, 95% confidence interval (CI)=0.79-1.48, Ptrend=0.23). Stratifying by cancer site (Pheterogeneity=0.48) or stage (Pheterogeneity=0.83) did not alter the relationship. Associations remained unchanged in subsets of participants for either caffeinated or decaffeinated coffee or when stratifying by several colorectal cancer risk factors. Similarly, greater tea intake was not associated with colorectal cancer risk overall (RR=0.77, 95% CI=0.55-1.09, Ptrend=0.17) or by cancer site (Pheterogeneity=0.14) or stage (Pheterogeneity=0.60). These associations were not modified by several colorectal cancer risk factors., Conclusion: The findings of this study do not provide evidence to suggest that drinking coffee or tea is beneficial in protecting against colorectal cancer.

Background: The association between ambient air pollution and heart rate variability (HRV) has been well-documented. Little is known about the association of HRV at night with indoor air pollution and coffee consumption. The aim of this study was to investigate the association of HRV indices with indoor air pollution, working time and coffee consumption., Methods: We recruited 60 young healthy convenient store workers to monitor indoor PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm) exposures, coffee consumption (yes vs. no) and HRV indices during daytime (0700-1500 hours) and nighttime (2300-0700 hours). We used linear mixed effects models to assess the associations of HRV indices with indoor PM2.5 exposures and coffee consumption., Results: We observed the inverse association between indoor PM2.5 exposures and HRV indices, with a decrease in all HRV indices with increased indoor PM2.5 exposures. However, the decrease was most pronounced during nighttime, where a 1 interquartile range (IQR) increase in indoor PM2.5 at 4-hr time-weighted moving average was associated with a change of -4.78% 5-min standard deviation (SD) of normal-to-normal intervals for 5-min segment (SDNN) and -3.23% 5-min square root of the mean squared differences of successive intervals for 5-min segment (r-MSSD). Effects of indoor PM2.5 were lowest for participants with coffee consumption during daytime., Conclusions: Indoor PM2.5 exposures were associated with decreased 5-min SDNN and 5-min r-MSSD, especially during nighttime. The effect of indoor PM2.5 on HRV indices may be modified by coffee consumption in young healthy convenient store workers.

This study was conducted to assess the association between the risks of spina bifida (SB) in relation to cigarette, alcohol, and caffeine consumption by women during the first month of pregnancy. Between 1988-2012, this multi-center case-control study interviewed mothers of 776 SB cases and 8,756 controls about pregnancy events and exposures. We evaluated cigarette smoking, frequency of alcohol drinking, and caffeine intake during the first lunar month of pregnancy in relation to SB risk. Logistic regression models were used to calculate adjusted odds ratios and 95% confidence intervals. Levels of cigarette smoking (1-9 and ≥10/day), alcohol intake (average ≥4 drinks/day) and caffeine intake (<1, 1, and ≥2 cups/day) were not likely to be associated with increased risk of SB. Further, results were similar among women who ingested less than the recommended amount of folic acid (400 μg/day).