The Potential Link between Episodes of Diverticulitis or Hemorrhoidal Proctitis and Diets with Selected Plant Foods: A Case–Control Study

Diverticulitis and hemorrhoidal proctitis in the population are significant public health problems. We studied the potential association between the intake of certain plant foods and diverticulitis or hemorrhoidal episodes through a case–control study including 410 cases and 401 controls. We used a semiquantitative food frequency questionnaire. The intake was additionally quantified according to a 24 h recall. The plant foods or derived food products were categorized by their main chemical components into ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods such as curcumin. The mean score for overall intake of plant foods under consideration was 6.3 points, and this was significantly higher in cases (8.5) than in controls (4.1). Overall intake was similar in cases presenting with diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (>7 points), compared to controls. Explanatory logistic regression models showed that the strongest association with diverticulitis and hemorrhoidal proctitis was shown by the chemical food group of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. Neither alliin nor miscellaneous food groups showed any association. High, frequent consumption of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids increase the risk of diverticulitis and hemorrhoidal proctitis.     

Cigarette smoking and benign proliferative epithelial disorders of the breast in women: a case-control study.

STUDY OBJECTIVE: The purpose of the study was to investigate the possible association between cigarette smoking and benign proliferative epithelial disorders of the breast. DESIGN: This was a case-control study with two different control groups. SETTING: The study was community based and took place in metropolitan Adelaide, South Australia. SUBJECTS: 506 biopsy proven cases between 18 and 75 years were identified, of whom 39 could not be approached because of surgeon refusal, 66 would not be interviewed and 18 were untraceable, leaving 383 for inclusion in the study. Controls were 192 women who had had a negative breast biopsy, out of a possible 259 (17 surgeon refusals, 39 interview refusals, 11 untraceable); and a randomly selected group of women matched to the index group for age and area of residence (582 subjects were approached to enrol 383 controls). MEASUREMENTS AND MAIN RESULTS: All breast biopsies were examined by one pathologist and classified using a standard system. Sociodemographic and medical information was collected by trained interviewers using structured questionnaires. Overall, and within menopausal strata, risk of benign proliferative epithelial disease for women who had ever smoked and for current and ex-smokers was similar to that for women who had never smoked. In premenopausal women, using community controls as the comparison group, risk decreased with cigarette-years of exposure, but the trend was not statistically significant. Risk appeared to increase when biopsy controls were used. There was no trend in the association when examined by degree of cytological atypia. CONCLUSIONS: The data suggest that cigarette smoking is not related to the risk of benign proliferative epithelial breast disease.     

The effect of methylxanthines on milk volume and composition, and growth of rat pups

A study was conducted to investigate the effect of differential dose levels of methylxanthines on lactational performance, with respect to milk volume and composition and pup growth. The methylxanthines; caffeine, theophylline and theobromine, were administered via drinking water in the proportions occurring in tea, at a dose of 50, 1 and 2 mg/kg body-weight respectively to Wistar albino rats throughout pregnancy and for up to the 14th day of lactation. A fourth group received a mixture of all three methylxanthines. Maternal food and fluid intake and weight changes, as well as weight gain in the litter were monitored thrice weekly. Milk samples were collected from the dams on days 7 and 14 of lactation, while milk volume was measured on days 12-13 by a method using tritiated water. Results showed that caffeine and theobromine significantly enhanced litter weight (P less than 0.01 and 0.05 respectively). In the caffeine group, enhanced litter growth was due to a significant increase (P less than 0.05) in milk volume, consequent to increased maternal food intake (P less than 0.05). In the theobromine group there was only a weak association between increased litter weight and milk volume. Theophylline had no effect on the volume or composition of milk, or litter weight. The combination of all three methylxanthines also failed to produce any of the positive effects observed with separate drug treatments.     

Collected Research on Phytonutrients: Alkaloids

Alkaloids are a very diverse group of compounds occurring naturally in plants. In general, they are basic in nature, are nitrogen containing, and act on the central nervous system. They have been used throughout history for medicinal purposes as well as feeding deterrents to animals. Some examples of alkaloids include poisons, neurotoxins, social drugs (such as nicotine and caffeine), and psychedelic drugs. This article will focus specifically on three phytonutrients: caffeine, theobromine, and theophylline from the methylxanthine family also known as “purine alkaloids.” They are readily available to consumers in foods and have many benefits when not taken in excess.     

Cigarette smoking and risk of benign proliferative epithelial disorders of the breast

Benign proliferative epithelial disorders (BPED) of the breast are conditions which are thought to have premalignant potential. The purpose of the present investigation was to study the association between cigarette smoking and risk of BPED. The study was undertaken within the 56,837 women within Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40–59 at recruitment.) During the course of the follow-up period, a total of 691 women in the dietary cohort were diagnosed with biopsy-confirmed incident BPED. For comparative purposes, a subcohort consisting of a random sample of 5681 women (including 65 of the subjects with BPED) was selected from the full cohort. After exclusions for various reasons, the analyses were based on 691 cases and 5443 non-cases. Overall, the results of the present study are almost uniformly null, and provide little support for an association between cigarette smoking and risk of BPED. Analyses conducted separately in the screened and control arms of the NBSS also failed to provide strong support for associations, and there was little difference between the results for screen-detected and interval-detected BPED. There was some suggestion of an increase in risk in post-menopausal ex-smokers, but the trend in risk with cigarette-years of exposure in this group was not statistically significant. Risk in ex-smokers varied little by years since smoking cessation. There was little evidence for associations with either atypical or non-atypical forms of BPED.     

Methylxanthines and benign breast disease

The relation between methylxanthine consumption and biopsied benign breast disease was investigated by using data from a case-control study which included 1,569 cases and 1,846 controls identified between 1973 and 1980 through a nationwide screening program. There was no evidence of an association between methylxanthine consumption and benign breast disease in the total study population. When histologic types of benign breast disease were examined, there were no trends in risk according to methylxanthine consumption among the 813 cases with fibrocystic disease, the 508 cases for whom detailed pathology data were not available, the 172 cases with benign neoplasms, or the 156 cases with other benign conditions. When cases with fibrocystic disease were examined according to presence of atypia, hyperplasia, sclerosing adenosis, or cysts, there was, again, no association between methylxanthine consumption and risk of disease. In addition, no relation was found between methylxanthine consumption and menstrual breast tenderness among premenopausal women with fibrocystic disease or unknown conditions.     

Risk factors for fibroadenoma: a case-control study in Australia.

Risk factors for fibroadenoma were examined in a case-control study involving 117 fibroadenoma cases ascertained by a major private pathology laboratory in Adelaide, Australia, between January 1983 and October 1985. For each case a population control was randomly selected from the electoral roll in Adelaide and matched to the corresponding case by sex, age, and socioeconomic grading of area of residence. Another 189 women whose first biopsy for benign breast disease was examined in the same laboratory during the same time period as those of the cases, but did not show evidence of epithelial proliferation, were also included in the study as a biopsy control group. Risk of fibroadenoma was associated inversely with the Quetelet index, but there was no evidence of an association with age at menarche or menopausal status. The risk of fibroadenoma decreased with an increasing number of full-term pregnancies and was increased in association with use of oral contraceptives at an early age (under 20 years); however, these two associations were observed only when cases were compared with the population controls. Alcohol consumption and dietary fat intake were found not to be associated with altered risk of fibroadenoma, while in multivariate analyses, duration of cigarette smoking and daily vitamin C intake were both shown to have inverse associations with risk of fibroadenoma. Although fibroadenoma does share some risk factors with breast cancer, there is insufficient evidence to suggest that it represents a precursor state.     

Prenatal caffeine assessment: fetal and maternal biomarkers or self-reported intake?

PURPOSE: We sought to examine associations among measures of caffeine exposure, including maternal urine, umbilical cord blood, and maternal self report. METHODS: Pregnant women were recruited from 56 obstetric practices and 15 clinics associated with six hospitals in Connecticut and Massachusetts between September 1996 and January 2000; 3633 women were enrolled. Maternal urine throughout pregnancy and umbilical cord blood samples were analyzed for caffeine, paraxanthine, theophylline, and theobromine. Maternal caffeine intake was assessed throughout pregnancy. RESULTS: Urinary and cord blood biomarkers were correlated with reported intake throughout pregnancy (range r = 0.35-0.66; p < 0.0001). Infants of smokers had greater cord blood concentrations of paraxanthine, reflecting faster caffeine metabolism in smokers, and cord blood paraxanthine levels were more strongly correlated with intake in smokers. CONCLUSION: Maternal self reported intake may still be the optimal and most valid measure of antenatal caffeine exposure, since biomarkers do not reflect exposure over pregnancy.     

液相色谱-串联质谱法同时测定饮料中的咖啡因、茶碱和可可碱

目的建立市售饮料中咖啡因、茶碱和可可碱的液相色谱-串联质谱法(LC-MS/MS)。方法将饮料用水稀释100倍后,采用三氯甲烷∶异丙醇(9∶1,V/V)进行提取,提取液经Allure PFP Propyl柱(100 mm×2.1 mm,5μm)分离,以5 mmol/L乙酸铵溶液(含5%甲醇、0.05%的甲酸)-甲醇为流动相进行梯度洗脱,采用电喷雾正离子化(ESI+)、多反应监测模式同时测定咖啡因、茶碱和可可碱。结果咖啡因、茶碱和可可碱在10 ng/ml^1000 ng/ml范围内方法的线性相关系数(r)均>0.9970,检出限为2 ng/ml^5 ng/ml,加标回收率均>60.68%,精密度均<14.41%。应用于实际市售饮料中,均检出咖啡因成分,部分饮品检出茶碱、可可碱成分。结论该方法简便、灵敏,可用于监测市售饮料中咖啡因、茶碱、可可碱的含量。     

Guarana: Paullinia cupana, P. sorbilis; also known as Brazilian cocoa and 'zoom'

The main constituent of guarana is caffeine, with smaller quantities of theophylline and theobromine. There is no evidence that the berries or extracts contain anything else that is therapeutically useful.Guarana is associated with many therapeutic properties, but there is no evidence to support these other than effects that can be attributed to caffeine. Guarana is widely available in herbal products and energy drinks. Excessive intake can cause the same effects as too much caffeine. It is not widely recognised that guarana has a high caffeine content and the labelling on some products is misleading.Although not specifically studied, guarana would be expected to exhibit the same range of adverse effects and drug interactions as those associated with caffeine.     

Effects of caffeine and its reactive metabolites theophylline and theobromine on the differentiating testis

A previous study in the rat (Pollard et al. 1990) established that caffeine, when administered during pregnancy, significantly inhibited the differentiation of the seminiferous cords and subsequent Leydig cell development in the interstitium. However, that study could not distinguish between the direct effects of caffeine and/or the intermediary secondary toxic effects of metabolites such as theophylline and theobromine. Because the fetus lacks the appropriate enzyme systems, clearance of toxic substances takes place via the placenta and maternal liver. Thus, a suitable in vitro system can effectively differentiate between primary and secondary drug effects. In the present study, 13-day-old fetal testis, at the stage of incipient differentiation, were cultured for 4 days in vitro in the presence of graded doses of caffeine, theophylline or theobromine. It was found that explants exposed to caffeine or theobromine differentiated normally, developing seminiferous cords made up of Sertoli and germ cells, soon followed by the differentiation of functionally active Leydig cells appearing in the newly formed interstitium. However, explants exposed to theophylline failed to develop seminiferous cords and, as a consequence, Leydig cells. In conclusion, insights obtained from different experimental methods, such as organ culture or whole organism studies, are not always identical. It may be prudent, therefore, to take into account that certain experimental techniques, despite providing valuable information, may require confirmation by other test methods in order to obtain an in-depth understanding of mechanisms of action involved.     

Association of caffeine intake and CYP1A2 genotype with ovarian cancer

Coffee and caffeine consumption has been associated with ovarian cancer risk in several epidemiological studies. CYP1A2 is a key enzyme in the metabolism of coffee and in the activation of heterocyclic aromatic compounds that may be carcinogenic. Data from a preliminary investigation conducted in Hawaii of 164 epithelial ovarian cancer cases and 194 controls were used to examine the hypothesis that coffee and caffeine intake increases the risk of ovarian cancer and that these relations are modified by the CYP1A2 high-inducibility A/A genotype. A personal interview and blood specimen were collected in the subjects' homes. A significant positive trend (p = 0.02) in the odds ratios (ORs) was found with increasing intake of caffeine but not with tea or soda. Regular coffee drinkers were at significantly increased risk (OR = 1.8, 95% confidence interval, CI = 1.1-2.8) of ovarian cancer compared with women who did not drink regular coffee. Women with any CYP1A2 C allele were at similar risk of ovarian cancer (OR = 1.1, 95% CI = 0.7-1.7) compared with women with the A/A genotype. The associations of caffeine and coffee intake with risk were stronger among women with the A/A genotype than among women with any C allele. Somewhat stronger relations of coffee and caffeine intake to risk were found among women with cruciferous vegetable consumption above the median and among cases with mucinous histology. These preliminary data suggest a modest positive association of caffeine and coffee consumption with the OR for ovarian cancer that may be modified by CYP1A2 genotype and exposures, such as cruciferous vegetable consumption, that influence CYP1A2 expression.     

Maternal caffeine consumption and fetal death: a case-control study in Uruguay

The objective of this study was to examine the association between caffeine intake during pregnancy and fetal mortality in Montevideo, the capital city of Uruguay, taking into account several potential confounding factors. A population-based case-control study was conducted between 1 August 2002 and 31 December 2003. A total of 382 cases and 792 controls were recruited. Cases consisted of women hospitalised with a medically confirmed diagnosis of spontaneous antepartum fetal death, in all maternity hospitals during the study period. Antepartum fetal death was defined as a fetal death in which the attending doctor certified that the death occurred prior to the onset of labour. Fetal deaths were included if they were of at least 20 weeks' gestational age or weighed >350 g. Controls were women who had a live, vigorous and term adequate-for-gestational-age newborn. Multiple gestations and fetuses/newborns with evident congenital malformations were excluded. Only a small proportion of the mothers (8.1% of the cases and 9.5% of the controls) did not consume caffeine during pregnancy. Among consumers, mate drinking was the most frequent source of caffeine in both cases and controls. After controlling for mother's and her partner's education, history of abortions and/or fetal deaths, vomiting/nausea during the first trimester of gestation and attendance for prenatal care, the category of mean caffeine intake of > or = 300 mg/day showed a significantly increased risk of fetal death (OR 2.33 [1.23; 4.41]) compared with no caffeine consumption during pregnancy. The study also found that less-educated women, mothers who did not attend for prenatal care and women with a history of abortions and fetal death were at an increased risk of fetal death. As mate drinking is highly consumed among pregnant women in Uruguay, the association found with fetal death makes it a preventable risk factor.     

Maternal exposure to tobacco smoke, alcohol and caffeine, and risk of anorectal atresia: National Birth Defects Prevention Study 1997–2003

Anorectal atresia is a congenital anomaly with mostly unknown risk factors. Studies have provided evidence of teratogenic effects of alcohol and tobacco, and animal studies have suggested that caffeine may potentiate their teratogenicity. However, it is unclear how these factors affect the risk of anorectal atresia. We analysed data from maternal telephone interviews in a multistate case-control study with 464 infants with anorectal atresia and 4940 infants with no major birth defects. We used unconditional logistic regression to determine the association of exposure to smoking, environmental tobacco smoke (ETS), alcohol or caffeine with anorectal atresia. Effect modification by caffeine intake was assessed on additive and multiplicative scales.
There was no association with alcohol intake in this analysis. However, there was some evidence of an association between anorectal atresia and maternal exposure to tobacco smoke and caffeine. Compared with non-smokers not exposed to ETS, the crude odds ratio (OR) and 95% confidence interval [CI] for cigarette smoking was 1.2 [95% CI 1.0, 1.5]. The association with anorectal atresia for non-smokers exposed to ETS at home and work was OR = 2.3 [95% CI 1.2, 4.1]. Compared with the lowest level of caffeine intake (<10 mg/day), the association for the highest caffeine intake (≥300 mg/day) was OR = 1.5 [95% CI 1.0, 2.2]. Results did not change after adjustment for covariates. This study found evidence of associations between anorectal atresia and caffeine intake, cigarette smoking and exposure to ETS. Because there are currently few additional data to support these results, further study is needed.     

Maternal dietary intake of vitamin A and risk of orofacial clefts: a population-based case-control study in Norway

A population-based case-control study was carried out in Norway between 1996 and 2001. The aim was to evaluate the association between maternal intake of vitamin A from diet and supplements and risk of having a baby with an orofacial cleft. Data on maternal dietary intake were available from 535 cases (188 with cleft palate only and 347 with cleft lip with or without cleft palate) and 693 controls. The adjusted odds ratio for isolated cleft palate only was 0.47 (95% confidence interval: 0.24, 0.94) when comparing the fourth and first quartiles of maternal intake of total vitamin A. In contrast, there was no appreciable association of total vitamin A with isolated cleft lip with or without cleft palate. An intake of vitamin A above the 95th percentile was associated with a lower estimated risk of all isolated clefts compared with the 40th-60th percentile (adjusted odds ratio = 0.48, 95% confidence interval: 0.20, 1.14). Maternal intake of vitamin A is associated with reduced risk of cleft palate only, and there is no evidence of increased risk of clefts among women in our study with the highest 5% of vitamin A intake.     

Caffeine Sources and Consumption among Saudi Adults Living with Diabetes and Its Potential Effect on HbA1c

Information regarding the spread and effect of coffee and caffeine intake by individuals with type II diabetes remains unclear. This study aims to identify the amount and sources of habitual caffeine intake by individuals with type II diabetes and to investigate its association with other health outcomes, especially HbA1c. This is a cross-sectional survey involving 100 people medically defined as having type II diabetes comprising both genders, recruited from a care centre. All participants completed a caffeine semi-quantitative food frequency questionnaire (C-FFQ) to estimate their caffeine consumption, a two day 24-h recall, and a detailed questionnaire. The average caffeine intake was calculated from all sources and the differences in mean by gender were tested using a regression model (adjusted to important confounders). Regression models were used to verify the association between average caffeine intake on HbA1c and other health outcomes with adjustment for important confounders. A p value < 0.05 represented statistical significance. Arabic coffee (gahwa) and tea were the most common sources of caffeine among Saudi adults living with diabetes. Average caffeine intake for the whole sample was 194 ± 165 mg/day, which is 2.3 ± 2 mg/kg. There was an inverse association between caffeine intake and age: difference in mean −3.26 mg/year (95%CI: −5.34, −1.18; p = 0.003). Males had significantly higher consumption of caffeine compared to females: difference in mean 90.7 mg/day (95%CI: 13.8, 167.6; p = 0.021). No association was found between average caffeine intake and HbA1C or any other cardiovascular risk factors. This information can help public health practitioners and policy makers when assessing the risk of caffeine consumption among this vulnerable group.     

A community case-control study of alcohol consumption in stroke

This study examines the hypothesis that there may be a clinically important association between alcohol intake and stroke. Alcohol consumption and the haematological and biochemical markers of alcohol intake were studied in hospital admissions for stroke and compared with community based control subjects from an occupational screening survey. In males, moderate to heavy alcohol consumption (greater than 30 units per week) was associated with an increased relative risk of stroke. Light drinking (less than 30 units per week) was associated with reduced relative risk when compared to teetotallers. The relative risk of stroke in moderate and heavy consumers of alcohol compared with teetotallers was elevated 1.8 times. Similar patterns of risk were present for increasing levels of aspartate transaminase and uric acid. Relative risk was increased for all levels of gamma-glutamyl transferase above the lowest. There was a decrease in relative risk associated with increasing levels of mean erythrocyte cell volume though this did not achieve statistical significance. There were few heavy drinkers among the female cases or controls. We conclude that high alcohol intake may be a significant preventable risk factor particularly among male strokes.     

Caffeine consumption during pregnancy and spontaneous abortion

We conducted a case-control study of spontaneous abortion in Santa Clara County, California between 1986 and 1987. We analyzed data on 607 cases and 1,284 controls to evaluate the potential association between caffeine consumption during the first trimester of pregnancy and spontaneous abortion. About 70% of the women consumed caffeinated coffee, tea, and/or soda; 7% of the women consumed more than an average of 300 mg of caffeine daily. The crude odds ratio (OR) for heavy caffeine consumption (greater than 300 mg/day) was 1.55 (95% CI: 1.04-2.31), which decreased to 1.22 (95% CI: 0.80-1.87) after controlling for confounding factors. For these heavy users, nausea modified the association of spontaneous abortion and caffeine; heavy caffeine consumers reporting nausea had a doubled risk for spontaneous abortion (adjusted OR = 2.10, 95% CI: 1.20-3.70), in contrast to those who did not report nausea (adjusted OR = 0.53, 95% CI: 0.27-1.04). Heavy caffeine consumers who decreased their caffeine intake early in pregnancy had a risk of spontaneous abortion similar to that of nonconsumers.     

The Relation between Caffeine Consumption and Endometriosis: An Updated Systematic Review and Meta-Analysis

While the contributing factors leading to endometriosis remain unclear, its clinical heterogeneity suggests a multifactorial causal background. Amongst others, caffeine has been studied extensively during the last decade as a putative contributing factor. In this systematic review and meta-analysis, we provide an overview/critical appraisal of studies that report on the association between caffeine consumption and the presence of endometriosis. In our search strategy, we screened PubMed and Scopus for human studies examining the above association. The main outcome was the relative risk of endometriosis in caffeine users versus women consuming little or no caffeine (<100 mg/day). Subgroup analyses were conducted for different levels of caffeine intake: high (>300 mg/day) or moderate (100–300 mg/day). Ten studies were included in the meta-analysis (five cohort and five case-control studies). No statistically significant association was observed between overall caffeine consumption and risk for endometriosis (RR 1.12, 95% confidence interval (CI) 0.97–1.28, I² = 70%) when compared to little or no (<100 mg/day) caffeine intake. When stratified according to level of consumption, high intake was associated with increased risk of endometriosis (RR 1.30, 95%CI 1.04–1.63, I² = 56%), whereas moderate intake did not reach nominal statistical significance (RR 1.18, 95%CI 0.99–1.40, I² = 37%). In conclusion, caffeine consumption does not appear to be associated with increased risk for endometriosis. However, further research is needed to elucidate the potential dose-dependent link between caffeine and endometriosis or the probable role of caffeine intake as a measurement of other unidentified biases.     

Effect of dietary caffeine and theophylline on urinary calcium excretion in the adult rat

The chronic effects of dietary caffeine or theophylline on urinary calcium excretion were investigated in the adult male rat. When caffeine was added at two concentrations, 0.75 and 1.50 g/kg diet, 24-h urinary calcium excretion rose 300 and 450% on d 7, and 200 and 330% on d 14, respectively. There were no changes in the 24-h urinary excretion of phosphate, sulfate, sodium and cAMP nor did urine volume change. The high dose of caffeine was compared to an equimolar dose of theophylline (1.39 g/kg diet) in both Wistar and Sprague-Dawley rats. Urinary calcium excretion in theophylline-treated rats was significantly greater than in caffeine-treated rats on all sampling days and in both strains of rat; the calciuric effect lasted at least 22 d. When rats were given indomethacin (3.3 mg/kg diet) the calciuria induced by caffeine and theophylline was abolished, and sodium excretion in all groups was reduced by 35-50%, but urine volume was unchanged. The calciuria of methylxanthine feeding may result from a prostaglandin-mediated process distinct from diuresis.