Article

Association of coffee consumption and CYP1A2 polymorphism with risk of impaired fasting glucose in hypertensive patients

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  • Sant'antonio hospital san daniele del friuli
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Abstract

Whether and how coffee use influences glucose metabolism is still a matter for debate. We investigated whether baseline coffee consumption is longitudinally associated with risk of impaired fasting glucose in a cohort of 18-to-45 year old subjects screened for stage 1 hypertension and whether CYP1A2 polymorphism modulates this association. A total of 1,180 nondiabetic patients attending 17 hospital centers were included. Seventy-four percent of our subjects drank coffee. Among the coffee drinkers, 87 % drank 1-3 cups/day (moderate drinkers), and 13 % drank over 3 cups/day (heavy drinkers). Genotyping of CYP1A2 SNP was performed by real time PCR in 639 subjects. At the end of a median follow-up of 6.1 years, impaired fasting glucose was found in 24.0 % of the subjects. In a multivariable Cox regression coffee use was a predictor of impaired fasting glucose at study end, with a hazard ratio (HR) of 1.3 (95 % CI 0.97-1.8) in moderate coffee drinkers and of 2.3 (1.5-3.5) in heavy drinkers compared to abstainers. Among the subjects stratified by CYP1A2 genotype, heavy coffee drinkers carriers of the slow *1F allele (59 %) had a higher adjusted risk of impaired fasting glucose (HR 2.8, 95 % CI 1.3-5.9) compared to abstainers whereas this association was of borderline statistical significance among the homozygous for the A allele (HR 1.7, 95 % CI 0.8-3.8). These data show that coffee consumption increases the risk of impaired fasting glucose in hypertension particularly among carriers of the slow CYP1A2 *1F allele.

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... It is also should be noted that the genetic variants of the liver enzyme Cytochrome P450 1A2 (CYP1A2), as the strongest predictors of caffeine metabolism, may modify the association coffee consumption and T2D [18]. Individuals homozygous for the CYP1A2 *1 A/*1 A genotype are fast caffeine metabolizers, whereas 'slow metabolizers' with *1 F allele have a higher circulating caffeine following coffee consumption and may therefore be affected by a greater impact of caffeine intake [18,19]. Coffee consumption have been reported to contribute to development of impaired fasting glucose in subjects who carries the slow CYP1A2 *1F allele [19]; heavy coffee drinking (>3 cup/day) in subject who had the slow *1F allele led to elevated risk of impaired fasting glucose (HR Z 2.8, 95% CI Z 1.3e5.9) ...
... Individuals homozygous for the CYP1A2 *1 A/*1 A genotype are fast caffeine metabolizers, whereas 'slow metabolizers' with *1 F allele have a higher circulating caffeine following coffee consumption and may therefore be affected by a greater impact of caffeine intake [18,19]. Coffee consumption have been reported to contribute to development of impaired fasting glucose in subjects who carries the slow CYP1A2 *1F allele [19]; heavy coffee drinking (>3 cup/day) in subject who had the slow *1F allele led to elevated risk of impaired fasting glucose (HR Z 2.8, 95% CI Z 1.3e5.9) [19]. ...
... Coffee consumption have been reported to contribute to development of impaired fasting glucose in subjects who carries the slow CYP1A2 *1F allele [19]; heavy coffee drinking (>3 cup/day) in subject who had the slow *1F allele led to elevated risk of impaired fasting glucose (HR Z 2.8, 95% CI Z 1.3e5.9) [19]. A genome-wide meta-analysis among coffee consumers indicated six novel loci located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine [20]. ...
Article
Background and aim: Here, we examined the potential effect of coffee consumption and total caffeine intake on the occurrence of pre-diabetes and T2D, in a population with low coffee consumption. Methods and Results: Adults men and women, aged 20–70 years, were followed for a median of 5.8 y. Dietary intakes of coffee and caffeine were estimated using a 168-food items validate semi-quantitative food frequency questionnaire, at baseline. Cox proportional hazards regression models, adjusted for potential cofounders, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between coffee and caffeine intakes and incidence of pre-diabetes and T2D. The total population was 1878 adults (844 men, 1034 women) and 2139 adults (971 men, 1168 women) for analysis of pre-diabetes and T2D, respectively. During the follow-up period the incidence of pre-diabetes and T2D was 30.8% and 6.6%, respectively. Forty-three percent of our subjects were no coffee drinker whereas 51.4% consumed 1 cup of coffee/week and 6.0% consumed more than 1 cup of coffee/week. A lower risk of pre-diabetes (HR = 0.73, 95% CI = 0.62–0.86) and T2D (HR = 0.66, 95% CI = 0.44–1.00) was observed in coffee drinkers compared to non-drinkers, in the fully adjusted models. Higher dietary intake of caffeine (≥152 vs. <65 mg/d) was accompanied with a borderline (P = 0.053) reduced risk of pre-diabetes (HR = 0.45, 95% CI = 0.19–1.00). Conclusion: Our findings indicated that coffee drinking may have favorable effect in prevention of pre-diabetes and T2D. © 2018 The Italian Society of Diabetology, 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
... There is a controversial discussion about caffeine's influence on glycemic control and type 2 diabetes risk (for review, see Palatini et al., 2015). Laboratory-based studies showed that doses of caffeine equivalent to 3-4 cups of coffee reduced glucose disposal by more than 20 % (Greer et al., 2001;Lane et al., 2004). ...
... This polymorphism causes interindividual differences in the inducibility of CYP1A2 enzyme activity, for example by caffeine (Sachse et al., 1999). Slow metabolizers (i.e., C-allele carriers of rs762551) are more exposed to the adverse effects of caffeine, and thus potentially, are more at risk of developing type 2 diabetes following habitual high coffee consumption (Palatini et al., 2015). ...
... This result was confirmed by the analysis of salivary caffeine concentrations at bedtime. This finding is pertinent given the ongoing controversy over the relationship between coffee intake and risk of type 2 diabetes (Freedman et al., 2012;Palatini et al., 2015). It supports our prediction that the diabetes group would consume more caffeine than controls. ...
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Objectives: To examine the possible links between type 2 diabetes, daytime sleepiness, sleep quality and caffeine consumption. Methods: In this case-control field study, comparing type 2 diabetic (n = 134) and non-type 2 diabetic (n = 230) participants, subjects completed detailed and validated questionnaires to assess demographic status, health, daytime sleepiness, sleep quality and timing, diurnal preference, mistimed circadian rhythms and habitual caffeine intake. All participants gave saliva under standardized conditions for CYP1A2 genotyping and quantification of caffeine concentration. Hierarchical linear regression analyses examined whether type 2 diabetes status was associated with caffeine consumption. Results: Type 2 diabetic participants reported greater daytime sleepiness (p = 0.001), a higher prevalence of sleep apnea (p = 0.005) and napping (p = 0.008), and greater habitual caffeine intake (p < 0.001), derived from the consumption of an extra cup of coffee each day. This finding was confirmed by higher saliva caffeine concentration at bedtime (p = 0.01). Multiple regression analyses revealed that type 2 diabetes status was associated with higher self-reported caffeine consumption (p < 0.02) and higher salivary caffeine (p < 0.02). Next to male sex, type 2 diabetes status was the strongest predictor of caffeine intake. Subjective sleep and circadian estimates were similar between case and control groups. Conclusions: Type 2 diabetic patients may self-medicate with caffeine to alleviate daytime sleepiness. High caffeine intake reflects a lifestyle factor that may be considered when promoting type 2 diabetes management.
... [16] Meanwhile, the genetic polymorphisms affecting caffeine metabolism are also associated with increased risk of several health impairments, including hypertension, impaired fasting glucose, and myocardial infarction. [17][18][19] Therefore, it is worth examining whether the effect of coffee on incident CKD is independent of genetic factors. ...
... Previous research reports a modification effect of the CYP1A2 genotype, which is responsible primarily for metabolizing caffeine, on some coffee-health outcome associations, such that slow metabolizers could not benefit from habitual coffee consumption. [17][18][19] Nonetheless, constructing a comprehensive allele score representing caffeine metabolism, we surprisingly found a stronger inverse association in slow metabolizers, but failed to confirm the gene-diet interaction. ...
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Background: The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee-CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association. Methods: A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data (n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results. Results: Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed (P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee-CKD association. Conclusions: In addition to the overall inverse coffee-CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.
... Several studies have indicated adverse effects from coffee intake, correlating with a higher risk of hypertension, cardiovascular events, acute coronary syndrome, coronary artery disease, and dyslipidemia, especially at higher doses (Grioni et al. 2015;Lopez-Garcia et al. 2016;Notara et al. 2015;Palatini et al. 2015). ...
... Furthermore, some studies have tried to relate SNP to coffee consumption and diabetes and heart disease. Individuals are considered to be slow metabolisers, and with high coffee consumption may present a higher chance of having impaired fasting glucose (Palatini et al. 2015). However, postprandial blood glucose may be more elevated in fast metabolisers than in slow metabolites (Robertson et al. 2018). ...
Article
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Coffee is a beverage consumed globally. Although few studies have indicated adverse effects, it is typically a beneficial health-promoting agent in a range of diseases, including depression, diabetes, cardiovascular disease, and obesity. Coffee is rich in caffeine, antioxidants, and phenolic compounds, which can modulate the composition of the gut microbiota and mitigate both inflammation and oxidative stress, common features of the burden of lifestyle diseases. This review will discuss the possible benefits of coffee on complications present in patients with diabetes, cardiovascular disease and chronic kidney disease, outwith the social and emotional benefits attributed to caffeine consumption.
... This compound has been investigated in numerous studies to elucidate its effect on the association between CYP1A2 gene variants and phenotypic traits. Individuals with the C allele of the GYP1A2 gene (gene variant rs762551) are considered slow metabolizers and tend to have an increased risk of hypertension, myocardial infarction, and elevated blood pressure when they consume more than 200 mg of caffeine per day, whereas AA homozygotes do not have these risks [52][53][54][55]. ...
... Nevertheless, extensive research on gene-diet interactions is still required. Further, to avoid misuse and protect the public, nutrigenetic advice should be grounded in clear evidence Individuals carrying the C allele of the CYP1A2 gene (rs762551), who are considered slow metabolizers, have an increased risk of hypertension, myocardial infarction, elevated blood pressure, and pre-diabetes when they consume more than 200 mg of caffeine per day, whereas people possessing the AA genotype (fast metabolizers) do not carry these risks [52][53][54][55]. TAS1R2 gene Ile19Val Encodes the sweet taste receptor 2 protein subunits, T1R2, which is specifically required to perceive sweet tastes Sugar Val carriers of the TAS1R2 gene tended to consume fewer sugars in comparison with those homozygous for the Ile allele [56]. ...
Article
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Direct-to-consumer genetic testing (DTC-GT) provides a means for consumers to gain insights into their genetic background and how it relates to their health without the involvement of medical institutions. In Korea, DTC-GT was introduced in 2016 in accordance with the legislation on Paragraph (3) 2 of Article 50 of the Bioethics and Safety Act. Only 12 genetic test items involving 46 genes were approved at first, but the approved items were expanded to 70 in November 2020. However, the genetic test items of DTC-GT services in Korea are still restricted to the wellness area, and access to disease risk related information is only permitted to medical institutions. Further, studies revealing the relationship between genotype differences and responses to nutrients, food components, or nutritional status are increasing, and this association appears to be robust for some genes. This strong association between genetic variations and nutrition suggests that DTC-GT can be used as an important tool by clinical nutritionists to gain insights into an individual's genetic susceptibilities and provide guidance on nutritional counseling and meal planning based on the patient's genetic information. This review summarized the history and current status of DTC-GT and investigated the relationship between genetic variations with associated phenotypic traits to clarify further the importance of DTC-GT in the field of clinical nutrition.
... CYP1A2 has been used to categorize individuals as "fast" or "slow" metabolizers of caffeine (24,49). Several elevated health risks have been reported in individuals with the AC or CC genotype (slow metabolizers) (4,8,40,41,52) with increasing caffeinated coffee consumption, whereas those with the AA genotype (fast metabolizers) show no such risk. Performance benefits among CYP1A2 fast metabolizers have also been reported in most (19,42,46,48), but not all (33,41), caffeine-exercise studies involving repeated muscular or aerobic endurance-type performance. ...
... Several elevated health risks have been reported in individuals with the AC or CC genotype (slow metabolizers) (4,8,40,41,52) with increasing caffeinated coffee consumption, whereas those with the AA genotype (fast metabolizers) show no such risk. Performance benefits among CYP1A2 fast metabolizers have also been reported in most (19,42,46,48), but not all (33,41), caffeine-exercise studies involving repeated muscular or aerobic endurance-type performance. The impact of CYP1A2 genotype in response to caffeine in other sport types remains equivocal (8,33,52). ...
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Guest, NS, Corey, P, Tyrrell, PN, and El-Sohemy, A. Effect of caffeine on endurance performance in athletes may depend on HTR2A and CYP1A2 genotypes. J Strength Cond Res XX(X): 000-000, 2020-This investigation determined whether variation in the HTR2A (serotonin receptor) gene modifies the ergogenic effects of caffeine on endurance and further modifies performance by the CYP1A2 genotype. Male athletes (n = 100; 25 ± 4 years) completed 10-km cycling time trials under 3 conditions as follows: 0, 2, or 4 mg of caffeine per kg body mass. Using a randomized, double-blinded, placebo-controlled design, data were analyzed using analysis of covariance to compare changes in cycling time between placebo (0 mg·kg) and each caffeine dose and adjusted for the placebo trial and order of treatment. A significance of ρ ≤ 0.05 was used. Subjects were genotyped for HTR2A (rs6313) and CYP1A2 (rs762551). A significant caffeine-HTR2A interaction (p = 0.003) was observed; however, after adjustment for placebo trials, the interaction was no longer significant (p = 0.37). Because of the strong caffeine-CYP1A2 interaction (p < 0.0001) previously reported in these subjects, where the 4-mg dose resulted in divergent effects (slower and faster) on the 10-km cycling time, we conducted a simplified model to examine these same factors by the HTR2A genotype. The post hoc analysis excluded HTR2A CT heterozygotes and 2-mg·kg caffeine trials. Among CYP1A2 fast metabolizers alone, a significant difference (1.7 minutes; p = 0.006) was observed when comparing (4- vs. 0-mg·kg caffeine trials) between the HTR2A CC (n = 16; 2.4 minutes) and TT (n = 7; 0.7 minutes) genotypes. Our results show that 4-mg·kg caffeine improves performance in individuals with the HTR2A CC genotype but only in those who are also CYP1A2 AA fast metabolizers. This study was registered with clinicaltrials.gov (NCT02109783).
... The effects of coffee are influenced by genetic differences in the population; i.e., rate of caffeine metabolism contributed significantly to physiological responses to coffee (Palatini et al., 2015;Robertson et al., 2018). Daily intake of coffee (174.4 mg CGA and 175.2 mg caffeine) reduced postprandial glucose levels in people who metabolizes caffeine slowly, but increased postprandial glucose levels in people who metabolize caffeine quickly after 12 weeks ( Robertson et al., 2018). ...
... Daily intake of coffee (174.4 mg CGA and 175.2 mg caffeine) reduced postprandial glucose levels in people who metabolizes caffeine slowly, but increased postprandial glucose levels in people who metabolize caffeine quickly after 12 weeks ( Robertson et al., 2018). However, a follow-up study reported that hypertensive patients who metabolize caffeine slowly had higher risk of impaired fasting glucose, compared to whom metabolize caffeine quickly or noncoffee drinkers ( Palatini et al., 2015). ...
Article
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Coffee consumption is associated with reduced risk of metabolic syndrome, obesity and diabetes, which may be related to the effects of coffee and its bioactive components on lipid metabolism. Coffee contains caffeine, a known neuromodulator that acts as an adenosine receptor antagonist, as well as other components, such as chlorogenic acids, trigonelline, cafestol and kahweol. Thus, this review discusses the up-to-date knowledge of mechanisms of action of coffee and its bioactive compounds on lipid metabolism. Although there is evidence that coffee and/or its bioactive compounds regulate transcription factors (e.g. peroxisome proliferator-activated receptors and sterol regulatory element binding proteins) and enzymes (e.g. AMP-activated protein kinase) involved in lipogenesis, lipid uptake, transport, fatty acid β-oxidation and/or lipolysis, needs for the understanding of coffee and its effects on lipid metabolism in humans remain to be answered.
... The j163A 9 C (rs762551) single nucleotide polymorphism (SNP) has been shown to alter CYP1A2 enzyme inducibility and activity (22,23) and has been used to categorize individuals as ''fast'' or ''slow'' metabolizers of caffeine. Individuals with the AC or CC genotype (slow metabolizers) have an elevated risk of myocardial infarction (24), hypertension (25), and prediabetes (26) with increasing caffeinated coffee consumption, whereas those with the AA genotype show no such risk. In addition, a few studies have shown that the rate of caffeine metabolism could also have implications for sports performance, but the findings remain equivocal (12,(27)(28)(29). ...
... For rs762551, AA corresponds to fast metabolizers, whereas AC and CC are considered slow metabolizers. In the present study, we genotyped subjects for both rs2472300 and rs762551 SNP and found 100% concordance, but we report the results for rs762551 because it is the one more commonly reported (12,(22)(23)(24)(25)(26)29). ...
Article
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Purpose: Many studies have examined the effect of caffeine on exercise performance, but findings have not always been consistent. The objective of this study was to determine whether variation in the CYP1A2 gene, which affects caffeine metabolism, modifies the ergogenic effects of caffeine in a 10-km cycling time trial. Methods: Competitive male athletes (n=101; age: 25 ± 4 years) completed the time trial under three conditions: 0, 2 or 4 mg of caffeine per kg body mass, using a split-plot randomized, double-blinded, placebo-controlled design. DNA was isolated from saliva and genotyped for the -163A>C polymorphism in the CYP1A2 gene (rs762551). Results: Overall, 4 mg/kg caffeine decreased cycling time by 3% (mean ± SEM) versus placebo (17.6 ± 0.1 vs. 18.1 ± 0.1 min, p = 0.01). However, a significant (p <0.0001) caffeine-gene interaction was observed. Among those with the AA genotype, cycling time decreased by 4.8% at 2 mg/kg (17.0 ± 0.3 vs. 17.8 ± 0.4 min, p = 0.0005) and by 6.8% at 4 mg/kg (16.6 ± 0.3 vs. 17.8 ± 0.4 min, p < .0001). In those with the CC genotype, 4 mg/kg increased cycling time by 13.7% versus placebo (20.8 ± 0.8 vs. 18.3 ± 0.5 min, p = 0.04). No effects were observed among those with the AC genotype. Conclusion: Our findings show that both 2 and 4 mg/kg caffeine improve 10-km cycling time, but only in those with the AA genotype. Caffeine had no effect in those with the AC genotype and diminished performance at 4 mg/kg in those with the CC genotype. CYP1A2 genotype should be considered when deciding whether an athlete should use caffeine for enhancing endurance performance.
... A growing body of evidence from in vitro and animal studies has shown that polyphenols can activate and/or silence transcription factors, and consequently influence gene expression, and regulate different signaling pathways in the muscle, the liver, pancreatic β-cells, the hypothalamus, and adipose tissue, thereby contributing to glucose homoeostasis [72,73]. Although promising data aimed at understanding how different polyphenol classes can modulate genetic regulation and expression have been published, few studies have investigated whether genetic predisposition modifies the relationship among polyphenols, intermediate phenotypes of insulin resistance, and T2D risk [74][75][76][77][78][79]. An initial and very preliminary track of evidence for genotype-polyphenol interaction is emerging from studies of coffee, the consumption of which is highly spread in Mediterranean regions. ...
... Along these lines, an independent study including 1180 nondiabetic young to middle-aged participants with stage 1 hypertension, baseline coffee consumption was longitudinally associated with the risk of impaired glucose tolerance only in carriers of CYP1A2 * 1F allele. Among participants homozygous for the * 1A allele, which is responsible for fast caffeine metabolism, the favorable action of polyphenols or other bioactive agents balanced the genetic and metabolic risk for T2D [75]. Finally, in a prospective epidemiological study from the EPIC-InterAct cohort, including 8086 incident T2D cases in 11,035 participants over 12.5 years, habitual coffee consumption was associated with a 7% T2D risk reduction among carriers of the diabetes increasing risk allele at transcription factor 7-like 2 locus (TCF7L2) [76]. ...
Article
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Dietary polyphenols come mainly from plant-based foods including fruits, vegetables, whole grains, coffee, tea, and nuts. Polyphenols may influence glycemia and type 2 diabetes (T2D) through different mechanisms, such as promoting the uptake of glucose in tissues, and therefore improving insulin sensitivity. This review aims to summarize the evidence from clinical trials and observational prospective studies linking dietary polyphenols to prediabetes and T2D, with a focus on polyphenol-rich foods characteristic of the Mediterranean diet. We aimed to describe the metabolic biomarkers related to polyphenol intake and genotype-polyphenol interactions modulating the effects on T2D. Intakes of polyphenols, especially flavan-3-ols, and their food sources have demonstrated beneficial effects on insulin resistance and other cardiometabolic risk factors. Several prospective studies have shown inverse associations between polyphenol intake and T2D. The Mediterranean diet and its key components, olive oil, nuts, and red wine, have been inversely associated with insulin resistance and T2D. To some extent, these associations may be attributed to the high amount of polyphenols and bioactive compounds in typical foods conforming this traditional dietary pattern. Few studies have suggested that genetic predisposition can modulate the relationship between polyphenols and T2D risk. In conclusion, the intake of polyphenols may be beneficial for both insulin resistance and T2D risk.
... In keeping with previous analyses from HARVEST [5,7,14,186 15], subjects were grouped into three categories of coffee drinking, 187 non-drinkers (none), moderate drinkers (1 to 3 cups daily) and heavy 188 drinkers (4 or more cups daily). Subjects were divided into three cate-189 gories of alcohol use (0 g, b50 g, N50 g of alcohol/day) [18,19]. Smokers ...
... polymorphism that has important influences on caffeine metabolism 394[50]. In our previous analyses of the HARVEST participants we showed that carriers of the *1F allele who are slow caffeine metabolizers, were at much higher risk of both hypertension[18] and impaired glucose metabolism[19] and could thus also be exposed to a greater risk of CVE.Unfortunately, genetic data were available in only 60% of the present sample (only including 28 CVE) thus preventing any meaningful statis-The relationship between coffee consumption and CVE might be explained by the association of coffee use with other unfavorable lifestyle factors. Indeed, in the HARVEST study coffee drinkers were more sedentary, were more frequently smokers and consumed larger amounts of alcohol. ...
... Out of the five CYP1A2 SNPs tested in the Lebanese study [28], only SNP rs762551 was examined for its interaction with caffeine on T2D in other populations. In a hypertensive adult Italian population (n = 1180), the "C" allele of the SNP rs762551 did not show any interaction with caffeine intake in relation to the glycaemic index [104]. Conversely, a British study of non-habitual coffee drinkers (n = 30) found that the "C" allele showed an interaction with caffeine, leading to a lower postprandial glycaemic index in healthy adults [105]. ...
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The increased prevalence of metabolic diseases in the Arab countries is mainly associated with genetic susceptibility, lifestyle behaviours, such as physical inactivity, and an unhealthy diet. The objective of this review was to investigate and summarise the findings of the gene–lifestyle interaction studies on metabolic diseases such as obesity and type 2 diabetes in Arab populations. Relevant articles were retrieved from a literature search on PubMed, Web of Science, and Google Scholar starting at the earliest indexing date through to January 2024. Articles that reported an interaction between gene variants and diet or physical activity were included and excluded if no interaction was investigated or if they were conducted among a non-Arab population. In total, five articles were included in this review. To date, among three out of twenty-two Arab populations, fourteen interactions have been found between the FTO rs9939609, TCF7L2 rs7903146, MC4R rs17782313, and MTHFR rs1801133 polymorphisms and diet or physical activity on obesity and type 2 diabetes outcomes. The majority of the reported gene–diet/ gene–physical activity interactions (twelve) appeared only once in the review. Consequently, replication, comparisons, and generalisation of the findings are limited due to the sample size, study designs, dietary assessment tools, statistical analysis, and genetic heterogeneity of the studied sample.
... In contrast to prior research that focused on caffeine, available data suggest that coffee may benefit CVD outcomes [243,244]. Epidemiological studies have shown that moderate coffee drinking reduces the risk of CVD disease [245,246]. ...
... Индивиди с AC и СС генотипи се считат за междинни и бавни метаболизатори съответно, а тези с генотип АА се считат за бързи метаболизатори (49). Установено е, че този полиморфизъм променя връзката между приема на кафе и риска от инфаркт на миокарда (47) и хипертония (50). Повишен сърдечносъдов риск е демонстриран при бавните метаболизатори с увеличаване на чашите кафе, консумирани на ден, докато при бързите метаболизатори увеличаването на чашите кафе на ден или се свързва с по-нисък риск, или не е установена връзка. ...
Article
Cardiovascular disease (CVD) is a major health problem worldwide and is a leading cause of disability and mortality. They include coronary heart disease, cerebrovascular disease, peripheral vascular disease and arterial atherosclerosis. In the most cases, CVDs are polygenic multifactorial socially significant diseases and result from the impact of predisposing environmental factors, mainly related to unhealthy lifestyles, acting on a sensitive genetic terrain. This is due to specific genetic variants that control the regulation of the renin-angiotensin-aldosterone system (RAAS), lipid metabolism, caffeine metabolism, omega-3 fatty acids, homocysteine, etc. Such common genetic variants are designated as SNPs (Single Nucleotide Polymorphisms). The more predisposing variants an individual carries, the more pronounced the genetic risk of developing CVD. Such genetic variations are: variations in the ACE (insertion/deletion—I/D) and AGT (C-344T) genes of the RAAS; variations in the ApoE gene (Apo E2, E3 and E4) associated with cholesterol metabolism, genetic polymorphism C3175G in the gene encoding apolipoprotein C— APOC3 ; CETP gene with polymorphism rs708272, 279 G>A, associated with high-density cholesterol metabolism; lipoprotein lipase ( LPL ) gene and polymorphism 1595C>G (Ser447X); a polymorphism in CYP1A2 associated with caffeine sensitivity; polymorphism rs174537 G>T in FADS1 involved in polyunsaturated fatty acid metabolism, and polymorphisms in MTHFR (677 C>T and 1298 A>C) associated with homocysteine metabolism.
... For example, some studies have suggested that slow metabolizers (AC or CC genotype) may be more sensitive to the potential adverse effects of high coffee consumption, such as an increased risk of myocardial infarction or hypertension [22][23][24][25]. ...
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This literature review aims to explore the data of articles published on the association between coffee, caffeine and atrial fibrillation and to analyze any differences between the two sexes. Several factors influence this complex relationship; genetic, environmental and psychosocial factors come into play in the pathophysiology of atrial fibrillation. These factors are expressed differently in women and men. However, the analysis of the literature has shown that comparison works between the two sexes are extremely rare. Most population-based and prospective studies either analyze aggregated data or focus on exclusively male or female populations. This results in a lack of information that could be useful in the prevention of and treatment approach to atrial fibrillation. It is necessary to deepen this issue with dedicated studies.
... Carriers of the slow à 1 F allele are at increased risk, and should therefore abstain from coffee, whereas individuals with the à 1 A/ à 1A genotype can safely drink coffee. Another study (Palatini et al. 2015) on the risk of impaired fasting glucose through coffee consumption demonstrated that among the subjects, stratified by CYP1A2 genotype, heavy coffee drinkers being carriers of the slow à 1 F allele (59%) had a higher adjusted risk of impaired fasting glucose (HR 2.8, 95% CI 1.3-5.9) compared to abstainers, whereas this association was of borderline statistical significance among those homozygous for the A allele (HR 1.7, 95% CI 0. 8-3.8). ...
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An Acute Reference Dose (ARfD) of 1 µg of delta-9-tetrahydrocannabinol (THC) per kilogram (kg) of body weight (bw) per day was recommended by the European Food Safety Authority (EFSA) for its assessment of possible acute health risks from the intake of industrial hemp food products. The scientific basis for this opinion, such as their choice of a Point of Departure for identification of the Lowest Observed Adverse Effect Level (LOAEL) for THC on the central nervous system, and the seeming absence of an experimental No Observed Adverse Effect Level (NOAEL), is critically reviewed. Moreover, the risk assessment for an ARfD derivation for THC is then reconsidered. In contrast to the EFSA Scientific Opinion of 2015, a higher LOAEL is presently identified from pharmacokinetic and pharmacodynamic studies, and forensic data, in representative cohorts of healthy humans after oral administrations of low THC doses. A NOAEL for THC is derived through this combination of results, demonstrating a threshold for impairment of psychomotor function only after intake of an oral THC bolus beyond 2.5 mg for the average healthy adult. This 2.5 mg dose produces mean THC blood serum levels of <2 ng/mL, as well as do two doses when taken daily within a time interval of ≥6 h. The forensic threshold of THC that is correlated with the impairment of psychomotor function is known to be between 2 and 5 ng/mL in blood serum for adults. For an appropriately spaced intake of 2 × 2.5 mg THC per day, an adult can therefore be regarded as being at the NOAEL. Applying a default uncertainty factor of 10 for intraspecies variability to a NOAEL of 2 × 2.5 mg (over ≥6 hours) for THC, yields a "daily dose of no concern" or a "tolerable upper intake level" of 0.50 mg, corresponding to 7 µg/kg bw. Starting with a NOAEL of only 2.5 mg, consumed as a single bolus, the lowest possible daily THC Acute Reference Dose would therefore be 0.25 mg, or 3.5 µg/kg bw for healthy adults, as the absolutely most conservative estimate. Other justifiable estimates have ranged up to 14 µg/kg bw per day.
... Less than half of the population carry the CYP1A2 gene associated with fast metabolism. Some evidence suggest that higher CA intakes increases the risk of insulin resistance [10], high blood pressure [11], and heart attacks [12] in intermediate and slow but not rapid caffeine metabolizers [8] with fast metabolizer seeing greater improvements in athletic performance [13,14] and reduced appetite [15,16]. ...
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Paraxanthine (PXN) is a metabolite of caffeine that has recently been reported to enhance cognition at a dose of 200 mg. Objective: To determine the acute and short-term (7-day) effects of varying doses of PXN on cognitive function and side effects. Methods: In a double blind, placebo-controlled, crossover, and counterbalanced manner, 12 healthy male and female volunteers (22.7 ± 4 years, 165 ± 7 cm, 66.5 ± 11 kg, 24.4 ± 3 kg/m2) ingested 200 mg of a placebo (PLA), 50 mg of PXN (ENFINITY™, Ingenious Ingredients, L.P.) + 150 mg PLA, 100 mg PXN + 100 mg PLA, or 200 mg of PXN. With each treatment experiment, participants completed side effect questionnaires and donated a fasting blood sample. Participants then performed a series of tests assessing cognition, executive function, memory, and reaction time. Participants then ingested one capsule of PLA or PXN treatments. Participants then completed side effects and cognitive function tests after 1, 2, 3, 4, 5, and 6 h of treatment ingestion. Participants continued ingesting one dose of the assigned treatment daily for 6-days and returned to the lab on day 7 to donate a fasting blood sample, assess side effects, and perform cognitive function tests. Participants repeated the experiment while ingesting remaining treatments in a counterbalanced manner after at least a 7-day washout period until all treatments were assessed. Results: The Sternberg Task Test (STT) 4-Letter Length Present Reaction Time tended to differ among groups (p = 0.06). Assessment of mean changes from baseline with 95% CI's revealed several significant differences among treatments in Berg-Wisconsin Card Sorting Correct Responses, Preservative Errors (PEBL), and Preservative Errors (PAR Rules). There was also evidence of significant differences among treatments in the Go/No-Go Task tests in Mean Accuracy as well as several time points of increasing complexity among STT variables. Finally, there was evidence from Psychomotor Vigilance Task Test assessment that response time improved over the series of 20 trials assessed as well as during the 6-h experiment in the PXN treatment. Acute and short-term benefits compared to PLA were seen with each dose studied but more consistent effects appeared to be at 100 mg and 200 mg doses. No significant differences were observed among treatments in clinical chemistry panels or the frequency or severity of reported side effects. Results provide evidence that acute ingestion of 100 mg and 200 mg of PXN may affect some measures of cognition, memory, reasoning, and response time as well as help sustain attention. Additionally, that acute and daily ingestion of PXN for 7 days is not associated with any clinically significant side effects. Conclusions: PXN may serve as an effective nootropic agent at doses as low as 50 mg.
... mmHg versus 131.8±12.0 mmHg (p = 0.72); diastolic BP: 81.5 ±8.1 mmHg versus 81.5±8.2 mmHg versus 81.0±8.0 mmHg (p = 0.79)) [58]. ...
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Purpose of Review Coffee is a very popular drink and an estimated 2.25 billion cups worldwide are consumed daily. Such popularity of coffee makes it the most consumed drink next to water. Numerous studies have shown a beneficial effect of habitual and moderate coffee consumption on the functioning of the nervous, digestive, and cardiovascular systems, as well as on kidney function. Taking into account the very high prevalence of arterial hypertension in the world (31.1% of adults), much controversy has been raised about the influence of coffee consumption on blood pressure and the risk of arterial hypertension. Moreover, there have been extensive discussions about the safety of coffee consumption for hypertensive persons. Recent Findings There are over 1000 chemical compounds in coffee. The best characterized of these are caffeine, chlorogenic acid, trigonelline, kahweol, cafestol, ferulic acid, and melanoidins. These compounds have bidirectional influences on blood pressure regulation. The results of numerous studies and meta-analyses indicate that moderate and habitual coffee consumption does not increase and may even reduce the risk of developing arterial hypertension. Conversely, occasional coffee consumption has hypertensinogenic effects. Moderate habitual coffee consumption in hypertensive persons does not appear to increase the risk of uncontrolled blood pressure and may even reduce the risk of death from any cause. Summary Moderate and habitual consumption of coffee (1-–3 cups / day) does not adversely affect blood pressure in most people, including those with arterial hypertension.
... Further, the role of genetics in investigating the relationship between coffee and blood glucose level is also notable. Genetic diversity in the cytochrome p-450 hepatic enzyme (P450 1A1 (CYP1A2)) can also affect the relationship between coffee and FPG [37]. This enzyme has also different alleles as the main factor of coffee metabolism in the liver. ...
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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.
... Further, the role of genetics in investigating the relationship between coffee and blood glucose level is also notable. Genetic diversity in the cytochrome p-450 hepatic enzyme (P450 1A1 (CYP1A2)) can also affect the relationship between coffee and FBS (32). This enzyme has also different alleles as the main factor of coffee metabolism in the liver. ...
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Objective: clinical studies suggest increasing prevalence of cardiovascular disease (CVD) risk factors and diabetes among the elderly. Meanwhile, coffee as a food compound can cause adverse effects on these 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 in this study were 70.04±4.87 years and 24.74±3.34 kg/m² respectively. Coffee consumption had a significant inverse relationship with FBG and DBP in the elderly with T2DM (r: - 0.117, 0.134; p: 0.046, 0.022). TG and 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 FBG, 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.
... The -163A > C (rs762551) single nucleotide polymorphism (SNP) has been shown to alter CYP1A2 enzyme inducibility and activity [132,134], and has been used to categorize individuals as 'fast' or 'slow' metabolizers of caffeine. In the general population, individuals with the AC or CC genotype (slow metabolizers) have an elevated risk of myocardial infarction [266], hypertension and elevated blood pressure [267,268], and pre-diabetes [269], with increasing caffeinated coffee consumption, whereas those with the AA genotype show no such risk. Additionally, regular physical activity appears to attenuate the increase in blood pressure induced by caffeine ingestion, but only in individuals with the AA genotype [268]. ...
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Following critical evaluation of the available literature to date, The International Society of Sports Nutrition (ISSN) position regarding caffeine intake is as follows: 1. Supplementation with caffeine has been shown to acutely enhance various aspects of exercise performance in many but not all studies. Small to moderate benefits of caffeine use include, but are not limited to: muscular endurance, movement velocity and muscular strength, sprinting, jumping, and throwing performance, as well as a wide range of aerobic and anaerobic sport-specific actions. 2. Aerobic endurance appears to be the form of exercise with the most consistent moderate-to-large benefits from caffeine use, although the magnitude of its effects differs between individuals. 3. Caffeine has consistently been shown to improve exercise performance when consumed in doses of 3–6 mg/kg body mass. Minimal effective doses of caffeine currently remain unclear but they may be as low as 2 mg/kg body mass. Very high doses of caffeine (e.g. 9 mg/kg) are associated with a high incidence of side-effects and do not seem to be required to elicit an ergogenic effect. 4. The most commonly used timing of caffeine supplementation is 60 min pre-exercise. Optimal timing of caffeine ingestion likely depends on the source of caffeine. For example, as compared to caffeine capsules, caffeine chewing gums may require a shorter waiting time from consumption to the start of the exercise session. 5. Caffeine appears to improve physical performance in both trained and untrained individuals. 6. Inter-individual differences in sport and exercise performance as well as adverse effects on sleep or feelings of anxiety following caffeine ingestion may be attributed to genetic variation associated with caffeine metabolism, and physical and psychological response. Other factors such as habitual caffeine intake also may play a role in between-individual response variation. 7. Caffeine has been shown to be ergogenic for cognitive function, including attention and vigilance, in most individuals. 8. Caffeine may improve cognitive and physical performance in some individuals under conditions of sleep deprivation. 9. The use of caffeine in conjunction with endurance exercise in the heat and at altitude is well supported when dosages range from 3 to 6 mg/kg and 4–6 mg/kg, respectively. 10. Alternative sources of caffeine such as caffeinated chewing gum, mouth rinses, energy gels and chews have been shown to improve performance, primarily in aerobic exercise. 11. Energy drinks and pre-workout supplements containing caffeine have been demonstrated to enhance both anaerobic and aerobic performance.
... The analysis of potential interaction with genetic factors, in particular, may in addition offer insight into the role caffeine per se might play in associations. The few studies of caffeine-containing beverages and cardiometabolic biomarkers that have considered genetic variation in caffeine metabolism have focused on CYP1A2, included relatively small sample sizes, and together yielded inconclusive results (64)(65)(66)(67). The current study considered a more comprehensive list of SNPs, none of which modified the associations between beverage consumption and cardiometabolic biomarkers, suggesting noncaffeine constituents of coffee and tea more likely underlie these associations. ...
Article
Background: Mechanisms linking habitual consumption of coffee and tea to the development of type 2 diabetes and cardiovascular diseases remain unclear. Objectives: We leveraged dietary, genetic, and biomarker data collected from the UK Biobank to investigate the role of different varieties of coffee and tea in cardiometabolic health. Methods: We included data from ≤447,794 participants aged 37-73 y in 2006-2010 who provided a blood sample and completed questionnaires regarding sociodemographic factors, medical history, diet, and lifestyle. Multivariable linear regression was used to examine the association between coffee or tea consumption and blood concentrations of glycated hemoglobin, fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, fasting triglycerides (TGs), apoA-1, apoB, lipoprotein-a, and C-reactive protein (CRP). Lifestyle and genetic factors affecting caffeine metabolism, responses, or intake were tested for interactions with beverage intake in relation to biomarker concentrations. Results: Compared with coffee nonconsumers, each additional cup of coffee was significantly associated with higher total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations and lower TG and CRP concentrations in both men and women (P-trend < 0.002). Higher consumption of espresso coffee (≥2 compared with 0 cups/d) was associated with higher LDL cholesterol in men (β: 0.110 mmol/L; 95% CI: 0.058, 0.163 mmol/L) and women (β: 0.161 mmol/L; 95% CI: 0.088, 0.234 mmol/L), whereas no substantial association was observed for instant coffee. Compared with tea nonconsumers, higher tea consumption was associated with lower total and LDL cholesterol and apoB and higher HDL cholesterol (P-trend < 0.002); these associations were similar for black and green tea. Associations were not modified by genetics. Conclusions: In the UK Biobank, consumption of certain coffee brews such as espresso had unfavorable associations with blood lipids, whereas consumption of tea had favorable associations. Findings were not modified by genetic variants affecting caffeine metabolism, suggesting a role of noncaffeine constituents of these beverages in cardiometabolic health.
... These findings contrast those of Cornelis et al. (4), who first reported that variation in cytochrome P450 family 1 subfamily A member 2 (CYP1A2), which affects the rate of caffeine metabolism and modifies the association between coffee consumption and the risk of myocardial infarction. Those earlier findings have since been extended to hypertension (5), impaired fasting glucose (6), and blood pressure (7), where in all cases coffee or caffeine was associated with adverse outcomes only in individuals with the CYP1A2 genotype associated with slow metabolism of caffeine. As such, the lack of a modifying effect of genetic differences in caffeine metabolism observed by Zhou and Hypponen seems unexpected (3). ...
... The CYP1A2 1*F genotype (rs762551) slows the metabolism of caffeine and in carriers of this variant the association with hypertension was found only in moderate and heavy coffee drinkers suggesting an interaction [72]. Then, other studies have found that the slow CYP1A2*1 F allele in coffee drinkers impairs fasting glucose level in hypertensive patients [73] but lowers post-prandial glycaemic and lipaemic curves in patients randomized to coffee intervention (four cups per day of instant coffee for 3 months) [74]. Indeed, the CYP1A2 rs2470890 variant is associated with type II diabetes mellitus only when the interaction with coffee is considered [75], Another study analysed 3 CYP1A2 variants including the CYP1A2 1*F (rs762551, rs1133323 and rs1378942) in observational and one quasi-experimental studies and fund a positive association with hypertension only in non-smokers (n.b. smoking can induce the CYP1A2 enzyme). ...
... Another challenge to eliminating confounding is posed by polymorphisms of multiple genes that influence caffeine and/or coffee consumption [76][77][78][79][80][81][82][83][84]. Some of these polymorphisms also influence the risk of diseases associated with caffeine and/or coffee consumption [85][86][87][88][89][90]. ...
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Consumption of coffee by women early in their pregnancy has been viewed as potentially increasing the risk of miscarriage, low birth weight, and childhood leukemias. Many of these reports of epidemiologic studies have not acknowledged the potential biases inherent in studying the relationship between early-pregnancy-coffee consumption and subsequent events. I discuss five of these biases, recall bias, misclassification, residual confounding, reverse causation, and publication bias. Each might account for claims that attribute adversities to early-pregnancy-coffee consumption. To what extent these biases can be avoided remains to be determined. As a minimum, these biases need to be acknowledged wherever they might account for what is reported.
... Some of these polymorphisms also influence the risk of diseases associated with caffeine and/or coffee consumption. [80][81][82][83][84][85] A common strategy to disentangle the contribution of genetic propensity to consume coffee/caffeine is to stratify the sample by possession of each gene variant. In essence, this amounts to exploring the caffeine/coffee association in those with and without a specific variant. ...
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Consumption of coffee by women early in their pregnancy has been viewed as potentially increasing the risk of miscarriage, low birth weight, and childhood leukemias. Many of these reports of epidemiologic studies have not acknowledged the potential biases inherent in studying the relationship between early-pregnancy-coffee consumption and subsequent events. I discuss five of these biases, recall bias, misclassification, residual confounding, reverse causation, and publication bias. Each might account for claims that attribute adversities to early-pregnancy-coffee consumption. To what extent these biases can be avoided remains to be determined. At a minimum, they need to be acknowledged wherever they might account for what is reported.
... 86 Individuals homozygous for the CYP1A2 *1 A/*1 A genotype are fast caffeine metabolizers, whereas carriers of the slow *1 F allele are more exposed to the effects of caffeine. 87,88 Results from a recent meta-analysis indicated that sex and ethnicity could also modify the association between the CYP1A2 polymorphism and habitual coffee intake. 89 Comparison of consumers of high amounts and consumers of low amounts of coffee demonstrated that a high caffeine intake was associated with the genotype conferring fast metabolism. ...
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Context Type 2 diabetes (T2D) is a major health problem worldwide that is associated with increased morbidity and mortality. There is increased interest in the value of different nutrition-based strategies for preventing the development of T2D. Objective This review aims to cover current knowledge regarding the effects of coffee consumption on development of T2D or modulation of adverse complications. A meta-analysis on coffee consumption and the risk of T2D was conducted. Moreover, bioactive components in coffee, polymorphisms, and potential underlying mechanism(s) in relation to T2D and adverse complications are discussed. Data sources PubMed was searched up to December 1, 2017, and prospective cohort and nested case–control studies of the association between coffee consumption and T2D risk were selected. Data extraction Two investigators independently extracted data from included studies. Results A total of 30 prospective studies with 1 185 210 participants and 53 018 incident T2D cases were included in the meta-analysis. The pooled relative risk (RR) was 0.71 (95% confidence interval [CI], 0.67–0.76) for the highest category of coffee consumption (median consumption, 5 cups/d) vs the lowest category (median consumption, 0 cups/d). The risk of T2D decreased by 6% (RR = 0.94; 95%CI, 0.93–0.95) for each cup-per-day increase in coffee consumption. Results were similar for caffeinated coffee consumption (per additional cup of coffee per day: RR = 0.93; 95%CI, 0.90–0.96) and decaffeinated coffee consumption (corresponding RR = 0.94; 95%CI, 0.90–0.98). Conclusions Available evidence indicates that coffee consumption is inversely associated with risk of T2D. Possible mechanisms behind this association include thermogenic, antioxidative, and anti-inflammatory effects; modulation of adenosine receptor signaling; and microbiome content and diversity.
... The rs762551 SNP in the CYP1A2 gene affects the rate of caffeine metabolism (14) , with carriers of the C allele being classed as 'slow' caffeine metabolisers whereas those who are homozygous for the A allele are considered to be of a 'fast' metaboliser phenotype. Associations between coffee drinking and increased risk of myocardial infarction (15) , hypertension (16,17) and IFG (18) have been observed in individuals who are carriers of the 'slow' C allele but not in those with the 'fast' AA genotype. It is likely that these polymorphisms in the CYP1A2 gene will modulate the effects of coffee on glucose and lipid metabolism however, to our knowledge, this has not previously been investigated. ...
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There is much epidemiological evidence suggesting a reduced risk of development of type 2 diabetes (T2D) in habitual coffee drinkers, however to date there have been few longer-term interventions, directly examining the effects of coffee intake on glucose and lipid metabolism. Previous studies may be confounded by inter-individual variation in caffeine metabolism. Specifically, the rs762551 SNP in the CYP1A2 gene has been demonstrated to influence caffeine metabolism, with carriers of the C allele considered to be of a ‘slow’ metaboliser phenotype. This study investigated the effects of regular coffee intake on markers of glucose and lipid metabolism in coffee-naïve individuals, with novel analysis by rs762551 genotype. Participants were randomised to either a coffee group ( n 19) who consumed four cups/d instant coffee for 12 weeks or a control group ( n 8) who remained coffee/caffeine free. Venous blood samples were taken pre- and post-intervention. Primary analysis revealed no significant differences between groups. Analysis of the coffee group by genotype revealed several differences. Before coffee intake, the AC genotype (‘slow’ caffeine metabolisers, n 9) displayed higher baseline glucose and NEFA than the AA genotype (‘fast’ caffeine metabolisers, n 10, P <0·05). Post-intervention, reduced postprandial glycaemia and reduced NEFA suppression were observed in the AC genotype, with the opposite result observed in the AA genotype ( P <0·05). These observed differences between genotypes warrant further investigation and indicate there may be no one-size-fits-all recommendation with regard to coffee drinking and T2D risk.
... Another cardiovascular case includes heart rate, wherein variability, regulated by the AT1R/A1166C and CYP11B2/C-344T polymorphisms, is dependent on dietary sodium intake [5]. Other examples of the echogenetic context include the intake of recreational beverages [6], which can influence cardiovascular risk depending on genetic patterns [7,8], and by cognitive/mental patterns, which are, in part, genetically determined and can be both the consequence and cause of cardiovascular risk [9][10][11]. ...
... CC and AA homozygous and AC heterozygous can be identified in general population. In recent times, the CC homozygous have been labelled as slow caffeine metabolizers and the AA homozygous as fast caffeine metabolizers [9], while the AC heterozygous have been attributed alternatively to the former or to the latter, or called intermediate metabolizers [7]. ...
... In one study, the risk of hypertension associated with coffee intake was shown to vary according to CYP1A2 genotype, with carriers of the slow-metabolism *1F allele (59% of the 323 young, hypertensive participants, aged 18-45 y) at increased risk with higher coffee intake but not participants with the fastmetabolism *1A/*1A genotype (50). In a more recent study from this same hypertensive cohort, the association between coffee intake and impaired fasting glucose was stronger in carriers of the *1F variant, with the highest risk in heavy drinkers [$4 cups/d (400 mL/d)] (51). In relation to myocardial infarction, in a case-control study coffee intake was only associated with an increased risk of nonfatal myocardial infarction among participants with slow-caffeine metabolism (*1F variant) (19). ...
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Cardiometabolic disease, comprising cardiovascular diseases, type 2 diabetes, and their associated risk factors including metabolic syndrome and obesity, is the leading cause of death worldwide. Plant foods are rich sources of different groups of bioactive compounds, which might not be essential throughout life but promote health and well-being by reducing the risk of age-related chronic diseases. However, heterogeneity in the responsiveness to bioactive compounds can obscure associations between their intakes and health outcomes, resulting in the hiding of health benefits for specific population groups and thereby limiting our knowledge of the exact role of the different bioactive compounds for health. The heterogeneity in response suggests that some individuals may benefit more than others from the health effects of these bioactive compounds. However, to date, this interindividual variation after habitual intake of plant bioactive compounds has been little explored. The aim of this review is to provide an overview of the existing research that has revealed interindividual variability in the responsiveness to plant-food bioactive compound consumption regarding cardiometabolic outcomes, focusing on polyphenols, caffeine and plant sterols, and the identified potential determinants involved. Adv Nutr 2017;8:558–70.
... CC and AA homozygous and AC heterozygous can be identified in general population. In recent times, the CC homozygous have been labelled as slow caffeine metabolizers and the AA homozygous as fast caffeine metabolizers [9], while the AC heterozygous have been attributed alternatively to the former or to the latter, or called intermediate metabolizers [7]. ...
Article
Background and aims The possible effect of caffeine as an enhancer of cognitive performance, particularly that on abstract reasoning, has never been studied in an epidemiological setting, especially in relation to –163C>A polymorphism of CYP1A2 gene, largely controlling caffeine metabolism. Aim of this study was to ascertain whether in general population free chronic caffeine intake modifies abstract reasoning, and if this effect is influenced by the above mentioned genotype, by age, schooling, ethanol intake and smoking habits. Methods We studied 1374 unselected men and women aged 51 ± 15 years (range 18–89) from a general population. Daily caffeine intake deriving from coffee, tea, chocolate or cola was calculated from an anamnestic questionnaire and from a 7-day dietary diary. Abstract reasoning was measured in the frame of a neuropsychological assessment as the ability to find a concept linking two words indicating objects or actions and explaining how they were connected. Results In age-schooling-adjusted linear regression, the higher the caffeine intake, the better the abstraction score. Abstract reasoning depended on caffeine in the –163C>A CC homozygous only (so-called slow metabolizers), where it was higher in the 3rd tertile of caffeine intake. Age and ethanol reduced while smoking and schooling enhanced this association. The interaction term between caffeine and the –163C>A polymorphism was accepted in linear regressions. Caffeine consumption resulted innocuous for the A-carriers (so-called fast metabolizers). Conclusions In general population, a positive association between caffeine intake and abstract reasoning exists in the CC homozygous of the –163C>A polymorphism of CYP1A2 gene.
... For example, coffee beans are roasted at high temperatures, and thus may contain compounds similar to those found in tobacco smoke or chargrilled meats -known inducers of CYP1A2 activity [29]. Moreover, coffee's diverse composition roots the existing controversy between coffee and caffeine consumption and risk of type-2 diabetes (see [30] for review). The limitations of this study include the reliance on selfreports to determine the timing of saliva sampling and the lack of information regarding habitual consumption of some dietary components known to influence CYP1A2 activity, e.g., chargrilled meat, as well as the intake of specific medications. ...
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Background: Coffee consumption is a known inducer of cytochrome P450 1A2 (CYP1A2) enzyme activity. We recently observed that a group of type-2 diabetes patients consumed more caffeine (coffee) on a daily basis than non-type-2 diabetes controls. Here, we investigated whether type-2 diabetes cases may metabolize caffeine faster than non-type-2 diabetes controls. Methods: To estimate CYP1A2 enzyme activity, an established marker of caffeine metabolism, we quantified the paraxanthine/caffeine concentration ratio in saliva in 57 type-2 diabetes and 146 non-type-2 diabetes participants in a case-control field study. All participants completed validated questionnaires regarding demographic status, health and habitual caffeine intake, and were genotyped for the functional -163C>A polymorphism of the CYP1A2 gene. Results: In the diabetes group, we found a larger proportion of participants with the highly inducible CYP1A2 genotype. Furthermore, the paraxanthine/caffeine ratio, time-corrected to mitigate the impact of different saliva sampling times with respect to the last caffeine intake, was higher than in the control group. Participants who reported habitually consuming more caffeine than the population average showed higher CYP1A2 activity than participants with lower than average caffeine consumption. Multiple regression analyses revealed that higher caffeine intake was potentially an important mediator of higher CYP1A2 activity. Conclusions: Estimated CYP1A2 enzyme activity, and thus speed of caffeine metabolism, was higher in our type-2 diabetes group; this was possibly due to higher intake of caffeine, a known inducer of CYP1A2 enzyme activity. Given the fairly small sample sizes, the results need to be considered as preliminary and require validation in larger populations.
... Thirty-three studies were assessed for eligibility. The following papers were excluded: four GWAS (Cornelis et al., 2011;Sulem et al., 2011;Amin et al., 2012;Rodenburg et al., 2012); four studies lacking coffee intake analysis (Sachse et al., 1999;Basvi et al., 2007;Ghotbi et al., 2007;Gunes et al., 2009); eight studies not providing coffee intake data according to rs762551 genotypes (Goodman et al., 2003;Kotsopoulos et al., 2009;Hallström et al., 2010;Schmidt et al., 2010;Guessous et al., 2012;Josse et al., 2012;Palatini et al., 2015;Yamamoto et al., 2015); two studies providing CC and combined AC + AA genotypes counts instead of AA and AC + CC genotype counts (Palatini et al., 2009;Pavanello et al., 2010); two studies using patient samples (Cornelis et al., 2007;Bågeman et al., 2008); and one study with a small sample size . Finally, 12 studies were included in the meta-analysis (Nordmark et al., 2002;Sata et al., 2005;Cornelis et al., 2006;Kotsopoulos et al., 2007;Tan et al., 2007;Jernström et al., 2008;Djordjevic et al., 2010;Popat et al., 2011;Kohno et al., 2013;Lowcock et al., 2013;Tian et al., 2013;Dik et al., 2014) (Figure 1). ...
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The association between the single nucleotide polymorphism rs762551 in the cytochrome P450 family 1, subfamily A2 gene (CYP1A2) and caffeine consumption remains controversial. We conducted a meta-analysis to clarify this potential association. Twelve studies were selected from articles retrieved from the and Google Scholar databases, and the data were analyzed to determine the odds ratio (OR) of genotypes AA (conferring fast caffeine metabolism) vs AC + CC (conferring slow caffeine metabolism). Comparisons were made between 6161 high caffeine consumers and 3219 low caffeine consumers. The overall analysis showed a significant association between genotype AA and coffee intake [OR = 1.13, 95% confidence interval (CI) = 1.03-1.24; Q = 19.23, P =0.06; I2 = 43%]. In subgroup analyses, the association was also found within male, younger, and Caucasian subjects (OR = 1.21, 95%CI = 1.08-1.35; OR = 1.71, 95%CI = 1.18-2.48; OR = 1.29, 95%CI = 1.12-1.49, respectively) but not in female, older, and Asian subjects (OR = 0.98, 95%CI = 0.83-1.15; OR = 0.83, 95%CI = 0.56-1.22; OR = 0.91, 95%CI= 0.71-1.17, respectively). Therefore, the rs762551 AA genotype may lead to higher coffee intake, especially in males, younger age groups,and individuals of Caucasian ethnicity. Our data highlight the need to test other CYP1A2 polymorphisms showing significance in genome-wide association studies to clarify the association with caffeine intake in the Asian population.
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In response to the current clinical debate regarding the causal relationship between coffee consumption and the risk of diabetic complications, we conducted a two-sample Mendelian randomization study to determine the impact of coffee on diabetic complications, and further explored this association in complications of diabetes subtypes. We collected summary statistics from 22 genome-wide association studies in the UK Biobank database and FinnGen R9 repository. Causal effects were assessed using the inverse variance weighted (IVW) method, MR pleiotropy residual sum and outlier (MR-PRESSO) model, maximum likelihood method, weighted median method, simple median method, and MR-Egger method. Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test were utilized for sensitivity analysis. Genetic evidence indicates a positive linkage between coffee intake and the risk of diabetes complications, with coffee significantly increasing the risk of diabetic nephropathy, diabetic neuropathy, and diabetic peripheral angiopathy, and possibly promoting the occurrence and progression of diabetic ocular complications. Coffee also contributed substantially to the complications of type 2 diabetes, while the connection between coffee consumption and complications of type 1 diabetes was modestly notable. These findings provide a scientific foundation for more targeted prevention and management of diabetes complications.
Article
Background and aims: Among an unselected cohort of men and women from general population (n = 1.668), the prognostic effects of being over the cut-off of all-source dietary caffeine intake were studied. Methods and results: Prognostic cut-off values for coronary events, incident heart failure (HF), cerebrovascular events (CBV) and arrhythmic events (ARR) were found by means of the receiver-operating-characteristic curves method. Those for HF (>230 mg/day), for CBV (>280 mg/day) and for ARR (>280 mg/day) were confirmed in multivariate Cox analysis adjusted for age, body mass index, circulating thyroid hormone, diabetes mellitus, arterial hypertension, smoking, dietary intake of ethanol, basal heart rate, low-density-lipoprotein cholesterol, forced expiratory volume in 1 s and β-blocking therapy. Being over these cut-off values was associated to a reduced hazard ratio during the follow-up in the whole cohort (HR 0.678, 95%CI 0.567-0.908, p = 0.009 for HF; 0.651, 95%CI 0.428-0.994, p = 0.018 for CBV; 0.395, 95%CI 0.395-0.933, p = 0.022 for ARR) and in men (0.652, 0.442-0.961, p = 0.029; 0.432, 0.201-0.927, p = 0.03; 0.553, 0.302-1.000, p = 0.05, respectively) but not in women. The caffeine-induced risk decrease observed in the whole cohort is therefore entirely attributable to men. In the case of HF, heart rate entered the risk equation in a positive manner without rejecting caffeine. The -163C>A polymorphism of the CYP1A2 gene, codifying for ability to metabolize caffeine, introduced in sensitivity analysis, did not alter the prognostic models. Conclusion: Men introducing >230 mg/day caffeine show a reduced risk of HF, and those introducing >280 mg/day a reduced risk of CBV and ARR independent of genetic pattern.
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The relationship between caffeine consumption and cardiometabolic health has been reported, however with heterogenous results. Discrepancies in study results may be due to inter‐individual variability between study participants. This systematic review aimed to identify the impact of genetics on the relationship between caffeine consumption and cardiometabolic outcomes. Electronic databases (PubMed and EMBASE) were searched for studies published until July 2021. Selected studies were of both intervention and observational design and included (1) analysis of at least one of the selected cardiometabolic outcome (type 2 diabetes, glucose/insulin levels, cardiovascular disease [CVD], blood pressure [BP] or hypertension, and blood lipid and catecholamine levels), (2) adults aged 18–65 years, and (3) genetic analysis of individuals consuming caffeine. Seventeen studies were included: four randomised controlled trials and an interventional and quasi‐experimental study, six population‐based prospective cohort studies, three cross‐sectional studies, and three case–control studies. CYP1A2 rs762551 and ADORA rs5751876 were associated with glucose response when caffeine was consumed with carbohydrates. CYP1A2 rs762551 moderated the association between coffee intake and hypertension. Moreover, ADORA2A rs5751876 and the ADRA2B I variants moderated the associations between caffeine and BP. Studies that investigated the effects of genetic variations on CVD and caffeine consumption reported equivocal findings (CYP1A2) or warrant replication (COMT, ADORA and TRIB1). Elucidating the extent to which these genes moderate the association between caffeine and cardiometabolic outcomes will enable caffeine consumption advice to be tailored to specific individuals to optimise health.
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Importance Caffeine is detoxified by cytochrome P450 1A2 (CYP1A2), and genetic variation in CYP1A2 impacts the rate of caffeine clearance. Factors that may modify the association between coffee intake and kidney disease remain unclear. Objective To assess whether CYP1A2 genotype modifies the association between coffee intake and kidney dysfunction. Design, Setting, and Participants The Hypertension and Ambulatory Recording Venetia Study (HARVEST) was a prospective cohort study of individuals with stage 1 hypertension in Italy; HARVEST began on April 1, 1990, and follow-up is ongoing. The current study used data from April 1, 1990, to June 30, 2006, with follow-up of approximately 10 years. Blood pressure and biochemical data were collected monthly during the first 3 months, then every 6 months thereafter. Data were analyzed from January 2019 to March 2019. Participants were screened and recruited from general practice clinics. The present study included 1180 untreated participants aged 18 to 45 years with stage 1 hypertension; those with nephropathy, diabetes, urinary tract infection, and cardiovascular disease were excluded. Exposures Coffee intake and CYP1A2 genotype rs762551 were exposures analyzed over a median follow-up of 7.5 (IQR, 3.1-10.9) years. Main Outcomes and Measures Albuminuria (defined as an albumin level of ≥30 mg/24 h) and hyperfiltration (defined as an estimated glomerular filtration rate of ≥150 mL/min/1.73 m ² ) were the primary outcomes as indicators of kidney dysfunction. Results Among 1180 participants, genotyping, lifestyle questionnaires, and urine analysis data were obtained from 604 individuals (438 [72.5%] male) with a mean (SD) age of 33.3 (8.5) years and a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 25.4 (3.4). A total of 158 participants (26.2%) consumed less than 1 cup of coffee per day, 379 (62.7%) consumed 1 to 3 cups per day, and 67 (11.1%) consumed more than 3 cups per day. Genotype frequencies for rs762551 (260 participants [43.1%] with genotype AA, 247 participants [40.8%] with genotype AC, and 97 participants [16.1%] with genotype CC) did not differ between coffee intake categories. The level of risk of developing albuminuria, hyperfiltration, and hypertension, assessed by Cox regression and survival analyses, was not associated with coffee intake in the entire group or among fast metabolizers. The risks of albuminuria (adjusted hazard ratio [aHR], 2.74; 95% CI, 1.63-4.62; P < .001), hyperfiltration (aHR, 2.11; 95% CI, 1.17-3.80; P = .01), and hypertension (aHR, 2.81; 95% CI, 1.51-5.23; P = .001) increased significantly among slow metabolizers who consumed more than 3 cups per day. Conclusions and Relevance In this study, the risks of albuminuria, hyperfiltration, and hypertension increased with heavy coffee intake only among those with the AC and CC genotypes of CYP1A2 at rs762551 associated with slow caffeine metabolism, suggesting that caffeine may play a role in the development of kidney disease in susceptible individuals.
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Kafein, psikoaktif etkileri nedeniyle uyarıcı olarak birçok insanın tercihi halini almıştır. Farklı türevleri ile birçok alan ve amaçla kullanılan kafein, egzersiz üzerindeki etkileri ile de spor bilimciler tarafından yakından takip edilmektedir. Yine, uzun yıllardır araştırılan bir konu olarak kafein ve genotip ilişkisi, ülkemiz için azınlıkta ve yeni sayılabilir. Bu çalışma, karaciğerde kafein metabolizmasından sorumlu Sitokrom P450 1A2 enzimini kodlayan CYP1A2 genotiplerine göre, kafein metabolizma hızlarının performansa etkisini incelemek amacıyla yapılmıştır. Çalışma, derleme türünde, konu ile yakından ilgili çalışmaların araştırılması, incelenmesi ve sonuçların yorumlanması oluşturulmuştur. İlgili araştırma sonuçlarına yoğun olarak, ulusal tıp kütüphanesi temelinde bilimsel araştırmalar içeren PubMed.gov sitesinden ulaşım sağlanmıştır. Kafein üzerine yapılan çalışmalarda, alım zamanı, dozu, egzersiz tipi gibi parametrelerde daha net ifadeler görülürken, sonuçların genotip ile olan ilişkisi ve nedeni ile ilgili henüz tam anlamıyla net ifadeler oluşmamıştır. Çünkü, kafein ile genotip ilişkisinde olumlu sonuçlar gösteren çalışmaların oranı kadar olumsuz sonuçlar gösteren çalışmalar da mevcuttur. Bu da çelişkiye neden olmaktadır. Şu anda, mevcut veriler, hangi genotipin kafein takviyesinden en fazla faydayı görebileceğini belirtmek için yetersiz gibi görünmektedir. AA homozigotlarının varlığını gösteren bazı kanıtlar olsa da zayıftır. Bu nedenle, CYP1A2 genotipini belirlemek için yapılan genetik testler şu anda yeterli sonuçlara ulaşma olanağı vermediğinden gerekli olup olmadığının tartışmaya açık olduğu düşünülmektedir.
Chapter
Hormesis is an adaptive compensatory response of cells to stress through dose-induced stimulation. Plants contain nutrients, phytochemicals, and secondary metabolites that can prevent and alleviate free radical-induced diseases or syndromes. Importantly, most of the health benefits of plant bioactives are generally explained due to their antioxidant properties. Recently, it has been observed that many plant bioactive molecules exhibit a hormetic effect by activating cells to effectively resist severe stress through signaling pathways and can result in cell toxicity depending on the concentrations/doses; this may be one of the mechanisms by which these phyto-compounds elicit health-promoting effects. Herein we have described the bioactives present in some plant sources and explained the hormetic effects relevant to aging intervention and promoting longevity.
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In the last few decades there has been much debate about the management of low-risk stage 1 hypertension in youth. In this article, we review the main findings of the HARVEST cohort accrued over 30 years, highlighting the contribution of this study to the existing literature. Tachycardia and sympathetic overdrive were closely intertwined in our HARVEST participants, promoting the development of sustained hypertension, metabolic abnormalities, and increased susceptibility to vascular complications. Short-term blood pressure variability in this age group had a prognostic power even greater than that of average 24h blood pressure. In the HARVEST participants, changes in left ventricular anatomy and contractility were the earliest signs of hypertensive cardiac involvement, whereas left ventricular filling was only marginally affected. Our results highlighted the role of glomerular hyperfiltration in determining microalbuminuria and renal damage in the early stage of hypertension. The genetic approach provided an important contribution to risk stratification and patient management. The HARVEST confirmed the importance of maintaining a good lifestyle for preventing the onset of hypertension, diabetes and cardiovascular events. Isolated systolic hypertension in the first decades of life appeared as a heterogeneous condition. To establish whether antihypertensive drug treatment should be started in this condition the clinician should consider the individual cardiovascular risk profile, the level of office mean BP and central BP. Despite recent progress in our knowledge, systolic hypertension still represents a challenging issue for the clinician. Hopefully, the HARVEST will continue to contribute data that help to fill the present gaps in evidence.
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Human cytochrome P450 enzymes (CYPs) play a critical role in various biological processes and human diseases. CYP1 family members, including CYP1A1, CYP1A2, and CYP1B1, are induced by aryl hydrocarbon receptors (AhRs). The binding of ligands such as polycyclic aromatic hydrocarbons activates the AhRs, which are involved in the metabolism (including oxidation) of various endogenous or exogenous substrates. The ligands that induce CYP1 expression are reported to be carcinogenic xenobiotics. Hence, CYP1 enzymes are correlated with the pathogenesis of cancers. Various endogenous substrates are involved in the metabolism of steroid hormones, eicosanoids, and other biological molecules that mediate the pathogenesis of several human diseases. Additionally, CYP1s metabolize and activate/inactivate therapeutic drugs, especially, anti-cancer agents. As the metabolism of drugs determines their therapeutic efficacy, CYP1s can determine the susceptibility of patients to some drugs. Thus, understanding the role of CYP1s in diseases and establishing novel and efficient therapeutic strategies based on CYP1s have piqued the interest of the scientific community.
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Scope: Coffee has been associated with a lower risk of cancer, cardiovascular disease and type 2 diabetes at the population level. However, individual susceptibility to the effects of coffee consumption will cause heterogeneity in health responses between individuals. In this critical review we systematically evaluated determinants of inter-individual variability in cancer and cardiometabolic health outcomes in response to coffee and caffeine consumption. Methods and results: Embase and MEDLINE were searched for observational studies and clinical trials that examined variation in the response to coffee consumption. A total of 74 studies met the inclusion criteria, which reported variation in cancer (n = 24) and cardiometabolic health (n = 50) outcomes. Our qualitative analysis showed that sex, BMI, smoking, alcohol intake, menopausal status and genetic polymorphisms are probable or possible determinants of inter-individual variability in cancer and cardiometabolic health outcomes in response to coffee and caffeine consumption, albeit that the majority of studies had insufficient statistical power to detect significant interaction between these factors and coffee consumption. Conclusion: We identified several genetic and non-genetic determinants of inter-individual variability in the responses to coffee and caffeine consumption, indicating that some of the health benefits of coffee may only occur in a subgroup of subjects. This article is protected by copyright. All rights reserved.
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An individual's dietary and supplement strategies can influence markedly their physical performance. Personalized nutrition in athletic populations aims to optimize health, body composition, and exercise performance by targeting dietary recommendations to an individual's genetic profile. Sport dietitians and nutritionists have long been adept at placing additional scrutiny on the one-size-fits-all general population dietary guidelines to accommodate various sporting populations. However, generic “one-size-fits-all” recommendations still remain. Genetic differences are known to impact absorption, metabolism, uptake, utilization and excretion of nutrients and food bioactives, which ultimately affects a number of metabolic pathways. Nutrigenomics and nutrigenetics are experimental approaches that use genomic information and genetic testing technologies to examine the role of individual genetic differences in modifying an athlete's response to nutrients and other food components. Although there have been few randomized, controlled trials examining the effects of genetic variation on performance in response to an ergogenic aid, there is a growing foundation of research linking gene-diet interactions on biomarkers of nutritional status, which impact exercise and sport performance. This foundation forms the basis from which the field of sport nutrigenomics continues to develop. We review the science of genetic modifiers of various dietary factors that impact an athlete's nutritional status, body composition and, ultimately athletic performance.
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div class="title">Longer-term effects of coffee on glucose and lipid metabolism - Volume 75 Issue OCE3 - T.M. Robertson, M.N. Clifford, S. Penson, M.D. Robertson
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Many disease states are independently influenced by both diet and genes. Dietary and genetic factors can also act synergistically to have a joint effect on human health through diet–gene interaction. For example, the protein products of genes (enzymes, transporters, receptors, hormones, etc.) may interact with nutritional constituents of foods to influence metabolic processes and health status. Commonly occurring polymorphisms in the genes that code for these protein products can lead to differences both in the amount of protein produced and in how efficiently that protein functions, thus leading to individual differences in processes such as digestion and metabolism. Among researchers and healthcare practitioners, there is a growing interest in utilizing genetic information to predict and manage the large interindividual differences in response to intake of food and nutrients. Recent advances in human genomics have enabled cost-effective and rapid detection of variations in genes affecting nutrient metabolism, but their full impact on nutrient requirements remains to be elucidated. The common haptoglobin polymorphism is an example of a polymorphism which may have an important influence on chronic disease via its impact on nutrient status. The objective of this chapter is to introduce the concept of diet–gene interactions and to discuss the various effects that genes can have on metabolic responses to food, focusing on the common haptoglobin polymorphism as an example.
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Higher coffee consumption has been associated with a lower risk of type 2 diabetes in cohort studies, but the physiological pathways through which coffee affects glucose metabolism are not fully understood. The aim of this study was to evaluate the associations between habitual coffee and tea consumption and glucose metabolism in a multi-ethnic Asian population and possible mediation by inflammation. We cross-sectionally examined the association between coffee, green tea, black tea and Oolong tea consumption and glycemic (fasting plasma glucose, HOMA-IR, HOMA-beta, plasma HbA1c) and inflammatory (plasma adiponectin and C-reactive protein) markers in a multi-ethnic Asian population (N = 4139). After adjusting for multiple confounders, we observed inverse associations between coffee and HOMA-IR (percent difference: - 8.8% for ≥ 3 cups/day versus rarely or never; Ptrend = 0.007), but no significant associations between coffee and inflammatory markers. Tea consumption was not associated with glycemic markers, but green tea was inversely associated with plasma C-reactive protein concentrations (percent difference: - 12.2% for ≥ 1 cup/day versus < 1 cup/week; Ptrend = 0.042). These data provide additional evidence for a beneficial effect of habitual caffeinated coffee consumption on insulin sensitivity, and suggest that this effect is unlikely to be mediated by anti-inflammatory mechanisms.
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Coffee consumption has been associated with a lower risk of diabetes, but little is known about the mechanisms responsible for this association, especially related to the time when coffee is consumed. We examined the long-term effect of coffee, globally and according to the accompanying meal, and of tea, chicory, and caffeine on type 2 diabetes risk. This was a prospective cohort study including 69,532 French women, aged 41-72 y from the E3N/EPIC (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale/European Prospective Investigation into Cancer and Nutrition) cohort study, without diabetes at baseline. Food and drink intakes per meal were assessed by using a validated diet-history questionnaire in 1993-1995. During a mean follow-up of 11 y, 1415 new cases of diabetes were identified. In multivariable Cox regression models, the hazard ratio in the highest category of coffee consumption [> or =3 cups (375 mL)/d] was 0.73 (95% CI: 0.61, 0.87; P for trend < 0.001), in comparison with no coffee consumption. This inverse association was restricted to coffee consumed at lunchtime (hazard ratio: 0.66; 95% CI: 0.57, 0.76) when comparing >1.1 cup (125 mL)/meal with no intake. At lunchtime, this inverse association was observed for both regular and decaffeinated coffee and for filtered and black coffee, with no effect of sweetening. Total caffeine intake was also associated with a statistically significantly lower risk of diabetes. Neither tea nor chicory consumption was associated with diabetes risk. Our data support an inverse association between coffee consumption and diabetes and suggest that the time of drinking coffee plays a distinct role in glucose metabolism.
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Coffee consumption has been reported to be inversely associated with risk of type 2 diabetes mellitus. Similar associations have also been reported for decaffeinated coffee and tea. We report herein the findings of meta-analyses for the association between coffee, decaffeinated coffee, and tea consumption with risk of diabetes. Relevant studies were identified through search engines using a combined text word and MeSH (Medical Subject Headings) search strategy. Prospective studies that reported an estimate of the association between coffee, decaffeinated coffee, or tea with incident diabetes between 1966 and July 2009. Data from 18 studies with information on 457 922 participants reported on the association between coffee consumption and diabetes. Six (N = 225 516) and 7 studies (N = 286 701) also reported estimates of the association between decaffeinated coffee and tea with diabetes, respectively. We found an inverse log-linear relationship between coffee consumption and subsequent risk of diabetes such that every additional cup of coffee consumed in a day was associated with a 7% reduction in the excess risk of diabetes relative risk, 0.93 [95% confidence interval, 0.91-0.95]) after adjustment for potential confounders. Owing to the presence of small-study bias, our results may represent an overestimate of the true magnitude of the association. Similar significant and inverse associations were observed with decaffeinated coffee and tea and risk of incident diabetes. High intakes of coffee, decaffeinated coffee, and tea are associated with reduced risk of diabetes. The putative protective effects of these beverages warrant further investigation in randomized trials.
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Caffeine and caffeinated coffee (CC) elicit acute insulin insensitivity when ingested before a carbohydrate load. The effects of CC on glucose tolerance and insulin sensitivity when co-ingested with a high carbohydrate meal and on postprandial metabolism of a subsequent (second) carbohydrate load have not been studied. In a randomised, crossover design, ten healthy males ingested either CC (5 mg caffeine/kg body weight), decaffeinated coffee (DC) or water (W; equal volume) co-ingested with a high glycaemic index cereal followed 3 h later by a 75 g oral glucose tolerance test. After the initial meal, insulin area under the curve (AUC) and insulin sensitivity index did not differ between treatments, although glucose AUC for CC (107 (sem 18) mmol/l x 3 h) and DC (74 (sem 15) mmol/l x 3 h) was greater than W ( - 0.2 (sem 29) mmol/l x 3 h, P < 0.05). After the second carbohydrate load, insulin AUC for CC was 49 % and 57 % greater (P < 0.01) than for DC and W, respectively. Despite the greater insulin response, glucose AUC for CC (217 (sem 24) mmol/l x 2 h) was greater than both DC (126 (sem 11) mmol/l x 2 h, P = 0.01) and W (55 (sem 34) mmol/l x 2 h, P < 0.001). Insulin sensitivity index after the second meal was lower after CC (8.2 (sem 0.9)) compared with both DC (12.4 (sem 1.2), P < 0.01) and W (13.4 (sem 1.4), P < 0.001). Co-ingestion of CC with one meal resulted in insulin insensitivity during the postprandial phase of a second meal in the absence of further CC ingestion. Thus, CC may play a role in daily glycaemic management.
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The longitudinal relationship between coffee use and hypertension is still controversial. Cytochrome P450 1A2 (CYP1A2) is the main responsible enzyme for the metabolism of caffeine. The aim of the present study was to investigate the effect of coffee intake on the risk of developing hypertension needing antihypertensive treatment in individuals stratified by CYP1A2 genotype. We assessed prospectively 553 young White individuals screened for stage 1 hypertension. Coffee intake was ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure. Genotyping of CYP1A2 SNP was performed by real time PCR. During a median follow-up of 8.2 years, 323 individuals developed hypertension. For carriers of the slow *1F allele (59%), hazard ratios of hypertension from multivariable Cox analysis were 1.00 in abstainers (reference), 1.72 (95%CI, 1.21-2.44) in moderate coffee drinkers (P = 0.03), and 3.00 (1.53-5.90) in heavy drinkers (P = 0.001). In contrast, hazard ratios for coffee drinkers with the rapid *1A/*1A genotype were 0.80 (0.52-1.23, P = 0.29) for moderate drinkers and 0.36 (0.14-0.89, P = 0.026) for heavy drinkers. In a two-way ANCOVA, a gene x coffee interactive effect was found on follow-up changes in systolic (P = 0.000) and diastolic (P = 0.007) blood pressure. Urinary epinephrine was higher in coffee drinkers than abstainers but only among individuals with slow *1F allele (P = 0.001). These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee.
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Caffeine is a central stimulant that increases the release of catecholamines. As a component of popular beverages, caffeine is widely used around the world. Its pharmacological effects are predominantly due to adenosine receptor antagonism and include release of catecholamines. We hypothesized that caffeine reduces insulin sensitivity, either due to catecholamines and/or as a result of blocking adenosine-mediated stimulation of peripheral glucose uptake. Hyperinsulinemic-euglycemic glucose clamps were used to assess insulin sensitivity. Caffeine or placebo was administered intravenously to 12 healthy volunteers in a randomized, double-blind, crossover design. Measurements included plasma levels of insulin, catecholamines, free fatty acids (FFAs), and hemodynamic parameters. Insulin sensitivity was calculated as whole-body glucose uptake corrected for the insulin concentration. In a second study, the adenosine reuptake inhibitor dipyridamole was tested using an identical protocol in 10 healthy subjects. Caffeine decreased insulin sensitivity by 15% (P < 0.05 vs. placebo). After caffeine administration, plasma FFAs increased (P < 0.05) and remained higher than during placebo. Plasma epinephrine increased fivefold (P < 0.0005), and smaller increases were recorded in plasma norepinephrine (P < 0.02) and blood pressure (P < 0.001). Dipyridamole did not alter insulin sensitivity and only increased plasma norepinephrine (P < 0.01). Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels. Because dipyridamole did not affect glucose uptake, peripheral adenosine receptor antagonism does not appear to contribute to this effect.
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The caffeine-induced impairment of insulin action is commonly attributed to adenosine receptor (AR) antagonism in skeletal muscle. However, epinephrine, a potent inhibitor of insulin actions, is increased after caffeine ingestion. We tested the hypothesis that the insulin antagonistic effects of caffeine are mediated by epinephrine, and not by AR antagonism, in seven healthy men. On four separate occasions, they received 1) dextrose (placebo, PL), 2) 5 mg/kg caffeine (CAF), 3) 80 mg of propranolol (PR), and 4) 5 mg/kg caffeine + 80 mg of propranolol (CAF + PR) before an oral glucose tolerance test (OGTT). Blood glucose was similar among trials before and during the OGTT. Plasma epinephrine was elevated (P < 0.05) in CAF and CAF + PR. Areas under the insulin and C-peptide curves were 42 and 39% greater (P < 0.05), respectively, in CAF than in PL, PR, and CAF + PR. In the presence of propranolol (CAF + PR), these responses were similar to PL and PR. These data suggest that the insulin antagonistic effects of caffeine in vivo are mediated by elevated epinephrine rather than by peripheral AR antagonism.
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Accumulating evidence suggests that certain dietary polyphenols have biological effects in the small intestine that alter the pattern of glucose uptake. Their effects, however, on glucose tolerance in humans are unknown. The objective was to investigate whether chlorogenic acids in coffee modulate glucose uptake and gastrointestinal hormone and insulin secretion in humans. In a 3-way, randomized, crossover study, 9 healthy fasted volunteers consumed 25 g glucose in either 400 mL water (control) or 400 mL caffeinated or decaffeinated coffee (equivalent to 2.5 mmol chlorogenic acid/L). Blood samples were taken frequently over the following 3 h. Glucose and insulin concentrations tended to be higher in the first 30 min after caffeinated coffee consumption than after consumption of decaffeinated coffee or the control (P < 0.05 for total and incremental area under the curve for glucose and insulin). Glucose-dependent insulinotropic polypeptide secretion decreased throughout the experimental period (P < 0.005), and glucagon-like peptide 1 secretion increased 0-120 min postprandially (P < 0.01) after decaffeinated coffee consumption compared with the control. Glucose and insulin profiles were consistent with the known metabolic effects of caffeine. However, the gastrointestinal hormone profiles were consistent with delayed intestinal glucose absorption. Differences in plasma glucose, insulin, and gastrointestinal hormone profiles further confirm the potent biological action of caffeine and suggest that chlorogenic acid might have an antagonistic effect on glucose transport. Therefore, a novel function of some dietary phenols in humans may be to attenuate intestinal glucose absorption rates and shift the site of glucose absorption to more distal parts of the intestine.
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