Estimate the prevalence of daily caffeine consumption, caffeine use disorder, caffeine withdrawal and perceived harm in Iran: a cross-sectional study.

One of the informal diagnoses in DSM-5 is Caffeine Use Disorder (CUD). CUD and high levels of caffeine consumption could impact mental health conditions. This study aimed to estimate the prevalence of CUD, caffeine consumption, caffeine-related harms, and related psychiatric symptoms in Iran. A cross-sectional survey with a convenience sample of 1228 adults were conducted in Iran. Caffeine consumption was assessed across 20 products in Iran. Caffeine Use Disorder Questionnaire (CUDQ), Caffeine Withdrawal Symptoms Questionnaire (CWSQ), 14-item Caffeine-related Harm Screening (CHS), and Symptom Checklist-25 (SCL-25) were used in the present study. We used SPSS (desktop version 26.0) to analyze the data using descriptive statistics, chi-square, and the least significant difference (LSD) post hoc test. The daily average caffeine consumption was 146.67 mg. The prevalence of CUD and caffeine withdrawal (C.W.) were estimated at 19.5% and 46.62%, respectively. Also, 12.9% of responders received CUD and C.W.s simultaneously. The prevalence of CUD was higher in men than females (25.08% vs. 13.93%). 95% of participants (n = 1166) reported using at least one caffeine product yesterday. Moreover, the most reported caffeine-related harms were the desire for sugar (42.9%), insomnia (39.3%), and caffeine dependence (38.3%). Age significantly correlates with CUD (- 0.07) and daily caffeine intake (0.08). Moreover, all SCL-90 subscales had a significant correlation with daily caffeine intake. Finally, responders at younger ages reported higher levels of CUD and caffeine consumption than older adults(P < 0.05). High rates of C.W. and CUD in the Iranian population suggest that it is necessary to develop evidence-based treatments.

Daily Caffeine Consumption May Increase the Risk of Acute Kidney Injury Related to Platinum-Salt Chemotherapy in Thoracic Cancer Patients: A Translational Study.

Although their efficacy has been well-established in Oncology, the use of platinum salts remains limited due to the occurrence of acute kidney injury (AKI). Caffeine has been suggested as a potential pathophysiological actor of platinum-salt-induced AKI, through its hemodynamic effects. This work aims to study the association between caffeine consumption and the risk of platinum-salt-induced AKI, based on both clinical and experimental data. The clinical study involved a single-center prospective cohort study including all consecutive thoracic cancer patients receiving a first-line platinum-salt (cisplatin or carboplatin) chemotherapy between January 2017 and December 2018. The association between daily caffeine consumption (assessed by a validated auto-questionnaire) and the risk of platinum-salt induced AKI or death was estimated by cause-specific Cox proportional hazards models adjusted for several known confounders. Cellular viability, relative renal NGAL expression and/or BUN levels were assessed in models of renal tubular cells and mice co-exposed to cisplatin and increasing doses of caffeine. Overall, 108 patients were included (mean age 61.7 years, 65% men, 80% tobacco users), among whom 34 (31.5%) experienced a platinum-salt-induced AKI (67% Grade 1) over a 6-month median follow-up. The group of high-caffeine consumption (≥386 mg/day) had a two-fold higher hazard of AKI (adjusted HR [95% CI], 2.19 [1.05; 4.57]), without any significant association with mortality. These results are consistent with experimental data confirming enhanced cisplatin-related nephrotoxicity in the presence of increasing doses of caffeine, in both in vitro and in vivo models. Overall, this study suggests a potentially deleterious effect of high doses of daily caffeine consumption on the risk of platinum-salt-related AKI, in both clinical and experimental settings.

Optimizing Short-Term Maximal Exercise Performance: The Superior Efficacy of a 6 mg/kg Caffeine Dose over 3 or 9 mg/kg in Young Female Team-Sports Athletes.

Caffeine (CAF) is among the most extensively researched dietary supplements worldwide. However, little is known about the relationship between dosage and performance enhancement, particularly in female athletes. This study aimed to explore the effects of three different CAF dosages (3 mg·kg-1, 6 mg·kg-1, and 9 mg·kg-1) on high-intensity exercise and the prevalence of undesirable side effects related to these doses among female team-sports athletes. All participants (n = 16; age: 16.9 ± 0.6 y; height: 1.64 ± 0.1 m; BMI: 21.6 ± 1.5 kg·m-2) were mild CAF consumers. This study had a randomized, crossover, double-blind design in which each athlete performed four experimental sessions after ingesting either a placebo (PLAC), 3 mg·kg-1 CAF (CAF-3), 6 mg·kg-1 CAF (CAF-6), or 9 mg·kg-1 of CAF (CAF-9), with an in-between washout period of at least 72 h. In each experimental session, 60 min after ingesting the capsules, participants underwent a countermovement jumps test (CMJ), modified agility t-test (MATT), repeated sprint ability (RSA) test, and a rating of perceived exertion (RPE) and completed the CAF side effects questionnaire. Our findings revealed that in comparison to the PLAC condition, the MATT, RSAmean, and RSAbest performances were significantly greater only under the CAF-6 and CAF-9 conditions. Although the RPE scores remained unchanged, CMJ performance improved under all CAF conditions. All the performance outcomes were better for the CAF-6 and CAF-9 conditions than for the CAF-3 condition. Notably, no significant difference between the CAF-6 and CAF-9 conditions was observed for any of these parameters despite the highest incidence of side effects being noted for the CAF-9 condition. In summary, our findings highlight the recommendation for a moderate CAF dosage of 6 mg·kg-1 rather than 3 or 9 mg·kg-1 to enhance various aspects of short-term maximal performance in mild-CAF-consumer female team-sports athletes while mitigating the occurrence of adverse CAF side effects.

The Association between High-Caffeine Drink Consumption and Anxiety in Korean Adolescents.

BACKGROUND: As excessive caffeine intake may be associated with anxiety disorders, one of the most prevalent mental illnesses among adolescents globally, this study investigated the association between high caffeine consumption and anxiety in a nationally representative sample of South Korean adolescents. METHODS: 46,873 participants from the Korea Youth Risk Behavior Web-based Survey (KYRBS) 2022 were included. The Generalized Anxiety Disorder-7 (GAD-7) questionnaire was used to evaluate anxiety symptoms. Survey questions determined the number of times each participant consumed high-caffeine drinks per week. The chi-square test was used to investigate and compare the general characteristics of the study population, and a modified Poisson regression was used to analyze the relationship. RESULTS: Both male and female participants reporting excessive high-caffeine drink consumption exhibited higher anxiety levels (adjusted prevalence ratio [aPR]: 1.19, 95% confidence interval [CI]: 1.08-1.31 in males; aPR: 1.14, CI: 1.05-1.23 in females). This association remained statistically significant in subgroup analyses, particularly among high school students and those with a shorter sleep duration. The relationship between high-caffeine drink consumption and anxiety strengthened with increasing anxiety levels. Additionally, there was a dose-dependent relationship between the prevalence of anxiety and high-caffeine drinks. CONCLUSION: High caffeine consumption increases anxiety in South Korean adolescents. This association proved consistent regardless of sex or other socioeconomic factors.

Prenatal caffeine consumption and neurobehavioral disorders - A systematic review.

Studies have suggested associations between gestational exposure to caffeine and adverse outcomes, however the evidence is still limited. Therefore, a systematic review was conducted to investigate the association between prenatal caffeine exposure and neurobehavioral disorders. The MEDLINE (PubMed), EMBASE, Scopus, Web of Science, and LILACS databases were searched. Observational studies involving women with documented caffeine consumption during pregnancy were eligible for inclusion. The outcomes evaluated were behavioral and intellectual development, Attention Deficit Hyperactivity Disorder, and related behaviors. The data were analyzed by qualitative synthesis. The ROBINS-I tool was employed to assess the risk of bias, and the certainty of evidence was evaluated using GRADE (PROSPERO: CRD42023421164). The search yielded fourteen studies that met the inclusion/exclusion criteria. The sample size among pregnant women ranged from 173 to 64,189, and among children ranged from 88 to 49,190. Maternal caffeine consumption during pregnancy ranged from 0 to 1000 mg/day, with the highest levels observed during mid-pregnancy. Seven studies indicated a potential association between prenatal caffeine exposure and neurobehavioral/neurodevelopment deficits, one study showed that prenatal caffeine exposure improved peer problems, and six studies did not show a significant effect of prenatal caffeine consumption on neurobehavioral disorders. The included studies were classified as moderate for the risk of bias and with very low certainty of evidence. Thus, the evidence is insufficient to confirm with certainty that the prenatal caffeine exposure leads to neurobehavioral disorders. Studies heterogenicity, as well as their variable quality and the presence of several confounding factors, generate uncertainty.

Habitual caffeinated beverage consumption and headaches among adults with episodic migraine: A prospective cohort study.

OBJECTIVE: To examine the relationship between habitual caffeinated beverage consumption and headache frequency, duration, and intensity in a prospective cohort of adults with episodic migraine. BACKGROUND: Caffeine is a commonly ascribed headache trigger in adults with migraine and clinicians may counsel patients to avoid caffeinated beverages; however, few studies have examined this association. METHODS: From March 2016 to August 2017, 101 adults with physician-confirmed episodic migraine completed baseline questionnaires, including information about caffeinated beverage consumption. For 6 weeks, they reported headache onset, duration, and pain intensity (scale 0-100) on twice-daily electronic diaries. Ninety-seven participants completed data collection. We examined associations between self-reported habitual caffeinated beverage consumption at baseline and headache outcomes prospectively captured over the following 6 weeks, adjusting for age, sex, and oral contraceptive use. RESULTS: The adjusted mean headache days per month was similar among the 20 participants reporting no habitual intake (7.1 days, 95% confidence interval [CI] 5.1-9.2), the 65 participants reporting 1-2 servings/day (7.4 days, 95% CI 6.1-8.7), and the 12 participants reporting 3-4 servings/day (5.9 days, 95% CI 3.3-8.4). Similarly, mean headache duration (no servings/day: 8.6 h, 95% CI 3.8-13.3; 1-2 servings/day: 8.5 h, 95% CI 5.5-11.5; 3-4 servings/day: 8.8 h, 95% CI 2.3-14.9) and intensity (no servings/day: 43.8, 95% CI 37.0-50.5; 1-2 servings/day: 43.1, 95% CI 38.9-47.4; 3-4 servings/day: 46.5, 95% CI 37.8-55.3) did not differ across levels of caffeinated beverage intake, though estimates were imprecise. CONCLUSIONS: We found no association between habitual caffeinated beverage intake and headache frequency, duration, or intensity. These data do not support a recommendation that patients with episodic migraine should avoid consuming caffeine. Further research is needed to understand whether deviating from usual caffeine intake may trigger migraine attacks.

Acute Effects of Coffee Consumption on Blood Pressure and Endothelial Function in Individuals with Hypertension on Antihypertensive Drug Treatment: A Randomized Crossover Trial.

INTRODUCTION: Coffee is a complex brew that contains several bioactive compounds and some of them can influence blood pressure (BP) and endothelial function (EF), such as caffeine and chlorogenic acids (CGAs). AIM: This study aimed to evaluate the acute effects of coffee on BP and EF in individuals with hypertension on drug treatment who were habitual coffee consumers. METHODS: This randomized crossover trial assigned 16 adults with hypertension to receive three test beverages one week apart: caffeinated coffee (CC; 135 mg caffeine, 61 mg CGAs), decaffeinated coffee (DC; 5 mg caffeine, 68 mg CGAs), and water. BP was continuously evaluated from 15 min before to 90 min after test beverages by digital photoplethysmography. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry evaluated EF before and at 90 min after test beverages. At the same time points, microvascular reactivity was assessed by laser speckle contrast imaging. Repeated-measures-ANOVA evaluated the effect of time, the effect of beverage, and the interaction between time and beverage (treatment effect). RESULTS: Although the intake of CC produced a significant increase in BP and a significant decrease in RHI, these changes were also observed after the intake of DC and were not significantly different from the modifications observed after the consumption of DC and water. Microvascular reactivity did not present significant changes after the 3 beverages. CONCLUSION: CC in comparison with DC and water neither promoted an acute increase in BP nor produced an improvement or deleterious effect on EF in individuals with hypertension on drug treatment who were coffee consumers.

The caffeine dilemma: unraveling the intricate relationship between caffeine use disorder, caffeine withdrawal symptoms and mental well-being in adults.

OBJECTIVE: This study aimed to explore the relationship between caffeine use disorder (CUD), caffeine withdrawal symptoms and the prevalence of depression, anxiety and stress (DASS) in adults. DESIGN: The study utilised a cross-sectional design to assess the relationships between CUD, caffeine withdrawal symptoms and DASS. SETTING: Participants' CUD was evaluated through the Caffeine Use Disorder Questionnaire (CUDQ), while the Depression Anxiety Stress Scale-21 (DASS-21) measured DASS levels. Caffeine withdrawal symptoms and total caffeine intake were calculated based on self-reported consumption of caffeine-rich products. PARTICIPANTS: The study involved 618 participants with an average age of 27·8 (sd 7·8) years. RESULTS: Participants consumed an average of 461·21 (sd 11·09) mg/d of caffeine, showing a positive correlation between CUD and total caffeine intake. The risk of CUD increased alongside levels of DASS. Individuals with caffeine withdrawal symptoms had higher CUDQ and DASS scores. A multiple linear regression model revealed significant associations between total caffeine intake (P < 0·001) and DASS-21 score (P < 0·001) with CUDQ score. CONCLUSIONS: The study concluded that caffeine, while recognised for its potential health benefits, also exhibits properties that may lead to addiction. The development of caffeine use disorder and cessation of caffeine intake can increase DASS levels in adults, indicating the need for awareness and appropriate interventions in public health nutrition.

Exploring the connection between caffeine intake and constipation: a cross-sectional study using national health and nutrition examination survey data.

BACKGROUND: Caffeine has been reported to increase gastrointestinal motility and change intestinal microbiota. Constipation may be caused by colonic motor dysfunction and colonic microbiomeis disturbances. In this study, we aimed to explore the association between caffeine intake and constipation. METHODS: This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). Caffeine intake was assessed using 24-h dietary recall method, and constipation was defined based on stool consistency or stool frequency. Logistic regression analysis was used to assess the association between caffeine intake and constipation, and results were expressed as odds ratio (OR) with 95% confidence intervals (95%CI). Subgroup analysis was performed based on age. RESULTS: A total of 13,816 participants were finally included for analysis. After adjusting potential confounders, high intake of caffeine was found to be associated with the low odds of constipation (Q3: OR = 0.60, 95%CI: 0.49-0.74; Q4: OR = 0.77, 95%CI: 0.59-0.99; Q5: OR = 0.72, 95%CI: 0.56-0.92). The similar association was found in young people and middle-age people (P < 0.05). CONCLUSION: High caffeine intake was associated with the low odds of constipation. Our finding indicated that individuals should develop consciousness and habit of consuming caffeinated foods and drinks to prevent and relief the constipation.

Caffeine intake during pregnancy and adverse outcomes: An integrative review.

Caffeine intake during pregnancy is common. Caffeine crosses the placenta, raising concerns about its possible deleterious effects on the developing embryo/fetus. Studies on this subject show conflicting results, and still there is no consensus on the recommended dose of caffeine during pregnancy. We performed an integrative review with studies from six databases, using broad MESH terms to allow the identification of publications that addressed the outcomes of caffeine use during pregnancy, with no date limit for publications, in English and Portuguese language. The research returned 16,192 articles. After removing duplicates, screening by title, abstract and full-text, we evaluated 257 and included 59 articles. We found association between caffeine intake and pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. The effects were often dose dependent. No association with prematurity has been demonstrated, but one study showed a small reduction in gestational age with increasing doses of caffeine intake. Defining a safe dose for caffeine intake during pregnancy is a challenging task due to the heterogeneity in study designs and results, as well as the difficulty of reliably assessing the amount of caffeine consumed. In some studies, exposures below the recommended level of caffeine intake during pregnancy (200 mg/day), as suggested by the guidelines, were associated with pregnancy loss, low birth weight, cardiac and genital anomalies, higher body mass, and neurodevelopmental and neurobehavioral outcomes. Well-designed studies with reliable quantification of caffeine intake are needed to assess the safety of low doses during pregnancy.

Monitoring Caffeine Intake: The Relevance of Adequate Assessment in the Population.

The present letter to editor comments on the manuscript "Bulczak EM, Chmurzynska AU. Caffeine Consumption in Polish Adults: Development and Validation of a Polish Questionnaire for Assessing Caffeine Intake. J Am Nutr Assoc. 2023 Feb 1:1-7. doi:10.1080/27697061.2023.2172749. Epub ahead of print. PMID: 36725370." regarding adequate monitoring of the consumption of caffeine.

Caffeine and kidney function at two years in former extremely low gestational age neonates.

BACKGROUND: Extremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months. METHODS: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates <28 weeks' gestation. Participants included if any kidney outcomes were collected at 22-26 months corrected age. Exposure was post-menstrual age of caffeine discontinuation. PRIMARY OUTCOMES: 'reduced eGFR' <90 ml/min/1.73 m2, 'albuminuria' (>30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used. RESULTS: 598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m2 (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25). CONCLUSIONS: Longer caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status. IMPACT: In participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age. When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD. More work is necessary to understand the long-term impact of caffeine on the developing kidney.

Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

Prenatal caffeine exposure induces autism-like behaviors in offspring under a high-fat diet via the gut microbiota-IL-17A-brain axis.

Prenatal caffeine exposure (PCE) is a significant contributor to intrauterine growth retardation (IUGR) in offspring, which has been linked to an increased susceptibility to autism spectrum disorder (ASD) later in life. Additionally, a high-fat diet (HFD) has been shown to exacerbate ASD-like behaviors, but the underlying mechanisms remain unclear. In this study, we first noted in the rat model of IUGR induced by PCE that male PCE offspring exhibited typical ASD-like behaviors post-birth, in contrast to their female counterparts. The female PCE offspring demonstrated only reduced abilities in free exploration and spatial memory. Importantly, both male and female PCE offspring displayed ASD-like behaviors when exposed to HFD. We further observed that PCE + HFD offspring exhibited damaged intestinal mucus barriers and disturbed gut microbiota, resulting in an increased abundance of Escherichia coli (E. coli). The induced differentiation of colonic Th17 cells by E. coli led to an increased secretion of IL-17A, which entered the hippocampus through peripheral circulation and caused synaptic damage in hippocampal neurons, ultimately resulting in ASD development. Our strain transplantation experiment suggested that E. coli-mediated increase of IL-17A may be the core mechanism of ASD with a fetal origin. In conclusion, PCE and HFD are potential risk factors for ASD, and E. coli-mediated IL-17A may play a crucial role in fetal-originated ASD through the gut-brain axis.

Caffeine administration to treat oversedation after general anesthesia: A retrospective analysis.

STUDY OBJECTIVE: Our institution has adopted an informal practice of administering postoperative caffeine to expedite anesthesia recovery for patients with excessive sedation. This study aimed to determine whether caffeine administration was associated with improved sedation recovery and reduced risk of respiratory complications. DESIGN: Single-center, retrospective, observational study. SETTING: Quaternary medical center. PATIENTS: We included adult patients who were admitted to a postanesthesia recovery care unit (PACU) after general anesthesia and had evidence of postoperative sedation (Richmond Agitation Sedation Score [RASS] < 0). Patients were seen from May 5, 2018, through December 31, 2020. INTERVENTIONS: Patients were categorized according to caffeine administration (0 vs 250 mg). MEASUREMENTS: Sedation was measured with RASS. To account for potential confounding, binary and ordinal logistic regression with inverse probability of treatment weighting (IPTW) were used to compare RASS and episodes of severe respiratory complications within 48 h after PACU discharge. MAIN RESULTS: We identified 47,222 adult surgical patients with evidence of sedation in the PACU, and of these, 1892 (4.0%) were intravenously administered caffeine. Patients who received caffeine had more sedation in the PACU. In the IPTW-adjusted analysis, caffeine administration was associated with improved sedation scores after PACU discharge (ordinal logistic regression odds ratio [OR], 1.13 [95% CI, 1.00-1.28]; P = .04 for the first RASS score after PACU discharge) but increased risk of respiratory complications (OR, 2.99 [95% CI, 1.44-6.24]; P = .003) and emergency response team activation (OR, 7.18 [95% CI, 2.85-18.10]; P < .001). CONCLUSIONS: In this observational study, caffeine administration during anesthesia recovery was associated with improved sedation scores. However, it was also associated with an increased risk of respiratory complications, possibly reflecting selection bias (ie, administering caffeine to higher-risk patients). Patients with signs of excessive sedation during anesthesia recovery may benefit from enhanced postoperative respiratory monitoring.