Association of coffee consumption with diabetes mellitus and gestational diabetes mellitus.

ABSTRACT Objectives To investigate the association between the intake of ultra-processed food (UPF) and short-term memory and mental concentration in young adults. Methods In this cross-sectional study, 416 university students aged 18–35 years were assessed. Dietary intake was collected using two non-consecutive 24-hour recalls and classified according to the NOVA system. The percentage of total energy derived from UPFs was modeled as a continuous variable (per 10% increment) using multivariable linear regression. Adjusted mean cognitive scores across tertiles of UPF intake were estimated using General Linear Models. Memory and concentration were evaluated using the Numerical Learning Test and the Toulouse-Pieron Test, respectively. Models were sequentially adjusted for sex, psychological variables, supplement use, caffeine intake, sleep duration, smoking status, and physical activity. Sensitivity analyses excluded participants with severe or extremely severe psychological distress. Results Mean UPF intake accounted for 29.5% of total energy. In fully adjusted models, each 10% increase in UPF intake was associated with a 0.54-point lower memory score (p < 0.001). Participants in the highest tertile had lower adjusted mean memory scores than those in the lowest tertile (17.59 vs. 19.60; p = 0.001). For concentration, each 10% increment in UPF intake was associated with a 0.138-point decrease in score (p = 0.036), although tertile differences were not statistically significant after full adjustment. Sensitivity analyses confirmed these findings. Discussion Higher UPF consumption was associated with poorer short-term memory and modestly lower concentration in young adults, suggesting a potential relationship between ultra-processed food intake and cognitive performance in early adulthood.

The influence of caffeine on human motor output is debated. We tested whether acute caffeine ingestion (6 mg·kg⁻¹) modulates motor unit behavior and preserves evoked torque during repeated tetanic contractions elicited by wide-pulse high-frequency neuromuscular electrical stimulation (WPHF). In a randomized, double-blind, crossover study, 24 adults completed caffeine and placebo sessions. High-density surface electromyography from soleus (SOL) and gastrocnemius medialis (GM) was decomposed to track motor units across time. We quantified indices linked to persistent inward currents (delta frequency, normalized delta frequency, brace height, and self-sustained firing duration), H reflex parameters and responses to WPHF (torque-time integral, extra torque-time integral, sustained electromyography) and used linear mixed models (LMMs) to assess the effect of time, condition, and their interaction. Caffeine selectively increased delta frequency and self-sustained firing duration in SOL, but not in GM. Normalized delta frequency and brace height as well as H-reflex parameters were unchanged. During repeated WPHF trains, caffeine reduced the decrease of evoked torque: mean torque-time integral and extra torque-time integral were higher than placebo across trains, and sustained electromyography was also higher in SOL and GM. These findings indicate that caffeine enhances motoneuron output in SOL but not in GM, while it tempered fatigue development in response to repeated WPHF trains. The pattern is consistent with spinal adjustments in response to caffeine, without excluding other mechanisms and highlights a simple, low-cost strategy to support neuromuscular electrical stimulation in practice.

This study aimed to explore the association between caffeine intake, physical activity (PA), and prostate cancer, machine learning algorithms to build predictive models of prostate cancer. A total of 1789 subjects from the National Health and Nutrition Examination Survey 2009 to 2018 waves were enrolled in this study. Multivariable-adjusted logistic regression was applied to evaluate the association. Then, we conducted 4 machine learning models, including extreme gradient boosting, AdaBoost, Catboos, and Boost tree to predict the occurrence of prostate cancer. In the fully adjusted model, compared to those reporting little caffeine consumption, those who reported large intake had a multivariate adjusted odd ratio (OR) with 95% confidence interval (CI) of 1.25 (2.21–15.52). Participants with large PA were more likely to develop prostate cancer (OR = 1.68, 95% CI: 1.47–3.80), whereas a significant inverse association between medium PA and prostate cancer was observed (OR = 0.66, 95% CI: 0.48–0.81). Extreme gradient boosting, Catboost, and Boost tree all have good prediction effects, with an AUC of up to 0.90 (95% CI: 0.87–0.93). No significant association was observed between small to medium caffeine intake and prostate cancer, large caffeine intake and PA was associated with increased prostate cancer. Moderate PA has the potential to favorably influence prostate cancer.

Coffee is one of the most widely consumed beverages globally. Caffeine has been linked to antioxidant, anti-inflammatory, antifibrotic, and anticancer effects. However, the relationship between caffeine consumption and the risk of chronic kidney disease (CKD) has yielded conflicting findings. Research on the health effects of caffeine relies mainly on exploratory observational studies, which may be affected by biases such as residual confounding. Variations in behaviour, health status, intake, and metabolism also influence outcomes. A comprehensive understanding of the mechanisms and population-specific factors mediating the impact of caffeine on kidney health is essential. In this article, we describe the metabolism and mechanism of action of caffeine, as well as its potential adverse effects. We synthesize current evidence and clarify the complex relationship between caffeine, CKD, and cardiovascular disease. Current evidence suggests that moderate caffeine intake is probably safe in CKD and may be potentially beneficial. Stronger evidence is needed before robust recommendations can be made for clinical practice.

Caffeine intake during pregnancy is widespread, yet it continues to raise public health concerns due to its implications for embryogenesis. Despite extensive research, the long-term consequences of prolonged high-dose caffeine exposure on critical phases of fetal organogenesis remain incompletely characterized. This study was aimed at investigating the impact of prolonged prenatal caffeine administration on kidney and liver development in Swiss albino mice. Pregnant mice (n = 18) received daily IP injections of caffeine (90mg/kg/day) or saline from GD 8.5 to 18.5. Neonatal offspring were assessed for growth parameters, and molecular as well as histological analyses were performed on kidney and liver tissues, focusing on apoptosis-related markers p53 and caspase-3. Caffeine-exposed offspring showed significant growth restriction with reduced body size and weight and shorter crown-rump length. In the kidneys, caffeine caused marked suppression of p53 expression, a 3.5-fold increase in caspase-3 activity, and significant tubular disorganization. The liver maintained p53 expression but exhibited a significant increase in caspase-3 protein. Our in silico transcriptomic analysis revealed caffeine-induced dysregulation of cholesterol biosynthesis pathways in liver cells and ribosome biogenesis in renal cells, identifying key hub genes linked to lipid metabolism and RNA processing. These findings support our in vitro observations of p53 downregulation and caspase-3 activation, suggesting caffeine's role in modulating apoptosis and cell cycle regulation. Prolonged high-dose caffeine exposure induces fetal growth impairment and organ-specific developmental toxicity, with different apoptotic dysregulation patterns in the kidneys by the p53-dependent pathway and in the liver by caspase-3-mediated pathways. This study highlights the importance of carefully considering caffeine dosage and duration of exposure during early pregnancy.

The insidious onset of osteoporosis and the high cost of DXA examination make it urgent to develop suitable prediction or screening tools. The NHANES cohort contains standardized DXA-BMD results and comprehensive nutrition-related information. Therefore, this study aimed to develop and validate a nomogram clinical prediction model dedicated to predicting the exact probability of osteoporosis occurrence in the elderly population. Data of elderly participants were extracted from the NHANES database and categorized into the training (n = 3181) and validation (n = 1622) groups. Clinical characteristics and BMD results were obtained and analyzed. Univariate and multivariate logistic regression analyses were performed. General and dynamic nomogram clinical prediction models were constructed. The models were validated using ROC curves, calibration curves, DCA curves, and clinical impact curves. Based on 11 variables, including age, gender, race, poverty income ratio (PIR), waist circumference, DBP, physical exercise, protein intake, carbohydrate intake, caffeine intake, and fracture history, a nomogram clinical prediction model was constructed. This model exhibited moderate predictive value (AUC = 0.795), alongside good calibration, clinical benefit, and clinical impact. The constructed online dynamic nomogram (https://jialinwang.shinyapps.io/OP-Prediction-Model/) is interactive, accessible, and user-friendly. This nomogram prediction model and the web-based dynamic nomogram exhibit good practical application value within the U.S. elderly population. However, external validation in non-U.S. cohorts is necessary before widespread global promotion. Ultimately, this tool could facilitate the early prediction, diagnosis, and treatment of osteoporosis, thus contributing to the bone health of the elderly population and promoting the development of public health.

The association between coffee or caffeine intake and cardiovascular diseases (CVDs) and their risk factors has been extensively researched. However, there has been conflicting evidence. Therefore, the current updated meta-analysis assessed the relationship between coffee or caffeine with CVDs, such as coronary heart diseases (CHDs), myocardial infarction (MI), heart failure (HF), stroke, cardiac arrhythmias, and CVD mortality. Five electronic databases, namely PubMed, Web of Science, Cochrane Library, Embase, and Scopus, were extensively searched for all records published between January 2000 and December 2025. Studies were included if they examined the effects of coffee on any CVD and reported the associations in terms of the hazard ratio (HR), relative risk (RR), or odds ratio (OR). Moreover, quality appraisal was conducted using the Newcastle Ottawa Scale for cohort studies and the Joanna Briggs Institute tool for case-control studies. After exclusions, 38 studies involving 2,856,002 participants were reviewed and analyzed. The pooled analysis showed no significant associations between coffee consumption and total CHDs or HF, when comparing the highest and lowest coffee consumption categories (HR: 0.98; p = 0.80 and HR: 1.03; p = 0.62, respectively). In contrast, the pooled results showed a significant positive association between higher coffee consumption and the risk of developing MI (OR: 1.48; p < 0.0001). The pooled analysis also showed an inverse relationship between coffee consumption and stroke or cardiac arrhythmias (HR: 0.89; p = 0.01 and HR: 0.94; p = 0.04, respectively). Furthermore, we observed a non-linear relationship between caffeine intake and CVD mortality among hypertensive patients (HR: 0.68; p = 0.001). Higher coffee intake might increase the risk of MI, but can also offer protective effects against stroke and cardiac arrhythmias. Moreover, higher caffeine intake can reduce the risk of CVD mortality in hypertensive patients. PROSPERO: CRD420251073620.

Biliary gastritis is an under-recognized inflammatory condition associated with duodenogastric bile reflux and nonspecific gastrointestinal symptoms, often leading to diagnostic challenges. Epidemiological data from the Kurdistan Region of Iraq are limited. This study aimed to estimate the prevalence of biliary gastritis among adults with available diagnostic data and to examine its associations with demographic, lifestyle, dietary, and clinical factors. A descriptive cross-sectional study was conducted between June 2024 and April 2025 among 638 adults recruited from urban and rural healthcare centers. Biliary gastritis was identified based on documented clinical diagnosis and/or prior endoscopic findings. Among participants with available diagnostic documentation (n = 486), the prevalence of biliary gastritis was 26.7%. The mean age of participants was 43.53 ± 15.25 years. Significant associations were observed with sex, marital status, occupation, dietary factors (fast food consumption, fruit and vegetable intake, and caffeine intake), gallstone disease, liver disease, and gastrointestinal symptoms including nausea, vomiting, and abdominal pain (p < 0.05). No significant associations were found with diabetes mellitus, gastroesophageal reflux disease, or physical activity. Multivariable logistic regression identified several demographic, dietary, and clinical variables associated with biliary gastritis. These findings suggest that biliary gastritis represents a notable health concern in this setting, highlighting the importance of dietary modification and improved access to diagnostic services. However, findings should be interpreted cautiously due to the cross-sectional design and reliance on facility-based data. Further longitudinal studies are warranted.

To investigate whether moderate systemic caffeine intake modulates the progression of apical periodontitis (AP) and associated alveolar bone loss, combining invivo rat experiments with in silico molecular docking to explore potential mechanisms. Male Wistar rats were randomly assigned to four groups (n = 8 per group): control, caffeine, AP, AP + caffeine. AP was induced by pulp exposure of mandibular first molars and allowed to develop for 28 days. Animals in caffeine groups received 10 mg/kg/day by orogastric gavage during the experimental period. The antioxidant capacity of caffeine was assessed by DPPH• and ABTS• + assays. Systemic oxidative status was evaluated by blood reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Histology, Picro-Sirius red staining for collagen, and micro-computed tomography (micro-CT) analysis of alveolar bone (BV/TV, Tb.N, Tb.Sp, porosity, lesion volume) were performed. Molecular docking against adenosine A1 and A2 A receptors was used to probe caffeine-receptor interactions. Caffeine showed relevant radical-scavenging activity invitro (DPPH• assay). AP induced systemic redox imbalance, marked inflammatory infiltration, collagen loss and increased lesion volume. Moderate caffeine intake restored redox markers (↑GSH, ↓TBARS), attenuated inflammatory infiltrate, preserved collagen content and reduced lesion volume (AP + caffeine vs. AP; p < 0.05). Micro-CT demonstrated improved alveolar bone microarchitecture in AP + caffeine group (increased BV/TV and Tb.N; reduced Tb.Sp and porosity). Molecular docking indicated stable hydrophobic and hydrogen-bond interactions of caffeine within A1 and A2 A receptor binding pockets, supporting an antagonistic effect on adenosine signalling consistent with reduced pro-inflammatory activation. Moderate systemic caffeine (10 mg/kg/day) attenuates apical periodontitis progression and preserves alveolar bone quality in rats, associated with antioxidant activity and a probable modulation of adenosine receptor-mediated inflammatory pathways.

Caffeine, a performance-enhancing substance, affects haemostasis. However, the interplay between caffeine, exercise, and circadian rhythms on haemostatic responses remains unclear. This study aimed to investigate the effects of acute caffeine intake on exercise-induced haemostatic responses in sedentary young men at different times of day. Thirty caffeine-naïve sedentary men completed a randomized, double-blind, placebo-controlled crossover study. Each participant performed 4 combined exercise sessions-2 at 07:00 and 2 at 18:00-after ingestion of either caffeine or a placebo. Blood samples were collected pre-exercise, post-exercise, and after 60 minutes of recovery. Across all conditions, exercise elicited increases in platelet aggregation, thrombin generation, tPA activity, and clot lysis time. PAI-1 activity was unchanged post-exercise but declined during recovery. Caffeine further augmented exercise-induced increase in platelet aggregation, thrombin generation, and clot lysis time-most notably in the morning-without significantly altering tPA or PAI-1 activity. There was lower platelet aggregation, thrombin generation, PAI-1 activity, and clot lysis time, alongside higher tPA activity in the evening compared to the morning. These findings indicate that morning exercise triggers a greater prothrombotic status than evening exercise, and that acute caffeine intake exacerbates this effect. The enhanced fibrinolytic capacity in the evening may create a more favourable haemostatic setting for exercise and cardiovascular safety, a hypothesis that warrants confirmation with denser sampling protocols.

Substance-induced manic episodes may occur in individuals without prior psychiatric illness and can be triggered by medications or stimulants. Selective serotonin reuptake inhibitors (SSRIs) and high caffeine intake have both been associated with mood destabilization. To describe a case of acute mania potentially precipitated by excessive fluoxetine use and high caffeine consumption. A 42-year-old male with no prior psychiatric history presented with symptoms of acute mania after recently starting fluoxetine and accidentally taking approximately twice the prescribed dose. Clinical evaluation, laboratory testing, urine drug screening, and collateral history were obtained. The patient exhibited elevated mood, grandiosity, pressured speech, and decreased need for sleep. Laboratory results were unremarkable except for cannabis on urine drug screening. Fluoxetine was discontinued, and he was treated with valproate and adjunctive haloperidol during inpatient hospitalization, leading to improvement in symptoms. The manic episode may have been triggered by excessive fluoxetine exposure combined with high caffeine intake. Fluoxetine may also inhibit CYP1A2, potentially increasing caffeine levels and amplifying stimulant effects. This case highlights a possible interaction between fluoxetine and caffeine contributing to mania and underscores the importance of assessing stimulant use and medication dosing when evaluating new-onset manic symptoms.

Background/Objectives: Melatonin (MEL) promotes sleep and recovery, while caffeine (CAF) enhances alertness and performance. Despite their common use among athletes, their potential interaction remains underexplored. This study examined the effects of MEL and CAF, administered separately or in combination, on sleep, physical performance, physiological, biochemical, and perceptual responses in trained males. Methods: In a randomized double-blind placebo-controlled crossover study, fourteen trained males (22.4 ± 2.9 years) underwent four conditions, designed to isolate the effects of each substance and their interaction: (1) PLA + PLA: placebo before sleep and placebo in the morning; (2) PLA + CAF: placebo before sleep and caffeine (3 mg·kg−1) in the morning; (3) MEL + PLA: melatonin (6 mg) before sleep and placebo in the morning; and (4) MEL + CAF: melatonin before sleep followed by caffeine in the morning. One hour after the morning ingestion, participants performed the 5 m shuttle run test (5mSRT). Blood samples were collected pre- and post-exercise to assess markers of muscle damage (creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) and inflammation (C-reactive protein). Peak heart rate (HRpeak) and rating of perceived exertion (RPE) were recorded throughout the test. Sleep was assessed only during the night following melatonin or placebo ingestion. Results: No differences were observed in sleep parameters between conditions (p > 0.05). Total distance in the 5mSRT increased following MEL + CAF and PLA + CAF conditions compared with PLA + PLA. Moreover, MEL + CAF reduced muscle damage and inflammation markers compared with PLA + PLA, MEL + PLA, and PLA + CAF conditions (p < 0.05). Conclusions: The ingestion of nocturnal MEL and next-day CAF was associated with improvements in certain high-intensity exercise performance outcomes, along with changes in muscle damage and inflammation.

Given the widespread use of caffeine among athletes, this meta-analysis quantifies the incidence of acute side effects associated with caffeine supplementation. Despite its well-established performance benefits, evidence on caffeine's side effects remains fragmented, as these outcomes are often reported only as secondary findings. To address this gap, we systematically reviewed and meta-analyzed evidence from randomized controlled trials on acute caffeine-related side effects in athletes. Following PRISMA guidelines, we searched five databases (MEDLINE, Scopus, Web of Science, Embase, Google Scholar) up to July 2025. Eligible studies were randomized controlled trials in athletes aged ≥ 15years examining acute caffeine ingestion versus placebo with reported side effects. Risk of bias was assessed using PEDro and Cochrane criteria. Data on frequency and magnitude of side effects were pooled using random-effects meta-analyses, with subgroup and dose-response analyses. A total of 48 studies (940 athletes; 63% male, 37% female) were included in the systematic review, of which 38 were eligible for meta-analysis. The mean caffeine dose was 4.9 ± 2.4mg/kg (range 1.3-12mg/kg), commonly ingested as capsules or beverages. Compared with placebo, athletes who ingested caffeine self-reported significantly higher odds of headache (Log OR = 0.74, p < 0.001), abdominal discomfort (Log OR = 1.12, p < 0.001), increased feelings of vigor/activeness (classified in this review as a side effect for methodological consistency, although it may also reflect an ergogenic benefit; Log OR = 1.14, p < 0.001), tachycardia (Log OR = 1.47, p < 0.001; > fourfold higher odds compared with placebo), insomnia (Log OR = 1.20, p < 0.001), increased urine output (Log OR = 1.04, p < 0.001), anxiety (Log OR = 1.29, p < 0.001), and nervousness (Log OR = 0.82, p < 0.001). Meta-regression of dose-response effects showed a significant association between caffeine dose and tachycardia (slope = 0.31, p < 0.001), headache (slope = 0.23, p < 0.001), abdominal discomfort (slope = 0.29, p < 0.001), vigor/activeness (slope = 0.18, p < 0.001), increased urine output (slope = 0.28, p < 0.001), and anxiety (slope = 0.37, p < 0.001). Caffeine intake in athletes increases the likelihood of side effects in a dose-dependent manner, with tachycardia, insomnia, abdominal discomfort, and anxiety being the most consistent. Evidence suggests that, compared with high doses (> 6 mg/kg), low to moderate doses (≤ 6mg/kg) of caffeine may reduce the risk of side effects.

Caffeine intake from different dietary sources and its association with sleep quality in employed adults.

The impact of caffeine on strength and endurance performance is well acknowledged, yet its influence on skill performance remains contentious. A potential scenario in which caffeine augments the efficacy of practice could be useful for sports brokers who diligently pursue every nuance to enhance performance. Therefore, the primary objective of this study was to examine the impact of 3 mg·kg-1 of caffeinated coffee intake combined with deliberate (DP) or maintenance practice (MP) on passing performance in adolescent football players. The study also discusses how DP and MP affect passing accuracy without considering caffeine or placebo conditions, as well as how athletes perceive DP and MP and whether caffeine supplementation influences these perceptions. Fourteen adolescent male football players (14.07 ± 0.26 years; 174.28 ± 3.12 cm; 57.21 ± 8.40 kg) participated in a double-blind, randomized, counterbalanced, and crossover research design. For the experimental protocols, each participant visited an artificial turf pitch on four occasions, separated by 48 h. They received 3 mg·kg-1 of caffeine sourced from coffee with DP (1), caffeinated coffee intake with MP (2), decaffeinated coffee with DP (3), and decaffeinated coffee with MP (4). Upon concluding the practice regimes, the athletes promptly expressed their evaluations of the practice on a scale of 1-10. The Loughborough Soccer Passing Test (LSPT), the One-Touch Passing Test (OTPT), and the Long Passing Test (LPT) were administered to evaluate participants' passing proficiency at both the beginning and end of each session. There was no difference in LSPT, OTPT, or LPT values following caffeine (CAF) and placebo (PLA) supplementation after DP or MP. Regardless of CAF-PLA conditions, although both practices improve the LSPT original time, penalty time, and performance time, only MP increases the LPT score (21.9%; p = 0.03). Caffeine also has no additional modifier effect on practice perceptions. DP is considered more mentally challenging than MP (4.18 ± 2.3 & 1.9 ± 1.2; p > 0.05), but both practices are similar in terms of relevancy, enjoyment, and physicality. 3 mg·kg-1 of caffeinated coffee has no additional effects on DP or MP for passing performance. Regardless of CAF or PLA intake, both practices improve short-term passing, yet only MP appears effective for enhancing long-term passing in players with average technical ability. Accordingly, coaches may consider incorporating these strategies into pre-match warm-ups or structured training programs. Moreover, CAF did not influence players' perceptions of the training sessions, particularly when physical demand was minimal. Similarly, when comparing DP and MP, athletes reported similar perceptions, suggesting that the practical application of DP in field-based settings may diverge from its original theoretical framework. Further research needs to clarify how DP principles are implemented and perceived in real-world practice.

Estimators of biological age, such as epigenetic clocks, are promising biomarkers for neurological disorders where the risk significantly increases with age, such as Parkinson's disease (PD). The purpose of this study was to prospectively investigate whether epigenetic age acceleration can predict PD risk, age at PD onset and time to phenoconversion. We conducted a prospective, nested case-control study within the Nurses' Health Study, including participants who provided two blood samples before being diagnosed with PD. DNA methylation profiles were obtained from 75 individuals who developed PD, 79 individuals who developed prodromal features suggestive of PD and 154 age-matched controls. We estimated epigenetic age acceleration using six different epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPACE and the cortical epigenetic clock) and assessed their associations with PD risk, age at PD onset and time to PD onset. Epigenetic age acceleration was not consistently associated with a higher PD risk, using estimates of biological ageing neither in the first sample (collected a median of 19 years before PD onset) nor in the second sample (collected a median of 8 years before PD onset). These results remained similar in multivariable models adjusted for smoking status, physical activity, body mass index, caffeine intake, alcohol intake and Mediterranean diet score. Furthermore, epigenetic age acceleration was not associated with earlier age at PD onset or time to PD phenoconversion. In our study, epigenetic clock-based biomarkers do not reliably predict PD risk, age at PD onset or time to PD phenoconversion.

Endurance performance is regulated through dynamic interactions between physiological capacity, nutritional status, and psychological control processes. While traditional endurance models have emphasized metabolic and cardiorespiratory determinants, growing evidence indicates that energy availability also influences cognitive function, perceived effort, and decision-making during prolonged exercise. This narrative review synthesizes current literature on the interplay between nutritional strategies and psychological regulation in endurance sports, with particular emphasis on low energy availability, carbohydrate availability, mental fatigue, and pacing behavior. Acute and chronic reductions in energy availability are associated not only with endocrine and metabolic disturbances but also with amplified perceived exertion, impaired executive functioning, reduced effort tolerance, and altered risk-related decision-making, even in the absence of overt physiological failure. Carbohydrate availability emerges as a central modulator operating through both peripheral mechanisms (substrate supply and glycogen preservation) and central neurocognitive pathways influencing perception, motivation, and fatigue regulation. Hydration status, caffeine ingestion, and gastrointestinal tolerance further interact with perceptual and cognitive processes to shape real-time pacing and endurance sustainability. Integrating sport nutrition and sport psychology provides a unifying framework for understanding endurance regulation as a multilevel process linking metabolic state to perceptual experience and behavioral decision-making. From an applied perspective, optimizing endurance performance requires maintenance of adequate long-term energy availability, strategic carbohydrate periodization aligned with training demands, and systematic monitoring of perceived effort alongside physiological load. Future research should prioritize interdisciplinary, ecologically valid designs combining metabolic, perceptual, and cognitive measurements, supported by wearable and data-driven technologies capable of capturing real-time endurance regulation. Bridging nutritional and psychological mechanisms within a unified conceptual model offers a stronger scientific basis for improving performance sustainability while safeguarding athlete health in modern endurance sport.

This study explores whether sleep restriction (SR) and caffeine intake affect migraine susceptibility by testing if each condition, alone or in combination, precipitates migraine-like responses to subthreshold doses of calcitonin gene-related peptide (CGRP) or pituitary adenylate cyclase-activating polypeptide (PACAP) in male and female rats. Migraine is a debilitating neurological syndrome that affects approximately 15% of the global population, with a three-fold higher prevalence in females compared to males. Among the peripheral mechanisms underlying migraine, the release of vasoactive peptides by trigeminal ganglion (TG) neurons, such as CGRP and PACAP, plays a crucial role. Various environmental triggers-including sleep or food deprivation, caffeine intake or withdrawal, stress, and light exposure-have been associated with the onset of migraine attacks; however, the mechanisms by which these factors modulate nociceptive sensitization remain poorly understood. Male and female Wistar rats were subjected to SR for 6 h daily over 3 consecutive days using the gentle handling method, and the periorbital mechanical allodynia was assessed using von Frey filaments before and after each day of SR. Next, a subthreshold dose of CGRP (38 ng/10 μL) or PACAP (0.1 ng/10 μL) was administered into the TG on the third day of SR to evaluate whether sleep loss enhances susceptibility to migraine-like responses. Finally, two additional experiments were conducted to investigate the influence of caffeine (50 mg/kg, orally) exposure in combination of SR in CGRP and PACAP effects. In all experiments, on day 4 (i.e., 24 h after the last SR), the animals were exposed for 1 h to an aversive light for verification of latent sensitization. The results demonstrated that SR alone did not alter the periorbital mechanical threshold in either male or female rats. However, when SR was combined with the administration of CGRP or PACAP at subthreshold doses, a significant periorbital mechanical allodynia developed in female, but not in male rats. The exposure to light in the subsequent day caused a transitory reactivation of mechanical allodynia only in females. In well-rested animals, a 3-day caffeine regimen enabled behaviorally subthreshold doses of CGRP or PACAP to elicit migraine-like responses in females, but not in males. In sleep-restricted animals, combining caffeine with subthreshold doses of CGRP or PACAP rendered males susceptible to migraine-like responses and markedly exacerbated these responses in females, including 1 day later, after light exposure. These findings suggest that SR facilitates trigeminovascular sensitization, promoting migraine-like responses in a sex-specific manner and highlighting caffeine as an enhancer of this interaction. Beyond reinforcing the association between poor sleep and migraine, the data offer new insights into the involvement of the purinergic system and sex differences in migraine pathophysiology.

This systematic review and meta-analysis aimed to comprehensively assess the acute effects of caffeine and caffeinated beverages on ocular microvasculature measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters, explicitly focusing on subfoveal choroidal thickness (SFCT) and superficial capillary vessel density (SVD), and deep capillary vessel density (DVD). A systematic search was conducted across PubMed, the Cochrane Database, and Embase for trials evaluating the acute effects of caffeine or caffeinated beverages on SFCT, SVD, and DVD, as measured by OCTA. Pooled mean differences (MD) were calculated using random-effects models, with heterogeneity assessed by I2 statistics. Subgroup analyses were performed by study design, intervention type, and refractive status. The protocol was prospectively registered in PROSPERO (CRD420251091123). Statistical analyses were performed using RStudio 2025.05.1+513. 18 studies comprising 630 patients were included. Pooled analysis demonstrated a significant reduction in SFCT after caffeine intake (-23.79μm; 95% CI: -31.43 to -16.15; p < 0.001), particularly with coffee and caffeine capsules, whereas no effect was observed with energy drinks or in highly myopic eyes. Regarding SVD, caffeine was associated with significant reductions across foveal, parafoveal, and perifoveal regions, mainly driven by coffee and capsule interventions. In DVD analyses, no overall significant effect was found; however, subgroup analyses indicated significant reductions with caffeine capsules and coffee, while energy drinks showed opposite trends. Acute caffeine intake, primarily from capsules or coffee, induces significant SFCT reduction and modest reductions in SVD, while changes in DVD were confined mainly to the caffeine-capsule subgroup, suggesting that energy drink ingredients may counteract caffeine-induced vasoconstriction. These findings offer valuable insights into the acute effects of caffeine on ocular microvasculature; however, the modest effect sizes necessitate caution regarding inherent physiological, measurement, and bioactive components variability. This study establishes a foundation for future investigations into the clinical significance of acute ocular microvascular fluctuations following caffeine intake.