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Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels
Abstract
Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake.
Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or 250 mg at 9:00 AM, 1:00 PM, and 6:00 PM, and cortisol was sampled from saliva collected at 8 times from 7:30 AM to 7:00 PM.
After 5 days of caffeine abstinence, caffeine challenge doses caused a robust increase in cortisol across the test day (p < .0001). In contrast, 5 days of caffeine intake at 300 mg/day and 600 mg/day abolished the cortisol response to the initial 9:00 AM caffeine dose, although cortisol levels were again elevated between 1:00 PM and 7:00 PM (p = .02 to .002) after the second caffeine dose taken at 1:00 PM. Cortisol levels declined to control levels during the evening sampling period.
Cortisol responses to caffeine are reduced, but not eliminated, in healthy young men and women who consume caffeine on a daily basis.
... Se ha demostrado que la ingesta diaria de cafeína, junto con la exposición al estrés, se asocia con la activación del SNS y el aumento de los niveles de AAs ( 3, 10, 11 ). Asimismo, se determinó que la cafeína, en dosis dietéticas, aumenta la secreción de cortisol plasmático y Corts durante una variedad de factores estresantes, debido, en parte, a un aumento en la liberación de hormona adrenocorticotrópica en la hipófisis ( 18,21,22 ). ...
... No obstante, en condiciones no estresantes, otros autores observaron que el consumo agudo de café activa Efectos del consumo de café sobre el cortisol y la alfa-amilasa salival en adultos jóvenes la AAs ( 12,25 ) y el Corts ( 22 ). Los efectos estimulantes de la cafeína sobre la AAs se asocian con su actividad simpaticomimética ( 26,27 ). ...
... En consecuencia, es viable que exista un nivel umbral de administración de cafeína necesario antes de que se alteren los niveles de los biomarcadores ( 3 ). Por ese motivo, en este estudio se controló la ingesta de café antes de las tomas de muestra, a fin de evitar los efectos agudos de la cafeína, que en otros estudios han provocado variabilidad de los resultados ( 12,22,25 Este estudio es uno de los primeros, hasta donde sabemos, en investigar los efectos del café sobre el Corts y la AAs en individuos sanos (hombres y mujeres), en condiciones no estresantes y con tomas de muestra salival en el hogar. Sin embargo, se deben tener en cuenta algunas limitaciones al considerar los resultados. ...
Objective: The purpose of this study was to determine the effects of coffee consumption on salivary cortisol (sCort) and alpha amylase (sAA) in young adults. Materials and methods: Sixty healthy university students, habitual coffee consumers, participated in this descriptive observational study. Participants were divided into three groups: G1 low consumption (≤ 2 cups of coffee per day, n= 20), G2 moderate consumption (2-5 cups of coffee per day, n = 20), and G3 high consumption (>5 cups of coffee per day, n = 20). Saliva self-collection was in the morning (6:30-7:30 AM) and at night (08:00-09:00 PM). sCort was analyzed using chemiluminescence and sAA activity by kinetic method. Statistical analysis of the data was performed using Student's t-test and analysis of variance. Results: The sample consisted of 30 women and 30 men, aged between 20 and 35 years. In all groups, sCort values were higher in the morning (AM 0,29 ± 0,19 vs. PM 0,09 ± 0,05 μg/dl, p < 0.0001). In contrast, sAA levels were higher in the night (PM 160,16 ± 60,42 vs. AM 32,79 ± 12,98 U/ml, p < 0.0001). No significant differences were detected, in the contents of Corts and AAs, between the groups. Conclusion: Coffee consumption, in non-stressful conditions, did not alter levels and patterns of sCort and sAA in young adults.
... Caffeine and the immune system Teas and coffees are consumed worldwide because of their antioxidant properties ( , ; , Horrigan et al. 2006Lovallo et al. 2005. Teas and coffees could play an essential role in preventing cancers (such as prostate, liver and lung cancers), diabetes, osteoporosis, heart, and neurological diseases due to their antioxidant properties ( , ) Iris et al. 2018(Chen et al., 2021 -NOT IN REFERENCES. ...
... Teas and coffees could play an essential role in preventing cancers (such as prostate, liver and lung cancers), diabetes, osteoporosis, heart, and neurological diseases due to their antioxidant properties ( , ) Iris et al. 2018(Chen et al., 2021 -NOT IN REFERENCES. However, teas and coffees contain caffeine, which lowers the immune system's ability to fight infections and eliminate dead cells and harmful substances when consumed in excess ( , ). Lovallo et al. 2005 Furthermore, the cortisol (a stress hormone) level in the body is strongly and positively associated with caffeine intake (Lovallo et al. 2005 , ). This hormone makes the body works even when stressed by releasing stored sugars and fats to produce energy for physical activity. ...
... However, teas and coffees contain caffeine, which lowers the immune system's ability to fight infections and eliminate dead cells and harmful substances when consumed in excess ( , ). Lovallo et al. 2005 Furthermore, the cortisol (a stress hormone) level in the body is strongly and positively associated with caffeine intake (Lovallo et al. 2005 , ). This hormone makes the body works even when stressed by releasing stored sugars and fats to produce energy for physical activity. ...
There exists an intricate and direct relationship between nutrition and immune function. The body employs innate and adaptive immune systems to protect itself against pathogenic invasions. Proper nutrition is required for the synthesis and formation ofi mmune cells. Nutrient deficiencies, therefore, adversely affect the immune system, suppressing immune functions fundamental to host protection during infection, such as the current Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19). Apart from poor nutrition, bad dietary and lifestyle habits have been reported to impact immune function negatively. Therefore, a compromised or weak immune system affects the body's natural defence to fight infections. Thus, an individual's nutritional status and lifestyle habits gravely jeopardise their ability to elicit an immune response before, during, or after pathogen invasion. The relationship between nutrition and immune function and some lifestyle habits that compromise immune function are elucidated, and strategies to improve one's immunity are suggested in this paper. Vaccines could also protect against diseases by improving one's immunity. Nutrients such as protein, zinc, iron and vitamins A, C, D, and E greatly influence immune cells' health and proper functioning. The study also gathered that bad dietary and lifestyle habits such as excessive intake of refined sugar, saturated fats, alcohol and caffeine; smoking; inadequate sleep and intake of water; lack of exercise and poor social relations adversely impact immune health and function. The consumption off ruits and vegetables, whole grains, root and tuber crops rich in proteins, zinc, iron and vitamins, good dietary and lifestyle habits, and the appropriate intake of certified vaccines are highly encouraged to improve immunity against infections, including the COVID-19 pandemic.
... Specifically, we test how natural variation in hydration status (i.e., serum osmolality) is associated with circulating pro-inflammatory cytokine levels and ex vivo LPS-stimulated pro-inflammatory cytokine production. Building on the biological plausibility that dehydration negatively affects immune function [50,[55][56][57]62], we hypothesized that greater levels of serum osmolality would be associated with lower levels of circulating and ex vivo LPS-stimulated pro-inflammatory cytokine production. ...
... were asked not to consume high-fat foods on the morning of their laboratory visit. Participants were also asked to avoid caffeine [56] and strenuous exercise [25] on the morning of their visit. During the appointment, height and weight were measured, demographic information was obtained, and a blood sample was collected. ...
... Additionally, vasopressin acts as a neuroendocrine immune modulator by stimulating the release of adrenocorticotropic hormone from the pituitary gland, resulting in activation of the hypothalamic-pituitary-adrenal (HPA) axis and the production of glucocorticoids such as cortisol [51,53,54]. Cortisol, in turn, suppresses immune system function [55][56][57], as well as suppressing the HPA axis [68]. Supporting this, research has found that even mild dehydration is associated with increased plasma [69] and salivary [70] cortisol levels. ...
Purpose: Suboptimal hydration has been linked to a variety of adverse health outcomes. Few studies have examined the impact of hydration status on immune function, a plausible physiological mechanism underlying these associations. Therefore, we tested how variation in hydration status was associated with circulating pro-inflammatory cytokine levels and ex vivo lipopolysaccharide (LPS)-stimulated pro-inflammatory cytokine production.
Methods: Blood samples were obtained from a community sample of healthy middle-to-older-aged adults (N = 72). These samples were used to assess serum osmolality, a biomarker of hydration status, markers of immune function including circulating pro-inflammatory cytokines and stimulated pro-inflammatory cytokine production after 4- and 24- hours of incubation with LPS. Multiple linear regressions were used to test the association between serum osmolality (as a continuous variable) and markers of immune function at baseline and after 4- and 24-hours adjusting for age, sex, and BMI. These models were re-estimated with serum osmolality dichotomized at the cutoff for dehydration (>300 mOsm/kg).
Results: While not significantly associated with circulating cytokines (B=-0.03, p=0.09), serum osmolality was negatively associated with both 4-hour (B=-0.05, p=0.048) and 24-hour (B=-0.05, p=0.03) stimulated cytokine production when controlling for age, sex and BMI. Similarly, dehydration was associated with significantly lower cytokine production at both 4-hours (B=-0.54, p=0.02) and 24-hours (B=-0.51, p=0.02) compared to adequate hydration.
Conclusion: These findings suggest that dehydration may be associated with suppressed immune function in generally healthy middle-to-older aged community-dwelling adults. Further longitudinal research is needed to more clearly define the role of hydration in immune function.
... In humans, several clinical observational studies with small sample size have witnessed the alterations of circadian sleepwake (Landolt et al., 1995a;Landolt et al., 1995b;McHill et al., 2014;Weibel et al., 2021), body temperature (Wright et al., 1997;Wright et al., 2000;McHill et al., 2014), blood pressure (Green and Suls, 1996;Guessous et al., 2014), heart rates (Green and Suls, 1996;Kohler et al., 2006;Crooks et al., 2019), melatonin (Wright et al., 1997;Wright et al., 2000;Burke et al., 2015), and cortisol rhythms (Lovallo et al., 2005;Rieth et al., 2016) in adults who consumed caffeine by comparison with placebo controls. ...
... However, the effects of caffeine on circadian body temperature rhythms have not been extensively studied. Similarly, although caffeine has been shown to affect melatonin (Wright et al., 1997;Wright et al., 2000;Burke et al., 2015) and cortisol (Lovallo et al., 2005;Rieth et al., 2016) rhythms in adults, these effects in premature infants still need to be addressed. ...
Caffeine is the globally consumed psychoactive substance and the drug of choice for the treatment of apnea of prematurity (AOP), but its therapeutic effects are highly variable among preterm infants. Many of the molecular underpinnings of the marked individual response have remained elusive yet. Interestingly, the significant association between Clock gene polymorphisms and the response to caffeine therapy offers an opportunity to advance our understanding of potential mechanistic pathways. In this review, we delineate the functions and mechanisms of human circadian rhythms. An up-to-date advance of the formation and ontogeny of human circadian rhythms during the perinatal period are concisely discussed. Specially, we summarize and discuss the characteristics of circadian rhythms in preterm infants. Second, we discuss the role of caffeine consumption on the circadian rhythms in animal models and human, especially in neonates and preterm infants. Finally, we postulate how circadian-based therapeutic initiatives could open new possibilities to promote precision caffeine therapy for the AOP management in preterm infants.
... No observational study has reported an association between caffeine consumption and long-term levels of cortisol. Only one interventional study examined cortisol responses measured in saliva to a caffeine challenge after controlled levels of daily caffeine intake over 4 weeks (Lovallo et al., 2005). They observed that taking caffeine capsules on the test day after 5 days of abstinence resulted in a significant elevation of cortisol throughout the entire day. ...
... Significant elevations of cortisol for about 6 hours on the test day were seen in the group that had caffeine intake of 300 mg for five days, but not 600 mg. Lovallo et al. (2005) concluded that daily caffeine intake caused a partial but not complete tolerance to caffeine's effects on cortisol secretion and that elevated cortisol levels may occur in the afternoon hours in those consuming repeated doses throughout the day. ...
Objectives: To critically review evidence for associations between long-term cortisol levels, mood, and lifestyle factors.Systematic searches of electronic databases (MEDLINE, EMBASE, PsycINFO, WoS, and CINAHL) were conducted up to 21/11/2020 to identify observational and interventional studies (n = 4971) reporting associations between one or more lifestyle or mood factor with cortisol outcomes measured over ≥4 weeks in healthy adults. Quality of included studies was assessed using Downs and Black checklist. The quality of evidence supporting the associations of lifestyle and mood with long-term cortisol levels was assessed as being of moderate-to-poor quality. Observational studies (n = 25) indicated positive associations for BMI/body weight (ESr, pooled effect size correlation = 0.15, p<.001), physical activity (ESr=0.16, p<.001), perceived stress (ESr=0.114, p = .02), and depression (ESr = 0.133, p = .02), but not stressors (ESr = 0.06, p = .29), anxiety (ESr = 0.08, p = .14), or specific features of stress (ESr = 0.25, p = .10). There was insufficient evidence to reliably estimate associations between long-term cortisol levels and sleep, smoking, alcohol consumption, caffeine consumption, and PTSD. Findings from interventional studies (n = 27) were mixed and did not always support the relationships found in observational studies. The findings of this review were limited by the quality of the evidence. Current evidence for associations between mood and lifestyle factors with long-term levels of cortisol is mixed. For many factors, there was considerable uncertainty regarding the size of association with long-term cortisol due to a paucity of evidence. Future research should aim to (1) follow more consistent sampling protocols between studies and (2) clearly describe the hypothesised mechanisms through which interventions would affect cortisol levels.
... 35 Koffein ist ein solcher Stoff, der zur vermehrten Aktivierung des sympathischen Nervensystems beiträgt und wird deshalb bei dem Energy-Drink bewusst nicht genutzt. 36 39 Um also das volle Stoffwechselpotenzial des Körpers ausnutzen zu können, sollten auch die von der Ernährungswissenschaft als nicht-essentiell eingestuften Nährstoffe in Betracht gezogen werden. Diverse sekundäre Pflanzenstoffe haben ebenfalls positive Wirkungen auf den Metabolismus, werden aber auch nicht als essentiell angesehen. ...
... Laut Euroforum ist bei 60% aller Menschen das Interesse an gesunder Ernährung vorhanden. 44% der Bevölkerung ist bereit für gesunde Ernährung mehr Geld auszugeben(36,4 Millionen). Ca. 41% greifen regelmäßig oder zu besonderen Anlässen auf Nahrungsergänzungsmittel zurück. ...
Die hier vorgestellten Produkte mit Schwerpunkt Nachhaltigkeit und Evidenz-basierten Inhaltsstoffen (Energy-Drink & Protein-Riegel) erhalten im Verbrauchermarkt aufsteigendes Interesse. Dies liegt unter anderem daran, dass Nahrungsmittel mit gesundheits- und leistungsfördernden Eigenschaften benötigt werden, um der steigenden Anzahl an Krankheiten präventiv entgegenzuwirken. Besonders wichtig ist die adäquate Zufuhr von Proteinen und sekundären Pflanzenstoffe, um langfristig gesund zu bleiben. Im Gegensatz zu anderen bereits bestehenden Unternehmen liegt der Fokus dieses Konzepts auf der wissenschaftlichen Bestätigung zur Wirksamkeit der einzelnen Inhaltsstoffe. Damit soll dem Käufer ein optimales Preis-Leistungsverhältnis, auch in Bezug auf den Geschmack, geboten werden. Zusätzlich steht der Ressourcen-schonende Umgang mit Rohstoffen und Verpackungsmaterialien im Vordergrund, sodass zukunftsfähiges Handeln ermöglicht wird. Gerade in einer Zeit von hohen menschengemachten Umweltbelastungen, wie beispielsweise durch Plastikaufkommen in den Meeren, ist eine moralische Firmenpolitik notwendiger denn je.
... Cortisol increased with coffee (≈ 7 μA/cm 2 ) as caffeine intake tends to stimulate the adrenocorticotropic hormone to secrete more cortisol. [77] MAP increased majorly from CPT and sardines, while HR changed by a small amount from CPT and coffee. Finally, meditation was included in the third case study, where only MAP increased by ≈7-8 mm Hg (Figure 5c). ...
Accurate health analysis demands real‐time tracking of multiple biomarkers and vital signs under dynamic physiological conditions. Current multimodal hybrid platforms provide biochemical and biophysical data but are limited by active sweat collection for biochemical sensing and bulky designs for biophysical sensing. Here a touch‐enabled platform is presented that simultaneously monitors vitals and metabolic markers. With a simple tri‐finger touch, the platform measures mean arterial pressure and heart rate using photoplethysmography, and glucose, uric acid, and cortisol at rest by leveraging the natural perspiration at the fingertip. Extended studies involving diverse activities reveal strong dynamic interplay among the metabolic and vital profiles, with mean arterial pressure showing the highest sensitivity to cortisol fluctuations. The platform delivers comprehensive health information linking diet, lifestyle, metabolism, and serves as an early metabolic or hormonal stress indicator. Valuable insights gained through the platform position it as a promising tool for personalized health and wellness management.
... Studies have revealed that acute consumption of caffeine can notably enhance cognitive and working memoryrelated brain functions in healthy adults, resulting in increased alertness, improved mood, and information processing, and enhanced attention. [12][13][14] In addition, caffeine stimulates metabolic activity while reducing the sensations of tiredness and hunger, ultimately supporting the assertion that caffeine enhances overall performance. 15 It also has positive inotropic and chronotropic effects on the cardiovascular system. ...
Background and Aims
Premature atrial contractions (PACs) and premature ventricular contractions (PVCs) are ectopic heart rhythm disorders with implications for cardiovascular health. This study explores the relationship between caffeine consumption and the risk of PACs and PVCs, with a focus on healthcare workers, such as doctors, nurses, pharmacists, and midwives, who often rely on caffeine to combat fatigue, especially during night shifts.
Methods
A thorough review was conducted through PubMed, Scopus, Google Scholar, and Web of Science, utilizing a combination of MeSH terms and keywords. Studies examining the link between caffeine consumption and PACs and PVCs, particularly in healthcare workers, were included.
Results
We found that caffeine shows various effects based on dosage and can impact arrhythmia risk. Individuals working long shifts, including healthcare professionals, are prone to increased caffeine intake, leading to higher cardiovascular risk. To mitigate these risks, tailored guidelines for caffeine consumption, flexible shift scheduling, and mental health support services are recommended. Promoting caffeine alternatives within healthcare institutions can be beneficial.
Conclusion
Although caffeine may have potential benefits, its drawbacks, particularly concerning cardiovascular health, may surpass its advantages, especially when consumed in high doses. A multidisciplinary approach is crucial for healthcare workers’ well‐being and quality of patient care. Further research is required to refine and support these recommendations.
... 9 The cocoa administration, twice a day after 9 AM and 1 PM, was carried out to avoid interactions between caffeine and cortisol during the circadian rhythm, which could affect the research results. 10 Gingival crevicular fluid (GCF) samples were retrieved using size #15 paper points (Dentsply, Germany) on the pressure side (distal to the incisor ) ( Figure 3). GCF retrieval was performed before and on the 1st, 7th, and 14th days after the orthodontics force application. ...
Background: Orthodontic tooth movement (OTM) is a process of tooth movement in the alveolar socket through a bone remodeling process. Cocoa contains caffeine as a bioactive component. The number of studies on the effects of caffeine on orthodontic tooth movement is rising. Purpose: This study aimed to determine the effect of caffeine in cocoa administration on TGF-β1 levels in the pressure side during orthodontic tooth movement. Methods: Twelve Cavia cobaya were divided into 4 groups: control group (ONC), treatment group with 2.3 mg caffeine in cocoa (OWC1), 3.45 mg dose (OWC2) and 4.6 mg dose (OWC3) (n=3). A NiTi open coil spring with light force was applied to two lower incisors tooth of Cavia cobaya. TGF-β1 level in GCF of the pressure side was analyzed using ELISA on days 0, 1, 7, and 14. Data were analyzed using the Two-way ANOVA test (p<0.05) and the LSD Post-Hoc test. Results: Research indicated improvement of TGF-β1 level from the control group with the least average followed group caffeine in cocoa 2.3 mg (OWC1), 3.45 mg (OWC2), and 4.6 mg (OWC3) (p<0.05). Conclusion: This study confirmed that caffeine in cocoa administration increase TGF-β1 level during orthodontics tooth movement on Cavia cobaya in the pressure side.
... Of potential importance is the fact that the elevation in cortisol secretion with caffeine appears to be blunted in habitual users, even if daily intake is relatively low (~200 mg/day) [205]. In those with high chronic intakes (300-600 mg/day), this cortisol response may be abolished completely [206,207]. There is also evidence that this increase in cortisol may be limited to the morning hours as this same effect has not consistently been seen with afternoon ingestion [205], perhaps suggesting a "priming" effect of the HPA axis during periods where ACTH response may be more sensitive. ...
Caffeine is a popular ergogenic aid that has a plethora of evidence highlighting its positive effects. A Google Scholar search using the keywords “caffeine” and “exercise” yields over 200,000 results, emphasizing the extensive research on this topic. However, despite the vast amount of available data, it is intriguing that uncertainties persist regarding the effectiveness and safety of caffeine. These include but are not limited to: 1. Does caffeine dehydrate you at rest? 2. Does caffeine dehydrate you during exercise? 3. Does caffeine pro- mote the loss of body fat? 4. Does habitual caffeine consump- tion influence the performance response to acute caffeine supplementation? 5. Does caffeine affect upper vs. lower body performance/strength differently? 6. Is there a relationship between caffeine and depression? 7. Can too much caffeine kill you? 8. Are there sex differences regarding caffeine’s effects? 9. Does caffeine work for everyone? 10. Does caffeine cause heart problems? 11. Does caffeine promote the loss of bone mineral? 12. Should pregnant women avoid caffeine? 13. Is caffeine addictive? 14. Does waiting 1.5–2.0 hours after waking to consume caffeine help you avoid the afternoon “crash?” To answer these questions, we performed an evidence-based scientific evaluation of the literature regarding caffeine supplementation.
... Our results also showed that the acute administration of caffeine significantly elevated the circulating level of cortisol in ewes. The correlation between caffeine consumption and the increased circulating concentration of cortisol has been previously reported in women and men; however, some sex-related differences in the cortisol response were found [37,38]. Stress-like elevations in circulating glucocorticoids are considered to suppress GnRH and gonadotropin secretion. ...
Caffeine is one of the most widely consumed psychoactive drugs in the world. It easily crosses the blood–brain barrier, and caffeine-interacting adenosine and ryanodine receptors are distributed in various areas of the brain, including the hypothalamus and pituitary. Caffeine intake may have an impact on reproductive and immune function. Therefore, in the present study performed on the ewe model, we decided to investigate the effect of peripheral administration of caffeine (30 mg/kg) on the secretory activity of the hypothalamic–pituitary unit which regulates the reproductive function in females during both a physiological state and an immune/inflammatory challenge induced by lipopolysaccharide (LPS; 400 ng/kg) injection. It was found that caffeine stimulated (p < 0.01) the biosynthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus of ewe under both physiological and inflammatory conditions. Caffeine also increased (p < 0.05) luteinizing hormone (LH) secretion in ewes in a physiological state; however, a single administration of caffeine failed to completely release the LH secretion from the inhibitory influence of inflammation. This could result from the decreased expression of GnRHR in the pituitary and it may also be associated with the changes in the concentration of neurotransmitters in the median eminence (ME) where GnRH neuron terminals are located. Caffeine and LPS increased (p < 0.05) dopamine in the ME which may explain the inhibition of GnRH release. Caffeine treatment also increased (p < 0.01) cortisol release, and this stimulatory effect was particularly evident in sheep under immunological stress. Our studies suggest that caffeine affects the secretory activity of the hypothalamic–pituitary unit, although its effect appears to be partially dependent on the animal’s immune status.
... A key difference between controlled laboratory experiments and the present study is that caffeine exposure in the present study represents the participants' habitual caffeine consumption. It has been hypothesized that habitual caffeine consumption may lead to the development of tolerance to caffeine, potentially reducing its effects on sleep in real-life circumstances [57,58]. A randomized experiment by Hindmarch et al. [59], for example, found that caffeine had a greater adverse effect on sleep health in adults with a lower habitual caffeine consumption compared to adults with a higher habitual caffeine consumption. ...
Poor sleep health is common in older adults and is associated with negative health outcomes. However, the relationship between caffeine consumption and sleep health at an older age is poorly understood. This study investigated the association between caffeine consumption and sleep health in community-dwelling older males and females in The Netherlands. Cross-sectional analyses were performed using data from 1256 participants aged 61–101 years from the Longitudinal Ageing Study Amsterdam. Self-reported questions assessed sleep disturbances (including sleep latency, continuity, and early awakening), sleep duration, and perceived sleep quality. Caffeine consumption was determined with questions about frequency, quantity, and type of coffee and tea consumption. Logistic and linear regression models were used, controlling for potential confounders, and interaction by sex and age was tested. Caffeine consumption showed significant interactions with sex (p < 0.005) in association with sleep health outcomes. Older females who abstained from caffeine consumption reported more sleep disturbances (β = 0.64 [95%CI 0.13; 1.15]) and had greater odds of short sleep duration (<7 h/day) (OR = 2.26 [95% CI 1.22; 4.20]) compared to those who consumed caffeine. No associations were observed for long sleep duration (>8 h/day) and perceived sleep quality. No associations were observed in older males. Caffeine abstinence was associated with more sleep disturbances and short sleep duration in older females, but not in males. The observed association in older females may reflect reverse causation, suggesting that females may have different motivations for discontinuing caffeine consumption than males.
... Consistent with previous studies (Hidalgo et al., 2021), biological sex (0 = male, 1 = female), age, and BMI were included as person-level covariates because prior research has demonstrated the potential relevance of those demographic features to diurnal cortisol variations (e.g., Gunn et al., 2016;Kudielka and Kirschbaum, 2005;Heaney et al., 2010;Ladwig et al., 2020). We also controlled for nicotine (i.e., the number of cigarettes smoked) and caffeine (i.e., the number of coffees) use because cigarette smoking and caffeine consumption can affect cortisol secretion during the day (Lovallo et al., 2005;Machiorlatti et al., 2023). ...
In the present ecological study, we analyzed the relations of a set of self-efficacy beliefs at work to parameters of diurnal cortisol variation. Specifically, using data collected during two consecutive working days from 166 workers, we tested a mediation model positing social and work-related self-efficacy beliefs as mediators of the relations between self-regulatory emotional self-efficacy beliefs in managing negative emotions and cortisol indicators. Results from the multilevel mediation analyses supported the proposed model for work-related self-efficacy, which resulted as a significant mediator of the relation between self-regulatory emotional self-efficacy beliefs in managing negative emotions and the overall cortisol daily production indexed by computing the area under the curve with respect to the ground. Findings suggest the importance of self-efficacy beliefs for workers' physiological adjustment. Theoretical and practical contributions of the findings are discussed.
... As caffeine increases cortisol secretion, it is proposed to influence the hypothalamic-pituitary-adrenal axis and, thus, the sleep-wake cycle. 29 Multiple studies indicate that the consumption of caffeine is associated with shorter sleep duration as well as elevated sleep onset latency and wake time after sleep onset. 30 A study conducted by Drake et al. demonstrated that the consumption of 400 mg caffeine 6 h prior to habitual sleep time resulted in a significant reduction of sleep duration in 12 healthy normal sleepers. ...
BACKGROUND: Energy drinks (EDs) are popular beverages among minors. To date, clinical studies investigating ED-induced effects
on the pediatric cardiovascular system are sparse. This study aimed to investigate the effects of a single, bodyweight-adjusted ED
dosage on 24-h ambulatory blood pressure monitoring (ABPM) in healthy children and adolescents.
METHODS: This study was a randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants received a
single, bodyweight-adjusted ED amount or a placebo drink on 2 consecutive days at similar morning hours. Twenty-four-hour
ABPM was assessed via an automated oscillometric blood pressure device after beverage consumption on both study days.
RESULTS: A total of 17 healthy children and teenagers (13.90 (12.29–17.89) years) were included in the final analysis. The ED
consumption led, compared to the placebo intake, to a significantly higher 24-h systolic (115.90 (110.22–118.04) vs. 110.64
(108.09–115.45) mmHg, p = 0.013) and diastolic blood pressure (66.08 (64.20–68.32) vs. 62.63 (61.40–66.46) mmHg, p = 0.005).
CONCLUSIONS: The single, bodyweight-adjusted ED consumption is linked with a significantly higher systolic as well as diastolic
24-h blood pressure in healthy children and adolescents. Minors, particularly those with an increased cardiovascular morbidity,
should be discouraged from drinking EDs.
... Salivary cortisol concentrations can be affected by several factors including body weight and body mass (96), daily rhythm (97), caffeine ingestion (98,99), alcohol consumption (100), antibiotic intake (101), and recent infection (97). Ideally, these factors should be controlled to improve reliability and accuracy of cortisol readings. ...
Stress is viewed as a state of real or perceived threat to homeostasis, the management of which involves the endocrine, nervous, and immune systems. These systems work independently and interactively as part of the stress response. The scientific stress literature, which spans both animal and human studies, contains heterogeneous findings about the effects of stress on the brain and the body. This review seeks to summarise and integrate literature on the relationships between these systems, examining particularly the roles of physiological and psychosocial stress, the stress hormone cortisol, as controlled by the hypothalamic-pituitary-adrenal (HPA) axis, and the effects of stress on cognitive functioning. Health conditions related to impaired HPA axis functioning and their associated neuropsychiatric symptoms will also be considered. Lastly, this review will provide suggestions of clinical applicability for endocrinologists who are uniquely placed to measure outcomes related to endocrine, nervous and immune system functioning and identify areas of intervention.
... Eighteen participants out of 72 were excluded from the data analysis; eight subjects were not exposed to the Cold-Pressor Task (i.e., their arm was placed in tepid water [28-36 • C] instead of cold water as a control condition in the study on intrusive memories reported in [56], six had poor quality (e.g., contaminated or degraded) saliva samples, and four did not correctly complete the diet questionnaire. However, six subjects were retained in the sample to maximize the sample size even though they did not follow all the instructions (i.e., they did not refrain from exercising twenty-four hours before the study, eating one hour before the study, or drinking caffeine or alcohol three hours before the study, or were taking antidepressants or contraceptives [58][59][60][61] Participants completed the DASS-21 and provided demographic information, including their age, gender, and whether they had exercised in the last twenty-four hours, eaten one hour before the session, and consumed caffeine or alcohol within three hours of the experiment. ...
There is increasing academic and clinical interest in understanding the nature of the relation between diet and response to stress exposure as a risk factor for mental illness. Cross-species evidence shows that conditions of chronic and acute stress increase the intake of, and preference for, caloric-dense palatable foods, a phenomenon thought to be explained by the mitigating effects of comfort foods on the activity of the stress-response network. It is largely unknown whether and how real-world dietary intake of saturated fat and sugars impacts stress responsivity in humans. Therefore, here we examined whether real-world dietary intake of saturated fat and sugars predicted salivary cortisol reactivity following an acute physiological stressor. Multilevel modelling of four salivary cortisol measures collected up to 65 min after the stressor on 54 participants (18–49 years old) were analyzed using a quadratic growth curve model. Sugar intake significantly predicted a weaker cortisol response following the Cold Pressor Test (CPT) controlling for BMI and gender, revealing an inhibitory effect of caloric-dense diets on cortisol reactivity to stress. As the consumption of sugar rose individuals had lower post-stressor cortisol levels, a smaller rate of increase in cortisol 20 and 35 min after the CPT, a lower cortisol peak, and an overall weaker quadratic effect. These observations add to a growing body of evidence reporting suppressive effects of high-energy foods on stress-associated glucocorticoids reactivity and are consistent with the comfort food hypothesis, where people are seen as motivated to eat palatable foods to alleviate the detrimental repercussions of stressor exposure.
... Given the potential effects of medication (Granger et al., 2009), caffeine (e.g., Lovallo et al., 2005), and nicotine (e.g., Steptoe & Ussher, 2006) on salivary cortisol, we asked participants to indicate whether or not they had recently used any of the following medications or substances: Antihistamines, oral contraceptives, nasal steroids, caffeine, and nicotine (coded as 0 for No and 1 for Yes in subsequent analyses). We adjusted for medication and substance use (following Ge et al., 2016) by first regressing the log-transformed cortisol values for saliva samples at each of the three time points on antihistamines, oral contraceptives, nasal steroids, caffeine, and nicotine. ...
The present study investigated links between self-compassion and responses to social stress. Participants (N = 102) were randomly assigned to a self-compassion training or a comparison condition and engaged in the Trier Social Stress Test for Groups (TSST-G). Measures of trait self-compassion, subjective perceptions of stress, and salivary cortisol were collected. Participants with higher trait self-compassion had significantly lower subjective and cortisol responses to stress during the TSST-G than did participants with lower trait self-compassion. Participants in the self-compassion training condition did not have significantly lower responses to stress. Results suggest that trait self-compassion is linked with subjective and physiological responses to a social-evaluative stressor. Implications for trait self-compassion and self-compassion training on subjective and physiological responses to stress are discussed.
... The test times were either morning or evening, depending on participants' availability. It was expected that the influence of the interview could be difficult to observe because of the circadian rhythm of cortisol [25,26], especially in the morning test. Therefore, control saliva was collected at the same time on another day. ...
The gas emanating from human skin is known to vary depending on one’s physical condition and diet. Thus, skin gas has been gaining substantial scholarly attention as an effective noninvasive biomarker for understanding different physical conditions. This study focuses on the relationship between psychological stress and skin gas, which has remained unclear to date. It has been deduced that when participants were subjected to interviews confirmed as stressful by physiological indicators, their skin emitted an odor similar to stir-fried leeks containing allyl mercaptan and dimethyl trisulfide. This characteristic, recognizable odor appeared reproducibly during the stress-inducing situations. Furthermore, the study deduced that individuals who perceive this stress odor experience subjective tension, confusion, and fatigue (Profile of Mood States scale). Thus, the study findings indicate the possibility of human nonverbal communication through odor, which could enhance our understanding of human interaction.
... Appropriate caffeine intake may enhance alertness, attention, and nerve cell activity and decrease the possibility of type 2 diabetes. However, excessive intake of caffeine may possibly cause a headache, high blood pressure, irregular small muscle movement, and allergy, especially in teenagers and pregnant women (Nehlig, et al., 1992;Rapuri, et al., 2001;Smith, 2002;Lovallo et al., 2005). Caffeine detection can be realised with costly and complex methods, such as HPLC-MS and immunoassay (Wu, et al., 2000;Oberleitner, et al., 2014). ...
... In vivo studies suggest different effects of single-dose versus chronic caffeine intake. After some days of abstinence, caffeine intake induces a significant increase in cortisol release, progressively decreased with regular caffeine intake [29][30][31]. ...
The current ideal goal of rheumatoid arthritis (RA) management is to resolve joint and systemic inflammation by using pharmacological interventions, assuming this will correspondingly lead to overall well-being. Nonetheless, it has emerged that a substantial number of RA patients do not reach optimal disease control. Thus suggesting the holistic management of subjective symptoms might be overlooked. This poses significant medical challenges; hence the proposal of incorporating lifestyle interventions as part of a multidimensional approach. Among these aspects, both patients and physicians perceive the important role of nutrition. This review shall examine how caffeine, one of the most studied bioactive components of the most widely consumed beverages, may potentially interfere with RA management. In particular, the mechanism by which caffeine affects RA pathogenesis, as a trigger for RA onset or flare, including its influence on rheumatic drug metabolism and the most common RA comorbidities and constitutional symptoms are outlined, highlighting important knowledge gaps and unmet research needs.
... Caffeine is often used as a study aid and tool to combat tiredness and/or low energy by university students, faculty, and staff (Ahmed et al., 2018;Carpenter-Aeby et al., 2007;McIlvain et al., 2011). Additionally, some studies have also showed that caffeine may increase cortisol production and delay its deactivation in the body (Gavrieli et al., 2011;Lovallo et al., 2005). The results for nicotine were somewhat surprising considering nicotine consumption has been shown to serve as a coping strategy by smokers experiencing stress (Battista et al., 2008;Canals et al., 1997). ...
Stress is oftentimes overlooked in societies, despite its life-threatening impact. Here, we assessed the feasibility of measuring endogenous stress hormones to estimate population-level stress by wastewater-based epidemiology. Two primary glucocorticoids, cortisol and cortisone, were monitored in wastewater by liquid chromatography tandem mass spectrometry (LC-MS/MS), to assess changes in these physiological markers of stress in a student population (n = 26,000 ± 7100) on a university campus in the southwestern U.S. Daily composite samples were collected for seven consecutive days each month during the Fall (Autumn) 2017 and Spring 2018 academic semesters (n = 134). Reproducible weekly patterns were seen in stress hormone excretion, with the highest levels occurring on Mondays (124 ± 44 μg d⁻¹ per person) and Tuesdays (127 ± 54 μg d⁻¹ per person) and the lowest on Sundays (87 ± 32 μg d⁻¹ per person). Stress levels on weekdays (defined by class schedules Monday-Thursday) were significantly higher than on weekends (p < 0.05). During both Fall and Spring semesters, per person stress levels of these hormones were significantly higher (p < 0.05) during the first two months of each semester, 162 ± 28 μg d⁻¹ per person (August), 104 ± 29 μg d⁻¹ per person (September), 180 ± 14 μg d⁻¹ per person (January), and 114 ± 54 μg d⁻¹ per person (February) than in the remaining measured weeks in the semester, including finals week captured in both semesters. Overall Spring semester stress levels (113 ± 45 μg d⁻¹ per person) were significantly higher than the Fall (94 ± 42 μg d⁻¹ per person), p < 0.01. These results suggest that endogenous biomarkers such as glucocorticoids may be used to monitor community health by wastewater assessments.
... In previous studies, researchers have studied the impacts of exercise [7] and caffeine [8,9] on circulating cortisol. In these double-blind controlled studies, patients were subjected to the activity (exercise/caffeine) in prescribed dosages at a fixed time of the day. ...
... Besky (2020:399) captures Sidney Mintz's (1979) characterization of tea (along with sugar and coffee) as "'proletarian hunger killer[s]' that fueled European industrial transformation and helped form laboring subjectivities." The caffeine in tea and coffee is known to increase circulation of cortisol, adrenaline, and dopamine and, through these effects, can influence a number of biological pathways, including the regulation of energy balance (Lovallo et al., 2005); in smaller doses, the effect can manifest in more focused and invigorated feelings. ...
The HFE gene variant allele C282Y connected with hereditary hemochromatosis occurs at a frequency of about 10%–11% in Ireland, the highest known frequency in the modern global population. In this synthesis, we draw together an interdisciplinary literature to offer an agriculturally‐grounded, biocultural example of modern human adaptation and microevolution that addresses Ireland's comparatively high C282Y frequency. We argue that changing subsistence‐, diet‐, and nutrition‐related stressors framed under colonial governance played a role shaping the biology of Ireland's population historically, maintaining the C282Y variant. A population accustomed to challenges of poverty and difficult living conditions, the Irish fell under the influence of massive ecological stress with the fungus (Phytophthora infestans), the failed potato crops, and the Great Famine of 1845–52. From there, in the post‐Famine era, diet and nutrition altered further as the potato was exchanged for gluten‐rich wheaten bread and stewed black tea. With risks for iron deficiency anemia heightened by the cultural construction of diet and niche, an adaptive iron‐conserving advantage continued to be offered by the C282Y allele, influencing survival into the post‐Famine era. More recently, however, C282Y has been reframed as a potential risk in the context of contemporary, iron fortified diets.
... Appropriate caffeine intake may enhance alertness, attention, and nerve cell activity and decrease the possibility of type 2 diabetes. However, excessive intake of caffeine may possibly cause a headache, high blood pressure, irregular small muscle movement, and allergy, especially in teenagers and pregnant women (Nehlig, et al., 1992;Rapuri, et al., 2001;Smith, 2002;Lovallo et al., 2005). Caffeine detection can be realised with costly and complex methods, such as HPLC-MS and immunoassay (Wu, et al., 2000;Oberleitner, et al., 2014). ...
In the present work, we have developed a new indicator displacement system based on pillararene for anionic water-soluble carboxylato pillar [6] arene (WP6) and aromatic fluorescent dye safranine T (ST). A large fluorescence enhancement and colour change of ST were observed after complexation with electron-rich cavity in WP6 because of host-guest twisted intramolecular charge-transfer interactions. The constructed pillararene-indicator displacement system can be applied for caffeine selective detection in water.
... In addition, cortisol levels only significantly decreased in the control and caffeine conditions pre to post-dose. It is somewhat surprising that the caffeine condition decreased cortisol levels because caffeine is known to induce the release of cortisol from the adrenal cortex [55]. Although the ability of TeaCrine® and Dynamine® to induce the release of cortisol is currently unclear, the increase in cortisol in the CDT group possibly reflects increased energy mobilization with this treatment. ...
Background
Involvement in video game activities and competitive video gaming (esports) is a rapidly growing field. Moreover, there is a marked interest in identifying nutritional supplements to safely improve egamer performance.
Methodology
We conducted a repeated-measure, randomized crossover study to compare the effects of caffeine (125 mg), caffeine (125 mg) + Dynamine® (75 mg) + TeaCrine® (50 mg) (CDT), and matched placebo across three testing sessions (one week apart) among 50 young male egamers. We tested the effect of each product on multiple measures of cognition, self-reported mood (anxiety, alertness, and headache), and biomarkers of arousal (cortisol and salivary alpha-amylase). We also measured electroencephalogram power during the cognitive tasks. Finally, we tested whether individual differences in xenobiotic metabolism would affect the study outcome measures by genotyping each participant for cytochrome P450 1A2*1F (CYP1A2*1F) allele status.
Results
Compared to pre-dose, CDT improved performance on the Flanker Test of Inhibitory Control and improved reaction time on the Psychomotor Vigilance Task post-dose. Compared to the placebo, caffeine increased self-reported anxiety whereas the CDT combination increased self-reported alertness. Compared to the CDT combination, caffeine increased self-reported headaches. Physiological measures suggested that increases in delta EEG power and cortisol production are associated with the effects observed in the CDT condition to optimize certain aspects of egamer performance. CYP1A2*1F allele status did not moderate outcome variables between conditions in this study.
Conclusions
CDT is a safe and effective product for improving cognitive performance among egamers without increasing self-reported anxiety or headaches. EEG changes demonstrate that CDT increased attention to internal processing (i.e., increased cortical delta power) and potentially increased cognitive control (i.e., increased cortical theta frequency), while the increases in cortisol suggest increased energy mobilization. Future work should aim to clarify the physiological underpinnings of CDT-induced changes in performance and examine the effects of CDT under naturalistic egamer conditions.
... Cortisol levels of saliva during the interviews were also signi cantly higher than those collected at baseline at the same time on another day. In particular, when the effects of the circadian rhythm [22] on cortisol was canceled and compared, the nding demonstrated that the stress level was high. The results suggested that the subjects were psychologically tense during the tensioninducing interviews. ...
Humans frequently experience the transmission of the psychological state of people around them. Gas emanating from human skin is known to vary depending on body condition and/or food intake. This characteristic is gaining substantial scholarly attention because skin gas can be an effective non-invasive biomarker to know body condition. The study focuses on the relationship between psychological status and skin gas, which remains unclear to date. It demonstrates that an identifiable odor containing allyl mercaptan and dimethyl trisulfide is released from human skin during psychological stress and tension. An interview confirms a possible scenario where such a characteristic odor reproducibly appears. Undoubtedly, the scene is extreme. Furthermore, the study found that individuals who perceive this tension-stress model odor experience psychological tension, confusion, and fatigue (Profile of Mood States scale). The result indicates the possibility of human non-verbal communication through odor, which could enhance understanding of human interaction.
... Penjelasan di atas tersebut juga didukung oleh beberapa penelitian sebelumnya, antara lain Lovallo et al. (2005) yang menyatakan bahwa peran kafein dalam mereduksi kadar kortisol. Kortisol adalah hormon yang banyak disekresi pada kondisi stres. ...
It is known that coffee has much phenolic components such as flavonoids and chlorogenic acids (CGAs) content for neutralizing oxidative stress. Gayo-arabica coffee is a typical arabica coffee which widely used by Gayo people in Aceh, Indonesia. The coffee plants also grow in Gayo. However, it has not clearly understood its effect for health. The study aimed is to analyze the Gayo-arabica coffee consumption on the levels of malondialdehyde (MDA) as an indicator of damage cells due to oxidative stress and superoxide dismutase (SOD) as a marker of antioxidant enzyme, after performing a single bout submaximal physical exercise. Male sedentary subjects (21-27 y.o), consisted of 36 men, divided into 3 groups: control (zero of coffee), Gayo1 (15 g coffee in 200 ml water), and Gayo2 (20 g coffee in 200 ml water). Coffee was given once, after rockport test as a single bout submaximal physical exercise. MDA serum and SOD serum were taken after 1 hour of coffee drinking. MDA serum decreased significantly in Gayo1 (8.01 uM) and Gayo2 (10.36 uM), compared to control (26.82 uM). SOD serum increased significantly in Gayo1 (114.81 ng/ ml) and Gayo2 (101.48 ng/ml), compared to control (24.024 ng/ml). Nevertheless, there was no significantly different between Gayo1 and Gayo2 on MDA and SOD serum (p≥0.05). We suggest that the Gayo-arabica coffee after single bout submaximal exercise can diminish stress oxidative in sedentary people.
... Avoidance of high coffee and energy drinks consumption is also suggested in order to eliminate the anxiogenic effect and eventual sleeping disorder. Caffeine increases cortisol secretion in people undergoing mental stress [41], impairing neuroendocrine response, circadian rhythm and hence affecting cognitive functions and performance, body weight, diet quality and mood [42]. Furthermore the combination of stress and caffeine causes additive increases in Blood Pressure [43,44]. ...
Healthcare professionals are exposed to several stress factors, especially during health emergency situations like Covid-19. Psychological distress in the COVID-19 era adversely affects both healthcare professionals' mental and physical health, decreasing performance and efficiency at work. Nevertheless, no sufficient emphasis has been placed so far on the role of nutrition against stress and anxiety among healthcare professionals. Consequently, worksite health promotion approaches and interventions are highly recommended, but also National Health Systems are praised to develop strategies and policies to satisfy nutritional requirements in health emergencies such as Covid-19 pandemic. In this brief paper, the important role of nutrition during periods of stress is highlighted, providing nutritional advice to enhance resilience in this risk group. In addition, practical lifestyle and diet tips for stress management among healthcare professionals exposed to Covid-19 are reported in this mini review.
... Avoidance of high coffee and energy drinks consumption is also suggested in order to eliminate the anxiogenic effect and eventual sleeping disorder. Caffeine increases cortisol secretion in people undergoing mental stress [41], impairing neuroendocrine response, circadian rhythm and hence affecting cognitive functions and performance, body weight, diet quality and mood [42]. Furthermore the combination of stress and caffeine causes additive increases in Blood Pressure [43,44]. ...
Healthcare professionals are exposed to several stress factors, especially during health emergency situations like Covid-19. Psychological distress in the COVID-19 era adversely affects both healthcare professionals' mental and physical health, decreasing performance and efficiency at work. Nevertheless, no sufficient emphasis has been placed so far on the role of nutrition against stress and anxiety among healthcare professionals. Consequently, worksite health promotion approaches and interventions are highly recommended, but also National Health Systems are praised to develop strategies and policies to satisfy nutritional requirements in health emergencies such as Covid-19 pandemic. In this brief paper, the important role of nutrition during periods of stress is highlighted, providing nutritional advice to enhance resilience in this risk group. In addition, practical lifestyle and diet tips for stress management among healthcare professionals exposed to Covid-19 are reported in this mini review.
... Similar patterns also emerged with respect to regular alcohol consumption . Findings regarding the potential impact of caffeine intake on basal cortisol levels have yielded mixed results, with some studies suggesting that caffeine intake may lead to increase in cortisol (Lovallo et al., 1996(Lovallo et al., , 2005, while others reporting no such association (MacKenzie et al., 2007;Steptoe et al., 2007). Somewhat more consistent evidence suggests that caffeine consumption is associated with increased cortisol reactivity in response to stress (al'Absi et al., 1998;Shepard et al., 2000). ...
Exposure to stressful events is omnipresent in modern human life, yet people show considerable heterogeneity in the impact of stress exposure(s) on their functionality and overall health. Encounter with stressor(s) is counteracted by an intricate repertoire of nervous-system responses. This narrative review starts with a brief summary of the vast evidence that supports heart rate variability, cortisol secretion, and large-scale cortical network interactions as kay physiological, endocrinological, and neural mechanisms of stress responsivity, respectively. The second section highlights potential sources for inter-individual variability in these mechanisms, by focusing on biological, environmental, social, habitual, and psychological factors that may influence stress responsivity patterns and thus contribute to heterogeneity in the impact of stress exposure on functionality and health. The third section introduces intra-individually variability in stress responsivity across functional domains as a novel putative source for heterogeneity in the impact of stress exposure. Challenges and future directions are further discussed. Parsing inter- and intra-individual variability in nervous-system mechanisms of stress responsivity and across functional domains is critical towards potential clinical translation.
... Participants were asked to avoid consuming high fat foods on the morning of their laboratory visits in order to reduce variability from postprandial inflammation (Herieka and Erridge, 2014). Participants were also asked to avoid caffeine (Lovallo et al., 2005) and strenuous exercise (Zhou et al., 2010) on the morning of each visit. At visit 1 (V1), height and weight were measured, and participants provided demographic information. ...
Background: Empirical and theoretical evidence suggest that because of the co-evolution of the endocrine and immune response systems, different types of stressors may lead to similar levels of physiological activation. The present analyses examined associations between two physiological stress responses: the cortisol response to an acute laboratory stressor and ex vivo lipopolysaccharide (LPS) stimulated inflammatory cytokine production.
Methods: Healthy middle-aged adults (N=65) completed testing at two appointments, two weeks apart. Blood was collected at each appointment to measure circulating inflammatory cytokine levels and stimulated inflammatory cytokine production after 4 and 24 hours of incubation with LPS. A cumulative standardized composite measure of inflammation was calculated using the cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and interferon-γ (IFN-γ). At visit two, after the blood draw, participants completed the Trier Social Stress Test (TSST); saliva samples were collected before and after to generate cortisol response curves (area under the curve with respect to ground [AUCG] and increase/decrease [AUCI]).
Results: AUCG was significantly associated with stimulated cytokine production at visit 2 after both 4 hours (B=6.89; p=0.007) and 24 hours (B=7.50; p=0.005) of incubation, controlling for age, sex, and BMI. AUCI was also significantly associated with stimulated cytokine production at visit 2 after 4 hours (B=6.28; p=0.004) and 24 hours (B=6.16; p=0.007) of incubation, controlling for age, sex, and BMI. Stimulated inflammatory cytokine production was strongly correlated across the two visits (2 weeks apart) after 4 hours of incubation (r=0.80, p<0.001) and after 24 hours (r=0.80, p<0.001). Within each visit, stimulated cytokine production after 4 hours was significantly correlated with stimulated inflammation at 24 hours (r=0.93-0.94, p<0.05)
Conclusions: These results suggest that LPS-stimulated inflammatory cytokine production and the cortisol response to the TSST contain comparable information about acute human physiological stress responses. Moreover, measurement of stimulated cytokines was highly stable across a two-week time period whether measured after 4 or 24 hours of incubation with LPS.
... The use of salivary cortisol implies several methodological constraints, such as that a stress/threat threshold needs to be exceeded in order for cortisol to be released [36,22]; there is a delay in peak response (ranging approximately between 20-40 mins depending on stressor-stimulus) for cortisol, resulting in long experimental procedures [22,35]; there exists bio-chemical interplay with other bodily functions related to circadian rhythm [35,22], food intake [32,55], and caffeine and nicotine consumption [44,36], requiring instructions/control prior to experimentation; and considerable efforts and costs for sampling and bio-chemical analysis of salivary probes. Compared to other physiological measures such as EDA or ECG, however, salivary cortisol is robust against physiological artifacts (e.g., resulting from body movements and/or external factors like lighting conditions or mild temperature fluctuation). ...
The understanding of stress and its impact on human performance is crucial to mitigate human error in the face of a threat. This is especially the case for critical incidents on a ship bridge, where human error can easily lead to severe danger for crew, cargo, and other vessels. To overcome the current limitations of robust objective stress measures that reliably detect (di-)stress under highly noisy conditions, we set out to explore whether salivary cortisol – the stress biomarker in medicine and psychology – is a valuable complementary assessment tool in a high stress/emergency context. In a controlled within-subjects experiment (N=12) using a ship bridge simulator, we measured stress levels under three conditions (80 minutes each): baseline, low stress (open water navigation task in autopilot), and high stress (open water emergency scenario). We sampled salivary cortisol at 10 minute intervals in conjunction with heart rate (variability) monitoring, and subjective stress assessments from both participants and expert evaluators. Results validate salivary cortisol as a successful tool for detecting distress. Unlike the other stress measures, salivary cortisol strongly correlated with expert stress assessments (r = .856) and overt stress behavior like instances of freezing and missing response cues. Surprisingly, data further revealed decreased salivary cortisol across periods of self assessed improved performance (i.e., eustress). In fact, data suggests an inverted u-relationship between performance and salivary cortisol. The findings have direct implications for the vast field of emergency training, and serve as a first important validation and benchmark to proceed with real life applications.
Kombucha, traditionally fermented from black or green tea, is well known for its potential health benefits. However, its high caffeine content may limit consumption for certain individuals. Therefore, this study aimed to develop a low-caffeine kombucha using lotus root tea as an alternative to black or green tea. Lotus root was roasted and brewed to prepare the tea base, to which sugar and a SCOBY were added for primary fermentation. Subsequently, Lactobacillus plantarum (1.0 × 109 and 3.0 × 109 CFU/mL) was inoculated to carry out secondary fermentation. The kombucha samples were assessed for their organic acid composition, antioxidant activity, antimicrobial effects, β-glucuronidase inhibition, and protective effects against Salmonella infection in a Caenorhabditis elegans model. The caffeine concentration of lotus root tea kombucha was significantly lower than that of conventional kombucha. L. plantarum fermentation increased the lactic acid concentration and enhanced antimicrobial activity, particularly against Escherichia coli OP50 and Salmonella Typhimurium. Additionally, β-glucuronidase inhibition significantly improved, suggesting potential gut health benefits. In C. elegans, kombucha consumption improved survival rates following Salmonella infection, indicating a protective effect. This study demonstrates that fermentation using Lactobacillus plantarum can enhance the bioactivity of lotus root kombucha, highlighting its potential as a low-caffeine functional beverage.
Background: Steroid hormone dysregulations have frequently been implicated in posttraumatic stress disorder (PTSD) pathogenesis. However, the translation into naturalistic clinical settings as markers of symptomatology and treatment success remains complex. Particularly, there is little longitudinal data on steroid secretion over the course of interventions.
Objective: This study examined the potential of long-term steroid hormone secretion assessed in hair as diagnostic and intervention-related biomarkers among medicated, multimorbid inpatients with PTSD.
Method: As part of a secondary analysis of a randomised controlled trial, 54 female inpatients with a primary diagnosis of PTSD received standardised treatment and provided hair samples at pre-treatment, post-treatment, and 3-month follow-up. Cortisol, cortisone, and dehydroepiandrosterone (DHEA) were determined, alongside clinical assessments.
Results: Cross-sectional results showed a negative association of pre-treatment DHEA with anxiety symptoms and a trend-level association with lifetime trauma exposure. While inpatients improved in PTSD symptomatology during treatment, neither pre-treatment steroids, nor treatment-induced steroid changes predicted PTSD symptoms at post-treatment or 3-month follow-up.
Conclusion: The study highlights the challenges of establishing biomarkers in naturalistic clinical populations. While the association of attenuated DHEA with anxiety symptoms warrants further exploration, our data points towards the potential necessity of patient sub-sample selection to understand, and in the long run clinically target, the endocrine mechanisms in PTSD.
Background: Recent research underscores a crucial connection between circadian rhythm disruption and cancer promotion, highlighting an urgent need for attention. Objectives: Explore the molecular mechanisms by which modern lifestyle factors—such as artificial light exposure, shift work, and dietary patterns—affect cortisol/melatonin regulation and cancer risk. Methods: Employing a narrative review approach, we synthesized findings from Scopus, Google Scholar, and PubMed to analyze lifestyle impacts on circadian health, focusing on cortisol and melatonin chronobiology as molecular markers. We included studies that documented quantitative changes in these markers due to modern lifestyle habits, excluding those lacking quantitative data or presenting inconclusive results. Subsequent sections focused solely on articles that quantified the effects of circadian disruption on adipogenesis and tumor microenvironment modifications. Results: This review shows how modern habits lead to molecular changes in cortisol and melatonin, creating adipose microenvironments that support cancer development. These disruptions facilitate immune evasion, chemotherapy resistance, and tumor growth, highlighting the critical roles of cortisol dysregulation and melatonin imbalance. Conclusions: Through the presented findings, we establish a causal link between circadian rhythm dysregulation and the promotion of certain cancer types. By elucidating this relationship, the study emphasizes the importance of addressing lifestyle factors that contribute to circadian misalignment, suggesting that targeted interventions could play a crucial role in mitigating cancer risk and improving overall health outcomes.
Introduction:
Light is a key factor in moderating human alertness, both subjective and objective. However, the methodology applies in research on the effects of exposure to light of different wavelengths and intensities on objective and subjective alertness varies greatly and evidence on objective alertness in particular is still inconclusive. Thus, the present, highly standardized within-subject laboratory study on N = 44 healthy males explored how LED light of different intensities (dim vs. bright light) and wavelengths (red vs. blue) affected objective (reaction time/RT) as well as subjective (sleepiness) alertness in the morning after wake-up.
Methods:
Participants spent two separate nights in the laboratory and were exposed to either one of the two light intensities or colors for 60 min after wake-up. Additionally, they indicated their sleepiness on the Karolinska Sleepiness Scale and participated in an auditory RT task before and after light intervention. It was hypothesized that both bright and blue light would lead to greater subjective and objective alertness when compared to dim and red light, respectively.
Results:
Results indicated that average RTs were longer for participants in the bright light condition (p = 0.004, f2 = 0.07) and that RTs decreased post-light exposure irrespective of light being dim or bright (p = 0.026, f2 = 0.07). However, dim versus bright light and RT did not interact (p = 0.758, f2 = 0.07). Chronotype was a significant covariate in the interaction of dim versus bright light and subjective sleepiness (p = 0.008, f2 = 0.22). There was no difference in RTs when comparing exposure to red or blue light (p = 0.488, f2 = 0.01). Findings on subjective sleepiness and light of different wavelengths revealed that sleepiness was reduced after light exposure (p = 0.007, f2 = 0.06), although the wavelength of light did not appear to play a role in this effect (p = 0.817, f2 = 0.06).
Conclusion:
Hence, neither of the hypotheses could be confirmed. However, they indicated that evening types might benefit from exposure to bright light regarding sleepiness, but not morning types.
Flow is an intrinsically rewarding state characterised by positive affect and total task absorption. Because cognitive and physical performance are optimal in flow, chemical means to facilitate this state are appealing. Caffeine, a non-selective adenosine receptor antagonist, has been emphasized as a potential flow-inducer. Thus, we review the psychological and biological effects of caffeine that, conceptually, enhance flow. Caffeine may facilitate flow through various effects, including: i) upregulation of dopamine D1/D2 receptor affinity in reward-associated brain areas, leading to greater energetic arousal and ‘wanting’; ii) protection of dopaminergic neurons; iii) increases in norepinephrine release and alertness, which offset sleep-deprivation and hypoarousal; iv) heightening of parasympathetic high frequency heart rate variability, resulting in improved cortical stress appraisal, v) modification of striatal endocannabinoid-CB1 receptor-signalling, leading to enhanced stress tolerance; and vi) changes in brain network activity in favour of executive function and flow. We also discuss the application of caffeine to treat attention deficit hyperactivity disorder and caveats. We hope to inspire studies assessing the use of caffeine to induce flow.
Coffee is a popular drink today. One of the coastal resources that can be processed into coffee-like products (analog coffee) is the mangrove fruits Rhizophora mucronata . The fruits of R. mucronata were reported to contain antioxidant substances that can support human health. This study aimed to characterize analog coffee products from the fruit of R. mucronata . The fruits were collected from Miulu village, Sangihe Islands, North Sulawesi. Mangrove fruits were soaked in a 2% lime solution for 72 hours and dried at 60 °C. Then it was roasted at 116-118 °C for 40 minutes, and the sample was ground until it resembled coffee grounds. The findings revealed that the water content of analog coffee was 4.14 ± 0.14%; ash 4.97 ± 0.02%; protein 14.38 ± 0.02%; fat 12.26 ± 0.08%; carbohydrate 63.67 ± 0.09%, energy 422.58 ± 1.01 kcal, caffeine 1.20 ± 0.00%, tannins 808.21 ± 2.02 mg/kg, and antioxidant capacity IC 50 131.28 ± 0.44 μg/mL. Furthermore, the analysis of compounds using GC-MS from the coffee analog of R. mucronata fruits was dominated by cis-9-Hexadecenal (50.95%) and 9-Octadecenal, (Z)-(33.97%). These research findings provide that analog coffee from the R. mucronata fruits has the potential to become a coffee-like product as a functional drink.
Obesity, affecting one in three pregnant women worldwide, is not only a major obstetric risk factor. The resulting low‐grade inflammation may have a long‐term impact on the offspring's HPA axis through dysregulation of maternal, placental and fetal corticosteroid metabolism, and children born of obese mothers have increased risk of diabetes and cardiovascular disease. The long‐term effects of maternal obesity on offspring neurodevelopment are, however, undetermined and could depend on the specific effects on placental and fetal cortisol metabolism. This systematic review evaluates how maternal obesity affects placental cortisol metabolism and the offspring's HPA axis. Pubmed, Embase and Scopus were searched for original studies on maternal BMI, obesity, and cortisol metabolism and transfer. Fifteen studies were included after the screening of 4556 identified records. Studies were small with heterogeneous exposures and outcomes. Two studies found that maternal obesity reduced placental HSD11β2 activity. In one study, umbilical cord blood cortisol levels were affected by maternal BMI. In three studies, an altered cortisol response was consistently seen among offspring in childhood (n = 2) or adulthood (n = 1). Maternal BMI was not associated with placental HSD11β1 or HSD11β2 mRNA expression, or placental HSD11β2 methylation. In conclusion, high maternal BMI is associated with reduced placental HSD11β2 activity and a dampened cortisol level among offspring, but the data is sparse. Further investigations are needed to clarify whether the HPA axis is affected by prenatal factors including maternal obesity and investigate if adverse effects can be ameliorated by optimising the intrauterine environment.
This study examines the predictive value of conflict and conflict-related variations in negative emotion dynamics, with respect to three cortisol indicators (cortisol awakening responses; overall cortisol output; diurnal cortisol slopes). A total of 166 workers provided momentary reports on conflict(s) with colleagues and negative emotions 10 times a day for 2 workdays and salivary cortisol samples 5 times a day. The results of latent growth curve piecewise multilevel models revealed that the occurrence of a conflict and the number of conflicts introduced significant variations in specific cortisol parameters indicating greater cortisol levels throughout the day. Moreover, the conflict-elicited negative emotion boost predicted a lower reduction of cortisol levels from morning to evening. Last, the postconflict decline in negative emotions was negatively associated with overall cortisol production. This study contributes to establishing a potential association between naturally occurring episodic conflicts at work and daily cortisol patterns, identifying within-person fluctuations in negative emotions as psychological mechanisms through which this occurs.
A novel thermostable caffeine dehydrogenase enzyme was isolated from Pichia manshurica strain CD1. At increased temperatures, the enzyme caffeine dehydrogenase exhibits increased activity. The enzyme also exhibits high stability after the heat treatment and remains up to 56% stable at 100 ºC compared to its untreated condition. A Comprehensive analysis was carried out to monitor the thermodynamic parameters (Ea, ΔG, ΔH, and ΔS) of the enzyme. In this study, the conformational changes of caffeine dehydrogenase in native and thermally treated states were investigated by CD spectroscopy and intrinsic tryptophan fluorescence spectroscopy. The far-UV CD spectra results showed that the protein was able to maintain its alpha-helical structure after the heat treatment and the near-UV CD spectra results showed that temperature had no such effect on the protein’s tertiary structure. The results of tryptophan fluorescence spectroscopy of the enzyme showed a temperature-dependent dynamic quenching. The fluorescence intensity of the protein was decreased as the degree of freedom in the tryptophan- region of the protein was increased with temperature. Thus, the enzyme does not undergo denaturation at high temperatures and can maintain its conformation to remain catalytically active. Therefore, it can be concluded that the thermal stability of caffeine dehydrogenase is an essential key factor in increasing commercial interest due to its high catalytic efficiency and specificity.
This research was aimed at analyzing the acute effects of Arabica black coffee consumption on blood glucose, insulin, and serum cortisol levels, as well as determining the pharmacological effects of black coffee as an antihyperglycemic. A randomized control trial with healthy female subjects was used in this study. There were 20 volunteers in total: 9 as the control group and 11 as the trial group. The treatment included brewing 10 grams of Gayo Arabica black coffee powder with 150 ml of boiling water. Blood glucose, insulin, and cortisol levels were measured twice, before and after 60 minutes of coffee consumption. An independent sample t-test (p < 0.05), Pearson correlation test (p < 0.05), and simple linear correlation test (p < 0.05) were used to analyze the data. Blood glucose levels and serum cortisol levels decreased significantly after coffee consumption in the trial group (p = 0.002* and p = 0.001*). There was no significant negative correlation between glucose and insulin levels (r = -0.122; p = 0.721). On the other hand, there was a significant positive correlation between cortisol levels and blood glucose (r = 0.651; p = 0.002*). In conclusion, a single cup of Gayo Arabica black coffee reduces blood sugar and serum cortisol levels, but does not increase serum insulin levels. Blood glucose levels correlate positively with serum cortisol levels in healthy female.
Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12–16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.
Morning coffee is a common remedy following disrupted sleep yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated.
In a randomised cross-over design, 29 adults (Mean ± SD; age: 21 ± 1 years, BMI: 24.4 ± 3.3 kg·m ⁻² ) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep ( Control ; in bed, lights-off trying to sleep ~2300-0700 h) the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), once with and once without morning coffee ~1 h after waking (~300 mg caffeine as black coffee 30 min prior to OGTT).
Peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (Mean [normalised confidence interval] for Control, Fragmented, and Fragmented+Coffee, respectively; Glucose: 8.20 [7.93-8.47] mmol∙L ⁻¹versus 8.23 [7.96-8.50] mmol∙L ⁻¹versus 8.96 [8.70-9.22] mmol.L ⁻¹ ; Insulin: 265 [247-283] pmol∙L ⁻¹ ; and 235 [218-253] pmol∙L ⁻¹ ; and 310 [284-337] pmol∙L ⁻¹ ). Likewise, iAUC for plasma glucose was higher in the Fragmented + Coffee trial compared to Fragmented.
Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed then a reduction in glucose tolerance can be expected.
Objective: The present randomized, placebo-controlled study aimed to assess the long-term safety and perceivable mental acuity benefits of EnXtra® in healthy individuals.
Methods: Study participants were administered EnXtra® with or without caffeine for a period of 12 weeks. The cardiovascular safety was evaluated by assessing change in QT interval, blood pressure and heart rate. Further, other efficacy variables evaluated were change in perceived alertness and calmness by Bond and Lader mood scales, Sleep disturbance by Pittsburgh sleep quality Index and daytime sleepiness by Epworth sleepiness scale.
Results: None of the study group showed any significant change in the ECG or haemodynamic parameters as compared to baseline (p > 0.05). Post consumption, alertness and calmness scores were significantly increased in the EnXtra®, and EnXtra® plus caffeine group (p < 0.001) as compared to placebo. Daytime sleep scores decreased in the EnXtra® group however change was not significant. Sleep quality remained undisturbed in all three arms.
Conclusion: The findings demonstrated the psychostimulant efficacy of EnXtra® with no safety concerns on long-term usage.
Caffeine is the most widely consumed centralnervous-system stimulant. Three main mechanisms of action of caffeine on the central nervous system have been described. Mobilization of intracellular calcium and inhibition of specific phosphodiesterases only occur at high non-physiological concentrations of caffeine. The only likely mechanism of action of the methylxanthine is the antagonism at the level of adenosine receptors. Caffeine increases energy metabolism throughout the brain but decreases at the same time cerebral blood flow, inducing a relative brain hypoperfusion. Caffeine activates noradrenaline neurons and seems to affect the local release of dopamine. Many of the alerting effects of caffeine may be related to the action of the methylxanthine on serotonine neurons. The methylxanthine induces dose-response increases in locomotor activity in animals. Its psychostimulant action on man is, however, often subtle and not very easy to detect. The effects of caffeine on learning, memory, performance and coordination are rather related to the methylxanthine action on arousal, vigilance and fatigue. Caffeine exerts obvious effects on anxiety and sleep which vary according to individual sensitivity to the methylxanthine. However, children in general do not appear more sensitive to methylxanthine effects than adults. The central nervous system does not seem to develop a great tolerance to the effects of caffeine although dependence and withdrawal symptoms are reported.
The caffeine content of all tea or coffee beverages consumed by 17 healthy adults over 24 hours was measured. Plasma caffeine, theophylline, theobromine, and paraxanthine concentrations were determined over the same 24 hours. The average caffeine content per drink was 60.4 +/- 21.8 mg for instant coffee (14-fold range), 80.1 +/- 19.2 mg for brewed coffee (2.8-fold range), and 28.8 +/- 13.7 mg for tea (5.5-fold range). The number of drinks of coffee and tea consumed was a poor index of actual caffeine intake (r2 = 0.42). Caffeine intake correlated poorly with the 24-hour average caffeine concentration (r2 = 0.41), but there was a very good correlation between a single plasma caffeine concentration measured at 5 PM and the 24-hour average concentration (r2 = 0.94). The same was true for paraxanthine (r2 = 0.86). Paraxanthine accounted for 67.3% of the total dimethylxanthines in plasma, while theobromine and theophylline accounted for 24.4% and 8.3%, respectively. Mean caffeine clearance was 1.2 +/- 0.3 ml/min/kg. Plasma caffeine concentration before the first drink in the morning correlated very poorly with caffeine clearance (r2 = 0.07), even when adjusted for caffeine intake (r2 = 0.21).
Uncertainty continues to surround the role of habitual caffeine consumption as a cardiovascular risk factor. The present study examined the effects of moderate caffeine intake on 24h blood pressure and heart rate in normotensive men and women.
A double-blind, placebo-controlled, crossover design with counterbalancing was used, in which 36 healthy men and women participated in four experimental conditions involving the ingestion of placebo or caffeine three times daily for 6 days, followed by a seventh ('challenge') day of placebo or caffeine ingestion.
When caffeine was consumed on the challenge day, blood pressure was found to be elevated immediately after caffeine ingestion and was either unchanged or decreased (hypotensive effect) after a period of abstinence from the drug. Some diminution of the peak pressor effects was found when participants ingested caffeine after habitual use of the drug (6.0/5.2 mmHg) compared with when they had been abstinent before the challenge day (7.7/6.8 mmHg). This diminution in the reaction was comparatively small, however, and pressor effects persisted on caffeine-challenge days even when caffeine was consumed on preceding days.
Habitual consumption diminished, but did not eliminate, the pressor effects of caffeine. Considering the almost universal consumption of caffeine beverages, the persistent pressor effects of the drug could have important implications for cardiovascular health.
The involvement of adenosine A(1) and A(2A) receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A(1) receptor agonist CPA and the A(2A) receptor agonist CGS 21680 by caffeine, the selective A(1) receptor antagonist CPT, and the A(2A) receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motor-activating effects of acutely administered caffeine in rats involve the central blockade of both A(1) and A(2A) receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true cross-tolerance to CPT. The present results suggest that development of tolerance to the effects of A(1) receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A(2A) receptor blockade.
Caffeine increases blood pressure (BP), and its pressor effects are larger in borderline hypertensive (BH) men than in controls.
This article extends findings of larger caffeine effects on BP at rest and to brief mental stress in BH to a new analysis
of caffeine and prolonged mental stress in BH. In a double-blind, crossover study, 24 male BH (140/90 mmHg < BP < 160/95 mmHg)
and 23 normotensive controls who were habitual caffeine consumers (NT; BP < 135/85 mmHg; negative parental history) worked
on alternating mental stressors for 35 min after placebo or caffeine (3.3 mg/kg). Caffeine raised systolic blood pressure
(SBP) and diastolic blood pressure (DBP) alone and during the extended tasks (all ps < .00001/.00001). BH had larger SBP and
DBP increases over all postcaffeine periods (ps < .04/04) and larger DBP rises to the extended tasks after caffeine (p = .007). These combined effects led to undesirably high BPs (> 140/82 mmHg) relative to controls (< 130/75) during the 100
min after caffeine intake. Caffeine taken by BH at times of extended behavioral stress may elevate BP to a clinically meaningful
degree.
The present study examined the effects of stereotaxic delivery of corticosterone to the amygdala on anxiety-like behavior and corticotropin-releasing factor (CRF) mRNA level in the central nucleus of the amygdala (CeA). Micropellets (30 μg) of crystalline corticosterone or cholesterol (control) were implanted bilaterally at the dorsal margin of the CeA in Wistar rats. Seven days post-implantation, anxiety-like behavior was accessed using an elevated plus-maze. CRF mRNA level in the CeA was determined by in situ hybridization 4 h after being tested on the elevated plus-maze. Corticosterone implants increased indices of anxiety on the elevated plus-maze and produced a concomitant increase in both basal level of CRF mRNA per neuron and the number of neurons with CRF hybridization signal in the CeA. The plus-maze increased CRF mRNA levels in the CeA of cholesterol implanted rats to the elevated basal levels observed in corticosterone treated animals. Exposure to the plus-maze did not increase CRF mRNA level in the CeA of corticosterone implanted rats beyond elevated basal levels. Taken together, these findings support the involvement of the amygdala in anxiety-like behaviors in response to chronically elevated corticosterone and suggests that elevated glucocorticoids may increase anxiety by inducing CRF expression in the CeA.
Using a double-blind, randomized, cross-over protocol, we studied the effect of a single dose of oral caffeine on plasma renin activity, catecholamines and cardiovascular control in nine healthy, young, non-coffee drinkers maintained in sodium balance throughout the study period. Caffeine (250 mg) or placebo was administered in a methylxanthine-free beverage to overnight-fasted supine subjects who had had no coffee, tea or cola in the previous three weeks. Caffeine increased plasma renin activity by 57 per cent, plasma norepinephrine by 75 per cent and plasma epinephrine by 207 per cent. Urinary normetanephrine and metanephrine were increased 52 per cent and 100 per cent respectively. Mean blood pressure rose 14/10 mm Hg one hour after caffeine ingestion. There was a slight fall and then a rise in heart rate. Plasma caffeine levels were usually maximal one hour after ingestion but there was considerable individual variation. A 20 per cent increase in respiratory rate correlated well with plasma caffeine levels. Under the conditions of study caffeine was a potent stimulator of plasma renin activity and adrenomedullary secretion. Whether habitual ingestion has similar effects remains to be determined.
Most of the biological actions of caffeine are possibly mediated through its antagonistic effects to adenosine.
Adenosine activates an inhibitory GTP‐binding protein (G i ).
One of the physiological actions of G i is the inhibition of cAMP formation. Caffeine overcomes this action thus leading to elevation of cAMP.
Firing of neurons and the release of neurotransmitters is also inhibited by adenosine.
Caffeine overcomes this effect, thus producing increased CNS‐activity.
During long term administration of caffeine many functions of the organism develope tolerance including cardiovascular and central nervous systems. Present evidence suggests that caffeine tolerance following continuous severe coffee ingestion is the response of the body against caffeine through the upregulation of adenosine receptors.
The effect of caffeine on blood cortisol levels and blood pressures was examined during rest and in response to a challenging psychomotor task in men with a low versus high risk of essential hypertension. Thirty-four healthy men ages 21-35 years were selected such that 17 were at high risk for hypertension (positive parental history and screening blood pressures of 135/85-155/95 mm Hg) and 17 were at low risk (negative parental history and no pressures above 132/84 mm Hg). Testing consisted of quiet rest (20 minutes); oral placebo (grapefruit juice) or caffeine administration (3.3 mg/kg in grapefruit juice); rest during a postdrug absorption period (40 minutes); work on an unsignalled simple reaction time task (15 minutes); and quiet rest (20 minutes). Blood pressures were recorded at 2-minute intervals, and blood samples were withdrawn via an indwelling catheter at the end of the baseline, drug absorption, task, and recovery periods. The combination of task plus caffeine produced the highest blood pressures in men at risk for hypertension. Cortisol levels were found to be sustained during rest in members of the high risk group after they had consumed caffeine, whereas members of the low risk group showed a modest decline. The high risk subjects also showed a significant rise in cortisol during (+3.7 micrograms/dl) and after (+4.0 micrograms/dl) work on the reaction time task after caffeine consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
Synthetic ovine corticotropin-releasing hormone (oCRH) is a potent and specific ACTH secretagogue in man. Threshold and maximal i.v. doses are 0.01-0.03 and 3-10 micrograms/kg or less, but increase in frequency, severity, and duration at higher doses. oCRH produces a biphasic plasma immunoreactive (IR)-ACTH response and has a prolonged duration of action that is probably due to its long circulating half-life. Other pro-opiomelanocortin IR-peptide are secreted concomitantly in equimolar amounts. Plasma IR-cortisol concentration tends to follow that of ACTH, but also reflects cortisol's longer circulating half-life and the fact that acutely the maximally-stimulating plasma IR-ACTH level is about 45 pg/ml. oCRH is as effective given s.c. as i.v., but intranasal administration is only 1% as effective. Sex and age have no effect on the plasma IR-ACTH and IR-cortisol responses to oCRH. The time of day of oCRH administration has little influence on the plasma IR-ACTH response, but the plasma IR-cortisol response is much greater to oCRH given later in the day than early in the morning. Plasma IR-ACTH response to oCRH is more dependent on the basal plasma IR-cortisol level than the time of day. Arginine vasopressin given at the same time as oCRH potentiates 4-fold the plasma IR-ACTH response to oCRH alone, almost to levels obtained with insulin-induced hypoglycemia. However, oCRH administered at the onset of insulin-induced hypoglycemia does not cause higher plasma IR-ACTH levels, indicating that endogenous CRH levels are maximally-stimulating during the hypoglycemic response.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenalectomy-induced increases in ACTH secretion in rats are returned to normal by an action of corticosterone on the brain, not on the pituitary. Five days after adrenalectomy with constant steroid replacement, the concentration of free corticosterone in plasma which reduces plasma ACTH by 50% is approximately 0.8 nM. By contrast, the concentration of free plasma corticosterone required for 50% reduction of thymus wet weight or plasma transcortin concentration (both targets for glucocorticoid action) is about 4.5 nM. These results suggested that the inhibition of ACTH by corticosterone might be mediated by association of the steroid with high affinity, type I corticosteroid receptors, whereas the inhibition of thymus weight and transcortin might be mediated by association of the steroid with lower affinity, type II receptors. The results of studies comparing the ability of corticosterone, dexamethasone and aldosterone to inhibit adrenalectomy-induced ACTH secretion support the hypothesis that basal ACTH secretion in rats is mediated by association of corticosterone with type I receptors.
Twenty-three patients with pituitary adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome were studied before and after treatment. The relationship between the amelioration of the depressive syndrome and changes in cortisol and ACTH levels was investigated. There was a significant difference in mean change in 24-hour urinary free cortisol (UFC) excretion for changes in the depressed mood score from first to last visit. There were also significant correlations between decreases in UFC and decreases in both the depressed mood score and the modified Hamilton depression score. These relationships were not found for ACTH. Furthermore, with cortisol decreased to normal levels, continued high ACTH levels did not prevent improvement in depressed mood. The possibility that cortisol may also play a role in the pathogenesis and/or maintenance of the mood disorder in psychiatric patients is discussed.
Caffeine, a potent central stimulant, is known to competitively inhibit the specific binding of both adenosine and benzodiazepine receptor ligands to brain membranes in vitro. In mice receiving a diet containing non-toxic doses of caffeine (200 or 400 mg/kg diet) for periods up to 40 days, a dose-related increase in the number of binding sites for [3H]-CHA and [3H] DPX was observed in whole brain membranes without modifications of the receptors' affinity. Furthermore, a transitory increase in the number of [3H]-DZP binding sites was observed. These preliminary data seem to confirm the involvement of the adenosine receptors in the mode of action of caffeine and may be relevant to the development of both tolerance and dependence to some of the central effects of this compound.
In order to test the hypothesis that cortisol secretion is inhibited during sleep, six healthy young men (ages 18-24) were studied in a 4-day protocol. A baseline nocturnal sleep period was followed by one night's total sleep deprivation, then sleep at 180 degrees phase shift, and then return to a normal nocturnal sleep episode (SP-3). Plasma cortisol concentrations were measured every 20 min (obtained by an indwelling venous catheter), rectal temperature was measured every minute, and sleep was polygraphically defined. During the first 4 h of sustained sleep, cortisol secretion was decreased even when sleep occurred during a time when the subject was usually awake; conversely, it was elevated if awake at the usual daily time of sleeping. This was not the case for the last 4 h of sleep. Body temperature was also decreased but during each entire 7- to 8-h sleep period. Meals produced only a small brief rise of cortisol and produced no change in body temperature. Stage 4 sleep was increased during the 180 degrees inverted sleep episode and decreased during SP-3, REM sleep however was increased during SP-3. A reciprocal relationship was found between REM and stages 3 and 4 for the second, third, and fourth, and sixth h of sleep for SP-3. These results demonstrate the inhibitory effect of the behavioral complex of sleeping on cortisol secretion superimposed on its endogenous circadian and ultradian rhythm. These neurophysiological events may be used to entrain and time the period and phase of biological rhythms in relation to shift work, sleep deprivation, and transmeridian jet travel.
Serum cortisol concentrations were compared in 18 borderline hypertensive (BH) and 20 normotensive (NT) men before and after mental stress. Two levels of demand, intermittent reaction time with brief rests and reaction time alternating continuously with mental arithmetic, were used in two consecutive protocols on different days in the laboratory. Continuous, but not intermittent, mental stress produced significant elevations in cortisol levels only in the BH subjects (p < .001). The continuous challenge produced slightly more self-reported distress in both groups than the intermittent condition, and performance on the mental arithmetic task was more strongly correlated with the cortisol response than was performance on the reaction time task, suggesting that the mental arithmetic task was a key contributor to the cortisol response. Therefore, adrenocortical activity appears sensitive to appropriate stressors in BH subjects. These results indicate the importance of including measures of adrenocortical function in studies of reactivity in subjects at high risk for hypertension.
Levels of tetanus-specific antibodies were assessed in free-ranging, yearling rhesus monkeys following prophylactic immunization with tetanus toxoid. Each subject's behavior had been observed between 11 and 25 weeks of age and approximately 2 months later during its mother's first concentrated mating period as a part of another study. Prior to immunization, at approximately 1 year of age, cardiovascular parameters, and several plasma parameters [cortisol, adrenocorticotrophic hormone (ACTH), growth hormone (GH), interleukin-2 (IL-2), and total plasma immunoglobulin G (IgG)] were measured during a brief period of captivity. Antibody titers noted approximately 2 weeks after immunization were related to cardiovascular parameters. Thus, yearlings with high heart rates and low heart rate variability during captivity had the highest tetanus-specific serum IgG. Levels of plasma cortisol, ACTH, total IgG, and IL-2 noted at the time of capture were unrelated to subsequent antibody levels. Antibody titers were, however, positively correlated with GH noted immediately following capture on the day prior to immunization. Antibody titers were also related to the infants' behavior observed during their mother's first concentrated mating period. Infants who were most distressed (high levels of distress vocalization) when their mother resumed mating (a time particularly stressful for free-ranging rhesus infants) showed lower antibody titers to tetanus immunization as a yearling. The present observations add support to the existence of a relationship between behavior during exposure to an early stressor and later immune regulation and that certain cardiovascular parameters may be related to certain indicators of immunoregulation.
Scientific literature cites a wide range of values for caffeine content in food products. The authors suggest the following standard values for the United States: coffee (5 oz) 85 mg for ground roasted coffee, 60 mg for instant and 3 mg for decaffeinated; tea (5 oz): 30 mg for leaf/bag and 20 mg for instant; colas: 18 mg/6 oz serving; cocoa/hot chocolate: 4 mg/5 oz; chocolate milk: 4 mg/6 oz; chocolate candy: 1.5-6.0 mg/oz. Some products from the United Kingdom and Denmark have higher caffeine content. Caffeine consumption survey data are limited. Based on product usage and available consumption data, the authors suggest a mean daily caffeine intake for US consumers of 4 mg/kg. Among children younger than 18 years of age who are consumers of caffeine-containing foods, the mean daily caffeine intake is about 1 mg/kg. Both adults and children in Denmark and UK have higher levels of caffeine intake.
Whether the vasoconstrictive actions of caffeine are enhanced in hypertensive persons has not been demonstrated. Thus, caffeine (3.3 mg/kg) versus placebo was tested in 48 healthy men (aged 20 to 35 years) selected after screening on 2 separate occasions. Borderline hypertensive men (n = 24) were selected with screening systolic blood pressure (BP) of 140 to 160 mm Hg and/or diastolic BP 90 to 99 mm Hg. Low-risk controls (n = 24) reported no parental history of hypertension and had screening BP < 130/85 mm Hg. Participants were then tested on 2 occasions after 12-hour abstinence from caffeine in each of 2 protocols; this required a total of 4 laboratory visits. Caffeine-induced changes in diastolic BP were 2 to 3 times larger in borderline subjects than in controls (+8.4 vs +3.8 mm Hg, p < 0.0001), and were attributable to larger changes in impedance-derived measures of systemic vascular resistance (+135 vs +45 dynes.s.cm-5, p < 0.004). These findings were consistent and reached significance in both protocols. The percentage of borderline subjects in whom diastolic BP changes exceeded the median control response was 96%. Consequently, whereas all participants exhibited normotensive levels during the resting predrug baseline, 33% of borderline subjects achieved hypertensive BP levels after caffeine ingestion. Thus, in borderline hypertensive men, exaggerated responses to caffeine were: selective for diastolic BP, consistent with greater vasoconstriction, replicated in 2 protocols, and representative of nearly all borderline hypertensives. We suspect that the potential for caffeine to stabilize high resistance states in susceptible persons suggests that its use may facilitate their disease progression, as well as hinder accurate diagnosis and treatment.
The effects of oral caffeine (3.3 mg/kg, equivalent to 2-3 cups of coffee) on plasma adrenocorticotropin (ACTH) and cortisol (CORT) were tested in 47 healthy young men at rest in a double-blind, placebo-controlled, crossover study. Following caffeine, ACTH was significantly elevated at all times from 30 min to 180 min, and CORT was elevated from 60 min to 120 min (Fs > or = 8.4, ps < 0.01). Peak increases relative to placebo were: ACTH, 33% (+5.2 pg/ml) and CORT, 30% (+2.7 micrograms/dl) at 60 min postcaffeine. The results suggest that caffeine can activate important components of the pituitary-adrenocortical response in humans during the resting state. Caffeine's known ability to increase CORT production appears at least partly due to an increase in ACTH release at the pituitary.
This study examined pituitary-adrenocortical responses to dietary doses of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee), alone and combined with behavioral stress, in men at high risk versus low risk for hypertension. A randomized, double-blind, caffeine-placebo crossover design was used.
Adrenocorticotropic hormone (ACTH) and cortisol levels in plasma were assessed at rest and in response to 60-minutes of continuous work on a mental stressor (arithmetic) and a psychomotor task (reaction time) on four test sessions held on separate days.
Tasks alone caused greater ACTH and cortisol increases in high risk men than in the low risk group. Caffeine alone elevated ACTH and cortisol in both groups, with more immediate responses in the high risk group. Both groups showed significant ACTH and cortisol responses to caffeine plus tasks, with the high risk group showing more persistent elevations. The high risk group also showed the highest levels of ACTH and cortisol after caffeine plus tasks.
These findings demonstrate for the first time the combined effects of caffeine plus stress on ACTH and demonstrate greater corticosteroid effects in hypertension-prone men. As such, they may have implications for the dietary use of caffeine during periods of stress and in those at risk for hypertension.
Caffeine has both positive effects that contribute to widespread consumption of caffeine-containing beverages and adverse unpleasant effects if doses are increased. Caffeine has weak reinforcing properties, but with little or no evidence for upward dose adjustment, possibly because of the adverse effects of higher doses. Withdrawal symptoms, although relatively limited with respect to severity, do occur, and may contribute to maintenance of caffeine consumption. Health hazards are small if any and caffeine use is not associated with incapacitation. Thus, although caffeine can be argued to fulfill regulatory criteria as a dependence-producing drug, the extensive use of caffeine-containing beverages poses little apparent risk to the consumer or to society. The positive stimulatory effects of caffeine appear in large measure to be due to blockade of A2A receptors that stimulate GABAergic neurons of inhibitory pathways to the dopaminergic reward system of the striatum. However, blockade of striatal A1 receptors may also play a role. The mechanisms underlying negative effects of higher doses of caffeine are as yet not well defined.
Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been only moderately well characterized in humans. Four double-blind experiments were conducted in independent groups of healthy participants to assess the conditions under which withdrawal symptoms occur upon cessation of low to moderate doses of caffeine. In experiment 1, there was no evidence that the range or magnitude of caffeine withdrawal symptoms differed when 300 mg of caffeine was consumed as a single dose in the morning versus 100 mg at three time points across the day. In experiment 2, both the range and severity of withdrawal increased as a function of caffeine maintenance dose (100, 300, and 600 mg/day), with even the lowest dose (100 mg) producing significant caffeine withdrawal. Experiment 3 showed that when individuals were maintained on 300 mg caffeine/day and tested with a range of lower doses (200, 100, 50, 25, and 0 mg/day), a substantial reduction in caffeine consumption (</=100 mg/day) was necessary for the manifestation of caffeine withdrawal. Experiment 4 manipulated duration of exposure to caffeine (1, 3, 7, or 14 days of 300 mg/day) and showed that caffeine withdrawal occurred after as little as 3 days of caffeine exposure, with a somewhat increased severity of withdrawal observed after 7 or 14 days of exposure. As a whole, this set of experiments provides the most complete parametric characterization of caffeine withdrawal to date and suggests that caffeine physical dependence can occur under more modest conditions (i.e., fewer doses per day, lower daily dose, shorter duration of exposure) than previously recognized.
The effects of various doses (40 microg/kg/hr, 300 microg/kg/hr, 600 microg/kg/hr or placebo) of hydrocortisone on tasks assessing working and declarative memory function were measured in 4 groups of 10 young men. During the infusion, participants were given an item-recognition working memory task, a paired-associate declarative memory task, and a continuous performance task used to control possible concomitant effects of corticosteroids on vigilance. The results revealed significant acute effects of the highest dose of hydrocortisone on working memory function, without any significant effect on declarative memory function or arousal-vigilance performance. These results suggest that working memory is more sensitive than declarative memory to the acute elevations of corticosteroids, which could explain the detrimental effects of corticosteroids on acquisition and consolidation of information, as reported in the literature.
Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.
Daily oscillations characterize the release of nearly every hormone. The circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, generates circadian, approximately 24-hour rhythms in many physiologic functions. However, the observed hormonal oscillations do not simply reflect the output of this internal clock. Instead, daily hormonal profiles are the product of a complex interaction between the output of the circadian pacemaker, periodic changes in behavior, light exposure, neuroendocrine feedback mechanisms, gender, age, and the timing of sleep and wakefulness. The interaction of these factors can affect hormonal secretory pulse frequency and amplitude, with each endocrine system differentially affected by these factors. This chapter examines recent advances in understanding the effects on endocrine rhythms of a number of these factors. Sleep exerts a profound effect on endocrine secretion. Sleep is a dynamic process that is characterized by periodic changes in electrophysiologic activity. These electrophysiologic changes, which are used to mark the state and depth of sleep, are associated with periodic, short-term variations in hormonal levels. The secretion of hormones such as renin and human growth hormone are strongly influenced by sleep or wake state, while melatonin and cortisol levels are relatively unaffected by sleep or wake state. In addition, sleep is associated with changes in posture, behavior, and light exposure, each of which is known to affect endocrine secretion. Furthermore, the tight concordance of habitual sleep and wake times with certain circadian phases has made it difficult to distinguish sleep and circadian effects on these hormones. Specific protocols, designed to extract circadian and sleep information semi-independently, have been developed and have yielded important insights into the effects of these regulatory processes. These results may help to account for changes in endocrine rhythms observed in circadian rhythm sleep disorders, including the dyssomnia of shift work and visual impairment. Yet to be fully investigated are the interactions of these factors with age and gender. Characterization of the factors governing hormone secretion is critical to understanding the temporal regulation of endocrine systems and presents many exciting areas for future research.
Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy.
The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment.
Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease.
Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.
Memory tends to be better for emotionally arousing information than for neutral information. Evidence from animal studies indicates that corticosteroids may be necessary for this memory enhancement to occur. We extend these findings to human memory performance. Following administration of cortisol (20 mg) or placebo, participants were exposed to pictures varying in emotional arousal. Incidental memory for the pictures was assessed one week later. We show that elevated cortisol levels during memory encoding enhances the long-term recall performance of emotionally arousing pictures relative to neutral pictures. These results extend previous work on corticosteroid enhancement of memory and suggest that high cortisol levels during arousing events result in enhanced memory in humans.
Exogenous cortisol's modulation of the acoustic startle reflex (ASR) was tested alone and during exposure to affectively valenced photographs in healthy men and women. During nonmodulated startle, oral hydrocortisone had a biphasic dose effect, with 5 mg increasing and 20 mg decreasing, eyeblink reflex magnitude compared to placebo. During emotion modulation, 20 mg of hydrocortisone reduced reflex magnitude without affecting the usual pattern of modulation across positive, neutral, and negatively affective slides. Gender differences were not found in either relationship. These findings illustrate dose-dependent effects of cortisol on the startle pathway independent of emotional state and consistent across genders.
Caffeine is an excellent model compound for understanding drugs of abuse/dependence. The results of self-administration and choice studies in humans clearly demonstrate the reinforcing effects of low and moderate doses of caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use. Recent studies provide compelling evidence that caffeine physical dependence potentiates the reinforcing effects of caffeine through the mechanism of withdrawal symptom avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine in humans has been demonstrated. Physical dependence as reflected in a withdrawal syndrome in humans has been repeatedly demonstrated in adults and recently demonstrated in children. Withdrawal severity is an increasing function of caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg per day. Increased cerebral blood flow may be the physiological mechanism for caffeine withdrawal headache. Case studies in adults and adolescents clearly demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance dependence syndrome on caffeine, including feeling compelled to continue caffeine use despite desires and recommendations to the contrary. Survey data suggest that 9% to 30% percent of caffeine consumers may be caffeine dependent according to DSM-IV criteria.
By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH) -producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control group consisted of individuals who had normal blood pressure and died of acute heart failure due to mechanical trauma. Both magno- and parvocellular populations of CRH neurons appeared to be more numerous in the PVN of hypertensive patients. Quantitative analysis showed approximately a twofold increase in the total number of CRH neurons and a more than fivefold increase in the amount of CRH mRNA in the hypertensive PVN compared with the control. It is suggested that synthesis of CRH in hypertensive PVN is enhanced. Increased activity of CRH-producing neurons in the PVN of hypertensive patients is proposed not only to entail hyperactivity of the hypothalamo-pituitary-adrenal axis, but also of the sympathetic nervous system and, thus, to be involved in the pathogenesis of hypertension.
It is widely held that tolerance develops to the effects of sustained caffeine consumption. This study was designed to investigate the effects of chronic, staggered caffeine ingestion on the responses of an acute caffeine challenge, during -euglycaemia.
Twelve healthy volunteers were randomized using a double-blind, cross-over design to take either 200 mg caffeine (C-replete) or placebo (C-naïve) twice daily for 1 week. Following baseline measurements being made, the responses to 200 mg caffeine (blood-pressure, middle cerebral artery velocity, mood and cognitive performance) were examined over the subsequent 120 min. Blood glucose was not allowed to fall below 4.0 mmol l-1.
After the caffeine challenge, middle cerebral artery blood velocity decreased in both conditions but was greater in the C-naïve condition (-8.0 [-10.0, -6.1] cm s-1 vs -4.9 [-6.8, -2.9] cm s-1 C-replete, P < 0.02). Systolic blood pressure rise was not significantly different in C-naïve, although this rise was more sustained over time (P < 0.04). Mood was adversely affected by regular caffeine consumption with tense aspect of mood significantly higher at baseline in C-replete 11.6 +/- 0.6 C-naïve vs 16.3 +/- 1.6 C-replete, P < 0.01). Cognitive performance was not affected by previous caffeine exposure.
Overall these results suggest that tolerance is incomplete with respect to both peripheral or central effects of caffeine.
Blood pressure (BP) and cardiovascular hemodynamics were assessed at baseline and after caffeine administration in a 4-week, placebo-controlled, double-blind, randomized, crossover trial of caffeine tolerance formation. Half of the subjects developed tolerance to the pressor effect of caffeine, whereas the other half continued to show increases in BP after caffeine ingestion (F = 16.7, p <0.0001). In the subjects who did not develop tolerance, peripheral resistance increased incrementally as the daily dose of caffeine increased (F = 2.8, p = 0.05).
Caffeine acutely raises blood pressure (BP). The clinical significance of this effect depends on whether BP responses persist in persons who consume caffeine on a daily basis. Accordingly, the ability of caffeine to raise BP after 5 days of regular daily intake was tested in a randomized controlled trial. Individual differences in tolerance formation were then examined. Men (n=49) and women (n=48) completed a double-blind, crossover trial conducted over 4 weeks. During each week, subjects abstained for 5 days from dietary caffeine and instead used capsules totaling 0 mg, 300 mg, and 600 mg of caffeine per day in 3 divided doses. On day 6, in the laboratory, they used capsules with either 0 mg or 250 mg of caffeine at 9:00 am and 1:00 pm. Systolic/diastolic BP increases as a result of 250 mg of caffeine remained significant (P<0.006/0.001) at all levels of previous daily consumption. Individual difference comparisons found that although half the subjects had complete loss of systolic and diastolic BP responses to the challenge doses, the other half showed no loss in BP response, even after using 600 mg of caffeine per day for the previous 5 days (F >7.90, P <0.001). The sexes did not differ in degree of tolerance formation. Daily caffeine consumption failed to eliminate the BP response to repeated challenge doses of caffeine in half of the healthy adults who were tested. Caffeine may therefore cause persistent BP effects in persons who are regular consumers, even when daily intake is at moderately high levels.
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Address correspondence and reprint requests to William R. Lovallo, PhD, VA Medical Center (151A), 921 NE 13th Street E-mail: bill@mindbody1.org Received for publication Supported by NHLBI grant HL32050, NIRR grant M01-RR14467, and the Department of Veterans Affairs Medical Research Service
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