Motor improvement in Parkinson's disease patients receiving caffeine adjuvants: A double-blind randomized controlled trial in Indonesia.

Parkinson's disease (PD) manifests as a movement and brain function disorder characterized by symptoms such as resting tremors, rigidity, bradykinesia, and postural instability, leading to disability among patients. The use of psychostimulants such as caffeine has been associated with the improvement of motor symptoms in PD patients; however, studies regarding the effect of caffeine adjuvant therapy on motor function among PD patients in the Indonesian population are lacking. The aim of this study was to evaluate motor improvement as measured by the change in scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) among PD patients receiving caffeine adjuvant. A double-blind randomized controlled trial (RCT) was conducted among PD patients at Dr. Soetomo General Academic Hospital and Universitas Airlangga Hospital, Surabaya, Indonesia, from April to August 2023. A total of 27 patients were enrolled and randomly assigned to an intervention (receiving caffeine adjuvant, n=15) and control group (receiving placebo, n=12). Motor improvement was measured using the UPDRS III score prior to intervention and three weeks after. The Chi-squared test was used to analyze the difference in UPDRS III scores between the two groups. Motor improvement, as demonstrated by a reduction in the UPDRS III score, was observed in patients receiving caffeine adjuvant compared to those receiving placebo (80.0% vs 16.7%; p=0.004). Regarding the safety profile, only four out of 15 (26.6%) patients treated with caffeine reported minor adverse events. These conditions improved over time during the intervention. None of the 12 patients in the placebo reported adverse events. This study provides valuable insights into the initial dosage of caffeine that improves motor function in PD patients with minimum adverse effects.

Consumption of a Coffee Rich in Phenolic Compounds May Improve the Body Composition of People with Overweight or Obesity: Preliminary Insights from a Randomized, Controlled and Blind Crossover Study.

This study analyzes the effects on body composition and variables related to metabolic syndrome of two coffees with different degree of roasting and phenolic content. Sixty participants with body mass index between 25 and 35 kg/m2 and a median age of 51.0 years (Interquartile range 46.3-56) were recruited. The study was a controlled, randomized, single-blind crossover trial consisting in drinking three cups/day of roasted coffee (RC) or lightly roasted coffee (LRC) during 12 weeks with 2-week wash-out stages before each coffee intervention. LRC contained ≈400 mg of hydroxycinnamic acids and ≈130 mg of caffeine per 200 mL/cup while RC contained ≈150 mg of hydroxycinnamic acids and ≈70 mg of caffeine per 200 mL/cup. Along the study, in each of the six visits, blood pressure, body composition by bioimpedance, anthropometric measurements, and blood biochemistry were analyzed. The mean differences and p values were calculated using a linear mixed model (JASP.v.0.18.0.3). A total of 38 participants completed the study. After the consumption of both coffees, fat mass and body fat percentage (LRC: -1.4%, p < 0.001; RC: -1.0%, p = 0.005) were reduced, whereas muscle mass and muscle mass percentage slightly increased (LRC: 0.8%, p < 0.001; RC: 0.7%, p = 0.002). The decrease in fat percentage was greater with LRC compared to RC (-0.8%; p = 0.029). There were no significant changes in metabolic syndrome variables or in body weight. In conclusion, LRC was slightly superior at inducing changes in body composition.

Matcha Does Not Affect Electroencephalography during Sleep but May Enhance Mental Well-Being: A Randomized Placebo-Controlled Clinical Trial.

Although theanine in matcha improves sleep quality and cognitive function, the caffeine in green tea is thought to worsen sleep quality. Therefore, this study investigated the factors behind the observed improvements in subjective sleep quality in matcha. A placebo-controlled randomized double-blind parallel-group study was conducted on healthy Japanese men and women aged 27-64 years. After 4 weeks of consuming 2.7 g of matcha daily (containing 50.3 mg theanine, 301.4 mg catechins, and 71.5 mg caffeine), no significant differences were observed between the control and matcha groups on total sleep time, sleep latency, wake after sleep onset, or sleep efficiency measured by electroencephalography (EEG). However, the sleep questionnaire Oguri-Shirakawa-Azumi Sleep Inventory, the Middle-age and Aged version (OSA-MA), administered immediately after waking showed a trend toward increased satisfaction with sleep time (p < 0.1), and EEG measurements indicated significantly shortened wake-up times after waking with matcha intake (p < 0.05). The Beck Depression Inventory-II scores also tended to decrease (p < 0.1). The continuous intake of matcha may offer improved subjective sleep quality and emotional stability despite not offering significant changes in objective sleep parameters.

Acute Effects of Oral Caffeine Intake on Human Global-Flash mfERG Responses: A Placebo-Controlled, Double-Masked, Balanced Crossover Study.

Purpose: To determine the acute effect of caffeine intake on the retinal responses as measured with a global-flash multifocal electroretinogram (gfmERG) protocol at different contrast levels. Methods: Twenty-four young adults (age = 23.3 ± 2.4 years) participated in this placebo-controlled, double-masked, balanced crossover study. On two different days, participants orally ingested caffeine (300 mg) or placebo, and retinal responses were recorded 90 minutes later using a gfmERG at three contrast levels (95%, 50%, and 29%). The amplitude response density and peak time of the direct and induced components (direct component [DC] and induced component [IC], respectively) were extracted for five different eccentricities (1.3°, 5.0°, 9.6°, 15.2°, and 21.9°). Axial length, spherical equivalent refraction, habitual caffeine intake, and body weight were considered as continuous covariates. Results: Increased IC amplitude response density was found after caffeine ingestion in comparison to placebo (P = 0.021, ƞp2 = 0.23), specifically for the 95% and 50% stimulus contrasts (P = 0.024 and 0.018, respectively). This effect of caffeine on IC amplitude response density was independent of the retinal eccentricity (P = 0.556). Caffeine had no effect on DC amplitude response density or DC and IC peak times. Conclusions: Our results show that oral caffeine intake increases the inner electro-retinal activity in young adults when viewing stimuli of high- (95%) to medium-contrast (50%). Given the increasing evidence that the inner retinal function is involved in the emmetropization process, these results may suggest that caffeine or its derivatives could potentially play a role in the mechanisms involved in eye growth.

Caffeine, but not paracetamol (acetaminophen), enhances muscular endurance, strength, and power.

BACKGROUND: Caffeine is one of the most popular ergogenic aids consumed by athletes. Caffeine's ergogenic effect has been generally explained by its ability to bind to adenosine receptors, thus modulating pain and reducing perceived exertion. Another pharmacological agent that may improve performance due to its analgesic proprieties is paracetamol. This study aimed to explore the effects of caffeine, paracetamol, and caffeine + paracetamol consumption on muscular endurance, strength, power, anaerobic endurance, and jumping performance. METHODS: In this randomized, crossover, double-blind study, 29 resistance-trained participants (11 men and 18 women) ingested either a placebo, caffeine (3 mg/kg), paracetamol (1500 mg) or caffeine + paracetamol 45 min before the testing sessions. The testing sessions included performing the bench press exercise with 75% of one-repetition maximum to momentary muscular failure, isokinetic knee extension and flexion at angular velocities of 60°/sec and 180°/sec, Wingate, and countermovement jump (CMJ) tests. RESULTS: Compared to placebo, isolated caffeine ingestion increased the number of repetitions performed in the bench press (p = 0.005; d = 0.42). Compared to placebo, isolated caffeine ingestion and/or caffeine + paracetamol consumption was ergogenic for strength (torque), muscular endurance (total work), or power in the isokinetic assessment, particularly at slower angular velocities (p = 0.027 to 0.002; d = 0.16 to 0.26). No significant differences between the conditions were observed for outcomes related to the Wingate and CMJ tests. CONCLUSION: This study provided novel evidence into the effectiveness of caffeine, paracetamol, and their combination on exercise performance. We found improvements in muscular endurance, strength, or power only when caffeine was consumed in isolation, or in combination with paracetamol. Isolated paracetamol consumption did not improve performance for any of the analyzed outcomes, thus calling into question its ergogenic potential.

Caffeine and Ovariectomy Debilitate Bone Health in Rats on Calcium-deficient Diet.

This study investigated the effects of ovariectomy and caffeine intake on bone health in rats on calcium-deficient diet. Forty adults female Wistar rats were divided into 4 groups in a 2x2 factorial design: Ovary (OVX/SHAM) and Caffeine (placebo/caffeine). The animals were housed in individual cages for 8 weeks, receiving 18-20g of AIN-93M diet per day, containing 50% of the daily recommended intake of calcium. The rats underwent ovariectomy (OVX) or laparotomy (SHAM) surgery. Caffeine groups received 6mg of caffeine/kg/day. After euthanasia, the tibia and femur were dissected to determine the calcium content and bone fracture strength, respectively. Blood sample was collected to determine serum Ostase. 24-hour urine was analyzed for excreted calcium and NTx. Reduced bone fracture strength and calcium content were observed in OVX and Caffeine groups. When observed separately, OVX group showed increased urinary NTx and lower bone weight, blood ostase, and urinary calcium. Caffeine groups showed elevated urinary calcium. There was a positive correlation between bone fracture strength and calcium content. NTx correlated negatively with bone calcium, fracture strength and thickness. In conclusion, both OVX and caffeine intake debilitate bone health in rats on calcium-deficient diet.

Effects of coffee on cognitive function.

This chapter thoroughly examines coffee's impact on cognitive function. It synthesizes research findings involving animals and humans, investigating coffee's influence on various memory and cognitive aspects, including short-term/working memory, long-term memory, attention, vigilance, executive functions, and processing speed. The chapter also discusses moderating factors, such as dose-response relationships, individual differences, age, and habitual consumption patterns, that influence the cognitive effects of coffee. Additionally, it addresses the potential risks and adverse effects associated with coffee intake, memory, and cognitive function, including stress and anxiety, sleep disturbances, cardiovascular effects, and addiction. Studies suggest moderate coffee intake improves attention, processing speed, decision-making, and certain executive functions. However, the effects vary depending on factors like dosage, individual traits, age, and sleep habits. Despite potential benefits, coffee consumption may lead to adverse effects such as anxiety, sleep issues, cardiovascular concerns, and dependency. Future research should address methodological concerns, incorporate neuroimaging methods, explore interactions with other substances, and investigate long-term effects and therapeutic uses. Understanding coffee's neuroscience can shed light on its role in daily life and health.

Coffee and mental disorders: How caffeine affects anxiety and depression.

Caffeine, the main psychoactive component in coffee, has garnered significant attention for its potential impact on the most prevalent mental health conditions like anxiety and depression. This chapter comprehensively examines the neurobiological effects of caffeine, its influence on anxiety and depression, and relevant clinical studies. Caffeine exerts its psychostimulant effects primarily through antagonizing adenosine receptors, modulating neurotransmitter systems, and influencing intracellular calcium signaling in the brain. Caffeine exhibits dose-dependent effects. While moderate caffeine consumption is safe in healthy adults and may offer benefits for mental health, excessive intake is linked to adverse effects on neurological and psychiatric health and can aggravate symptoms, highlighting the importance of adjusting consumption patterns. High caffeine intake correlates with elevated anxiety levels, especially in individuals predisposed to anxiety disorders. However, the relationship between caffeine consumption and the risk of depression is intricate, with some studies suggesting a potential protective effect of moderate intake, while others find no significant association. Individual variations in caffeine metabolism, sensitivity, and genetic factors considerably impact responses to caffeine. The chapter also explores the therapeutic potential of caffeine as an adjunct treatment and outlines challenges and future research directions in elucidating caffeine's multifaceted role in mental health.

Coffee and sleep: Benefits and risks.

Consuming coffee, a widely enjoyed beverage with caffeine, can impact the central nervous system and disturb sleep if taken too close to bedtime. Caffeine impacts sleep by slowing the onset, blocking adenosine receptors, lowering deep sleep levels, disrupting sleep patterns, and lessening rapid eye movement sleep. Although coffee can help with alertness in the morning, it may disturb sleep in the evening, particularly for individuals who are sensitive to caffeine. To enhance the quality of sleep, reduce the consumption of caffeine in the afternoon and evening, refrain from drinking caffeine before going to bed, and choose decaffeinated drinks instead. Variables such as personal reactions, ability to handle caffeine, and engagement with other compounds also influence the impact of coffee on sleep. Keeping track of how much caffeine you consume and your sleeping habits can assist in recognizing any disturbances and making needed changes. Furthermore, taking into account variables such as metabolism, age, and the timing of coffee consumption can assist in lessening the effects of coffee on sleep. In general, paying attention to the amount of caffeine consumed from different sources and consuming it at the right times can assist in preserving healthy sleep patterns even while enjoying coffee.

Coffee, antioxidants, and brain inflammation.

Coffee is the most popular beverage in the world and, aside from tea and water, the most often consumed caffeine-containing beverage. Because of its high caffeine concentration, it is typically classified as a stimulant. There are other bioactive ingredients in coffee besides caffeine. The coffee beverage is a blend of several bioactive substances, including diterpenes (cafestol and kahweol), alkaloids (caffeine and trigonelline), and polyphenols (particularly chlorogenic acids in green beans and caffeic acid in roasted coffee beans). Caffeine has also been linked to additional beneficial benefits such as antioxidant and anti-inflammatory properties, which change cellular redox and inflammatory status in a dose-dependent manner. Pyrocatechol, a constituent of roasted coffee that is created when chlorogenic acid is thermally broken down, has anti-inflammatory properties as well. It is postulated that coffee consumption reduces neuroinflammation, which is intimately linked to the onset of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). This review provides an overview of the most recent studies regarding coffee's possible benefits in preventing brain inflammation and neurodegenerative disorders.

Exploring the complex relationship between caffeine consumption and schizophrenia: A review of epidemiological and clinical studies.

This review delves into the intricate interplay between caffeine consumption and schizophrenia, examining evidence from epidemiological and clinical studies. While epidemiological research offers conflicting findings regarding the association between coffee intake and schizophrenia risk, clinical studies reveal diverse impacts of caffeine on symptomatology and cognition in individuals with schizophrenia. Some epidemiological studies suggest a potential protective effect of coffee consumption against schizophrenia, whereas others fail to establish a significant correlation. Clinical investigations highlight the complexity of caffeine's influence, with varied effects on symptom severity and cognitive function observed among schizophrenia patients. Notably, caffeine may exacerbate positive symptoms while alleviating negative symptoms and cognitive deficits in this population. However, limitations such as small sample sizes and reliance on self-reported data hinder the generalizability of these findings. Furthermore, genetic factors, prenatal exposure, and substance abuse contribute to the complexity of the relationship between caffeine and schizophrenia. Studies indicate that individuals with a genetic predisposition to schizophrenia may be more vulnerable to the effects of caffeine, while prenatal exposure to caffeine may elevate the risk of schizophrenia in offspring. Additionally, substance abuse, including high caffeine and nicotine consumption, is prevalent among individuals with schizophrenia, exacerbating symptom severity. Future research directions include addressing methodological limitations, such as small sample sizes and reliance on self-reported data, and exploring the effects of caffeine on schizophrenia using larger, more diverse cohorts and controlled methodologies. A deeper understanding of caffeine's impact on schizophrenia is crucial for informing clinical practice and developing personalized interventions for patients. Ultimately, this review underscores the need for further investigation into the complex relationship between caffeine consumption and schizophrenia to improve patient outcomes and inform evidence-based interventions.

From bean to brain: Coffee, gray matter, and neuroprotection in neurological disorders spectrum.

Coffee is a popular drink enjoyed around the world, and scientists are very interested in studying how it affects the human brain. This chapter looks at lots of different studies to understand how drinking coffee might change the brain and help protect it from neurodegenerative disorders especially like schizophrenia. With the help of available literature a link between the coffee mechanism and neurodegenerative disorders is established in this chapter. Researchers have found that drinking coffee can change the size of certain parts of the brain that control things like thinking and mood. Scientists also study how coffee's ingredients, especially caffeine, can change how the brain works. They think these changes could help protect the brain from diseases. This chapter focuses on how coffee might affect people with schizophrenia as hallucination is caused during and after excess consumption of caffeine. There's still a lot we don't know, but researchers are learning more by studying how different people's brains respond to coffee over time. Overall, this chapter shows that studying coffee and the brain could lead to new ways to help people with brain disorders. This study also draws ideas for future research and ways to help people stay healthy.

Methylxanthine use in infants with hypoxic-ischemic encephalopathy: a retrospective cohort study.

Therapeutic hypothermia is the standard treatment for hypoxic-ischemic encephalopathy (HIE), but despite its widespread use, the rates of mortality and neurodevelopmental impairment for moderate to severe HIE remain around 30%. Methylxanthines, such as caffeine and aminophylline, have potential neuroprotective effects in the setting of hypoxic-ischemic injury. However, data on the safety and efficacy of methylxanthines in the setting of therapeutic hypothermia for HIE are limited. This retrospective multicenter study examined in-hospital outcomes in 52 infants with HIE receiving methylxanthines and therapeutic hypothermia. The frequency of mortality and in-hospital morbidities were similar to those of infants enrolled in clinical trials undergoing therapeutic hypothermia without adjunctive therapies. Clinical trials of methylxanthines for neuroprotection in HIE are needed to determine safety and efficacy and should explore optimal dosing and timing of methylxanthine administration.

Exploring the link between physicians' caffeine use disorders with sleep quality and professional burnout: a cross-sectional study.

BACKGROUND: The objective of this research was to examine how caffeine use disorder among physicians across different specialties relates to both sleep quality and professional burnout. METHODS: This research represents a single-center, prospective, cross-sectional study involving 240 physicians meeting inclusion criteria and working within a training and research hospital. Participants were enrolled in the study after obtaining informed consent. A web-based survey methodology was employed, administering a participant information form crafted following an exhaustive literature review, alongside assessments utilizing the Caffeine Use Disorder Questionnaire, the Pittsburgh Sleep Quality Index, and the Maslach Burnout Inventory. A significance level of p < 0.05 was considered statistically significant. RESULTS: In our study, participants had a median age of 30.0 years, and 60% reported poor sleep quality. A positive and statistically significant relationship (rho=0.148, p = 0.022) was found between the Caffeine Use Disorder Questionnaire and Pittsburgh Sleep Quality Index scores. In the generalized linear model analysis, setting the Caffeine Use Disorder Questionnaire score as the dependent variable, statistically significant contributions were observed for gender (women), daily total caffeine intake, and Maslach-depersonalization score variables (p = 0.012, p < 0.001, 0.035, respectively). CONCLUSIONS: Higher levels of caffeine use disorder have been observed among women, smokers, and individuals with increased caffeine intake. Notably, an increase in professional depersonalization is associated with a rise in caffeine use disorder. Studying physicians' professional depersonalization could aid in addressing caffeine use disorders. Additionally, exploring the caffeine consumption patterns of healthcare professionals displaying depersonalization towards patients' needs is also worthwhile.

Evaluation of the Caffeine Content in Servings of Popular Coffees in Terms of Its Safe Intake-Can We Drink 3-5 Cups of Coffee per Day, as Experts Advise?

The spreading knowledge of the health benefits of coffee and the development of gastronomy with a wide range of coffees prompt an evaluation of their caffeine content in terms of safe intake. The study analyzed the caffeine content of popular coffees in comparison with recommendations for a safe single dose (200 mg) and daily caffeine intake (400 mg), and guidelines for drinking 3-5 cups of coffee per day. A total of 299 coffee samples from franchise shops and homemade coffees were tested. The "takeaway" coffees had a three times higher mean caffeine content (p < 0.005) compared to homemade coffees. Americano coffee was the "strongest" (143 mg caffeine/serving on average), while coffee prepared by pouring hot water over one teaspoon of ground coffee was the "lightest" (23 mg caffeine/serving on average) (p < 0.05). Over 200 mg of caffeine per serving was found in 4% of samples. Over 400 mg of caffeine would be consumed by people drinking "on the go" 4-5 servings of many types of coffee, except espresso. In this respect, homemade coffees are safer. Therefore, recommendations on drinking coffee should be more practical, and indicate not only the number of cups, but also the "strength" of various types of coffee, in order to avoid the regular intake of high amounts of caffeine.

Combined Impact of Creatine, Caffeine, and Variable Resistance on Repeated Sprint Ability in Young Soccer Players.

There is evidence that both intra-serial variable resistance (I-sVR), as pre-activation within the post-activation performance enhancement cycle (PAPE), and creatine and caffeine supplementation increase athletic performance in isolation. However, the effect of the three conditioning factors on 30 m repeated sprint ability (RSA) performance in young soccer players is unknown. This study determined the summative and isolation effect of ergogenic aids and pre-activation in half-back squats (HBSs) with I-sVR on performance in an RSA test in young soccer players. Twenty-eight young soccer players were randomly assigned to either EG1 (n = 7, creatine + caffeine + I-sVR), EG2 (n = 7, creatine + placebo2 + I-sVR), EG3 (n = 7, placebo1 + caffeine + I-sVR), or EG4 (n = 7, placebo1 + placebo2 + I-sVR), using a factorial, four-group-matched, double-blind, placebo-controlled design. Creatine supplementation included 0.3 g/kg/day for 14 days, caffeine supplementation included 0.3 mg/kg per day, and pre-activation in HBS with I-sVR (1 × 5 at 30% 1RM [1.0-1.1 m/s] + 1 × 4 at 60% 1RM [0.6-0.7 m/s]). The RSA test and HBS outcomes were evaluated. Three-way ANOVA showed non-significant differences for the RSA test and HBS outcomes (p > 0.05). At the end of this study, it was found that the three ergogenic aids, together, do not generate a summative effect on the physical performance of young soccer players. However, it is important to analyze individual responses to these specific protocols.

Effects of caffeine intake on pupillary parameters in humans: a systematic review and meta-analysis.

Caffeine is a widely used drug that broadly affects human cognition and brain function. Caffeine acts as an antagonist to the adenosine receptors in the brain. Previous anecdotal reports have also linked caffeine intake with changes in pupil diameter. By modifying the retinal irradiance, pupil diameter modulates all ocular light exposure relevant for visual (i.e., perception, detection and discrimination of visual stimuli) and non-visual (i.e., circadian) functions. To date, the extent of the influence of caffeine on pupillary outcomes, including pupil diameter, has not been examined in a systematic review. We implemented a systematic review laid out in a pre-registered protocol following PRISMA-P guidelines. We only included original research articles written in English reporting studies with human participants, in which caffeine was administered, and pupil diameter was measured using objective methods. Using broad search strategies, we consulted various databases (PsycINFO, Medline, Embase, Cochrane Library, bioRxiv and medRxiv) and used the Covidence platform to screen, review and extract data from studies. After importing studies identified through database search (n = 517 imported, n = 46 duplicates), we screened the title and abstracts (n = 471), finding 14 studies meeting our eligibility criteria. After full-text review, we excluded seven studies, leaving only a very modest number of included studies (n = 7). Extraction of information revealed that the existing literature on the effect of caffeine on pupil parameters is very heterogeneous, differing in pupil assessment methods, time of day of caffeine administration, dose, and protocol timing and design. The evidence available in the literature does not provide consistent results but studies rated as valid by quality assessment suggest a small effect of caffeine on pupil parameters. We summarize the numeric results as both differences in absolute pupil diameter and in terms of effect sizes. More studies are needed using modern pupil assessment methods, robust study design, and caffeine dose-response methodology.

Sonophoresis mediated diffusion of caffeine loaded Transcutol® enriched cerosomes for topical management of cellulite.

The goal of this research was to augment the deposition of caffeine loaded Transcutol® enriched cerosomes (TECs) gel for efficient topical treatment of cellulite utilizing the sonophoresis technique. Caffeine-loaded TECs were prepared using thin film hydration method applying 23 factorial design to study the impact of different factors, each with two levels on the entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of the formulated TECs. The studied factors were cetyl trimethyl ammonium bromide (CTAB) amount (mg) (X1), phosphatidylcholine (PC) amount (mg) (X2), and Transcutol® amount (mg) (X3). Design-Expert® software was utilized to determine the optimum TECs formulation. Afterward, the optimum TECs formulation was loaded into a gel and subjected to extra investigations. The optimum TECs formulation was (TEC5) which was prepared using 10 mg of CTAB, 150 mg of PC, and 10 mg of Transcutol®. TEC5 presented EE% of 87.44 ± 0.14 %, PS of 308.60 ± 13.38 nm, PDI of 0.455 ± 0.030, and ZP of 50.20 ± 1.55 mV. TEC5 had a fiber-like morphology, with elongated tubules of ceramide. Further, the optimum TECs formulation showed a high stability profile. Moreover, an in vivo dermatokinetic study showed superior deposition of caffeine from TEC5 gel coupled with the sonophoresis on rat skin compared to TEC5 gel and caffeine gel. Moreover, the histopathological study of TEC5 on rat skin confirmed the non-irritant nature of TEC 5 gel mediated by ultrasonic waves through the skin. Overall, the outcomes exposed the obvious superiority of sonophoresis delivered TECs-gel for topical delivery of caffeine for cellulite management.

Caffeine and modafinil modulate the effects of sleep deprivation on thalamic resting-state functional connectivity: A double-blind pilot study.

BACKGROUND: Studies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. METHODS: A double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. RESULTS: The subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. CONCLUSIONS: After 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.