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Lader, Malcolm, Claire Cardwell, Philip Shine, and Nigel Scott. "Caffeine withdrawal symptoms and rate of metabolism." Journal of Psychopharmacology 10, no. 2 (March 1996): 110–18. http://dx.doi.org/10.1177/026988119601000205.
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Ashihara, Hiroshi, Hisayo Shimizu, Yoshiyuki Takeda, Takeo Suzuki, Fiona M. Gillies, and Alan Crozier. "Caffeine Metabolism in High and Low Caffeine Containing Cultivars of Camellia sinensis." Zeitschrift für Naturforschung C 50, no. 9-10 (October 1, 1995): 602–7. http://dx.doi.org/10.1515/znc-1995-9-1002.
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Abstract The metabolism of [8-14C ]adenine and [2-14C]caffeine was examined in leaf segments from flush shoots of tea cultivars with high and low caffeine content. The caffeine biosynthesis pathway from AMP via theobromine was operative in both high and low caffeine containing cultivars. There was a m ore rapid rate of caffeine biosynthesis from [8-14C ]adenine in the high caffeine cultivars while the rate of degradation of both adenine nucleotides and caffeine into CO2 was greatest in cultivars with a low endogenous caffeine content. Cell-free p reparations from tea shoots contained an N-methyltransferase, that is a keyenzyme in the caffeine biosynthesis pathway; more in-vitro activity was detected in preparations from high caffeine containing cultivars. The data obtained suggest that the high caffeine containing cultivars have a more rapid rate of caffeine biosynthesis and a slower rate of caffeine catabolism than cultivars with a low endogenous caffeine content
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Vaughan, Roger A., Randi Garcia-Smith, Marco Bisoffi, Kristina A. Trujillo, and Carole A. Conn. "Effects of Caffeine on Metabolism and Mitochondria Biogenesis in Rhabdomyosarcoma Cells Compared with 2,4-Dinitrophenol." Nutrition and Metabolic Insights 5 (January 2012): NMI.S10233. http://dx.doi.org/10.4137/nmi.s10233.
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Purpose This work investigated if treatment with caffeine or 2,4-dinitrophenol (DNP) induce expression of peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and increase both mitochondrial biosynthesis and metabolism in skeletal muscle. Methods Human rhabdomyosarcoma cells were treated with either ethanol control (0.1% final concentration) caffeine, or DNP at 250 or 500 μM for 16 or 24 hours. PGC-1α RNA levels were determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). PGC-1α protein and mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was determined by quantification of extracellular acidification rate and oxygen consumption rate. Results Treatment with either caffeine or DNP induced PGC-1α RNA and protein as well as mitochondrial content compared with control. Treatment with caffeine and DNP also significantly increased oxidative metabolism and total metabolic rate compared with control. Caffeine similarly increased metabolism and mitochondrial content compared with DNP. Conclusion This work identified that both caffeine and DNP significantly induce PGC-1α, and increase both metabolism and mitochondrial content in skeletal muscle.
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Bracco, D., J. M. Ferrarra, M. J. Arnaud, E. Jequier, and Y. Schutz. "Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women." American Journal of Physiology-Endocrinology and Metabolism 269, no. 4 (October 1, 1995): E671—E678. http://dx.doi.org/10.1152/ajpendo.1995.269.4.e671.
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The magnitude of coffee-induced thermogenesis and the influence of coffee ingestion on substrate oxidation were investigated in 10 lean and 10 obese women, over two 24-h periods in a respiratory chamber. On one occasion the subjects consumed caffeinated coffee and on the other occasion, decaffeinated coffee. The magnitude of thermogenesis was smaller in obese (4.9 +/- 2.0%) than in lean subjects (7.6 +/- 1.3%). The thermogeneic response to caffeine was prolonged during the night in lean women only. The coffee-induced stimulation of energy expenditure was mediated by a concomitant increase in lipid and carbohydrate oxidation. During the next day, in postabsorptive basal conditions, the thermogenic effect of coffee had vanished, but a significant increase in lipid oxidation was observed in both groups. The magnitude of this effect was, however, blunted in obese women (lipid oxidation increased by 29 and 10% in lean and obese women, respectively). Caffeine increased urinary epinephrine excretion. Whereas urinary caffeine excretion was similar in both groups, obese women excreted more theobromine, theophylline, and paraxanthine than lean women. Despite the high levels of urinary methylxanthine excretion, thermogenesis and lipid oxidation were less stimulated in obese than in lean subjects.
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Fenster, L., C. Quale, R. A. Hiatt, M. Wilson, G. C. Windham, and N. L. Benowitz. "Rate of Caffeine Metabolism and Risk of Spontaneous Abortion." American Journal of Epidemiology 147, no. 5 (March 1, 1998): 503–10. http://dx.doi.org/10.1093/oxfordjournals.aje.a009477.
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Masi, Camilla, Caterina Dinnella, Nicola Pirastu, John Prescott, and Erminio Monteleone. "Caffeine metabolism rate influences coffee perception, preferences and intake." Food Quality and Preference 53 (October 2016): 97–104. http://dx.doi.org/10.1016/j.foodqual.2016.06.002.
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Wu, Shou En, and Wei-Liang Chen. "Exploring the Association between Urine Caffeine Metabolites and Urine Flow Rate: A Cross-Sectional Study." Nutrients 12, no. 9 (September 13, 2020): 2803. http://dx.doi.org/10.3390/nu12092803.
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Examination of urine excretion of caffeine metabolites has been a simple but common way to determine the metabolism and effect of caffeine, but the relationship between urinary metabolites and urine flow rate is less discussed. To explore the association between urinary caffeine metabolite levels and urine flow rate, 1571 participants from the National Health and Nutrition Examination Survey (NHANES) 2011–2012 were enrolled in this study. We examined the association between urinary caffeine metabolites and urine flow rate with linear regression models. Separate models were constructed for males and females and for participants aged <60 and ≥60 years old. A positive association was found between concentrations of several urinary caffeine metabolites and urine flow rate. Three main metabolites, namely, paraxanthine, theobromine, and caffeine, showed significance across all subgroups. The number of caffeine metabolites that revealed flow-dependency was greater in males than in females and was also greater in the young than in the elderly. Nevertheless, the general weakness of NHANES data, a cross-sectional study, is that the collection is made at one single time point rather than a long-term study. In summary, urinary concentrations of several caffeine metabolites showed a positive relationship with the urine flow rate. The trend is more noticeable in males and in young subgroups.
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Brown, Christopher R., Peyton Jacob III, Margaret Wilson, and Neal L. Benowitz. "Changes in rate and pattern of caffeine metabolism after cigarette abstinence." Clinical Pharmacology and Therapeutics 43, no. 5 (May 1988): 488–91. http://dx.doi.org/10.1038/clpt.1988.63.
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Pascua, Stephanie M., Gabrielle E. McGahey, Ning Ma, Justin J. Wang, and Michelle A. Digman. "Caffeine and Cisplatin Effectively Targets the Metabolism of a Triple-Negative Breast Cancer Cell Line Assessed via Phasor-FLIM." International Journal of Molecular Sciences 21, no. 7 (April 1, 2020): 2443. http://dx.doi.org/10.3390/ijms21072443.
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Triple-negative tumor cells, a malignant subtype of breast cancer, lack a biologically targeted therapy. Given its DNA repair inhibiting properties, caffeine has been shown to enhance the effectiveness of specific tumor chemotherapies. In this work, we have investigated the effects of caffeine, cisplatin, and a combination of the two as potential treatments in energy metabolism for three cell lines, triple-negative breast cancer (MDA-MB-231), estrogen-receptor lacking breast cancer (MCF7) and breast epithelial cells (MCF10A) using a sensitive label-free approach, phasor-fluorescence lifetime imaging microscopy (phasor-FLIM). We found that solely using caffeine to treat MDA-MB-231 shifts their metabolism towards respiratory-chain phosphorylation with a lower ratio of free to bound NADH, and a similar trend is seen in MCF7. However, MDA-MB-231 cells shifted to a higher ratio of free to bound NADH when cisplatin was added. The combination of cisplatin and caffeine together reduced the survival rate for MDA-MD231 and shifted their energy metabolism to a higher fraction of bound NADH indicative of oxidative phosphorylation. The FLIM and viability results of MCF10A cells demonstrate that the treatments targeted cancer cells over the normal breast tissue. The identification of energy metabolism alteration could open up strategies of improving chemotherapy for malignant breast cancer.
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Lopes, Cátia R., Andreia Oliveira, Ingride Gaspar, Matilde S. Rodrigues, Joana Santos, Eszter Szabó, Henrique B. Silva, et al. "Effects of Chronic Caffeine Consumption on Synaptic Function, Metabolism and Adenosine Modulation in Different Brain Areas." Biomolecules 13, no. 1 (January 4, 2023): 106. http://dx.doi.org/10.3390/biom13010106.
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Adenosine receptors mainly control synaptic function, and excessive activation of adenosine receptors may worsen the onset of many neurological disorders. Accordingly, the regular intake of moderate doses of caffeine antagonizes adenosine receptors and affords robust neuroprotection. Although caffeine intake alters brain functional connectivity and multi-omics analyses indicate that caffeine intake modifies synaptic and metabolic processes, it is unclear how caffeine intake affects behavior, synaptic plasticity and its modulation by adenosine. We now report that male mice drinking caffeinated water (0.3 g/L) for 2 weeks were behaviorally indistinguishable (locomotion, mood, memory) from control mice (drinking water) and displayed superimposable synaptic plasticity (long-term potentiation) in different brain areas (hippocampus, prefrontal cortex, amygdala). Moreover, there was a general preservation of the efficiency of adenosine A1 and A2A receptors to control synaptic transmission and plasticity, although there was a tendency for lower levels of endogenous adenosine ensuring A1 receptor-mediated inhibition. In spite of similar behavioral and neurophysiological function, caffeine intake increased the energy charge and redox state of cortical synaptosomes. This increased metabolic competence likely involved a putative increase in the glycolytic rate in synapses and a prospective greater astrocyte–synapse lactate shuttling. It was concluded that caffeine intake does not trigger evident alterations of behavior or of synaptic plasticity but increases the metabolic competence of synapses, which might be related with the previously described better ability of animals consuming caffeine to cope with deleterious stimuli triggering brain dysfunction.
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Del Rio, G., R. Menozzi, G. Zizzo, A. Avogaro, P. Marrama, and A. Velardo. "Increased cardiovascular response to caffeine in perimenopausal women before and during estrogen therapy." European Journal of Endocrinology 135, no. 5 (November 1996): 598–603. http://dx.doi.org/10.1530/eje.0.1350598.
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Del Rio G, Menozzi R, Zizzo G, Avogaro A, Marrama P, Velardo A. Increased cardiovascular response to caffeine in perimenopausal women before and during estrogen therapy. Eur J Endocrinol 1996; 135:598–603. ISSN 0804–4643 Perimenopause and menopause may be associated with an increased risk of cardiovascular disease, so we have investigated the cardiovascular and catecholamine response to caffeine in perimenopausal women compared to young cycling premenopausal subjects. Caffeine (250 mg per os) was administered to nine perimenopausal women and nine premenopausal women. The perimenopausal women repeated the test after 4 months of percutaneous estrogen replacement therapy. Systolic and diastolic blood pressure, pulse rate, plasma norepinephrine, epinephrine, glucose, insulin and free fatty acids were determined at 0, 15, 30, 45, 60, 90 and 120 min after caffeine administration. No differences were found in the basal values of systolic blood pressure, diastolic blood pressure, pulse rate, norepinephrine, epinephrine, insulin, glucose and free fatty acids between perimenopausal women, both before and after therapy, and premenopausal women. Caffeine induced a higher increase of systolic (F = 4.9; p < 0.05) and diastolic blood pressure (F = 4.7; p < 0.05) in perimenopausal women before and during estrogen therapy as compared with premenopausal women. Pulse rate increased significantly only in perimenopausal women before therapy (F = 6.5; p < 0.03). These data show that perimenopause either before or during short-term estrogen therapy is associated with enhanced cardiovascular reactivity to caffeine. This phenomenon is not due to increased adrenergic and metabolic responses. Graziano Del Rio, Department of Internal Medicine via del Pozzo, 71 41100 Modena, Italy
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Arciero, Paul J., and Michael J. Ormsbee. "Relationship of blood pressure, behavioral mood state, and physical activity following caffeine ingestion in younger and older women." Applied Physiology, Nutrition, and Metabolism 34, no. 4 (August 2009): 754–62. http://dx.doi.org/10.1139/h09-068.
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The purpose of this study was to examine the age-related differences in blood pressure, heart rate, and behavioral mood state after caffeine ingestion in younger and older women. Using a placebo-controlled, double-blind design, 10 younger (Y; 18–22 years) and 10 older (O; 50–67 years) healthy women who were moderate consumers of caffeine (self-reported mean intake: Y, 139 ± 152 mg·day–1; O, 204 ± 101 mg·day–1) were investigated. All volunteers were characterized for fasting plasma glucose, insulin, free-fatty acids and caffeine levels, body composition, cardiovascular fitness, physical activity, and energy intake. Before and after placebo and caffeine ingestion (5 mg·kg–1 fat-free mass; ~208–270 mg) test days, the following variables were measured in all subjects: plasma caffeine levels, heart rate, blood pressure, and behavioral mood state. Results showed that, following caffeine ingestion: (i) both systolic and diastolic blood pressure (SBP and DBP, respectively) increased significantly (p < 0.05) in the older women (SBP, 128.4 ± 14.2 vs. 132.1 ± 13.0 mm Hg (3%); DBP, 80.2 ± 6.9 vs. 83.4 ± 7.5 mm Hg (4%), whereas only DBP increased in the youger women (67.1 ± 4.7 vs. 69.9 ± 5.4 mm Hg (4.2%); p < 0.05); (ii) heart rate decreased significantly (Y, 59.2 ± 8.7 to 53.9 ± 10.6 beats·min–1 (p < 0.05); O, 61.9 ± 9.2 to 59.2 ± 8.4 beats·min–1 (p < 0.05)) in both groups; and (iii) self-reported feelings of tension and vigor increased and feelings of fatigue decreased (p < 0.05) in younger women, whereas depression decreased (p ≤ 0.05) in older women. Self-reported level of physical activity was inversely related to change in DBP following caffeine ingestion in younger women. In conclusion, blood pressure response is augmented and subjective feelings of behavioral mood state are attenuated to a greater degree in older than in younger women following acute caffeine ingestion. Less physically active younger women are more vulnerable to the pressor response to caffeine than more active younger women. It should be noted that these findings are limited to moderate consumers of caffeine who abstained for 48 h prior to testing, and who ingested caffeine in pill form (~240 mg).
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Polinski, Kristen, Alexandra Purdue-Smithe, Sonia Robinson, Sifang Kathy Zhao, Sunni Mumford, Karen Schliep, Robert Silver, Enrique Schisterman, and Edwina Yeung. "Maternal Caffeine Intake and DNA Methylation in Newborn Cord Blood." Current Developments in Nutrition 5, Supplement_2 (June 2021): 802. http://dx.doi.org/10.1093/cdn/nzab046_099.
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Abstract Objectives Prior research has suggested that epigenetic mechanisms may underly associations between maternal caffeine intake and adverse childhood metabolic outcomes. We examined preconception and early pregnancy maternal caffeine exposure with DNA methylation (DNAm) patterns in the cord blood of 378 neonates. Methods DNAm was profiled by the Infinium MethylationEPIC BeadChip in women enrolled in the EAGeR Trial. Maternal serum was collected 1–2 cycles preconception and at 8 weeks gestation as was self-reported caffeinated beverage intake through standardized questionnaires or daily diaries. Serum caffeine, paraxanthine, and theobromine were measured by liquid chromatography mass spectrometry. We performed multivariable robust linear regression to assess associations between maternal caffeine and methylation β-values and Ingenuity Pathway Analysis to evaluate biologic implications. Results Preconceptionally, 65%, 21% and 7% reported any soda, coffee or tea intake, respectively with the majority consuming on average ≤ 1 serving/day. Preconception self-reported intake compared to no intake was associated with DNAm at cg09002832 near GLIS3 (false discovery rate [FDR] p = 0.036). No associations with self-reported intake were found during pregnancy. Preconception serum markers were not associated with individual CpG sites (FDR > 5%), though pregnancy theobromine (tertile 2 vs 1) was associated with DNAm at cg09460369 near RAB2A (FDR p = 0.012). Overlapping pathways for the top 100 CpG sites identified in the preconception intake and pregnancy theobromine analyses elucidated cell cycle and lipid metabolism processes. Conclusions Few differences in DNAm were identified in association with maternal caffeine intake in this low consumption population. DNAm changes from preconception caffeine or pregnancy theobromine exposure may be linked to signaling networks involving lipid metabolism, but further research among women with higher caffeine and theobromine exposure is warranted. Funding Sources Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
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Dumont, Larry J., Swaroopa Yerrabothala, Gregory J. Tsongalis, Xiaoyun Fu, James C. Zimring, and John Roback. "Correlation Between Red Blood Cell Survival and Cytochrome P450 1A2 Enzyme Activity." Blood 122, no. 21 (November 15, 2013): 3658. http://dx.doi.org/10.1182/blood.v122.21.3658.3658.
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Abstract Background Autologous red blood cell (RBC) 24h recovery in healthy volunteers is known to be highly variable between subjects, but repeatable within subjects. We previously performed metabolic screening on 2 subjects (HR) with consistently high historical 24h recoveries (85%, 88%) and 2 subjects (LR) with lower recoveries (74%, 74%). We observed that the HR subjects had lower RBC caffeine levels than the grand average for the study, while LR subjects had higher levels. Because these differences were not explained by the subjects’ self-reported caffeine consumption, we hypothesized that they may be due to differences in caffeine metabolism and clearance that correlate with RBC survival following storage and transfusion Caffeine (1,3,7-trimethylxanthine - 137X ) is demethylated by cytochrome P450 1A2 (CYP1A2) to form 81.5% paraxanthine (1,7-dimethylxanthine -17X), 5.4% theophylline, and 10.8% theobromine. Single nucleotide polymorphisms (SNPs) in CYP1A2 results in variation in enzyme activity. Polymorphisms in the aromatic hydrocarbon receptor (AHR) may also affect caffeine clearance. Caffeine clearance is the gold standard assay for in vivo determination of CYP1A2 activity, and a 4 hour point estimate may be obtained using the plasma 17X/137X ratio following caffeine challenge. Methods We performed focused genotyping of the 4 index subjects for 3 CYP1A2 SNPs (rs762551, rs24708932, and rs2472297) and 2 AHR SNPs (rs6968865 and rs4410790), all previously reported as affecting caffeine metabolism. DNA was extracted from whole blood and SNP genotyping performed using real time PCR with Taqman probes on the AB 7500 FAST system. Caffeine metabolic clearance was determined in 3 of 4 index subjects by a controlled challenge. 100mg caffeine PO was administered in apple juice to subjects that had abstained from caffeine for 24h. Venous blood was obtained pre and 4h post caffeine administration. Plasma was separated and frozen within 2h of collection. Caffeine and metabolites were quantified by liquid chromatography-mass spectrometry (LC-MS) with isotopically labeled internal standards. The single point clearance rate of caffeine was estimated as the ratio of the 4h difference from baseline in (17x+theophiline):caffeine. Results The one HR who could be recalled for caffeine challenge had the highest 4h caffeine metabolic clearance ratio; the two LR subjects had lower ratios (see Table). HR were homozygous (A/A) for CYP1A2 rs762551, while the 2 LR subjects were heterozygous (A/C) for CYP1A2 rs762551. The correlations between SNP results and caffeine clearance agree with known CYP1A2 activities for these genotypes. Other CYP1A2 and AHR SNPs did not partition with the RBC recoveries, caffeine levels or caffeine metabolic ratios. Conclusion In a small number of subjects (n-=2 from each group), historical in vivo RBC recovery was observed to be associated with peripheral blood caffeine levels, caffeine metabolic clearance, and known functional polymorphisms in the CYP1A2 gene. In the event that these associations persist upon subsequent studies with more participants, then additional trials will be needed to test if the caffeine (or its metabolites) has a direct effect upon RBCs or if caffeine clearance is a surrogate marker of CYP1A2 function or activity of other metabolic pathways that can regulate RBC survival after storage and transfusion. Disclosures: Zimring: Immucor Inc.: Research Funding; Terumo: Research Funding; Haemonetics: Consultancy; Cerus: Honoraria.
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Packard, P. T., and R. R. Recker. "Caffeine does not affect the rate of gain in spine bone in young women." Osteoporosis International 6, no. 2 (March 1996): 149–52. http://dx.doi.org/10.1007/bf01623939.
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Arnanda, Bramita Beta, Sri Suparwitri, and Pinandi Sri Pudyani. "Effect of caffeine in chocolate (Theobroma cacao) on the alveolar bone mineral density in guinea pigs (Cavia cobaya) with orthodontic tooth movement." Dental Journal (Majalah Kedokteran Gigi) 53, no. 3 (September 15, 2020): 164. http://dx.doi.org/10.20473/j.djmkg.v53.i3.p164-169.
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Background: The benefits of chocolate have attracted significant attention from clinicians, especially the active compound of caffeine on bone metabolism. The bone density significantly affected the rate of tooth movement. Purpose: This study aims to analyse the effect of the dose and the duration of caffeine consumption in chocolate on alveolar bone mineral density in orthodontic tooth movement. Methods: Forty-eight male guinea pigs (Cavia cobaya) aged between 3-4 months and weighing 300-350 grams were divided into four groups (group A control, group B caffeine dose of 2.3 mg, group C caffeine dose of 3.45 mg, and group D caffeine dose of 4.6 mg). An open coil spring was applied to the mandibular inter-incisor with an orthodontic force of 35 grams. Guinea pigs were sacrificed using lethal doses of anaesthetics on days 0, 1, 7, and 14 after an orthodontic appliance installation. Mandibular alveolar bone mineral density in compression sites was analysed with an atomic absorption spectrophotometer (AAS). Experiment data results were analysed using two-way ANOVA with a 95% degree of confidence. Results: Caffeine consumption with a dose of 4.6 mg on day 7 had the lowest alveolar bone mineral density and the highest was at a dose of 2.3 mg on day 14, but there were no differences between the dose groups, the duration groups and interactions between both of them (p>0.05). Conclusion: The consumption of caffeine in chocolate did not decrease the bone mineral density in the compression site of orthodontic tooth movement.
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Suvi, Silva, Saima Timpmann, Maria Tamm, Martin Aedma, Kairi Kreegipuu, and Vahur Ööpik. "Effects of caffeine on endurance capacity and psychological state in young females and males exercising in the heat." Applied Physiology, Nutrition, and Metabolism 42, no. 1 (January 2017): 68–76. http://dx.doi.org/10.1139/apnm-2016-0206.
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Acute caffeine ingestion is considered effective in improving endurance capacity and psychological state. However, current knowledge is based on the findings of studies that have been conducted on male subjects mainly in temperate environmental conditions, but some physiological and psychological effects of caffeine differ between the sexes. The purpose of this study was to compare the physical performance and psychological effects of caffeine in young women and men exercising in the heat. Thirteen male and 10 female students completed 2 constant-load walks (60% of thermoneutral peak oxygen consumption on a treadmill until volitional exhaustion) in a hot-dry environment (air temperature, 42 °C; relative humidity, 20%) after caffeine (6 mg·kg–1) and placebo (wheat flour) ingestion in a double-blind, randomly assigned, crossover manner. Caffeine, compared with placebo, induced greater increases (p < 0.05) in heart rate (HR) and blood lactate concentrations in both males and females but had no impact on rectal or skin temperatures or on walking time to exhaustion in subjects of either gender. Caffeine decreased (p < 0.05) ratings of perceived exertion and fatigue in males, but not in females. In females, but not in males, a stronger belief that they had been administered caffeine was associated with a shorter time to exhaustion. In conclusion, acute caffeine ingestion increases HR and blood lactate levels during exercise in the heat, but it has no impact on thermoregulation or endurance capacity in either gender. Under exercise-heat stress, caffeine reduces ratings of perceived exertion and fatigue in males but not in females.
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Bottoms, L., H. Hurst, A. Scriven, F. Lynch, J. Bolton, L. Vercoe, Z. Shone, G. Barry, and J. Sinclair. "The effect of caffeine mouth rinse on self-paced cycling performance." Comparative Exercise Physiology 10, no. 4 (January 1, 2014): 239–45. http://dx.doi.org/10.3920/cep140015.
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The aim of the study was to determine whether caffeine mouth rinse would improve 30 min self-paced cycling trial. Twelve healthy active males (age 20.5±0.7 years, mass 87.4±18.3 kg) volunteered for the study. They attended the laboratory on 3 separate occasions performing a 30 min self-paced cycling trial. On one occasion water was given as a mouth rinse for 5 s (PLA), on another occasion a 6.4% maltodextrin (CHO) solution was given for 5 s and finally a caffeine solution (containing 32 mg of caffeine dissolved in 125 ml water; CAF) was given for 5 s. Distance cycled, heart rate, ratings of perceived exertion, cadence, speed and power output were recorded throughout all trials. Distance cycled during the CAF mouth rinse trial (16.2±2.8 km) was significantly greater compared to PLA trial (14.9±2.6 km). There was no difference between CHO and CAF trials (P=0.89). Cadence, power and velocity were significantly greater during the CAF trial compared to both PLA and CHO (P<0.05). There were no differences between trials for heart rate and perceived exertion (P>0.05). Caffeine mouth rinse improves 30 min cycling performance by allowing the participant to increase cadence, power and velocity without a concurrent increase in perceived exertion and heart rate.
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Marinda Sukmawanta, Shafara Najla, Dyah Ratna Wulan, Kristina Widjajanti, Noor Isnaini Azkiya, and Yanty Maryanty. "Ekstrak Kafein sebagai Inhibitor Korosi Alami pada Logam Aluminium dalam Media Larutan Asam Sulfat dan Biosolar." Jurnal Riset Kimia 13, no. 1 (March 13, 2022): 68–75. http://dx.doi.org/10.25077/jrk.v13i1.488.
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This research, the caffeine extract of arabica coffee beans, cacao beans, and black tea leaves will be tested as a corrosion inhibitor on aluminium in an acidic environment and in biodiesel containing acid. This condition resembles the metabolism of microorganisms in biodiesel which produces H2SO4 as one of the causes of corrosion. Arabica coffee, cacao beans and black tea are natural organic ingredients containing caffeine which can inhibit corrosion. In the maceration process used a variable ratio of 70% ethanol solvent with organic matter, namely 225 grams of organic matter with 450 grams of ethanol and 150 grams of organic matter with 450 grams of ethanol. Concentration of caffeine extract from arabika coffee, cacao beans, and black tea leaves was obtained based on HPLC analysis at an effluent rate of 0.8 mL/min. The corrosion inhibition efficiency test on aluminium was observed at 0, 1, 4, 7 and 10 days of immersion. The previously used aluminium has been corroded with 12% H2SO4. The corrosion inhibition efficiency test on aluminium was observed at 0, 1, 4, 7 and 10 days of immersion. The best inhibitor results on aluminium soaked in biosolar containing 12% H2SO4 is tea 1.234,313 ppm with a corrosion rate of 1.6x10-4 g/cm2 day on day 1 to 2.5x10-4 g/ cm2 day on day 10 with an inhibition efficiency of 99%. While the aluminium soaked in H2SO4 12% is tea containing caffeine of 684.373 ppm with a corrosion rate of 1.3 x10-4 g/ cm2 day on day 1 to 3.3x10-4 g/ cm2 day on day 10 with an inhibition efficiency of 64%. The longer the immersion time of aluminium in H2SO4 media with the addition of organic inhibitors, the lower the corrosion rate value because the inhibitors form a layer that protects the aluminium.
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Snowdowne, K. W. "Subcontracture depolarizations increase sarcoplasmic ionized calcium in frog skeletal muscle." American Journal of Physiology-Cell Physiology 248, no. 5 (May 1, 1985): C520—C526. http://dx.doi.org/10.1152/ajpcell.1985.248.5.c520.
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The hypothesis that the sarcoplasmic concentration of ionized calcium (Cai) of frog skeletal muscle may control its rate of metabolism was examined by monitoring the changes in Cai due to perturbations that are known, from the work of previous investigators, to alter the rate of metabolism. Cai was measured with aequorin, which was microinjected into isolated fibers in sufficient quantity to detect basal Cai. When these fibers were exposed to 5-18 mM KCl, 75 mM RbCl2, or 100 mM CsCl2, there was an increase in the aequorin signal. The potassium-evoked increase in the aequorin signal was diminished by an increase in the extracellular concentration of Ca or by Ca-free media containing 3.6 mM Mg, Mn, Sr, or Zn but was enhanced by subcontracture concentrations of caffeine or media containing nitrate instead of chloride. These results are consistent with the hypothesis that Cai may control the rate of metabolism in frog skeletal muscle fibers.
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Beaven, C. Martyn, Peter Maulder, Adrian Pooley, Liam Kilduff, and Christian Cook. "Effects of caffeine and carbohydrate mouth rinses on repeated sprint performance." Applied Physiology, Nutrition, and Metabolism 38, no. 6 (June 2013): 633–37. http://dx.doi.org/10.1139/apnm-2012-0333.
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Our purpose was to examine the effectiveness of carbohydrate and caffeine mouth rinses in enhancing repeated sprint ability. Previously, studies have shown that a carbohydrate mouth rinse (without ingestion) has beneficial effects on endurance performance that are related to changes in brain activity. Caffeine ingestion has also demonstrated positive effects on sprint performance. However, the effects of carbohydrate or caffeine mouth rinses on intermittent sprints have not been examined previously. Twelve males performed 5 × 6-s sprints interspersed with 24 s of active recovery on a cycle ergometer. Twenty-five milliliters of either a noncaloric placebo, a 6% glucose, or a 1.2% caffeine solution was rinsed in the mouth for 5 s prior to each sprint in a double-blinded and balanced cross-over design. Postexercise maximal heart rate and perceived exertion were recorded, along with power measures. A second experiment compared a combined caffeine-carbohydrate rinse with carbohydrate only. Compared with the placebo mouth rinse, carbohydrate substantially increased peak power in sprint 1 (22.1 ± 19.5 W; Cohen's effect size (ES), 0.81), and both caffeine (26.9 ± 26.9 W; ES, 0.71) and carbohydrate (39.1 ± 25.8 W; ES, 1.08) improved mean power in sprint 1. Experiment 2 demonstrated that a combination of caffeine and carbohydrate improved sprint 1 power production compared with carbohydrate alone (36.0 ± 37.3 W; ES, 0.81). We conclude that carbohydrate and (or) caffeine mouth rinses may rapidly enhance power production, which could have benefits for specific short sprint exercise performance. The ability of a mouth-rinse intervention to rapidly improve maximal exercise performance in the absence of fatigue suggests a central mechanism.
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Lopes-Silva, João Paulo, Jonatas Ferreira da Silva Santos, and Emerson Franchini. "Can caffeine supplementation reverse the effect of time of day on repeated-sprint exercise performance?" Applied Physiology, Nutrition, and Metabolism 44, no. 2 (February 2019): 187–93. http://dx.doi.org/10.1139/apnm-2018-0373.
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The aim of this study was to evaluate if caffeine can reduce the negative influence of diurnal variations on repeated-sprint performance, in addition to investigating if caffeine in the afternoon would potentiate performance compared with the morning. Thirteen physically active men took part in this randomized, double-blind, placebo-controlled and crossover study. All participants underwent a repeated-sprint ability test (10 × 6 s cycle sprints, with 30 s of rest) at 60 min after ingestion of either 5 mg·kg−1 or placebo under 4 different conditions: morning with caffeine ingestion, morning with placebo ingestion, afternoon with caffeine ingestion, and afternoon with placebo ingestion. Total work, peak power (PP) and anaerobic power reserve (APR) were assessed. Oxygen uptake, heart rate, lactate concentration, and rating of perceived exertion were also measured during the repeated-sprint test. Total work (+8%, d = 0.2, small), PP (+6%, d = 0.2), and APR (+9%, d = 0.2) were significantly higher in the afternoon when compared with morning. However, physiological responses were not different between caffeine and placebo conditions. Repeated-sprint (10 × 6 s cycle sprint) performance was influenced by time of day, with lower performance in the morning compared with the afternoon. However, caffeine supplementation did not prevent the reduction in performance in the morning or improve performance in the afternoon.
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Delleli, Slaheddine, Ibrahim Ouergui, Hamdi Messaoudi, Khaled Trabelsi, Achraf Ammar, Jordan M. Glenn, and Hamdi Chtourou. "Acute Effects of Caffeine Supplementation on Physical Performance, Physiological Responses, Perceived Exertion, and Technical-Tactical Skills in Combat Sports: A Systematic Review and Meta-Analysis." Nutrients 14, no. 14 (July 21, 2022): 2996. http://dx.doi.org/10.3390/nu14142996.
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Although the effects of caffeine supplementation on combat sports performance have been extensively investigated, there is currently no consensus regarding its ergogenic benefits.This systematic review with meta-analysis aimed to summarize the studies investigating the effects of caffeine supplementation on different aspects of performance in combat sports and to quantitatively analyze the results of these studies to better understand the ergogenic effect of caffeine on combat sports outcomes. A systematic search for randomized placebo-controlled studies investigating the effects of caffeine supplementation on combat sports’ performance was performed through Scopus, Pubmed, Web of Science and Cochrane Library databases up to 18 April 2022. Random-effects meta-analyses of standardized mean differences (Hedge’s g) were performed to analyze the data. Twenty-six studies of good and excellent methodological quality (based on the Pedro scale) fulfilled the inclusion criteria. The meta-analysis results revealed caffeine has a small but evident effect size (ES) on handgrip strength (ES = 0.28; 95% CI: 0.04 to 0.52; p = 0.02), and total number of throws during the special judo fitness test (SJFT) (ES = 0.42; 95% CI: 0.06 to 0.78; p = 0.02). Regarding the physiological responses, caffeine increased blood lactate concentration ([La]) in anaerobic exercise (ES = 1.23; 95% CI: 0.29 to 2.18; p = 0.01) and simulated combat (ES = 0.91; 95% CI: 0.34 to 1.47; p = 0.002). For Heart Rate (HR), caffeine increased HR final (ES = 0.31; 95% CI: 0.11 to 0.52; p = 0.003), and HR 1min (ES = 0.20; 95% CI 0.004 to 0.40; p = 0.045). However, caffeine had no impact on the countermovement jump height, the SJFT index, the judogi strength-endurance test, the number and duration of offensive actions, HR at the end of the fight, and the rating of perceived exertion. Caffeine supplementation may be ergogenic for a range of combat sports aspects involving isometric strength, anaerobic power, reaction time, and anaerobic metabolism. However, supplementation effects might be ineffective under certain circumstances, indicating supplementation needs to take into account the performance metric in question prior to creating a dosing protocol.
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Moschino, Laura, Sanja Zivanovic, Caroline Hartley, Daniele Trevisanuto, Eugenio Baraldi, and Charles Christoph Roehr. "Caffeine in preterm infants: where are we in 2020?" ERJ Open Research 6, no. 1 (January 2020): 00330–2019. http://dx.doi.org/10.1183/23120541.00330-2019.
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The incidence of preterm birth is increasing, leading to a growing population with potential long-term pulmonary complications. Apnoea of prematurity (AOP) is one of the major challenges when treating preterm infants; it can lead to respiratory failure and the need for mechanical ventilation. Ventilating preterm infants can be associated with severe negative pulmonary and extrapulmonary outcomes, such as bronchopulmonary dysplasia (BPD), severe neurological impairment and death. Therefore, international guidelines favour non-invasive respiratory support. Strategies to improve the success rate of non-invasive ventilation in preterm infants include pharmacological treatment of AOP. Among the different pharmacological options, caffeine citrate is the current drug of choice. Caffeine is effective in reducing AOP and mechanical ventilation and enhances extubation success; it decreases the risk of BPD; and is associated with improved cognitive outcome at 2 years of age, and pulmonary function up to 11 years of age. The commonly prescribed dose (20 mg·kg−1 loading dose, 5–10 mg·kg−1 per day maintenance dose) is considered safe and effective. However, to date there is no commonly agreed standardised protocol on the optimal dosing and timing of caffeine therapy. Furthermore, despite the wide pharmacological safety profile of caffeine, the role of therapeutic drug monitoring in caffeine-treated preterm infants is still debated. This state-of-the-art review summarises the current knowledge of caffeine therapy in preterm infants and highlights some of the unresolved questions of AOP. We speculate that with increased understanding of caffeine and its metabolism, a more refined respiratory management of preterm infants is feasible, leading to an overall improvement in patient outcome.
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Zhang, Meijia, Haiyan Hong, Bo Zhou, Shiying Jin, Chao Wang, Maoyong Fu, Songbo Wang, and Guoliang Xia. "The expression of atrial natriuretic peptide in the oviduct and its functions in pig spermatozoa." Journal of Endocrinology 189, no. 3 (June 2006): 493–507. http://dx.doi.org/10.1677/joe.1.06483.
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Locally synthesized atrial natriuretic peptide (ANP) and its receptors have been found in reproductive tissues of various mammals, and play an important role in the acrosome reaction of human sperm. The objective of the present study was to examine the expression of ANP and its receptors in pig spermatozoa and oviduct, and the effect of ANP on pig spermatozoa function. The expression of ANP and its receptors was analyzed by RT-PCR. Only natriuretic peptide receptors-A (NPRA) mRNA was detected in fresh sperm. While the levels of natriuretic peptide receptors-C (NPRC) mRNA were low with no obvious change among different oviductal phases, the levels of ANP mRNA were high in oviduct(OT)1 , OT3 and OT5, but were very low in OT2. On the other hand, the levels of NPRA mRNA were low in OT1 and OT2, increased in OT3 and reached a maximum in OT4 and OT5. Western blot analysis revealed that the level of ANP was high in OT1, decreased in OT2 and OT3, and arrived at the nadir in OT4 and OT5. The effect of ANP on spermatozoa function was studied by the acrosome reaction and IVF. Incubation with ANP for 1 h significantly induced acrosome reaction of preincubated spermatozoa, and maximal response of acrosome reaction (34.1 ± 2.3%) was achieved at 1 nM ANP treatment. Both C-ANP-(4–23), a selective ligand of NPRC, and caffeine had no effect on the acrosome reaction. The stimulatory effect of ANP on acrosome reaction could be mimicked by the permeable cGMP analog, 8-Br-cGMP. ANP and caffeine had a similar effect on improving the oocytes penetration rate, polyspermy rate and the average number of sperm per penetrated oocyte. Also, ANP treatment had a similar effect on cleavage rate, blastocyst formation rate and the number of cells per blastocyst as that of caffeine treatment. The effects of ANP on the acrosome reaction and the parameters of oocyte penetration could be blocked by cGMP-dependent protein kinase (PKG) inhibitors KT5823 and/or Rp-8-pCPT-cGMPS. These results suggest that the expression of ANP in the oviduct may be involved in the regulation of the acrosome reaction and the fertilising ability of pig spermatozoa, and the PKG pathway possibly participates in the process.
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Antonov, A. G., V. D. Vybornov, M. Y. Balandin, P. D. Rybakova, V. A. Badtieva, D. B. Nikityuk, and Ye A. Rozhkova. "Practical guidelines for standardising the measurement of resting metabolism by indirect calorimetry: a literature review." Sports medicine: research and practice 12, no. 2 (November 3, 2022): 96–104. http://dx.doi.org/10.47529/2223-2524.2022.2.11.
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Accurate resting metabolic rate readings are essential for dietary planning and body composition monitoring not only for healthy individuals but also for athletes. A number of factors can alter resting metabolic rate during its measurement by indirect calorimetry. The methodology used may affect the results of the study. A clear standardisation of this procedure is needed to obtain the most accurate results.Purpose: To review the literature to determine the optimal subject condition and methodology for the resting metabolism measurement procedure using indirect calorimetry.Materials and methods: A literature search was conducted in PubMed, MEDLINE and Cochrane Library databases. The query included key words and logical phrases: “calorimetry”, “indirect calorimetry”, “resting metabolic rate”, “energy metabolism”, “basal metabolism”, “standards”. Only English-language studies and human studies were considered. Additional information was identified because of the review and included in the review.Results: the parameters of standardization during the resting metabolism measurement procedure are described: consumption of food, ethanol, caffeine, nicotine; daily activities and physical activity; body position in space and environmental conditions during the measurement; actions of the specialist performing the procedure, etc. The article outlines effective methods for measuring resting metabolism to obtain the most accurate results in both healthy individuals and athletes.Conclusion: an attempt has been made to formulate precise methodological rules for standardisation and recommendations for measuring resting metabolism by indirect calorimetry.
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Jackson, Joshua G., and Stanley A. Thayer. "Mitochondrial Modulation of Ca2+-Induced Ca2+-Release in Rat Sensory Neurons." Journal of Neurophysiology 96, no. 3 (September 2006): 1093–104. http://dx.doi.org/10.1152/jn.00283.2006.
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Ca2+-induced Ca2+-release (CICR) from ryanodine-sensitive Ca2+ stores provides a mechanism to amplify and propagate a transient increase in intracellular calcium concentration ([Ca2+]i). A subset of rat dorsal root ganglion neurons in culture exhibited regenerative CICR when sensitized by caffeine. [Ca2+]i oscillated in the maintained presence of 5 mM caffeine and 25 mM K+. Here, CICR oscillations were used to study the complex interplay between Ca2+ regulatory mechanisms at the cellular level. Oscillations depended on Ca2+ uptake and release from the endoplasmic reticulum (ER) and Ca2+ influx across the plasma membrane because cyclopiazonic acid, ryanodine, and removal of extracellular Ca2+ terminated oscillations. Increasing caffeine concentration decreased the threshold for action potential-evoked CICR and increased oscillation frequency. Mitochondria regulated CICR by providing ATP and buffering [Ca2+]i. Treatment with the ATP synthase inhibitor, oligomycin B, decreased oscillation frequency. When ATP concentration was held constant by recording in the whole cell patch-clamp configuration, oligomycin no longer affected oscillation frequency. Aerobically derived ATP modulated CICR by regulating the rate of Ca2+ sequestration by the ER Ca2+ pump. Neither CICR threshold nor Ca2+ clearance by the plasma membrane Ca2+ pump were affected by inhibition of aerobic metabolism. Uncoupling electron transport with carbonyl cyanide p-trifluoromethoxy-phenyl-hydrazone or inhibiting mitochondrial Na+/Ca2+ exchange with CGP37157 revealed that mitochondrial buffering of [Ca2+]i slowed oscillation frequency, decreased spike amplitude, and increased spike width. These findings illustrate the interdependence of energy metabolism and Ca2+ signaling that results from the complex interaction between the mitochondrion and the ER in sensory neurons.
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Júdice, Pedro B., João P. Magalhães, Diana A. Santos, Catarina N. Matias, Ana Isabel Carita, Paulo A. S. Armada-Da-Silva, Luís B. Sardinha, and Analiza M. Silva. "A moderate dose of caffeine ingestion does not change energy expenditure but decreases sleep time in physically active males: a double-blind randomized controlled trial." Applied Physiology, Nutrition, and Metabolism 38, no. 1 (January 2013): 49–56. http://dx.doi.org/10.1139/apnm-2012-0145.
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Research on the effect of caffeine on energy expenditure (EE), physical activity (PA), and total sleep time (TST) during free-living conditions using objective measures is scarce. We aimed to determine the impact of a moderate dose of caffeine on TST, resting EE (REE), physical activity EE (PAEE), total EE (TEE), and daily time spent in sedentary, light, moderate, and vigorous intensity activities in a 4-day period and the acute effects on heart rate (HR) and EE in physically active males. Using a double-blind crossover trial (ClinicalTrials.gov ID: NCT01477294) with two conditions (4 days each with 3-day washout) randomly ordered as caffeine (5 mg/kg of body mass/day) and placebo (maltodextrin) administered twice per day (2.5 mg/kg), 30 nonsmoker males, low-caffeine users (<100 mg/day), aged 20–39, were followed. Body composition was assessed by dual-energy X-ray absorptiometry. PA was assessed by accelerometry, while a combined HR and movement sensor estimated EE and HR on the second hour after the first administration dose. REE was assessed by indirect calorimetry, and PAEE was calculated as [TEE − (REE + 0.1TEE)]. TST and daily food records were obtained. Repeated measures ANOVA and ANCOVA were used. After a 4-day period, adjusting for fat-free mass, PAEE, and REE, TST was reduced (p = 0.022) under caffeine intake, while no differences were found between conditions for REE, PAEE, TEE, and PA patterns. Also, no acute effects on HR and EE were found between conditions. Though a large individual variability was observed, our findings revealed no acute or long-term effects of caffeine on EE and PA but decreased TST during free-living conditions in healthy males.
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Masodsai, Kunanya, Thanachai Sahaschot, and Rungchai Chaunchaiyakul. "Cardiorespiratory, Metabolic, and Performance Changes from the Effects of Creatine and Caffeine Supplementations in Glucose–Electrolyte-Based Sports Drinks: A Double-Blind, Placebo-Controlled Study." Sports 11, no. 1 (December 22, 2022): 4. http://dx.doi.org/10.3390/sports11010004.
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The purpose of this study is to investigate the additive effects of creatine and caffeine on changes in the cardiorespiratory system, metabolism, and performance of soccer players. Seventeen male soccer players randomly ingested three sports drinks comprising the following: glucose–electrolyte-based (Drink 1, control; D1), glucose–electrolyte-based drink + 5 g creatine (Drink 2; D2), and glucose–electrolyte-based drink + 5 g creatine + 35 mg caffeine (Drink 3; D3) during a 15 min recovery period after the modified Loughborough Intermittent Shuttle Test (LIST) on a standard outdoor soccer field. Then, a 20-m repeated intermittent sprinting activity was performed. The results showed no significant differences in cardiorespiratory and gas exchange variables. The non-significant levels of blood glucose concentrations among drinks with higher blood lactate concentrations were detected in parallel with increased heart rate during intermittent sprinting as a result of exercise intensities. Significantly longer sprinting time was found in D3 than D1 (p < 0.05), with no significant differences between D2 and D3. From this study, we conclude that the additive effect of caffeine–creatine supplements in a glucose–electrolyte drink during the 15 min recovery period enhances repeated 20-m high-intensity running in soccer players with no negative effect on cardiorespiratory functions.
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Oskarsson, Johanna, and Kerry McGawley. "No individual or combined effects of caffeine and beetroot-juice supplementation during submaximal or maximal running." Applied Physiology, Nutrition, and Metabolism 43, no. 7 (July 2018): 697–703. http://dx.doi.org/10.1139/apnm-2017-0547.
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Dietary supplements such as caffeine and beetroot juice are used by athletes in an attempt to optimize performance and therefore gain an advantage in competition. The aim of this study was to investigate the individual and combined effects of caffeine and beetroot-juice supplementation during submaximal and maximal treadmill running. Seven males (maximal oxygen uptake: 59.0 ± 2.9 mL·kg–1·min–1) and 2 females (maximal oxygen uptake: 53.1 ± 11.4 mL·kg–1·min–1) performed a preliminary trial followed by 4 experimental test sessions. Each test session consisted of two 5-min submaximal running bouts (at ∼70% and 80% of maximal oxygen uptake) and a maximal 1-km time trial (TT) in a laboratory. Participants ingested 70 mL of concentrated beetroot juice containing either 7.3 mmol of nitrate (BR) or no nitrate (PBR) 2.5 h prior to each test session, then either caffeine (C) at 4.8 ± 0.4 (4.3–5.6) mg/kg of body mass or a caffeine placebo (PC) 45 min before each test session. The 4 test sessions (BR-C, BR-PC, PBR-C, and PBR-PC) were presented in a counterbalanced and double-blind manner. No significant differences were identified between the 4 interventions regarding relative oxygen uptake, running economy, respiratory exchange ratio, heart rate (HR), or rating of perceived exertion (RPE) at the 2 submaximal intensities (P > 0.05). Moreover, there were no significant differences in performance, maximum HR, peak blood lactate concentration, or RPE during the maximal TT when comparing the interventions (P > 0.05). In conclusion, no beneficial effects of supplementing with typical doses of caffeine, beetroot juice, or a combination of the two were observed for physiological, perceptual, or performance responses during submaximal or maximal treadmill running exercise.
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Kennedy, Michael D., Ashley V. Galloway, Leanne J. Dickau, and Megan K. Hudson. "The cumulative effect of coffee and a mental stress task on heart rate, blood pressure, and mental alertness is similar in caffeine-naïve and caffeine-habituated females." Nutrition Research 28, no. 9 (September 2008): 609–14. http://dx.doi.org/10.1016/j.nutres.2008.06.003.
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Richardson, T., A. Rozkovec, P. Thomas, J. Ryder, C. Meckes, and D. Kerr. "Influence of Caffeine on Heart Rate Variability in Patients With Long-Standing Type 1 Diabetes." Diabetes Care 27, no. 5 (April 26, 2004): 1127–31. http://dx.doi.org/10.2337/diacare.27.5.1127.
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Talanian, Jason L., and Lawrence L. Spriet. "Low and moderate doses of caffeine late in exercise improve performance in trained cyclists." Applied Physiology, Nutrition, and Metabolism 41, no. 8 (August 2016): 850–55. http://dx.doi.org/10.1139/apnm-2016-0053.
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The aim of the present study was to assess if low and moderate doses of caffeine delivered in a carbohydrate-electrolyte solution (CES) late in exercise improved time-trial (TT) performance. Fifteen (11 male, 4 female) cyclists (age, 22.5 ± 0.9 years; body mass, 69.3 ± 2.6 kg; peak oxygen consumption, 64.6 ± 1.9 mL·min−1·kg−1) completed 4 double-blinded randomized trials. Subjects completed 120 min of cycling at ∼60% peak oxygen consumption with 5 interspersed 120-s intervals at ∼82% peak oxygen consumption, immediately followed by 40-s intervals at 50 W. Following 80 min of cycling, subjects either ingested a 6% CES (PL), a CES with 100 mg (low dose, 1.5 ± 0.1 mg·kg body mass−1) of caffeine (CAF1), or a CES with 200 mg (moderate dose, 2.9 ± 0.1 mg·kg body mass−1) of caffeine (CAF2). Following the 120-min cycling challenge, cyclists completed a 6-kJ·kg body mass−1 TT. There was no difference between respiratory, heart rate, glucose, free fatty acid, body mass, hematocrit, or urine specific gravity measurements between treatments. The CAF2 (26:36 ± 0:22 min:s) TT was completed faster than CAF1 (27:36 ± 0:32 min:s, p < 0.05) and both CAF1 and CAF2 TTs were completed faster than PL (28:41 ± 0:38 min:s, p < 0.05). Blood lactate was similar between trials and rose to a greater extent during the TT (p < 0.05). In summary, both doses of caffeine delivered late in exercise improved TT performance over the PL trial and the moderate dose (CAF2) improved performance to a greater extent than the low dose (CAF1).
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Turley, Kenneth R., Travis DeSisso, and Jonathan W. Gerst. "Effects of Caffeine on Physiological Responses to Exercise: Boys versus Men." Pediatric Exercise Science 19, no. 4 (November 2007): 481–92. http://dx.doi.org/10.1123/pes.19.4.481.
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We compared the influence of caffeine on physiological responses to exercise between boys and men. Fifty-two participants (26 boys and 26 men) participated in a double blind, randomized, double crossover study. Each participant received the caffeinated (5 mg/kg) drink (CAF) and placebo (PL) twice each on 4 separate days. One hour after drink consumption preexercise heart rate (HR) and blood pressure (BP) were measured. Then while the participants rode stationary cycle ergometers at two different exercise intensities, HR, BP, and oxygen consumption (VO2) were measured. Blood pressure was not significantly affected by CAF, although on average it was always higher in boys for diastolic BP (3 mmHg) and systolic BP (3–4 mmHg) and men for diastolic BP (2–3 mmHg) and systolic BP (1–6 mmHg) both at rest and during exercise. HR was significantly (p < .05) lower at rest, 25W and 50W in CAF versus PL in boys, with no change in adults. During exercise, VO2 and respiratory exchange ratio (RER) were not different in CAF versus PL in either group. In conclusion, metabolism is not affected by a moderate caffeine dose in children or adults. The same dose has a similar effect on BP in both groups. The effect on HR was different, however, with a significant (p < .05) lowering in children in CAF versus PL, with no adult effects.
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Green, James M., Alyssa Olenick, Caroline Eastep, and Lee Winchester. "Caffeine effects on velocity selection and physiological responses during RPE production." Applied Physiology, Nutrition, and Metabolism 41, no. 10 (October 2016): 1077–82. http://dx.doi.org/10.1139/apnm-2016-0098.
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Caffeine (CAF) blunts estimated ratings of perceived exertion (RPE) but the effects on RPE production are unclear. This study examined effects of acute caffeine ingestion during treadmill exercise where participants exercised at prescribed RPE 4 and 7. Recreational runners (maximal oxygen consumption = 51.4 ± 9.8 mL·kg−1·min−1) (n = 16) completed a maximal treadmill test followed by trials where they selected treadmill velocity (VEL) (1% grade) to produce RPE 4 and RPE 7 (10 min each). RPE production trials followed CAF (6 mg·kg−1) or placebo (PLA) (counterbalanced) ingestion. Participants were blinded to treadmill VEL but the Omni RPE scale was in full view. Repeated-measures ANOVA showed a main effect (trial) for VEL (CAF ∼5 m·min−1 faster) for RPE 4 (p = 0.07) and RPE 7 (p = 0.03). Mean heart rate and oxygen consumption responses were consistently higher for CAF but failed to reach statistical significance. Individual responses to CAF were labeled positive using a criterion of 13.4 m·min−1 faster for CAF (vs. PLA). Ten of 32 trials (31%) were positive responses. In these, systematic increases were observed for heart rate (∼12 beats·min−1) and oxygen consumption (∼5.7 mL·kg−1·min−1). Blunted/stable respiratory exchange ratio values at higher VEL for positive responders suggest increased free fatty acid reliance during CAF. In conlusion, mean results show a mild effect of CAF during RPE production. However, individual responses more clearly indicate whether a true effect is possible. Trainers and individuals should consider individual responses to ensure effectively intensity regulation.
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Andreazzi, Ana Eliza, Sabrina Grassiolli, Paula Beatriz Marangon, Adriana Gallego Martins, Júlio Cézar de Oliveira, Rosana Torrezan, Clarice Gravena, Raúl Marcel González Garcia, and Paulo Cezar de Freitas Mathias. "Impaired Sympathoadrenal Axis Function Contributes to Enhanced Insulin Secretion in Prediabetic Obese Rats." Experimental Diabetes Research 2011 (2011): 1–11. http://dx.doi.org/10.1155/2011/947917.
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The involvement of sympathoadrenal axis activity in obesity onset was investigated using the experimental model of treating neonatal rats with monosodium L-glutamate. To access general sympathetic nervous system activity, we recorded the firing rates of sympathetic superior cervical ganglion nerves in animals. Catecholamine content and secretion from isolated adrenal medulla were measured. Intravenous glucose tolerance test was performed, and isolated pancreatic islets were stimulated with glucose and adrenergic agonists. The nerve firing rate of obese rats was decreased compared to the rate for lean rats. Basal catecholamine secretion decreased whereas catecholamine secretion induced by carbachol, elevated extracellular potassium, and caffeine in the isolated adrenal medulla were all increased in obese rats compared to control. Both glucose intolerance and hyperinsulinaemia were observed in obese rats. Adrenaline strongly inhibited glucose-induced insulin secretion in obese animals. These findings suggest that low sympathoadrenal activity contributes to impaired glycaemic control in prediabetic obese rats.
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Nawaji, Tasuku, Natsumi Yamashita, Haruka Umeda, Shuangyi Zhang, Naohiro Mizoguchi, Masanori Seki, Takio Kitazawa, and Hiroki Teraoka. "Cytochrome P450 Expression and Chemical Metabolic Activity before Full Liver Development in Zebrafish." Pharmaceuticals 13, no. 12 (December 11, 2020): 456. http://dx.doi.org/10.3390/ph13120456.
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Zebrafish are used widely in biomedical, toxicological, and developmental research, but information on their xenobiotic metabolism is limited. Here, we characterized the expression of 14 xenobiotic cytochrome P450 (CYP) subtypes in whole embryos and larvae of zebrafish (4 to 144 h post-fertilization (hpf)) and the metabolic activities of several representative human CYP substrates. The 14 CYPs showed various changes in expression patterns during development. Many CYP transcripts abruptly increased at about 96 hpf, when the hepatic outgrowth progresses; however, the expression of some cyp1s (1b1, 1c1, 1c2, 1d1) and cyp2r1 peaked at 48 or 72 hpf, before full liver development. Whole-mount in situ hybridization revealed cyp2y3, 2r1, and 3a65 transcripts in larvae at 55 hpf after exposure to rifampicin, phenobarbital, or 2,3,7,8-tetrachlorodibenzo-p-dioxin from 30 hpf onward. Marked conversions of diclofenac to 4′-hydroxydiclofenac and 5-hydroxydiclofenac, and of caffeine to 1,7-dimethylxanthine, were detected as early as 24 or 50 hpf. The rate of metabolism to 4’-hydroxydiclofenac was more marked at 48 and 72 hpf than at 120 hpf, after the liver had become almost fully developed. These findings reveal the expression of various CYPs involved in chemical metabolism in developing zebrafish, even before full liver development.
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Vicente-Salar, Néstor, Encarna Fuster-Muñoz, and Alejandro Martínez-Rodríguez. "Nutritional Ergogenic Aids in Combat Sports: A Systematic Review and Meta-Analysis." Nutrients 14, no. 13 (June 22, 2022): 2588. http://dx.doi.org/10.3390/nu14132588.
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Nutritional ergogenic aids (NEAs) are substances included within the group of sports supplements. Although they are widely consumed by athletes, evidence-based analysis is required to support training outcomes or competitive performance in specific disciplines. Combat sports have a predominant use of anaerobic metabolism as a source of energy, reaching peak exertion or sustained effort for very short periods of time. In this context, the use of certain NEAs could help athletes to improve their performance in those specific combat skills (i.e., the number of attacks, throws and hits; jump height; and grip strength, among others) as well as in general physical aspects (time to exhaustion [TTE], power, fatigue perception, heart rate, use of anaerobic metabolism, etc.). Medline/PubMed, Scopus and EBSCO were searched from their inception to May 2022 for randomised controlled trials (RCTs). Out of 677 articles found, 55 met the predefined inclusion criteria. Among all the studied NEAs, caffeine (5–10 mg/kg) showed strong evidence for its use in combat sports to enhance the use of glycolytic pathways for energy production during high-intensity actions due to a greater production of and tolerance to blood lactate levels. In this regard, abilities including the number of attacks, reaction time, handgrip strength, power and TTE, among others, were improved. Buffering supplements such as sodium bicarbonate, sodium citrate and beta-alanine may have a promising role in high and intermittent exertion during combat, but more studies are needed in grappling combat sports to confirm their efficacy during sustained isometric exertion. Other NEAs, including creatine, beetroot juice or glycerol, need further investigation to strengthen the evidence for performance enhancement in combat sports. Caffeine is the only NEA that has shown strong evidence for performance enhancement in combat sports.
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Basrai, Maryam, Anna Schweinlin, Juliane Menzel, Hans Mielke, Cornelia Weikert, Birgit Dusemund, Kersten Putze, Bernhard Watzl, Alfonso Lampen, and Stephan C. Bischoff. "Energy Drinks Induce Acute Cardiovascular and Metabolic Changes Pointing to Potential Risks for Young Adults: A Randomized Controlled Trial." Journal of Nutrition 149, no. 3 (February 26, 2019): 441–50. http://dx.doi.org/10.1093/jn/nxy303.
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ABSTRACTBackgroundCase reports suggest a link between energy drinks (EDs) and adverse events, including deaths.ObjectivesWe examined cardiovascular and metabolic effects of EDs and mixtures providing relevant ingredients of EDs compared to a similarly composed control product (CP) without these components.MethodsThis randomized, crossover trial comprised 38 adults (19 women, mean BMI 23 kg/m2, mean age 22 y). We examined effects of a single administration of a commercial ED, the CP, and the CP supplemented with major ED-ingredients at the same concentrations as in the ED. The study products were administered at 2 volumes, 750 or 1000 mL.ResultsBoth volumes of the study products were acceptably tolerated with no dose-dependent effects on blood pressure (BP, primary outcome), heart rate, heart rate corrected duration of QT-segment in electrocardiography (QTc interval), and glucose metabolism. After ED consumption, 11% of the participants reported symptoms, in contrast to 0–3% caused by other study products. After 1 h, administration of an ED caused an increase in systolic BP (116.9 ± 10.4 to 120.7 ± 10.7 mmHg, mean ± SD, P < 0.01) and a QTc prolongation (393.3 ± 20.6 to 400.8 ± 24.1 ms, P < 0.01). Also caffeine, but not taurine or glucuronolactone, caused an increase in BP, but no QTc prolongation. The BP effects were most pronounced after 1 h and returned to normal after a few hours. All study products caused a decrease in serum glucose and an increase in insulin concentrations after 1 h compared to baseline values, corresponding to an elevation in the HOMA-IR (ED + 4.0, other products + 1.0–2.8, all P < 0.001).ConclusionA single high-volume intake of ED caused adverse changes in BP, QTc, and insulin sensitivity in young, healthy individuals. These effects of EDs cannot be easily attributed to the single components caffeine, taurine, or glucuronolactone. This trial was registered at clinicaltrials.gov as NCT01421979.
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Rebollo-Hernanz, Miguel, Yolanda Aguilera, Maria A. Martin-Cabrejas, and Elvira Gonzalez de Mejia. "Bioactives From Coffee By-Products Stimulate Liver Metabolism and Mitochondrial Bioenergetics via AMPK/PGC-1α/Nrf2 and IRS/AKT/GLUT2 Pathways In Vitro." Current Developments in Nutrition 6, Supplement_1 (June 2022): 332. http://dx.doi.org/10.1093/cdn/nzac053.073.
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Abstract Objectives This study aimed to investigate the effect of the main bioactive compounds from the coffee silverskin and coffee husk on hepatic lipid and glucose metabolism and mitochondrial bioenergetics using an in vitro model mimicking non-alcoholic fatty liver disease. Methods HepG2 cells were treated with 50 μmol L−1 caffeine, chlorogenic, caffeic, protocatechuic, or gallic acids, or kaempferol, or the aqueous extracts from the coffee silverskin (CSE, 100 μg mL−1) or the coffee husk (CHE, 100 μg mL−1) in the presence of palmitic acid (500 μmol L−1). Cell metabolism biomarkers were assessed 24 h after the co-treatment in cell lysates and supernatants using chemical and immunochemical techniques. Differences among treatments were considered significant at p < 0.05. Results Bioactive compounds in coffee by-products, CSE, and CHE decreased lipid accumulation (53–115%) by reducing fatty acid synthase expression (44–76%) and stimulated β-oxidation by triggering carnitine palmitoyltransferase I activity (1.6 to 2.6-fold) and up-phosphorylating AMP-activated protein kinase (AMPK, 1.5–2.4-fold). Glucose uptake was promoted via the increase in the insulin receptor substrate (IRS)-1 (1.5 to 2.1-fold) and protein kinase B (Akt1, 1.7–2.4-fold) phosphorylation, and glucose transporter (GLUT)-2 expression (2.1 to 3.7-fold). Mitochondrial function was enhanced (ATP production and O2 consumption rate, 1.7–2.5-fold and 1.8 to 2.5-fold, respectively), and oxidative phosphorylation complexes and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α expression restored (30–105%). Oxidative stress was diminished (56 − 85%) through augmented superoxide dismutase (1.3 to 1.7-fold) and catalase (1.5 to 2.0-fold) activities, and nuclear factor-erythroid 2-related factor 2 (Nrf2) expression (2.3 to 3.8-fold). Conclusions The major bioactive compounds in coffee by-products, primarily chlorogenic and protocatechuic acids, could regulate hepatic lipid and glucose metabolism and prevent oxidative stress and mitochondrial dysfunction by activating AMPK/PGC-1α/Nrf2 and IRS/AKT/GLUT2 signaling pathways. Altogether, our results suggest the use of coffee by-products as a sustainable source of natural bioactives to counteract non-alcoholic fatty liver disease. Funding Sources USDA-NIFA-HATCH and the Spanish Ministry of Science and Innovation.
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Andrade-Souza, Victor Amorim, Romulo Bertuzzi, Gustavo Gomes de Araujo, David Bishop, and Adriano Eduardo Lima-Silva. "Effects of isolated or combined carbohydrate and caffeine supplementation between 2 daily training sessions on soccer performance." Applied Physiology, Nutrition, and Metabolism 40, no. 5 (May 2015): 457–63. http://dx.doi.org/10.1139/apnm-2014-0268.
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This study aimed to investigate whether isolated or combined carbohydrate (CHO) and caffeine (CAF) supplementation have beneficial effects on performance during soccer-related tests performed after a previous training session. Eleven male, amateur soccer players completed 4 trials in a randomized, double-blind, and crossover design. In the morning, participants performed the Loughborough Intermittent Shuttle Test (LIST). Then, participants ingested (i) 1.2 g·kg−1 body mass·h−1 CHO in a 20% CHO solution immediately after and 1, 2, and 3 h after the LIST; (ii) CAF (6 mg·kg−1 body mass) 3 h after the LIST; (iii) CHO combined with CAF (CHO+CAF); and (iv) placebo. All drinks were taste-matched and flavourless. After this 4-h recovery, participants performed a countermovement jump (CMJ) test, a Loughborough Soccer Passing Test (LSPT), and a repeated-sprint test. There were no main effects of supplementation for CMJ, LSPT total time, or best sprint and total sprint time from the repeated-sprint test (p > 0.05). There were also no main effects of supplementation for heart rate, plasma lactate concentration, rating of perceived exertion (RPE), pleasure–displeasure, and perceived activation (p > 0.05). However, there were significant time effects (p < 0.05), with heart rate, plasma lactate concentration, RPE, and perceived activation increasing with time, and pleasure–displeasure decreasing with time. In conclusion, isolated and/or combined CHO and CAF supplementation is not able to improve soccer-related performance tests when performed after a previous training session.
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Freerksen, D. L., N. A. Schroedl, G. V. Johnson, and C. R. Hartzell. "Increased aerobic glucose oxidation by cAMP in cultured regenerated skeletal myotubes." American Journal of Physiology-Cell Physiology 250, no. 5 (May 1, 1986): C713—C719. http://dx.doi.org/10.1152/ajpcell.1986.250.5.c713.
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Previous studies of embryonic rat skeletal muscle cultures suggested that there was a correlation between intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration and activities of enzymes of oxidative energy metabolism. We investigated the ability of agents that elevate intracellular cAMP by three different mechanisms (activation of adenylate cyclase, inhibition of phosphodiesterase, and analogues) to alter not only the activities of 11 glycolytic and mitochondrial enzymes but also the rate of flux through aerobic glucose oxidation in intact myotubes derived from regenerating rat muscle satellite cells. The enzyme activities were not consistently altered when cAMP was elevated, with the exception of the electron transport enzyme, NADH cytochrome c reductase, whose activity was elevated by exposure of the myotubes to cholera toxin (110% of control), 3-isobutyl-1-methylxanthine (112%), caffeine (119%), and 8-bromoadenosine 3',5'-cyclic monophosphate (120%). The rate of flux of aerobic glucose oxidation was elevated by all agents (116-157% of control) except cholera toxin. This study allowed us to compare the metabolic characteristics of myotube cultures derived from satellite cells with those from embryonic muscle, from a previous study. Despite differences between these two models, together, the data present strong evidence that an increase in intracellular cAMP can cause an increase in oxidative capacity.
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Porto, Andrey Alves, Cicero Jonas R. Benjamim, Luana Almeida Gonzaga, Mariana Luciano de Almeida, Carlos Roberto Bueno Júnior, David M. Garner, and Vitor Engrácia Valenti. "Caffeine intake and its influences on heart rate variability recovery in healthy active adults after exercise: A systematic review and meta-analysis." Nutrition, Metabolism and Cardiovascular Diseases 32, no. 5 (May 2022): 1071–82. http://dx.doi.org/10.1016/j.numecd.2022.01.015.
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Mahdavi, Sara, Paolo Palatini, and Ahmed El-Sohemy. "CYP1A2 Genetic Variation, Coffee Intake, and Kidney Dysfunction." JAMA Network Open 6, no. 1 (January 26, 2023): e2247868. http://dx.doi.org/10.1001/jamanetworkopen.2022.47868.
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ImportanceCaffeine is detoxified by cytochrome P450 1A2 (CYP1A2), and genetic variation in CYP1A2 impacts the rate of caffeine clearance. Factors that may modify the association between coffee intake and kidney disease remain unclear.ObjectiveTo assess whether CYP1A2 genotype modifies the association between coffee intake and kidney dysfunction.Design, Setting, and ParticipantsThe Hypertension and Ambulatory Recording Venetia Study (HARVEST) was a prospective cohort study of individuals with stage 1 hypertension in Italy; HARVEST began on April 1, 1990, and follow-up is ongoing. The current study used data from April 1, 1990, to June 30, 2006, with follow-up of approximately 10 years. Blood pressure and biochemical data were collected monthly during the first 3 months, then every 6 months thereafter. Data were analyzed from January 2019 to March 2019. Participants were screened and recruited from general practice clinics. The present study included 1180 untreated participants aged 18 to 45 years with stage 1 hypertension; those with nephropathy, diabetes, urinary tract infection, and cardiovascular disease were excluded.ExposuresCoffee intake and CYP1A2 genotype rs762551 were exposures analyzed over a median follow-up of 7.5 (IQR, 3.1-10.9) years.Main Outcomes and MeasuresAlbuminuria (defined as an albumin level of ≥30 mg/24 h) and hyperfiltration (defined as an estimated glomerular filtration rate of ≥150 mL/min/1.73 m2) were the primary outcomes as indicators of kidney dysfunction.ResultsAmong 1180 participants, genotyping, lifestyle questionnaires, and urine analysis data were obtained from 604 individuals (438 [72.5%] male) with a mean (SD) age of 33.3 (8.5) years and a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 25.4 (3.4). A total of 158 participants (26.2%) consumed less than 1 cup of coffee per day, 379 (62.7%) consumed 1 to 3 cups per day, and 67 (11.1%) consumed more than 3 cups per day. Genotype frequencies for rs762551 (260 participants [43.1%] with genotype AA, 247 participants [40.8%] with genotype AC, and 97 participants [16.1%] with genotype CC) did not differ between coffee intake categories. The level of risk of developing albuminuria, hyperfiltration, and hypertension, assessed by Cox regression and survival analyses, was not associated with coffee intake in the entire group or among fast metabolizers. The risks of albuminuria (adjusted hazard ratio [aHR], 2.74; 95% CI, 1.63-4.62; P &lt; .001), hyperfiltration (aHR, 2.11; 95% CI, 1.17-3.80; P = .01), and hypertension (aHR, 2.81; 95% CI, 1.51-5.23; P = .001) increased significantly among slow metabolizers who consumed more than 3 cups per day.Conclusions and RelevanceIn this study, the risks of albuminuria, hyperfiltration, and hypertension increased with heavy coffee intake only among those with the AC and CC genotypes of CYP1A2 at rs762551 associated with slow caffeine metabolism, suggesting that caffeine may play a role in the development of kidney disease in susceptible individuals.
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Lindqvist, Anders, Karl Dreja, Karl Swärd, and Per Hellstrand. "Effects of oxygen tension on energetics of cultured vascular smooth muscle." American Journal of Physiology-Heart and Circulatory Physiology 283, no. 1 (July 1, 2002): H110—H117. http://dx.doi.org/10.1152/ajpheart.00040.2001.
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Chronic hypoxia is a clinically important condition known to cause vascular abnormalities. To investigate the cellular mechanisms involved, we kept rings of a rat tail artery for 4 days in hypoxic culture (HC) or normoxic culture (NC) (Po 2 = 14 vs. 110 mmHg) and then measured contractility, oxygen consumption ( J o2 ), and lactate production ( J lac) in oxygenated medium. Compared with fresh rings, basal ATP turnover ( J ATP) was decreased in HC, but not in NC, with a shift from oxidative toward glycolytic metabolism. J o2 during mitochondrial uncoupling was reduced by HC but not by NC. Glycogen stores were increased 40-fold by HC and fourfold by NC. Maximum tension in response to norepinephrine and the Jo2 versus tension relationship ( J o2 vs. high K+ elicited force) were unaffected by either HC or NC. Force transients in response to caffeine were increased in HC, whereas intracellular Ca2+ wave activity during adrenergic stimulation was decreased. Protein synthesis rate was reduced by HC. The results show that long-term hypoxia depresses basal energy turnover, impairs mitochondrial capacity, and alters Ca2+homeostasis, but does not affect contractile energetics. These alterations may form a basis for vascular damage by chronic hypoxia.
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Devenney, Simon, Shane Mangan, Marcus Shortall, and Kieran Collins. "Effects of carbohydrate mouth rinse and caffeine on high-intensity interval running in a fed state." Applied Physiology, Nutrition, and Metabolism 43, no. 5 (May 2018): 517–21. http://dx.doi.org/10.1139/apnm-2017-0458.
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The current study aims to identify if mouth rinsing with a 6% carbohydrate mouth-rinse (CMR) solution and mouth rinsing and ingestion of caffeine (CMR+CAFF) can affect exercise performance during steady-state (SS) running and high-intensity intervals (HIIT) in comparison with a 0% control solution (PLA) when in a fed state. Eight recreationally trained males completed 3 trials (CMR, CMR+CAFF, and PLA) of 45 min SS running and an HIIT protocol (90% peak treadmill velocity) until fatigue in a double blinded, repeated-measures study. Participants ingested a capsule of either CAFF or PLA before and after SS. Participants received a 25-mL bolus of carbohydrate solution (CMR and CMR+CAFF trials) or taste-matched PLA (PLA trial) prior to HIIT protocol and after every second effort. Heart rate and lactate responses were recorded throughout the SS and HIIT protocol. CMR+CAFF was significantly different when compared with PLA (p = 0.001; Cohens d = 1.34) and CMR (p = 0.031; Cohens d = 0.87) in relation to distance covered before fatigue. Although there was no significant difference between CMR and PLA, there was a small benefit for CMR (p = 0.218; Cohens d = 0.46). Results indicate that CMR and ingestion of CAFF leads to improvements in performance during interval sessions while participants were in a fed state. These findings indicate that the regular use of CMR can decrease the risk of gastrointestinal distress reported by athletes, which can be applicable to athletes in a real-world setting.
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Jaffe, Craig A., D. Kim Turgeon, Kenneth Lown, Roberta Demott-Friberg, and Paul B. Watkins. "Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans." American Journal of Physiology-Endocrinology and Metabolism 283, no. 5 (November 1, 2002): E1008—E1015. http://dx.doi.org/10.1152/ajpendo.00513.2001.
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The importance of gender-specific growth hormone (GH) secretion pattern in the regulation of growth and metabolism has been demonstrated clearly in rodents. We recently showed that GH secretion in humans is also sexually dimorphic. Whether GH secretion pattern regulates the metabolic effects of GH in humans is largely unknown. To address this question, we administered the same daily intravenous dose of GH (0.5 mg · m−2 · day−1) for 8 days in different patterns to nine GH-deficient adults. Each subject was studied on four occasions: protocol 1 (no treatment), protocol 2 (80% daily dose at 0100 and 10% daily dose at 0900 and 1700), protocol 3 (8 equal boluses every 3 h), and protocol 4 (continuous GH infusion). The effects of GH pattern on serum IGF-I, IGF-binding protein (IGFBP)-3, osteocalcin, and urine deoxypyridinoline were measured. Hepatic CYP1A2 and CYP3A4 activities were assessed by the caffeine and erythromycin breath tests, respectively. Protocols 3 and 4 were the most effective in increasing serum IGF-I and IGFBP-3, whereas protocols administering pulsatile GH had the greatest effects on markers of bone formation and resorption. All GH treatments decreased CYP1A2 activity, and the effect was greatest for pulsatile GH. Pulsatile GH decreased, whereas continuous GH infusion increased, CYP3A4 activity. These data demonstrate that GH pulse pattern is an independent parameter of GH action in humans. Gender differences in drug metabolism and, potentially, gender differences in growth rate may be explained by sex-specific GH secretion patterns.
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Bantu, Sravani, Shirisha R. Vallepu, Mouna Gunda, and Vaishali Thudi. "Incidental Pheochromocytoma: Silent but Violent." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A137—A138. http://dx.doi.org/10.1210/jendso/bvab048.277.
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Abstract Background: Pheochromocytoma is a rare catecholamine secreting neuroendocrine tumor. It arises from the chromaffin cells of adrenal medulla. It is diagnosed in 5–6.5% of adrenal incidentalomas which is not common. The usual clinical presentation includes the classic triad of sweating, headache and tachycardia. However, asymptomatic cases are seen in 8% of the patients with pheochromocytoma. We present a clinically asymptomatic patient diagnosed during work up of adrenal incidentaloma. The possible etiology for silent presentation includes one of the following:(i) Presence of a smaller functional tissue (ii)Accelerated turnover of the tumor causing release of the unmetabolized catecholamines in small amounts (iii) Pulsatile tumor secretion (iv)Tumors triggered by stress (v) Laboratory errors due to inappropriate handling of specimen at high-temperature (vi) False negative test results secondary to caffeine ingestion in the prior 24 hours. Clinical Case: 59 years old Caucasian female with past medical history of type 2 diabetes mellitus, obesity, essential hypertension, nonischemic cardiomyopathy, and asthma presented to the emergency room with complaints of worsening shortness of breath and pedal edema for 1 month. Physical exam: Blood pressure 146/78 mm of Hg and heart rate 82 beats/min, mild pedal edema, no pulmonary crackles. On imaging, CT angio chest showed irregularly enhancing right adrenal mass measuring 3.4 cm. This adrenal incidentaloma was not visualized on imaging done 5 years ago. Further, MRI abdomen revealed 4.1 cm right adrenal mass. Laboratory testing showed high total plasma metanephrines: 890 pg/ml (< or = 205), 24-hour urine metanephrines: 2337 (140–785), A1C: 10%. This confirmed the diagnosis of adrenal pheochromocytoma. Preoperatively, she was started on phenoxybenzamine 10 mg BID and encouraged on liberal salt intake. During the course, her blood pressure and heart rate were monitored daily. She underwent right adrenalectomy. Surgical pathology revealed 4.1 cm pheochromocytoma, negative margins with extension to the adipose tissues and vascular invasion, PASS score = 4. Post operatively, patient declined to get labs done. Due to high risk behavior of the tumor, patient needs to be monitored annually for lifelong. Conclusion: Pheochromocytoma is an uncommon tumor with varied clinical presentation. It can manifest itself widely from being silent to aggressive disease. This warrants high suspicion, early detection and management, thereby reducing the morbidity and mortality. Lately, there has been increased incidence of adrenal incidentalomas owing to widespread use of radiological investigations. We report a case of incidental pheochromocytoma which is biochemically active but clinically asymptomatic. This emphasizes the importance of being more vigilant during the evaluation of adrenal incidentalomas.
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Nesbeth, Paula-Dene, Veronika Fedirko, Dean Jones, Tianwei Yu, Roberd Bostick, Elizabeth Barry, and John Baron. "An Untargeted Metabolomic Study of the Effects of Vitamin D and/or Calcium Supplementation Among Individuals at High Risk for Colorectal Neoplasms." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 343. http://dx.doi.org/10.1093/cdn/nzaa044_042.
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Abstract Objectives To obtain preliminary data on the independent and synergistic anti-neoplastic effects of 1-year supplementation with vitamin D3 and/or calcium on the plasma metabolome and metabolic pathways among individuals at high risk for colorectal neoplasms. Methods This study was an untargeted metabolomic analysis that used data and biosamples from a completed, large, multicenter, randomized, placebo-controlled, clinical trial of vitamin D3 (1000 IU/d) and/or calcium (1200 mg/d via calcium carbonate) for preventing colorectal adenoma recurrence. High resolution liquid chromatography-mass spectrometry with positive and negative ion modes was used to measure >20,000 metabolites in the baseline and year 1 follow-up plasma samples from the four treatment groups (n = 30/group). The data were processed for peak extraction and quantification of ion intensities using xMSanalyzer software with apLCMS. Using repeated measures mixed models and false discovery rate adjustment, top features associated with each treatment combination were identified. Significant features (unadjusted P < 0.05) were analyzed in mummichog 2.0 to identify enriched metabolic pathways associated with each treatment agent. Results Following 1 year of treatment, in the calcium treatment group relative to placebo, pathways related to carnitine shuttle; prostaglandin formation from arachidonate; fructose and caffeine metabolism were significantly modulated (P < 0.05). Prostaglandin formation from arachidonate; carnitine shuttle; N-glycan and keratan sulfate degradation were significantly associated with calcium plus vitamin D3 treatment (P < 0.05). Metabolic pathways significantly modulated with vitamin D3 treatment were leukotriene, vitamin D3, vitamin E, vitamin A, arachidonic acid metabolism, and fatty acid activation (P < 0.05). Conclusions Our preliminary results suggest significant changes in prostaglandin formation pathway in plasma of individuals at high risk for colorectal cancer supplemented for 1 year with calcium alone and calcium plus vitamin D3. Vitamin D3 supplementation modulated the arachidonic acid pathway supporting its effects on inflammation. Our study supports continued investigation of vitamin D3 and calcium's anti-carcinogenic actions. Funding Sources National Cancer Institute.
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Yuan, Shuai, and Susanna C. Larsson. "An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomisation study." Diabetologia 63, no. 11 (September 8, 2020): 2359–71. http://dx.doi.org/10.1007/s00125-020-05253-x.
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Abstract Aims/hypothesis The aim of this study was to use Mendelian randomisation (MR) to identify the causal risk factors for type 2 diabetes. Methods We first conducted a review of meta-analyses and review articles to pinpoint possible risk factors for type 2 diabetes. Around 170 possible risk factors were identified of which 97 risk factors with available genetic instrumental variables were included in MR analyses. To reveal more risk factors that were not included in our MR analyses, we conducted a review of published MR studies of type 2 diabetes. For our MR analyses, we used summary-level data from the DIAbetes Genetics Replication And Meta-analysis consortium (74,124 type 2 diabetes cases and 824,006 controls of European ancestry). Potential causal associations were replicated using the FinnGen consortium (11,006 type 2 diabetes cases and 82,655 controls of European ancestry). The inverse-variance weighted method was used as the main analysis. Multivariable MR analysis was used to assess whether the observed associations with type 2 diabetes were mediated by BMI. We used the Benjamini–Hochberg method that controls false discovery rate for multiple testing. Results We found evidence of causal associations between 34 exposures (19 risk factors and 15 protective factors) and type 2 diabetes. Insomnia was identified as a novel risk factor (OR 1.17 [95% CI 1.11, 1.23]). The other 18 risk factors were depression, systolic BP, smoking initiation, lifetime smoking, coffee (caffeine) consumption, plasma isoleucine, valine and leucine, liver alanine aminotransferase, childhood and adulthood BMI, body fat percentage, visceral fat mass, resting heart rate, and four plasma fatty acids. The 15 exposures associated with a decreased risk of type 2 diabetes were plasma alanine, HDL- and total cholesterol, age at menarche, testosterone levels, sex hormone binding globulin levels (adjusted for BMI), birthweight, adulthood height, lean body mass (for women), four plasma fatty acids, circulating 25-hydroxyvitamin D and education years. Eight associations remained after adjustment for adulthood BMI. We additionally identified 21 suggestive risk factors (p < 0.05), such as alcohol consumption, breakfast skipping, daytime napping, short sleep, urinary sodium, and certain amino acids and inflammatory factors. Conclusions/interpretation The present study verified several previously reported risk factors and identified novel potential risk factors for type 2 diabetes. Prevention strategies for type 2 diabetes should be considered from multiple perspectives on obesity, mental health, sleep quality, education level, birthweight and smoking. Graphical abstract