Caffeine Inhibits NLRP3 Inflammasome Activation by Downregulating TLR4/MAPK/NF-κB Signaling Pathway in an Experimental NASH Model

Caffeine elicits protective effects against liver diseases, such as NASH; however, its mechanism of action involving the pyrin domain-containing-3 (NLRP3) inflammasome signaling pathway remains to be elucidated. This study aimed to evaluate the effect of caffeine on the NLRP3 inflammasome signaling pathway in a rat model of NASH. NASH was induced by feeding rats a high-fat, -sucrose, and -cholesterol diet (HFSCD) for 15 weeks along with a weekly low dose (400 mg/kg, i.p.) of CCl₄. Caffeine was administered at 50 mg/kg p.o. The effects of HFSCD+CCl₄ and caffeine on the liver were evaluated using biochemical, ultrastructural, histological, and molecular biological approaches. The HFSCD+CCl₄-treated rats showed fat accumulation in the liver, elevated levels of inflammatory mediators, NLRP3 inflammasome activation, antioxidant dysregulation, and liver fibrosis. Caffeine reduced necrosis, cholestasis, oxidative stress, and fibrosis. Caffeine exhibited anti-inflammatory effects by attenuating NLRP3 inflammasome activation. Moreover, caffeine prevented increases in toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) protein levels and mitigated the phosphorylation of mitogen-activated protein kinase (MAPK). Importantly, caffeine prevented the activation of hepatic stellate cells. This study is the first to report that caffeine ameliorates NASH by inhibiting NLRP3 inflammasome activation through the suppression of the TLR4/MAPK/NF-κB signaling pathway.     

Effects of Three Different Doses of Inter-Alpha Inhibitor Proteins on Severe Hypoxia–Ischemia-Related Brain Injury in Neonatal Rats

Hypoxia–ischemia (HI)-related brain injury is an important cause of morbidity and long-standing disability in newborns. We have previously shown that human plasma-derived inter-alpha inhibitor proteins (hIAIPs) attenuate HI-related brain injury in neonatal rats. The optimal dose of hIAIPs for their neuroprotective effects and improvement in behavioral outcomes remains to be determined. We examined the efficacy of 30, 60, or 90 mg/kg of hIAIPs administered to neonatal rats after exposure to HI for 2 h. Postnatal day 7 (P7) Wistar rats were exposed to either sham-surgery or unilateral HI (right carotid artery ligation, 2 h of 8% O₂) brain injury. A placebo, 30, 60, or 90 mg/kg of hIAIPs were injected intraperitoneally at 0, 24 and 48 h after HI (n = 9–10/sex). We carried out the following behavioral analyses: P8 (righting reflex), P9 (negative geotaxis) and P10 (open-field task). Rats were humanely killed on P10 and their brains were stained with cresyl violet. Male extension/contraction responses and female righting reflex times were higher in the HI placebo groups than the sham groups. Female open-field exploration was lower in the HI placebo group than the sham group. hIAIPs attenuated these behavioral deficits. However, the magnitude of the responses did not vary by hIAIP dose. hIAIPs reduced male brain infarct volumes in a manner that correlated with improved behavioral outcomes. Increasing the hIAIP dose from 30 to 90 mg/kg did not further accentuate the hIAIP-related decreases in infarct volumes. We conclude that larger doses of hIAIPs did not provide additional benefits over the 30 mg/kg dose for behavior tasks or reductions in infarct volumes in neonatal rats after exposure to severe HI.     

Interleukin-1 Receptor Antagonist Reduces Neonatal Lipopolysaccharide-Induced Long-Lasting Neurobehavioral Deficits and Dopaminergic Neuronal Injury in Adult Rats

Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1β (IL-1β) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1β may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1β might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure.     

Pioglitazone Ameliorates Lipopolysaccharide-Induced Behavioral Impairment,Brain Inflammation,White Matter Injury and Mitochondrial Dysfunction in Neonatal Rats

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague–Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1β (IL-1β) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1β levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1β induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.     

Erythropoietin Ameliorates Neonatal Hypoxia-Ischemia-Induced Neurobehavioral Deficits,Neuroinflammation, and Hippocampal Injury in the Juvenile Rat

The hematopoietic growth factor erythropoietin (EPO) has been shown to be neuroprotective against hypoxia-ischemia (HI) in Postnatal Day 7 (P7)–P10 or adult animal models. The current study was aimed to determine whether EPO also provides long-lasting neuroprotection against HI in P5 rats, which is relevant to immature human infants. Sprague-Dawley rats at P5 were subjected to right common carotid artery ligation followed by an exposure to 6% oxygen with balanced nitrogen for 1.5 h. Human recombinant EPO (rEPO, at a dose of 5 units/g) was administered intraperitoneally one hour before or immediately after insult, followed by additional injections at 24 and 48 h post-insult. The control rats were injected with normal saline following HI. Neurobehavioral tests were performed on P8 and P20, and brain injury was examined on P21. HI insult significantly impaired neurobehavioral performance including sensorimotor, locomotor activity and cognitive ability on the P8 and P20 rats. HI insult also resulted in brain inflammation (as indicated by microglia activation) and neuronal death (as indicated by Jade B positive staining) in the white matter, striatum, cortex, and hippocampal areas of the P21 rat. Both pre- and post-treatment with rEPO significantly improved neurobehavioral performance and protected against the HI-induced neuronal death, microglia activation (OX42+) as well as loss of mature oligodendrocytes (APC-CC1+) and hippocampal neurons (Nissl+). The long-lasting protective effects of rEPO in the neonatal rat HI model suggest that to exert neurotrophic activity in the brain might be an effective approach for therapeutic treatment of neonatal brain injury induced by hypoxia-ischemia.     

紫外分光光度法测可乐中咖啡因的含量

目的:用紫外分光光度法测定可乐中咖啡因的含量,建立测定可乐中咖啡因的含量的紫外分光光度法的最佳工作条件。方法:采用离心的方法提取样品中的咖啡因,用紫外分光光度法在276 nm处测含量。结果:咖啡因浓度在5～50μg/mL范围内与紫外吸收有较好的线性关系(y=0.0489x-0.0084,R2=0.9991)。可口可乐中咖啡因的含量为93.5μg/mL,回收率为99.1%,RSD%为0.94%;百事可乐中咖啡因的含量为101.0μg/mL,回收率为100.4%,RSD%为0.64%。结论:此方法准确、简单、快速,适合可乐中咖啡因的含量测定。     

Central Nervous System Stimulants Limit Caffeine Transport at the Blood–Cerebrospinal Fluid Barrier

Caffeine, a common ingredient in energy drinks, crosses the blood–brain barrier easily, but the kinetics of caffeine across the blood–cerebrospinal fluid barrier (BCSFB) has not been investigated. Therefore, 127 autopsy cases (Group A, 30 patients, stimulant-detected group; and Group B, 97 patients, no stimulant detected group) were examined. In addition, a BCSFB model was constructed using human vascular endothelial cells and human choroid plexus epithelial cells separated by a filter, and the kinetics of caffeine in the BCSFB and the effects of 4-aminopyridine (4-AP), a neuroexcitatory agent, were studied. Caffeine concentrations in right heart blood (Rs) and cerebrospinal fluid (CSF) were compared in the autopsy cases: caffeine concentrations were higher in Rs than CSF in Group A compared to Group B. In the BCSFB model, caffeine and 4-AP were added to the upper layer, and the concentration in the lower layer of choroid plexus epithelial cells was measured. The CSF caffeine concentration was suppressed, depending on the 4-AP concentration. Histomorphological examination suggested that choroid plexus epithelial cells were involved in inhibiting the efflux of caffeine to the CSF. Thus, the simultaneous presence of stimulants and caffeine inhibits caffeine transfer across the BCSFB.     

Caffeine and Its Antioxidant Properties—It Is All about Dose and Source

Caffeine is the most frequently used substance with a central nervous system stimulant effect, but its consumption is most often due to the intake of foods and drinks that contain it (coffee, tea, chocolate, food supplements with plant extracts of Guarana, Mate herba, Cola nuts). Due to its innocuity, caffeine is a safe xanthine alkaloid for human consumption in a wide range of doses, being used for its central nervous stimulating effect, lipolytic and diuresis-enhancing properties, but also as a permitted ergogenic compound in athletes. In addition to the mechanisms that explain the effects of caffeine on the targeted organ, there are many proposed mechanisms by which this substance would have antioxidant effects. As such, its consumption prevents the occurrence/progression of certain neurodegenerative diseases as well as other medical conditions associated with increased levels of reactive oxygen or nitrogen species. However, most studies that have assessed the beneficial effects of caffeine have used pure caffeine. The question, therefore, arises whether the daily intake of caffeine from food or drink has similar benefits, considering that in foods or drinks with a high caffeine content, there are other substances that could interfere with this action, either by potentiating or decreasing its antioxidant capacity. Natural sources of caffeine often combine plant polyphenols (phenol-carboxylic acids, catechins) with known antioxidant effects; however, stimulant drinks and dietary supplements often contain sugars or artificial sweeteners that can significantly reduce the effects of caffeine on oxidative stress. The objective of this review is to clarify the effects of caffeine in modulating oxidative stress and assess these benefits, considering the source and the dose administered.     

"ABR+SBR"工艺处理咖啡因生产废水的中试研究

实验采用"ABR SBR"工艺及EMO复合菌微生物技术处理咖啡因生产废水.结果显示,在实验条件下,该技术对咖啡因生产废水有良好的处理效果,出水COD基本在300 mg/L以下,去除率在90%以上;出水氰根的均值为0.683 mg/L,平均去除率为84.85%;新增吹脱工艺对NH3-N有较好去除效果.整套工艺具有较好的经济效益.     

Ex Vivo Antioxidant and Cholinesterase Inhibiting Effects of a Novel Galantamine–Curcumin Hybrid on Scopolamine-Induced Neurotoxicity in Mice

Oxidative stress is an essential factor in the development and progression of Alzheimer’s disease (AD). An excessive amount of reactive oxygen species (ROS) induces the peroxidation of lipid membranes, reduces the activity of antioxidant enzymes and causes neurotoxicity. In this study, we investigated the antioxidant and cholinesterase inhibitory potential of a novel galantamine–curcumin hybrid, named 4b, administered orally in two doses (2.5 mg/kg and 5 mg/kg) in scopolamine (SC)-induced neurotoxicity in mice. To evaluate the effects of 4b, we used galantamine (GAL) (3 mg/kg) and curcumin (CCN) (25 mg/kg) as positive controls. Ex vivo experiments on mouse brains showed that the higher dose of 4b (5 mg/kg) increased reduced glutathione (GSH) levels by 46%, catalase (CAT) and superoxide dismutase (SOD) activity by 57%, and glutathione peroxidase (GPx) activity by 108%, compared with the SC-treated group. At the same time, 4b (5 mg/kg) significantly reduced the brain malondialdehyde (MDA) level by 31% and acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities by 40% and 30%, respectively, relative to the SC-impaired group. The results showed that 4b acted as an antioxidant agent and brain protector, making it promising for further experimental research in the field of neurodegenerative diseases.     

Dose response effects of a caffeine-containing energy drink on muscle performance: a repeated measures design

Background

Energy drinks have become the most used caffeine-containing beverages in the sport setting. The aim of this study was to determine the effects of two doses of a caffeine-containing energy drink on muscle performance during upper- and lower-body power-load tests.

Methods

In a randomized order, twelve active participants ingested 1 and 3?mg of caffeine per kg of body weight using a commercially available energy drink (Fure?, ProEnergetics) or the same drink without caffeine (placebo; 0?mg/kg). After sixty minutes, resting metabolic rate, heart rate and blood pressure were determined. Then, half-squat and bench-press power production with loads from 10 to 100% of 1 repetition maximum was determined using a rotator encoder.

Results

In comparison to the placebo, the ingestion of the caffeinated drink increased mean arterial pressure (82?±?7?P?<?59?±?8?<?62?±?8 beats/min, respectively; P?P?P?Conclusions A caffeine dose of at least 3?mg/kg in the form of an energy drink is necessary to significantly improve half-squat and bench-press maximal muscle power.     

Comparative Metabolism,Bioavailability, and Toxicokinetics of Benzo[ a ]pyrene in Rats After Acute Oral,Inhalation, and Intravenous Administration

The metabolic fate of high doses of B a P is not fully established. To fill this important data need, a comprehensive metabolism, bioavailability, and toxicokinetic study has been undertaken to track the fate of B a P subsequent to single acute exposures. Doses of 100 mg/kg body weight, 0.1 mg/m 3 (equivalent to 19 mg/kg oral dose), and 4.5 w g/kg B a P were administered to 8-week-old male F-344 rats via oral, inhalation (nose only), and intravenous routes, respectively. Rats were sacrificed at 0, 0.5, 1, 2, 4, 6, 24, 48, and 72 hr postexposure. Blood, liver, lung, brain, reproductive tissues, urine, and feces samples were analyzed for parent B a P and metabolites by HPLC with fluorescence detection. Most of the administered B a P was metabolized 4, 6, and 72 hr postexposure for inhalation, intravenous, and oral routes, respectively. The following metabolites were detected: 4,5-dihydrodiol, 7,8-dihydrodiol, 9,10-dihydrodiol, 3,6-dione, 3-hydroxy, and 9-hydroxy B a P (organic fraction), glucuronides, sulfates, and glutathione conjugates (aqueous fraction). Toxicokinetic data revealed a high mean residence time, and low clearance values for B a P metabolites in lung, liver, and brain relative to plasma. Findings of this study establish the relationship between bioavailability and the acute toxic effects of B a P observed in our laboratory at these high doses.     

Downregulation of the Cd38-Cyclic ADP-Ribose Signaling in Cardiomyocytes by Intermittent Hypoxia via Pten Upregulation

Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia, IH), and it is a risk factor for cardiovascular disease (CVD) and insulin resistance/type 2 diabetes. However, the mechanisms linking IH stress and CVD remain elusive. We exposed rat H9c2 and mouse P19.CL6 cardiomyocytes to experimental IH or normoxia for 24 h to analyze the mRNA expression of the components of Cd38-cyclic ADP-ribose (cADPR) signaling. We found that the mRNA levels of cluster of differentiation 38 (Cd38), type 2 ryanodine receptor (Ryr2), and FK506-binding protein 12.6 (Fkbp12.6) in H9c2 and P19.CL6 cardiomyocytes were significantly decreased by IH, whereas the promoter activities of these genes were not decreased. By contrast, the expression of phosphatase and tensin homolog deleted from chromosome 10 (Pten) was upregulated in IH-treated cells. The small interfering RNA for Pten (siPten) and a non-specific control RNA were introduced into the H9c2 cells. The IH-induced downregulation of Cd38, Ryr2, and Fkbp12.6 was abolished by the introduction of the siPten, but not by the control RNA. These results indicate that IH stress upregulated the Pten in cardiomyocytes, resulting in the decreased mRNA levels of Cd38, Ryr2, and Fkbp12.6, leading to the inhibition of cardiomyocyte functions in SAS patients.     

Caffeine-Induced Acute and Delayed Responses in Cerebral Metabolism of Control and Schizophrenia-like Wisket Rats

Recently, morphological impairments have been detected in the brain of a triple-hit rat schizophrenia model (Wisket), and delayed depressive effects of caffeine treatment in both control and Wisket animals have also been shown. The aims of this study were to determine the basal and caffeine-induced acute (30 min) and delayed (24 h) changes in the cerebral ¹⁸fluorodeoxyglucose (¹⁸F-FDG) uptake by positron emission tomography (PET) in control and Wisket rats. No significant differences were identified in the basal whole-brain metabolism between the two groups, and the metabolism was not modified acutely by a single intraperitoneal caffeine (20 mg/kg) injection in either group. However, one day after caffeine administration, significantly enhanced ¹⁸F-FDG uptake was detected in the whole brain and the investigated areas (hippocampus, striatum, thalamus, and hypothalamus) in the control group. Although the Wisket animals showed only moderate enhancements in the ¹⁸F-FDG uptake, significantly lower brain metabolism was observed in this group than in the caffeine-treated control group. This study highlights that the basal brain metabolism of Wisket animals was similar to control rats, and that was not influenced acutely by single caffeine treatment at the whole-brain level. Nevertheless, the distinct delayed responsiveness to this psychostimulant in Wisket model rats suggests impaired control of the cerebral metabolism.     

Chitin-Derived AVR-48 Prevents Experimental Bronchopulmonary Dysplasia (BPD) and BPD-Associated Pulmonary Hypertension in Newborn Mice

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and a key contributor to the large health care burden associated with prematurity, longer hospital stays, higher hospital costs, and frequent re-hospitalizations of affected patients through the first year of life and increased resource utilization throughout childhood. This disease is associated with abnormal pulmonary function that may lead to BPD-associated pulmonary hypertension (PH), a major contributor to neonatal mortality and morbidity. In the absence of any definitive treatment options, this life-threatening disease is associated with high resource utilization during and after neonatal intensive care unit (NICU) stay. The goal of this study was to test the safety and efficacy of a small molecule derivative of chitin, AVR-48, as prophylactic therapy for preventing experimental BPD in a mouse model. Two doses of AVR-48 were delivered either intranasally (0.11 mg/kg), intraperitoneally (10 mg/kg), or intravenously (IV) (10 mg/kg) to newborn mouse pups on postnatal day (P)2 and P4. The outcomes were assessed by measuring total inflammatory cells in the broncho-alveolar lavage fluid (BALF), chord length, septal thickness, and radial alveolar counts of the alveoli, Fulton’s Index (for PH), cell proliferation and cell death by immunostaining, and markers of inflammation by Western blotting and ELISA. The bioavailability and safety of the drug were assessed by pharmacokinetic and toxicity studies in both neonatal mice and rat pups (P3-P5). Following AVR-48 treatment, alveolar simplification was improved, as evident from chord length, septal thickness, and radial alveolar counts; total inflammatory cells were decreased in the BALF; Fulton’s Index was decreased and lung inflammation and cell death were decreased, while angiogenesis and cell proliferation were increased. AVR-48 was found to be safe and the no-observed-adverse-effect level (NOAEL) in rat pups was determined to be 100 mg/kg when delivered via IV dosing with a 20-fold safety margin. With no reported toxicity and with a shorter half-life, AVR-48 is able to reverse the worsening cardiopulmonary phenotype of experimental BPD and BPD-PH, compared to controls, thus positioning it as a future drug candidate.     

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.     

Bazedoxifene,a Selective Estrogen Receptor Modulator,Promotes Functional Recovery in a Spinal Cord Injury Rat Model

In research on various central nervous system injuries, bazedoxifene acetate (BZA) has shown two main effects: neuroprotection by suppressing the inflammatory response and remyelination by enhancing oligodendrocyte precursor cell differentiation and oligodendrocyte proliferation. We examined the effects of BZA in a rat spinal cord injury (SCI) model. Anti-inflammatory and anti-apoptotic effects were investigated in RAW 264.7 cells, and blood-spinal cord barrier (BSCB) permeability and angiogenesis were evaluated in a human brain endothelial cell line (hCMEC/D3). In vivo experiments were carried out on female Sprague Dawley rats subjected to moderate static compression SCI. The rats were intraperitoneally injected with either vehicle or BZA (1mg/kg pre-SCI and 3 mg/kg for 7 days post-SCI) daily. BZA decreased the lipopolysaccharide-induced production of proinflammatory cytokines and nitric oxide in RAW 264.7 cells and preserved BSCB disruption in hCMEC/D3 cells. In the rats, BZA reduced caspase-3 activity at 1 day post-injury (dpi) and suppressed phosphorylation of MAPK (p38 and ERK) at dpi 2, hence reducing the expression of IL-6, a proinflammatory cytokine. BZA also led to remyelination at dpi 20. BZA contributed to improvements in locomotor recovery after compressive SCI. This evidence suggests that BZA may have therapeutic potential to promote neuroprotection, remyelination, and functional outcomes following SCI.     

Evidence for the existence of a specific g protein-coupled receptor activated by guanosine

Guanosine, released extracellularly from neurons and glial cells, plays important roles in the central nervous system, including neuroprotection. The innovative DELFIA Eu‐GTP binding assay was optimized for characterization of the putative guanosine receptor binding site at rat brain membranes by using a series of novel and known guanosine derivatives. These nucleosides were prepared by modifying the purine and sugar moieties of guanosine at the 6‐ and 5′‐positions, respectively. Results of these experiments prove that guanosine, 6‐thioguanosine, and their derivatives activate a G protein‐coupled receptor that is different from the well‐characterized adenosine receptors.     

The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine

Background

Although caffeine supplementation improves performance, the ergogenic effect is variable. The cause(s) of this variability are unknown. A (C/A) single nucleotide polymorphism at intron 1 of the cytochrome P450 (CYP1A2) gene influences caffeine metabolism and clinical outcomes from caffeine ingestion. The purpose of this study was to determine if this polymorphism influences the ergogenic effect of caffeine supplementation.

Methods

Thirty-five trained male cyclists (age = 25.0 ± 7.3 yrs, height = 178.2 ± 8.8 cm, weight = 74.3 ± 8.8 kg, VO₂max = 59.35 ± 9.72 ml·kg^-1·min^-1) participated in two computer-simulated 40-kilometer time trials on a cycle ergometer. Each test was performed one hour following ingestion of 6 mg·kg^-1 of anhydrous caffeine or a placebo administered in double-blind fashion. DNA was obtained from whole blood samples and genotyped using restriction fragment length polymorphism-polymerase chain reaction. Participants were classified as AA homozygotes (N = 16) or C allele carriers (N = 19). The effects of treatment (caffeine, placebo) and the treatment × genotype interaction were assessed using Repeated Measures Analysis of Variance.

Results

Caffeine supplementation reduced 40 kilometer time by a greater (p < 0.05) magnitude in AA homozygotes (4.9%; caffeine = 72.4 ± 4.2 min, placebo = 76.1 ± 5.8 min) as compared to C allele carriers (1.8%; caffeine = 70.9 ± 4.3 min, placebo = 72.2 ± 4.2 min).

Conclusions

Results suggest that individuals homozygous for the A allele of this polymorphism may have a larger ergogenic effect following caffeine ingestion.