Protective Effect Of Caffeine Research Articles

Protective Effect of Caffeine and Chlorogenic Acids of Coffee in Liver Disease

Coffee is one of the most widely consumed beverages in the world due to its unique aroma and psychostimulant effects, mainly due to the presence of caffeine. In recent years, experimental evidence has shown that the moderate consumption of coffee (3/4 cups per day) is safe and beneficial to human health, revealing protective effects against numerous chronic metabolic diseases such as diabetes, cardiovascular, neurodegenerative, and hepatic diseases. This review focuses on two of coffee’s main bioactive compounds, i.e., caffeine and chlorogenic acids, and their effects on the progression of chronic liver diseases, demonstrating that regular coffee consumption correlates with a lower risk of the development and progression of non-alcoholic steatohepatitis, viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. In particular, this review analyzes caffeine and chlorogenic acid from a pharmacological point of view and explores the molecular mechanism through which these compounds are responsible for the protective role of coffee. Both bioactive compounds, therefore, have antifibrotic effects on hepatic stellate cells and hepatocytes, induce a decrease in connective tissue growth factor, stimulate increased apoptosis with anti-cancer effects, and promote a major inhibition of focal adhesion kinase, actin, and protocollagen synthesis. In conclusion, coffee shows many beneficial effects, and experimental data in favor of coffee consumption in patients with liver diseases are encouraging, but further prospective studies are needed to demonstrate its preventive and therapeutic role in chronic liver diseases.

Protective Effects of Caffeine on Chikungunya and Zika Virus Infections: An in-vitro and in-silico Study.

Infection by viruses Chikungunya (CHIKV) and Zika (ZIKV) continue to be serious problems in tropical and subtropical areas of the world. Here, we evaluated the antiviral and virucidal activity of caffeine against CHIKV and ZIKV in Vero, A549, and Huh-7 cell lines. Results showed that caffeine displays antiviral properties against both viruses. By pre-and post-infection treatment, caffeine significantly inhibited CHIKV and ZIKV replication in a dose-dependent manner. Furthermore, caffeine showed a virucidal effect against ZIKV. Molecular docking suggests the possible binding of caffeine with envelope protein and RNA-dependent RNA polymerase of CHIKV and ZIKV. This is the first study that showed an antiviral effect of caffeine against CHIKV and ZIKV. Although further studies are needed to better understand the mechanism of caffeine-mediated repression of viral replication, caffeine appears to be a promising compound that could be used for in vivo studies, perhaps in synergy with other compounds present in daily beverages.

Modifiable Risk Factors and Preventative Strategies for Severe Retinopathy of Prematurity.

Severe ROP is characterized by the development of retinal fibrovascular proliferation that may progress to retinal detachment. The purpose of this report is to review five of the most common and well-studied perinatal and neonatal modifiable risk factors for the development of severe ROP. Hyperoxemia, hypoxia, and associated prolonged respiratory support are linked to the development of severe ROP. While there is a well-established association between clinical maternal chorioamnionitis and severe ROP, there is greater variability between histologic chorioamnionitis and severe ROP. Neonatal sepsis, including both bacterial and fungal subtypes, are independent predictors of severe ROP in preterm infants. Although there is limited evidence related to platelet transfusions, the risk of severe ROP increases with the number and volume of red blood cell transfusions. Poor postnatal weight gain within the first six weeks of life is also strongly tied to the development of severe ROP. We also discuss preventative strategies that may reduce the risk of severe ROP. Limited evidence-based studies exist regarding the protective effects of caffeine, human milk, and vitamins A and E.

Caffeine improves memory and cognition via modulating neural progenitor cell survival and decreasing oxidative stress in Alzheimer's rat model.

Caffeine possesses potent antioxidant, anti-inflammatory and anti-apoptotic activities against a variety of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). The goal of this study was to investigate the protective role of a psychoactive substance like caffeine on hippocampal neurogenesis and memory functions in streptozotocin (STZ)-induced neurodegeneration in rats. Caffeine is a natural CNS stimulant, belonging to the methylxanthine class, and is a widely consumed psychoactive substance. It is reported to abate the risk of various abnormalities that are cardiovascular system (CVS) related, cancer related, or due to metabolism dysregulation. Short-term caffeine exposure has been widely evaluated, but its chronic exposure is less explored and pursued. Several studies suggest a devastating role of caffeine in neurodegenerative disorders. However, the protective role of caffeine on neurodegeneration is still unclear. Here, we examined the effects of chronic caffeine administration on hippocampal neurogenesis in intracerebroventricular STZ injection induced memory dysfunction in rats. The chronic effect of caffeine on proliferation and neuronal fate determination of hippocampal neurons was evaluated by co-labeling of neurons by thymidine analogue BrdU that labels new born cells, DCX (a marker for immature neurons) and NeuN that labels mature neurons. STZ (1 mg/kg, 2 μl) was injected stereotaxically into the lateral ventricles (intracerebroventricular injection) once on day 1, followed by chronic treatment with caffeine (10 mg/kg, i.p) and donepezil (5 mg/kg, i.p.). Protective effect of caffeine on cognitive impairment and adult hippocampal neurogenesis was evaluated. Our findings show decreased oxidative stress burden and amyloid burden following caffeine administration in STZ lesioned SD rats. Further, double immunolabeling with bromodeoxyuridine+/doublecortin+ (BrdU+/DCX+) and bromodeoxyuridine+/ neuronal nuclei+ (BrdU+/NeuN+) has indicated that caffeine improved neuronal stem cell proliferation and long term survival in STZ lesioned rats. Our findings support the neurogenic potential of caffeine in STZ induced neurodegeneration.

Mitigative effect of caffeine against diclofenac-induced hepato-renal damage and chromosomal aberrations in male albino rats.

Among the most commonly consumed non-steroidal anti-inflammatory drugs (NSAID) is Diclofenac (Dic), especially in low-income countries due to its high efficiency and affordable price. However, the continuous administration of Diclofenac may induce toxic effects on various body organs including the liver and kidney. Caffeine (Caf) (1,3,7-trimethylxanthine) is a pharmacologically active alkaloid type with antioxidant and anti-inflammatory actions. The current study aims to evaluate the ameliorative effect of Caffeine against Dic-induced hepato-renal toxicity and damage. Twenty-four male albino rats type were assigned randomly into four groups (n = 6): (Group 1): Control group, (Group 2): Six male rats were exposed to Dic 10mg/kg intraperitoneally (I.P) for 28 days, (Group 3): Six male rats were exposed to Caf (15mg/kg orally) for 28 days; (Groups 4): Six male rats were exposed to Dic (10mg/kg, i.p) + Caf (15mg/kg, orally) for 28 days. Histopathological study and various biological parameters were estimated among the four groups including hemoglobin (Hb%) red blood cells (RBCs), Hematocrit (HT%), total leucocyte count (WBCs), lipid peroxidation (LPO), glutathione peroxidase (GPx), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine, tumor necrosis factor-α (TNF-α), and nitric oxide (NO). The administration of Diclofenac resulted in significant deteriorations in the histopathological findings and estimated biological parameters. Whereas, daily Caffeine administration ameliorated Diclofenac-induced toxicity in the kidney and liver by three mechanisms including antioxidant, anti-inflammatory, and DNA damage inhibition. The current study demonstrated the promising ameliorative and protective effects of Caffeine against Diclofenac-induced hepatic and renal injury.

The Conflicting Role of Caffeine Supplementation on Hyperoxia-Induced Injury on the Cerebellar Granular Cell Neurogenesis of Newborn Rats.

Preterm birth disrupts cerebellar development, which may be mediated by systemic oxidative stress that damages neuronal developmental stages. Impaired cerebellar neurogenesis affects several downstream targets important for cognition, emotion, and speech. In this study, we demonstrate that oxidative stress induced with high oxygen (80%) for three or five postnatal days (P3/P5) could significantly damage neurogenesis and proliferative capacity of granular cell precursor and Purkinje cells in rat pups. Reversal of cellular neuronal damage after recovery to room air (P15) was augmented by treatment with caffeine. However, downstream transcripts important for migration and differentiation of postmitotic granular cells were irreversibly reduced by hyperoxia, without rescue by caffeine. Protective effects of caffeine in the cerebellum were limited to neuronal survival but failed to restore important transcript signatures.

Caffeine prevents oxalate-induced epithelial-mesenchymal transition of renal tubular cells by its anti-oxidative property through activation of Nrf2 signaling and suppression of Snail1 transcription factor

Caffeine is an active ingredient found in coffee and energy beverages. Its hepatoprotective effects against liver fibrosis are well-documented. Nonetheless, its renoprotective effects against renal fibrogenesis and epithelial-mesenchymal transition (EMT) processes remain unclear and under-investigated. In this study, the protective effects of caffeine against oxalate-induced EMT in renal tubular cells were evaluated by various assays to measure expression levels of epithelial and mesenchymal markers, cell migrating activity, level of oxidized proteins, and expression of Nrf2 and Snail1. Oxalate at sublethal dose significantly suppressed cell proliferation but increased cell elongation, spindle index and migration. Oxalate also decreased expression of epithelial markers (zonula occludens-1 (ZO-1) and E-cadherin) but increased expression of mesenchymal markers (fibronectin, vimentin and α-smooth muscle actin (α-SMA)). All of these EMT-inducing effects of oxalate could be prevented by pretreatment with caffeine. While oxalate increased oxidized proteins and Snail1 levels, it decreased Nrf2 expression. Caffeine could preserve all these molecules to their basal (control) levels. Finally, silencing of Nrf2 expression by small interfering RNA (siRNA) could abolish such protective effects of caffeine on oxalate-induced EMT. Our data indicate that the renoprotective effects of caffeine against oxalate-induced EMT is mediated, at least in part, by its anti-oxidative property through activation of Nrf2 signaling and suppression of Snail1 transcription factor.

Protective effect of caffeine and/or taurine on the 6-hydroxydopamine-induced rat model of Parkinson’s disease: Behavioral and neurochemical evidence

Caffeine and taurine, which possess neuro-modulatory activity happen to be consumed together as part of the constituents of energy drinks, could have beneficial effects and prevent neuronal deterioration in Parkinson's disease (PD). This study aimed to investigate behavioral and neurochemical effects of these two agents in an animal model of PD at two time points to evaluate possible neuro-protective or neuro-modulatory effects. Stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum was used to model PD-like behavior in animals. Motor behavior was assessed by a characteristic rotation behavior response to the apomorphine challenge and dopamine levels in the striatum were quantified using HPLC-ED. A reduction in apomorphine induced rotations following administration of caffeine and/or taurine as compared to the untreated lesioned group (controls) was shown. Significant decreases in dopamine levels were also seen in the ipsilateral side of 6-OHDA group, this effect was not significantly reversed in caffeine and taurine treated groups. Treatments partially restored the content of DA levels in the lesioned striatum. Current results demonstrated beneficial effects for the combination of caffeine and taurine in PD animal model, suggesting that consumption of both agents could be a new added therapeutic target for Parkinson's disease prevention and treatment.

Protective Effects of Caffeine and Artemisinin against Initiation of Breast Tumour in 7, 12-Dimethylbenzanthracene treated Albino Rats

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New insights into the effects of caffeine on adult hippocampal neurogenesis in stressed mice: Inhibition of CORT-induced microglia activation.

Chronic stress-evoked depression has been implied to associate with the decline of adult hippocampal neurogenesis. Caffeine has been known to combat stress-evoked depression. Herein, we aim to investigate whether the protective effect of caffeine on depression is related with improving adult hippocampus neurogenesis and explore the mechanisms. Mouse chronic water immersion restraint stress (CWIRS) model, corticosterone (CORT)-established cell stress model, a coculture system containing CORT-treated BV-2 cells and hippocampal neural stem cells (NSCs) were utilized. Results showed that CWIRS caused obvious depressive-like disorders, abnormal 5-HT signaling, and elevated-plasma CORT levels. Notably, microglia activation-evoked brain inflammation and inhibited neurogenesis were also observed in the hippocampus of stressed mice. In comparison, intragastric administration of caffeine (10 and 20mg/kg, 28days) significantly reverted CWIRS-induced depressive behaviors, neurogenesis recession and microglia activation in the hippocampus. Further evidences from both in vivo and in vitro mechanistic experiments demonstrated that caffeine treatment significantly suppressed microglia activation via the A2AR/MEK/ERK/NF-κB signaling pathway. The results suggested that CORT-induced microglia activation contributes to stress-mediated neurogenesis recession. The antidepression effect of caffeine was associated with unlocking microglia activation-induced neurogenesis inhibition.

Protective effect of caffeine and curcumin versus silymarin on nonalcoholic steatohepatitis in rats

Objective To compare between the effect of curcumin, caffeine with silymarin on an animal model of nonalcoholic steatohepatitis induced by a high-fat and high-sucrose (HFHS) diet. Background Nonalcoholic fatty liver disease is recognized as the most common cause of chronic liver disease. Pro-inflammatory and anti-inflammatory cytokines play a part in the pathogenesis of nonalcoholic fatty liver disease, oxidative stress, and insulin resistance. Materials and methods Fifty male albino rats were divided into five groups: control group; group B receives a HFHS diet for 16 weeks; group C receives a HFHS diet for 16 weeks and was treated by silymarin in the last 8 weeks; group D receives a HFHS diet for 16 weeks and was treated with curcumin in the last 8 weeks; and group E receives a HFHS diet for 16 weeks and was treated with caffeine in the last 8 weeks. Results The HFHS group shows a significant increase in body weight, insulin, tumor necrosis factor α, malonaldehyde, total cholesterol, and triglycerides; compared with the control group, silymarin-treated, curcumin-treated, and caffeine-treated groups show a significant decrease in these parameters. Conclusion Silymarin-treated, curcumin-treated, and caffeine-treated groups show a significant protection against HFHS (western) diet-induced nonalcoholic steatohepatitis.

The protective effects of caffeine and melatonin on antioxidant enzymes in rat fetal lung tissues

Aim: Teratogenic substances such as nicotine, alcohol, caffeine, and derivatives, which pregnant women may get exposed to unconsciously or use consciously can harm the mother and directly or indirectly damage embryonal and fetal tissues. Melatonin has been shown to exert direct free radical trapping and indirect antioxidant effects in different organs and tissues. In this study, we aimed to biochemically evaluate the effects of melatonin, a powerful antioxidant battling the oxidative effects of high and low doses of caffeine administered to pregnant rats in fetal lung tissues. Methods: In our study, 35 pregnant adult female Sprague-Dawley rats were used. Pregnant rats were divided into 7 groups with 5 rats in each. Caffeine and melatonin were administered for 20 days during the pregnancy. The gestational period lasted 21 days in average. The offspring were sacrificed, and lung tissues were removed. Superoxide dismutase (SOD), glutathione (GSH), glutathione disulfide (GSSG), total oxidant status (TOS), total antioxidant status (TAS), calcium (Ca) and vitamin D (Vit D) were measured by spectrophotometric assay. The oxidative stress index (OSI) and total glutathione (GSH/GSSG) were determinants of oxidative stress and were calculated as TOS/TAS and GSH/GSSG ratios, respectively.Results: The highest TAS value was obtained in the Melatonin group (M) group. GSH and GSH/GSSG was highest in the control group, whereas GSSG was the highest in the high-dose caffeine group (HDC) group. HDC group had the highest SOD value compared to the other groups (P<0.05).Conclusions: According to these data, it was determined that caffeine used during pregnancy delayed the development of lung, and melatonin, which is a strong antioxidant, minimized the delay.

Combination of Caffeine and Liver Albumin Plus Protects against Smoking-Induced Liver Injury in Rats

Background: A number of studies have revealed the hepatoprotective effect of coffee and tea. However, the role of caffeine on smoking-induced liver injury is not well elucidated. Liver Albumin Plus (LAP) is a liver supplement given in different liver diseases; to our knowledge, its role in smoking-induced liver injury is not clear. Objectives: This study aimed to find out the protective effect of caffeine and LAP alone and in combination in attenuation of smoking-induced liver injury. Methods: Thirty male albino rats were divided into a control group and a smoking group; the smoking group was then subdivided into a smoking group, a smoking + caffeine group, a smoking + LAP group, and a smoking + caffeine + LAP group. At the end of the experimental study, blood samples were collected for assessment of liver enzymes, alpha-fetoprotein (AFP), and interleukin 6, and livers were excised. Biochemical analysis of hydrogen peroxide (H₂O₂), superoxide dismutase (SOD), and hypoxia-inducible factor (HIF) as well as histological examination were done. Results: The results showed that smoking elevated liver enzymes, AFP, H₂O₂, and HIF and decreased SOD; histologically, deterioration of the liver was observed. On administration of caffeine, significant (p < 0.05) improvement in all measured parameters and preserved liver histological structure were observed, while intake of LAP alone showed some improvement. In combination, all liver parameters were improved and histological structure was preserved in contrast to each drug alone. Conclusion: It is better to give a combination of caffeine and LAP with cigarettes smoking to attenuate smoking-induced liver injury.

Involvement of acetylcholinesterase and protein kinase C in the protective effect of caffeine against β-amyloid-induced alterations in red blood cells.

It is well known the role of oxidative stress in the pathophysiology of Alzheimer's disease (AD) and of other neurodegenerative pathologies. We have previously documented that Amyloid beta peptide (1-42) (Abeta) dependent-oxidative modifications affect red blood cell (RBC) morphology and function. Experimental studies show that caffeine (CF) consumption is inversely correlated with AD. In this study, we investigated the role played by RBC in the protective mechanism elicited by CF against Abeta mediated toxicity. PS exposure levels by FACS analysis, as well as protein band 3 functionality analysis, indicated that CF at 100μM protected against Abeta-mediated membrane alterations, which are known to occur in AD. Moreover, CF counteracts inhibition of ATP release from RBC by Abeta, restoring its ability to modulate vasodilation. Concurrently, analysis of protein kinase C (PKC) and caspase 3 activities, responsible for cytoskeleton alterations, revealed that unlike to caspase 3, PKCα activation induced by Abeta was fully abolished by CF through a mechanism involving Acetylcholinesterase (AChE), located on external face of RBC plasma membrane. These results provide support for the hypothesis concerning the protective role of CF in AD patients could include also a peripheral mechanism involving RBC.

Caffeine prevents human prion protein-mediated neurotoxicity through the induction of autophagy.

The human prion protein (PrP) fragment PrP(106‑126) possesses the majority of the pathogenic properties associated with the infectious scrapie isoform of PrP, known as PrPSc. The accumulation of PrPSc in the brain of humans and animals affects the central nervous system. Recent epidemiological studies have suggested that caffeine, one of the major components of coffee, exerts protective effects against the development of neurodegeneration. However, the protective effects of caffeine against prion disease have not been reported to date. In this study, we therefore investigated the effects of caffeine on PrP-mediated neurotoxicity. The protein expression of the autophagosomal marker, LC3-II, was increased by caffeine in a dose-dependent manner, and the autophagy induced by caffeine protected the neuronal cells against PrP(106‑126)‑induced cell death. On the contrary, the downregulation of LC3-II using the autophagy inhibitors, 3-methyladenine (3-ΜΑ) and wortmannin, prevented the caffeine-mediated neuroprotective effects. To the best of our knowledge, the present study provides the first evidence that treatment with caffeine protects human neuronal cells against prion‑mediated neurotoxicity and these neuroprotective effects are mediated by caffeine-induced autophagy signals. Our data suggest that treatment with caffeine may be a novel therapeutic strategy for prion peptide‑induced apoptosis.

Protective effect of caffeine on ethyl methanesulfonate-induced wing primordial cells of Drosophila melanogaster.

Objectives:The antimutagenic effect of caffeine is evaluated against ethyl methanesulfonate (EMS)-induced mutation rate in Drosophila.Materials and Methods:The mutation rate is evaluated using wing mosaic assay. In transheterozygous larvae, multiple wing hair (mwh 0.3-3) and flare (flr 3-38.8) genes were used as markers of the extent of mutagenicity.Results:The results at 0.5 and 1.0 mM EMS concentration at both 48 ± 4 and 72 ± 4 h have shown consistent increase in mutation rate, which was being measured as frequency of clone formation per 105 cells. Toxicity of caffeine at 5 mM concentration was parallel to that of distilled water alone. At 0.5 mM EMS concentration at 42 ± 4 and 72 ± 4 h, Drosophila larvae mutation rate was significantly increased. Although caffeine prevented mutation rate in all pre, post, and combined treatment, it was more significant in pretreatment experiments where it was found to be effective in reducing the genotoxicity of EMS. However, the concentration of caffeine as recommended in dietary allowance did not induce the frequency of mutant clones in somatic mutation and recombination test (SMART) recorded.Conclusion:This study shows that caffeine significantly reduced the genotoxicity induced by EMS. However, the limitation in completely abolishing genotoxicity induced by EMS as observed at the dietary allowance of caffeine makes it interesting for further in-depth study. Further studies on the molecular mechanism of antigenotoxic effect of caffeine will also be interesting.

Increased expression and possible role of chitinase 3-like-1 in a colitis-associated carcinoma model.

To investigate the possible role of chitinase 3-like-1 (CHI3L1) in the progression of colitis-associated carcinoma (CAC). Thirty-four Balb/c mice were randomly assigned to five groups, including the control, CAC control, CAC + caffeine, colitis control and colitis + caffeine. Three animals were sacrificed every two weeks for blinded macroscopic inspection, histological analysis, and total RNA extraction. An immunofluorescent assay was performed using specimens from the colitis control and colitis + caffeine groups to investigate whether the protective effect of caffeine was associated with less oxidative DNA damage. In vitro, HT29 cells pre-stimulated with different concentrations of recombinant CHI3L1 protein and H2O2 were loaded with the DCFH-DA fluorescent probe to determine the effect of CHI3L1 on intracellular reactive oxygen species production. CHI3L1 mRNA was increased during the progression of colon carcinogenesis. Tumors were mostly located in the distal end of the colon where the expression of CHI3L1 was higher than in the proximal colon. Caffeine-treated mice developed fewer tumors and milder inflammation than untreated mice. CHI3L1 protein increased reactive oxygen species in HT29 cells when exposed to H2O2. Caffeine reduces tumor incidence by decreasing oxidative DNA damage. CHI3L1 may contribute to CAC by increasing reactive oxygen species production.

Prevention of hyperoxia-mediated pulmonary inflammation in neonatal rats by caffeine

In preterm human infants, briefly elevated concentrations of oxygen are associated with a prolonged increase in blood chemokine concentrations and the development of bronchopulmonary dysplasia (BPD). Caffeine given to preterm infants for the prevention or treatment of apnoea has been shown to reduce the rate of BPD. We tested the hypotheses that infant rats exposed to a combination of caffeine and hyperoxia would be less susceptible to lung injury than those exposed to hyperoxia alone and that caffeine decreases the pulmonary tissue expression of chemokines and leukocyte influx following hyperoxia. Using 6-day-old rat pups, we demonstrated that 24 h of 80% oxygen exposure caused pulmonary recruitment of neutrophils and macrophages. High levels of oxygen upregulated the expression of: the CXC chemokines, cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2; the CC-chemokine monocyte chemoattractant protein-1; the pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6, as measured by realtime PCR after the administration of caffeine (10 mg · kg(-1) body weight); and attenuated chemokine and cytokine upregulation, as well as the influx of CD11b(+), ED-1(+) and myeloperoxidase(+) leukocytes. These experiments suggest that protective effects of caffeine in the neonatal lung are mediated, at least in part, by reduction of pulmonary inflammation.

Protective effect of caffeine and a selective A2A receptor antagonist on impairment of memory and oxidative stress of aged rats

In this study, the effects of caffeine (CAF) and SCH58261, a selective A2A receptor antagonist, on memory impairment and oxidative stress generated by aging in rats were investigated. Young and aged rats were treated daily per 10days with CAF (30mg/kg p.o.) or SCH58261 (0.5mg/kg, p.o.) or vehicle (1ml/kg p.o.). Rats were trained and tested in a novel object recognition task. After the behavioral test, ascorbic acid and oxygen and nitrogen reactive species levels as well as Na+K+ ATPase activity were determined in rat brain. The results demonstrated that the age-related memory deficit was reversed by treatment with CAF or SCH58261. Treatment with CAF or SCH58261 significantly normalized oxygen and nitrogen reactive species levels increased in brains of aged rats. Na+K+ ATPase activity inhibited in brains of aged rats was also normalized by CAF or SCH58261 treatment. A decrease in basal ascorbic acid levels in brains of aged rats was not changed by CAF or SCH58261. These results demonstrated that CAF and SCH58261, modulators of adenosinergic receptors, were able to reverse age-associated memory impairment and to partially reduce oxidative stress.

Caffeine Intake and Dementia: Systematic Review and Meta-Analysis

A recent meta-analysis of 4 studies published up to January 2004 suggests a negative association between coffee consumption and Alzheimer's disease, despite important heterogeneity in methods and results. Several epidemiological studies on this issue have been published since then, warranting an update of the insights on this topic. We conducted a systematic review and meta-analysis of published studies quantifying the relation between caffeine intake and cognitive decline or dementia. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort and case-control studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Nine cohort and two case-control studies were included. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. The outcomes of the studies considered for meta-analysis were Alzheimer's disease in four studies, dementia or cognitive impairment in two studies, and cognitive decline in three studies. The summary relative risk (RR) for the association between caffeine intake and different measures of cognitive impairment/decline was 0.84 [95% Confidence Interval (95% CI): 0.72-0.99; I2=42.6%]. When considering only the cohort studies, the summary RR was 0.93 (95% CI: 0.83-1.04, I2= 0.0%), and 0.77 (95% CI: 0.63-0.95, I2= 34.7%), if the most influential study was excluded. This systematic review and meta-analysis found a trend towards a protective effect of caffeine, but the large methodological heterogeneity across a still limited number of epidemiological studies precludes robust and definite statements on this topic. and definite statements on this topic.