Increasing evidence suggests that regular consumption of coffee, tea and dark chocolate (cacao) can promote brain health and may reduce the risk of age-related neurodegenerative disorders. However, the complex array of phytochemicals in coffee and cacao beans and tea leaves has hindered a clear understanding of the component(s) that affect neuronal plasticity and resilience. One class of phytochemicals present in relatively high amounts in coffee, tea and cacao are methylxanthines. Among such methylxanthines, caffeine has been the most widely studied and has clear effects on neuronal network activity, promotes sustained cognitive performance and can protect neurons against dysfunction and death in animal models of stroke, Alzheimer’s disease and Parkinson’s disease. Caffeine’s mechanism of action relies on antagonism of various subclasses of adenosine receptors. Downstream xanthine metabolites, such as theobromine and theophylline, may also contribute to the beneficial effects of coffee, tea and cacao on brain health.
... Coffee is popularly consumed as a caffeine-containing beverage (CCO) and has potential health benefits and risks based on the food-based dietary guidelines of the Food and Agriculture Organization (FAO) of the United Nations . Epidemiological studies have demonstrated that coffee consumption reduces the risk of neurological diseases, including Alzheimer's disease and Parkinson's disease . For example, coffee consumption ameliorated cognitive impairment induced by Alzheimer's disease . ...
... For example, coffee consumption ameliorated cognitive impairment induced by Alzheimer's disease . Another report showed a negative association between moderate consumption of coffee and the risk of age-related cognitive disorders and Parkinson's disease . Coffee consumption has been also linked to potential health benefits as a consequence of their chemopreventive and anti-inflammatory effects. ...
Coffee is one of the most widely consumed beverages, which has several effects on the human body. In particular, current evidence suggests that coffee consumption is associated with a reduced risk of inflammation, various types of cancers, and certain neurodegenerative diseases. Among the various constituents of coffee, phenolic phytochemicals, more specifically chlorogenic acids, are the most abundant, and there have been many attempts to utilize coffee chlorogenic acid for cancer prevention and therapy. Due to its beneficial biological effect on the human body, coffee is regarded as a functional food. In this review article, we summarize the recent advances and knowledge on the association of phytochemicals contained in coffee as nutraceuticals, with a particular focus on phenolic compounds, their intake, and nutritional biomarkers, with the reduction of disease risk, including inflammation, cancer, and neurological diseases.
... Metabolites associated with caffeine intake in our study, such as AAMU, theophylline, paraxanthine, caffeine, quinate, trigonelline, 1-methylxanthine, and 1-methylurate, replicated previous findings [39,40]. Methylxanthines are a class of phytochemicals, including caffeine, theophylline, and 1-methylxanthine, that act as vasodilators and can reduce the risk of stroke, preventing further neurological damage . Other findings such as 1,7-dimethylurate, 1,3-dimethylurate, 3-hydroxypyridine sulfate, and hippurate are also of interest. ...
Modifiable factors can influence the risk for Alzheimer's disease (AD) and serve as targets for intervention; however, the biological mechanisms linking these factors to AD are unknown. This study aims to identify plasma metabolites associated with modifiable factors for AD, including MIND diet, physical activity, smoking, and caffeine intake, and test their association with AD endophenotypes to identify their potential roles in pathophysiological mechanisms. The association between each of the 757 plasma metabolites and four modifiable factors was tested in the wisconsin registry for Alzheimer's prevention cohort of initially cognitively unimpaired, asymptomatic middle-aged adults. After Bonferroni correction, the significant plasma metabolites were tested for association with each of the AD endophenotypes, including twelve cerebrospinal fluid (CSF) biomarkers, reflecting key pathophysiologies for AD, and four cognitive composite scores. Finally, causal mediation analyses were conducted to evaluate possible mediation effects. Analyses were performed using linear mixed-effects regression. A total of 27, 3, 23, and 24 metabolites were associated with MIND diet, physical activity, smoking, and caffeine intake, respectively. Potential mediation effects include beta-cryptoxanthin in the association between MIND diet and preclinical Alzheimer cognitive composite score, hippurate between MIND diet and immediate learning, glutamate between physical activity and CSF neurofilament light, and beta-cryptoxanthin between smoking and immediate learning. Our study identified several plasma metabolites that are associated with modifiable factors. These metabolites can be employed as biomarkers for tracking these factors, and they provide a potential biological pathway of how modifiable factors influence the human body and AD risk.
... It is known as the most widely consumed central nervous system (CNS) stimulant and is found in coffee, tea, chocolate, some foods, and in medicinal drugs [3,4]. CAF has high solubility in water and is rapidly absorbed from the gastrointestinal tract, reaching its highest plasma concentration within minutes [3,5]. The main reason why its consumption is so common is that it keeps people alert and awake, as a result of CAF having the same basic structure as adenosine, an endogenous sleep factor in the brain that controls the potent and enhancing effect of acetylcholine in the thalamus and cortex. ...
Objective: Caffeine (CAF), which is in the methylxanthines group (1,3,7-trimethylxanthine), is a neurologically active food component that is widely consumed and has a stimulating effect on the central nervous system. CAF taken in high doses during pregnancy rapidly crosses the placenta and causes many negative conditions such as low birth weight infants, premature births, spontaneous abortion, stillbirth, and principally fetal growth retardation. On the other hand, melatonin (MEL) is an endogenous hormone secreted from the pineal gland that plays a role in the regulation of many biological functions such as sleep, biological rhythm, reproduction, immunity and has neuroprotective effects. In this study, we aimed to investigate the possible effects of exogenous MEL on the fetal hippocampus damage caused by high-dose CAF administration in pregnant rats.
Methods: In the study, 32 adult Wistar albino female rats were divided into four experimental groups after conception (n=8). No compound was administered to the control group. In the MEL group, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day at 9-20 days of pregnancy. In the CAF group, i.p. CAF was administered at a dose of 60 mg/kg/day at 9-20 days of pregnancy. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 mg/kg/day and 10 mg/kg/day, respectively at 9-20 days of pregnancy. Histological tissue processing procedures were performed after the extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy. Hippocampal regions of fetal brains were analyzed by Hematoxylin and Eosin (H&E) and Cresyl Echt Violet (CEV) histochemical staining, anti-GFAP and anti-synaptophysin immunohistochemical staining methods.
Results: While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. In histological examinations, while the MEL group showed similar characteristics with the control group, it was observed that the pyramidal cell layer consisted of 8-10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group. It was found that these findings decreased in the CAF plus MEL group.
Conclusion: Ultimately, it was determined that high-dose CAF administration caused delays and deterioration in neurogenesis in the fetal hippocampus region, and it was also shown that MEL administration was effective in reducing these findings.
... Fermented tea such as dark tea contains more abundant oxidized polyphenols, theophylline, polysaccharides, ellagic acid and fatty acids, which can target to regulate AMPK and G-protein coupled receptors to promote lipid metabolism and delay degenerative diseases . Liupao tea has the characteristics of red, thick, aged and mellow flavor quality. ...
Aging and metabolic disorders feedback and promote each other and are closely related to the occurrence and development of cardiovascular disease, type 2 diabetes, neurodegeneration and other degenerative diseases. Liupao tea is a geographical indication product of Chinese dark tea, with a “red, concentrated, aged and mellow” flavor quality. In this study, the aqueous extract of aged Liupao tea (ALPT) administered by continuous gavage significantly inhibited the increase of visceral fat and damage to the intestinal–liver–microbial axis in high-fat modeling of SAMP8 (P8+HFD) mice. Its potential mechanism is that ALPT significantly inhibited the inflammation and aggregation formation pathway caused by P8+HFD, increased the abundance of short-chain fatty acid producing bacteria Alistipes, Alloprevotella and Bacteroides, and had a calorie restriction effect. The results of the whole target metabolome network pharmacological analysis showed that there were 139 potential active components in the ALPT aqueous extract, and the core targets of their actions were SRC, TP53, AKT1, MAPK3, VEGFA, EP300, EGFR, HSP90AA1, CASP3, etc. These target genes were mainly enriched in cancer, neurodegenerative diseases, glucose and lipid metabolism and other pathways of degenerative changes. Molecular docking further verified the reliability of network pharmacology. The above results indicate that Liupao tea can effectively delay the body’s degenerative changes through various mechanisms and multi-target effects. This study revealed that dark tea such as Liupao tea has significant drinking value in a modern and aging society.
... Caffeine is a methylxanthine that has been the most widely studied and has apparent effects on neuronal network activity, promotes sustained cognitive performance and can protect neurons against dysfunction and death in animal models of stroke, Alzheimer's disease and Parkinson's disease (Camandola et al., 2019). ...
... The reason for this effect may be that tea intake is very common in the dietary pattern of the Chinese population. Previous studies reported that tea is mainly rich in xanthine and other derivative substances, such a caffeine . Furthermore, the intake of foods rich in xanthine, such as tea, was found to be associated with decreased OC occurrence and better prognosis . ...
Current biological evidence suggests that purine involvement in purine metabolism may contribute to the development and progression of ovarian cancer (OC), but the epidemiological association is currently unknown.
A total of 703 newly diagnosed patients with OC aged 18-79 years were included in this prospective cohort study. Utilizing a verified food-frequency questionnaire, the participants' dietary consumption was gathered. Using medical records and ongoing follow-up, the deaths up until 31 March 2021 were determined. To assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of purine intake with OC mortality, Cox proportional-hazard models were utilized.
During the median follow-up of 31 months (interquartile: 20-47 months), 130 deaths occurred. We observed an improved survival for the highest tercile of total purine intake compared with the lowest tercile (HR = 0.39, 95% CI = 0.19-0.80; p trend < 0.05), and this protective association was mainly attributed to xanthine intake (HR = 0.52, 95% CI = 0.29-0.94, p trend < 0.05). Additionally, we observed a curving relationship in which OC mortality decreased with total purine intake, and the magnitude of the decrease was negatively correlated with intake (p non-linear < 0.05). Significant inverse associations were also observed in subgroup analyses and sensitivity analyses according to demographic and clinical characteristics. Moreover, we observed that xanthine intake and hypoxanthine intake had a multiplicative interaction with ER and PR expression (p < 0.05), respectively.
A high total purine and xanthine intake was linked to a lower risk of OC mortality. Further clarification of these findings is warranted.
... A majority of these DEPs are involved in root architecture, energy metabolism, ROS detoxification, cell signaling, primary and secondary metabolisms, and molecular transport systems (Kumar and Majeti 2014). Cocoa is a dry, powdered, non-fat component product prepared from seeds of the Theobroma cacao L. tree and is known to contain biologically active substances that are beneficial for human health (Ellam and Williamson 2013;Camandola et al. 2019). Both T. cacao and its products are highly contaminated with Pb, therefore stress. ...
Medicinal plants are the richest sources of a diverse range of phytochemicals which can be validated for their efficacy to develop new therapeutic molecules against a spectrum of human diseases. Despite the fact that these phytochemicals are present at low concentrations, their abundance is influenced by the dynamic metabolic pathways which are modulated at the genome and proteome level. A variety of environmental factors including biotic (e.g., pathogen infection and herbivore attack) and abiotic factors (e.g., light, temperature, drought, salinity, heavy metals and other toxic chemicals) influence these metabolic pathways and other cellular processes, often posing a threat to the yield of crops including medicinal plants crops. Emerging omics technologies have gained interest in the recent years to provide insights on the underlying stress tolerance molecular mechanisms exhibited by plants to cope with different environmental stresses at system biology level. Proteomics, bridging the gap between genomics and transcriptomics, offers a useful approach to study and characterize the proteome (the total set of proteins present in a cell). Mass-spectroscopy-based proteomics has been widely used for characterization and quantification of stress effect at protein and subproteome levels to gain insights on the key biomarker proteins and their post translation modification, which subsequently can be used for developing new breeding strategies to modulate the plant stress tolerance. This chapter discusses the medicinal plants’ proteomics in response to a variety of stress factors including light (UV-B and UV-D), temperature (high temperature and low temperature), drought (water deficit), salinity (salt stress) and heavy metals (lead, cadmium, chromium, and Copper).KeywordsMedicinal plantsProteomicsMass spectrometryAbiotic stressTemperature stressSalt stressDrought stressMetal stressUV stress
A bidirectional relationship between chronic pain (CP) and mental disorders has been reported, and coffee was believed to be associated with both. However, the association of coffee in this bidirectional relationship remains unclear. We aim to analyze the association of coffee consumption on the relationship of CP with depression and anxiety.
A total of 376,813 participants from UK Biobank were included. We collected data on anxiety, depression and CP from objects of our study population. The association of coffee consumption on the relationship of CP with depression and anxiety was assessed through logistic/linear regression models. Moreover, seemingly unrelated estimation test (SUEST) was used to compare whether the coefficients differed in two different groups.
We observed significant associations of coffee consumption in the interaction of CP with depression and anxiety, such as the association of multisite chronic pain (MCP) on self-reported depression (βcoffee = 0.421, βnon-coffee = 0.488, PSUEST = 0.001), and the association of MCP on generalized anxiety disorder-7 (GAD-7) scores (βcoffee = 0.561, βnon-coffee = 0.678, PSUEST = 0.004) were significantly different between coffee drinking and non-coffee drinking groups. Furthermore, in analysis stratified by gender, we found headache (βmale = 0.392, βfemale = 0.214, PSUEST = 0.022) and hip pain (βmale = 0.480, βfemale = 0.191, PSUEST = 0.021) had significant associations with self-reported depression between males and females groups in coffee drinkers.
Our results suggested that coffee consumption has a significant association on the relationship of CP with depression and anxiety.
The aim of this study was to explore urine caffeine metabolites in relation to cognitive performance among 2011-2014 National Health and Nutrition Examination Survey participants aged ≥60 years. We hypothesized that urine caffeine metabolites were positively associated with cognition in older adults. Caffeine and 14 of its metabolites were quantified in urine by use of high-performance liquid chromatography-electrospray ionization-tandem quadruple mass spectrometry with stable isotope labeled internal standards. Cognitive assessment was based on scores from the word learning and recall modules. Participants were categorized based on the quartiles of caffeine and its metabolites level. The association between caffeine metabolites and each cognitive dimension was analyzed using multiple logistic regression analysis in adjusted models. Stratification analyses by gender were also performed. For CERAD test, there was a significant association between 1-methyluric acid (OR=0.62, 95% CI: 0.42 to 0.92), 7-methylxanthine(OR=0.49, 95% CI: 0.27 to 0.89), theophylline (OR=0.52, 95% CI: 0.29 to 0.92), as well as paraxanthine (OR=0.49, 95% CI: 0.27 to 0.88) and cognitive function. For animal fluency test, there was a positive association between theophylline (TP) (OR=0.44, 95% CI: 0.22 to 0.89) and cognitive function. The trend that the risk of low cognitive function decreased with increasing concentration of 1-methylxanthine (P trend=0.0229) was also observed. Furthermore, the same trend existed for 3-methylxanthine (p trend = 0.0375) in men. In conclusion, there was a significant positive association between urine caffeine metabolites and cognitive performance in older adults, particularly for theophylline, paraxanthine and caffeine; and the association might be dependent on gender.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is generally accepted that dopamine replacement therapy substantially improves motor symptoms; however, there is a worldwide tendency to include nutrients in treatment strategies. In the present review, caffeine and chocolate are discussed. Caffeine use seems to postpone the occurrence of PD in men, and perhaps also in women who do not take postmenopausal hormone replacement therapy. There are contradictory data concerning possible caffeine-induced improvements in PD symptoms. Given that the basic action of caffeine is the antagonism of adenosine receptors, adenosine antagonists may be a new option for treating PD patients. Furthermore, PD patients tend to have increased chocolate consumption; this may be causally related to ingredients such as phenylethylamine. Thus, nutrients such as caffeine and chocolate may play an important role in postponing and/or improving symptoms in PD.
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10⁻⁹) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10⁻²⁰). Locus 1p36.12 is significantly associated (P=2.2 × 10⁻⁸) with epigenetic ageing of the prefrontal cortex, independent of the proportion of neurons. Our GWAS of the proportion of neurons identified two genome-wide significant loci (10q26 and 12p13.31) and resulted in a gene set that overlaps significantly with sets found by GWAS of age-related macular degeneration (P=1.4 × 10⁻¹²), ulcerative colitis (P<1.0 × 10⁻²⁰), type 2 diabetes (P=2.8 × 10⁻¹³), hip/waist circumference in men (P=1.1 × 10⁻⁹), schizophrenia (P=1.6 × 10⁻⁹), cognitive decline (P=5.3 × 10⁻⁴) and Parkinson's disease (P=8.6 × 10⁻³).
Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress.
Alzheimer’s disease is a common neurodegenerative disorder in elderly. This study was aimed to systematically evaluate the association between tea intake and the risk of cognitive disorders by meta-analysis.
Methods and Findings
PubMed, Embase and Wanfang databases were systematically searched and a total of 26 observational studies were included in this study. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated and pooled by using fixed or random effects models according to the degree of heterogeneity.
The overall pooled analysis indicated that tea intake could significantly reduce the risk of cognitive disorders (OR = 0.65, 95%CI = 0.58–0.73). Subgroup analyses were conducted based on study design, population, frequency of tea drinking and type of cognitive disorders. The results showed that tea drinking was significantly associated with the reduced incidence of cognitive disorders in all of subgroups based on study design and frequency of tea drinking. In particular, tea drinking was inversely associated with the risk of cognitive impairment (CoI), mild cognitive impairment (MCI), cognitive decline and ungrouped cognitive disorders. Moreover, for population subgroups, the significant association was only found in Chinese people.
Our study suggests that daily tea drinking is associated with decreased risk of CoI, MCI and cognitive decline in the elderly. However, the association between tea intake and Alzheimer’s disease remains elusive.
1. The locomotor stimulatory effects induced by caffeine (1,3, 7-trimethylxanthine) in rodents have been attributed to antagonism of adenosine A(1) and A(2A) receptors. Little is known about its locomotor depressant effects seen when acutely administered at high doses. The roles of adenosine A(1) and A(2A) receptors in these activities were investigated using a Digiscan actimeter in experiments carried out in mice. Besides caffeine, the A(2A) antagonist SCH 58261 (5-amino-7-(beta-phenylethyl)-2-(8-furyl)pyrazolo[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine), the A(1) antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), the A(1) agonist CPA (N(6)-cyclopentyladenosine) and A(2A) receptor knockout mice were used. 2. Caffeine had a biphasic effect on locomotion of wild-type mice not habituated to the open field, stimulating locomotion at 6.25 - 25 mg kg(-1) i.p. doses, while depressing it at 100 mg kg(-1). In sharp contrast, caffeine dose-dependently decreased locomotion in A(2A) receptor knockout mice over the whole range of tested doses. 3. The depressant effects induced by high doses of caffeine were lost in control CD1 mice habituated to the open field. 4. The A(1) agonist CPA depressed locomotion at 0.3 - 1 mg kg(-1) i.p. doses. 5. The A(1) antagonist DPCPX decreased locomotion of A(2A) receptor knockouts and CD1 mice at 5 mg kg(-1) i.p. and 25 mg kg(-1) i.p. respectively. 6. DPCPX (0.2 - 1 mg kg(-1) i.p.) left unaltered or even reduced the stimulant effect of SCH 58261 (1 - 3 mg kg(-1) i.p.) on CD1 mice. 7. These results suggest therefore that the stimulant effect of low doses of caffeine is mediated by A(2A) receptor blockade while the depressant effect seen at higher doses under some conditions is explained by A(1) receptor blockade.
Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial effects of caffeine on health.We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10⁻⁸) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10⁻⁶). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolismand confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism.