Dietary Caffeine Research Articles

Effect of Green Coffee Consumption on Resting Energy Expenditure, Blood Pressure, and Body Temperature in Healthy Women: A Pilot Study

ABSTRACTObjective: This study was conducted to determine the effects of green coffee consumption on resting energy expenditures (REEs), blood pressure, and body temperature of individuals.Method: The study was conducted with 24 women. The REE values of the individuals were measured with the COSMED Fitmate PRO. After the first REE measurements, individuals were given 1 cup of green coffee that was prepared to contain 6 mg caffeine per kg of lean body mass. After coffee consumption, REE measurements were made at 30, 60, 120, and 180 minutes. Blood pressure (mm Hg) and body temperature values (°C) were measured simultaneously with REE measurement.Results: There was a positive correlation between the caffeine amounts given with green coffee and 30-minute (p < 0.05), 60-minute (p = 0.06), and 120-minute (p < 0.05) REE (kcal/d) values. There was also a positive correlation between the total chlorogenic acid taken with green coffee and 30-minute (p < 0.05), 60-minute (p = 0.06), and 120-minute (p < 0.05) REE (kcal/d) values. The intracellular and extracellular fluid amounts liter(l) before and after consumption of green coffee by individuals were 18.7 ± 1.57 versus 18.6 ± 1.44 (p < 0.05) and 11.4 ± 1.01 versus 11.2 ± 0.97 (p < 0.05), respectively. The body temperature (°C) changes observed in the individuals whose usual dietary caffeine intake was less than or equal to the 50th percentile after green coffee consumption were statistically significant (p < 0.05). Similarly, the diastolic blood pressure changes observed in the individuals whose usual dietary caffeine intake was less than or equal to the 50th percentile after green coffee consumption was almost statistically significant (p = 0.06).Conclusions: The results of this study showed that 6 mg caffeine/kg (lean body mass) intake among women changed body temperature and blood pressure values and liquid balance depending on the usual dietary coffee intake. In addition, chlorogenic acid is also correlated with REE values besides green coffee caffeine.Key teaching points• There are several findings, and chlorogenic acid may have antihypertensive effects.• There is a significant correlation between green coffee chlorogenic acid amount and REE.• Intracellular and extracellular liquid amounts decrease following green coffee consumption (215–280 mg caffeine), and these changes are observed in individuals whose usual dietary caffeine intake is relatively both low and high.• The body temperature values of individuals whose usual dietary caffeine intake was in the 50th percentile or greater (relatively high) increased after green coffee consumption.

Abstract P163: Coffee Consumption and Risk of Heart Failure in the Physicians’ Health Study

Background: Coffee consumption is highly prevalent in the United States (US). While previous studies have reported a positive association of coffee consumption with hypertension (HTN) and coronary artery disease, only a few studies have examined the association of coffee consumption with risk of heart failure. Hence, we sought to examine the relation between coffee consumption and risk of heart failure among male physicians. Hypothesis: We hypothesized that coffee consumption is inversely associated with the risk of heart failure. Method: We prospectively studied 20,433 middle-aged and older men from The Physicians’ Health Study. Coffee consumption was assessed using a semi-quantitative food frequency questionnaire. The incidence of heart failure was assessed using annual questionnaires and validated in a subsample using review of medical records. We used Cox Proportional hazard model to compute the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) across categories of coffee and calorie adjusted caffeine intake, and cubic spline to estimate nonlinear trend. Results: The average age was 66.4 years. During a mean follow-up of 9.3 years, a total of 901 new cases of heart failure were reported. In a Cox model adjusting for age, diabetes, smoking, atrial fibrillation, exercise, and alcohol intake, the HRs (95% CIs) of heart failure were 1.0(reference), 0.89(0.67-1.20), 1.27(1.00-1.62), 0.99 (0.80 - 1.22), 1.19 (0.99- 1.43), and 1.37 (1.05 - 1.80) for coffee consumption of almost never, &lt;=1 cup/week, 2-6cups/week, 1cup/day, 2-3cups/day, and 4+cups/day, respectively; P for nonlinear trend = 0.02. In a secondary analysis, higher caffeine intake was associated with a higher risk of heart failure, with Multivariable HRs (95% CIs) from the lowest to the highest quintile of dietary caffeine were 1.00(reference), 1.10 (0.90-1.35), 1.00 (0.81-1.25), 1.17 (0.95-1.45), and 1.25 (1.00-1.56), respectively; P for nonlinear trend = 0.06. Conclusion: Heavy (+4 cups/day), but not light to moderate, coffee consumption is associated with a higher risk of heart failure.

Reply to Areta et al.: Time to withdraw and let the myth rest

Letter to the EditorReply to Areta et al.: Time to withdraw and let the myth restB. Gualano, L. d. S. Gonçalves, V. d. S. Painelli, G. Yamaguchi, L. F. de Oliveira, B. Saunders, R. P. da Silva, E. Maciel, G. G. Artioli, and H. RoschelB. GualanoUniversity of Sao Paulo, São Paulo, Brazil, L. d. S. GonçalvesUniversity of Sao Paulo, São Paulo, Brazil, V. d. S. PainelliUniversity of Sao Paulo, São Paulo, Brazil, G. YamaguchiUniversity of Sao Paulo, São Paulo, Brazil, L. F. de OliveiraUniversity of Sao Paulo, São Paulo, Brazil, B. SaundersUniversity of Sao Paulo, São Paulo, Brazil, R. P. da SilvaUniversity of Sao Paulo, São Paulo, Brazil, E. MacielUniversity of Sao Paulo, São Paulo, Brazil, G. G. ArtioliUniversity of Sao Paulo, São Paulo, Brazil, and H. RoschelUniversity of Sao Paulo, São Paulo, BrazilPublished Online:22 Nov 2017https://doi.org/10.1152/japplphysiol.00567.2017MoreSectionsPDF (30 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat to the editor: It is undisputable that caffeine variation in coffee—which is not as dramatic in Brazil as reported elsewhere (2)—is a potential bias pertaining to our, and any, study assessing its habitual dietary intake. In fact, such variability exists in any natural food due to differences in environment, genetics, and food processing. Therefore, if one is to take the point made by Areta et al. (1), the entire literature involving assessment of natural foods should be disregarded, which is obviously not the case. The suggestion that “reported caffeine intakes” could be verified through direct measurement of caffeine is, at least, curious; considering that caffeine half-life is ~5 h, it is puzzling how this measure could reflect one’s habitual caffeine consumption.Notably, we carefully assessed caffeine intake following Food and Drug Administration recommendations for high-quality food composition assessment. Briefly, caffeine intake was determined using a questionnaire adapted (and not replicated, as incorrectly assumed) from a validated instrument; the questionnaire was completed with the help of a qualified nutritionist who extracted as much detail and specific information as possible. Exact brands of products were identified to determine exact caffeine content. Although Areta et al. claimed that our dietary assessment was flawed, no scientific evidence was provided to support this assumption.We used a 24-h caffeine withdrawal to isolate the acute effect of supplementation from diet. Areta et al. argue that this influenced our results. Nonetheless, meta-analytical data show that caffeine withdrawal does not influence the ergogenic effect of caffeine (3). Indeed, caffeine consumption has previously been shown to be equally effective in habitual consumers following no, 2 days, and 4 days of withdrawal. In fact, some of the authors themselves have confirmed that a withdrawal period from dietary caffeine does not enhance or reduce the effect of an acute dose of caffeine on exercise performance. Thus we feel justified in our use of a withdrawal period to ensure rigorous control of our protocol.Although we acknowledge that our rationale regarding increased adenosine upregulation has been shown only in experimental (animal) models, which we drew attention to within the text, if true as hypothesized, 24-h withdrawal will not have led to any significant reduction herein and therefore will unlikely have influenced results.The criticism of our sample size is unfounded: 1) the lack of correlation between habitual intake and performance improvements was based on our entire sample; and 2) even when broken down to habitual intake, each tertile showed a greater number of subjects than in previous studies addressing this topic. Certainly, the numerous analyses performed in this study mitigate the odds of type-2 error.Since Areta et al. doubt our conclusions due to supposed inaccuracies in caffeine measurement, we provide a requiem to their uncertainties by reanalyzing all data following removal of coffee as the “less stable” source of caffeine, thus considering only other sources (e.g., cola drinks, tea, supplements). Only two participants moved between tertiles, which remained significantly different regarding intake (P < 0.0001). Neither significant between-group differences in performance (P = 0.81) nor correlation between habitual intake and performance changes (r = 0.00023; P = 0.92) was shown. Finally, when participants were distributed into quintiles, with the lower quintile consuming no coffee at all and the higher quintile consuming 6–8 coffees/day, differences in performance were still absent. These sensitivity analyses reinforce our original conclusion that habitual dietary caffeine does not affect the response to caffeine supplementation (4), putting this myth to rest.GRANTSThis work was supported by CAPES-PROEX.AUTHOR CONTRIBUTIONSL.d.S.G., V.d.S.P., B.S., and B.G. drafted manuscript; L.d.S.G., V.d.S.P., B.S., G.G.A., H.R., and B.G. edited and revised manuscript; L.d.S.G., V.d.S.P., G.Y., L.F.d.O., B.S., R.P.d.S., E.M., G.G.A., H.R., and B.G. approved final version of manuscript.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the authors.

Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.

Plant-derived caffeine is regarded as a defensive compound produced to prevent herbivory. Caffeine is generally repellent to insects and often used to study the neurological basis for aversive responses in the model insect, Drosophila melanogaster. Caffeine is also studied for its stimulatory properties where sleep or drowsiness is suppressed across a range of species. Since limiting access to food also inhibits fly sleep-an effect known as starvation-induced sleep suppression-we tested whether aversion to caffeinated food results in reduced nutrient intake and assessed how this might influence fly studies on the stimulatory effects of caffeine. We measured sleep and total consumption during the first 24 hours of exposure to caffeinated diets containing a range of sucrose concentrations to determine the relative influence of caffeine and nutrient ingestion on sleep. Experiments were replicated using three fly strains. Caffeine reduced total consumption and nighttime sleep, but only at intermediate sucrose concentrations. Although sleep can be modeled by an exponential dose response to nutrient intake, caffeine-mediated sleep loss cannot be explained by absolute caffeine or sucrose ingestion alone. Instead, reduced sleep strongly correlates with changes in total consumption due to caffeine. Other bitter compounds phenocopy the effect of caffeine on sleep and food intake. Our results suggest that a major effect of dietary caffeine is on fly feeding behavior. Changes in feeding behavior may drive caffeine-mediated sleep loss. Future studies using psychoactive compounds should consider the potential impact of nutrition when investigating effects on sleep.

Determination of caffeine and identification of undeclared substances in dietary supplements and caffeine dietary exposure assessment

Caffeine is one of the most consumed stimulants in the world, and is a frequent ingredient of dietary supplements. The aims of this work were to validate a GC-MS method for the quantitation of caffeine and identification of other substances in supplements, mainly weight loss products, and to estimate the caffeine intake by consumers. Sample preparation included extraction with chloroform:water in ultrasonic bath, centrifugation and analysis of the organic layer for caffeine quantitation, and extraction with methanol for identification of other substances. A total of 213 samples of 52 supplement products not registered in Brazil and seized by the Brazilian Federal Police were analyzed. From the 109 samples that declared the amount of caffeine present, 26.6% contained more than 120% of the specified content. Considering the maximum recommended dose stated on the product labels, the consumption of 47.9% of the samples would lead to a daily intake of caffeine above the safe limit of 400 mg. Undeclared drugs, including sibutramine, phenolphthalein, amphepramone and femproporex were found in 28 samples. These results show that consumers of dietary supplements should be aware that these products might contain caffeine at levels that could represent potential health risks, in addition to undeclared pharmaceutical drugs.

Cytochrome P450 2A6 Phenotyping Using Dietary Caffeine Salivary Metabolite Ratios and Genotyping Using Blood on Storage Cards in Non-smoking Japanese Volunteers.

A simple method of genotyping and phenotyping cytochrome P450 2A6 (CYP2A6) was previously reported using individual blood samples and urinary caffeine metabolite ratios of 1,7-dimethyluric acid (17U) to 1-methylxanthine (1X). Blood spotted onto storage cards and salivary caffeine metabolites were analyzed in 27 healthy non-smoking Japanese volunteers with no prior abstention from dietary caffeine intake. 1,7-Dimethylxanthine (17X), 17U, 1X, and caffeine levels in spot saliva samples were determined in Japanese non-smokers by high-performance liquid chromatography under normal dietary caffeine consumption. 17U/17X ratios in saliva were almost constant over time, but those of 17U/1X were variable in two subjects tested before and 1-2.5 h after caffeine treatment (a cup of black tea). In seven subjects, 17U/17X ratios in saliva were highly correlated with those in plasma (r = 0.98, p < 0.01) and well correlated with those in urine samples (r = 0.78, p < 0.05). The average 17U/17X ratios, but not 17U/1X ratios, in saliva under dietary caffeine consumption obtained from subjects with CYP2A6*1/*4 (n=11) and CYP2A6*4/*4 (whole-gene deletion, n=2) genotypes were significantly lower than those from subjects with wild-type CYP2A6*1/*1 (n=14). Genotyping was done by a multiplex real-time polymerase chain reaction method using blood spotted onto storage cards. The present results suggest that the decreased CYP2A6 function associated with the whole-gene deletion genotype (determined using blood samples) could be detected using 17U/17X ratios, but not 17U/1X ratios, in spot saliva samples under normal dietary caffeine consumption in Japanese non-smokers, just as it could be detected using urinary 17U/1X ratios.

The Dark Age(ing) of the Inflammasome

Mechanisms that contribute to healthy aging remain obscure. In a recent issue of Nature Medicine, Furman etal. (2017) describe that dietary caffeine inhibits the NLRC4 inflammasome, which is associated with disease-free aging.

Water and Beverage Consumption: Analysis of the Australian 2011-2012 National Nutrition and Physical Activity Survey.

Background: Water consumption as a vital component of the human diet is under-researched in dietary surveys and nutrition studies. Aim: To assess total water and fluid intakes and examine demographic, anthropometric, and dietary factors associated with water consumption in the Australian population. Methods: Dietary intake data from the 2011 to 2012 National Nutrition and Physical Activity Survey were used. Usual water, fluid and food and nutrient intakes were estimated from two days of dietary recalls. Total water includes plain drinking water and moisture from all food and beverage sources; total fluids include plain drinking water and other beverages, but not food moisture. Results: The mean (SD) daily total water intakes for children and adolescents aged 2–18 years were 1.7 (0.6) L for males and 1.5 (0.4) L for females, and for adults aged 19 years and over were 2.6 (0.9) L for males and 2.3 (0.7) L for females. The majority of the population failed to meet the Adequate Intake (AI) values for total water intake (82%) and total fluids intake (78%) with the elderly at highest risk (90%–95%). The contributions of plain drinking water, other beverages and food moisture to total water intake were 44%, 27%, and 29%, respectively, among children and adolescents, and 37%, 37% and 25% among adults. The main sources of other beverages were full-fat plain milk and regular soft drinks for children and adolescents, and tea, coffee, and alcoholic drinks for adults. For adults, higher total water intake was associated with lower percent energy from fat, saturated fat, and free sugars, lower sodium and energy-dense nutrient poor food intakes but higher dietary fibre, fruit, vegetable, caffeine, and alcohol intakes. No associations were found between total water consumption and body mass index (BMI) for adults and BMI z-score for children and adolescents. Conclusion: Reported water consumption was below recommendations. Higher water intakes were suggestive of better diet quality.

Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior.

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 = 94343, 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 metabolism and 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.

Relationship between dietary caffeine intake and blood pressure in adults

The aim of this study was to determine the consumption frequency of caffeinated foods and beverages and daily caffeine consumption amounts, and examine relation between caffeine and blood pressure (BP). A cross sectional door-to-door interview was conducted with 1329 volunteers between the ages of 20 and 60 (mean ages 29.9 ± 10.8 years) and based in Ankara/Turkey. The rate of individuals whose BPs were above 140/90 mmHg was 13.5%. The median caffeine consumption was 150.0 ± 122.06 mg. Although no significant correlation was found between total caffeine intake and diastolic blood pressure (DBP) of individuals, a positive correlation was observed between daily total caffeine and systolic blood pressure (SBP) (p < .05). Also, when analyzed factors that could be associated with DBP and SBP, BMI had effect in the model formed for both types of BP (p < .05). While smoking status associated with SBP (p = .002), gender and waist circumference related to DBP (p < .05) As a result relationship between caffeine intake and BP was affected other factors.

Dietary Caffeine and Polyphenol Supplementation Enhances Overall Metabolic Rate and Lipid Oxidation at Rest and After a Bout of Sprint Interval Exercise.

Jo, E, Lewis, KL, Higuera, D, Hernandez, J, Osmond, AD, Directo, DJ, and Wong, M. Dietary caffeine and polyphenol supplementation enhances overall metabolic rate and lipid oxidation at rest and after a bout of sprint interval exercise. J Strength Cond Res 30(7): 1871-1879, 2016-The purpose of this study was to investigate the effects of a caffeine-polyphenolic supplement on (a) metabolic rate and fat oxidation at rest and after a bout of sprint interval exercise (SIE) and (b) SIE performance. In a double-blind, randomized, placebo-controlled, crossover study and after an initial familiarization visit, 12 subjects (male: n = 11; female: n = 1) (body mass = 76.1 ± 2.2 kg; height = 169.8 ± 1.6 cm; body mass index = 22.7 ± 3.0 kg·m; body fat % = 21.6 ± 2.0%) underwent 2 testing sessions during which time they consumed either a caffeine-polyphenol supplement or placebo. After supplementation, resting energy expenditure, heart rate (HR), and blood pressure (BP) were assessed. Subsequently, subjects performed 30 minutes of SIE while researchers collected performance data. Subjects were then tested for post-SIE energy expenditure, HR, and BP. The caffeine-polyphenol treatment resulted in significantly (p ≤ 0.05) greater energy expenditure (+7.99% rest; +10.16% post-SIE), V[Combining Dot Above]O2 (+9.64% rest; +12.10% post-SIE), and fat oxidation rate (+10.60% rest; +9.76% post-SIE) vs. placebo at rest and post-SIE. No significant differences were detected for peak and average power at all sprint intervals between treatments. Post-SIE HR was significantly (p ≤ 0.05) greater with caffeine-polyphenol supplementation vs. placebo (90.8 ± 3.5 vs. 85.1 ± 3.6 b·min). There were no significant between-treatment differences for BP. It may be concluded that the observed thermogenic response after SIE was directly attributable to caffeine-polyphenol supplementation as opposed to an indirect manifestation of enhanced performance and work output. Collectively, these results corroborate the use of dietary caffeine and polyphenols to support efforts to reduce adiposity and improve overall body composition especially in conjunction with SIE.

Correlation of Adolescent Caffeine Intake with Blood Pressure in Adolescence and Adulthood

ObjectiveHigh blood pressure (HBP) is one of the leading causes of premature death worldwide. Currently, 1 in 3 adults has HBP. Recent studies have shown that caffeine leads to an acute increase in blood pressure after exposure, but the long–term effects of caffeine on blood pressure are unclear. Our study aimed to assess the longer‐term relationships between dietary caffeine intake and blood pressure using data collected in two longitudinal epidemiologic studies: the Princeton Lipid Research Study and the NHLBI Growth Health Study (NGHS).MethodsThe Princeton cohort included 623 subjects who were seen as children/adolescents and again in adulthood. The NGHS cohort included 870 black and white females ages 9 or 10 at enrollment who were followed yearly for up to ten years. Caffeine intake was assessed using a 24‐hour recall for Princeton (childhood only) and 3‐day diet records for NGHS (at 8 of 10 visits). Blood pressure in both studies was assessed using standard mercury sphygmomanometer, and systolic and diastolic z‐scores were calculated for childhood measurements. The relationship between caffeine intake and blood pressure was analyzed for individuals in each visit.ResultsIn the NGHS cohort, caffeine intake increased from a median of 15 mg to 40 mg/day between ages 10 and 19 years, and was significantly higher in white vs. black participants at all ages (p&lt;0.0001). Similar patterns were noted in Princeton. In NGHS, SBP z‐score and DBP z‐scores were higher in black vs. white participants from age 17–19 (p&lt;0.01); in Princeton, BP z‐scores did not differ by race at any childhood age. Cross‐sectionally, neither cohort demonstrated significant correlations between caffeine intake and blood pressure z‐scores during childhood/adolescence, except for a negative correlation seen in NGHS with DBP z‐score at age 16.0 (Spearman correlation=−0.085, p=0.04). Longitudinally, in Princeton, caffeine intake in childhood/adolescence was not associated with systolic or diastolic blood pressure in adult follow up (both p&gt;0.4), adjusting for sex, race, and age and BMI at adult follow up. In NGHS, neither caffeine intake at age 12, nor the change in caffeine intake between ages 12 and 19, were associated with blood pressure z‐scores at participants’ final visits, adjusting for age at final visit and BMI z‐score.DiscussionThe results of these two long‐term studies suggest that caffeine consumption during childhood/adolescence is not associated with blood pressure in either later adolescence or adulthood.Support or Funding InformationEE supported by a grant from the American Heart Association and the CCHMC Schmidlapp Young Women's Scholarship.

Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women.

Theacrine is a purine alkaloid found primarily in the leaves of the Camellia Kucha plant and is now included within dietary supplements. To compare the effects of a theacrine-containing dietary supplement with caffeine and placebo on energy and mood, as well as objective measures of cognitive performance, heart rate, and blood pressure, 10 healthy men (20.8 ± 0.7 years) and 10 healthy women (22.2 ± 1.1 years) ingested the dietary supplement TheaTrim (Purus Labs; containing a branded form of theacrine (Teacrine™) and caffeine (150 mg)), caffeine only (150 mg), or a placebo on three different days, separated by approximately one week. Before, and for up to 4 h following, ingestion of the assigned condition, subjects completed a subjective assessment of energy and mood, as well as tests of cognitive performance (trail making test (TMT), digit symbol substitution test (DSST)), and reaction time. Heart rate and blood pressure were measured. No condition or interaction effects were noted for TMT, DSST, or reaction time, despite a trend for improvement in selected variables with both TheaTrim and caffeine treatment. Condition effects or trends were noted for subjective feelings, with values for attentive, alert, focused, and energetic higher for TheaTrim than for placebo and caffeine, while values for lethargic and groggy were lower for TheaTrim than for placebo and caffeine. Heart rate and blood pressure were largely unaffected by treatment. These data indicate that TheaTrim treatment does not result in a statistically significant improvement in cognitive performance but may favorably impact multiple subjective feelings related to energy and mood.

Effect of Dietary Calcium, Caffeine Intake, and Body Mass Index on Bone Mineral Density of Young Female Adults

Effect of Dietary Calcium, Caffeine Intake, and Body Mass Index on Bone Mineral Density of Young Female Adults

The Role of Uric Acid and Methyl Derivatives in the Prevention of Age-Related Neurodegenerative Disorders.

High uric acid (UA levels have been correlated with a reduced risk of many neurodegenerative diseases through mechanisms involving chelating Fenton reaction transitional metals, antioxidant quenching of superoxide and hydroxyl free radicals, and as an electron donor that increases antioxidant enzyme activity (e.g. SOD. However, the clinical usefulness of UA is limited by its' low water solubility and propensity to form inflammatory crystals at hyperuricemic levels. This review focuses on the role of UA in neuroprotection, as well as potential strategies aimed at increasing UA levels in the soluble range, and the potential therapeutic use of more water-soluble methyl-UA derivatives from the natural catabolic end-products of dietary caffeine, theophylline, and theobromine.

The effects of levetiracetam, sumatriptan, and caffeine in a rat model of trigeminal pain: interactions in 2-component combinations.

Levetiracetam is an antiepileptic drug with analgesic efficacy shown in pain models and small clinical trials. Sumatriptan is used in acute migraine treatment. Caffeine is widely consumed in some beverages/foods and is also an adjuvant in analgesic formulations. We examined the effects of systemic levetiracetam, sumatriptan, and caffeine and their interactions in 2-component combinations in the rat orofacial formalin test, a model of trigeminal pain. Rats received a subcutaneous injection of formalin solution into the perinasal area, and the total time spent in nociceptive behavior (face rubbing) was quantified. The antinociceptive effect of drugs/drug combinations was assessed 1 hour after per os administration. The type of interaction between levetiracetam/sumatriptan and caffeine was examined by comparing the effects of a fixed, effective dose of levetiracetam/sumatriptan alone with the effects of the same dose applied with increasing, subeffective doses of caffeine. The type of interaction between levetiracetam and sumatriptan was determined by isobolographic analysis. Levetiracetam (1-50 mg/kg) and sumatriptan (0.5-5 mg/kg) produced significant and dose-dependent antinociceptive effects in both phases of the orofacial formalin test (P ≤ 0.001). Caffeine (7.5-100 mg/kg) produced significant antinociception in the second phase of the test (P = 0.04). Caffeine (1-7.5 mg/kg) significantly reduced the antinociceptive effects of levetiracetam (25 mg/kg) (first phase P = 0.002, second phase P < 0.001) and sumatriptan (2.5 mg/kg) (first phase P = 0.014, second phase P = 0.027); dose-dependent inhibition was observed in the second phase. Levetiracetam and sumatriptan exerted an additive interaction in the second phase of the orofacial formalin test. Results indicate that levetiracetam may be useful for treatment of pain in the trigeminal region. Dietary caffeine might decrease the effects of levetiracetam and sumatriptan; this needs to be considered in clinical settings. A levetiracetam-sumatriptan combination could also be useful in trigeminal pain treatment. Its efficacy and adverse effects should be examined clinically.

Caffeine intake in Hungary – A population based estimation

Caffeine is a bitter, white crystalline xanthine alkaloid that is synthesized in different parts of more than 60 plant species. In a previous study, caffeine content of 377 food samples obtained from the Hungarian market was measured by a validated HPLC technique. These analytical data were built up into a food composition database called NutriComp. Dietary caffeine intake of the Hungarian population was estimated based on the data of the National Nutritional Status Survey 2009. Daily caffeine intake of Hungarian adult males and females were 147±6.2 mg per capita (95% CI: 135–160), and 138±4.2 mg per capita (95% CI: 129–147), respectively. There was no significant difference between genders. The oldest men and women consumed significantly less caffeine than the people between 35–64 years of age. The main sources of caffeine are coffee and tea with 58–59%, and 35–37% of the total intake in men and women, respectively.

Urine Excretion of Caffeine and Select Caffeine Metabolites Is Common in the US Population and Associated with Caffeine Intake1–4

Background: Caffeine is a widely consumed psychoactive stimulant and is of epidemiologic interest. Major sources of caffeine are challenging to standardize, and the use of biomarkers is proposed as an alternative means of assessing intake.Objective: We described urine caffeine and caffeine metabolite concentrations (n = 2466) and excretion rates (n = 2261) in the US population ≥6 y by age, sex, race-ethnicity, and caffeine intake (from foods, beverages, and dietary supplements).Methods: We measured caffeine and 14 of its metabolites in spot urine samples from the cross-sectional NHANES 2009–2010 by use of LC-tandem mass spectrometry.Results: Caffeine and its metabolites were detectable in the urine of most persons, generally at concentrations ≥1 μmol/L. Median concentrations (95% CI) ranged from 0.560 (0.497, 0.620) μmol/L to 58.6 (48.6, 67.2) μmol/L; median excretion rates from 0.423 (0.385, 0.468) nmol/min to 46.0 (40.7, 50.2) nmol/min. Urine concentrations and excretion rates for 9 analytes (caffeine, theophylline, paraxanthine, 1-methylxanthine, 1-methyluric acid, 1,3-dimethyluric acid, 1,7-dimethyluric acid, 1,3,7-trimethyluric acid, and 5-acetylamino-6-amino-3-methyluracil) had moderate correlations with caffeine intake (Spearman ρ = 0.55–0.68, P < 0.0001); the remaining analytes had low correlations (ρ = 0.15–0.33, P < 0.0001). We observed larger differences in geometric mean concentrations and excretion rates between the highest vs. lowest quartiles of caffeine intake for these 9 compounds than the rest. Consistent with dietary caffeine intake, we observed that urine concentrations and excretion rates for most compounds were significantly (P < 0.05) higher in men than women, non-Hispanic whites than Hispanics and non-Hispanic blacks, and highest in persons aged 40–59 y.Conclusion: Excretion of caffeine and its metabolites in urine is common in the US population. According to the observed associations between spot urine concentrations or excretion rates with caffeine intake, several of these compounds show promise as potential biomarkers of caffeine intake.

Depression and Cognitive Impairment Are Associated with Low Education and Literacy Status and Smoking but Not Caffeine Consumption in Urban African Americans and White Adults.

Background: Recent research has linked caffeine consumption with a lower risk for depression and cognitive decline. However, no studies have examined the relationship in an African American compared to a white, socioeconomically diverse representative urban sample. Methods: Data from a cross-sectional study were used to determine the associations of caffeine use with depressive symptomatology and cognition in a sample of 1,724 participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. The United States Department of Agriculture's Automated Multiple Pass Method was used by trained interviewers to collect two, in-person 24-hour dietary recalls. Depressive symptoms and global cognition were assessed using two well-validated measures: the Center for Epidemiologic Studies Depressive Scale (CES-D) and Mini Mental State Examination (MMSE), respectively. Usual caffeine intake was based on both recalls. Data were analyzed with t- and chi-square tests, correlation analysis, and ordinal logistic regression. Results: African Americans consumed significantly less caffeine than did whites (89.0±3.2 and 244.0±8.7 mg respectively). Caffeine consumption was not associated with depressive symptomatology or global cognition. Age, less than 5th grade literacy, and less than high school education were significantly associated with both depressive symptoms and cognitive function. Smokers had a 43% greater risk for depression but only a 3% higher risk for cognitive impairment. Conclusion: The low level of dietary caffeine intake in combination with smoking among HANDLS study participants may have influenced the lack of association with depressive symptomatology or global cognition. For this sample, low literacy and education appear more highly associated with depressive symptoms and cognitive function than caffeine intake.

A beating heart cell model to predict cardiotoxicity: Effects of the dietary supplement ingredients higenamine, phenylethylamine, ephedrine and caffeine

Some dietary supplements may contain cardiac stimulants and potential cardiotoxins. In vitro studies may identify ingredients of concern. A beating human cardiomyocyte cell line was used to evaluate cellular effects following phenylethylamine (PEA), higenamine, ephedrine or caffeine treatment. PEA and higenamine exposure levels simulated published blood levels in humans or animals after intravenous administration. Ephedrine and caffeine levels approximated published blood levels following human oral intake. At low or midrange levels, each chemical was examined plus or minus 50 µM caffeine, simulating human blood levels reported after consumption of caffeine-enriched dietary supplements. To measure beats per minute (BPM), peak width, etc., rhythmic rise and fall in intracellular calcium levels following 30 min of treatment was examined. Higenamine 31.3 ng/ml or 313 ng/ml significantly increased BPM in an escalating manner. PEA increased BPM at 0.8 and 8 µg/ml, while 80 µg/ml PEA reduced BPM and widened peaks. Ephedrine produced a significant BPM dose response from 0.5 to 5.0 µM. Caffeine increased BPM only at a toxic level of 250 µM. Adding caffeine to PEA or higenamine but not ephedrine further increased BPM. These in vitro results suggest that additional testing may be warranted in vivo to further evaluate these effects.