title: The economic burden of dry eye disease in the United States: a decision tree analysis.

text: PURPOSE: The aim of this study was to estimate both the direct and indirect annual cost of managing dry eye disease (DED) in the United States from a societal and a payer's perspective. METHODS: A decision analytic model was developed to estimate the annual cost for managing a cohort of patients with dry eye with differing severity of symptoms and treatment. The direct costs included ocular lubricants, cyclosporine, punctal plugs, physician visits, and nutritional supplements. The indirect costs were measured as the productivity loss because of absenteeism and presenteeism. The model was populated with data that were obtained from surveys that were completed by dry eye sufferers who were recruited from online databases. Sensitivity analyses were employed to evaluate the impact of changes in parameters on the estimation of costs. All costs were converted to 2008 US dollars. RESULTS: Survey data were collected from 2171 respondents with DED. Our analysis indicated that the average annual cost of managing a patient with dry eye at $783 (variation, $757-$809) from the payers' perspective. When adjusted to the prevalence of DED nationwide, the overall burden of DED for the US healthcare system would be $3.84 billion. From a societal perspective, the average cost of managing DED was estimated to be $11,302 per patient and $55.4 billion to the US society overall. CONCLUSIONS: DED poses a substantial economic burden on the payer and on the society. These findings may provide valuable information for health plans or employers regarding budget estimation.


title: Keratomalacia.

text: Xerophthalmia and keratomalacia are public health problems of great magnitude which are usually associated with multiple vitamin and protein deficiencies. The authors report the case of a 27-year-old commune member who subjected herself to a bizarre protein and vitamin deficient diet for many months. This ultimately produced nyctalopia, xerophthalmia and keratomalacia with bilateral corneal perforation. Despite therapy, she remained comatose and expired shortly after admission. Ocular pathological changes included bilateral corneal melting with prolapse of intraocular contents, conjunctival epidermidalization, goblet cell atrophy and thinning of the outer nuclear layer of the retina. It is noted that ocular findings in pure avitaminosis A produced experimentalyy include epithelial atrophy followed by keratinization.


title: Pharmaceutical and herbal products that may contribute to dry eyes.

text: BACKGROUND: Symptomatic dryness of the eyes is a most common blepharoplasty complication. The authors reviewed the medications and herbal products that may potentiate this complication. METHODS: The MEDLINE and PubMed databases were searched for the years 1991 to 2011. Search terms included "dry eye syndrome," "keratitis sicca," "keratoconjunctivitis sicca," "ocular side effects," "herbal supplements," "herbals and dry eye," "dry eye risk factors," "etiology of dry eye," "drugs side effects," "drugs and dry eye," "dietary supplements," "ocular toxicity," and "tear film." References from herbal product reviews and eligible medication reports were searched for additional articles. A manual search was also conducted based on citations in the published literature. RESULTS: Of 232 articles found to be related to dry eye syndrome and possible risk factors, 196 were excluded because they did not discuss medications or herbal products as risk factors in dry eye syndrome. Thirty-six articles that examined the pathophysiology and risk factors of dry eye were included. Nine books were reviewed that contained some information regarding the association of medications and herbal products with dry eye. These agents were then categorized based on mechanism of action and usage. Medications listed include antihistamines, decongestants, antidepressants, anticonvulsants, antipsychotics, antiparkinson drugs, beta-blockers, and hormone replacement therapy. The three main herbal products that contribute to dry eye are niacin, echinacea, and kava. There was a strong association between anticholinergic alkaloids and dry eye. CONCLUSION: This study identifies the medications and herbal products that should be considered when a patient undergoes blepharoplasty and complains of symptoms associated with dryness of the eyes.


title: Post-LASIK Tear Dysfunction and Dysesthesia

text: Symptoms of tear dysfunction after laser in situ keratomileusis (LASIK) occur in nearly all patients and resolve in the vast majority. Although dry eye complaints are a leading cause of patient discomfort and dissatisfaction after LASIK, the symptoms are not uniform, and the disease is not a single entity. Post-LASIK tear dysfunction syndrome or dry eye is a term used to describe a spectrum of disease encompassing transient or persistent post-operative neurotrophic disease, tear instability, true aqueous tear deficiency, and neuropathic pain states. Neural changes in the cornea and neuropathic causes of ocular surface discomfort may play a separate or synergistic role in the development of symptoms in some patients. Most cases of early post-operative dry eye symptoms resolve with appropriate management, which includes optimizing ocular surface health before and after surgery. Severe symptoms or symptoms persisting after 9 months rarely respond satisfactorily to traditional treatment modalities and require aggressive management. This review covers current theories of post-LASIK dry eye disease, pathophysiology, risk factors, and management options for this disease spectrum of post-LASIK tear dysfunction and neuropathic pain.


title: Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye

text: Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies.


title: Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes

text: Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.


title: Effect of diet on excretion of estrogens in pre- and postmenopausal women.

text: Fecal, urinary, and plasma estrogens and plasma androgens were studied in healthy pre- and postmenopausal vegetarian and omnivorous women. Dietary histories of the subjects revealed that omnivores consumed a higher percentage of total protein and fat from animal sources. The total 72-hr fecal excretion as measured by dry weight was higher for vegetarians. Preliminary results indicate that vegetarian women excrete 2 to 3 times more estrogens in feces than do omnivores and that omnivores have about 50% higher mean plasma level of unconjugated estrone and estradiol than vegetarians. Estriol-3-glucuronide, a compound that is formed upon reabsorption of free estriol from the intestine, is found in lower concentrations in the urine of vegetarians. These data suggest that in vegetarians a greater amount of the biliary estrogens escape reabsorption and are excreted with the feces. The differences in estrogen metabolism may explain the lower incidence of breast cancer in vegetarian women.


title: Phytochemicals and their impact on adipose tissue inflammation and diabetes.

text: Type 2 diabetes mellitus is an inflammatory disease and the mechanisms that underlie this disease, although still incompletely understood, take place in the adipose tissue of obese subjects. Concurrently, the prevalence of obesity caused by Western diet's excessive energy intake and the lack of exercise escalates, and is believed to be causative for the chronic inflammatory state in adipose tissue. Overnutrition itself as an overload of energy may induce the adipocytes to secrete chemokines activating and attracting immune cells to adipose tissue. But also inflammation-mediating food ingredients like saturated fatty acids are believed to directly initiate the inflammatory cascade. In addition, hypoxia in adipose tissue as a direct consequence of obesity, and its effect on gene expression in adipocytes and surrounding cells in fat tissue of obese subjects appears to play a central role in this inflammatory response too. In contrast, revisiting diet all over the world, there are also some natural food products and beverages which are associated with curative effects on human health. Several natural compounds known as spices such as curcumin, capsaicin, and gingerol, or secondary plant metabolites catechin, resveratrol, genistein, and quercetin have been reported to provide an improved health status to their consumers, especially with regard to diabetes, and therefore have been investigated for their anti-inflammatory effect. In this review, we will give an overview about these phytochemicals and their role to interfere with inflammatory cascades in adipose tissue and their potential for fighting against inflammatory diseases like diabetes as investigated in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.


title: Meat Consumption as a Risk Factor for Type 2 Diabetes

text: Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern.


title: Dietary fiber, weight gain, and cardiovascular disease risk factors in young adults.

text: CONTEXT: Dietary composition may affect insulin secretion, and high insulin levels, in turn, may increase the risk for cardiovascular disease (CVD). OBJECTIVE: To examine the role of fiber consumption and its association with insulin levels, weight gain, and other CVD risk factors compared with other major dietary components. DESIGN AND SETTING: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter population-based cohort study of the change in CVD risk factors over 10 years (1985-1986 to 1995-1996) in Birmingham, Ala; Chicago, III; Minneapolis, Minn; and Oakland, Calif. PARTICIPANTS: A total of 2909 healthy black and white adults, 18 to 30 years of age at enrollment. MAIN OUTCOME MEASURES: Body weight, insulin levels, and other CVD risk factors at year 10, adjusted for baseline values. RESULTS: After adjustment for potential confounding factors, dietary fiber showed linear associations from lowest to highest quintiles of intake with the following: body weight (whites: 174.8-166.7 lb [78.3-75.0 kg], P<.001; blacks: 185.6-177.6 lb [83.5-79.9 kg], P = .001), waist-to-hip ratio (whites: 0.813-0.801, P = .004; blacks: 0.809-0.799, P = .05), fasting insulin adjusted for body mass index (whites: 77.8-72.2 pmol/L [11.2-10.4 microU/mL], P = .007; blacks: 92.4-82.6 pmol/L [13.3-11.9 microU/mL], P = .01) and 2-hour postglucose insulin adjusted for body mass index (whites: 261.1-234.7 pmol/L [37.6-33.8 microU/mL], P = .03; blacks: 370.2-259.7 pmol/L [53.3-37.4 microU/mL], P<.001). Fiber was also associated with blood pressure and levels of triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fibrinogen; these associations were substantially attenuated by adjustment for fasting insulin level. In comparison with fiber, intake of fat, carbohydrate, and protein had inconsistent or weak associations with all CVD risk factors. CONCLUSIONS: Fiber consumption predicted insulin levels, weight gain, and other CVD risk factors more strongly than did total or saturated fat consumption. High-fiber diets may protect against obesity and CVD by lowering insulin levels.


title: Plant-based foods as a source of lipotropes for human nutrition: a survey of in vivo studies.

text: Increased consumption of plant products is associated with lower chronic disease prevalence. This is attributed to the great diversity of healthy phytochemicals present in these foods. The most investigated physiological effects have been their antioxidant, anti-carcinogenic, hypolipidemic, and hypoglycemic properties. Although less studied in humans, some compounds were very early on shown to be lipotropic in animals, i.e., the capacity to hasten the removal of fat from liver and/or reduce hepatic lipid synthesis or deposits by mainly increasing phospholipid synthesis via the transmethylation pathway for triglyceride-rich lipoprotein exportation from the liver and enhanced fatty acid β-oxidation and/or down- and up-regulation of genes involved in lipogenic and fatty acid oxidation enzyme synthesis, respectively. The main plant lipotropes are choline, betaine, myo-inositol, methionine, and carnitine. Magnesium, niacin, pantothenate, and folates also indirectly support the overall lipotropic effect. The exhaustive review of rat studies investigating phytochemical effect on hepatic lipid metabolism suggests that some fatty acids, acetic acid, melatonin, phytic acid, some fiber compounds, oligofructose, resistant starch, some phenolic acids, flavonoids, lignans, stilbenes, curcumin, saponins, coumarin, some plant extracts, and some solid foods may be lipotropic. However, this remains to be confirmed in humans, for whom intervention studies are practically non-existent. Supplemental materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition® to view the free supplemental file.


title: Reactive oxygen species have a causal role in multiple forms of insulin resistance.

text: Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.


title: Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver.

text: Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. FFA also produces low-grade inflammation in skeletal muscle and liver through activation of nuclear factor-kappaB, resulting in release of several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which contributes to the development of atherosclerotic vascular diseases and NAFLD.


title: Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy

text: Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-α/β-actin mRNA ratio was 1.4 ± 0.5 on H-AGE and 0.9 ± 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 ± 429 and 698 ± 347 ng/ml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-α rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.


title: Meat consumption, diabetes, and its complications.

text: Several prospective studies have reported that risk of type 2 diabetes (T2DM) is elevated in meat consumers, especially when processed meats are consumed. Elevated risks of coronary heart disease (CHD) and stroke in meat consumers have also been reported. In this overview, the evidence regarding meat consumption and the risk of diabetes, both type 1 diabetes (T1DM) and T2DM and their macro- and microvascular complications, is reviewed. For T2DM, we performed a new meta-analysis including publications up to October 2012. For T1DM, only a few studies have reported increased risks for meat consumers or for high intake of saturated fatty acids and nitrates and nitrites. For T2DM, CHD, and stroke, the evidence is strongest. Per 100 g of total meat, the pooled relative risk (RR) for T2DM is 1.15 (95 % CI 1.07-1.24), for (unprocessed) red meat 1.13 (95 % CI 1.03-1.23), and for poultry 1.04 (95 % CI 0.99-1.33); per 50 g of processed meat, the pooled RR is 1.32 (95 % CI 1.19-1.48). Hence, the strongest association regarding T2DM is observed for processed (red) meat. A similar observation has been made for CHD. For stroke, however, a recent meta-analysis shows moderately elevated risks for meat consumers, for processed as well as for fresh meats. For the microvascular complications of diabetes, few prospective data were available, but suggestions for elevated risks can be derived from findings on hyperglycemia and hypertension. The results are discussed in the light of the typical nutrients and other compounds present in meat--that is, saturated and trans fatty acids, dietary cholesterol, protein and amino acids, heme-iron, sodium, nitrites and nitrosamines, and advanced glycation end products. In light of these findings, a diet moderate to low in red meat, unprocessed and lean, and prepared at moderate temperatures is probably the best choice from the public health point of view.


title: Association between dietary meat consumption and incident type 2 diabetes: the EPIC-InterAct study.

text: AIMS/HYPOTHESIS: A diet rich in meat has been reported to contribute to the risk of type 2 diabetes. The present study aims to investigate the association between meat consumption and incident type 2 diabetes in the EPIC-InterAct study, a large prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: During 11.7 years of follow-up, 12,403 incident cases of type 2 diabetes were identified among 340,234 adults from eight European countries. A centre-stratified random subsample of 16,835 individuals was selected in order to perform a case-cohort design. Prentice-weighted Cox regression analyses were used to estimate HR and 95% CI for incident diabetes according to meat consumption. RESULTS: Overall, multivariate analyses showed significant positive associations with incident type 2 diabetes for increasing consumption of total meat (50 g increments: HR 1.08; 95% CI 1.05, 1.12), red meat (HR 1.08; 95% CI 1.03, 1.13) and processed meat (HR 1.12; 95% CI 1.05, 1.19), and a borderline positive association with meat iron intake. Effect modifications by sex and class of BMI were observed. In men, the results of the overall analyses were confirmed. In women, the association with total and red meat persisted, although attenuated, while an association with poultry consumption also emerged (HR 1.20; 95% CI 1.07, 1.34). These associations were not evident among obese participants. CONCLUSIONS/INTERPRETATION: This prospective study confirms a positive association between high consumption of total and red meat and incident type 2 diabetes in a large cohort of European adults.


title: mTOR: from growth signal integration to cancer, diabetes and ageing

text: Preface In all eukaryotes, the target of rapamycin (TOR) signaling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress, and, in metazoan, growth factors. Mammalian TOR complexes 1 and 2 (mTORC1 and mTORC2) exert their actions by regulating other important kinases, such as S6K and Akt. In the last few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed its critical involvement in the onset and progression of diabetes, cancer and ageing.


title: Persistent organic pollutants and diabetes: a review of the epidemiological evidence.

text: The prevalence of diabetes and obesity has increased rapidly over the last few decades in both developed and developing countries. While it is intuitively appealing to suggest that lifestyle risk factors such as decreased physical activity and adoption of poor diets can explain much of the increase, the evidence to support this is poor. Given this, there has been an impetus to look more widely than traditional lifestyle and biomedical risk factors, especially those risk factors, which arise from the environment. Since the industrial revolution, there has been an introduction of many chemicals into our environment, which have now become environmental pollutants. There has been growing interest in one key class of environmental pollutants known as persistent organic pollutants (POPs) and their potential role in the development of diabetes. This review will summarise and appraise the current epidemiological evidence relating POPs to diabetes and highlight gaps and flaws in this evidence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.


title: Leucine signaling in the pathogenesis of type 2 diabetes and obesity

text: Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.


title: Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic nephropathy

text: Endogenous advanced glycation endproducts (AGEs) include chemically crosslinking species (glycotoxins) that contribute to the vascular and renal complications of diabetes mellitus (DM). Renal excretion of the catabolic products of endogenous AGEs is impaired in patients with diabetic or nondiabetic kidney disease (KD). The aim of this study was to examine the oral absorption and renal clearance kinetics of food AGEs in DM with KD and whether circulating diet-derived AGEs contain active glycotoxins. Thirty-eight diabetics (DM) with or without KD and five healthy subjects (NL) received a single meal of egg white (56 g protein), cooked with (AGE-diet) or without fructose (100 g) (CL-diet). Serum and urine samples, collected for 48 hr, were monitored for AGE immunoreactivity by ELISA and for AGE-specific crosslinking reactivity, based on complex formation with 125I-labeled fibronectin. The AGE-diet, but not the CL-diet, produced distinct elevations in serum AGE levels in direct proportion to amount ingested (r = 0.8, P < 0.05): the area under the curve for serum (≈10% of ingested AGE) correlated directly with severity of KD; renal excretion of dietary AGE, although normally incomplete (only ≈30% of amount absorbed), in DM it correlated inversely with degree of albuminuria, and directly with creatinine clearance (r = 0.8, P < 0.05), reduced to <5% in DM with renal failure. Post-AGE-meal serum exhibited increased AGE-crosslinking activity (two times above baseline serum AGE, three times above negative control), which was inhibited by aminoguanidine. In conclusion, (i) the renal excretion of orally absorbed AGEs is markedly suppressed in diabetic nephropathy patients, (ii) daily influx of dietary AGEs includes glycotoxins that may constitute an added chronic risk for renal-vascular injury in DM, and (iii) dietary restriction of AGE food intake may greatly reduce the burden of AGEs in diabetic patients and possibly improve prognosis.


title: Coffee, tea, and the risk of hip fracture: a meta-analysis.

text: The present meta-analysis shows no clear association between coffee consumption and the risk of hip fractures. There was a nonlinear association between tea consumption and the risk of hip fracture. Compared to no tea consumption, drinking 1-4 cups of tea daily was associated with a lower risk of hip fracture. INTRODUCTION: Prospective cohort and case-control studies have suggested that coffee and tea consumption may be associated with the risk of hip fracture; the results have, however, been inconsistent. We conducted a meta-analysis to assess the association between coffee and tea consumption and the risk of hip fracture. METHODS: We performed systematic searches using MEDLINE, EMBASE, and OVID until February 20, 2013, without limits of language or publication year. Relative risks (RRs) with 95% confidence intervals (CI) were derived using random-effects models throughout all analyses. We conducted categorical, dose-response, heterogeneity, publication bias, and subgroup analyses. RESULTS: Our study was based on 195,992 individuals with 9,958 cases of hip fractures from 14 studies, including six cohort and eight case-control studies. The pooled RRs of hip fractures for the highest vs. the lowest categories of coffee and tea consumption were 0.94 (95% CI 0.71-1.17) and 0.84 (95% CI 0.66-1.02), respectively. For the dose-response analysis, we found evidence of a nonlinear association between tea consumption and the risk of hip fracture (p(nonlinearity) < 0.01). Compared to no tea consumption, 1-4 cups of tea per day may reduce the risk of hip fracture by 28% (0.72; 95% CI 0.56-0.88 for 1-2 cups/day), 37% (0.63; 95% CI 0.32-0.94 for 2-3 cups/day), and 21% (0.79; 95% CI 0.62-0.96 for 3-4 cups/day). CONCLUSIONS: We found no significant association between coffee consumption and the risk of hip fracture. A nonlinear association emerged between tea consumption and the risk of hip fracture; individuals drinking 1-4 cups of tea per day exhibited a lower risk of hip fractures than those who drank no tea. The association between 5 daily cups of tea, or more, and hip fracture risk should be investigated.


title: Caffeine intake and its association with urinary incontinence in United States men: results from National Health and Nutrition Examination Surveys ...

text: PURPOSE: Epidemiological studies in women have revealed an association between caffeine intake and urinary incontinence, although evidence among men is limited. Therefore, we evaluated the association between caffeine intake and urinary incontinence in United States men. MATERIALS AND METHODS: Data were used from male NHANES (National Health and Nutrition Examination Surveys) 2005-2006 and 2007-2008 participants. Urinary incontinence was defined using a standard questionnaire with Incontinence Severity Index scores 3 or greater categorized as moderate to severe. Structured dietary recall was used to determine caffeine consumption (mg per day), water intake (gm per day) and total dietary moisture (gm per day). Stepwise multivariable logistic regression models were used to assess the association between caffeine intake at or above the 75th and 90th percentiles and moderate to severe urinary incontinence, controlling for potential confounders, urinary incontinence risk factors and prostate conditions in men age 40 years or older. RESULTS: Of the 5,297 men 3,960 (75%) were 20 years old or older with complete data. Among these men the prevalence of any urinary incontinence was 12.9% and moderate to severe urinary incontinence was 4.4%. Mean caffeine intake was 169 mg per day. Caffeine intake at the upper 75th percentile (234 mg or more daily) and 90th percentile (392 mg or more per day) was significantly associated with having moderate to severe urinary incontinence (1.72, 95% 1.18-2.49 and 2.08, 95% 1.15-3.77, respectively). In addition, after adjusting for prostate conditions, the effect size for the association between caffeine intake and moderate to severe urinary incontinence remained. CONCLUSIONS: Caffeine consumption equivalent to approximately 2 cups of coffee daily (250 mg) is significantly associated with moderate to severe urinary incontinence in United States men. Our findings support the further study of caffeine modification in men with urinary incontinence. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.


title: Coffee consumption and risk of fractures: a systematic review and dose-response meta-analysis.

text: PURPOSE: The data on the association between coffee consumption and the risk of fractures are inconclusive. We performed a comprehensive literature review and meta-analysis to better quantify this association. METHODS: We identified all potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, and CINAHL (until February 2013). The keywords "coffee," "caffeine," "drink," and "beverage" were used as the exposure factors, and the keyword "fracture" was used as the outcome factor. We determined the overall relative risk (RR) and confidence interval (CI) for the highest and lowest levels of coffee consumption. A dose-response analysis was performed to assess the risk of fractures based on the level of coffee consumption. RESULTS: We included 253,514 participants with 12,939 fracture cases from 9 cohort and 6 case-control studies. The estimated RR of fractures at the highest level of coffee consumption was 1.14 (95% CI: 1.05-1.24; I(2)=0.0%) in women and 0.76 (95% CI: 0.62-0.94; I(2)=7.3%) in men. In the dose-response analysis, the pooled RRs of fractures in women who consumed 2 and 8 cups of coffee per day were 1.02 (95% CI: 1.01-1.04) and 1.54 (95% CI: 1.19-1.99), respectively. CONCLUSIONS: Our meta-analysis suggests that daily consumption of coffee is associated with an increased risk of fractures in women and a contrasting decreased risk in men. However, future well-designed studies should be performed to confirm these findings. Copyright © 2014 Elsevier Inc. All rights reserved.


title: Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.

text: Coffee, after water, is the most widely consumed beverage in the United States, and is the principal source of caffeine intake among adults. The biological effects of coffee may be substantial and are not limited to the actions of caffeine. Coffee is a complex beverage containing hundreds of biologically active compounds, and the health effects of chronic coffee intake are wide ranging. From a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type 2 diabetes mellitus and hypertension, as well as other conditions associated with CV risk such as obesity and depression; but it may adversely affect lipid profiles depending on how the beverage is prepared. Regardless, a growing body of data suggests that habitual coffee consumption is neutral to beneficial regarding the risks of a variety of adverse CV outcomes including coronary heart disease, congestive heart failure, arrhythmias, and stroke. Moreover, large epidemiological studies suggest that regular coffee drinkers have reduced risks of mortality, both CV and all-cause. The potential benefits also include protection against neurodegenerative diseases, improved asthma control, and lower risk of select gastrointestinal diseases. A daily intake of ∼2 to 3 cups of coffee appears to be safe and is associated with neutral to beneficial effects for most of the studied health outcomes. However, most of the data on coffee's health effects are based on observational data, with very few randomized, controlled studies, and association does not prove causation. Additionally, the possible advantages of regular coffee consumption have to be weighed against potential risks (which are mostly related to its high caffeine content) including anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and possibly increased risk of fractures. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.


title: Effect of decaffeination of coffee or tea on gastro-oesophageal reflux.

text: BACKGROUND: Coffee and tea are believed to cause gastro-oesophageal reflux; however, the effects of these beverages and of their major component, caffeine, have not been quantified. The aim of this study was to evaluate gastro-oesophageal reflux induced by coffee and tea before and after a decaffeination process, and to compare it with water and water-containing caffeine. METHODS: Three-hour ambulatory pH-metry was performed on 16 healthy volunteers, who received 300 ml of (i) regular coffee, decaffeinated coffee or tap water (n = 16), (ii) normal tea, decaffeinated tea, tap water, or coffee adapted to normal tea in caffeine concentration (n = 6), and (iii) caffeine-free and caffeine-containing water (n = 8) together with a standardized breakfast. RESULTS: Regular coffee induced a significant (P < 0.05) gastro-oesophageal reflux compared with tap water and normal tea, which were not different from each other. Decaffeination of coffee significantly (P < 0.05) diminished gastro-oesophageal reflux, whereas decaffeination of tea or addition of caffeine to water had no effect. Coffee adapted to normal tea in caffeine concentration significantly (P < 0.05) increased gastro-oesophageal reflux. CONCLUSIONS: Coffee, in contrast to tea, increases gastro-oesophageal reflux, an effect that is less pronounced after decaffeination. Caffeine does not seem to be responsible for gastro-oesophageal reflux which must be attributed to other components of coffee.


title: The effect of caffeine on intraocular pressure: a systematic review and meta-analysis.

text: BACKGROUND: Caffeine is widely consumed, and its effect on intraocular pressure (IOP) has been reported in conflicting data. The aim of this meta-analysis was to quantitatively summarize the effect of caffeine on IOP in normal individuals and in patients with glaucoma or ocular hypertension (OHT). METHODS: A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify pertinent randomized controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and EMBASE. A systematic review and meta-analysis was performed. IOP at 0.5 hour (h), 1 h and 1.5 h after caffeine ingestion was the main outcome measurement. RESULTS: Six RCTs (two parallel-designed and four crossover-designed) evaluating 144 participants fulfilled inclusion criteria. The risk of bias for these studies was uncertain. Among the participants, 103 were normal individuals and 41 were patients with glaucoma or OHT. In normal individuals, the IOPs measured at 0.5 h, 1 h and 1.5 h post-intervention were not affected by ingestion of caffeine. The weighted mean difference (WMD) with 95% confidence intervals (95%CI) for each measurement point were -0.740 (-2.454, 0.974), 0.522 (-0.568, 1.613) and 0.580 (-1.524, 2.684). However, in patients with glaucoma or OHT, IOP increased at each measurement point, with the WMD and 95%CI being 0.347 (0.078, 0.616), 2.395 (1.741,3.049) and 1.998 (1.522,2.474) respectively. No publication bias was detected by either Begg's or Egger's test. CONCLUSION: Available evidences showed that caffeine had different effects on IOP in different groups of individuals. For normal individuals, IOP was not changed by ingestion of caffeine, while for patients with glaucoma or OHT, IOP increased significantly. More high-quality RCTs are warranted to confirm this. The mechanisms underlying this phenomenon and the clinical significance are to be explored.


title: Caffeine Consumption and the Risk of Primary Open - Angle Glaucoma: A Prospective Cohort Study

text: Purpose We investigated whether caffeine, which transiently increases intraocular pressure (IOP) is associated with risk of primary open-angle glaucoma (POAG). Methods We followed 79,120 women from 1980 and 42,052 men from 1986 to 2004 who were 40+ years old, did not have POAG, and reported receiving eye examinations. Information on caffeine consumption, potential confounders and POAG diagnoses were repeatedly updated in validated follow-up questionnaires. We confirmed 1,011 incident POAG cases with medical record review. Cohort-specific and pooled analyses across cohorts were conducted to calculate multivariable rate ratios (RR). Results Compared with daily intake of < 150 mg, the pooled multivariable RRs were 1.05 [95% Confidence Interval (CI), 0.89–1.25] for consuming 150–299 mg, 1.19 [95% CI, 0.99–1.43] for 300 – 449 mg/day, 1.13 [95% CI, 0.89–1.43] for 450–559 mg and 1.17 [95% CI, 0.90, 1.53] for 600+ mg+ [p for trend = 0.11]. However, for consuming 5+ cups of caffeinated coffee daily, RR was 1.61 [95% CI, 1.00, 2.59; p for trend=0.02]; tea or caffeinated cola intake were not associated with risk. Greater caffeine intake was more adversely associated with POAG among those reporting family history of glaucoma, particularly in relation to POAG with elevated IOP (p for trend =0.0009; p-interaction=0.04). Conclusion Overall caffeine intake was not associated with increased risk of POAG. However, in secondary analyses, caffeine appeared to elevate risk of high-tension POAG among those with a family history of glaucoma; this may be due to chance, but warrants further study.


title: Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse.

text: The use of substances as the substrate for atrial fibrillation is not frequently recognized. Chocolate is derived from the roasted seeds of the plant theobroma cacao and its components are the methylxanthine alkaloids theobromine and caffeine. Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. Normal consumption of caffeine was not associated with risk of atrial fibrillation or flutter. Sympathomimetic effects, due to circulating catecholamines cause the cardiac manifestations of caffeine overdose toxicity, produce tachyarrhythmias such as supraventricular tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation.The commonly used doses of inhaled or nebulized salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart rate variability in patients with coronary artery disease and clinically stable asthma or chronic obstructive pulmonary disease. Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. We present a case of atrial fibrillation associated with chocolate intake abuse in a 19-year-old Italian woman with chronic salbutamol inhalation abuse. This case focuses attention on chocolate intake abuse associated with chronic salbutamol abuse as the substrate for atrial fibrillation. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.


title: Coffee and its consumption: benefits and risks.

text: Coffee is the leading worldwide beverage after water and its trade exceeds US $10 billion worldwide. Controversies regarding its benefits and risks still exist as reliable evidence is becoming available supporting its health promoting potential; however, some researchers have argued about the association of coffee consumption with cardiovascular complications and cancer insurgence. The health-promoting properties of coffee are often attributed to its rich phytochemistry, including caffeine, chlorogenic acid, caffeic acid, hydroxyhydroquinone (HHQ), etc. Many research investigations, epidemiological studies, and meta-analyses regarding coffee consumption revealed its inverse correlation with that of diabetes mellitus, various cancer lines, Parkinsonism, and Alzheimer's disease. Moreover, it ameliorates oxidative stress because of its ability to induce mRNA and protein expression, and mediates Nrf2-ARE pathway stimulation. Furthermore, caffeine and its metabolites help in proper cognitive functionality. Coffee lipid fraction containing cafestol and kahweol act as a safeguard against some malignant cells by modulating the detoxifying enzymes. On the other hand, their higher levels raise serum cholesterol, posing a possible threat to coronary health, for example, myocardial and cerebral infarction, insomnia, and cardiovascular complications. Caffeine also affects adenosine receptors and its withdrawal is accompanied with muscle fatigue and allied problems in those addicted to coffee. An array of evidence showed that pregnant women or those with postmenopausal problems should avoid excessive consumption of coffee because of its interference with oral contraceptives or postmenopausal hormones. This review article is an attempt to disseminate general information, health claims, and obviously the risk factors associated with coffee consumption to scientists, allied stakeholders, and certainly readers. © Taylor and Francis Group, LLC


title: A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases.

text: Several prospective studies considered the relation between coffee consumption and mortality. Most studies, however, were underpowered to detect an association, since they included relatively few deaths. To obtain quantitative overall estimates, we combined all published data from prospective studies on the relation of coffee with mortality for all causes, all cancers, cardiovascular disease (CVD), coronary/ischemic heart disease (CHD/IHD) and stroke. A bibliography search, updated to January 2013, was carried out in PubMed and Embase to identify prospective observational studies providing quantitative estimates on mortality from all causes, cancer, CVD, CHD/IHD or stroke in relation to coffee consumption. A systematic review and meta-analysis was conducted to estimate overall relative risks (RR) and 95 % confidence intervals (CI) using random-effects models. The pooled RRs of all cause mortality for the study-specific highest versus low (≤1 cup/day) coffee drinking categories were 0.88 (95 % CI 0.84-0.93) based on all the 23 studies, and 0.87 (95 % CI 0.82-0.93) for the 19 smoking adjusting studies. The combined RRs for CVD mortality were 0.89 (95 % CI 0.77-1.02, 17 smoking adjusting studies) for the highest versus low drinking and 0.98 (95 % CI 0.95-1.00, 16 studies) for the increment of 1 cup/day. Compared with low drinking, the RRs for the highest consumption of coffee were 0.95 (95 % CI 0.78-1.15, 12 smoking adjusting studies) for CHD/IHD, 0.95 (95 % CI 0.70-1.29, 6 studies) for stroke, and 1.03 (95 % CI 0.97-1.10, 10 studies) for all cancers. This meta-analysis provides quantitative evidence that coffee intake is inversely related to all cause and, probably, CVD mortality.


title: Heavy coffee drinking and epilepsy.

text: Dietary habits have been rarely associated with seizure frequency in patients with epilepsy. We report a case of a man with a partial symptomatic epilepsy whose daily habit of heavy coffee drinking was associated with an increased seizure frequency. This patient witnessed a dramatic decrease in the frequency of his seizures after stopping coffee ingestion. Caffeine is a global stimulant and the reduction of its intake may help in the treatment of epilepsy.


title: Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies.

text: BACKGROUND: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, and risk factors are well established. Caffeine exposure has been associated with increased risk of AF, but heterogeneous data exist in the literature. OBJECTIVE: To evaluate the association between chronic exposure to caffeine and AF. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: PubMed, CENTRAL, ISI Web of Knowledge and LILACS to December 2012. Reviews and references of retrieved articles were comprehensively searched. STUDY SELECTION: Two reviewers independently searched for studies and retrieved their characteristics and data estimates. DATA SYNTHESIS: Random-effects meta-analysis was performed, and pooled estimates were expressed as OR and 95% CI. Heterogeneity was assessed with the I(2) test. Subgroup analyses were conducted according to caffeine dose and source (coffee). RESULTS: Seven observational studies evaluating 115 993 individuals were included: six cohorts and one case-control study. Caffeine exposure was not associated with an increased risk of AF (OR 0.92, 95% CI 0.82 to 1.04, I(2)=72%). Pooled results from high-quality studies showed a 13% odds reduction in AF risk with lower heterogeneity (OR 0.87; 95% CI 0.80 to 0.94; I(2)=39%). Low-dose caffeine exposure showed OR 0.85 (95% CI 0.78 to 92, I(2)=0%) without significant differences in other dosage strata. Caffeine exposure based solely on coffee consumption also did not influence AF risk. CONCLUSIONS: Caffeine exposure is not associated with increased AF risk. Low-dose caffeine may have a protective effect.


title: Tea consumption didn’t modify the risk of fracture: a dose–response meta-analysis of observational studies

text: Background Fractures are important causes of healthy damage and economic loss nowadays. The conclusions of observational studies on tea consumption and fracture risk are still inconsistent. The objective of this meta-analysis is to determine the effect of tea drinking on the risk of fractures. Methods A comprehensive literature search was conducted in PubMed, Embase and reference lists of the relevant articles. Observational studies that reported an estimate of the association between tea drinking and incidence of fractures were included. A meta-analysis was conducted by the STATA software. Results A total of 9 studies involving 147,950 individuals that examined the association between tea consumption and risk of fractures were included in this meta-analysis. The odds risks (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. The pooled OR of 9 observational studies for the tea consumption on risk of fracture was 0.89 (95% CI, 0.78-1.04). In the subgroup analyses, no significant association was detected in neither cohort studies (n = 3; OR, 0.97; 95% CI, 0.89-1.06) nor case–control studies (n = 6; OR, 0.91; 95% CI, 0.70-1.19), respectively. No significant association was detected in the dose–response meta-analysis. Conclusions Tea consumption might not be associated with the risk of fractures. The following large-sample and well-designed studies are required to confirm the existing conclusions. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5309904231178427.


title: CAFFEINE AND URINARY INCONTINENCE IN US WOMEN

text: Introduction and Hypothesis The goal of this study was to characterize associations between caffeine consumption and severity of urinary incontinence (UI) in US women. We hypothesized that moderate and high caffeine intake would be associated with UI in US women when controlling for other factors associated with UI. Methods US women participated in the 2005–2006 and 2007–2008 National Health and Nutrition Examination Survey (NHANES), a cross-sectional, nationally representative survey. Using the Incontinence Severity Index, UI was categorized as “any” and “moderate/severe”. Types of UI included stress, urge, mixed, and other. Food diaries were completed and average water (gm/day), total dietary moisture (gm/day), and caffeine (mg/day) intake were calculated into quartiles. Step-wise logistic regression models were constructed adjusting for: sociodemographics, chronic diseases, body mass index, self-rated health, depression, alcohol use, dietary water and moisture in take, and reproductive factors. Results From the 4309 non-pregnant women (aged ≥20 years) who had complete UI and dietary data, UI prevalence for any UI was 41.0% and 16.5% for moderate/severe UI, with stress UI the most common UI type (36.6%). Women consumed a mean caffeine intake of 126.7 mg/day. After adjusting for multiple factors, caffeine in take in the highest quartile (≥204 mg/day) was associated with any UI (prevalence odds ratio (POR)1.47, 95% CI 1.07, 2.01), but not moderate/severe UI (POR 1.42, 95% CI 0.98, 2.07). Type of UI (stress, urgency, mixed) was not associated with caffeine intake. Conclusions Caffeine intake ≥204 mg/day was associated with any UI, but not moderate/severe UI, in US women.


title: Caffeine intake and atrial fibrillation incidence: dose response meta-analysis of prospective cohort studies.

text: BACKGROUND: The association between habitual caffeine intake with incident atrial fibrillation (AF) was unknown. We conducted a meta-analysis to investigate the association between chronic exposure of caffeine and the risk of AF and to evaluate the potential dose-response relation. METHODS: We searched PubMed, EMBASE, and the Cochrane Library up to November 2013 and references of relevant retrieved articles. Prospective cohort studies were included with relative risk (RR) or hazard ratio and 95% confidence intervals (CIs) for AF according to coffee/caffeine intake. RESULTS: Six prospective cohort studies with 228,465 participants were included. In the primary meta-analysis, caffeine exposure was weakly associated with a reduced risk of AF (RR, 0.90; 95% CI, 0.81-1.01; P = 0.07; I(2) = 73%). In subgroup analyses, pooled results from studies with adjustment of potential confounders showed an 11% reduction for low doses (RR, 0.89; 95% CI, 0.80-0.99, P = 0.032; I(2) = 30.9%, P = 0.227) and 16% for high doses (RR, 0.84; 95% CI, 0.75-0.94, P = 0.002; I(2) = 24.1%, P = 0.267) of caffeine consumption in AF risk. An inverse relation was found between habitual caffeine intake and AF risk (P for overall trend = 0.015; P for nonlinearity = 0.27) in dose-response meta-analysis and the incidence of AF decreased by 6% (RR, 0.94; 95% CI, 0.90-0.99) for every 300 mg/d increment in habitual caffeine intake. CONCLUSIONS: It is unlikely that caffeine consumption causes or contributes to AF. Habitual caffeine consumption might reduce AF risk. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.


title: No Association of Coffee Consumption with Gastric Ulcer, Duodenal Ulcer, Reflux Esophagitis, and Non-Erosive Reflux Disease: A Cross-Sectional Study of 8,013 Healthy Subjects in Japan

text: Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.


title: Tea consumption and cardiovascular disease risk.

text: BACKGROUND: The present analysis was conducted in response to inconsistent epidemiologic studies on the relation between consumption of tea and cardiovascular diseases. OBJECTIVE: We undertook a literature review of the consistency and strength of the associations between tea and cardiovascular diseases on the basis of published observational studies and meta-analyses addressing tea or tea flavonoids and cardiovascular disease risk. DESIGN: We performed a search in 3 databases for meta-analyses and compared them with studies they subsumed. We performed an additional search for subsequent studies to determine whether the conclusions were consistent. RESULTS: Many epidemiologic studies have been conducted and summarized in 5 meta-analyses on either tea consumption or flavonoid consumption and cardiovascular disease or the subset of stroke. Heterogeneity of effect was seen when the outcome included all cardiovascular diseases. In the case of stroke, a consistent, dose-response association with tea consumption on both incidence and mortality was noted with RRs of 0.80 (95% CI: 0.65, 0.98) for flavonoids and 0.79 (95% CI: 0.73, 0.85) for tea when high and low intakes were compared or the addition of 3 cups/d was estimated. CONCLUSION: Thus, the strength of this evidence supports the hypothesis that tea consumption might lower the risk of stroke.


title: Association of Coffee Drinking with Total and Cause-Specific Mortality

text: Background Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear. Methods We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229,119 men and 173,141 women in the National Institutes of Health–AARP Diet and Health Study who were 50 to 71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline. Results During 5,148,760 person-years of follow-up between 1995 and 2008, a total of 33,731 men and 18,784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P<0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (P<0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline. Conclusions In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data. (Funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.)


title: Association of coffee consumption with all-cause and cardiovascular disease mortality

text: Objective To evaluate the association between coffee consumption and mortality from all causes and cardiovascular disease (CVD). Patients and Methods Data from the Aerobics Center Longitudinal Study (ACLS) representing a total of 43,727 participants contributing to 699,632 person-years of follow-up time, were included. Baseline data were collected by an in-person interview based on standardized questionnaires and a medical examination, including fasting blood chemistry analysis, anthropometry, blood pressure, electrocardiography, and a maximal graded exercise test, between February 3, 1971 and December 30, 2002. Cox regression analysis was used to quantify the association between coffee consumption and all-cause and cause-specific mortality. Results During the 17-year median follow-up period, 2512 deaths occurred (32% due to CVD). In multivariate analyses, coffee intake was positively associated with all-cause mortality in men. Men who drank >28 cups coffee per week had higher all-cause mortality (hazard ratio (HR): 1.21; 95% confidence interval (CI): 1.04–1.40). However, after stratification based on age, both younger (<55 years) men and women showed a statistically significant association between high coffee consumption (>28 cups/week) and all-cause mortality, after adjusting for potential confounders and fitness level (HR: 1.56; 95% CI: 1.30–1.87 for men and HR: 2.13; 95% CI: 1.26–3.59 for women, respectively). Conclusion In this large cohort, a positive association between coffee consumption and all-cause mortality was observed among men and both men and women <55 years of age. Based on our findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups/day). However, this finding should be assessed in future studies from other populations.


title: Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients.

text: OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial-dependent vasodilatation is impaired during the postprandial state, and oxidative stress could play a key role in its development. METHODS: Twenty-one hypercholesterolemic volunteers received two breakfasts, using a randomized sequential crossover design. Both arms received the same olive oil, but one had its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake. Postprandial plasma concentrations of lipid fractions, lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x)) were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function, as well as a greater increase in concentrations of NO(x) (p < 0.001) and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p < 0.001) than the ones induced by the low polyphenol fat meal. A positive correlation was found to exist between NO(x) and enhanced endothelial function at the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postprandial state. This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites.


title: Differential Effects of Two Isoenergetic Meals Rich in Saturated or Monounsaturated Fat on Endothelial Function in Subjects With Type 2 Diabetes

text: OBJECTIVE—To examine the acute effects of consumption of monounsaturated (MUFAs) and saturated fatty acids (SAFAs) on endothelial function in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 33 participants were examined after consumption of two different isocaloric meals: one rich in MUFA and one rich in SAFA, in the form of extra-virgin olive oil and butter, respectively. Endothelial function was assessed by determination of flow-mediated dilatation (FMD). RESULTS—FMD did not change significantly after the MUFA-rich meal but declined after the SAFA-rich meal. The FMD during the experiment, expressed as incremental area under the curve, increased after the MUFA-rich meal by 5.2 ± 2.5% and decreased after the SAFA-rich meal by 16.7 ± 6.0% (Δ = −11.5 ± 6.4%; P = 0.008). CONCLUSIONS—Consumption of an SAFA-rich meal is harmful for the endothelium, while a MUFA-rich meal does not impair endothelial function in subjects with type 2 diabetes.


title: Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial.

text: CONTEXT: The metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood. OBJECTIVE: To assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III. INTERVENTIONS: Patients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat, <30%). MAIN OUTCOME MEASURES: Nutrient intake; endothelial function score as a measure of blood pressure and platelet aggregation response to l-arginine; lipid and glucose parameters; insulin sensitivity; and circulating levels of high-sensitivity C-reactive protein (hs-CRP) and interleukins 6 (IL-6), 7 (IL-7), and 18 (IL-18). RESULTS: After 2 years, patients following the Mediterranean-style diet consumed more foods rich in monounsaturated fat, polyunsaturated fat, and fiber and had a lower ratio of omega-6 to omega-3 fatty acids. Total fruit, vegetable, and nuts intake (274 g/d), whole grain intake (103 g/d), and olive oil consumption (8 g/d) were also significantly higher in the intervention group (P<.001). The level of physical activity increased in both groups by approximately 60%, without difference between groups (P =.22). Mean (SD) body weight decreased more in patients in the intervention group (-4.0 [1.1] kg) than in those in the control group (-1.2 [0.6] kg) (P<.001). Compared with patients consuming the control diet, patients consuming the intervention diet had significantly reduced serum concentrations of hs-CRP (P =.01), IL-6 (P =.04), IL-7 (P = 0.4), and IL-18 (P = 0.3), as well as decreased insulin resistance (P<.001). Endothelial function score improved in the intervention group (mean [SD] change, +1.9 [0.6]; P<.001) but remained stable in the control group (+0.2 [0.2]; P =.33). At 2 years of follow-up, 40 patients in the intervention group still had features of the metabolic syndrome, compared with 78 patients in the control group (P<.001). CONCLUSION: A Mediterranean-style diet might be effective in reducing the prevalence of the metabolic syndrome and its associated cardiovascular risk.


title: Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil.

text: High postprandial serum lipid concentrations are associated with increased oxidative stress which, in turn, increases the risk of atherosclerosis. Epidemiological studies correlate lower incidence of cardiovascular disease with adherence to the Mediterranean diet. The aim of this study was to evaluate changes in inflammatory (TXB(2) and LTB(4)) and oxidative stress markers (urinary hydrogen peroxide levels and serum antioxidant capacity), in addition to classic lipid parameters, after a fat-rich meal administered to 12 normolipemic, healthy subjects. Following a Latin square design, subjects were divided into three groups, each one receiving a different kind of oil (extra virgin olive oil; EVOO, olive oil; OO or corn oil; CO, together with 150g of potatoes), with 2-week washout periods between treatments. Blood samples were drawn at baseline and after 1, 2, and 6h after the meal. A significant decrease in inflammatory markers, namely TXB(2) and LTB(4), after 2 and 6h after EVOO (but not OO or CO) consumption and a concomitant increase of serum antioxidant capacity were recorded. These data reinforce the notion that the Mediterranean diet reduces the incidence of coronary heart disease partially due to the protective role of its phenolic components, including those of extra virgin olive oil.


title: Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects.

text: BACKGROUND: Persons following current dietary guidelines have a lower risk of mortality from coronary heart disease. OBJECTIVE: The objective was to compare the short-term effect of a high-fat meal and a high-carbohydrate meal, with and without dietary antioxidants, on vasomotor, antiplatelet, and hemostatic functions of the endothelium in healthy subjects. DESIGN: In an observer-blinded, randomized crossover study, 25 (13 men and 12 women) healthy subjects were given each of 3 meals in random order at 1-wk intervals: a high-fat meal (760 kcal), an isoenergetic high-carbohydrate meal, and a high-fat meal with dietary antioxidants from vegetables (865 kcal). Endothelial functions, as assessed by hemodynamic and rheologic responses to L-arginine--the natural precursor of nitric oxide--were evaluated before and 4 h after each meal. RESULTS: Unlike the high-carbohydrate meal, the high-fat meal increased the plasma concentrations of triacylglycerol (P < 0.01); both meals activated hemostasis. The high-carbohydrate meal did not modify blood pressure, and platelet aggregation decreased in response to the L-arginine load (-7.1 +/- 2.3 mm Hg and -8.5 +/- 4.5%, respectively). After the high-fat meal, the decrease in blood pressure in response to L-arginine was reduced (-1 +/- 0.8 mm Hg), and platelet aggregation showed a paradoxical increase (4.1 +/- 2.1%; P < 0.01 compared with the high-carbohydrate meal). The high-fat meal with antioxidants partially restored the vascular response to L-arginine. CONCLUSION: Compared with a high-carbohydrate meal, a high-fat meal can modify endothelial functions toward a more atherogenetic profile, which is partially prevented by dietary antioxidants.


title: Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men.

text: Current National Cholesterol Education Program guidelines consider desirable total and low-density lipoprotein cholesterol levels to be < 200 and < 160 mg/dl, respectively, for healthy individuals without multiple coronary risk factors. To determine the extent to which these levels affect vascular function, we assessed flow-mediated (endothelium-dependent) brachial artery vasoactivity noninvasively before, during, and after cholesterol lowering (simvastatin 10 mg/day) in 7 healthy middle-aged men with cholesterol levels meeting current recommendations. Flow-mediated brachial artery vasoactivity was measured using 7.5 MHz ultrasound and expressed as percent diameter change from baseline to hyperemic conditions (1 minute following 5 minutes of blood pressure cuff arterial occlusion). Flow-mediated vasoactivity rose from 5.0 +/- 3.6% at baseline to 10.5 +/- 5.6%, 13.3 +/- 4.3%, and 15.7 +/- 4.9% (all p < 0.05) as cholesterol fell from 200 +/- 12 to 161 +/- 18, 169 +/- 16, and 153 +/- 11 mg/dl after 2, 4, and 12 weeks, respectively, of cholesterol-lowering therapy. Vasoactivity and cholesterol returned to baseline levels 12 weeks after simvastatin discontinuation. Overall, vasoactivity was found to correlate inversely with cholesterol levels (r = -0.47, p = 0.004). These data suggest that flow-mediated brachial artery vasoactivity responds rapidly to changes in cholesterol levels and that endothelial function improves by lowering cholesterol levels below recommendations of current guidelines.


title: Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men.

text: BACKGROUND: The regulatory function of the endothelium is altered in hypercholesterolemia, and the subsequent endothelial dysfunction plays a central role in the development of atherosclerosis. OBJECTIVE: To determine whether endothelial function in hypercholesterolemic patients is affected by replacing a saturated fat-enriched diet with a low-fat, low-saturated fat diet (the U.S. National Cholesterol Education Program stage 1 [NCEP-1] diet) or a diet rich in monounsaturated fat (such as that common in Mediterranean countries). DESIGN: Intervention dietary study with a baseline phase and two randomized crossover dietary periods. SETTING: Hospital Universitario Reina Sofía, Córdoba, Spain. PATIENTS: 22 hypercholesterolemic men. INTERVENTION: Patients followed a diet high in saturated fat, then were assigned in a crossover design to the NCEP-1 diet or a Mediterranean diet. Each dietary period lasted 28 days. MEASUREMENTS: Plasma P-selectin levels, lipid concentrations, and endothelial function. RESULTS: Compared with the saturated fat diet, flow-mediated dilatation increased during the Mediterranean diet but not during the NCEP-1 diet. In addition, levels of plasma cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and P-selectin decreased during the NCEP-1 and Mediterranean diets. CONCLUSION: In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial function.


title: Olive oil intake and CHD in the European Prospective Investigation into Cancer and Nutrition Spanish cohort.

text: Olive oil is well known for its cardioprotective properties; however, epidemiological data showing that olive oil consumption reduces incident CHD events are still limited. Therefore, we studied the association between olive oil and CHD in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 % male), free of CHD events at baseline, recruited from five EPIC-Spain centres from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle information was collected using interview-administered questionnaires. Cox proportional regression models were used to assess the relationship between validated incident CHD events and olive oil intake (energy-adjusted quartiles and each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential confounders. During a 10·4-year follow-up, 587 (79 % male) CHD events were recorded. Olive oil intake was negatively associated with CHD risk after excluding dietary mis-reporters (hazard ratio (HR) 0·93; 95 % CI 0·87, 1·00 for each 10 g/d per 8368 kJ (2000 kcal) and HR 0·78; 95 % CI 0·59, 1·03 for upper v. lower quartile). The inverse association between olive oil intake (per 10 g/d per 8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced CHD risk (P = 0·048)), in never/low alcohol drinkers (25 % reduced CHD risk (P < 0·001)) and in virgin olive oil consumers (14 % reduced CHD risk (P = 0·072)). In conclusion, olive oil consumption was related to a reduced risk of incident CHD events. This emphasises the need to conserve the traditional culinary use of olive oil within the Mediterranean diet to reduce the CHD burden.


title: Olive, soybean and palm oils intake have a similar acute detrimental effect over the endothelial function in healthy young subjects.

text: BACKGROUND AND AIM: Currently, more than 30% of the caloric intake in the Colombian population comes from vegetable oil consumption mainly by the ingestion of deep-fried foods. Recently, it has been reported that unsaturated fatty acid rich oils have a beneficial effect on the endothelial function. Nevertheless, it is well know that the deep-frying process alters the chemical composition of vegetable oils and can produce adverse effects in the endothelial function. OBJECTIVE: To evaluate the acute effect of the ingestion of large amounts of olive, soybean and palm oils, fresh and at two different deep-fry levels, on the glucose and lipid profiles and the endothelial function. METHODS AND RESULTS: Ten healthy young volunteers were included in the study. After performing a baseline evaluation of cardiovascular risk factors and drawing a fasting blood sample, subjects were exposed to a randomly assigned potato soup meal containing 60 mL of one of three different vegetable oils (olive, soybean and palm), either fresh or at one of two different deep-fry levels (10 and 20 fries, respectively). Flow-mediated vasodilation (FMD) was performed in fasting conditions and 3h after the intake of the oil rich meal. Furthermore, blood samples were taken at these stages for the lipid profiles and plasma glucose determinations. All the meals resulted in a similar acute endothelial impairment (FMD decrease of 32.1%, confidence interval [CI] 95%, 28.0-36.2) and postprandial increase in triglycerides (27.03%, CI 95%, 20.5-33.3), independently of the type of oil ingested (p=0.44) and regardless of its deep-fry level (p=0.62). No correlation was found between endothelial impairment and postprandial triglyceride increment (r=-0.22, p=0.09). CONCLUSIONS: No difference was found in the acute adverse effect of the ingestion of different vegetable oils on the endothelial function. All the vegetable oils, fresh and deep-fried, produced an increase in the triglyceride plasma levels in healthy subjects.


title: Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependen...

text: Abnormalities in endothelial function may be associated with increased cardiovascular risk in diabetic patients. We examined the effect of an oleic-acid-rich diet on insulin resistance and endothelium-dependent vasoreactivity in type 2 diabetes. Eleven type 2 diabetic patients were changed from their usual linoleic-acid-rich diet and treated for 2 months with an oleic-acid-rich diet. Insulin-mediated glucose transport was measured in isolated adipocytes. Fatty acid composition of the adipocyte membranes was determined by gas-liquid chromatography and flow-mediated endothelium-dependent and -independent vasodilatation were measured in the superficial femoral artery at the end of each dietary period. There was a significant increase in oleic acid and a decrease in linoleic acid on the oleic-acid-rich diet (p<0.0001). Diabetic control was not different between the diets, but there was a small but significant decrease in fasting glucose/insulin on the oleic-acid-rich diet. Insulin-stimulated (1 ng/ml) glucose transport was significantly greater on the oleic- acid-rich diet (0.56+/-0.17 vs. 0.29+/-0.14 nmol/10(5) cells/3 min, p<0.0001). Endothelium-dependent flow-mediated vasodilatation (FMD) was significantly greater on the oleic-acid-rich diet (3.90+/-0.97% vs. 6.12+/-1.36% p<0.0001). There was a significant correlation between adipocyte membrane oleic/linoleic acid and insulin-mediated glucose transport (p<0.001) but no relationship between insulin-stimulated glucose transport and change in endothelium-dependent FMD. There was a significant positive correlation between adipocyte membrane oleic/linoleic acid and endothelium-dependent FMD (r=0.61, p<0.001). Change from polyunsaturated to monounsaturated diet in type 2 diabetes reduced insulin resistance and restored endothelium-dependent vasodilatation, suggesting an explanation for the anti-atherogenic benefits of a Mediterranean-type diet.


title: The postprandial effect of components of the Mediterranean diet on endothelial function.

text: OBJECTIVES: This study investigated the postprandial effect of components of the Mediterranean diet on endothelial function, which may be an atherogenic factor. BACKGROUND: The Mediterranean diet, containing olive oil, pasta, fruits, vegetables, fish, and wine, is associated with an unexpectedly low rate of cardiovascular events. The Lyon Diet Heart Study found that a Mediterranean diet, which substituted omega-3-fatty-acid-enriched canola oil for the traditionally consumed omega-9 fatty-acid-rich olive oil, reduced cardiovascular events. METHODS: We fed 10 healthy, normolipidemic subjects five meals containing 900 kcal and 50 g fat. Three meals contained different fat sources: olive oil, canola oil, and salmon. Two olive oil meals also contained antioxidant vitamins (C and E) or foods (balsamic vinegar and salad). We measured serum lipoproteins and glucose and brachial artery flow-mediated vasodilation (FMD), an index of endothelial function, before and 3 h after each meal. RESULTS: All five meals significantly raised serum triglycerides, but did not change other lipoproteins or glucose 3 h postprandially. The olive oil meal reduced FMD 31% (14.3 +/- 4.2% to 9.9 +/- 4.5%, p = 0.008). An inverse correlation was observed between postprandial changes in serum triglycerides and FMD (r = -0.47, p < 0.05). The remaining four meals did not significantly reduce FMD. CONCLUSIONS: In terms of their postprandial effect on endothelial function, the beneficial components of the Mediterranean and Lyon Diet Heart Study diets appear to be antioxidant-rich foods, including vegetables, fruits, and their derivatives such as vinegar, and omega-3-rich fish and canola oils.


title: Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial...

text: Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.


title: Differential anti-inflammatory effects of phenolic compounds from extra virgin olive oil identified in human whole blood cultures.

text: OBJECTIVE: The olive oil-rich Mediterranean diet protects against cardiovascular disease, which involves inflammatory processes. This study investigated the effects of phenolic compounds found in extra virgin olive oil on inflammatory mediator production by human mononuclear cells. METHODS: Diluted human blood cultures were stimulated with lipopolysaccharide in the presence of phenolics (vanillic, p-coumaric, syringic, homovanillic and caffeic acids, kaempferol, oleuropein glycoside, and tyrosol) at concentrations of 10(-7) to 10(-4) M. Concentrations of the inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 and of the inflammatory eicosanoid prostaglandin E2 were measured by enzyme-linked immunosorbent assay. RESULTS: Oleuropein glycoside and caffeic acid decreased the concentration of interleukin-1beta. At a concentration of 10(-4) M, oleuropein glycoside inhibited interleukin-1beta production by 80%, whereas caffeic acid inhibited production by 40%. Kaempferol decreased the concentration of prostaglandin E2. At a concentration of 10(-4) M, kaempferol inhibited prostaglandin E2 production by 95%. No effects were seen on concentrations of interleukin-6 or tumor necrosis factor-alpha and there were no effects of the other phenolic compounds. CONCLUSIONS: Some, but not all, phenolic compounds derived from extra virgin olive oil decrease inflammatory mediator production by human whole blood cultures. This may contribute to the antiatherogenic properties ascribed to extra virgin olive oil.


title: Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension.

text: BACKGROUND: Olive oil polyphenols have been associated with several cardiovascular health benefits. This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure (BP) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension. METHODS: We conducted a double-blind, randomized, crossover dietary-intervention study. After a run-in period of 4 months (baseline values), two diets were used, one with polyphenol-rich olive oil (∼30 mg/day), the other with polyphenol-free olive oil. Each dietary period lasted 2 months with a 4-week washout between diets. Systolic and diastolic BP, serum or plasma biomarkers of endothelial function, oxidative stress, and inflammation, and ischemia-induced hyperemia in the forearm were measured. RESULTS: When compared to baseline values, only the polyphenol-rich olive oil diet led to a significant (P < 0.01) decrease of 7.91 mm Hg in systolic and 6.65 mm Hg of diastolic BP. A similar finding was found for serum asymmetric dimethylarginine (ADMA) (-0.09 ± 0.01 µmol/l, P < 0.01), oxidized low-density lipoprotein (ox-LDL) (-28.2 ± 28.5 µg/l, P < 0.01), and plasma C-reactive protein (CRP) (-1.9 ± 1.3 mg/l, P < 0.001). The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates (+4.7 ± 6.6 µmol/l, P < 0.001) and hyperemic area after ischemia (+345 ± 386 perfusion units (PU)/sec, P < 0.001). CONCLUSIONS: We concluded that the consumption of a diet containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension.


title: Absence of postprandial surge in coronary blood flow distal to significant stenosis: a possible mechanism of postprandial angina.

text: OBJECTIVES: This study was designed to investigate a possible mechanism of postprandial angina. BACKGROUND: Postprandial angina has been recognized for more than two centuries; however, its mechanism is still controversial. The most widely accepted mechanism involves increased myocardial oxygen demand after food intake. Recently, the redistribution in coronary blood flow (CBF) was suggested as a possible mechanism. METHODS: Twenty young, healthy volunteer controls and 20 patients with significant stenosis in the left anterior descending (LAD) or left main coronary artery were enrolled in the study. Coronary blood flow was evaluated in the distal LAD by using transthoracic Doppler echocardiography before and 15, 30, 45, and 60 min after food intake. In the CBF curve, the time velocity integral of diastolic flow (Dtvi) and the product of Dtvi and heart rate (HR) were measured. In six patients, these measurements were repeated after successful coronary intervention. RESULTS: In the healthy volunteer controls, Dtvi and Dtvi x HR increased after food intake with a peak value at 15 min, which indicates the presence of postprandial surge in the CBF. Fasting values and peak values at 15 min were significantly different (Dtvi: 15.1 +/- 4.9 cm/s vs. 18.9 +/- 5.9 cm/s, p = 0.04, Dtvi x HR: 862.2 +/- 261.5 cm/min vs. 1,174.2 +/- 307.5, p = 0.002). In contrast with the controls, despite postprandial increase in double product (HR x blood pressure), Dtvi and Dtvi x HR in the patient group decreased after food intake, with a nadir value at 45 min. Fasting values and nadir values at 45 min were significantly different (Dtvi: 24.0 +/- 19.6 cm/s vs. 19.3 +/- 17.1 cm/s, p < 0.001, Dtvi x HR: 1,449.6 +/- 1,044.0 cm/min vs. 1,273.4 +/- 1,000.9 cm/min, p = 0.002). In six patients, the CBF pattern resumed the normal pattern of postprandial surge in the CBF after successful coronary intervention. CONCLUSIONS: Results of our study suggest that "steal phenomenon" may play a role in the mechanism of postprandial angina.


title: 8:45-90:00. The Influence of a High Fat Meal Compared to an Olestra Meal on Coronary Artery Endothelial Dysfunction by Rubidium (Rb)-82 Positron Em...

text: Background: Cellular changes lead to coronary artery endothelial dysfunction (ED) and precede plaque formation. Clinical events, such as unstable angina and acute coronary syndromes, are common consequences of ED. Coronary artery ED, as characterized by Rb-82 PE, is a perfusion abnormality at rest, which improves following stress. In risk factor modification studies, particularly in cholesterol-lowering trials, coronary artery ED has been demonstrated to be reversible. Other studies have correlated low fat diet modification with improvement in coronary artery disease.Purpose: This study evaluates changes in myocardial perfusion following meals with low versus high TG content, and its influence on post prandial serum TG.Methods: With a randomized, double blind placebo controlled, cross over design, we investigated 19 patients (10 with ED and 9 with normal perfusion) with Rb-82 PET for myocardial blood flow at rest and with adenosine stress. PET images and serum triglycerides were obtained before and after an olestra (OA) meal (2.7g TG, 44g olestra) and a high-fat meal (46.7g TG). Meals were matched for carbohydrate, protein, and cholesterol content.Results: Myocardial perfusion (uCi/cc) increased 11 - 12% following the OA meal compared to the high-fat meal in patients with ED. For all patients combined, serum TG increased significantly (p < 0.01) in the non-OA group with the median change from baseline to 170.0 mg/dl, compared to 21.5 mg/dl in the OA group during the 6 hours following the meal.Conclusions: A single olestra meal significantly diminishes post prandial serum TG levels and improves myocardial perfusion in patients with endothelial disease.


title: Effect of fat and carbohydrate consumption on endothelial function.

text: Consumption of a meal high in monounsaturated fat was associated with acute impairment of endothelial function when compared with a carbohydrate-rich meal. Such a divergent response in endothelial function may be important in the modulation of vascular function in health and disease.


title: Brachial artery ultrasound: a noninvasive tool in the assessment of triglyceride-rich lipoproteins.

text: In recent years, endothelial dysfunction has been identified as an early feature of atherosclerosis. Endothelial function can be measured noninvasively by using brachial artery ultrasound. A variety of factors associated with atherosclerosis also impair endothelial function. Some of these factors are lipoproteins such as various forms of low-density lipoproteins, postprandial chylomicron remnants, fasting triglyceride-rich particles, and free fatty acids. A high-fat diet also has an adverse effect on endothelial function. Several interventions can improve endothelial function and, at the same time, reduce cardiovascular events. Measuring endothelial function may eventually serve as a useful index to determine an individual's risk for coronary artery disease.


title: Impairment of endothelial function after a high-fat meal in patients with coronary artery disease.

text: OBJECTIVE: To determine the effect of postprandial lipid changes on endothelial function in patients with coronary artery disease (CAD) after a high-fat meal. METHODS: We studied 50 CAD patients and 25 control participants, who were all normocholesterolemic. Flow-mediated vasodilatation of the brachial artery was evaluated by the high-resolution ultrasound technique before and after a single high-fat meal (800 calories; 50 g fat). RESULTS: Postprandial serum triglyceride level increased significantly at 2-7 h and mean flow-mediated vasodilatation was impaired significantly (from 4.22 +/- 0.44 to 2.75 +/- 0.33%, P < 0.01) for 75 subjects. The increment in 2 h serum triglyceride level correlated positively with the decrement in postprandial flow-mediated vasodilatation (r = 0.459, P < 0.01). Postprandial triglyceride level was significantly higher in CAD patients than in control participants. Flow-mediated vasodilatation was significantly impaired in CAD patients (from 3.04 +/- 0.39 to 1.69 +/- 0.23%, P < 0.01) and control participants (from 6.58 +/- 0.52 to 4.87 +/- 0.19%, P < 0.05) after a high-fat meal. The impairment of flow-mediated dilatation was more severe in CAD patients (44.41%) than in control participants (25.99%, P < 0.01). CONCLUSION: Postprandial endothelium-dependent vasodilatation after a single high-fat meal was severely impaired in normocholesterolemic CAD patients and control participants. The disordered postprandial metabolism of triglyceride-rich lipoproteins may play an atherogenic role by inducing endothelial dysfunction.