query: Healthy Chocolate Milkshakes

positive: Cherry Consumption and the Risk of Recurrent Gout Attacks Objective To study the relation between cherry intake and the risk of recurrent gout attacks among individuals with gout. Methods We conducted a case-crossover study to examine associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed online for one year. Participants were asked about the following information when experiencing a gout attack: the onset date of the gout attack, symptoms and signs, medications (including anti-gout medications), and potential risk factors (including daily intake of cherries and cherry extract) during the 2-day period prior to the gout attack. We assessed the same exposure information over 2-day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Results Our study included 633 individuals with gout. Cherry intake over a 2-day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate odds ratio [OR] = 0.65, 95% CI: 0.50-0.85). Cherry extract intake showed a similar inverse association (multivariate OR=0.55, 95% CI: 0.30-0.98). The effect of cherry intake persisted across subgroups by sex, obesity status, purine intake, alcohol use, diuretic use, and use of anti-gout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than periods without either exposure (OR=0.25, 95% CI: 0.15-0.42). Conclusions These findings suggest that cherry intake is associated with a lower risk of gout attacks.

positive: Cherries and health: a review. Cherries, and in particular sweet cherries, are a nutritionally dense food rich in anthocyanins, quercetin, hydroxycinnamates, potassium, fiber, vitamin C, carotenoids, and melatonin. UV concentration, degree of ripeness, postharvest storage conditions, and processing, each can significantly alter the amounts of nutrients and bioactive components. These constituent nutrients and bioactive food components support the potential preventive health benefits of cherry intake in relation to cancer, cardiovascular disease, diabetes, inflammatory diseases, and Alzheimer's disease. Mechanistically, cherries exhibit relatively high antioxidant activity, low glycemic response, COX 1 and 2 enzyme inhibition, and other anti-carcinogenic effects in vitro and in animal experiments. Well-designed cherry feeding studies are needed to further substantiate any health benefits in humans.

positive: Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans. Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans. Copyright © 2012 Elsevier Inc. All rights reserved.

positive: Evaluation of Antiradical Activity of Different Cocoa and Chocolate Products: Relation with Lipid and Protein Composition Chocolate antioxidant properties are often claimed; however, they are frequently different from the parent natural sources due to the industry or artisan transformation. In particular, antioxidant property of chocolate and cocoa are not adequately taken into consideration by consumers who normally make use of this food just for its flavor and taste properties. In this study, we have investigated the antioxidant capacity and total phenolic content of cocoa nibs, cocoa masses, and corresponding chocolate bars with different percentages of cocoa from different origins. The antioxidant capacity of the different samples was measured by two different assays [1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and ferric reducing antioxidant of potency (FRAP) tests]. The Folin–Ciocalteu reagent was used to assess the total phenolic content. The masses showed a higher antioxidant power than the nibs, and this has been attributed to the fact that in the nibs is still present the lipid part, which will form the cocoa butter. The influence of milk, whey, and soy proteins was also investigated. Our results showed that the extra dark cocoa bar, 100% cocoa chocolate, is the best in terms of total polyphenol content and in terms of antioxidant capacity according to the DPPH and FRAP tests. In addition, the bars of organic dark chocolate 80%, dark Tanzania 80%, and Trinidad 80% products are well performing in all respects. As highlighted by us, the antiradical properties of cocoa products are higher than many antioxidant supplements in tablets.

positive: Dark chocolate improves coronary vasomotion and reduces platelet reactivity. BACKGROUND: Dark chocolate has potent antioxidant properties. Coronary atherosclerosis is promoted by impaired endothelial function and increased platelet activation. Traditional risk factors, high oxidative stress, and reduced antioxidant defenses play a crucial role in the pathogenesis of atherosclerosis, particularly in transplanted hearts. Thus, flavonoid-rich dark chocolate holds the potential to have a beneficial impact on graft atherosclerosis. METHODS AND RESULTS: We assessed the effect of flavonoid-rich dark chocolate compared with cocoa-free control chocolate on coronary vascular and platelet function in 22 heart transplant recipients in a double-blind, randomized study. Coronary vasomotion was assessed with quantitative coronary angiography and cold pressor testing before and 2 hours after ingestion of 40 g of dark (70% cocoa) chocolate or control chocolate, respectively. Two hours after ingestion of flavonoid-rich dark chocolate, coronary artery diameter was increased significantly (from 2.36+/-0.51 to 2.51+/-0.59 mm, P<0.01), whereas it remained unchanged after control chocolate. Endothelium-dependent coronary vasomotion improved significantly after dark chocolate (4.5+/-11.4% versus -4.3+/-11.7% in the placebo group, P=0.01). Platelet adhesion decreased from 4.9+/-1.1% to 3.8+/-0.8% (P=0.04) in the dark chocolate group but remained unchanged in the control group. CONCLUSIONS: Dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion 2 hours after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration.

positive: Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers. BACKGROUND: Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). METHODS: Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. RESULTS: The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. CONCLUSION: This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

positive: Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits; however, the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function (EF) have yet to be established. METHODS: 44 adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover trial. Participants were randomly assigned to a treatment sequence: sugar-free cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free placebo. Treatments were administered daily for 6 weeks, with a 4-week washout period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001 and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater, but not significantly. Other biomarkers of cardiac risk did not change appreciably from baseline. BMI remained stable throughout the study. CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk, and does not cause weight gain. Sugar-free preparations may further augment endothelial function. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

positive: Chocolate--guilty pleasure or healthy supplement? Dark chocolate and other cocoa products are popular in the population as a whole, but their overall health benefit remains controversial. Observations from the Kuna Indian population have shown an impressive cardiovascular health benefit from cocoa. For various reasons, this benefit has not been as robust as in other populations. Additionally, several mechanisms have been proposed that might confer cocoa's possible health benefit, but no consensus has been reached on cocoa's physiologic role in promoting cardiovascular health. Flavanols, as well as theobromine, may contribute to enhancements in endothelial function and subsequent improvements in various contributors to cardiovascular disease (CVD) including hypertension, platelet aggregation and adhesion, insulin resistance, and hypercholesterolemia. While the benefits of cocoa may be altered at the various stages of growth, development, and production, it appears that for many people "healthy" dark chocolate may, indeed, provide a pleasurable role in CVD risk reduction. The objectives of this review are to discuss the associations of cocoa with decreased blood pressure and improved CVD risk, to describe the possible mechanisms for these potential benefits, and to highlight considerations for the use of cocoa as a dietary supplement.

positive: Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. BACKGROUND: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). OBJECTIVE: The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. DESIGN: We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. RESULTS: We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. CONCLUSIONS: We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.

positive: The role of cyclooxygenase in gastric mucosal protection. COX-1 and COX-2 are two cyclooxygenase enzymes responsible for prostanoid production. COX-2 is expressed in inflammatory cells and fibroblasts of the gastric mucosa, and through the production of various growth factors including hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), plays a key role in the tissue repair process. Aspirin induces and acetylates COX-2 to produce 15-(R)-epi-lipoxinA4, an anti-inflammatory mediator thought to protect the gastric mucosa against aspirin-induced injury. Recently, three different PGE synthases have been identified, that convert COX-2 metabolites into PGE2. mPGE synthase (mPGES)-1 has been shown to be inducible, and to colocalize with COX-2 in fibroblasts and macrophages infiltrating the gastric ulcer bed. cPGES and mPGES-2 have been found expressed in normal gastric mucosa, with no change in expression levels seen in gastritis or gastric ulcer tissue. Finally, this review discusses the role of these enzymes in the pathophysiology of the gastric mucosa, as well as the biologcal significance of their inhibition.

positive: Cyclooxygenase inhibitory and antioxidant cyanidin glycosides in cherries and berries. Anthocyanins from tart cherries, Prunus cerasus L. (Rosaceae) cv. Balaton and Montmorency; sweet cherries, Prunus avium L. (Rosaceae); bilberries, Vaccinum myrtillus L. (Ericaceae); blackberries, Rubus sp. (Rosaceae); blueberries var. Jersey, Vaccinium corymbosum L. (Ericaceae); cranberries var. Early Black, Vaccinium macrocarpon Ait. (Ericaceae); elderberries, Sambucus canadensis (Caprifoliaceae); raspberries, Rubus idaeus (Rosaceae); and strawberries var. Honeoye, Fragaria x ananassa Duch. (Rosaceae), were investigated for cyclooxygenase inhibitory and antioxidant activities. The presence and levels of cyanidin-3-glucosylrutinoside 1 and cyanidin-3-rutinoside 2 were determined in the fruits using HPLC. The antioxidant activity of anthocyanins from cherries was comparable to the commercial antioxidants, tert-butylhydroquinone, butylated hydroxytoluene and butylated hydroxyanisole, and superior to vitamin E, at a test concentration of 125 microg/ml. Anthocyanins from raspberries and sweet cherries demonstrated 45% and 47% cyclooxygenase-I and cyclooxygenase-II inhibitory activities, respectively, when assayed at 125 microg/ml. The cyclooxygenase inhibitory activities of anthocyanins from these fruits were comparable to those of ibuprofen and naproxen at 10 microM concentrations. Anthocyanins 1 and 2 are present in both cherries and raspberry. The yields of pure anthocyanins 1 and 2 in 100 g Balaton and Montmorency tart cherries, sweet cherries and raspberries were 21, 16.5; 11, 5; 4.95, 21; and 4.65, 13.5 mg, respectively. Fresh blackberries and strawberries contained only anthocyanin 2 in yields of 24 and 22.5 mg/100 g, respectively. Anthocyanins 1 and 2 were not found in bilberries, blueberries, cranberries or elderberries.

positive: Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. Nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs in many countries. Use of the majority of NSAIDs increases with age, primarily for symptoms associated with osteoarthritis and other chronic musculoskeletal conditions. Population-based studies have shown that, on any given day, 10-20% of elderly people (> or = 65 years old) have a current or recent NSAID prescription. Over a 6-month period in Alberta, Canada, 27% of elderly people were prescribed NSAIDs. Furthermore, in Tennessee (USA), 40% of elderly people received at least one NSAID prescription annually, and 6% had NSAID prescriptions for > 75% of the year. NSAIDs cause a wide variety of side-effects. The most clinically important side-effects are upper gastrointestinal tract dyspepsia, peptic ulceration, hemorrhage, and perforation, leading to death in some patients. Gastrointestinal side-effects are common; the most common NSAID-associated side-effect is epigastric pain/indigestion. Gastrointestinal side-effects are also a frequent reason both for withdrawal of NSAIDs and for co-treatment with another drug. Indeed, in two population-based studies of people aged > or = 65 years, the use of agents to prevent peptic ulcers or relieve dyspepsia was nearly twice as common in regular NSAID users (20-26%) than in non-NSAID users (11%). In Alberta, Canada, it has been estimated that NSAID use accounts for 28% of all prescriptions for anti-ulcer drugs in people aged at least 65 years. Many studies have now shown that NSAIDs increase the risk of peptic ulcer complications by 3-5-fold, and in several different populations it has been estimated that 15-35% of all peptic ulcer complications are due to NSAIDs. In the United States alone, there are an estimated 41,000 hospitalizations and 3,300 deaths each year among the elderly that are associated with NSAIDs. Factors that increase the risk of serious peptic ulcer disease include older age, history of peptic ulcer disease, gastrointestinal hemorrhage, dyspepsia, and/or previous NSAID intolerance, as well as several measures of poor health.

positive: Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use Background Some people who suffer an upper gastrointestinal bleed or perforation die. The mortality rate was estimated at 12% in studies published before 1997, but a systematic survey of more recent data is needed. Better treatment is likely to have reduced mortality. An estimate of mortality is helpful in explaining to patients the risks of therapy, especially with NSAIDs. Methods A systematic review of studies published before 1997, and between 1997 and 2008. Any study architecture was acceptable if it reported on cases who died from any cause of upper gastrointestinal bleed or perforation. Analyses were conducted separately for all cases, and those prescribed NSAID or aspirin. Results Information was available for 61,067 cases (81% published since 1997) of whom 5,001 died. The mortality rate in all cases fell significantly, from 11.6% (95% confidence interval, 11.0 to 12.2) in pre-1997 studies to 7.4% (7.2 to 7.6) in those published since 1997. In 5,526 patients taking NSAID or aspirin, mortality increased, from 14.7% (13.6 to 15.8) before 1997 to 20.9% (18.8 to 22.9) since 1997. Conclusion Upper gastrointestinal bleed or perforation still carries a finite risk of death. Differences in study architecture, population characteristics, risk factors, definition of mortality, and reporting of outcomes impose limitations on interpreting effect size. Data published since 1997 suggest that mortality in patients suffering from an upper gastrointestinal bleed or perforation has fallen to 1 in 13 overall, but remains higher at about 1 in 5 in those exposed to NSAID or aspirin.

positive: Consumption of Bing sweet cherries lowers circulating concentrations of inflammation markers in healthy men and women. The purpose of this study was to determine the effects of consuming sweet cherries on plasma lipids and markers of inflammation in healthy humans. Healthy men and women (n = 18) supplemented their diets with Bing sweet cherries (280 g/d) for 28 d. After a 12-h fast, blood samples were taken before the start of cherry consumption (study d 0 and 7), 14 and 28 d after the start of cherry supplementation (study d 21 and 35), and 28 d after the discontinuation (study d 64) of cherry consumption. After cherries were consumed for 28 d, circulating concentrations of C-reactive protein (CRP), regulated upon activation, normal T-cell expressed, and secreted (RANTES), and NO decreased by 25 (P < 0.05), 21 (P < 0.05), and 18% (P = 0.07) respectively. After the discontinuation of cherry consumption for 28 d (d 64), concentrations of RANTES continued to decrease (P = 0.001), whereas those of CRP and NO did not differ from either d 7 (pre-cherries) or d 35 (post-cherries). Plasma concentrations of IL-6 and its soluble receptor, intercellular adhesion molecule-1, and tissue inhibitor of metalloproteinases-2 did not change during the study. Cherry consumption did not affect the plasma concentrations of total-, HDL-, LDL-, and VLDL- cholesterol, triglycerides, subfractions of HDL, LDL, VLDL, and their particle sizes and numbers. It also did not affect fasting blood glucose or insulin concentrations or a number of other chemical and hematological variables. Results of the present study suggest a selective modulatory effect of sweet cherries on CRP, NO, and RANTES. Such anti-inflammatory effects may be beneficial for the management and prevention of inflammatory diseases.

positive: COX-2 inhibitors: a story of greed, deception and death. In 1999, drug manufacturers introduced a class of NSAIDs called COX-2 inhibitors or coxibs. The drugs were avidly promoted directly to the consumers and became bestsellers from the start. Arthritis sufferers were eager to take medications that eased joint pain with less risk of causing gastrointestinal pain, bleeding and other side-effects. In the year after their introduction, doctors wrote over 100 million prescriptions for celecoxib (Celebrex) and rofecoxib (Vioxx). Celebrex is the sixth best-selling drug, with sales of more than US$ 4 billion since its debut in 1999. Vioxx had sales of US$ 2.6 billion in 2001. However, the coxibs increase the risk of heart attacks and strokes, and their price, in the USA, is obscene. The manufacturers faced a possibly complicit, toothless and bloodless FDA, and used every maneuvering to fleece the patients. We must now reflect on attitudes that we thought only belong to the tobacco industry. Fortunately, safe and active alternatives exist.

positive: Processed tart cherry products--comparative phytochemical content, in vitro antioxidant capacity and in vitro anti-inflammatory activity. Processing of fruits and vegetables affects their phytochemical and nutrient content. Tart cherries are commercially promoted to possess antioxidant and anti-inflammatory activity. However, processing affects their phytochemical content and may affect their related health benefits. The current study compares the in vitro antioxidant capacity and anti-inflammatory cyclooxygenase activity of processed tart cherry (Prunus cerasus) products-cherry juice concentrate, individually quick-frozen cherries, canned cherries, and dried cherries. Cherry products were analyzed for total anthocyanin and proanthocyanidin content and profile. On a per serving basis, total anthocyanins were highest in frozen cherries and total proanthocyanidins were highest in juice concentrate. Total phenolics were highest in juice concentrate. Juice concentrate had the highest oxygen radical absorbance capacity (ORAC) and peroxynitrite radical averting capacity (NORAC). Dried cherries had the highest hydroxyl radical averting capacity (HORAC) and superoxide radical averting capacity (SORAC). Processed tart cherry products compared very favorably to the U.S. Dept. of Agriculture-reported ORAC of other fresh and processed fruits. Inhibition of in vitro inflammatory COX-1 activity was greatest in juice concentrate. In summary, all processed tart cherry products possessed antioxidant and anti-inflammatory activity, but processing differentially affected phytochemical content and in vitro bioactivity. On a per serving basis, juice concentrate was superior to other tart cherry products. © 2012 Institute of Food Technologists®

positive: Role of cyclooxygenase isoforms in gastric mucosal defence. A complex system of interacting mediators exists in the gastric mucosa to strengthen its resistance against injury. In this system prostaglandins play an important role. Prostaglandin biosynthesis is catalysed by the enzyme cyclooxygenase (COX), which exists in two isoforms, COX-1 and COX-2. Initially the concept was developed that COX-1 functions as housekeeping enzyme, whereas COX-2 yields prostaglandins involved in pathophysiological reactions such as inflammation. In the gastrointestinal tract, the maintenance of mucosal integrity was attributed exclusively to COX-1 without a contribution of COX-2 and ulcerogenic effects of non-steroidal anti-inflammatory drugs (NSAIDs) were believed to be the consequence of inhibition of COX-1. Recent findings, however, indicate that both COX-1 and COX-2 either alone or in concert contribute to gastric mucosal defence. Thus, in normal rat gastric mucosa specific inhibition of COX-1 does not elicit mucosal lesions despite near-maximal suppression of gastric prostaglandin formation. When a selective COX-2 inhibitor which is not ulcerogenic when given alone is added to the COX-1 inhibitor, severe gastric damage develops. In contrast to normal gastric mucosa which requires simultaneous inhibition of COX-1 and COX-2 for breakdown of mucosal resistance, in the acid-challenged rat stomach inhibition of COX-1 alone results in dose-dependent injury which is further increased by additional inhibition of COX-2 enzyme activity or prevention of acid-induced up-regulation of COX-2 expression by dexamethasone. COX-2 inhibitors do not damage the normal or acid-challenged gastric mucosa when given alone. However, when nitric oxide formation is suppressed or afferent nerves are defunctionalized, specific inhibition of COX-2 induces severe gastric damage. Ischemia-reperfusion of the gastric artery is associated with up-regulation of COX-2 but not COX-1 mRNA. COX-2 inhibitors or dexamethasone augment ischemia-reperfusion-induced gastric damage up to four-fold, an effect abolished by concurrent administration of 16,16-dimethyl-PGE(2). Selective inhibition of COX-1 is less effective. Furthermore, COX-2 inhibitors antagonize the protective effect of a mild irritant or intragastric peptone perfusion in the rat stomach, whereas the protection induced by chronic administration of endotoxin is mediated by COX-1. Finally, an important function of COX-2 is the acceleration of ulcer healing. COX-2 is up-regulated in chronic gastric ulcers and inhibitors of COX-2 impair the healing of ulcers to the same extent as non-selective NSAIDs. Taken together, these observations show that both COX isoenzymes are essential factors in mucosal defence with specific contributions in various physiological and pathophysiological situations.

positive: Melatonin in traditional Mediterranean diets. Compared with other industrialized countries, the lower incidence of chronic-degenerative disorders in Mediterranean populations has been emphasized in recent decades. The health-promoting effects arising from Mediterranean dietary habits have been attributed to the large intake of plant foodstuffs rich in bioactive phytochemicals, such as melatonin. Recently, it has been suggested that melatonin present in edible plants may improve human health, by virtue of its biological activities and its good bioavailability. Plant melatonin, besides contributing to optimize the physiological functions regulated, in humans, by endogenous melatonin, may be involved in nutritional therapy to reduce the risk of cancer, cardiovascular and neurodegenerative diseases in western populations. In this view, the presence of melatonin in some Mediterranean foods and beverages adds a new element to the hypothesis of health benefits associated to Mediterranean dietary patterns, although the available data are still preliminary and incomplete.

positive: Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. BACKGROUND: Tart Montmorency cherries have been reported to contain high levels of phytochemicals including melatonin, a molecule critical in regulating the sleep-wake cycle in humans. PURPOSE: The aim of our investigation was to ascertain whether ingestion of a tart cherry juice concentrate would increase the urinary melatonin levels in healthy adults and improve sleep quality. METHODS: In a randomised, double-blind, placebo-controlled, crossover design, 20 volunteers consumed either a placebo or tart cherry juice concentrate for 7 days. Measures of sleep quality recorded by actigraphy and subjective sleep questionnaires were completed. Sequential urine samples over 48 h were collected and urinary 6-sulfatoxymelatonin (major metabolite of melatonin) determined; cosinor analysis was used to determine melatonin circadian rhythm (mesor, acrophase and amplitude). In addition, total urinary melatonin content was determined over the sampled period. Trial differences were determined using a repeated measures ANOVA. RESULTS: Total melatonin content was significantly elevated (P < 0.05) in the cherry juice group, whilst no differences were shown between baseline and placebo trials. There were significant increases in time in bed, total sleep time and sleep efficiency total (P < 0.05) with cherry juice supplementation. Although there was no difference in timing of the melatonin circardian rhythm, there was a trend to a higher mesor and amplitude. CONCLUSIONS: These data suggest that consumption of a tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and quality in healthy men and women and might be of benefit in managing disturbed sleep.

positive: No influence of melatonin on cerebral blood flow in humans. Melatonin has been attributed a role in a number of physiological processes. Changes in distal skin temperature and blood pressure after intake of melatonin suggest that melatonin induces peripheral vasodilation. The effect on the cerebral blood flow is still unknown. We examined the effect of a single pulse of melatonin on cerebral and peripheral blood flow, using the latter as a positive control. Ten male healthy volunteers (mean age, 22 +/- 3.2 yr) participated in a double-blind, randomized, placebo-controlled, cross-over study. On one occasion 10 microg melatonin were infused i.v., and on the other occasion saline was infused as the matching placebo. Cerebral blood flow was measured using phase contrast magnetic resonance imaging. Peripheral blood flow was determined from changes in the distal to proximal skin temperature gradient and finger pulse volume. Serum melatonin concentration increased from 12 +/- 5 pg/ml at baseline to 487 +/- 377 pg/ml at 5 min and 156 +/- 68 pg/ml at 10 min after melatonin administration. There was no significantly different time course for cerebral blood flow and cerebrovascular resistance. Compared with placebo, melatonin significantly increased peripheral blood flow, as measured by distal to proximal skin temperature gradient and finger pulse volume. These data demonstrate that melatonin does not have an acute regulatory effect on cerebral blood flow in humans.

positive: Sweet and sour cherry phenolics and their protective effects on neuronal cells. The identification of phenolics from various cultivars of fresh sweet and sour cherries and their protective effects on neuronal cells were comparatively evaluated in this study. Phenolics in cherries of four sweet and four sour cultivars were extracted and analyzed for total phenolics, total anthocyanins, and their antineurodegenerative activities. Total phenolics in sweet and sour cherries per 100 g ranged from 92.1 to 146.8 and from 146.1 to 312.4 mg gallic acid equivalents, respectively. Total anthocyanins of sweet and sour cherries ranged from 30.2 to 76.6 and from 49.1 to 109.2 mg cyanidin 3-glucoside equivalents, respectively. High-performance liquid chromatography (HPLC) analysis revealed that anthocyanins such as cyanidin and peonidin derivatives were prevalent phenolics. Hydroxycinnamic acids consisted of neochlorogenic acid, chlorogenic acid, and p-coumaric acid derivatives. Glycosides of quercetin, kaempferol, and isorhamnetin were also found. Generally, sour cherries had higher concentrations of total phenolics than sweet cherries, due to a higher concentration of anthocyanins and hydroxycinnamic acids. A positive linear correlation (r2 = 0.985) was revealed between the total anthocyanins measured by summation of individual peaks from HPLC analysis and the total anthocyanins measured by the pH differential method, indicating that there was in a close agreement with two quantifying methods for measuring anthocyanin contents. Cherry phenolics protected neuronal cells (PC 12) from cell-damaging oxidative stress in a dose-dependent manner mainly due to anthocyanins. Overall results showed that cherries are rich in phenolics, especially in anthocyanins, with a strong antineurodegenerative activity and that they can serve as a good source of biofunctional phytochemicals in our diet.

positive: Non-vertebrate melatonin. Melatonin has been detected in bacteria, eukaryotic unicells, macroalgae, plants, fungi and various taxa of invertebrates. Although precise determinations are missing in many of these organisms and the roles of melatonin are still unknown, investigations in some species allow more detailed conclusions. Non-vertebrate melatonin is not necessarily circadian, and if so, not always peaking at night, although nocturnal maxima are frequently found. In the cases under study, the major biosynthetic pathway is identical with that of vertebrates. Mimicking of photoperiodic responses and concentration changes upon temperature decreases have been studied in more detail only in dinoflagellates. In plants, an involvement in photoperiodism seems conceivable but requires further support. No stimulation of flowering has been demonstrated to date. A participation in antioxidative protection might be possible in many aerobic non-vertebrates, although evidence for a contribution at physiological levels is mostly missing. Protection from stress by oxidotoxins or/and extensions of lifespan have been shown in very different organisms, such as the dinoflagellate Lingulodinium, the ciliate Paramecium, the rotifer Philodina and Drosophila. Melatonin can be taken up from the food, findings with possible implications in ecophysiology as well as for human nutrition and, with regard to high levels in medicinal plants, also in pharmacology.

positive: Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration. Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6-sulfatoxymelatonin concentrations in morning urine. Ninety-four healthy women aged 24-55 were recruited through a city public health center in Japan. The women randomly allocated to the intervention group were requested to consume high amounts of six selected vegetables, with a target of 350 g/day for 65 days, while those in the control group were asked to avoid the same six vegetables during the same period. First-void morning urine was collected before and at the end of the intervention period, and creatinine-adjusted 6-sulfatoxymelatonin concentrations were measured. At the end of the intervention period, daily mean intake of melatonin from the six vegetables was 1288.0 ng in the intervention group and 5.3 ng in the control group. In the intervention group, the mean concentration of 6-sulfatoxymelatonin changed from 48.1 [95% confidence interval (CI): 40.4-57.2] ng/mg creatinine to 49.6 (95% CI: 42.8-57.3) ng/mg creatinine across the intervention period. In the control group, the mean concentration of 6-sulfatoxymelatonin changed from 55.5 (95% CI: 48.7-63.2) ng/mg creatinine to 50.8 (95% CI: 44.0-58.7) ng/mg creatinine across the intervention period. A comparison of the two groups with regard to the changes in the 6-sulfatoxymelatonin concentrations across the intervention period showed a significant difference (P = 0.03). The results indicate that increased consumption of vegetables raises circulatory melatonin concentrations.

positive: Diet promotes sleep duration and quality. Sleep, much like eating, is an essential part of life. The mechanisms of sleep are only partially clear and are the subject of intense research. There is increasing evidence showing that sleep has an influence on dietary choices. Both cross-sectional and epidemiologic studies have demonstrated that those who sleep less are more likely to consume energy-rich foods (such as fats or refined carbohydrates), to consume fewer portions of vegetables, and to have more irregular meal patterns. In this narrative review, we pose the opposite question: can ingested food affect sleep? The purpose of this review is to discuss the evidence linking diet and sleep and to determine whether what we eat and what kind of nutrients we obtain from the food consumed before bedtime matter. In addition, scientific evidence behind traditional sleep-promoting foods such as milk and some herbal products is briefly described. These are reviewed using data from clinical trials, mostly in healthy subjects. In addition, we discuss the possible mechanisms behind these observations. Lastly, we summarize our findings that emerging evidence confirms a link between diet and sleep. Overall, foods impacting the availability of tryptophan, as well as the synthesis of serotonin and melatonin, may be the most helpful in promoting sleep. Although there are clear physiological connections behind these effects, the clinical relevance needs to be studied further. Copyright © 2012 Elsevier Inc. All rights reserved.

positive: Normative data on the daily profile of urinary 6-sulfatoxymelatonin in healthy subjects between the ages of 20 and 84. Although the hormone melatonin is a key factor for the proper functioning of the circadian timing system (CTS) and exogenous melatonin has been shown to be beneficial in cases of CTS disturbances, a deficit of melatonin has yet to be defined as a disorder. The aim of our study was to collect a normative data set on 24-h melatonin excretion in healthy human adults living in a natural environment. Urine samples were collected from 75 healthy subjects (45 women/30 men; mean age 47.2, SD 19.5, range 20-84) after five consecutive periods: 2300-0700, 0700-1100, 1100-1800, 1800-2300 and 2300-0700 h. 6-Sulfatoxymelatonin (aMT6s) concentrations were analyzed in duplicate by IBL (Hamburg) using a highly sensitive, competitive ELISA kit. Twenty-four hour-aMT6s total amount (rho=-0.68, p<0.001), aMT6s nighttime excretion (rho=-0.69, p<0.001), aMT6s morning excretion (rho=-0.66, p<0.001) and evening excretion (r=-0.26, p=0.023) were negatively associated with age, whereas daytime excretion (r=-0.17, p=0.15) was not. The intra-subject night-day ratio varied up to 10.5 (mean 6.0) in young subjects (aged 20-35) and up to 5.4 (mean 2.8) in older individuals (age>65). The total amount of 24 h-aMT6s (range 7.5-58 microg) as well as the amount of aMT6s excreted during the nighttime period (range 327-6.074 ng/h) varied as much as 20-fold between individuals. Our data show an age-related decline in melatonin excretion in healthy subjects living in a natural environment. The high inter-individual variability of excretion rates may explain why a normative data set is of no use in replacement strategies.

positive: Jerte Valley cherry-enriched diets improve nocturnal rest and increase 6-sulfatoxymelatonin and total antioxidant capacity in the urine of middle-a... Tryptophan, serotonin, and melatonin, present in Jerte Valley cherries, participate in sleep regulation and exhibit antioxidant properties. The effect of the intake of seven different Jerte Valley cherry cultivars on the sleep-wake cycle, 6-sulfatoxymelatonin levels, and urinary total antioxidant capacity in middle-aged and elderly participants was evaluated. Volunteers were subjected to actigraphic monitoring to record and display the temporal patterns of their nocturnal activity and rest. 6-sulfatoxymelatonin and total antioxidant capacity were quantified by enzyme-linked immunosorbent assay and colorimetric assay kits, respectively. The intake of each of the cherry cultivars produced beneficial effects on actual sleep time, total nocturnal activity, assumed sleep, and immobility. Also, there were significant increases in 6-sulfatoxymelatonin levels and total antioxidant capacity in urine after the intake of each cultivar. These findings suggested that the intake of Jerte Valley cherries exerted positive effect on sleep and may be seen as a potential nutraceutical tool to counteract oxidation.

positive: Melatonin for the prevention and treatment of jet lag. BACKGROUND: : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.

positive: Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus). The antioxidant melatonin was recently identified in a variety of edible plants and seeds in high concentrations. In plants, as in animals, melatonin is believed to function as a free radical scavenger and possibly in photoperiodism. In this study, melatonin was detected and quantified in fresh-frozen Balaton and Montmorency tart cherries (Prunus cerasus) using high-performance liquid chromatography. Both cherry species contain high levels of melatonin compared to the melatonin concentrations in the blood of mammals. Montmorency cherries (13.46 +/- 1.10 ng/g) contain approximately 6 times more melatonin than do Balaton cherries (2.06 +/- 0.17 ng/g). Neither the orchard of origin nor the time of harvest influenced the amount of melatonin in fresh cherries. The implication of the current findings is that consuming cherries could be an important source of dietary melatonin inasmuch as melatonin is readily absorbed when taken orally. Also, previously published data and the results presented here show that melatonin is not only endogenously produced but also present in the diet.

positive: Effect of kiwifruit consumption on sleep quality in adults with sleep problems. Numerous studies have revealed that kiwifruit contains many medicinally useful compounds, among which antioxidants and serotonin may be beneficial in the treatment of the sleep disorders. The aim of this study was to evaluate the effects of kiwifruit on sleep patterns, including sleep onset, duration, and quality. In this study, we applied a free-living, self-controlled diet design. Twenty-four subjects (2 males, 22 females) 20 to 55 years of age consumed 2 kiwifruits 1 hour before bedtime nightly for 4 weeks. The Chinese version of the Pittsburgh Sleep Quality Index (CPSQI), a 3-day sleep diary, and the Actigraph sleep/activity logger watch were used to assess the subjective and objective parameters of sleep quality, including time to bed, time of sleep onset, waking time after sleep onset, time of getting up, total sleep time, and self-reported sleep quality and sleep onset latency, waking time after sleep onset, total sleep time, and sleep efficiency before and after the intervention. After 4 weeks of kiwifruit consumption, the subjective CPSQI score, waking time after sleep onset, and sleep onset latency were significantly decreased (42.4%, 28.9%, and 35.4%, respectively). Total sleep time and sleep efficiency were significantly increased (13.4% and 5.41%, respectively). Kiwifruit consumption may improve sleep onset, duration, and efficiency in adults with self-reported sleep disturbances. Further investigation of the sleep-promoting properties of kiwifruit may be warranted.

positive: Simultaneous analysis of serotonin, melatonin, piceid and resveratrol in fruits using liquid chromatography tandem mass spectrometry. An analytical method was developed for the simultaneous quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol using reversed-phase high performance liquid chromatography coupled to mass spectrometry (HPLC-MS) with electrospray ionization (ESI) in both positive and negative ionization modes. HPLC optimal analytical separation was achieved using a mixture of acetonitrile and water with 0.1% formic acid as the mobile phase in linear gradient elution. The mass spectrometry parameters were optimized for reliable quantification and the enhanced selectivity and sensitivity selected reaction monitoring mode (SRM) was applied. For extraction, the direct analysis of initial methanol extracts was compared with further ethyl acetate extraction. In order to demonstrate the applicability of this analytical method, serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol from 24 kinds of commonly consumed fruits were quantified. The highest serotonin content was found in plantain, while orange bell peppers had the highest melatonin content. Grape samples possessed higher trans- and cis-piceid, and trans- and cis-resveratrol contents than the other fruits. The results indicate that the combination of HPLC-MS detection and simple sample preparation allows the rapid and accurate quantification of serotonin, melatonin, trans- and cis-piceid, and trans- and cis-resveratrol in fruits. Copyright © 2011 Elsevier B.V. All rights reserved.

positive: Antioxidant and antiinflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries. The anthocyanins (1-3) and cyanidin isolated from tart cherries exhibited in vitro antioxidant and antiinflammatory activities comparable to commercial products. The inhibition of lipid peroxidation of anthocyanins 1-3 and their aglycon, cyanidin, were 39, 70, 75, and 57%, respectively, at 2-mM concentrations. The antioxidant activities of 1-3 and cyanidin were comparable to the antioxidant activities of tert-butylhydroquinone and butylated hydroxytoluene and superior to vitamin E at 2-mM concentrations. In the antiinflammatory assay, cyanidin gave IC50 values of 90 and 60 mM, respectively, for prostaglandin H endoperoxide synthase-1 and prostaglandin H endoperoxide synthase-2 enzymes.

positive: Application of LC and LC-MS to the analysis of melatonin and serotonin in edible plants. Melatonin is a neurohormone produced by the pineal gland of animals. Serotonin is a monoamine neurotransmitter and one of the precursors of melatonin biosynthesis. These two indoleamines have recently been reported to have widespread occurrence in many edible plants. Consuming foodstuffs containing melatonin and serotonin could raise their physiologic concentrations in blood and enhance human health. Literature concerning analytical methods suitable for determination of melatonin and serotonin in edible plants is limited, although several liquid chromatographic (LC) techniques have been used for their quantification. Liquid chromatography-mass spectrometry (LC-MS) methods combine selectivity, sensitivity, and high precision, and enable the simultaneous determination of melatonin and serotonin. This work reviews LC and LC-MS techniques used to determine melatonin and serotonin, and the available data on melatonin and serotonin levels in edible plants. © 2011 Crown Copyright

positive: Effects of a Tart Cherry Juice Beverage on the Sleep of Older Adults with Insomnia: A Pilot Study This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible. The results of this pilot study suggest that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia with effect sizes equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the two most studied natural products for insomnia. These effects, however, were considerably less than those for evidence-based treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.

positive: Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage Background Numerous antioxidant and anti‐inflammatory agents have been identified in tart cherries. Objective To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage. Methods This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 × 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect. Results Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p  =  0.017). Relaxed elbow angle (time by treatment p  =  0.85) and muscle tenderness (time by treatment p  =  0.81) were not different between trials. Conclusions These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.

positive: Date fruits (Phoenix dactylifera Linn): an emerging medicinal food. Date palm is one of the oldest trees cultivated by man. In the folk-lore, date fruits have been ascribed to have many medicinal properties when consumed either alone or in combination with other herbs. Although, fruit of the date palm served as the staple food for millions of people around the world for several centuries, studies on the health benefits are inadequate and hardly recognized as a healthy food by the health professionals and the public. In recent years, an explosion of interest in the numerous health benefits of dates had led to many in vitro and animal studies as well as the identification and quantification of various classes of phytochemicals. On the basis of available documentation in the literature on the nutritional and phytochemical composition, it is apparent that the date fruits are highly nutritious and may have several potential health benefits. Although dates are sugar-packed, many date varieties are low GI diet and refutes the dogma that dates are similar to candies and regular consumption would develop chronic diseases. More investigations in these areas would validate its beneficial effects, mechanisms of actions, and fully appreciate as a potential medicinal food for humans all around the world. Therefore, in this review we summarize the phytochemical composition, nutritional significance, and potential health benefits of date fruit consumption and discuss its great potential as a medicinal food for a number of diseases inflicting human beings.

positive: Glycemic indices of five varieties of dates in healthy and diabetic subjects Background This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus. Methods Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. The glycemic indices were determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Statistical analyses were performed using the Mann-Whitney U test and repeated measures analysis of variance. Results Mean glycemic indices ± SEM of the dates for the healthy individuals were 54.0 ± 6.1, 53.5 ± 8.6, 46.3 ± 7.1, 49.1 ± 3.6 and 55.1 ± 7.7 for Fara'd, Lulu, Bo ma'an, Dabbas and Khalas, respectively. Corresponding values for those with type 2 diabetes were very similar (46.1 ± 6.2, 43.8 ± 7.7, 51.8 ± 6.9, 50.2 ± 3.9 and 53.0 ± 6.0). There were no statistically significant differences in the GIs between the control and the diabetic groups for the five types of dates, nor were there statistically significant differences among the dates' GIs (df = 4, F = 0.365, p = 0.83). Conclusion The results show low glycemic indices for the five types of dates included in the study and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. These findings point to the potential benefits of dates for diabetic subjects when used in a healthy balanced diet. Trial Registration Number ClinicalTrials.gov NCT01307904

positive: Daily apple versus dried plum: impact on cardiovascular disease risk factors in postmenopausal women. BACKGROUND: Evidence suggests that consumption of apple or its bioactive components modulate lipid metabolism and reduce the production of proinflammatory molecules. However, there is a paucity of such research in human beings. OBJECTIVE: Women experience a lower rate of cardiovascular disease before menopause compared with men. However, after the onset of menopause, the risk of cardiovascular disease increases drastically due to ovarian hormone deficiency. Hence, we conducted a 1-year clinical trial to evaluate the effect of dried apple vs dried plum consumption in reducing cardiovascular disease risk factors in postmenopausal women. DESIGN: One-hundred sixty qualified postmenopausal women were recruited from the greater Tallahassee, FL, area during 2007-2009 and were randomly assigned to one of two groups: dried apple (75 g/day) or dried plum (comparative control). Fasting blood samples were collected at baseline, 3, 6, and 12 months to measure various parameters. Physical activity recall and 7-day dietary recall were also obtained. RESULTS: Neither of the dried fruit regimens significantly affected the participants' reported total energy intake throughout the study period. On the contrary, women who consumed dried apple lost 1.5 kg body weight by the end of the study, albeit not significantly different from the dried plum group. In terms of cholesterol, serum total cholesterol levels were significantly lower in the dried apple group compared with the dried plum group only at 6 months. Although dried plum consumption did not significantly reduce serum total cholesterol and low-density lipoprotein cholesterol levels, it lowered their levels numerically by 3.5% and 8%, respectively, at 12 months compared with baseline. This may explain the lack of significance observed between the groups. However, within the group, women who consumed dried apple had significantly lower serum levels of total cholesterol and low-density lipoprotein cholesterol by 9% and 16%, respectively, at 3 months compared with baseline. These serum values were further decreased to 13% and 24%, respectively, after 6 months but stayed constant thereafter. The within-group analysis also reported that daily apple consumption profoundly improved atherogenic risk ratios, whereas there were no significant changes in lipid profile or atherogenic risk ratios as a result of dried plum consumption. Both dried fruits were able to lower serum levels of lipid hydroperoxide and C-reactive protein. However, serum C-reactive protein levels were significantly lower in the dried plum group compared with the dried apple group at 3 months. CONCLUSIONS: There were no significant differences between the dried apple and dried plum groups in altering serum levels of atherogenic cholesterols except total cholesterol at 6 months. However, when within treatment group comparisons are made, consumption of 75 g dried apple (about two medium-sized apples) can significantly lower atherogenic cholesterol levels as early as 3 months. Furthermore, consumption of dried apple and dried plum are beneficial to human health in terms of anti-inflammatory and antioxidative properties. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

positive: Effects of date ( Phoenix dactylifera L., Medjool or Hallawi Variety) consumption by healthy subjects on serum glucose and lipid levels and on seru... The present pilot study analyzed, for the first time, the in vivo effect of Medjool or Hallawi date consumption by healthy subjects on serum glucose, lipids, and oxidative stress. Total phenolics concentration in the Hallawi versus Medjool dates was greater by 20-31%. The major proportion of the soluble phenolics in both date varieties consisted of phenolic acids, mainly ferulic acid and coumaric acid derivatives, and also chlorogenic and caffeic acid derivatives. Unlike the Medjool dates, Hallawi dates contained a significant proportion of catechins as well. In addition, both varieties contained a quercetin derivative. Both date varieties possess antioxidative properties in vitro, but the ferric ion reducing antioxidant power of Hallawi versus Medjool dates was higher by 24%. Ten healthy subjects consumed, for a period of 4 weeks 100 g/day of either Medjool or Hallawi dates. The date consumption did not significantly affect the subjects' body mass index (BMI), their serum total cholesterol, or their cholesterol levels in the VLDL, LDL, or HDL fractions. Most important, fasting serum glucose and triacylglycerol levels were not increased after consumption of either date variety, and serum triacylglycerol levels even significantly (p < 0.05) decreased, by 8 or 15% after Medjool or Hallawi date consumption, respectively. Basal serum oxidative status was significantly (p < 0.01) decreased by 33%, as compared to the levels observed before consumption, after Hallawi (but not Medjool) date consumption. Similarly, the susceptibility of serum to AAPH-induced lipid peroxidation decreased by 12%, but only after Hallawi date consumption. In agreement with the above results, serum activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) significantly increased, by 8%, after Hallawi date consumption. It is concluded that date consumption (and mainly the Hallawi variety) by healthy subjects, despite their high sugar content, demonstrates beneficial effects on serum triacylglycerol and oxidative stress and does not worsen serum glucose and lipid/lipoprotein patterns, and thus can be considered an antiatherogenic nutrient .

positive: Effect of Consumption of Dried California Mission Figs on Lipid Concentrations Background Figs are a rich source of soluble fiber. We evaluated the effect of consuming dried California Mission figs on serum lipids in hyperlipidemic adults. Methods In a crossover trial men and women aged 30–75 years with elevated low-density lipoprotein cholesterol (100–189 mg/dl) were randomized to add dried California Mission figs (120 g/day) to their usual diet for 5 weeks or eat their usual diet for 5 weeks, then crossed over to the other condition for another 5 weeks. Six 24-hour dietary recalls were obtained. Results Low- and high-density lipoprotein cholesterol and triglyceride concentrations did not differ between usual and figs-added diets (Bonferroni-corrected p > 0.017), while total cholesterol tended to increase with fig consumption (p = 0.02). Total cholesterol increased in participants (n = 41) randomized to usual followed by figs-added diet (p = 0.01), but remained unchanged in subjects (n = 42) who started with figs-added followed by usual diet (p = 0.4). During the figs-added diet, soluble fiber intake was 12.6 ± 3.7 versus 8.2 ± 4.1 g/day in the usual diet (p < 0.0001). Sugar intake increased from 23.4 ± 6.5 to 32.2 ± 6.3% of kcal in the figs-added diet (p < 0.0001). Body weight did not change (p = 0.08). Conclusions Daily consumption of figs did not reduce low-density lipoprotein cholesterol. Triglyceride concentrations were not significantly changed despite an increase in sugar intake.

positive: Potassium intake, stroke, and cardiovascular disease a meta-analysis of prospective studies. OBJECTIVES: The objective of this study was to assess the relation between the level of habitual potassium intake and the incidence of cardiovascular disease (CVD). BACKGROUND: Prospective cohort studies have evaluated the relationship between habitual potassium intake and incidence of vascular disease, but their results have not been not entirely consistent. METHODS: We performed a systematic search for prospective studies published, without language restrictions (1966 to December 2009). Criteria for inclusion were prospective adult population study, assessment of baseline potassium intake, assessment of vascular events as outcome, and follow-up of at least 4 years. For each study, relative risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using a random-effect model, weighted for the inverse of the variance. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. RESULTS: Eleven studies were identified, providing 15 cohort samples that included 247,510 male and female participants (follow-up 5 to 19 years), 7,066 strokes, 3,058 coronary heart disease (CHD) events, and 2,497 total CVD events. Potassium intake was assessed by 24-h dietary recall (n = 2), food frequency questionnaire (n = 6), or 24-h urinary excretion (n = 3). In the pooled analysis, a 1.64-g (42 mmol) per day higher potassium intake was associated with a 21% lower risk of stroke (RR: 0.79; 95% CI: 0.68 to 0.90; p = 0.0007), with a trend toward lower risk of CHD and total CVD that attained statistical significance after the exclusion of a single cohort, based on sensitivity analysis (RR: 0.93; 95% CI: 0.87 to 0.99; p = 0.03 and RR: 0.74; 95% CI: 0.60 to 0.91; p = 0.0037). CONCLUSIONS: Higher dietary potassium intake is associated with lower rates of stroke and might also reduce the risk of CHD and total CVD. These results support recommendations for higher consumption of potassium-rich foods to prevent vascular diseases. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

positive: Nuts and healthy body weight maintenance mechanisms. Nuts are rich sources of multiple nutrients and phytochemicals associated with health benefits, including reduced cardiovascular disease risk. This has prompted recommendations to increase their consumption. However, they are also high in fat and are energy dense. The associations between these properties, positive energy balance and body weight raise questions about such recommendations. Numerous epidemiological and clinical studies show that nuts are not associated with weight gain. Mechanistic studies indicate this is largely attributable to the high satiety and low metabolizable energy (poor bioaccessibility leading to inefficient energy absorption) properties of nuts. Compensatory dietary responses account for 55-75% of the energy provided by nuts. Limited data suggest that routine nut consumption is associated with elevated resting energy expenditure and the thermogenic effect of feeding, resulting in dissipation of another portion of the energy they provide. Additionally, trials contrasting weight loss through regimens that include or exclude nuts indicate improved compliance and greater weight loss when nuts are permitted. Nuts may be included in the diet, in moderation, to enhance palatability, nutrient quality, and chronic disease risk reduction without compromising weight loss or maintenance.

positive: Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health. Over the past 20 years, growing interest in the biochemistry, nutrition, and pharmacology of L-arginine has led to extensive studies to explore its nutritional and therapeutic roles in treating and preventing human metabolic disorders. Emerging evidence shows that dietary L-arginine supplementation reduces adiposity in genetically obese rats, diet-induced obese rats, finishing pigs, and obese human subjects with Type-2 diabetes mellitus. The mechanisms responsible for the beneficial effects of L-arginine are likely complex, but ultimately involve altering the balance of energy intake and expenditure in favor of fat loss or reduced growth of white adipose tissue. Recent studies indicate that L-arginine supplementation stimulates mitochondrial biogenesis and brown adipose tissue development possibly through the enhanced synthesis of cell-signaling molecules (e.g., nitric oxide, carbon monoxide, polyamines, cGMP, and cAMP) as well as the increased expression of genes that promote whole-body oxidation of energy substrates (e.g., glucose and fatty acids) Thus, L-arginine holds great promise as a safe and cost-effective nutrient to reduce adiposity, increase muscle mass, and improve the metabolic profile in animals and humans.

negative: Chocolate, lifestyle, and health. Interest in the biological activities of cocoa polyphenols is increasing steadily. In fact, the high polyphenol content of cocoa, coupled with its widespread presence in many food items, render this food of particular interest from the nutritional and "pharmacological" viewpoints. This paper summarizes the new findings and developments regarding the effects of cocoa and chocolate consumption on human health as presented at the International Conference "Chocolate, Lifestyle, and Health" (Milan, Italy, March 2, 2007) regarding the effects of cocoa and chocolate consumption on human health.

negative: The Neural Correlates of “Food Addiction” Context Research has implicated an addictive process in the development and maintenance of obesity. Although parallels in neural functioning between obesity and substance dependence have been found, no studies have examined the neural correlates of addictive-like eating behavior. Objective To test the hypothesis that elevated “food addiction” scores are associated with similar patterns of neural activation as substance dependence. Design Between-Subjects fMRI study. Participants Forty-eight healthy adolescent females ranging from lean to obese recruited for a healthy weight maintenance trial. Main Outcome Measure The relation between elevated “food addiction” scores and blood oxygen level-dependent fMRI activation in response to receipt and anticipated receipt of palatable food (chocolate milkshake). Results Food addiction scores (N = 39) correlated with greater activation in the anterior cingulate cortex (ACC), medial orbitofrontal cortex (OFC), and amygdala in response to anticipated receipt of food (P <0.05, false-discovery rate (FDR) corrected for multiple comparisons in small volumes). Participants with higher (n=15) versus lower (n=11) food addiction scores showed greater activation in the dorsolateral prefrontal cortex (DLPFC) and the caudate in response to anticipated receipt of food, but less activation in the lateral OFC in response to receipt of food (pFDR <0.05). Conclusions Similar patterns of neural activation are implicated in addictive-like eating behavior and substance dependence; elevated activation in reward circuitry in response to food cues and reduced activation of inhibitory regions in response to food intake.

negative: Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. BACKGROUND: Studies suggest cardioprotective benefits of dark chocolate containing cocoa. OBJECTIVE: This study examines the acute effects of solid dark chocolate and liquid cocoa intake on endothelial function and blood pressure in overweight adults. DESIGN: Randomized, placebo-controlled, single-blind crossover trial of 45 healthy adults [mean age: 53 y; mean body mass index (in kg/m(2)): 30]. In phase 1, subjects were randomly assigned to consume a solid dark chocolate bar (containing 22 g cocoa powder) or a cocoa-free placebo bar (containing 0 g cocoa powder). In phase 2, subjects were randomly assigned to consume sugar-free cocoa (containing 22 g cocoa powder), sugared cocoa (containing 22 g cocoa powder), or a placebo (containing 0 g cocoa powder). RESULTS: Solid dark chocolate and liquid cocoa ingestion improved endothelial function (measured as flow-mediated dilatation) compared with placebo (dark chocolate: 4.3 +/- 3.4% compared with -1.8 +/- 3.3%; P < 0.001; sugar-free and sugared cocoa: 5.7 +/- 2.6% and 2.0 +/- 1.8% compared with -1.5 +/- 2.8%; P < 0.001). Blood pressure decreased after the ingestion of dark chocolate and sugar-free cocoa compared with placebo (dark chocolate: systolic, -3.2 +/- 5.8 mm Hg compared with 2.7 +/- 6.6 mm Hg; P < 0.001; and diastolic, -1.4 +/- 3.9 mm Hg compared with 2.7 +/- 6.4 mm Hg; P = 0.01; sugar-free cocoa: systolic, -2.1 +/- 7.0 mm Hg compared with 3.2 +/- 5.6 mm Hg; P < 0.001; and diastolic: -1.2 +/- 8.7 mm Hg compared with 2.8 +/- 5.6 mm Hg; P = 0.014). Endothelial function improved significantly more with sugar-free than with regular cocoa (5.7 +/- 2.6% compared with 2.0 +/- 1.8%; P < 0.001). CONCLUSIONS: The acute ingestion of both solid dark chocolate and liquid cocoa improved endothelial function and lowered blood pressure in overweight adults. Sugar content may attenuate these effects, and sugar-free preparations may augment them.

negative: Survey of commercially available chocolate- and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat co... A survey of a broad range of chocolate- and cocoa-containing products marketed in the United States was conducted to provide a more detailed analysis of flavan-3-ol monomers, oligomers, and polymers, which can be grouped into a class of compounds called procyanidins. Samples consisted of the three or four top-selling products within the following six categories: natural cocoa powder, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized for percent fat (% fat), percent nonfat cocoa solids (% NFCS), antioxidant level by ORAC, total polyphenols, epicatechin, catechin, total monomers, and flavan-3-ol oligomers and polymers (procyanidins). On a gram weight basis epicatechin and catechin content of the products follow in decreasing order: cocoa powder > baking chocolate > dark chocolate = baking chips > milk chocolate > chocolate syrup. Analysis of the monomer and oligomer profiles within product categories shows there are two types of profiles: (1) products that have high monomers with decreasing levels of oligomers and (2) products in which the level of dimers is equal to or greater than the monomers. Results show a strong correlation (R(2) = 0.834) of epicatechin to the level of % NFCS and also very good correlations for N = 2-5 oligomers to % NFCS. A weaker correlation was observed for catechin to % NFCS (R(2) = 0.680). Other analyses show a similar high degree of correlation with epicatechin and N = 2-5 oligomers to total polyphenols, with catechin being less well correlated to total polyphenols. A lesser but still good correlation exists between the calculated percent cacao (calcd % cacao) content, a proxy for percent cacao, and these same flavanol measures, with catechin again showing a lesser degree of correlation to calcd % cacao. Principal component analysis (PCA) shows that the products group discretely into five classes: (1) cocoa powder, (2) baking chocolate, (3) dark chocolate and semisweet chips, (4) milk chocolates, and (5) syrup. PCA also shows that most factors group closely together including the antioxidant activity, total polyphenols, and the flavan-3-ol measures with the exception of catechin and % fat in the product, which group separately. Because catechin distribution appears to be different from the other flavan-3-ol measures, an analysis of the epicatechin to catechin ratio was done, indicating there is a >5-fold variation in this measure across the products studied. The cocoa-containing products tested range from cocoa powder with 227.34 +/- 17.23 mg of procyanidins per serving to 25.75 +/- 9.91 mg of procyanidins per serving for chocolate syrup. These results are discussed with respect to other studies on commercial products, the bioavailability of the flavanols, and the possible role of processing on the amount of catechin in products.

negative: Can a statin neutralize the cardiovascular risk of unhealthy dietary choices? The cardiovascular risk reduction associated with different statins for the prevention of cardiovascular disease and the cardiovascular risk increase associated with excess dietary intake of fat have been quantified. However, these relative risks have never been directly juxtaposed to determine whether an increase in relative risk by 1 activity could be neutralized by an opposing change in relative risk from a second activity. The investigators compared the increase in relative risk for cardiovascular disease associated with the total fat and trans fat content of fast foods against the relative risk decrease provided by daily statin consumption from a meta-analysis of statins in primary prevention of coronary artery disease (7 randomized controlled trials including 42,848 patients). The risk reduction associated with the daily consumption of most statins, with the exception of pravastatin, is more powerful than the risk increase caused by the daily extra fat intake associated with a 7-oz hamburger (Quarter Pounder) with cheese and a small milkshake. In conclusion, statin therapy can neutralize the cardiovascular risk caused by harmful diet choices. In other spheres of human activity, individuals choosing risky pursuits (motorcycling, smoking, driving) are advised or compelled to use measures to minimize the risk (safety equipment, filters, seatbelts). Likewise, some individuals eat unhealthily. Routine accessibility of statins in establishments providing unhealthy food might be a rational modern means to offset the cardiovascular risk. Fast food outlets already offer free condiments to supplement meals. A free statin-containing accompaniment would offer cardiovascular benefits, opposite to the effects of equally available salt, sugar, and high-fat condiments. Although no substitute for systematic lifestyle improvements, including healthy diet, regular exercise, weight loss, and smoking cessation, complimentary statin packets would add, at little cost, 1 positive choice to a panoply of negative ones.

negative: Essentials of Healthy Eating: A Guide Enough solid evidence now exists to offer women several fundamental strategies for healthy eating. They include emphasizing healthful unsaturated fats, whole grains, good protein “packages,” and fruits and vegetables; limiting consumption of trans and saturated fats, highly refined grains, and sugary beverages; and taking a multivitamin with folic acid and extra vitamin D as a nutritional safety net. A diet based on these principles is healthy through virtually all life stages, from young adulthood through planning for pregnancy, pregnancy, and on into old age.

negative: Healthy lifestyle characteristics among adults in the United States, 2000. BACKGROUND: Many public health recommendations and clinical guidelines emphasize the importance of healthy lifestyles. Recent epidemiologic studies demonstrate that following a healthy lifestyle has substantial health benefits. The objectives of this study were to report on the prevalence of healthy lifestyle characteristics (HLCs) and to generate a single indicator of a healthy lifestyle. METHODS: National data for the year 2000 were obtained from the Behavioral Risk Factor Surveillance System, which consists of annual, statewide, random digit-dialed household telephone surveys. We defined the following 4 HLCs: nonsmoking, healthy weight (body mass index [calculated as weight in kilograms divided by the square of height in meters] of 18.5-25.0), consuming 5 or more fruits and vegetables per day, and regular physical activity (> or =30 minutes for > or =5 times per week). The 4 HLCs were summed to create a healthy lifestyle index (range, 0-4), and the pattern of following all 4 HLCs was defined as a single healthy lifestyle indicator. We report prevalences of each HLC and the indicator by major demographic subgroups. RESULTS: By using data from more than 153 000 adults, the prevalence (95% confidence interval) of the individual HLCs was as follows: nonsmoking, 76.0% (75.6%-76.4%); healthy weight, 40.1% (39.7%-40.5%); 5 fruits and vegetables per day, 23.3% (22.9%-23.7%); and regular physical activity, 22.2% (21.8%-22.6%). The overall prevalence of the healthy lifestyle indicator (ie, having all 4 HLCs) was only 3.0% (95% confidence interval, 2.8%-3.2%), with little variation among subgroups (range, 0.8%-5.7%). CONCLUSION: These data illustrate that a healthy lifestyle-defined as a combination of 4 HLCs-was undertaken by very few adults in the United States, and that no subgroup followed this combination to a level remotely consistent with clinical or public health recommendations.

negative: Longevity and diet. Myth or pragmatism? Longevity is a very complex phenomenon, because many environmental, behavioral, socio-demographic and dietary factors influence the physiological pathways of aging and life-expectancy. Nutrition has been recognized to have an important impact on overall mortality and morbidity; and its role in extending life expectancy has been the object of extensive scientific research. This paper reviews the pathophysiological mechanisms that potentially link aging with diet and the scientific evidence supporting the anti-aging effect of the traditional Mediterranean diet, as well as of some specific foods. The diet and several of its components have additionally been shown to have beneficial effects on the co-morbidities typical of elderly populations. Furthermore, the epigenetic effects of diet on the aging process - through calorie restriction and the consumption of foods like red wine, orange juice, probiotics and prebiotics - have attracted scientific interest. Some, such as dark chocolate, red wine, nuts, beans, avocados are being promoted as anti-aging foods, due to their anti-oxidative and anti-inflammatory properties. Finally, an important moderator in the relationship between diet, longevity and human health remains the socio-economic status of individual, as a healthy diet, due to its higher cost, is closely related to higher financial and educational status. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

negative: The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide Background A plant-based diet protects against chronic oxidative stress-related diseases. Dietary plants contain variable chemical families and amounts of antioxidants. It has been hypothesized that plant antioxidants may contribute to the beneficial health effects of dietary plants. Our objective was to develop a comprehensive food database consisting of the total antioxidant content of typical foods as well as other dietary items such as traditional medicine plants, herbs and spices and dietary supplements. This database is intended for use in a wide range of nutritional research, from in vitro and cell and animal studies, to clinical trials and nutritional epidemiological studies. Methods We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table. Results The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values. Conclusions This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.

negative: Creation of a databank for content of antioxidants in food products by an amperometric method. Oxidative stress, i.e. excessive content of reactionary, oxygen, and nitrogen compounds (ROAC), including free radicals, is one of the causes of various dangerous diseases as well as premature aging. The adverse effect of free radicals can be neutralized by antioxidants. In order to carry out antioxidant therapy, one needs to know the contents of antioxidants in food products. We have created the databank for the contents of antioxidants in 1,140 food products, beverages, etc. Apart from water-soluble antioxidants, fat-soluble antioxidants in dairy and fish products, cacao, chocolate, nuts etc. were determined for the first time using an amperometric method.

negative: Candy consumption was not associated with body weight measures, risk factors for cardiovascular disease, or metabolic syndrome in US adults: NHANES... There is limited research examining the relationship of candy consumption by adults on diet and health. The purpose of this study was to determine total, chocolate, or sugar candy consumption and their effect on energy, saturated fatty acid and added sugar intake, weight, risk factors for cardiovascular disease, metabolic syndrome (MetS), and diet quality in adults 19 years and older (n = 15,023) participating in the 1999-2004 National Health and Nutrition Examination Survey. Twenty-four-hour dietary recalls were used to determine intake. Covariate-adjusted means ± SE and prevalence rates were determined for candy consumption groups. Odds ratios were used to determine the likelihood of cardiovascular risk factors and MetS. A total of 21.8%, 12.9%, and 10.9% of adults consumed total, chocolate, and sugar candy, respectively. Mean daily per capita intake of total, chocolate, and sugar candy was 9.0 ± 0.3, 5.7 ± 0.2, and 3.3 ± 0.2 g, respectively; intake in consumers was 38.3 ± 1.0, 39.9 ± 1.1, and 28.9 ± 1.3 g, respectively. Energy (9973 ± 92 vs 9027 ± 50 kJ; P < .0001), saturated fatty acid (27.9 ± 0.26 vs 26.9 ± 0.18 g; P = .0058), and added sugar (25.7 ± 0.42 vs 21.1 ± 0.41 g; P < .0001) intake were higher in candy consumers than nonconsumers. Body mass index (27.7 ± 0.15 vs 28.2 ± 0.12 kg/m(2); P = .0092), waist circumference (92.3 ± 0.34 vs 96.5 ± 0.29 cm; P = .0051), and C-reactive protein (0.40 ± 0.01 vs 0.43 ± 0.01 mg/dL; P = .0487) levels were lower in candy consumers than nonconsumers. Candy consumers had a 14% decreased risk of elevated diastolic blood pressure (P = .0466); chocolate consumers had a 19% decreased risk of lower high-density lipoprotein cholesterol (P = .0364) and a 15% reduced risk of MetS (P = .0453). Results suggest that the current level of candy consumption was not associated with health risks. Copyright © 2011 Elsevier Inc. All rights reserved.

negative: The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. Flavanols are the main flavonoids found in cocoa and chocolate, and can be especially abundant in certain cocoas. Research over the past decade has identified flavanols as showing diverse beneficial physiologic and antioxidant effects, particularly in context of vascular function. The present study employed functional magnetic resonance imaging based on blood oxygenation level-dependent (BOLD) contrast to explore the effect of flavanols on the human brain. Magnetic resonance imaging was used to measure BOLD responses to a cognitive task in 16 healthy young subjects. The data presented show an increase in the BOLD signal intensity in response to a cognitive task following ingestion of flavanol-rich cocoa (5 days of 150 mg of cocoa flavanols). This may arise either as a result of altered neuronal activity, or a change in vascular responsiveness, or both--the net effect then being dependent on which of the two effects is dominant. No significant effects were evident in behavioral reaction times, switch cost, and heart rate after consumption of this moderate dose of cocoa flavanols. A pilot study evaluated the relationship between cerebral blood flow and a single acute dose (450 mg flavanols) of flavanol-rich cocoa and showed that flavanol-rich cocoa can increase the cerebral blood flow to gray matter, suggesting the potential of cocoa flavanols for treatment of vascular impairment, including dementia and strokes, and thus for maintaining cardiovascular health.

negative: Healthy living is the best revenge: findings from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. BACKGROUND: Our objective was to describe the reduction in relative risk of developing major chronic diseases such as cardiovascular disease, diabetes, and cancer associated with 4 healthy lifestyle factors among German adults. METHODS: We used data from 23,153 German participants aged 35 to 65 years from the European Prospective Investigation Into Cancer and Nutrition-Potsdam study. End points included confirmed incident type 2 diabetes mellitus, myocardial infarction, stroke, and cancer. The 4 factors were never smoking, having a body mass index lower than 30 (calculated as weight in kilograms divided by height in meters squared), performing 3.5 h/wk or more of physical activity, and adhering to healthy dietary principles (high intake of fruits, vegetables, and whole-grain bread and low meat consumption). The 4 factors (healthy, 1 point; unhealthy, 0 points) were summed to form an index that ranged from 0 to 4. RESULTS: During a mean follow-up of 7.8 years, 2006 participants developed new-onset diabetes (3.7%), myocardial infarction (0.9%), stroke (0.8%), or cancer (3.8%). Fewer than 4% of participants had zero healthy factors, most had 1 to 3 healthy factors, and approximately 9% had 4 factors. After adjusting for age, sex, educational status, and occupational status, the hazard ratio for developing a chronic disease decreased progressively as the number of healthy factors increased. Participants with all 4 factors at baseline had a 78% (95% confidence interval [CI], 72% to 83%) lower risk of developing a chronic disease (diabetes, 93% [95% CI, 88% to 95%]; myocardial infarction, 81% [95% CI, 47% to 93%]; stroke, 50% [95% CI, -18% to 79%]; and cancer, 36% [95% CI, 5% to 57%]) than participants without a healthy factor. CONCLUSION: Adhering to 4 simple healthy lifestyle factors can have a strong impact on the prevention of chronic diseases.

negative: Dioxins, dibenzofurans, dioxin-like PCBs, and DDE in U.S. fast food, 1995. Food, especially dairy products, meat, and fish, is the primary source of environmental exposure to dioxins in the general population. Little data exists on dioxin levels in the popular and widely consumed "fast foods". Data presented in a previously published pilot study was limited to measuring only the levels of dioxins and dibenzofurans in three types of U.S. fast food. This study adds to the previous paper by presenting data, in addition to dioxins and dibenzofurans, on the closely related dioxin-like polychlorinated biphenyls (PCBs), and the persistent metabolite of DDT, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE), in four types of popular U.S. fast food. These include McDonald's Big Mac Hamburger, Pizza Hut's Personal Pan Pizza Supreme, Kentucky Fried Chicken (KFC) three piece original recipe mixed dark and white meat luncheon package, and Häagen-Daz chocolate-chocolate chip ice cream. Dioxin plus dibenzofuran dioxin toxic equivalents (TEQ) ranged from 0.03 to 0.28 TEQ pg/g wet or whole weight for the Big Mac, from 0.03 to 0.29 for the Pizza, from 0.01 to 0.31 for the KFC, and from 0.03 to 0.49 TEQ pg/g for the ice cream. Daily TEQ consumption per kilogram body weight (kg/BW), assuming an average 65 kg adult and a 20 kg child, from one serving of each of these fast food ranged between 0.046 and 1.556 pg/kg in adults whereas in children the values were between 0.15 and 5.05 pg/kg. Total measured PCDD/Fs in the Big Mac, Personal Pan Pizza, KFC, and the Häagen-Daz ice cream varied from 0.58 to 9.31 pg/g. Measured DDE levels in the fast foods ranged from 180 to 3170 pg/g. Total mono-ortho PCB levels ranged up to 500 pg/g or 1.28 TEQ pg/g for the KFC and for di-ortho PCBs up to 740 pg/g or 0.014 TEQ pg/g for the pizza sample. Total PCB values in the four samples ranged up to 1170 pg/g or 1.29 TEQ pg/g for the chicken sample.

negative: Glucose and insulin responses to manufactured and whole-food snacks. To determine whether realistic snacks containing added sugar evoke excessive insulin responses, 10 healthy subjects consumed four different snack meals, similar in fat and total energy content. Two snacks were based on sugary, manufactured products (chocolate-coated candy bar; cola drink with crisps) and two on whole foods (raisins and peanuts; bananas and peanuts). After the processed-food snacks, plasma-glucose levels tended to rise higher and to fall lower than after the whole-food snacks. The area under the plasma insulin curve was 70% greater after the manufactured snacks than after the raisin-peanut snack. The banana-peanut snack evoked an intermediate insulin response. One subject had pathological insulinaemia after both manufactured snacks but normal responses after both whole-food snacks. These findings suggest that foods and drinks containing added fiber-depleted sugars stress and sometimes overwhelm homeostatic mechanisms but also suggest that the insulin response to food is influenced by the physical state of the food.

negative: Healthy lifestyle behaviors and all-cause mortality among adults in the United States. OBJECTIVE: To examine the links between three fundamental healthy lifestyle behaviors (not smoking, healthy diet, and adequate physical activity) and all-cause mortality in a national sample of adults in the United States. METHOD: We used data from 8375 U.S. participants aged ≥ 20 years of the National Health and Nutrition Examination Survey 1999-2002 who were followed through 2006. RESULTS: During a mean follow-up of 5.7 years, 745 deaths occurred. Compared with their counterparts, the risk for all-cause mortality was reduced by 56% (95% confidence interval [CI]: 35%-70%) among adults who were nonsmokers, 47% (95% CI: 36%, 57%) among adults who were physically active, and 26% (95% CI: 4%, 42%) among adults who consumed a healthy diet. Compared with participants who had no healthy behaviors, the risk decreased progressively as the number of healthy behaviors increased. Adjusted hazard ratios and 95% confidence interval were 0.60 (0.38, 0.95), 0.45 (0.30, 0.67), and 0.18 (0.11, 0.29) for 1, 2, and 3 healthy behaviors, respectively. CONCLUSION: Adults who do not smoke, consume a healthy diet, and engage in sufficient physical activity can substantially reduce their risk for early death. Published by Elsevier Inc.

negative: Effects of acute administration of caffeine on vascular function. Caffeine is the most widely used pharmacologic substance in the world. It is found in common nonessential grocery items (e.g., coffee, tea, cocoa, and chocolate). The effects of caffeine on cardiovascular diseases, including hypertension, remain controversial, and there is little information on its direct effect on vascular function. The purpose of this study was to determine the effect of caffeine on endothelial function in humans. This study was a double-blind, randomized placebo and active drug study. Forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and to sodium nitroprusside, an endothelium-independent vasodilator, were evaluated in healthy young men before and after the oral administration of caffeine 300 mg (n = 10) or placebo (n = 10). FBF was measured by using a strain-gauge plethysmograph. Caffeine significantly increased systolic and diastolic blood pressures by 6.0 +/- 6.0 and 2.6 +/- 3.1 mm Hg (p <0.05), respectively, but did not alter heart rate or baseline FBF. Caffeine augmented the FBF responses to ACh from 21.2 +/- 7.1 to 26.6 +/- 8.1 ml/min/100 ml tissue (p <0.05), whereas sodium nitroprusside-stimulated vasodilation was not altered by caffeine administration. The intra-arterial infusion of N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, abolished the caffeine-induced augmentation of FBF response to ACh. In the placebo group, the ACh- and sodium nitroprusside-stimulated vasodilation was similar before and after the follow-up period. In conclusion, these findings suggest that the acute administration of caffeine augments endothelium-dependent vasodilation in healthy young men through an increase in nitric oxide production.

negative: A diet low in animal fat and rich in N-hexacosanol and fisetin is effective in reducing symptoms of Parkinson's disease. This study describes how foods rich in fisetin and hexacosanol added to a strict diet reversed most symptoms of Parkinson's disease (PD) in one patient. This is a case report involving outpatient care. The subject was a dietitian diagnosed with idiopathic PD in 2000 at the age of 53 years old, with a history of exposure to neurotoxins and no family history of PD. A basic diet started in 2000 consisted of predominantly fruits, vegetables, 100% whole grains, extra virgin olive oil, nuts, seeds, nonfat milk products, tea, coffee, spices, small amounts of dark chocolate, and less than 25 g of animal fat daily. The basic diet alone failed to prevent decline due to PD. In 2009, the basic diet was enhanced with a good dietary source of both fisetin and hexacosanol. Six months after the patient started the enhanced diet rich in fisetin and hexacosanol, a clinically significant improvement in symptoms was noted; the patient's attending neurologist reported that the clinical presentation of cogwheel rigidity, micrographia, bradykinesia, dystonia, constricted arm swing with gait, hypomimia, and retropulsion appeared to be resolved. The only worsening of symptoms occurred when the diet was not followed precisely. Little improvement in tremor or seborrhea was observed. The clinical improvement has persisted to date. To the best of our knowledge, this is the first case where adjunctive diet therapy resulted in a significant reduction of symptoms of PD without changing the type or increasing the amount of medications.

negative: Background music genre can modulate flavor pleasantness and overall impression of food stimuli. This study aimed to determine whether background music genre can alter food perception and acceptance, but also to determine how the effect of background music can vary as a function of type of food (emotional versus non-emotional foods) and source of music performer (single versus multiple performers). The music piece was edited into four genres: classical, jazz, hip-hop, and rock, by either a single or multiple performers. Following consumption of emotional (milk chocolate) or non-emotional food (bell peppers) with the four musical stimuli, participants were asked to rate sensory perception and impression of food stimuli. Participants liked food stimuli significantly more while listening to the jazz stimulus than the hip-hop stimulus. Further, the influence of background music on overall impression was present in the emotional food, but not in the non-emotional food. In addition, flavor pleasantness and overall impression of food stimuli differed between music genres arranged by a single performer, but not between those by multiple performers. In conclusion, our findings demonstrate that music genre can alter flavor pleasantness and overall impression of food stimuli. Furthermore, the influence of music genre on food acceptance varies as a function of the type of served food and the source of music performer. Published by Elsevier Ltd.

negative: Dietary sensitivities and ADHD symptoms: thirty-five years of research. Artificial food colors (AFCs) have not been established as the main cause of attention-deficit hyperactivity disorder (ADHD), but accumulated evidence suggests that a subgroup shows significant symptom improvement when consuming an AFC-free diet and reacts with ADHD-type symptoms on challenge with AFCs. Of children with suspected sensitivities, 65% to 89% reacted when challenged with at least 100 mg of AFC. Oligoantigenic diet studies suggested that some children in addition to being sensitive to AFCs are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and orange. Some studies found "cosensitivity" to be more the rule than the exception. Recently, 2 large studies demonstrated behavioral sensitivity to AFCs and benzoate in children both with and without ADHD. A trial elimination diet is appropriate for children who have not responded satisfactorily to conventional treatment or whose parents wish to pursue a dietary investigation.

negative: Caffeine in pregnancy. Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Because of its wide consumption at different levels by most segments of the population, the public and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. Reproductive-aged and pregnant women are 'at risk' subgroups of the population who may require specific advice on moderating their daily caffeine intake. This article highlights the implications of caffeine intake in pregnancy, reviews the latest evidence-based information available on this subject, and offers recommendations (practical advice) for the obstetrician-gynecologists proving peripartum care to these potentially complicated pregnancies.

negative: Temporal and Regional Trends in the Prevalence of Healthy Lifestyle Characteristics: United States, 1994–2007 Objectives. We examined temporal and regional trends in the prevalence of health lifestyles in the United States. Methods. We used 1994 to 2007 data from the Behavioral Risk Factor Surveillance System to assess 4 healthy lifestyle characteristics: having a healthy weight, not smoking, consuming fruits and vegetables, and engaging in physical activity. The concurrent presence of all 4 characteristics was defined as a healthy overall lifestyle. We used logistic regression to assess temporal and regional trends. Results. The percentages of individuals who did not smoke (4% increase) and had a healthy weight (10% decrease) showed the strongest temporal changes from 1994 to 2007. There was little change in fruit and vegetable consumption or physical activity. The prevalence of healthy lifestyles increased minimally over time and varied modestly across regions; in 2007, percentages were higher in the Northeast (6%) and West (6%) than in the South (4%) and Midwest (4%). Conclusions. Because of the large increases in overweight and the declines in smoking, there was little net change in the prevalence of healthy lifestyles. Despite regional differences, the prevalence of healthy lifestyles across the United States remains very low.

negative: Adherence to healthy lifestyle habits in US adults, 1988-2006. BACKGROUND: Lifestyle choices are associated with cardiovascular disease and mortality. The purpose of this study was to compare adherence to healthy lifestyle habits in adults between 1988 and 2006. METHODS: Analysis of adherence to 5 healthy lifestyle trends (>or=5 fruits and vegetables/day, regular exercise >12 times/month, maintaining healthy weight [body mass index 18.5-29.9 kg/m(2)], moderate alcohol consumption [up to 1 drink/day for women, 2/day for men] and not smoking) in the National Health and Nutrition Examination Survey 1988-1994 were compared with results from the National Health and Nutrition Examination Survey 2001-2006 among adults aged 40-74 years. RESULTS: Over the last 18 years, the percent of adults aged 40-74 years with a body mass index >or=30 kg/m(2) has increased from 28% to 36% (P <.05); physical activity 12 times a month or more has decreased from 53% to 43% (P <.05); smoking rates have not changed (26.9% to 26.1%); eating 5 or more fruits and vegetables a day has decreased from 42% to 26% (P <.05), and moderate alcohol use has increased from 40% to 51% (P <.05). Adherence to all 5 healthy habits has gone from 15% to 8% (P <.05). Although adherence to a healthy lifestyle was lower among minorities, adherence decreased more among non-Hispanic Whites over the period. Individuals with a history of hypertension/diabetes/cardiovascular disease were no more likely to be adherent to a healthy lifestyle than people without these conditions. CONCLUSIONS: Generally, adherence to a healthy lifestyle pattern has decreased during the last 18 years, with decreases documented in 3 of 5 healthy lifestyle habits. These findings have broad implications for the future risk of cardiovascular disease in adults.

negative: An after-school snack of raisins lowers cumulative food intake in young children. Snacks are an important part of children's dietary intake, but the role of dried fruit on energy intake in children is unknown. Therefore, the effect of ad libitum consumption of an after-school snack of raisins, grapes, potato chips, and chocolate chip cookies on appetite and energy intake in twenty-six 8- to 11-y-old normal-weight (15th to 85th percentile) children was examined. On 4 separate weekdays, 1 wk apart, children (11 M, 15 F) were given a standardized breakfast, morning snack (apple), and a standardized lunch. After school, children randomly received 1 of 4 ad libitum snacks and were instructed to eat until "comfortably full." Appetite was measured before and 15, 30, and 45 min after snack consumption. Children consumed the least calories from raisins and grapes and the most from cookies (P < 0.001). However, weight of raisins consumed was similar to potato chips (about 75 g) and lower compared to grapes and cookies (P < 0.009). Raisins and grapes led to lower cumulative food intake (breakfast + morning snack + lunch + after-school snack) (P < 0.001), while the cookies increased cumulative food intake (P < 0.001) compared to the other snacks. Grapes lowered appetite compared to all other snacks (P < 0.001) when expressed as a change in appetite per kilocalorie of the snack. Ad libitum consumption of raisins has potential as an after-school snack to achieve low snack intake prior to dinner, similar to grapes, compared to potato chips, and cookies in children 8 to 11 y old. © 2013 Institute of Food Technologists®

negative: Turning back the clock: adopting a healthy lifestyle in middle age. PURPOSE: To determine the frequency of adopting a healthy lifestyle (5 or more fruits and vegetables daily, regular exercise, BMI 18.5-29.9 kg/m2, no current smoking) in a middle-aged cohort, and determine the subsequent rates of cardiovascular disease (CVD) and mortality among those who adopt a healthy lifestyle. METHODS: We conducted a cohort study in a diverse sample of adults age 45-64 in the Atherosclerosis Risk in Communities survey. Outcomes are all-cause mortality and fatal or non-fatal cardiovascular disease. RESULTS: Of 15,708 participants, 1344 (8.5%) had 4 healthy lifestyle habits at the first visit, and 970 (8.4%) of the remainder had newly adopted a healthy lifestyle 6 years later. Men, African Americans, individuals with lower socioeconomic status, or a history of hypertension or diabetes were less likely to newly adopt a healthy lifestyle (all P <.05). During the following 4 years, total mortality and cardiovascular disease events were lower for new adopters (2.5% vs 4.2%, chi2P <.01, and 11.7% vs 16.5%, chi2P <.01 respectively) compared to individuals who did not adopt a healthy lifestyle. After adjustment, new adopters had lower all-cause mortality (OR 0.60, 95% Confidence Interval [CI], 0.39-0.92) and fewer cardiovascular disease events (OR 0.65, 95% CI, 0.39-0.92) in the next 4 years. CONCLUSIONS: People who newly adopt a healthy lifestyle in middle-age experience a prompt benefit of lower rates of cardiovascular disease and mortality. Strategies to encourage adopting healthy lifestyles should be implemented, especially among people with hypertension, diabetes, or low socioeconomic status.

negative: Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach. OBJECTIVE: To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. METHODS: United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. RESULTS: The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. CONCLUSIONS: Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences. Copyright © 2011 Wiley Periodicals, Inc.

negative: Effect of blueberry ingestion on natural killer cell counts, oxidative stress, and inflammation prior to and after 2.5 h of running. Blueberries are rich in antioxidants known as anthocyanins, which may exhibit significant health benefits. Strenous exercise is known to acutely generate oxidative stress and an inflammatory state, and serves as an on-demand model to test antioxidant and anti-inflammatory compounds. The purpose of this study was to examine whether 250 g of blueberries per day for 6 weeks and 375 g given 1 h prior to 2.5 h of running at ∼72% maximal oxygen consumption counters oxidative stress, inflammation, and immune changes. Twenty-five well-trained subjects were recruited and randomized into blueberry (BB) (N = 13) or control (CON) (N = 12) groups. Blood, muscle, and urine samples were obtained pre-exercise and immediately postexercise, and blood and urine 1 h postexercise. Blood was examined for F₂-isoprostanes for oxidative stress, cortisol, cytokines, homocysteine, leukocytes, T-cell function, natural killer (NK), and lymphocyte cell counts for inflammation and immune system activation, and ferric reducing ability of plasma for antioxidant capacity. Muscle biopsies were examined for glycogen and NFkB expression to evaluate stress and inflammation. Urine was tested for modification of DNA (8-OHDG) and RNA (5-OHMU) as markers of nucleic acid oxidation. A 2 (treatment) × 3 (time) repeated measures ANOVA was used for statistical analysis. Increases in F₂-isoprostanes and 5-OHMU were significantly less in BB and plasma IL-10 and NK cell counts were significantly greater in BB vs. CON. Changes in all other markers did not differ. This study indicates that daily blueberry consumption for 6 weeks increases NK cell counts, and acute ingestion reduces oxidative stress and increases anti-inflammatory cytokines.

negative: Healthy lifestyle on the risk of breast cancer. BACKGROUND: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer. METHODS: A population-based case-control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association. RESULTS: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29-0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11-0.37) when highest versus lowest index quintiles were compared. CONCLUSIONS: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles. IMPACT: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. ©2011 AACR.

negative: Physician disclosure of healthy personal behaviors improves credibility and ability to motivate. CONTEXT: While some studies have shown that physicians with healthy personal habits are especially likely to discuss prevention with their patients, to our knowledge no one has published information testing whether physician credibility and patient motivation to adopt healthier habits are enhanced by physician's disclosures of their own healthy behaviors. DESIGN: Two brief health education videos about improving diet and exercise were produced and shown to subjects (n1 = 66, n2 = 65) in an Emory University general medical clinic waiting room in Atlanta, Ga. In one video, the physician revealed an additional half minute of information about her personal healthy dietary and exercise practices and had a bike helmet and an apple visible on her desk (physician-disclosure video). In the other video, discussion of personal practices and the apple and bike helmet were not included (control video). RESULTS: Viewers of the physician-disclosure video considered the physician to be generally healthier, some-what more believable, and more motivating than did viewers of the control video. They also rated this physician to be specifically more believable and motivating regarding exercise and diet (P < or = .001). CONCLUSION: Physicians' abilities to motivate patients to adopt healthy habits can be enhanced by conveying their own healthy habits. Educational institutions should consider encouraging health professionals-in-training to practice and demonstrate healthy personal lifestyles.

negative: Aging and vascular responses to flavanol-rich cocoa. OBJECTIVES: Strong evidence has secured aging as a powerful predictor of both cardiovascular risk and endothelial dysfunction, yet specific treatment is not available. We tested the hypothesis that vascular responsiveness to flavanol-rich cocoa increases with advancing age. We have previously shown that flavanol-rich cocoa induced peripheral vasodilation, improving endothelial function via a nitric oxide (NO)-dependent mechanism. METHODS: We studied blood pressure and peripheral arterial responses to several days of cocoa in 15 young (< 50 years) and 19 older (> 50) healthy subjects. RESULTS: The nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME) induced significant pressor responses following cocoa administration only among the older subjects: systolic blood pressure (SBP) rose 13 +/- 4 mmHg, diastolic blood pressure (DBP) 6 +/- 2 mmHg (P = 0.008 and 0.047, respectively); SBP was significantly higher in the older subjects (P < 0.05). Flow-mediated vasodilation, measured by tonometry in the finger, was enhanced with flavanol-rich cocoa in both groups, but significantly more so among the old (P = 0.01). Finally, basal pulse wave amplitude (PWA) followed a similar pattern. Four to six days of flavanol-rich cocoa caused a rise in PWA in both groups. At peak vasodilation following acute cocoa intake on the final day, both groups showed a further, significant rise in PWA. The response in the older subjects was more robust; P < 0.05. L-NAME significantly reversed dilation in both groups. CONCLUSIONS: Flavanol-rich cocoa enhanced several measures of endothelial function to a greater degree among older than younger healthy subjects. Our data suggest that the NO-dependent vascular effects of flavanol-rich cocoa may be greater among older people, in whom endothelial function is more disturbed.

negative: Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium. The telomere length is an indicator of biologic aging, and shorter telomeres have been associated with coronary artery calcium (CAC), a validated indicator of coronary atherosclerosis. It is unclear, however, whether healthy lifestyle behaviors affect the relation between telomere length and CAC. In a sample of subjects aged 40 to 64 years with no previous diagnosis of coronary heart disease, stroke, diabetes mellitus, or cancer (n = 318), healthy lifestyle behaviors of greater fruit and vegetable consumption, lower meat consumption, exercise, being at a healthy weight, and the presence of social support were examined to determine whether they attenuated the association between a shorter telomere length and the presence of CAC. Logistic regression analyses controlling for age, gender, race/ethnicity, and Framingham risk score revealed that the relation between having shorter telomeres and the presence of CAC was attenuated in the presence of high social support, low meat consumption, and high fruit and vegetable consumption. Those with shorter telomeres and these characteristics were not significantly different from those with longer telomeres. Conversely, the subjects with shorter telomeres and less healthy lifestyles had a significantly increased risk of the presence of CAC: low fruit and vegetable consumption (odds ratio 3.30, 95% confidence interval 1.61 to 6.75), high meat consumption (odds ratio 3.33, 95% confidence interval 1.54 to 7.20), and low social support (odds ratio 2.58, 95% confidence interval 1.24 to 5.37). Stratification by gender yielded similar results for men; however, among women, only fruit and vegetable consumption attenuated the shorter telomere length and CAC relation. In conclusion, the results of the present study suggest that being involved in healthy lifestyle behaviors might attenuate the association between shorter telomere length and coronary atherosclerosis, as identified using CAC. 2010 Elsevier Inc. All rights reserved.

negative: Body weight status and cardiovascular risk factors in adults by frequency of candy consumption Background Limited information is available regarding the impact of candy consumption on health. The purpose of this study was to investigate associations between typical frequency of candy consumption and body weight status and select cardiovascular risk factors among adults in the United States. Methods Using data collected in the 2003–2006 National Health and Nutrition Examination Surveys (NHANES), adults were categorized as infrequent (≤ 3 eating occasions [EO]/month), moderate (> 3 EO/month and ≤ 3.5 EO/week), or frequent (> 3.5 EO/week) candy consumers based on the combined frequency of chocolate and other candy consumption over the previous 12 months. Weight and adiposity status were analyzed using logistic regression models, and blood pressure, lipids, and insulin sensitivity were analyzed using linear regression models. Models were adjusted for age, sex and race/ethnicity, and also for additional covariates with potential associations with the outcomes. Appropriate statistical weights were used to yield results generalizable to the US population. Results Frequency of candy consumption was not associated with the risk of obesity, overweight/obesity, elevated waist circumference, elevated skinfold thickness, blood pressure, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol, triglycerides, or insulin resistance. Increased frequency of candy consumption was associated with higher energy intakes and higher energy adjusted intakes of carbohydrates, total sugars and added sugars, total fat, saturated fatty acids and monounsaturated fatty acids (p < 0.05), and lower adjusted intakes of protein and cholesterol (p < 0.001). Conclusions Increased frequency of candy consumption among adults in the United States was not associated with objective measures of adiposity or select cardiovascular risk factors, despite associated dietary differences. Given the cross-sectional study design, however, it cannot be concluded that candy consumption does not cause obesity or untoward levels of cardiovascular risk markers. The lack of an association between frequency of candy consumption and cardiovascular risk factors could be due to reduced intake of candy among the overweight due to dieting or a health professional’s recommendations. Additionally, it is important to note that the analysis was based on frequency of candy consumption and not amount of candy consumed. Longitudinal studies are needed to confirm the lack of associations between frequency of candy consumption and cardiovascular risk factors.