The protective effect of the Mediterranean diet on endothelial resistance to GLP-1 in type 2 diabetes: a preliminary report Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis A systematic review protocol examining the effect of vitamin D supplementation on endothelial function An oil mixture with trans-10, cis-12 conjugated linoleic acid increases markers of inflammation and in vivo lipid peroxidation compared with cis-9, trans-11 conjugated linoleic acid in postmenopausal women. CLA Does Not Impair Endothelial Function and Decreases Body Weight as Compared with Safflower Oil in Overweight and Obese Male Subjects Extra virgin olive oil consumption reduces the risk of osteoporotic fractures in the PREDIMED trial. Lack of effect of supplementation with EPA or DHA on platelet-monocyte aggregates and vascular function in healthy men. Digital Education in Health Professions: The Need for Overarching Evidence Synthesis Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients. Effects of gastric bypass surgery followed by supervised physical training on inflammation and endothelial function: A randomized controlled trial. Olive oil and walnut breakfasts reduce the postprandial inflammatory response in mononuclear cells compared with a butter breakfast in healthy men. Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. Exercise in the treatment of rotator cuff impingement: a systematic review and a synthesized evidence-based rehabilitation protocol. The Effects of Maternal Supplementation of Polyunsaturated Fatty Acids on Visual, Neurobehavioural, and Developmental Outcomes of the Child: A Systematic Review of the Randomized Trials Acute and Chronic Effects of Endurance Running on Inflammatory Markers: A Systematic Review Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors Comparison of the effects of n-3 long chain polyunsaturated fatty acids and fenofibrate on markers of inflammation and vascular function, and on the serum lipoprotein profile in overweight and obese subjects. A meal rich in oleic acid beneficially modulates postprandial sICAM-1 and sVCAM-1 in normotensive and hypertensive hypertriglyceridemic subjects. Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian women: the EPICOR Study.
Background In type 2 diabetes , acute hyperglycemia worsens endothelial function and inflammation , while resistance to GLP-1 action occurs . All these phenomena seem to be related to the generation of oxidative stress . A Mediterranean diet , supplemented with olive oil , increases plasma antioxidant capacity , suggesting that its implementation can have a favorable effect on the aforementioned phenomena . In the present study , we test the hypothesis that a Mediterranean diet using olive oil can counteract the effects of acute hyperglycemia and can improve the resistance of the endothelium to GLP-1 action . Methods Two groups of type 2 diabetic patients , each consisting of twelve subjects , participated in a r and omized trial for three months , following a Mediterranean diet using olive oil or a control low-fat diet .  Plasma antioxidant capacity , endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels were evaluated at baseline and at the end of the study . The effect of GLP-1 during a hyperglycemic clamp , was also studied at baseline and at the end of the study . Results Compared to the control diet , the Mediterranean diet increased plasma antioxidant capacity and improved basal endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . The Mediterranean diet also reduced the negative effects of acute hyperglycemia , induced by a hyperglycemic clamp , on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . Furthermore , the Mediterranean diet improved the protective action of GLP-1 on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels , also increasing GLP-1-induced insulin secretion . Conclusions These data suggest that the Mediterranean diet , using olive oil , prevents the acute hyperglycemia effect on endothelial function , inflammation and oxidative stress , and improves the action of GLP-1 , which may have a favorable effect on the management of type 2 diabetes , particularly for the prevention of cardiovascular disease BACKGROUND Olive oil polyphenols have been associated with several cardiovascular health benefits . This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure ( BP ) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension . METHODS We conducted a double-blind , r and omized , crossover dietary-intervention study . After a run-in period of 4 months ( baseline values ) , two diets were used , one with polyphenol-rich olive oil ( ∼30 mg/day ) , the other with polyphenol-free olive oil . Each dietary period lasted 2 months with a 4-week washout between diets . Systolic and diastolic BP , serum or plasma biomarkers of endothelial function , oxidative stress , and inflammation , and ischemia-induced hyperemia in the forearm were measured . RESULTS When compared to baseline values , only the polyphenol-rich olive oil diet led to a significant ( P < 0.01 ) decrease of 7.91 mm Hg in systolic and 6.65 mm Hg of diastolic BP . A similar finding was found for serum asymmetric dimethylarginine ( ADMA ) ( -0.09 ± 0.01 µmol/l , P < 0.01 ) , oxidized low-density lipoprotein ( ox-LDL ) ( -28.2 ± 28.5 µg/l , P < 0.01 ) , and plasma C-reactive protein ( CRP ) ( -1.9 ± 1.3 mg/l , P < 0.001 ) . The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates ( + 4.7 ± 6.6 µmol/l , P < 0.001 ) and hyperemic area after ischemia ( + 345 ± 386 perfusion units (PU)/sec , P < 0.001 ) . CONCLUSIONS We concluded that the consumption of a diet containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension Purpose Diets rich in plant-derived polyphenols such as olive oil ( OO ) and /or catechins such as epigallocatechin 3-gallate ( EGCG ) have been shown to reduce the incidence of cardiovascular diseases , potentially by improving endothelial function , an important surrogate for atherosclerosis . The possible augmentation of endothelial function with the combined efforts of OO and EGCG is intriguing , yet unknown . Methods Eighty-two patients with early atherosclerosis ( presence of endothelial dysfunction ) were enrolled in this double-blind , r and omized trial with 52 completing the study . The aim of the study was to compare the effect of a daily intake of 30 ml simple OO , with 30 ml of EGCG-supplemented OO , on endothelial function as well as on inflammation and oxidative stress after a period of 4 months . Endothelial function was assessed noninvasively via peripheral arterial tonometry ( Endo-PAT ® ) . Results After 4 months , when OO and EGCG-supplemented OO groups were combined , OO significantly improved endothelial function ( RHI , 1.59 ± 0.25–1.75 ± 0.45 ; p < 0.05 ) . However , there were no significant differences in results between the two olive oil groups . Interestingly , with OO supplementation there was a significant reduction in inflammatory parameters : sICAM ( 196 to 183 ng/mL , p = < 0.001 ) ; white blood cells ( WBCs ) ( 6.0 × 109/L–5.8 × 109/L , p < 0.05 ) ; monocytes ( 0.48 × 109/L to 0.44 × 109/L , p = 0.05 ) ; lymphocytes ( 1.85 × 109/L to 1.6 × 109/L , p = 0.01 ) ; and platelets ( 242–229 × 109/L , p = 0.047 ) . Conclusions Improvement in endothelial dysfunction in patients with early atherosclerosis in association with significant reduction in leukocytes may suggest an important role of early cellular inflammatory mediators on endothelial function . The current study supports one potential mechanism for the role of olive oil , independent of EGCG , modestly supplemented to a healthy cardiovascular diet Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 A mixture of trans-10 , cis-12 ( t10,c12 ) and cis-9 , trans-11 ( c9,t11 ) conjugated linoleic acid ( CLA mixture ) reduced atherosclerosis in animals , thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest . We gave 75 healthy postmenopausal women a daily supplement of 5.5 g of oil rich in either CLA mixture , an oil rich in the naturally occurring c9,t11 CLA ( CLA milk ) , respectively , or olive oil for 16 wk in a double-blind , r and omized , parallel intervention study . We sample d blood and urine before and after the intervention . The ratios of total cholesterol : HDL cholesterol and concentrations of C-reactive protein , fibrinogen , and plasminogen activator inhibitor-1 were significantly higher in women supplemented with the CLA mixture than in those supplemented with CLA milk .  Plasma triacylglycerol was significantly higher and HDL cholesterol was lower in women supplemented with the CLA mixture than with olive oil . Both CLA supplements increased lipid peroxidation , a marker of in vivo oxidative stress measured as urinary free 8-iso-prostagl and in F(2alpha ) . However , the CLA mixture increased lipid peroxidation more than the CLA milk did . The plasma cytokines interleukin-6 and tumor necrosis factor-alpha were not affected by the treatments , nor were any of the other variables measured . In conclusion , oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease , whereas the c9,t11 CLA isomer is more neutral , except for a small but significant increase in lipid peroxidation compared with olive oil Objective : Conjugated linoleic acid ( CLA ) showed a wide range of beneficial biological effects with relevance for cardiovascular health in animal models and humans . Most human studies used olive oil as a reference . This study assessed the effect of CLA as compared with safflower oil on endothelial function and markers of cardiovascular risk in overweight and obese men .  Heated safflower oil and olive oil were given for additional descriptive control . Methods : Eighty-five overweight men ( aged 45–68 years , body mass index 25–35 kg/m2 ) were r and omized to receive 4.5 g/d of the CLA isomeric mixture , safflower oil , heated safflower oil , or olive oil in a 4-week double-blind study .  Endothelial function was assessed by peripheral arterial tonometry ( PAT ) index determination in the fasting and postpr and ial state ( i.e. , 4 hours after consumption of a fat- and sucrose-rich meal ) . Results : CLA as compared with safflower oil consumption did not impair fasting or postpr and ial PAT index but decreased body weight .  CLA as compared with safflower oil did not change total , low-density lipoprotein ( LDL ) , or high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; insulin sensitivity indices ; C-reactive protein ; soluble adhesion molecules ; oxidized LDL ; lipoprotein a ( Lp[a ] ) ; paraoxonase ; or platelet-activating factor acetylhydrolase ( PAF-AH ) activity , but significantly reduced arylesterase activity and increased concentrations of the F2-isoprostane 8-iso-prostagl and in F (PGF)2α . Conclusion : CLA did not impair endothelial function . Other parameters associated with metabolic syndrome and oxidative stress were not changed or were slightly improved . Results suggest that CLA does not increase cardiovascular risk . Increased F2-isoprostane concentrations in this context may not indicate increased oxidative stress BACKGROUND & AIMS The incidence of osteoporotic fractures is lower in countries in the Mediterranean basin .  Virgin olive oil , a key component of the Mediterranean Diet ( MDiet ) , with recognised beneficial effects on metabolism and cardiovascular health , may decrease the risk of osteoporotic fractures . The aim to this study was to explore the effect of chronic consumption of total olive oil and its varieties on the risk of osteoporosis-related fractures in a middle-aged and elderly Mediterranean population . METHODS We included all participants ( n = 870 ) recruited in the Reus ( Spain ) centre of the PREvención con DIeta MEDiterránea ( PREDIMED ) trial . Individuals , aged 55 - 80 years at high cardiovascular risk , were r and omized to a MedDiet supplemented with extra-virgin olive oil , a MedDiet supplemented with nuts , or a low-fat diet . The present analysis was an observational cohort study nested in the trial . A vali date d food frequency question naire was used to assess dietary habits and olive oil consumption . Information on total osteoporotic fractures was obtained from a systematic review of medical records . The association between yearly repeated measurements of olive oil consumption and fracture risk was assessed by multivariate Cox proportional hazards . RESULTS We documented 114 incident cases of  osteoporosis-related fractures during a median follow-up of 8.9 years . Treatment allocation had no effect on fracture risk . Participants in the highest tertile of extra-virgin olive oil consumption had a 51 % lower risk of fractures ( HR:0.49 ; 95 % CI:0.29 - 0.81 . P for trend = 0.004 ) compared to those in the lowest tertile after adjusting for potential confounders . Total and common olive oil consumption was not associated with fracture risk . CONCLUSIONS Higher consumption of extra-virgin olive oil is associated with a lower risk of osteoporosis-related fractures in middle-aged and elderly Mediterranean population at high cardiovascular risk BACKGROUND AND AIMS Eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) found in fish oil are postulated to have favourable effects on platelet , endothelial and vascular function . We investigated whether EPA has differential effects on in vivo platelet aggregation and other markers of cardiovascular risk compared to DHA . METHODS AND RESULTS Following a 2 wk run-in taking encapsulated refined olive oil , 48 healthy young men were r and omly allocated using a parallel design to receive EPA-rich ( 3.1 g EPA/d ) or DHA-rich ( 2.9 g DHA/d ) triglyceride concentrates or refined olive oil ( placebo ) , for a total supplementary lipid intake of 5 g/d . The specified primary outcome was change in platelet monocyte aggregates ( PMA ) ; secondary outcomes were capillary density , augmentation index , digital pulse volume measurements , 24 h ambulatory BP , plasma 8-isoprostanes-F2α . Changes in the proportions of DHA and EPA  in erythrocytes and non-esterified fatty acid composition indicated compliance to the intervention . There was no significant treatment effect on PMA ( P = 0.382 ) ; mean changes ( % ) ( 95 % CI ) were placebo -0.5 ( -2.0 , 1.04 ) , EPA 0.4 ( -0.8 , 1.6 ) , DHA 0.3 ( -1.5 , 2.0 ) . R-QUICKI , an index of insulin sensitivity , was greater following EPA compared to placebo ( P < 0.05 ) . No other significant differences were noted . CONCLUSION Neither EPA- nor DHA-rich fish oil supplementation influence platelet-monocyte aggregation or several markers of vascular function after 6 wk in healthy young males . This trial was registered at clinical trials.gov as NCT01735357 Synthesizing evidence from r and omized controlled trials of  digital health education  poses some challenges . These include a lack of clear categorization of digital health education in the literature ; constantly evolving concepts , pedagogies , or theories ; and a multitude of methods , features , technologies , or delivery setting s. The Digital Health Education Collaboration was established to evaluate the evidence on digital education in health professions ; inform policymakers , educators , and students ; and ultimately , change the way in which these professionals learn and are taught . The aim of this paper is to present the overarching methodology that we use to synthesize evidence across our digital health education review s and to discuss challenges related to the process . For our research , we followed Cochrane recommendations for the conduct of systematic review s ; all review s are reported according to the PRISMA ( Preferred Reporting Items for Systematic Review s and Meta-Analyses ) guidance . This included assembling experts in various digital health education fields ; identifying gaps in the evidence base ; formulating focused research questions , aims , and outcome measures ; choosing appropriate search terms and data bases ; defining inclusion and exclusion criteria ; running the search es jointly with librarians and information specialists ; managing abstract s ; retrieving full-text versions of papers ; extracting and storing large data sets , critically appraising the quality of studies ; analyzing data ; discussing findings ; drawing meaningful conclusions ; and drafting research papers . The approach used for synthesizing evidence from digital health education trials is commonly regarded as the most rigorous benchmark for conducting systematic review s. Although we acknowledge the presence of certain biases ingrained in the process , we have clearly highlighted and minimized those biases by strictly adhering to scientific rigor , method ological integrity , and st and ard operating procedures . This paper will be a valuable asset for research ers and method ologists undertaking systematic review s in digital health education OBJECTIVES The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity . BACKGROUND Endothelial-dependent vasodilatation is impaired during the postpr and ial state , and oxidative stress could play a key role in its development . METHODS Twenty-one hypercholesterolemic volunteers received two breakfasts , using a r and omized sequential crossover design . Both arms received the same olive oil , but one had its phenolic acid content reduced from 400 to 80 ppm . Ischemic reactive hyperemia ( IRH ) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake . Postpr and ial plasma concentrations of lipid fractions , lipoperoxides ( LPO ) , 8-epi prostagl and in-F(2alpha ) , and nitrates/nitrites ( NO(x ) ) were obtained at baseline and after 2 h of the fat meal . RESULTS The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function , as well as a greater increase in concentrations of NO(x ) ( p < 0.001 ) and a lower increase in LPO ( p < 0.005 ) and 8-epi prostagl and in-F2alpha ( p < 0.001 ) than the ones induced by the low polyphenol fat meal . A positive correlation was found to exist between NO(x ) and enhanced endothelial function at the second hour ( r = 0.669 ; p < 0.01 ) . Furthermore , a negative correlation was found between IRH and LPO ( r = -0.203 ; p < 0.05 ) and 8-epi prostagl and in-F2alpha levels ( r = -0.440 ; p < 0.05 ) . CONCLUSIONS A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postpr and ial state . This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites BACKGROUND AND AIMS Obesity and physical inactivity are both associated with low- grade inflammation and endothelial dysfunction .  Bariatric surgery improves markers of inflammation and endothelial function , but it is unknown if physical training after bariatric surgery can improve these markers even further . Therefore , we aim ed to investigate the effects of Roux-en-Y gastric bypass ( RYGB ) followed by physical training on markers of low- grade inflammation and endothelial function . METHODS Sixty patients approved for RYGB underwent examinations pre-surgery , 6 , 12 , and 24 months post-surgery . Six months post-surgery , they were r and omized 1:1 to an intervention group or a control group . The interventions consisted of two weekly sessions of supervised moderate intensity physical training for a period of 26 weeks . Fasting blood sample s were analyzed for concentrations of interleukin 6 ( IL-6 ) , C-reactive protein ( CRP ) , intercellular adhesion molecule 1 ( ICAM-1 ) , tissue-type plasminogen activator antigen ( t-PA : Ag ) and von Willebr and factor ( vWF ) . RESULTS RYGB markedly improved markers of inflammation ( IL-6 , CRP ) ( p < 0.001 ) and endothelial function ( ICAM-1 , t-PA : Ag , vWF ) ( p < 0.05 ) , and the improvements were sustained 24 months post-surgery ( p < 0.01 ) , except for the effects on vWF . We found no correlations between the changes in weight or BMI and the changes in markers of inflammation and endothelial function , except that the change in vWF was found to be inversely correlated with the changes in weight and BMI . We observed no effects of supervised physical training on markers on inflammation or endothelial function ( p>0.1 for all ) . CONCLUSIONS RYGB causes substantial and sustained favorable effects on markers of inflammation and endothelial function .  Supervised physical training after RYGB did not cause additional improvements BACKGROUND Inflammation is crucial in all stages of atherosclerosis , and few studies have investigated the effect of dietary fat on markers of inflammation related to this disease during the postpr and ial period . OBJECTIVE To evaluate the chronic effects of dietary fat on the postpr and ial expression of proinflammatory genes in peripheral blood mononuclear cells ( P BMC s ) in healthy subjects . DESIGN 20 healthy men followed three different diets for 4 weeks each , according to a r and omized crossover design : Western diet : 15 % protein , 47 % carbohydrates ( CHO ) , 38 % fat ( 22 % saturated fatty acid ( SFA ) ) ; Mediterranean diet : 15 % protein , 47 % CHO , 38 % fat ( 24 % monounsaturated fatty acid ( MUFA ) ) ; CHO-rich and n-3 diet : 15 % protein , 55 % CHO , < 30 % fat ( 8 % polyunsaturated fatty acid ( PUFA ) ) . After 12-h fast , volunteers were given a breakfast with a fat composition similar to that consumed in each of the diets-butter breakfast : 35 % SFA ; olive oil breakfast : 36 % MUFA ; walnut breakfast : 16 % PUFA , 4 % alpha-linolenic acid ( LNA ) . RESULTS The butter breakfast induced a higher increase in tumor necrosis factor (TNF)-alpha messenger RNA ( mRNA ) expression than the olive oil or walnut breakfasts ( P=0.014 ) in P BMC s. Moreover , we found a higher postpr and ial response in the mRNA of interleukin (IL)-6 with the intake of butter and olive oil breakfasts than with the walnut breakfast ( P=0.025 ) in these cells . However , the effects of the three fatty breakfasts on the plasma concentrations of these proinflammatory parameters showed no significant differences ( P = N.S. ) . CONCLUSION Consumption of a butter-enriched meal elicits greater postpr and ial expression of proinflammatory cytokine mRNA in P BMC s , compared to the olive oil and walnut breakfasts Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 Inflammation is involved in cardiovascular diseases . Some studies have found that the Mediterranean diet ( MD ) can reduce serum concentrations of inflammation markers . However , none of these studies have analyzed the influence of genetic variability in such a response . Our objective was to study the effect of the -765G > C polymorphism in the cyclooxygenase-2 ( COX-2 ) gene and the -174G > C polymorphism in the interleukin-6 ( IL-6 ) gene on serum concentrations of IL-6 , C-reactive protein , intercellular adhesion molecule 1 ( ICAM-1 ) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD . An intervention study in a high cardiovascular risk Mediterranean population ( 314 men and 407 women ) was undertaken . Participants were r and omly assigned to consume a low-fat control diet or a MD supplemented with virgin olive oil or nuts . Measures were obtained at baseline and after a 3-mo intervention period . At baseline , the COX-2 -765G > C polymorphism was associated with lower serum IL-6 ( 5.85 + /- 4.82 in GG vs. 4.74 + /- 4.14 ng/L in C-allele carriers ; P = 0.002 ) and ICAM-1 ( 265.8 + /- 114.8 in GG vs. 243.0 + /- 107.1 microg/L in C-carriers ; P = 0.018 ) concentrations . These differences remained significant after multivariate adjustment . The IL-6 -174G > C polymorphism was associated with higher ( CC vs. G-carriers ) serum ICAM-1 concentrations in both men and women and with higher serum IL-6 concentrations in men . Following the dietary intervention , no significant gene x diet interactions were found . In conclusion , although COX-2 -765G > C and IL-6 -174G > C polymorphisms were associated with inflammation , consuming a MD ( either supplemented with virgin olive oil or nuts ) reduced the concentration of inflammation markers regardless of these polymorphisms The aim of the study was to assess whether benefits associated with the traditional Mediterranean diet ( TMD ) and virgin olive oil ( VOO ) consumption could be mediated through changes in the expression of atherosclerosis-related genes . A r and omized , parallel , controlled clinical trial in healthy volunteers ( n=90 ) aged 20 to 50 yr was performed . Three-month intervention groups were as follows : 1 ) TMD with VOO ( TMD+VOO ) , 2 ) TMD with washed virgin olive oil ( TMD+WOO ) , and 3 ) control with participants ' habitual diet . WOO was similar to VOO , but with a lower polyphenol content ( 55 vs. 328 mg/kg , respectively ) . TMD consumption decreased plasma oxidative and inflammatory status and the gene expression related with both inflammation [ INF-gamma ( INFgamma ) , Rho GTPase-activating protein15 ( ARHGAP15 ) , and interleukin-7 receptor ( IL7R ) ] and oxidative stress [ adrenergic beta(2)-receptor ( ADRB2 ) and polymerase ( DNA-directed ) kappa ( POLK ) ] in peripheral blood mononuclear cells . All effects , with the exception of the decrease in POLK expression , were particularly observed when VOO , rich in polyphenols , was present in the TMD dietary pattern . Our results indicate a significant role of olive oil polyphenols in the down-regulation of proatherogenic genes in the context of a TMD . In addition , the benefits associated with a TMD and olive oil polyphenol consumption on cardiovascular risk can be mediated through nutrigenomic effects A systematic review of the literature was performed to evaluate the role of exercise in treating rotator cuff impingement and to synthesize a st and ard evidence -based rehabilitation protocol . Eleven r and omized , controlled trials ( level 1 and 2 ) evaluating the effect of exercise in the treatment of impingement were identified . Data regarding demographics , methodology , and outcomes of pain , range of motion , strength , and function were recorded . Individual components of each rehabilitation program were catalogued . Effectiveness was determined by statistical and clinical significance . Although many articles had method ologic concerns , the data demonstrate that exercise has statistically and clinical ly significant effects on pain reduction and improving function , but not on range of motion or strength .  Manual therapy augments the effects of exercise  , yet supervised exercise was not different than home exercise programs . Information regarding specific components of the exercise programs was synthesized into a gold st and ard rehabilitation protocol for future studies on the nonoperative treatment of rotator cuff impingement Polyunsaturated fatty acid ( PUFA ) use in pregnancy has been promoted as beneficial for visual and neurobehavioural development in the fetus . However , no systematic review of the r and omized trials has been conducted . The objective of this review was to evaluate potential advantages of this regiment by review ing all r and omized trials in pregnancy . Methods . Systematic review of r and omized controlled studies comparing cognitive and visual achievements among infants whose mothers were treated and untreated with PUFA during gestation . Results . Nine studies met the inclusion criteria , three focusing on  visual and six on neurobehavioural development . Due to differing outcome measurements in the infants , the studies could not be combined into a formal meta- analysis . Synthesizing the existing data , for both visual and neurobehavioural development , most studies could not show sustained benefits to infant cognition or visual development . Conclusion . At the present time a recommendation to change practice and supplement all expecting mothers with PUFA  to improve offspring vision or neurobehavioural function is not supported by existing evidence In order to underst and the effect of endurance running on inflammation , it is necessary to quantify the extent to which acute and chronic running affects inflammatory mediators . The aim of this study was to summarize the literature on the effects of endurance running on inflammation mediators . Electronic search es were conducted on PubMED and Science Direct with no limits of date and language of publication . R and omized controlled trials ( RCTs ) and non-r and omized controlled trials ( N RCTs ) investigating the acute and chronic effects of running on inflammation markers in runners were review ed by two research ers for eligibility . The modified Downs and Black checklist for the assesssments of the method ological quality of studies was subsequently used . Fifty-one studies were finally included . There were no studies with elite athletes . Only two studies were chronic interventions . Results revealed that acute and chronic endurance running may affect anti- and pro-inflammatory markers but method ological differences between studies do not allow comparisons or generalization of the results . The information provided in this systematic review would help practitioners for better design ing further studies while providing reference values for a better underst and ing of inflammatory responses after different running events . Further longitudinal studies are needed to identify the influence of training load parameters on inflammatory markers in runners of different levels and training background Context Some experts attribute a low incidence of heart disease in Mediterranean countries to dietary habits . Contribution In this multicenter , 3-group trial , investigators r and omly assigned 772 adults at high risk for cardiovascular disease to a low-fat diet or to a Mediterranean diet supplemented with either virgin olive oil ( 1 L per week ) or nuts ( 30 g per day ) . After 3 months , the Mediterranean diet groups had lower mean plasma glucose level , systolic blood pressure , and total cholesterolhigh-density lipoprotein cholesterol ratio than the low-fat diet group . Caution s The Mediterranean diet groups received more nutritional education than the low-fat diet group . Implication s Mediterranean diets supplemented with olive oil or nuts may improve cardiovascular risk factors . The Editors Cardiovascular disease is the main cause of death in industrialized countries , but incidence rates have marked geographic differences . The low incidence of coronary heart disease ( CHD ) in Mediterranean countries has been partly ascribed to dietary habits ( 1 - 3 ) . Recent findings from large European cohort studies ( 4 - 6 ) suggest that a high degree of adherence to the Mediterranean diet is associated with a reduction in mortality . In small clinical studies , the Mediterranean diet or some of its components have reduced blood pressure ( 7 ) and have improved lipid profiles ( 8 , 9 ) and endothelial function ( 10 ) . Moreover , a recent cross-sectional study ( 11 ) and a 2-year feeding trial ( 12 ) have shown that adherence to the Mediterranean diet is associated with reduced markers of vascular inflammation . These beneficial effects on surrogate markers of cardiovascular risk add biological plausibility to the epidemiologic evidence that supports a protective effect of the Mediterranean diet . Olive oil , a rich source of monounsaturated fatty acids , is a main component of the Mediterranean diet . Virgin olive oil retains all the lipophilic components of the fruit , -tocopherol , and phenolic compounds with strong antioxidant and anti-inflammatory properties ( 13 , 14 ) . Tree nuts , which are also typical in the Mediterranean diet , have a favorable fatty acid profile and are a rich source of nutrients and other bioactive compounds that may beneficially influence the risk for CHD , such as fiber , phytosterols , folic acid , and antioxidants ( 15 ) . Frequent nut intake has been associated with decreased CHD rates in prospect i ve studies ( 15 ) . Walnuts differ from all other nuts through their high content of polyunsaturated fatty acids , particularly -linolenic acid , a plant n-3 fatty acid ( 16 ) , which may confer additional antiatherogenic properties ( 17 ) . Therefore , we design ed a large-scale feeding trial in high-risk participants to assess the effects of 2 Mediterranean diets , one supplemented with virgin olive oil and the other supplemented with mixed nuts , compared with a low-fat diet on cardiovascular outcomes . We report the results of a 3-month intervention on intermediate markers of cardiovascular risk in the first 772 participants who were recruited into the trial . Supplement . Original Version ( PDF ) Methods Study Design The Prevencin con Dieta Mediterrnea ( PREDIMED ) Study is a large , parallel-group , multicenter , r and omized , controlled , 4-year clinical trial that aims to assess the effects of the Mediterranean diet on the primary prevention of cardiovascular disease ( www.predimed.org ) . An estimated 9000 high-risk participants ( > 5000 participants are already recruited ) will be assigned to 3 interventions : Mediterranean diet with virgin olive oil , Mediterranean diet with mixed nuts , or low-fat diet . The main outcome is an aggregate of cardiovascular events ( cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke ) . The anticipated completion date of the trial is December 2010 . We design ed our present study to assess the 3-month effects of the dietary interventions on surrogate markers of cardiovascular risk in participants entering the study during the first 6 months of recruitment . The institutional review boards of the 10 participating centers approved the study protocol . Participants and Recruitment From October 2003 to March 2004 , we selected 930 potential participants in primary care centers affiliated with 10 teaching hospitals across Spain . Eligible participants were community-dwelling men , 55 to 80 years of age , and women , 60 to 80 years of age , who fulfilled at least 1 of 2 criteria : type 2 diabetes or 3 or more CHD risk factors ( current smoking , hypertension [ blood pressure > 140/90 mm Hg or treatment with antihypertensive drugs ] , low-density lipoprotein [ LDL ] cholesterol level 4.14 mmol/L [ 160 mg/dL ] [ or treatment with hypolipidemic drugs ] , high-density lipoprotein [ HDL ] cholesterol level 1.04 mmol/L [ 40 mg/dL ] , body mass index [ BMI ] 25 kg/m2 , or a family history of premature CHD ) . Exclusion criteria were history of cardiovascular disease , any severe chronic illness , drug or alcohol addiction , history of allergy or intolerance to olive oil or nuts , or low predicted likelihood of changing dietary habits according to the stages-of-change model ( 18 ) . The primary care physicians based participants ' eligibility on review of clinical records and a screening visit . They obtained a list of c and i date s from computer-based records of patients who attended each participating center and review ed their clinical records to exclude those who did not meet eligibility criteria . They then invited suitable c and i date s by telephone to attend a screening visit . The visit included an interview with administration of a 26-item question naire to inquire about medical conditions and risk factors related to eligibility . Of the eligible c and i date s who met entry requirements , 95 % agreed to participate and provided informed consent . R and omization and Intervention After the screening visit , each center r and omly assigned eligible participants to 1 of 3 diet groups by using a computer-generated r and om-number sequence . The coordinating center constructed the r and omization table , and participants were r and omly assigned into blocks of 50 participants balanced by center , sex , and age group ( < 70 years and 70 years ) . We concealed allocation into the intervention groups by using closed envelopes with correlative numbers by prespecified subgroups of sex and age . The baseline examination included the administration of a 14-item question naire , an extension of a previously vali date d question naire ( 19 ) , that assessed the degree of adherence to the traditional Mediterranean diet . We assigned values of 0 or 1 to each item ( Appendix Table 1 ) . We also administered a 137-item vali date d food frequency question naire ( 20 ) ; the vali date d Spanish version ( 21 ) of the Minnesota Leisure Time Physical Activity Question naire ; and a 47-item question naire about education , lifestyle , history of illnesses , and medication use . We performed anthropometric and blood pressure measurements and obtained sample s of fasting blood and spot urine . We repeated all examinations at 3 months . The same dietitian delivered the interventions to the 3 r and omized groups in each center . On the basis of the assessment of individual Mediterranean diet scores , the dietitian gave personalized dietary advice during a 30-minute session to each participant , with recommendations on the desired frequency of intake of specific foods . We advised participants who were allocated to the low-fat diet to reduce intake of all types of fat , and we gave them a leaflet with written recommendations according to the American Heart Association guidelines ( 22 ) . For total fat intake , these recommendations were opposite to those given to participants in the 2 Mediterranean diet groups , who received instructions intended to increase the 14-item Mediterranean diet score , including increased consumption of vegetable fats and oils . We did not suggest any energy restriction . While the participants who were allocated to the low-fat diet did not receive further intervention , those assigned the 2 Mediterranean diet groups had access to more intense intervention in 2 ways . First , they were given a free provision of typical Mediterranean fatty foods ( olive oil or nuts ) . Depending on group assignment , participants were given either free virgin olive oil ( 15 L [ 1 L/wk ] for 3 months ) or free sachets of walnuts , hazelnuts , and almonds ( 1350 g of walnuts [ 15 g/d ] , 675 g of hazelnuts [ 7.5 g/d ] , and 675 g of almonds [ 7.5 g/d ] for 3 months ) . To improve adherence and account for family needs , participants in the corresponding Mediterranean diet groups were given excess olive oil or additional 1000-g packets of nuts . We analyzed the nutrient composition of the olive oil and nuts used in the study by st and ard methods in a reference laboratory ( Appendix Table 2 ) ) . Second , 1 week after inclusion , the dietitian delivered a 1-hour group session with up to 20 participants , with separate sessions for each Mediterranean diet group . Each group session consisted of informative talks and provision of written material s with elaborate descriptions of typical Mediterranean foods and seasonal shopping lists , meal plans , and cooking recipes . Throughout the study , all participants had free and continuous access to their center dietitian for advice and consultation . Measurements Trained personnel measured weight and height by using calibrated scales and a wall-mounted stadiometer , respectively ; waist circumference midway between the lowest rib and the iliac crest by using an anthropometric tape ; and blood pressure in triplicate with a vali date d semiautomatic oscillometer ( Omron HEM-705CP , Hoofddorp , the Netherl and s ) . We calculated energy and nutrient intake from Spanish food composition tables ( 23 ) . At the 3-month visit and when consulted by participants , dietitians assessed any adverse effects from the interventions by administering a checklist of symptoms and gave advice on how to remedy them . The checklist included mouth symptoms ; bloating , fullness , or indigestion ; altered bowel BACKGROUND AND AIMS To compare the effects of n-3 long chain polyunsaturated fatty acids ( n-3 LCPUFA ) , with those of fenofibrate , on markers of inflammation and vascular function , and on the serum lipoprotein profile in overweight and obese subjects . METHODS AND RESULTS Twenty overweight and obese subjects participated in a r and omized , double-blind , placebo-controlled intervention trial and received 3.7 g/d n-3 fatty acids ( providing 1.7 g/d EPA and 1.2 g/d DHA ) , 200 mg fenofibrate or placebo treatment for 6 weeks separated by a 2 weeks wash-out period . Fish oil and fenofibrate treatment reduced triglyceride ( -0.61 ± 0.81 mmol/L , P < 0.001 , and -0.34 ± 0.85 mmol/L , P = 0.048 , respectively ) and increased HDL cholesterol concentrations ( 0.13 ± 0.21 mmol/L , P = 0.013 , and 0.10 ± 0.18 mmol/L , P = 0.076 ) , as reflected by a decrease of large very VLDL particles and increases of large HDL particles and medium size HDL particles . Fish oil increased serum LDL cholesterol concentrations ( 0.34 ± 0.59 mmol/L , P = 0.013 ) . Fenofibrate reduced concentrations of soluble endothelial selectin ( sE-selectin ) ( -4.1 ± 7.5 ng/mL , P = 0.032 ) , but increased those of macrophage chemoattractant protein 1 ( MCP1 ) ( 28 ± 55 ng/mL , P = 0.034 ) . Fish oil had no effects on these markers . CONCLUSION Although n-3 LCPUFA and fenofibrate can both activate PPARα , they have differential effects on cardiovascular risk markers . In overweight and obese subjects fenofibrate ( 200 mg/d ) or n-3 LCPUFA ( 3.7 g/d ) treatment for 6 weeks did not improve markers for low- grade systemic inflammation , while fenofibrate had more profound effects on plasma lipids and markers for vascular activity compared to fish oil . Registration number clinical trials EudraCT 2006 - 005743 - 28 This study investigated whether subjects with permanent activated endothelium have altered soluble forms of intercellular adhesion molecule 1 ( sICAM-1 ) and vascular cell adhesion molecule 1 ( sVCAM-1 ) postpr and ial response to a high-fat meal and whether this phenomenon is modulated by the nature of dietary fats . Twenty-eight hypertriglyceridemic ( 14 normotensives and 14 hypertensives ) and 14 healthy male subjects were placed in a r and omized and crossover design on diets enriched in refined olive oil ( ROO ) or high-palmitic sunflower oil ( HPSO ) for a 1-week lead-in period . Thereafter , subjects ate the corresponding fat-rich meal as a breakfast and underwent sampling hourly for 8 h. Plasma triglycerides ( TG ) , sICAM-1 and sVCAM-1 were assayed . sICAM-1 and sVCAM-1 postpr and ial peak levels were significantly higher and occurred later in hypertriglyceridemic subjects ( all P<.001 ) compared with healthy subjects . ROO meal result ed in smaller areas under the curve for sICAM-1 and sVCAM-1 in hypertriglyceridemic ( normotensive and hypertensive ) and healthy subjects compared to HPSO meal . Hypertension did not aggravate the postpr and ial response of TG , sICAM-1 and sVCAM-1 . We conclude that the challenge of a meal with ROO appears to have a significant postpr and ial benefit on sICAM-1 and sVCAM-1 as surrogate markers of endothelial activation and vascular inflammation in healthy and more importantly in hypertriglyceridemic ( normotensive and hypertensive ) subjects Summary . Background : Evidence from in vitro studies suggests that antioxidant olive oil phenolic compounds can prevent LDL oxidation . However , in vivo evidence in support of this hypothesis is sparse . Aim of the study : to establish the antioxidant effect of olive oils with differences in their phenolic compounds content in humans Methods : A controlled , double blind , cross-over , r and omized , clinical trial using three similar olive oils with increasing phenolic concentration ( from 0 to 150 mg/Kg ) was conducted in 30 healthy volunteers .  Olive oils were administered over three periods of 3 weeks preceded by two-week washout periods . Results : Urinary tyrosol and hydroxytyrosol increased ( p < 0.020 ) , in vivo plasma oxidized LDL decreased ( p = 0.006 ) , and ex vivo resistance of LDL to oxidation increased ( p = 0.012 ) with the phenolic content of the olive oil administered . After virgin olive oil administration , an increase ( p = 0.029 ) was observed in HDL cholesterol levels . Conclusions : Sustained consumption of virgin olive oil with the high phenolic content was more effective in protecting LDL from oxidation and in rising HDL cholesterol levels than that of other type of olive oils . Dose-dependent changes in oxidative stress markers , and phenolic compounds in urine , were observed with the phenolic content of the olive oil administered . Our results support the hypothesis that virgin olive oil consumption could provide benefits in the prevention of oxidative processes BACKGROUND Many observational studies support the recommendation to eat sufficient amounts of fruit and vegetables as part of a healthy diet . OBJECTIVE The present study aim ed to investigate the association between consumption of fruit , vegetables , and olive oil and the incidence of coronary heart disease ( CHD ) in 29,689 women enrolled between 1993 and 1998 in 5 European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohorts in northern ( Turin and Varese ) , central ( Florence ) , and southern ( Naples and Ragusa ) Italy . DESIGN Baseline dietary , anthropometric , and lifestyle characteristics were collected . Major events of CHD ( fatal and nonfatal myocardial infa rct ion and coronary revascularization ) were identified through a review of clinical records . Analyses were stratified by center and adjusted for hypertension , smoking , education , menopause , physical activity , anthropometric measures , nonalcohol energy , alcohol , total meat , vegetables in analyses for fruit , and fruit in analyses for vegetables . RESULTS During a mean follow-up of 7.85 y , 144 major CHD events were identified . A strong reduction in CHD risk among women in the highest quartile of consumption of leafy vegetables ( hazard ratio : 0.54 ; 95 % CI : 0.33 , 0.90 ; P for trend = 0.03 ) and olive oil ( hazard ratio : 0.56 ; 95 % CI : 0.31 , 0.99 ; P for trend = 0.04 ) was found . In contrast , no association emerged between fruit consumption and CHD risk . CONCLUSION An inverse association between increasing consumption of leafy vegetables and olive oil and CHD risk emerged in this large cohort of Italian women
These results provide evidence that olive oil might exert beneficial effects on endothelial function as well as markers of inflammation and endothelial function , thus representing a key ingredient contributing to the cardiovascular-protective effects of a Mediterranean diet .
The aim of the present systematic review was to synthesize data from r and omized controlled trials investigating the effects of olive oil on markers of inflammation or endothelial function .