A Meta-Epidemiological Study of Positive Results in Clinical Nutrition Research: The Good, the Bad and the Ugly of Statistically Significant Findings.

Positive (statistically significant) findings are easily produced in nutrition research when specific aspects of the research design and analysis are not accounted for. To address this issue, recently, a pledge was made to reform nutrition research and improve scientific trust on the science, encompass research transparency and achieve reproducibility. The aim of the present meta-epidemiological study was to evaluate the statistical significance status of research items published in three academic journals, all with a focus on clinical nutrition science and assessing certain methodological/transparency issues. All research items were published between the years 2015 and 2019. Study design, primary and secondary findings, sample size and age group, funding sources, positivist findings, the existence of a published research protocol and the adjustment of nutrients/dietary indexes to the energy intake (EI) of participants, were extracted for each study. Out of 2127 studies in total, those with positive findings consisted of the majority, in all three journals. Most studies had a published research protocol, however, this was mainly due to the randomized controlled trials and not to the evidence-synthesis studies. No differences were found in the distribution of positive findings according to the existence/inexistence of a published research protocol. In the pooled sample of studies, positive findings differed according to study design and more significant findings were reported by researchers failing to report any funding source. The majority of items published in the three journals (65.9%) failed to account for the EI of participants. The present results indicate that there is still room for the improvement of nutrition research in terms of design, analyses and reporting.

Effect of Moderate Wine Consumption on Oxidative Stress Markers in Coronary Heart Disease Patients.

Evidence from research studies reports that wine consumption is associated with lower cardiovascular disease risk, partly through the amelioration of oxidative stress. The aim of the present study was to examine the effect of regular light to moderate wine consumption from coronary heart disease (CHD) patients compared to the effect induced by alcohol intake without the presence of wine microconstituents, on oxidation-induced macromolecular damage as well as on endogenous antioxidant enzyme activity. A randomized, single-blind, controlled, three-arm parallel intervention was carried out, in which 64 CHD patients were allocated to three intervention groups. Group A consumed no alcohol, and Group B (wine) and Group C (ethanol) consumed 27 g of alcohol/day for 8 weeks. Blood and urine samples were collected at baseline and at 4 and 8 weeks. Urine oxidized guanine species levels, protein carbonyls, thiobarbituric acid substances (TBARS) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were measured. Oxidized guanine species and protein carbonyl levels were significantly increased in the ethanol group during the intervention and were significantly decreased in the wine group. These results support the idea that wine's bioactive compounds may exert antioxidant actions that counteract the macromolecular oxidative damage induced by alcohol in CHD patients.

Development of a DHA-Losartan hybrid as a potent inhibitor of multiple pathway-induced platelet aggregation.

Despite the scientific progression in the prevention and treatment of cardiovascular diseases (CVDs) they remain the leading cause of mortality and disability worldwide. The classic treatment involves the simultaneous dosing of two antiplatelet drugs, aspirin and clopidogrel/prasugrel. However, besides drug resistance, severe side effects have been also manifested including acute bleeding and toxicity. Thus, new therapeutic agents with enhanced efficacy and diminished side effects are of importance. Towards this end, omega-3 (ω-3) fatty acids have demonstrated potent efficacy against CVDs through inhibiting platelet aggregation that bears a pivotal role in atherothrombosis. Another factor that displays a critical role in the pathogenesis of cardiovascular diseases is the renin-angiotensin system (RAS), and especially the AT1R blocker losartan that has been reported to exert antiplatelet activity mediated by this receptor. Along these lines, we envisaged developing a molecular hybrid consisted of docosahexaenoic acid (ω-3 fatty acid) and losartan, that could exert a notable antiplatelet effect against CVDs. The design and synthesis of the new DHA-losartan hybrid, designated DHA-L, bestowed with the additive properties of the parent compounds, is reported. In silico studies were first exploited to validate the potential of DHA-L to retain losartan's ability to bind AT1R. The antiplatelet activity of DHA-L was evaluated against in vitro platelet aggregation induced by several platelet agonists. Notably, the hybrid illustrated a pleiotropic antiplatelet profile inhibiting platelet aggregation through multiple platelet activation pathways including P2Y12, PAR-1 (Protease-Activated Receptor-1), PAF (Platelet Activating Factor), COX-1 (cyclooxygenase-1) and collagen receptors. The stability of DHA-L in human plasma and in a wide range of pH values was also evaluated over time using an HPLC protocol. The hybridization approach described herein could pave the way for the development of novel potent multitargeted therapeutics with enhanced antiplatelet profile.Communicated by Ramaswamy H. Sarma.

Postprandial Metabolic and Oxidative Stress Responses to Grape Pomace Extract in Healthy Normal and Overweight/Obese Women: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

Postprandial oxidative stress has been shown to promote atherosclerosis. Grape pomace (GP) is a source of similar-to-wine bioactive micro-constituents with known antioxidant properties. The aim of the present study was to evaluate metabolic and oxidative stress responses after the intake of grape pomace (GP) extract along with a high-fat meal, in normal and overweight healthy women. In a randomized, double-blind, placebo-controlled crossover study, 18 women were finally included, 11 with BMI < 25 kg/m2 and 7 with BMI > 25 kg/m2, and consumed a high-fat meal with placebo or GP extract capsules in two separate visits. Blood samples were collected before and 6 h after the consumption. Measurements included basic biochemical markers, uric acid (UA), protein carbonyls (PC), thiobarbituric acid substance (TBARS) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. At certain time points, the GP extract consumption in normal-weight women reduced UA, TBARS levels, and SOD activity, whereas it increased UA and reduced PC levels in overweight/obese women, compared to the placebo. GP-derived bioactive compounds may exert antioxidant actions during the postprandial state in healthy women, through different mechanisms according to their BMI status.

Evaluation of Anti-Inflammatory, Anti-Platelet and Anti-Oxidant Activity of Wine Extracts Prepared from Ten Different Grape Varieties.

Inflammation, thrombosis and oxidative stress are rarely studied together when wine's biological activity is concerned; hence the existing literature lacks a holistic point of view in the biological outcome. The scope of the present study is to parallel evaluate the effect of wine extracts on those mechanisms. Ten wine varieties and two different extraction methods were used leading to five extracts for each wine: total lipids (TL) and fractions with different phenolic compound classes (FI, FII, FIII and FIV). Their effect on oxidative stress, platelet aggregation and the secretion of cytokines from mononuclear cells was measured and a biological score was calculated. FII of white wines is the most potent extract and the extracts FIII and TL are following. Specifically, FII had higher anti-oxidant and anti-inflammatory score while all three fractions had a similar anti-platelet score. Furthermore, FII and FIII extracts were the most potent red wine extracts and revealed the highest anti-oxidant and anti-inflammatory scores. White wine FII extracts were more potent than the red wine ones while FI and FIV extracts of red wine were more potent than the white wine ones. In conclusion, the protective effect of a wine is independent of its color but is strongly associated with its microconstituents profile. FII extract revealed the highest biological score and further examination is needed in order to identify the compounds that are responsible for the aforementioned actions.

Evaluation of anti-platelet activity of grape pomace extracts.

Platelets aggregation plays a crucial role in atherothrombosis. Therefore, the aim of the present study was to examine the anti-platelet activity of winery by-products extracts, to find the most potent one and to be further analyzed in order to be used for food fortification. For this purpose, grape pomace from four red varieties was extracted with four solvents of different polarity. The extracts' phenolic content, antioxidant capacity and their ability to inhibit human platelet aggregation against PAF, ADP, TRAP were determined by Light Transmission Aggregometry. The ethanolic extract was further analyzed concerning its anti-platelet effect and its chemical composition by LC-MS/MS and GC-MS. The ethanolic and Bligh-Dyer water phase extracts showed the highest phenolic compounds/anthocyanin content and the best antioxidant activity. However, the most potent inhibition of platelet aggregation was revealed by ethanol extracts, followed by the Bligh-Dyer lipoid phase extracts. Ethanolic extract, found to contain micro-constituents such as phospho-compounds, phenolic compounds and fatty acids. The most abundant phenolic compounds were catechin, epicatechin and quercetin and the most abundant fatty acids were linoleic acid (C18:2n6), linolenic acid (C18:3n3) and palmitic acid (C16:0). Ethanolic extract was capable of inhibiting platelets aggregation in a wide range of agonist concentrations and it also seems that its action is sustained when platelets from coronary heart disease patient were used. Ethanol extract of winery by-products exerts a potent anti-platelet effect and its valorization could lead to the production of functional foods with cardioprotective properties.

Suppression of DNA/RNA and protein oxidation by dietary supplement which contains plant extracts and vitamins: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Excessive oxidative stress may impair bio-molecules and cellular function. Multi antioxidant supplementation is thought to be more effective than a single antioxidant probably through the synergistic or complementary action of natural substances that could enhance the prospective effect. METHODS: In order to estimate the effect of a plant extract based supplement in apparently healthy volunteers' oxidative stress markers, a double-blind and placebo controlled intervention was performed. 62 apparently healthy volunteers, overweight with medium adherence to the Mediterranean diet, were recruited and randomly allocated into two intervention groups (supplement or placebo) for 8 weeks. Basic biochemical markers, oxidized LDL (oxLDL), resistance of serum in oxidation, protein carbonyls in serum and 8-isoprostane and DNA/RNA damage in urine were measured. RESULTS: No differentiation was observed in basic biochemical markers, in oxLDL levels as well as in serum resistance against oxidation, during intervention in the examined groups. A significant resistance regarding urine isoprostanes levels in the supplement group compared to the placebo one, was observed. Reduction on DNA/RNA damage and on protein carbonyls levels (almost 30% and 20% respectively, at 8 weeks) was detected in volunteers who consumed the supplement compared to the control group. CONCLUSION: Consumption of plant extract based supplement seems to reduce DNA/RNA and protein oxidation and in less extent lipids peroxidation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier for this study is: NCT02837107.

Wine and its metabolic effects. A comprehensive review of clinical trials.

The introduction of the term "French Paradox" motivated an extensive and in-depth research into health benefits of moderate wine consumption. The superiority of wine is thought to be attributed to its micro-constituents and consequent effort was made to isolate and identify these bioactive compounds as well as to elucidate the mechanisms of their action. Controlled trials offer more concrete answers to several raised questions than observational studies. Under this perspective, clinical trials have been implemented, mainly in healthy volunteers and rarely in patients, in order to investigate the acute or chronic effect of wine consumption on metabolism and physio-pathological systems, which are mainly associated with cardiovascular diseases. The aim of this review is to update the knowledge about the acute and long term effect of wine consumption on lipid and glucose/insulin metabolism as well as on the inflammatory and haemostatic systems, based on the reported data of controlled clinical trials. In conclusion, the most repeated result of wine consumption is on lipid metabolism, attributed mainly to ethanol, while wine micro-constituents seem to have an important role mainly in haemostatic and inflammatory/endothelial systems.