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To conduct a systematic review of the literature on the scientific evidence of the oral intake of omega-3 and omega-6 FAs and metabolic syndrome (MS) in adolescents.The study was registered in PROSPERO (number 42020185370). Studies were carried out with adolescents aged 10-19 years, who presented as intervention/exposure the oral intake of omega-3 and/or omega-6 fatty acids (FAs), in the databases PubMed, Scopus, Web of Science, LILACS, CENTRAL, and PQDT Global e BDTD. The tools used to assess the risk of bias were RoB 2.0, Agency for Healthcare Research and Quality (AHRQ), and Newcastle-Ottawa Scale. Fifteen papers retrieved published from 2010 to 2019 were included (n = 3534); nine were randomized studies and controlled clinical trials, four were cross-sectional studies, one was a retrospective cohort study, and one case-control study. No studies have evaluated the effect or association of omega-3 and/or of omega-6 FAs with actual MS, only with its components. The randomized clinical trials identified the effects of omega-3 FA on the decrease in blood pressure (n = 1 out of six), glycemia (n = 2 out of seven), and triglycerides (n = 5 out of eight), and the increase in HDL-c (n = 2 out of eight) considering the comparison between the group that received omega-3 FA and the control group.Scientific evidence is controversial on the association between oral intake of omega-3 FAs and MS in adolescents, due to the heterogeneity between studies and the divergence of results for the same MS component.

Aims To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. Data synthesis During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. Conclusions It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident.

Aims: Long-term clinical trials evaluating the effects of metabolic-bariatric surgery (MBS) on type 2 diabetes (T2D) demonstrate that a significant proportion of patients either fail to achieve remission or experience T2D recurrence over time. Furthermore, patients with recurrent T2D might require reinstitution of pharmacotherapy to control comorbidities (hypertension, dyslipidemia). This paper reviews therapeutic options in patients with T2D relapse. Data synthesis: Although presently there is no recommended pharmacological strategy, the available data support GLP-1 analogues (GLP-1a) as the most suitable option to control hyperglycemia post-MBS. Beside their efficacy in lowering glycemia and body weight while preserving lean mass, GLP-1a exert cardiovascular/renal-protection and are also safe and well tolerated in surgical patients. In addition, the s.c. route of administration of these medications circumvents the problem of changes in oral drugs bioavailability following MBS. Of note, the available data refers to liraglutide and needs to be confirmed with weekly GLP-1a agents. Information regarding the impact of MBS on the pharmacokinetics of lipid lowering and anti-hypertensive drugs is scarce and inconclusive. The findings indicate that timing from intervention is particularly important because of adaptive intestinal mechanisms. Conclusions: The recurrence of T2D following MBS is a clinically relevant issue. GLP-1a therapy represents the best option to improve glycemic and weight control with good tolerability. Long-term clinical trials will clarify the impact of these drugs on cardiovascular outcomes. A close monitoring of MBS patients is advised to guide drug dosage adjustments and ensure the control of cardiovascular risk factors.

Background & aims The effect of pasta consumption within a low-energy Mediterranean diet on body weight regulation has been scarcely explored. This paper investigates the effect of two Mediterranean diets, which differed for lower or higher pasta intake, on body weight change in individuals with obesity. Methods & Results Forty-nine volunteers finished a quasi-experimental 6-month two–parallel group dietary intervention. Participants were assigned to a low-energy high pasta (HP) or to a low-energy low Pasta (LP) group on the basis of their pasta intake (HP ≥ 5 or LP ≤ 3 times/week). Anthropometrics, blood pressure and heart rate were measured every month. Weight maintenance was checked at month 12. Body composition (bioelectrical impedance analysis, BIA), food intake (24-h recall plus a 7-day carbohydrate record) and the perceived quality of life (36-item short-form health survey, SF-36) were assessed at baseline, 3 and 6 months. Blood samples were collected at baseline and month 6 to assess glucose and lipid metabolism. After 6-month intervention, body weight reduction was −10 ± 8% and −7 ± 4% in HP and LP diet, respectively, and it remained similar at month 12. Both dietary interventions improved anthropometric parameters, body composition, glucose and lipid metabolism, but no significant differences were observed between treatment groups. No differences were observed for blood pressure and heart rate between treatments and among times. HP diet significantly improved perception of quality of life for the physical component. Conclusions Independent of pasta consumption frequency, low-energy Mediterranean diets were successful in improving anthropometrics, physiological parameters and dietary habits after a 6-month weight-loss intervention. This trial was registered at clinicaltrials.gov as NCT03341650.

Aims Dietary pattern (DP) analysis has emerged as a holistic method to understand the effects of food intake on health outcomes. Though dietary intake has been associated with cardiovascular disease, the association of DPs and carotid intima-media thickness (CIMT), a robust early marker of cardiovascular disease progression has not been comprehensively investigated. This study systematically explores the association of a posteriori and a priori DPs and CIMT. Data synthesis Through a systematic search of MEDLINE, CINAHL, and Web of Science, twenty studies that derived DPs using a posteriori or a priori methods with CIMT as an outcome were included. Four cross-sectional studies and 1 cohort paper reported a statistically significant association between increased consumption of ‘unhealthy’ foods (i.e processed meat, soda drinks and refined grain) and increased CIMT. While four cross-sectional studies reported a statistically significant association of DPs characterized by increased consumption of ‘healthy’ foods (i.e fruit and vegetables, fish) and decreased CIMT. DPs derived from each study varied depending on derivation method, study design and use of dietary data collection method. Conclusion Findings from this review are generally supportive of a trend between DPs with higher consumption of ‘healthy’ foods and lower consumption of ‘unhealthy’ foods and decreased CIMT; however, the association was largely not statistically significant. Evidence was overwhelmingly heterogeneous due to differences seen in DPs based on location and culture, sample characteristics and adjustment for confounders. Long-term prospective observational and interventional studies with standardized sample selection and dietary data collection are needed to significantly establish the role of DPs on CIMT.

Aims This review aimed at investigating fruit, vegetable and legume consumption, salt/sodium intake, and the adherence to the Mediterranean dietary pattern in adolescents, three key aspects towards the adoption of a healthy diet. Data synthesis Three separate searches were carried out on PubMed and Scopus, using the same procedure, searching for studies published in the previous decade with data on fruit and/or vegetable or legume consumption, salt or sodium intake, and adherence to the Mediterranean Diet assessed using the KIDMED questionnaire. The review included a total of 58 papers, which describe original investigations on healthy adolescents (10–19 years old) living in North America, Europe or Oceania, with a sample size >150 participants. The average fruit and vegetable consumption has been found strongly below the recommended values of 400 grams or 5 portions per day in almost all the examined populations. Very little is known about adolescents' legume consumption. Few available data have been found also for sodium intake and, for the majority of the screened populations, levels were far above the recommended 5 grams per day. Lastly, a medium–low adherence to the Mediterranean Diet has been found for adolescents living in Mediterranean Countries. Conclusions Adolescents living in North America, Europe or Oceania are far from being compliant with the nutritional recommendations for fruit, vegetables, legumes, and sodium, and they do not follow the principles of the Mediterranean Diet. Educational and behavioural interventions are required to improve adolescents' dietary patterns.

Aims To determine whether oral antioxidant therapies, of various types and doses, are able to prevent or treat women with preeclampsia. Data synthesis The following databases were searched: MEDLINE, CENTRAL, LILACS, and Web of Science. Inclusion criteria were: a) randomized clinical trials; b) oral antioxidant supplementation; c) study in pregnant women; d) control group, treated or not with placebo. Papers were excluded if they evaluated antioxidant nutrient supplementation associated with other non-antioxidant therapies. Data were extracted and the risk of bias of each study was assessed. Heterogeneity was analyzed using the Cochran Q test, and I2 statistics and pre-specified sensitivity analyses were performed. Meta-analyses were conducted on prevention and treatment studies, separately. The primary outcome was the incidence of preeclampsia in prevention trials, and of perinatal death in treatment trials. Twenty-nine studies were included in the analysis, 19 for prevention and 10 for treatment. The antioxidants used in these studies were vitamins C and E, selenium, l -arginine, allicin, lycopene and coenzyme Q10, none of which showed beneficial effects on the prevention of preeclampsia (RR: 0.89, CI 95%: [0.79–1.02], P = 0.09; I2 = 39%, P = 0.04) and other outcomes. The antioxidants used in the treatment studies were vitamins C and E, N-acetylcysteine, l -arginine, and resveratrol. A beneficial effect was found in intrauterine growth restriction. Conclusions Antioxidant therapy had no effects in the prevention of preeclampsia but did show beneficial effects in intrauterine growth restriction, when used in the treatment of this condition.

Olive oil is the foremost source of fat in the Mediterranean area and, among other features, sets the Mediterranean diet apart from other dietary regimens. In January 2018, the International Olive Council convened several worldwide experts at the Robert Mondavi Institute (Davis, CA), to discuss and summarize the available data on the effects of olive oil consumption on human health. In this paper, we critically provide a synthesis of the main reported findings, which underscore how and why consuming this oil as part of a balanced diet and healthful lifestyle improves prognosis and extends life- and health-spans.

Background and aims: Increasing the intake of potassium has been shown to lower blood pressure, but whether it also affects heart rate (HR) is largely unknown. We therefore assessed the effect of potassium supplementation on HR in a meta-analysis of randomized controlled trials.Methods and results: We searched PubMed (1966-October 2014) for randomized, placebo-controlled trials in healthy adults with a minimum duration of two weeks in which the effect of increased potassium intake on HR was assessed. In addition, reference lists from meta-analysis papers on potassium and blood pressure were hand-searched for publications. Two investigators independently extracted the data. We performed random effects meta-analyses, subgroup and meta-regression analyses for characteristics of the study (e.g. design, intervention duration, potassium dose and salt type, change in potassium excretion, sodium excretion during intervention) and study population (e.g. gender, age, hypertensive status, pre-study HR, pre-study potassium excretion). A total of 22 trials (1086 subjects), with a median potassium dose of 2.5 g/day (range: 0.9-4.7 g/day), and median intervention duration of 4 weeks (range: 2 -24 weeks) were included. The meta-analysis showed no overall effect of increased potassium intake on HR (0.19 bpm, 95% CI: -0.44, 0.82). Stratified analyses yielded no significant effects of potassium intake on HR in subgroups, and there was no evidence for a dose-response relationship in meta-regression analyses.Conclusion: A chronic increase in potassium intake with supplemental doses of 2-3 g/day is unlikely to affect HR in apparently healthy adults. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Background and aims Plant sterols (PS) lower plasma LDL-cholesterol through partial inhibition of intestinal cholesterol absorption. Although PS themselves are poorly absorbed, increased intakes of PS result in elevated plasma concentrations. In this paper, we report time curves of changes in plasma PS during 12 weeks of PS intake. Furthermore, the impact of cholesterol synthesis and absorption on changes in plasma PS is explored. Methods and results The study was a double-blind, randomized, placebo-controlled, parallel-group study with the main aim to investigate the effects of PS on vascular function (clinicaltrials.gov: NCT01803178 ). Hypercholesterolemic but otherwise healthy men and women (n = 240) consumed low-fat spreads without or with added PS (3 g/d) for 12 weeks after a 4-week run-in period. Blood sampling was performed at week 0, 4, 8 and 12. Basal cholesterol-standardized concentrations of lathosterol and sitosterol + campesterol were used as markers of cholesterol synthesis and absorption, respectively. In the PS group, plasma sitosterol and campesterol concentrations increased within the first 4 weeks of intervention by 69% (95%CI: 58; 82) starting at 7.2 μmol/L and by 28% (95%CI: 19; 39) starting at 11.4 μmol/L, respectively, and remained stable during the following 8 weeks. Placebo-corrected increases in plasma PS were not significantly different between high and low cholesterol synthesizers (P-values >0.05). Between high and low cholesterol absorbers, no significant differences were observed, except for the cholesterol-standardized sum of four major plasma PS (sitosterol, campesterol, brassicasterol and stigmasterol) showing larger increases in low absorbers (78.3% (95%CI: 51.7; 109.5)) compared to high absorbers (40.8% (95%CI: 19.9; 65.5)). Conclusions Increases in plasma PS stabilize within 4 weeks of PS intake and do not seem impacted by basal cholesterol synthesis or absorption efficiency. This study was registered at clinicaltrials.gov ( NCT01803178 ).

Background and aims The deregulation of neurohormonal systems, including the natriuretic peptide (NP) and endothelin (ET) systems, may increase the possibility of developing obesity-related risk. The aim of our paper was to evaluate ET system mRNA variation in heart of the Zucker rat model together with the simultaneous evaluation of the NP system transcriptomic profile. In order to analyze the link between the ET-1 system and the inflammatory process, the cardiac expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α was also measured. Methods and results Zucker rats of 11–13 weeks were subdivided into obese rats (O, n = 20) and controls (CO, n = 20): half of them were studied under fasting conditions (CO fc –O fc ) and the remainder after the induction of acute hyperglycemia (CO AH –O AH ). Cardiac mRNA expression of TNF-α, IL-6, and NP/ET-1 systems was evaluated by Real-Time polymerase chain reaction. No significant difference for pre-proET-1, ET-A, and ET-B mRNA expression was detected between O and CO, whereas significantly lower mRNA levels of the ECE-1 were observed in O ( p = 0.02). Regarding NPs, only BNP mRNA expression decreased significantly in O with respect to CO ( p = 0.01). A down-regulation of NPR-B and NPR-C and an up-regulation of NPR-A were observed in O. No significant difference for IL-6 and TNF-α mRNA was revealed. Subdividing into fasting and hyperglycemic rats, many of the genes studied maintained their mRNA expression pattern almost unchanged. Conclusions The modulation of ET-1/NP systems in obesity could be a useful starting point for future studies aimed at identifying new therapeutic strategies for the treatment of cardiometabolic syndrome.

Aims The purpose of this paper is to provide a general framework for thinking about pathways and potential mechanisms through which complementary feeding may influence the risk of developing non-communicable diseases (NCDs). Data synthesis To provide a context for the lack of clear and consistent evidence relating complementary feeding to NCD risk, methodological challenges faced in trying to develop an evidence base are described. Potential pathways through which complementary feeding may influence obesity-related NCD risk are described and illustrated with examples. Conclusions Numerous aspects of complementary feeding, including diet composition as well as patterns of feeding have the potential to influence the early development of obesity, which in turn predicts later obesity and NCD risk. Specific dietary exposures during the period of complementary feeding also have the potential to program future disease risk through pathways that are independent of adiposity. These factors all require consideration when making recommendations for optimal complementary feeding practices aimed at prevention of future NCDs.

Glutathione peroxidase-1 (GPx-1) is an endogenous anti-oxidant enzyme. The T allele of the GPx-1 rs1050450 (C > T) gene variant is associated with reduced enzyme activity. Our aim was to examine the association between this gene variant and peripheral neuropathy in two cross-sectional samples of subjects with diabetes: (i) 773 Caucasian subjects were genotyped from the UCL Diabetes and Cardiovascular disease Study (UDACS) and (ii) 382 Caucasian subjects from the Ealing Diabetes Study (EDS). Peripheral neuropathy status (and oxidised-LDL [Ox-LDL:LDL] and plasma Total Ant-ioxidant Status [TAOS] in UDACS), were analysed in relation to genotype. We observed that: (i) In UDACS, the odds ratio (OR) for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.61 [1.10-2.28], p = 0.01. This remained significant after adjustment for other risk factors. Ox-LDL:LDL ratio was significantly elevated in T allele carriers (CC vs. CT/TT: 16.3 ± 2.4 v 18.0 ± 2.9 U/mmol LDL, p = 0.02). (ii) In EDS, the OR for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.95 [1.11-3.42], p = 0.02. This remained significant after adjustment for other risk factors. In conclusion, we observed a significant association between the T allele and peripheral neuropathy and LDL oxidation. This is the first paper to examine the rs1050450 variant in two samples of Caucasian subjects with diabetes. Prospective analysis of the gene variant is required in diabetic and healthy cohorts with measured plasma markers of oxidative stress to investigate the described association further.

The metabolic syndrome (MS) represents a cluster of cardiovascular (CV) risk factors associated to CV disease and type 2 diabetes. It is still under debate whether MS is a mere aggregation of risk factors or it represents a clinical entity with visceral obesity as underlying pathophysiological trigger. The publication of several diagnostic criteria of MS by scientific associations or experts panels reflects this uncertainty in understanding the real nature of MS. Besides the metabolic disturbances of MS, as visceral obesity, hypertriglyceridemia, low HDL cholesterol, hypertension and hyperglycemia, novel mechanisms of arterial damage have been identified. This paper reviews the evidence showing that MS and MS factors are characterized by increased oxidative stress, a relevant factor contributing to the development of metabolic and cardiovascular complications. In the next future, the measure of plasma oxidative stress may contribute to identify a subset of MS patients at increased CV risk, candidates to more intensive therapies.

Background and aim The recent interest in the development of evidence-based nutrition recommendations has resulted in the development of frameworks which enable a more structured evaluation of the link between diet and chronic disease. This paper examines the application of the frameworks produced by the Scottish Intercollegiate Guidelines Network (SIGN) and the World Cancer Research Fund (WCRF), by using as a case study the association between trans unsaturated fatty acids (TFAs) and coronary heart disease. TFAs arise during industrial hydrogenation of vegetable or fish fats and oils and the natural digestion process in ruminant animals. Data synthesis Numerous studies have examined the effects of TFA intake on serum lipids and lipoproteins and the association between TFA consumption and cardiovascular disease. Metabolic studies and meta-analyses show a clear and consistent association between increasing TFA intakes and an adverse lipid profile. Evidence from case–control and prospective cohort studies examining the association between TFA intakes and coronary heart disease is more heterogeneous and there are limitations in several of the studies. Conclusion While the evidence is sufficient to suggest a probable positive association between TFAs and coronary heart disease, and thus to justify a firm recommendation for a reduction in dietary TFA intake, the evaluation of the data underlines the difficulties in extrapolating the principles of evidence-based medicine to evidence-based nutrition. Furthermore, there is a paucity of research into the effects of animal-derived TFAs in amounts typically consumed in a western diet and their association with adverse lipid profiles or cardiovascular outcomes.

Diabetic dyslipidaemia contributes to the increased risk of cardiovascular disease in patients with Type 2 diabetes. This paper examines the effectiveness of adding pioglitazone to metformin or a sulphonylurea (SU) compared with a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia in patients with Type 2 diabetes.Patients (n=250) treated with metformin (or =3g/day) or an SU as monotherapy at a stable dose foror =3 months were randomised to receive either pioglitazone (15-30 mg/day) in addition to their metformin or SU, or a fixed-dose combination tablet containing metformin (400mg) and glibenclamide (2.5 mg) [up to 3 tablets daily] for 6 months. Addition of pioglitazone tended to increase plasma high-density lipoprotein-cholesterol (HDL-C) [0.04 mmol/L; P=0.051] at 6 months and significantly reduced plasma triglycerides (-0.25 mmol/L; P=0.013) compared with baseline. Patients treated with metformin/glibenclamide for 6 months had reduced HDL-C (-0.09 mmol/L; P0.01) and no change in plasma triglyceride levels (0.03 mmol/L; P=0.733). Both treatment regimes resulted in a similar level of glycaemic control.The beneficial effects of pioglitazone on diabetic dyslipidaemia may help combat the increased cardiovascular morbidity and mortality observed in patients with Type 2 diabetes while providing stable glycaemic control.

Objective MIAMI was a prospective multicenter clinical study designed to investigate the relationship between changes in carotid intima-media thickness (C-IMT) and those in the levels of circulating markers of inflammation, thrombosis and endothelial dysfunction. The study was performed in a group of stable coronary patients treated for two years with a moderate dosage of atorvastatin (20 mg/day). In this paper the cross-sectional relationship between C-IMT and the same circulating markers of inflammation, thrombosis and endothelial dysfunction measured at baseline was investigated. Methods Eighty-five subjects that had not used statins for at least two months were enrolled in the study. At time of enrollment, the levels of vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), tissue factor (TF), tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), fibrinogen, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), and triglycerides were measured, in parallel with C-IMT assessment. Results In cross-sectional analyses, markers of endothelial perturbation (i.e. E-selectin) and TFPI were more strongly correlated with arherosclerotic burden than markers of inflammation. The baseline picture in this study indicates that E-selectin and TFPI are linked with atherosclerotic burden.

Summary Aim Homocysteine (Hcy), a sulfur-containing amino acid product of methionine metabolism, may play an important role in the development of cardiovascular disease. In this paper we review available knowledge on the pathways leading to synthesis and degradation of Hcy, as well as on the genetic and environmental factors affecting its plasma levels, focussing on its potential role in the development of coronary heart disease. Data synthesis Hyperhomocysteinemia (HHcy) is determined by genetic and environmental factors and represents a modifiable cardiovascular risk factor since vitamin supplementation has been shown to effectively lower plasma homocysteine levels. While case-control and cross-sectional studies consistently showed an association of HHcy with cardiovascular disease, prospective studies have given conflicting results. Thus, the role of HHcy in the development of coronary heart disease is still under debate. Furthermore, it remains unclear which patients should be screened for HHcy and treated to correct HHcy. Conclusions Available information collectively suggests that although HHcy can be regarded as a minor risk factor for coronary heart disease, it interacts with other risk factors in triggering new events in patients with known CAD. Thus, the treatment of mild HHcy with folate supplementation is appropriate in particular in high risk patients or patients with established CAD who do not present with the “traditional” risk factors.