Antonio Garcia-Rios

Mediterranean diet reduces endothelial damage and improves the regenerative capacity of endothelium

BACKGROUND Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Activation or injury of the endothelium leads to a variety of inflammatory disorders, including the release of microparticles. Endothelial progenitor cells may contribute to the maintenance of the endothelium by replacing injured mature endothelial cells. OBJECTIVE We studied the influence of dietary fat on the release of endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) in elderly subjects. DESIGN Twenty healthy, elderly subjects (10 men and 10 women) consumed 3 diets following a randomized crossover design, each for 4 wk: a saturated fatty acid diet; a low-fat, high-carbohydrate diet; and a Mediterranean diet (MedDiet) enriched in monounsaturated fatty acids. We investigated total microparticles, EMPs from activated endothelial cells (activated EMPs), EMPs from apoptotic endothelial cells (apoptotic EMPs), EPCs, oxidative stress variables, and ischemic reactive hyperemia (IRH). RESULTS The MedDiet led to lower total microparticle, activated EMP, and apoptotic EMP concentrations and higher EPC numbers than did the other diets (P < 0.001). We detected lower superoxide dismutase activity (P < 0.001), a higher plasma β-carotene concentration (P < 0.001), and lower urinary isoprostane and plasma nitrotyrosine concentrations after consumption of the MedDiet than after consumption of the other 2 diets (P < 0.05). Furthermore, the occurrence of IRH was higher after consumption of the MedDiet than after consumption of the other 2 diets (P < 0.05). CONCLUSION Consumption of the MedDiet induces a reduction in endothelial damage and dysfunction, which is associated with an improvement in the regenerative capacity of the endothelium, in comparison with 2 other diets.

Mediterranean Diet Rich in Olive Oil and Obesity, Metabolic Syndrome and Diabetes Mellitus

After decades of epidemiological, clinical and experimental research, it has become clear that consumption of Mediterranean dietary patterns rich in olive oil has a profound influence on health outcomes, including obesity, metabolic syndrome (MetS) and diabetes mellitus. Traditionally, many beneficial properties associated with this oil have been ascribed to its high oleic acid content. Olive oil, however, is a functional food that, besides having high-monounsaturated (MUFA) content, contains other minor components with biological properties. In this line, phenolic compounds have shown antioxidant and antiinflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Research into the pharmacological properties of the minor components of olive oil is very active and could lead to the formulation of functional food and nutraceuticals. Although more data are mandatory the Mediterranean diet rich in olive oil does not contribute to obesity and appears to be a useful tool in the lifestyle management of the MetS. Moreover there is good scientific support for MUFA diets, especially those based on olive oil, as an alternative approach to low-fat diets for the medical nutritional therapy in diabetes. The objective of this review is to present evidence illustrating the relationship between Mediterranean diet, olive oil and metabolic diseases, including obesity, MetS and diabetes mellitus and to discuss potential mechanisms by which this food can help in disease prevention and treatment.

Association between the APOA2 promoter polymorphism and body weight in Mediterranean and Asian populations: replication of a gene-saturated fat interaction.

Objective:The APOA2 gene has been associated with obesity and insulin resistance (IR) in animal and human studies with controversial results. We have reported an APOA2–saturated fat interaction determining body mass index (BMI) and obesity in American populations. This work aims to extend our findings to European and Asian populations.Methods:Cross-sectional study in 4602 subjects from two independent populations: a high-cardiovascular risk Mediterranean population (n=907 men and women; aged 67±6 years) and a multiethnic Asian population (n=2506 Chinese, n=605 Malays and n=494 Asian Indians; aged 39±12 years) participating in a Singapore National Health Survey. Anthropometric, clinical, biochemical, lifestyle and dietary variables were determined. Homeostasis model assessment of insulin resistance was used in Asians. We analyzed gene–diet interactions between the APOA2 −265T>C polymorphism and saturated fat intake (<or ⩾22 g per day) on anthropometric measures and IR.Results:Frequency of CC (homozygous for the minor allele) subjects differed among populations (1–15%). We confirmed a recessive effect of the APOA2 polymorphism and replicated the APOA2–saturated fat interaction on body weight. In Mediterranean individuals, the CC genotype was associated with a 6.8% greater BMI in those consuming a high (P=0.018), but not a low (P=0.316) saturated fat diet. Likewise, the CC genotype was significantly associated with higher obesity prevalence in Chinese and Asian Indians only, with a high-saturated fat intake (P=0.036). We also found a significant APOA2–saturated fat interaction in determining IR in Chinese and Asian Indians (P=0.026).Conclusion:The influence of the APOA2 −265T>C polymorphism on body-weight-related measures was modulated by saturated fat in Mediterranean and Asian populations.

Postprandial oxidative stress is modified by dietary fat: evidence from a human intervention study.

Previous evidence supports the concept that increased oxidative stress may play an important role in MetS (metabolic syndrome)-related manifestations. Dietary fat quality has been proposed to be critical in oxidative stress and the pathogenesis of the MetS. In the present study, we investigated whether oxidative stress parameters are affected by diets with different fat quantity and quality during the postprandial state in subjects with the MetS. Patients were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality for 12 weeks: a high-saturated-fatty-acid (HSFA) diet, a high-mono-unsaturated-fatty-acid (HMUFA) diet and two low-fat/high-complex carbohydrate diets [supplemented with 1.24 g/day of long-chain n-3 polyunsaturated fatty acid (LFHCC n-3) or with 1 g/day of sunflower oil high in oleic acid (LFHCC) as placebo]. The HMUFA diet enhanced postprandial GSH (reduced glutathione) levels and the GSH/GSSH (oxidized glutathione) ratio, compared with the other three diets. In addition, after the HMUFA-rich diet postprandial lipid peroxide levels, protein carbonyl concentrations, SOD (superoxide dismutase) activity and plasma H2O2 levels were lower compared with subjects adhering to the HSFA-rich diet. Both LFHCC diets had an intermediate effect relative to the HMUFA and HSFA diets. In conclusion, our data support the notion that the HMUFA diet improves postprandial oxidative stress in patients with the MetS. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with mono-unsaturated dietary fat, particularly in subjects with the MetS.

Dietary fat differentially influences regulatory endothelial function during the postprandial state in patients with metabolic syndrome: from the LIPGENE study.

OBJECTIVE To investigate whether endothelium-dependent vasomotor function and plasma levels of cellular adhesion molecules are affected by diets with different fat quantity and quality during the postprandial state in subjects with the metabolic syndrome (MetS). METHODS Patients were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality: high-SFA (HSFA); high-MUFA (HMUFA) and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with 1.24g/day of long chain n-3 PUFA (LC n-3 PUFA) or placebo for 12 weeks each. Flow-associated vasodilatation of the brachial artery and postprandial plasma levels of total nitrites, nitric oxide (NO) synthase, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and P-selectin were assessed post-intervention. RESULTS Post-intervention postprandial flow-associated vasodilatation was significantly higher after the HMUFA diet (P<0.05) compared to subjects adhering to the other three diets. Consistently, the postprandial NO synthase response significantly increased during the HMUFA compared with the HSFA and LFHCC (placebo) diets. Postprandial sICAM-1 levels were lower during the HMUFA than during the HSFA and LFHCC n-3 diets. CONCLUSIONS Our data support the notion that the HMUFA diet improves postprandial endothelial cell function and decreases postprandial plasma sICAM-1 concentrations in patients with the MetS. These findings suggest that the postprandial state is important for understanding possible cardio-protective effects associated with the Mediterranean diet particularly in subject with the MetS.

Dietary fat modifies the postprandial inflammatory state in subjects with metabolic syndrome: the LIPGENE study

SCOPE Our aim was to investigate whether the inflammatory state associated to metabolic syndrome (MetS) patients is affected by diets with different fat quality and quantity. METHODS AND RESULTS Seventy-five subjects from LIPGENE cohort were included in this feeding trial and randomly assigned to one of four diets: high saturated fatty acids (HSFA); high monounsaturated fatty acids (HMUFA) and two low-fat, high complex carbohydrate (LFHCC) diets, supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12 weeks each. A postprandial fat challenge, reflecting the intervention dietary fat composition, was conducted post-intervention. The HMUFA diet significantly reduced postprandial nuclear transcription factor-kappaB (NF-kB) activity and the nuclear p65 protein levels relative to fasting values (p < 0.05). Furthermore, we observed a postprandial decrease in this protein with the HMUFA diet compared with the HSFA and LFHCC diets (p < 0.05). The postprandial response of inhibitory molecule from NF-kB mRNA levels increased with the HMUFA diet compared with the HSFA and LFHCC n-3 diets (p < 0.05). Postprandial tumor necrosis factor-α and Metalloproteinase 9 mRNA levels were also reduced after the HMUFA diet compared with the HSFA diet (p < 0.05). CONCLUSION Our results indicate that the long-term consumption of a healthy diet model with HMUFA attenuates the postprandial inflammatory state associated with MetS.

Consumption of diets with different type of fat influences triacylglycerols-rich lipoproteins particle number and size during the postprandial state☆

BACKGROUND AND AIMS Previous evidence suggests that dietary fat could influence the composition and size of triacylglycerols-rich lipoproteins (TRL). In a controlled intervention study on healthy subjects, we evaluated the influence of 3 dietary interventions, with different types of fat on postprandial TRL particle size and number. METHODS AND RESULTS Volunteers followed three different diets for four weeks each, according to a randomized 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)); high CHO enriched with ALNA diet: 15% protein, 55% CHO, <30% fat (8% polyunsaturated fatty acid (PUFA)). After a 12-h fast, volunteers consumed a breakfast with 1g fat and 7 mg cholesterol per kg body weight and a fat composition similar to that consumed in each of the diets: Butter meal: 35% SFA; Olive oil meal: 36% MUFA; Walnut meal: 16% PUFA, 4% α-linolenic acid. Tryglicerides (TG) in TRL (large and small TRL) were determined by ultracentrifugation and size and number of lipoprotein particles were measured with Nuclear Magnetic Resonance Spectroscopy at different time points. The olive oil meal reduced the number of total TRL postprandial particles compared with the other meals (P=0.002). Moreover, the olive oil meal also increased the TRL particle size compared with the walnut meal (P=0.001). CONCLUSION Our data showed that short-term intake of the Mediterranean diet and the acute intake of an olive oil meal lead to the formation of a reduced number and higher-size TRL particle compared with other fat sources. These novel findings have implications for understanding the postprandial lipoprotein mechanisms, and could favour the lower cardiovascular risk in Mediterranean countries.

Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men

The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism, we studied the effects of nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism. Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 -2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886 (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples were extracted for 11 h after the meal. Total cholesterol and fractions [HDL-cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma concentration during this state. APOC3 -640 was associated with altered TG kinetics but not its magnitude. We have identified new associations between SNPs in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.

Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: From the LIPGENE study

AIMS/HYPOTHESIS Variants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR). METHODS Fasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS. RESULTS Several single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure. CONCLUSIONS/INTERPRETATION SNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.

Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.