Mediterranean Diet, Energy Restriction, Physical Activity, and Atherogenicity of Very-Low Density Lipoproteins: Findings from Two Randomized Controlled Trials.

SCOPE: Some very-low density lipoprotein (VLDL) properties may render them more pro-atherogenic. We aimed to assess whether a Mediterranean diet (MedDiet) or an energy-reduced MedDiet with increased physical activity improves them. METHODS AND RESULTS: In a sample of the PREvención con DIeta MEDiterránea (PREDIMED) study, a 1-year intervention with MedDiet with extra-virgin olive oil (n = 89) or nuts (MedDiet-Nuts; n = 79) is compared with a low-fat diet (n = 90). In the PREDIMED-Plus study, a 1-year intervention with energy-reduced MedDiet and physical activity (n = 103) is compared with an ad libitum MedDiet (n = 101). VLDL levels of apolipoprotein C-I, C-III, triglycerides, and cholesterol; the apolipoprotein E-/C-I ratio; and VLDL ex-vivo triglyceride transfer are measured. In PREDIMED participants in both MedDiet groups combined, VLDL apolipoprotein C-III levels are nominally reduced (-0.023 SD units, 95% CI -0.44 to -0.014, p = 0.037). VLDL triglyceride transfer is nominally increased in the MedDiet-Nuts group (+0.39 SD units, 95% CI 0.012-0.78, p = 0.045). In PREDIMED-Plus, no inter-group differences are detected. CONCLUSIONS: In older adults at high cardiovascular risk, MedDiet is associated with lower VLDL atherogenicity versus a low-fat diet. No differences are seen after an energy-reduced MedDiet with physical activity.

Modification of High-Density Lipoprotein Functions by Diet and Other Lifestyle Changes: A Systematic Review of Randomized Controlled Trials.

High-density lipoprotein (HDL) functional traits have emerged as relevant elements that may explain HDL antiatherogenic capacity better than HDL cholesterol levels. These properties have been improved in several lifestyle intervention trials. The aim of this systematic review is to summarize the results of such trials of the most commonly used dietary modifications (fatty acids, cholesterol, antioxidants, alcohol, and calorie restriction) and physical activity. Articles were screened from the Medline database until March 2021, and 118 randomized controlled trials were selected. Results from HDL functions and associated functional components were extracted, including cholesterol efflux capacity, cholesteryl ester transfer protein, lecithin-cholesterol acyltransferase, HDL antioxidant capacity, HDL oxidation status, paraoxonase-1 activity, HDL anti-inflammatory and endothelial protection capacity, HDL-associated phospholipase A2, HDL-associated serum amyloid A, and HDL-alpha-1-antitrypsin. In mainly short-term clinical trials, the consumption of monounsaturated and polyunsaturated fatty acids (particularly omega-3 in fish), and dietary antioxidants showed benefits to HDL functionality, especially in subjects with cardiovascular risk factors. In this regard, antioxidant-rich dietary patterns were able to improve HDL function in both healthy individuals and subjects at high cardiovascular risk. In addition, in randomized trial assays performed mainly in healthy individuals, reverse cholesterol transport with ethanol in moderate quantities enhanced HDL function. Nevertheless, the evidence summarized was of unclear quality and short-term nature and presented heterogeneity in lifestyle modifications, trial designs, and biochemical techniques for the assessment of HDL functions. Such findings should therefore be interpreted with caution. Large-scale, long-term, randomized, controlled trials in different populations and individuals with diverse pathologies are warranted.

A lifestyle intervention with an energy-restricted Mediterranean diet and physical activity enhances HDL function: a substudy of the PREDIMED-Plus randomized controlled trial.

BACKGROUND: Consumption of a Mediterranean diet, adequate levels of physical activity, and energy-restricted lifestyle interventions have been individually associated with improvements in HDL functions. Evidence of intensive interventions with calorie restriction and physical activity is, however, scarce. OBJECTIVES: To determine whether an intensive lifestyle intervention with an energy-restricted Mediterranean diet plus physical activity enhanced HDL function compared to a non-hypocaloric Mediterranean eating pattern without physical activity. METHODS: In 391 older adults with metabolic syndrome (mean age, 65 years; mean BMI, 33.3 kg/m2) from 1 of the Prevención con Dieta Mediterránea-Plus trial centers, we evaluated the impact of a 6-month intervention with an energy-restricted Mediterranean diet plus physical activity (intensive lifestyle; n = 190) relative to a nonrestrictive Mediterranean diet without physical activity (control; n = 201) on a set of HDL functional traits. These included cholesterol efflux capacity, HDL oxidative/inflammatory index, HDL oxidation, and levels of complement component 3, serum amyloid A, sphingosine-1-phosphate, triglycerides, and apolipoproteins A-I, A-IV, C-III, and E in apoB-depleted plasma. RESULTS: The intensive-lifestyle intervention participants displayed greater 6-month weight reductions (-3.83 kg; 95% CI: -4.57 to -3.09 kg) but no changes in HDL cholesterol compared with control-diet participants. Regarding HDL functional traits, the intensive lifestyle decreased triglyceride levels (-0.15 mg/g protein; 95% CI: -0.29 to -0.014 mg/g protein) and apoC-III (-0.11 mg/g protein; 95% CI: -0.18 to -0.026 mg/g protein) compared to the control diet, with weight loss being the essential mediator (proportions of mediation were 77.4% and 72.1% for triglycerides and apoC-III levels in HDL, respectively). CONCLUSIONS: In older adults with metabolic syndrome, an energy-restricted Mediterranean diet plus physical activity improved the HDL triglyceride metabolism compared with a nonrestrictive Mediterranean diet without physical activity. This trial is registered at isrctn.com as ISRCTN89898870.

Dietary Polyphenol Intake is Associated with HDL-Cholesterol and A Better Profile of other Components of the Metabolic Syndrome: A PREDIMED-Plus Sub-Study.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus.

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini-Hochberg-adjusted p-value were >1.30 and their absolute z-scores were >2.0 (≥2.0 meant "upregulation" and ≤ -2.0 "downregulation"). Cancer signaling pathways were the most upregulated ones in T2D (z-score = 2.63, -log(p-value) = 32.3; 88.5% (n = 906) of the total differentially expressed genes located in these pathways). In particular, integrin (z-score = 2.52, -log(p-value) = 2.03) and paxillin (z-score = 2.33, -log(p-value) = 1.46) signaling pathways were predicted to be upregulated, whereas the Rho guanosine diphosphate (Rho-GDP) dissociation inhibitor signaling pathway was predicted to be downregulated in T2D individuals (z-score = -2.14, -log(p-value) = 2.41). Our results suggest that, at transcriptional expression level, elderly individuals with T2D present an increased activation of signaling pathways related to neoplastic processes, T-cell activation and migration, and inflammation.

Increased Consumption of Virgin Olive Oil, Nuts, Legumes, Whole Grains, and Fish Promotes HDL Functions in Humans.

SCOPE: To evaluate whether increases in the consumption of cardioprotective food groups (virgin olive oil, nuts, fruits/vegetables, legumes, whole grains, fish, and wine) are associated with improvements in high-density lipoprotein (HDL) functions in high cardiovascular risk subjects. METHODS AND RESULTS: The association between 1-year changes in food group consumption and HDL functionality traits in 296 high cardiovascular risk subjects is assessed. Increases in virgin olive oil (10 g d-1 ) and whole grain consumption (25 g d-1 ) are associated with increments in cholesterol efflux capacity (+0.7%, P = 0.026, and +0.6%, P = 0.017, respectively). Increases in nut (30 g d-1 ) and legume intake (25 g d-1 ) are linked to increments in paraoxonase-1 activity (+12.2%, P = 0.049, and +11.7%, P = 0.043, respectively). Legume intake increases are also related to decreases in cholesteryl ester transfer protein activity (-4.8%, P = 0.028). Fish consumption increments (25 g d-1 ) are associated with increases in paraoxonase-1 activity (+3.9%, P = 0.030) and declines in cholesteryl ester transfer protein activity (-1.6%, P = 0.021), HDL cholesterol concentrations (-1.1%, P = 0.039), and functions related to HDL levels (cholesterol efflux capacity, -1.1%, P = 0.010). CONCLUSION: Increases in the consumption of virgin olive oil, nuts, legumes, whole grains, and fish (achievable through a regular diet) were associated with improvements in HDL functions in high cardiovascular risk subjects.

Cross-sectional associations of objectively-measured sleep characteristics with obesity and type 2 diabetes in the PREDIMED-Plus trial.

Study Objectives: To examine independent and combined associations of sleep duration and sleep variability with body composition, obesity and type 2 diabetes (T2D) in elders at high cardiovascular risk. Methods: Cross-sectional analysis of 1986 community-dwelling elders with overweight/obesity and metabolic syndrome from PREDIMED-Plus trial. Associations of accelerometry-derived sleep duration and sleep variability with body mass index (BMI), waist circumference (WC) and body composition were assessed fitting multivariable-adjusted linear regression models. Prevalence ratios (PR) and 95% confidence intervals (CI) for obesity and T2D were obtained using multivariable-adjusted Cox regression with constant time. "Bad sleepers" (age-specific non-recommended sleep duration plus sleep variability above the median) and "good sleepers" (age-specific recommended sleep duration plus sleep variability below the median) were characterized by combining sleep duration and sleep variability, and their associations with these outcomes were examined. Results: One hour/night increment in sleep duration was inversely associated with BMI (ß -0.38 kg/m2 [95% CI -0.54, -0.23]), WC (ß -0.86 cm [95% CI -1.25, -0.47]), obesity (PR 0.96 [95% CI 0.93, 0.98]), T2D (PR 0.93 [95% CI 0.88, 0.98]) and other DXA-derived adiposity-related measurements (android fat and trunk fat, all p < .05). Each 1-hour increment in sleep variability was positively associated with T2D (PR 1.14 [95% CI 1.01, 1.28]). Compared with "good sleepers," "bad sleepers" were positively associated with obesity (PR 1.12 [95% CI 1.01, 1.24]) and T2D (PR 1.62 [95% CI 1.28, 2.06]). Conclusions: This study revealed cross-sectional associations of sleep duration with adiposity parameters and obesity. Sleep duration and sleep variability were associated with T2D. Considering simultaneously sleep duration and sleep variability could have additional value, particularly for T2D, as they may act synergistically.