Background: Diet is considered the cornerstone of lipid management in hyperlipidemic children but evidence to demonstrate the effects of nutrient benefits on the lipid profile is limited. Aim: The aim of this study is to evaluate the impact of the Mediterranean diet on low-density lipoprotein (LDL-C) and non-high density lipoprotein (HDL-C) decrease in primary hyperlipidemia affected children and in the achievement of therapeutical target levels. Methods: A retrospective cohort study was used, recruiting n = 223 children (10.05 ± 3.26 mean age years) with familial hypercholesterolemia (FH) (n = 61, 27%) and polygenic hypercholesterolemia (PH) (n =162, 73%). Secondary hyperlipidemias were excluded. Based on LDL-C and non-HDL-C decrease, participants were divided into two groups, named the Responder Group and Non-Responder Group. Participants and their families underwent dietary education by an expert nutritionist and were asked to fill in a weekly diary to be delivered at visits. Dietary indications were in line with daily caloric requirement, daily food quality and quantity intakes typical of the Mediterranean diet. These include carbohydrates, extra virgin olive oil, yoghurt and milk derivatives, fish and vegetable proteins, fresh seasonal vegetables and fresh fruits. Nuts or almonds were also recommended. The advice to limit intakes of meat, in particular red meat, and caution against junk food and sugar added food and beverages was provided. At medical visits, carried out at baseline (T0) and 6 months later (T1), children underwent anthropometric measurements and blood collection. Standard kits and methods were applied for lipid analysis. Statistical methods were performed by SAS version 9.4 (SAS Institute, Cary, NC, USA). Signed informed consent was given by parents according to the Declaration of Helsinki and the study was approved by the Local Committee. Results: The Responder Group (n = 156/223, 70%) included 45 FH and 111 PH children, while the Non-Responder Group (n = 67/223, 30%) included 16 FH and 51 PH children. The Responder Group showed total cholesterol (TC), LDL-C and non-HDL-C median percentage decreases of 9.45, 13.51 and 10.90, respectively. These statistically significant changes (p ≤ 0.0001) were similar in the FH and PH subgroups but just PH subjects reached the LDL-C and non-HDL-C target, which fell below 130 mg/dL and 145 mg/dL, respectively. Saturated fatty acids (SFAs) were the main dietary parameter that distinguished between the Responder Group and the Non-Responder Group (p = 0.014). Positive correlations were found at T1 between dietary total lipids, SFAs and cholesterol with serum LDL-C, non-HDL-C and TC variations. These latter serum parameters had an inverse correlation with dietary carbohydrate at T1. Among macronutrients, SFAs were finally demonstrated to be the predictor of serum lipids variation at T1. Conclusions: The dietary intervention with a Mediterranean diet in children with primary hyperlipidemia significantly improves the lipid profile both in FH and PH subgroups and allows target levels of LDL-C and non-HDL-C in PH subjects to be reached. Responsiveness benefits should be primarily attributed to the reduction in SFAs, but changes in dietary lipids, cholesterol and carbohydrate intake may also play a role. In contrast, the Non-Responder Group showed a worsening of lipid profile regarding the unchanged diet. Full article

Lifestyle management is the first line of treatment for moderately elevated blood lipids in healthy individuals. We investigated the effectiveness of providing food-based written advice for lowering low-density lipoprotein (LDL) cholesterol (intervention) or triglycerides (control) in a pragmatic randomized controlled trial with two parallel arms from 2018–2019 at a rural primary health care center. We sent feedback letters after 3 weeks and 6 months. Out of the 113 adult primary care patients randomized, 112 completed the study. There were no differences between the intervention and control groups for changes in LDL cholesterol after 3 weeks (mean ± standard deviation −0.21 ± 0.38 vs. −0.11 ± 0.34 mmol/L, p = 0.45) or 6 months (−0.05 ± 0.47 vs. 0.02 ± 0.41 mmol/L, p = 0.70) (primary outcome). Following the advice to consume plant sterols and turmeric was associated with a reduction in LDL cholesterol after 3 weeks. Following the advice to consume less carbohydrates was associated with reduced triglycerides. In the intervention arm, 14 individuals (25%) reduced their LDL cholesterol by ≥10% after three weeks. Their reduction was attenuated but maintained after six months (−7.1 ± 9.2% or −0.31 ± 0.38 mmol/L, p = 0.01 compared with baseline). They differed only in higher adherence to the advice regarding turmeric. In conclusion, this undemanding intervention had little effect on blood lipids for most individuals. Full article

Advanced glycation end products (AGEs) result from a non-enzymatic reaction of proteins with reactive carbohydrates. Heat-processed food, such as bread, contains high amounts of AGEs. The activation of the NF-κB signaling pathway by bread crust extract (BCE) is well understood. However, it is largely unknown whether NRF2, the master regulator of oxidative stress resistance in mammalian cells, is affected by BCE. We have investigated the molecular mechanisms by which BCE induces antioxidant gene expression in cellular models. Our data showed that soluble extracts from bread crust are capable of stimulating the NRF2 signaling pathway. Furthermore, NRF2 pathway activation was confirmed by microarray and reporter-cell analyses. QRT-PCR measurements and Western blot analyses indicated an induction of antioxidative genes such as HMOX1, GCLM and NQO1 upon BCE treatment. Moreover, BCE pretreated cells had a survival advantage compared to control cells when exposed to oxidative stress. BCE induces phosphorylation of AKT and ERK kinase in EA.hy926 cells. By mass spectrometry, several new, potentially active modifications in BCE were identified. Our findings indicate that BCE activates NRF2-dependent antioxidant gene expression, thus provoking a protection mechanism against oxidative stress-mediated tissue injury. Hence, BCE can be considered as functional food with antioxidative and cardioprotective potential. Full article

We examined the associations of dietary cholesterol and egg intakes with cardiometabolic and all-cause mortality among Chinese and low-income Black and White Americans. Included were 47,789 Blacks, 20,360 Whites, and 134,280 Chinese aged 40–79 years at enrollment. Multivariable Cox models with restricted cubic splines were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes using intakes of 150 mg cholesterol/day and 1 egg/week as the references. Cholesterol intake showed a nonlinear association with increased all-cause mortality and a linear association with increased cardiometabolic mortality among Black Americans: HRs (95% CIs) associated with 300 and 600 mg/day vs. 150 mg/day were 1.07 (1.03–1.11) and 1.13 (1.05–1.21) for all-cause mortality (P-linearity = 0.04, P-nonlinearity = 0.002, and P-overall < 0.001) and 1.10 (1.03–1.16) and 1.21 (1.08–1.36) for cardiometabolic mortality (P-linearity = 0.007, P-nonlinearity = 0.07, and P-overall = 0.005). Null associations with all-cause or cardiometabolic mortality were noted for White Americans (P-linearity ≥ 0.13, P-nonlinearity ≥ 0.06, and P-overall ≥ 0.05 for both). Nonlinear inverse associations were observed among Chinese: HR (95% CI) for 300 vs. 150 mg/day was 0.94 (0.92–0.97) for all-cause mortality and 0.91 (0.87–0.95) for cardiometabolic mortality, but the inverse associations disappeared with cholesterol intake > 500 mg/day (P-linearity ≥ 0.12; P-nonlinearity ≤ 0.001; P-overall < 0.001 for both). Similarly, we observed a positive association of egg intake with all-cause mortality in Black Americans, but a null association in White Americans and a nonlinear inverse association in Chinese. In conclusion, the associations of cholesterol and egg intakes with cardiometabolic and all-cause mortality may differ across ethnicities who have different dietary patterns and cardiometabolic risk profiles. However, residual confounding remains possible. Full article

Background: Diet has been associated with poor glycemic control in diabetes. Few studies have examined this association in people with type 1 diabetes (T1D), who are at a higher risk for cardiovascular disease than people without diabetes. Methods: We report data from cross-sectional and longitudinal analyses from a coronary artery calcification in type 1 diabetes (CACTI) study (n = 1257; T1D: n = 568; non-diabetic controls: n = 689) collected between the years 2000 and 2002. Participants completed a validated food frequency questionnaire, a physical examination, and biochemical analyses. Dietary patterns based on variations in food group intake were created with principal components analysis. Linear regression was used to examine the associations of dietary patterns, macronutrients, and food groups with HbA1c in a model adjusted for relevant covariates and stratified by diabetes status. Results: Three dietary patterns were identified: “fruits, veggies, meats, cereal”, “baked desserts” and “convenience foods and alcohol” patterns. At baseline, a higher intake of the “baked dessert” pattern was significantly associated with higher HbA1c in T1D at baseline as well at year 6 of the study when adjusted for age, sex, BMI, total calories, and diabetes duration. No such associations were observed in the case of non-diabetic controls. Dietary saturated fats and animal fats were also positively associated with HbA1c in adults with T1D at baseline and/or at year 6. Conclusions: The habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts, may increase risks of poor glycemic control in T1D. Full article

It is unknown whether a healthy diet or unhealthy diet combined with specific supplements may jointly contribute to incidence of obesity and cardiovascular disease (CVD). We included 69,990 participants from the 45 and Up Study who completed both baseline (2006–2009) and follow-up (2012–2015) surveys. We found that compared to participants with a long-term healthy diet and no supplement consumption, those with a long-term healthy diet combined with multivitamins and minerals (MVM) or fish oil consumption were associated with a lower incidence of CVD (p < 0.001); whilst those with an unhealthy diet and no MVM or fish oil consumption were associated with a higher risk of obesity (p < 0.05). Compared to participants with a long-term healthy diet and no calcium consumption, the combination of a long-term healthy diet and calcium consumption was linked to a lower risk of CVD (IRR = 0.87, 95% CI: 0.78; 0.96). In conclusion, a long-term healthy diet combined with MVM or fish oil was associated with a lower incidence of CVD. Participants who maintained a healthy diet and used calcium supplements were associated with a lower incidence of obesity. However, these associations were not found among those with an unhealthy diet, despite taking similar supplements. Full article