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Purpose: Dyslipidemia is a major health issue worldwide. There is growing interest in understanding the potential role of kimchi consumption on serum lipid profiles. However, there are limited epidemiological studies available on this topic. Therefore, this study aims to investigate the association between kimchi intake and serum lipid profiles. Methods: We conducted an epidemiological study on participants (aged 40–69 years old) selected from the Health Examinees (HEXA) cohort study (n = 61,761). Four types of kimchi, including Baechu kimchi (cabbage kimchi), Kkakdugi (radish kimchi), Nabak kimchi/Dongchimi (a type of water kimchi made with fermented vegetables), and other kimchi, were assessed by a 106-food item semi-quantitative validated food frequency questionnaire (FFQ). Each kimchi intake is the average value calculated from the FFQ of the baseline and follow-up surveys. Fasting blood data were obtained at baseline and follow-up visits. Linear regression was used to examine the relationship between the intake of kimchi and the change in serum lipid profiles. Results: The mean years between the baseline survey and a follow-up survey was 4.97 years. In this study, compared to the lowest category (< 1 serving/day), Baechu kimchi intake (2− < 3 servings/day) had more negative correlations with the change in values of total cholesterol (β: −1.600, 95% confidence interval [CI, −2.744, −0.456]), triglycerides (β: −3.372, 95% CI [−5.414, −1.330]), and low-density lipoprotein cholesterol (β: −1.155, 95% CI [−2.214, −0.095]) in women. In men, Baechu kimchi intake (2− < 3 servings/day) had a more positive correlation associated with the changes in values of high-density lipoprotein cholesterol (β: 0.049, 95% CI [0.031, 0.907]) compared to the lowest intake category (< 1 serving/day). Conclusions: Among Korean adults, consumption of kimchi, particularly Baechu kimchi, was found to be associated with improvements in serum lipid profiles. Further studies are required to conduct additional interventions to confirm the association between kimchi and serum lipid profiles. [ABSTRACT FROM AUTHOR]

Purpose: The original aim of the study was to determine, in a double-blind 3-arm crossover human trial (n = 7), the effect of supplemental levels of iron (25 mg) and zinc (30 mg) on β-carotene (synthetic) bioavailability (10 h postprandial). However, despite the high dose of supplemental β-carotene (15 mg) consumed with the high fat (18 g), dairy-based breakfast test meal, there was a negligible postprandial response in plasma and triglyceride rich fraction β-carotene concentrations. We then systematically investigated the possible reasons for this low bioavailability of β-carotene. Methods: We determined (1) if the supplemental β-carotene could be micellised and absorbed by epithelial cells, using a Caco-2 cell model, (2) if the fat from the test meal was sufficiently bioavailable to facilitate β-carotene bioavailability, (3) the extent to which the β-carotene could have been metabolised and converted to retinoic acid/retinol and (4) the effect of the test meal matrix on the β-carotene bioaccessibility (in vitro digestion) and Caco-2 cellular uptake. Results: We found that (1) The supplemental β-carotene could be micellised and absorbed by epithelial cells, (2) the postprandial plasma triacylglycerol response was substantial (approximately 75–100 mg dL−1 over 10 h), indicating sufficient lipid bioavailability to ensure β-carotene absorption, (3) the high fat content of the meal (approximately 18 g) could have resulted in increased β-carotene metabolism, (4) β-carotene bioaccessibility from the dairy-based test meal was sixfold lower (p < 0.05) than when digested with olive oil. Conclusion: The low β-carotene bioavailability is probably due to a combination of the metabolism of β-carotene to retinol by BCMO1 and interactions of β-carotene with the food matrix, decreasing the bioaccessibility. Trail registration: The human trail was retrospectively registered (ClinicalTrail.gov ID: NCT05840848). [ABSTRACT FROM AUTHOR]

Purpose: Dairy foods are often a major contributor to dietary saturated fatty acids (SFA) intake. However, different SFA-rich foods may not have the same effects on cardiovascular risk factors. We compared full-fat yogurt with low-fat yogurt and butter for their effects on cardiometabolic risk factors in healthy individuals. Methods: Randomized, two-period crossover trial conducted from October 2022 to April 2023 among 30 healthy men and women (15 to receive full-fat yogurt first, and 15 to receive low-fat yogurt and butter first). Participants consumed a diet with 1.5-2 servings of full-fat (4%) yogurt or low-fat (< 1.5) yogurt and 10–15 g of butter per day for 4 weeks, with 4 weeks wash-out when they consumed 1.5-2 servings of low-fat milk. At baseline, and the end of each 4 weeks, fasting blood samples were drawn and plasma lipids, glycemic and inflammatory markers as well as expression of some genes in the blood buffy coats fraction were determined. Results: All 30 participants completed the two periods of the study. Apolipoprotein B was higher for the low-fat yogurt and butter [changes from baseline, + 10.06 (95%CI 4.64 to 15.47)] compared with the full-fat yogurt [–4.27 (95%CI, -11.78 to 3.23)] and the difference between two treatment periods was statistically significant (p = 0.004). Non-high-density lipoprotein increased for the low-fat yogurt and butter [change, + 5.06 (95%CI (-1.56 to 11.69) compared with the full-fat yogurt [change, − 4.90 (95%CI, -11.61 to 1.81), with no significant difference between two periods (p = 0.056). There were no between-period differences in other plasma lipid, insulin, and inflammatory biomarkers or leukocyte gene expression of ATP-binding cassette transporter 1 and CD36. Conclusion: This study suggests that short-term intake of SFAs from full-fat yogurt compared to intake from butter and low-fat yogurt has fewer adverse effects on plasma lipid profile. ClinicalTrials.gov: NCT05589350, 10/15/2022. [ABSTRACT FROM AUTHOR]

Purpose: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo. Methods: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed. Results: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured. Conclusion: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function. [ABSTRACT FROM AUTHOR]

Purpose: Coffee intake and apolipoprotein B levels have been linked to gastric, colorectal, and esophageal cancers in numerous recent studies. However, whether these associations are all causal remains unestablished. This study aimed to assess the potential causal associations of apolipoprotein B and coffee intake with the risk of gastric, colorectal, and esophageal cancers using Mendelian randomization analysis. Methods: In this study, we utilized a two-sample Mendelian randomization analysis to access the causal effects of coffee intake and apolipoprotein B on gastric, colorectal, and esophageal cancers. The summary statistics of coffee intake (n = 428,860) and apolipoprotein B (n = 439,214) were obtained from the UK Biobank. In addition, the summary statistics of gastric cancer, colorectal cancer, and esophageal cancer were obtained from the FinnGen biobank (n = 218,792). Inverse variance weighted, MR–Egger, weighted median, and weighted mode were applied to examine the causal relationship between coffee intake, apolipoprotein B and gastric, colorectal, and esophageal cancers. MR–Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. Steiger filtering and bidirectional mendelian randomization analysis were performed to evaluate the possible reverse causality. Results: The result of the inverse variance weighted method indicated that apolipoprotein B levels were significantly associated with a higher risk of gastric cancer (OR = 1.392, 95% CI 1.027–1.889, P = 0.0333) and colorectal cancer (OR = 1.188, 95% CI 1.001–1.411, P = 0.0491). Furthermore, multivariable Mendelian randomization analysis also revealed a positive association between apolipoprotein B levels and colorectal cancer risk, but the effect of apolipoprotein B on gastric cancer risk disappeared after adjustment of coffee intake, body mass index or lipid-related traits. However, we did not discover any conclusive evidence linking coffee intake to gastric, colorectal, or esophageal cancers. Conclusions: This study suggested a causal association between genetically increased apolipoprotein B levels and higher risk of colorectal cancer. No causal relationship was observed between coffee intake and gastric, colorectal, or esophageal cancers. [ABSTRACT FROM AUTHOR]

Purpose: Fucoxanthin extract (FX) is a type of carotenoid with a beneficial effect against obesity. The purpose of this study was to explore its precise action mechanism of losing weight. Methods: A high-fat diet induced obesity mouse model was established to study the effects of different doses of FX on C57BL/6J male mice for 12 weeks. Following intervention, serum indices, tissue sections, liver gene expression, and intestinal microorganisms were analyzed. Results: FX at low, medium, and high dosages (80, 160, and 320 mg/kg/day, respectively) for 12 weeks was associated with the lower body weight of mice when compared to that of high-fat-diet fed mice. It also improved glucose tolerance as well as serum lipid levels, and reduced fat accumulation. Significant regulation of bile acid metabolism and intestinal microbiota may contribute to the above effects. The bile acids in the FXH group were significantly increased. A low-dose and a medium-dose FX increased the level of transmembrane G protein-coupled receptor 5 (TGR5); a low-dose and high-dose FX increased the farnesoid X receptor (FXR) expression, and a medium-dose had no effect. 16S rRNA sequencing indicated that the Lachnospiraceae and Oscillospiraceae contributed to the beneficial effects of FX. Conclusion: Our study sheds light on mechanisms behind the weight-lowering of FX, and manifested that bile acid metabolism and gut microbiota may be potential therapies. These results support that FX is a valuable candidate for promoting health and alleviating obesity. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with vitamin D (VD) insufficiency have a greater tendency to develop obesity and have increased systemic inflammation. Gut microbiota are involved in the regulation of host inflammation and energy metabolism, which plays a role in the pathogenesis of obesity. Thus, we aimed to evaluate the effects of different doses of VD3 on body weight, serum lipids, inflammatory factors, and intestinal barrier function in obese mice and to explore the regulatory effect of VD3 on gut microbiota in obese mice. Methods: Male C57BL/6 J mice received a normal chow diet (NCD, 10% fat) or high-fat diet (HFD, 60% fat) to induce obesity within 10 weeks. Then, HFD mice were supplemented with 5650, 8475, or 11,300 IU VD3/kg diet for 8 weeks. Finally, 16 s rRNA analysis was performed to analyze gut microbiota composition in cecal contents. In addition, body weight, serum lipids, inflammatory factors, and intestinal barrier function were analyzed. Results: VD3 supplementation reduced body weight and the levels of TG, TC, HDL-C, TNF-α, IL-1β and LPS, and increased ZO-1 in HFD-fed mice. Moreover, it increased α-diversity, reduced F/B ratio and altered microbiota composition by increasing relative abundance of Bacteroidetes, Proteobacteria, Desulfovibrio, Dehalobacterium, Odoribacter, and Parabacteroides and reducing relative abundance of Firmicutes and Ruminococcus. There were significant differences between HFD and NCD groups in several metabolic pathways, including endotoxin biosynthesis, tricarboxylic acid cycle, lipid synthesis and metabolism, and glycolysis. Conclusions: Low, medium, and high doses of VD3 inhibited weight gain, reduced levels of blood lipids and inflammatory factors, and improved endotoxemia and gut barrier function in obese mice. It also increased the α-diversity of gut microbiota in obese mice and reduced the relative abundance of some intestinal pathogenic bacteria, increased the relative abundance of some beneficial bacteria, and corrected the intestinal flora disorder of obese mice, with the low- and high-dose groups showing better effects than the medium-dose group. [ABSTRACT FROM AUTHOR]

Purpose: To assess the relationship of early pregnancy maternal diet quality (DQ) with maternal plasma lipids and indicators of cardiometabolic health, including blood pressure (BP), gestational diabetes mellitus (GDM) and gestational weight gain (GWG). Methods: Women (n = 215) aged 18–40 years with singleton pregnancies were recruited at 10–20 weeks gestation. Diet quality was assessed by the Dietary Guideline Index, calculated at early ([mean ± SD]) (15 ± 3 weeks) and late (35 ± 2 weeks) pregnancy. Lipidomic analysis was performed, and 698 species across 37 lipid classes were measured from plasma blood samples collected at early (15 ± 3 weeks) and mid (27 ± 3 weeks)-pregnancy. Clinical measures (BP, GDM diagnosis, weight) and blood samples were collected across pregnancy. Multiple linear and logistic regression models assessed associations of early pregnancy DQ with plasma lipids at early and mid-pregnancy, BP at three antenatal visits, GDM diagnosis and total GWG. Results: Maternal DQ scores ([mean ± SD]) decreased significantly from early (70.7 ± 11.4) to late pregnancy (66.5 ± 12.6) (p < 0.0005). At a false discovery rate of 0.2, early pregnancy DQ was significantly associated with 13 plasma lipids at mid-pregnancy, including negative associations with six triglycerides (TGs); TG(54:0)[NL-18:0] (neutral loss), TG(50:1)[NL-14:0], TG(48:0)[NL-18:0], TG(52:1)[NL-18:0], TG(54:1)[NL-18:1], TG(50:0)[NL-18:0]. No statistically significant associations were found between early pregnancy DQ and BP, GDM or GWG. Conclusion: Maternal diet did not adhere to Australian Dietary Guidelines. Diet quality was inversely associated with multiple plasma TGs. This study provides novel insights into the relationship between DQ, lipid biomarkers and cardiometabolic health during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the possible clinical effects of vitamin K4 supplementation in individuals with type 2 diabetes namely insulin resistance, glycaemic control, and lipid profile. Methods: This was a prospective randomised double-blind placebo-controlled clinical trial. A total of 106 patients were randomised to receive either 1 mg of vitamin K4 (menadiol diacetate) or placebo for 24 weeks. Results: Ninety patients (n = 45 in each study group) were included in the final analysis. After 24 weeks, homeostatic model assessment of insulin resistance (HOMA-IR) (16.54 ± 7.81 vs. 29.09 ± 36.56, P = 0.027) and fasting serum insulin (FSI) (6.86 ± 3.45 vs. 11.13 ± 12.66 µU/ml, P = 0.032) were significantly lower in the vitamin K group compared to placebo. Additionally, triglycerides (TG) (144.94 ± 50.7 vs. 172.8 ± 101.5 mg/dl, P = 0.031) and very low-density lipoproteins (VLDL) levels (28.9 ± 9.88 vs. 34.6 ± 20.30 mg/dl, P = 0.027) decreased significantly in the vitamin K group after 24 weeks compared to baseline. Moreover, more patients in the vitamin K group (35.6%) had their antidiabetic medication doses reduced after 24 weeks compared to placebo (13.3%, P = 0.029). Conclusion: Vitamin K4 supplementation for 24 weeks is capable of improving insulin resistance and TG levels in individuals with type 2 diabetes. In addition, the improvement in insulin resistance was reflected in the decrease in antidiabetic medication doses. However, it did not affect fasting plasma glucose (FPG) or glycated haemoglobin (HbA1c). Trial registration: The study was registered on clinicaltrials.gov with ID: NCT04285450. [ABSTRACT FROM AUTHOR]

Purpose: Dietary intake may have pronounced effects on circulating biomarker concentrations. Therefore, the aim was to provide a descriptive overview of serum metabolite concentrations in relation to time since last meal, focusing on amino acids, lipids, one-carbon metabolites, and biomarkers of vitamin status. Methods: We used baseline data from the observational community-based Hordaland Health Study, including 2960 participants aged 46–49 years and 2874 participants aged 70–74 years. A single blood draw was taken from each participant, and time since last meal varied. Estimated marginal geometric mean metabolite concentrations were plotted as a function of time since last meal, up to 7 h, adjusted for age, sex, and BMI. Results: We observed a common pattern for nearly all amino acids and one-carbon metabolites with highest concentrations during the first 3 h after dietary intake. Homocysteine and cysteine were lowest the 1st hour after a meal, while no patterns were observed for glutamate and glutamic acid. The concentrations of phylloquinone and triglycerides were highest 1 h after dietary intake. Thiamine and thiamine monophosphate concentrations were highest, while flavin mononucleotide concentrations were lowest within the first 2 h after a meal. No clear patterns emerged for the other fat-soluble vitamins, blood lipids, or B-vitamin biomarkers. Conclusion: Our findings suggest that distinguishing between "fasting" and "non-fasting" blood samples may be inadequate, and a more granular approach is warranted. This may have implications for how to account for dietary intake when blood sampling in both clinical and research settings. [ABSTRACT FROM AUTHOR]

Background and aims: Non-alcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver disease. We explored simple and effective ways to improve NAFLD and investigate the mechanism of action. Methods: NAFLD was induced in 40 rats fed a high-fat diet (HFD). Magnetic resonance imaging was used to evaluate the progression and improvement of NAFLD. The treatment-related interventions included aerobic exercise (E) and vitamin E (VE) supplementation. Expression levels of proteins related to fat metabolism were also assessed. The activities of antioxidant enzymes in the liver and serum lipid metabolism were analyzed using biochemical methods. Results: Aerobic exercise and vitamin E effectively improved NAFLD in rats, resulting in decreased hepatic fat accumulation, reduced hepatocyte ballooning, and decreased triglyceride levels. Combination therapy achieved the best effect. Both aerobic exercise and vitamin E activate the AMPK pathway to phosphorylate acetyl-CoA carboxylase (ACC) and reduce fatty acid synthesis. The expression of sterol regulatory element-binding protein-1 (SREBP-1) was decreased significantly in the treated groups, particularly in the E + VE + HFD group. The expression of carnitine palmitoyl-transferase 1C (CPT1C) significantly increased in the treated groups, particularly in the E + VE + HFD group. Compared with the control group, reactive oxygen species (ROS) in the E + HFD group were slightly decreased, while that in the VE + HFD group were significantly decreased, with the even greater reduction observed in the E + VE + HFD group. Conclusion: Aerobic exercise and vitamin E supplementation can improve HFD-induced NAFLD in rats by regulating the AMPK pathway and reducing oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: Bacillus coagulans GBI-30, 6086 (BC30) was previously shown to improve nutrient digestibility and amino acid absorption from milk protein in vitro. However, the effect of supplementation with this probiotic on lactose digestibility has not yet been evaluated in vivo. Methods: Wistar female rats were exposed to an acute high-lactose diet (LD; 35% lactose) meal challenge after 7 days of administration of BC30 (LD-BC; n = 10) or vehicle (LD-C; n = 10). Rats treated with vehicle and exposed to control diet (CD; 35% corn starch) meal were used as controls (CD-C; n = 10). Carbohydrate oxidation (CH_OX) and lipid oxidation (L_OX) were monitored by indirect calorimetry before and after lactose challenge. After the challenge, rats were treated daily with vehicle or probiotic for an additional week and were fed with CD or LD ad libitum to determine the effects of BC30 administration in a lactose-induced diarrhoea and malnutrition model. Results: LD-C rats showed lower CH_OX levels than CD rats, while LD-BC rats showed similar CH_OX levels compared to CD rats during the lactose challenge, suggesting a better digestion of lactose in the rats supplemented with BC30. BC30 completely reversed the increase in the small intestine length of LD-C animals. LD-BC rats displayed increased intestinal mRNA Muc2 expression. No significant changes were observed due to BC30 administration in other parameters, such as serum calprotectin, intestinal MPO activity, intestinal A1AT and SGLT1 levels or intestinal mRNA levels of Claudin2 and Occludin. Conclusion: Treatment with BC30 improved the digestibility of lactose in an acute lactose challenge and ameliorated some of the parameters associated with lactose-induced malnutrition. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies indicate that dysbiosis of gut microbiota and low-grade inflammation are important pathogenic determinants of type two diabetes mellitus (T2DM). The aim of this study is to investigate the effects of Lactobacillus GG on glycemic control, lipid profile, inflammatory parameters, and some gene expression levels in individuals with T2DM. Methods: In a randomized, placebo-controlled trial, 34 women, aged 30–60 years with T2DM consumed daily probiotics or placebo for 8 weeks. The probiotic group consumed 10 × 109 Cfu/day Lactobacillus rhamnosus GG ATCC 53,103 (LGG), approved by the TR Ministry of Food, Agriculture, and Livestock. Anthropometric measurements, food diary, fasting blood, and fecal samples were taken at baseline and post-treatment. Results: Fasting blood glucose was significantly decreased in probiotic (p = 0.049) and placebo (p = 0.028), but there was no difference between the groups. In the probiotic group, no significant difference was observed in HbA1c, fructosamine, lipid profile, and inflammatory variables compared to baseline. In this group, with LGG supplementation, mucin 2 and 3A (MUC2 and MUC3A) gene expressions increased more than ninefolds (p = 0.046 and p = 0.008, respectively) at post-treatment. Meanwhile, there was no significant change in any of the gene expressions in the placebo group. There was no significant difference in energy, protein, dietary fiber, and cholesterol intakes between placebo and probiotic groups during the study. However, daily fat intake (p = 0.003), body weight (p = 0.014), and body fat (p = 0.015) in the probiotic group were significantly decreased. Conclusion: In this study, the effects of a single probiotic strain were investigated for 8 weeks. At the end of the study, although there was no finding that clearly reflected on the glycemic parameters of T2DM, its beneficial effects on the expression of mucin genes, which are responsible for weight loss and protection of intestinal barrier functions, cannot be denied. Further studies are needed to reveal the importance of these findings. Clinical trial registration: ID: NCT05066152, October 4, 2021 retrospectively registered in ClinicalTrials.gov PRS web site. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study was to assess the impact of the daily consumption of bread enriched with hydroxytyrosol on HbA1c and blood lipid levels, inflammatory markers and weight loss. Methods: Sixty adults with overweight/obesity and type 2 diabetes mellitus (29 male, 31 female) participated in a 12-week dietary intervention based on the Mediterranean diet and consumed daily 60 g of conventional whole wheat bread (WWB) or whole wheat bread enriched with hydroxytyrosol (HTB). Anthropometric characteristics were measured and venous blood samples were collected at baseline and at the end of the intervention. Results: Both groups experienced significant weight loss, body fat and waist circumference decrease (p < 0.001). Nonetheless, a greater body fat mass decrease was observed in the HTB group compared to the WWB group (14.4 ± 1.6 vs 10.2 ± 1.1%, p = 0.038). Significant reductions were also reported in fasting glucose, HbA1c and blood pressure in both groups (p < 0.05). Regarding glucose and HbA1c, greater decreases were observed in the intervention group (101.4 ± 19.9 vs. 123.2 ± 43.4 mg/dL, p = 0.015 and 6.0 ± 0.6 vs. 6.4 ± 0.9%, p = 0.093, respectively). At HTB group, significant reductions in blood lipid, insulin, TNF-αand adiponectin levels (p < 0.05) and a marginally significant reduction in leptin levels (p = 0.081) were also reported. Conclusion: Enrichment of bread with HT resulted in significant body fat mass reduction and positive effects on fasting glucose, insulin and HbA1c levels. It also contributed to reductions in inflammatory markers and blood lipid levels. Incorporation of HT in staple foods, like bread, may improve their nutritional profile and, in terms of a balanced diet, may contribute to the management of chronic diseases. Trial registration: The study was prospectively registered in clinicaltrials.gov (24th May 2021). ClinicalTrials.gov Identifier: NCT04899791. [ABSTRACT FROM AUTHOR]

Purpose: Previous evidence indicated anti-ageing potential of docosahexaenoic acid (DHA), but the underlying mechanism remains unclear. We investigated protective effect of DHA on telomere attrition and lipid disturbance in male mice with premature ageing caused by telomerase deficiency. Methods: Wild-type (WT) and fourth-generation telomerase-deficient (G4 Terc−/−, Terc knockout, KO) male mice (C57BL/6, 2 months old) were fed control diet (WT-C and KO-C groups) or DHA-enriched diet containing 0.80% DHA by weight (WT-DHA and KO-DHA groups) for 10 months. The ageing phenotypes and metabolic level [carbon dioxide emission, oxygen consumption, and respiratory exchange ratio (RER)] were assessed at the end of the experiment. Telomere length in various tissues and the hepatic gene and protein expression for regulating lipid synthesis and lipolysis were measured. Data were tested using one- or two-factor ANOVA. Results: In KO male mice, DHA prevented weight loss, corrected high RER, and reduced fat loss. Telomere shortening was reduced by 22.3%, 25.5%, and 13.5% in heart, liver, and testes of the KO-DHA group compared with those in the KO-C group. The KO-DHA group exhibited higher gene transcription involved in glycerol-3-phosphate pathway [glycerol-3-phosphate acyltransferase (Gpat)], lower gene expression of β-oxidation [carnitine palmitoyltransferase 1a (Cpt1a)], and upregulation of proteins in lipid synthesis [mammalian target of rapamycin complex 1 (mTORC1) and sterol responsive element binding protein 1 (SREBP1)] in liver than the KO-C group. Conclusion: Long-term DHA intervention attenuates telomere attrition and promotes lipid synthesis via the tuberous sclerosis complex 2 (TSC2)-mTORC1-SREBP1 pathway in KO male mice. [ABSTRACT FROM AUTHOR]

Background and aims: Atherosclerosis is associated with a reduction in the bioavailability and/or bioactivity of endogenous nitric oxide (NO). Dietary nitrate has been proposed as an alternate source when endogenous NO production is reduced. Our previous study demonstrated a protective effect of dietary nitrate on the development of atherosclerosis in the apoE−/− mouse model. However most patients do not present clinically until well after the disease is established. The aims of this study were to determine whether chronic dietary nitrate supplementation can prevent or reverse the progression of atherosclerosis after disease is already established, as well as to explore the underlying mechanism of these cardiovascular protective effects. Methods: 60 apoE−/− mice were given a high fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis. The mice were then randomized to (i) control group (HFD + 1 mmol/kg/day NaCl), (ii) moderate-dose group (HFD +1 mmol/kg/day NaNO3), or (iii) high-dose group (HFD + 10 mmol/kg/day NaNO3) (20/group) for a further 12 weeks. A group of apoE−/− mice (n = 20) consumed a normal laboratory chow diet for 24 weeks and were included as a reference group. Results: Long-term supplementation with high dose nitrate resulted in ~ 50% reduction in plaque lesion area. Collagen expression and smooth muscle accumulation were increased, and lipid deposition and macrophage accumulation were reduced within atherosclerotic plaques of mice supplemented with high dose nitrate. These changes were associated with an increase in nitrite reductase as well as activation of the endogenous eNOS-NO pathway. Conclusion: Long-term high dose nitrate significantly attenuated the progression of established atherosclerosis in the apoE−/− mice fed a HFD. This appears to be mediated in part through a XOR-dependent reduction of nitrate to NO, as well as enhanced eNOS activation via increased Akt and eNOS phosphorylation. [ABSTRACT FROM AUTHOR]

Purpose: Studies show that dairy fat consumed in the form of cheese reduce LDL-cholesterol concentration (LDL-c) compared to butter and mechanistic suggestions include the calcium content of cheese leading to enhanced faecal fat excretion. The aim of this study was to test the effect of varying the calcium content within a cheese, on faecal fat excretion as a primary outcome, and blood lipid markers, fasting glucose and calcium excretion as secondary outcomes. Methods: 7 healthy males (BMI 18–25) participated in this randomized, cross-over control intervention, of 3 × 2 week periods. Diets contained 240 g/day cheese; a High Calcium Cheese (HCC) diet, a Reduced Calcium Cheese (RCC) diet, and a control arm: Reduced Calcium Cheese + CaCO3 Supplement (RCC + Supp) diet. Diets differed in calcium content and form but were otherwise controlled for energy and key macronutrients. Blood and 5-day faecal samples were collected. Results: There was no significant difference in faecal fat excretion (g/day) between the diets (P = 0.066). Percent fat of faecel excretion was higher after RCC + Supp (P = 0.016). None of the individual fatty acids were different. Fasting LDL-c was significantly lower following the HCC diet vs. the other arms (P = 0.002). Faecal Ca was different across all diets (P = 0.001), lowest after RCC, and greatest after RCC + Supp. No differences were observed for fasting blood parameters or changes in anthropometry. Conclusion: Varying the calcium content within a cheese matrix significantly affected fasting LDL-c values. Results did not support higher faecal fat excretion as an underlying mechanism, but the high attrition rate was a limitation. Trial registerer Trial Registered at ISRCTN.org, registration number ISRCTN11663659 on 12.07.2022. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Purpose: To examine the associations of healthy dietary patterns with cardiometabolic biomarkers and all-cause mortality among individuals with prediabetes. Methods: This cohort study included 8363 adults with prediabetes from the National Health and Nutrition Examination Survey 1999–2014. Healthy dietary patterns including Alternate Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet score (AMED), Dietary Approaches to Stop Hypertension score (DASH), and Healthy Eating Index-2015 (HEI-2015) were calculated based on 24-h dietary recall data. Mortality status was obtained by linkage to National Death Index records. Cardiometabolic biomarkers, including blood glucose, insulin, HbA1c, C-reactive protein (CRP), and lipids, were measured at recruitment. Results: During 61,991 person-years of follow-up, 991 deaths occurred. Comparing the extreme quartiles, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were 0.65 (0.49, 0.85) for AHEI-2010 (P-trend = 0.002), 0.68 (0.50, 0.92) for AMED (P-trend = 0.004), 0.72 (0.53, 0.98) for DASH (P-trend = 0.03), and 0.78 (0.58, 1.05) for HEI-2015 (P-trend = 0.08). Besides, the HRs (95% CIs) for all-cause mortality per 20-percentile increment in scores were 0.78 (0.67, 0.90) for AHEI-2010 (P = 0.001), 0.73 (0.62, 0.86) for AMED (P < 0.001), 0.84 (0.69, 1.02) for DASH (P = 0.08), and 0.86 (0.74, 1.00) for HEI-2015 (P = 0.04). In addition, higher dietary scores were associated with favorable blood glucose, insulin, HOMA-IR, blood lipids, and CRP (all P-trend < 0.05). The high-density lipoprotein cholesterol and CRP explained 1.53–9.21% of the associations between dietary patterns and all-cause mortality (P < 0.05). Conclusions: Diets with higher AHEI-2010, AMED, DASH, and HEI-2015 were associated with improved cardiometabolic factors and lower all-cause mortality among individuals with prediabetes. These findings suggest that multiple healthy dietary patterns instead of a one-size-fits-all diet plan might be beneficial and acceptable for individuals with prediabetes. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic changes during the perinatal period are known to promote obesity and type-2 diabetes in adulthood via perturbation of the microbiota. The risk factors for metabolic disorders include a high-fat diet (HFD) and exposure to pesticide residues. The objective of the present study was to evaluate the effects of perigestational exposure to a HFD and chlorpyrifos (CPF) on glycemia, lipid profiles, and microbial populations in Wistar dams and their female offspring. We also tested a preventive strategy based on treatment with the prebiotic inulin. Methods: From 4 months before gestation to the end of the lactation period, six groups of dams were exposed to either a standard diet, a HFD alone, CPF alone, a combination of a HFD and CPF, and/or inulin supplementation. All female offspring were fed a standard diet from weaning to adulthood. We measured the impacts of these exposures on glycemia, the lipid profile, and the microbiota (composition, metabolite production, and translocation into tissues). Results: HFD exposure and CPF + HFD co-exposure induced dysmetabolism and an imbalance in the gut flora in both the dams and the female offspring. Inulin mitigated the impact of exposure to a HFD alone but not that of CPF + HFD co-exposure. Conclusion: Our results provide a better understanding of the complex interactions between environmental pollutants and diet in early life, including in the context of metabolic diseases. [ABSTRACT FROM AUTHOR]

Aims: Overconsumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of metabolic disorders, including obesity and diabetes. However, accumulating evidence also suggests the potential negative impact of consuming nonnutritive sweeteners (NNSs) on weight and glycaemic control. The metabolic effects of sucralose, the most widely used NNS, remain controversial. This study aimed to compare the impact of intake of dietary sucralose (acceptable daily intake dose, ADI dose) and sucrose-sweetened water (at the same sweetness level) on lipid and glucose metabolism in male mice. Materials and methods: Sucralose (0.1 mg/mL) or sucrose (60 mg/mL) was added to the drinking water of 8-week-old male C57BL/6 mice for 16 weeks, followed by oral glucose and intraperitoneal insulin tolerance tests, and measurements of bone mineral density, plasma lipids, and hormones. After the mice were sacrificed, the duodenum and ileum were used for examination of sweet taste receptors (STRs) and glucose transporters. Results: A significant increase in fat mass was observed in the sucrose group of mice after 16 weeks of sweetened water drinking. Sucrose consumption also led to increased levels of plasma LDL, insulin, lipid deposition in the liver, and increased glucose intolerance in mice. Compared with the sucrose group, mice consuming sucralose showed much lower fat accumulation, hyperlipidaemia, liver steatosis, and glucose intolerance. In addition, the daily dose of sucralose only had a moderate effect on T1R2/3 in the intestine, without affecting glucose transporters and plasma insulin levels. Conclusion: Compared with mice consuming sucrose-sweetened water, daily drinking of sucralose within the ADI dose had a much lower impact on glucose and lipid homeostasis. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the association between coffee consumption and serum lipid profile in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This is a cross-sectional study on baseline data from participants of the cohort ELSA-Brasil. Only participants of São Paulo Research Center who underwent a nuclear magnetic resonance (NMR) spectroscopy examination of lipid profile were included (N = 4736). Coffee intake was categorized into four categories (cups/day, in reference cup size of 50 mL, which is the household measure adopted in Brazil): never/almost never, ≤ 1, 1–3, and > 3. Serum lipid profile [i.e., Total Cholesterol (TC), Total Triglycerides (TG), Very Low-Density Lipoprotein-cholesterol (VLDL-c), Low-Density Lipoprotein-cholesterol (LDL-c), High-Density Lipoprotein-cholesterol (HDL-c), Triglyceride-rich Lipoprotein Particles (TRLP) and subfractions particles] was analyzed. To estimate the effect of coffee consumption on serum lipid profile, multivariate Generalized Linear Models were performed. Results: Compared to participants who never or almost never drink coffee, individuals who consumed more than 3 cups/day showed an increase in concentrations of TC (β: 4.13; 95% CI 0.81, 7.45), TG (β: 9.53; 95% CI 1.65, 17.42), VLDL-c (β: 1.90; 95% CI 0.38, 3.42), TRLP (β: 8.42; 95% CI 1.24, 15.60), and Very Small-TRLP and Medium-TRLP subfractions (β: 7.36; 95% CI 0.21, 14.51; β: 2.53; 95% CI 0.89, 4.16, respectively), but not with HDL-c and LDL-c. Among individuals with low (≤ 1 cup/day) and moderate (1–3 cups/day) coffee consumption, no significant associations with lipids was observed. Conclusion: High coffee consumption (more than 3 cups per day) was associated with an increase in serum lipids, namely TC, TG, VLDL-c, and TRL particles, highlighting the importance of a moderate consumption of this beverage. [ABSTRACT FROM AUTHOR]

Purpose: Public health interventions to address stunting and wasting should be evaluated for possibly contributing to obesity risk. The present study tested the hypothesis that small-quantity lipid-based nutrient supplements (SQ-LNS) might increase fat deposition, and that additional zinc provided via SQ-LNS or in the form of dispersible tablets would increase fat-free mass (FFM) accretion. Methods: Using a two-stage, cluster-randomized trial design, 34 communities were randomly assigned to the intervention cohort (IC) or non-intervention cohort (NIC), and family compounds within the IC were randomly assigned to receive different amounts of zinc (0, 5 or 10 mg zinc) incorporated in SQ-LNS or 5 mg zinc in the form of dispersible tablets along with treatment for diarrhea, malaria and fever. Body composition was assessed in a subset of IC (n = 201) and NIC (n = 74) children at 9 and 18 months using the deuterium dilution method. A mixed linear model was used to examine average change in FFM and % fat mass (%FM) among intervention groups and by cohort. Results: Children in the IC had significantly greater change in FFM (Mean (95% Confidence Interval)) (1.57 (1.49, 1.64) kg) compared to the NIC (1.35 (1.23, 1.46) kg; p = 0.005). There were no significant differences in the change in %FM between the NIC and IC or among the intervention groups. Conclusion: SQ-LNS, along with morbidity treatment increased weight gain and FFM in young children from 9 to 18 months of age without increasing FM deposition. Additional zinc supplementation did not affect changes in FFM or %FM. Trial registration: The study was registered as a clinical trial with the US National Institute of Health (www.ClinicalTrials.gov; NCT00944281). [ABSTRACT FROM AUTHOR]

Aims: To compare the effects of replacing regular dietary oils intake with sesame (SO), canola (CO), and sesame–canola (SCO) oils (a novel blend), on cardiometabolic markers in adults with type 2 diabetes mellitus (T2DM), in a triple-blind, three-way, randomized, crossover clinical trial. Methods: Participants were assigned to receive SO, CO, and SCO in three 9-week phases (4 weeks apart). Cardiometabolic makers (serum lipids, Apolipoprotein, cardiovascular risk scores, kidney markers, and blood pressure) were considered at the beginning and the end of intervention phases. Results: Ninety-two, ninety-five, and ninety-five participants completed the SO, SCO, and CO periods, respectively. After CO consumption, serum Apo A-1 concentrations were significantly higher compared with the SCO period in the whole population (p < 0.05). A considerable reduction in visceral adiposity index values was seen in the CO compared with the SO period in males (p < 0.05). Serum high-density lipoprotein concentration was also significantly higher after the SO intake compared with SCO in females (p < 0.05). The between-period analysis showed a substantial reduction in diastolic blood pressure in the SCO period compared with the CO and SO periods and lower systolic blood pressure after SCO versus CO intake in males (p < 0.05). Conclusions: Canola oil might protect CVD through improving Apo A-1 levels in patients with T2DM (particularly in females) and visceral adiposity index in male patients. However, the blend oil might beneficially affect blood pressure in men. Future sex-specific studies might warrant the current findings. Registry of clinical trials: This trial was registered in the Iranian Registry of Clinical Trials (IRCT, registration ID: IRCT2016091312571N6). [ABSTRACT FROM AUTHOR]

Background: Ash-Kardeh is one of the few fermented foods without a dairy base in Iran, which is traditionally prepared from cereals and plants in the presence of microorganisms (mainly lactic acid bacteria). Purpose: This study aimed to assess the effects of Ash-Kardeh consumption on blood glucose, lipid profile, and blood pressure in type 2 diabetic patients. Methods: Forty-six patients with type 2 diabetes were studied in this randomized controlled clinical trial. Subjects were randomly allocated into intervention (n = 23) and control (n = 23) groups. Individuals of both groups received the usual treatment of diabetic patients, while those in the intervention group, in addition to the usual treatment, received 250 g of Ash-Kardeh daily for 6 weeks. Fasting blood glucose, blood pressure, and lipid profiles were measured before and after the intervention. Results: Compared to the control group, Ash-Kardeh consumption led to a significant decrease in fasting blood glucose (P = 0.003), total cholesterol (P = 0.025), triglyceride (P = 0.003), systolic (P < 0.001), and diastolic blood pressure (P = 0.014) in the intervention group. Also, a significant increase in the concentrations of high-density lipoprotein cholesterol (P = 0.048) was observed after Ash-Kardeh consumption. Conclusion: It seems that Ash-Kardeh consumption could improve high blood glucose, lipid profile, and hypertension in type 2 diabetic patients but does not affect low-density lipoprotein cholesterol concentrations. This study was registered on 2019-09-15 in the Iranian Registry of Clinical Trials (www.irct.ir) with the code number IRCT20170202032367N3. [ABSTRACT FROM AUTHOR]

Background: Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21–5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46–0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31–0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27–0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.Methods: Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21–5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46–0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31–0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27–0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.Results: Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21–5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46–0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31–0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27–0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.Conclusions: Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21–5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46–0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31–0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27–0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to determine the influence of the CYP1A2 c.-163 A > C (rs762551) polymorphism on the effect of oral caffeine intake on fat oxidation during exercise.Using a pilot randomized, double-blind, crossover, placebo-controlled trial, 32 young and healthy individuals (women = 14, men = 18) performed an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Participants performed this test after the ingestion of (a) placebo; (b) 3 mg/kg of caffeine; (c) 6 mg/kg of caffeine. Fat oxidation rate during exercise was measured by indirect calorimetry. The influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation rates during exercise was established with a three-way ANOVA (substance × genotype × intensity).Eight participants were genotyped as AA, 18 participants were CA heterozygotes, and 6 participants were CC. There was a main effect of substance (F = 3.348, p = 0.050) on fat oxidation rates during exercise with no genotype effect (F = 0.158, p = 0.959). The post hoc analysis revealed that, in comparison to the placebo, 3 and 6 mg/kg of caffeine increased fat oxidation at 40–50% VO2max in AA (all p < 0.050) and 50–60% VO2max in CA and CC participants (all p < 0.050).Oral intake of 3 and 6 mg/kg of caffeine increased fat oxidation rate during aerobic exercise in individuals with AA, CA and CC genotypes. This suggests that the effect of caffeine to enhance fat oxidation during exercise is not influenced by the CYP1A2 c.-163 A > C polymorphism.The study was registered on clinicaltrials.gov with ID: NCT05975489.Methods: The aim of this study was to determine the influence of the CYP1A2 c.-163 A > C (rs762551) polymorphism on the effect of oral caffeine intake on fat oxidation during exercise.Using a pilot randomized, double-blind, crossover, placebo-controlled trial, 32 young and healthy individuals (women = 14, men = 18) performed an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Participants performed this test after the ingestion of (a) placebo; (b) 3 mg/kg of caffeine; (c) 6 mg/kg of caffeine. Fat oxidation rate during exercise was measured by indirect calorimetry. The influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation rates during exercise was established with a three-way ANOVA (substance × genotype × intensity).Eight participants were genotyped as AA, 18 participants were CA heterozygotes, and 6 participants were CC. There was a main effect of substance (F = 3.348, p = 0.050) on fat oxidation rates during exercise with no genotype effect (F = 0.158, p = 0.959). The post hoc analysis revealed that, in comparison to the placebo, 3 and 6 mg/kg of caffeine increased fat oxidation at 40–50% VO2max in AA (all p < 0.050) and 50–60% VO2max in CA and CC participants (all p < 0.050).Oral intake of 3 and 6 mg/kg of caffeine increased fat oxidation rate during aerobic exercise in individuals with AA, CA and CC genotypes. This suggests that the effect of caffeine to enhance fat oxidation during exercise is not influenced by the CYP1A2 c.-163 A > C polymorphism.The study was registered on clinicaltrials.gov with ID: NCT05975489.Results: The aim of this study was to determine the influence of the CYP1A2 c.-163 A > C (rs762551) polymorphism on the effect of oral caffeine intake on fat oxidation during exercise.Using a pilot randomized, double-blind, crossover, placebo-controlled trial, 32 young and healthy individuals (women = 14, men = 18) performed an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Participants performed this test after the ingestion of (a) placebo; (b) 3 mg/kg of caffeine; (c) 6 mg/kg of caffeine. Fat oxidation rate during exercise was measured by indirect calorimetry. The influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation rates during exercise was established with a three-way ANOVA (substance × genotype × intensity).Eight participants were genotyped as AA, 18 participants were CA heterozygotes, and 6 participants were CC. There was a main effect of substance (F = 3.348, p = 0.050) on fat oxidation rates during exercise with no genotype effect (F = 0.158, p = 0.959). The post hoc analysis revealed that, in comparison to the placebo, 3 and 6 mg/kg of caffeine increased fat oxidation at 40–50% VO2max in AA (all p < 0.050) and 50–60% VO2max in CA and CC participants (all p < 0.050).Oral intake of 3 and 6 mg/kg of caffeine increased fat oxidation rate during aerobic exercise in individuals with AA, CA and CC genotypes. This suggests that the effect of caffeine to enhance fat oxidation during exercise is not influenced by the CYP1A2 c.-163 A > C polymorphism.The study was registered on clinicaltrials.gov with ID: NCT05975489.Conclusion: The aim of this study was to determine the influence of the CYP1A2 c.-163 A > C (rs762551) polymorphism on the effect of oral caffeine intake on fat oxidation during exercise.Using a pilot randomized, double-blind, crossover, placebo-controlled trial, 32 young and healthy individuals (women = 14, men = 18) performed an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Participants performed this test after the ingestion of (a) placebo; (b) 3 mg/kg of caffeine; (c) 6 mg/kg of caffeine. Fat oxidation rate during exercise was measured by indirect calorimetry. The influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation rates during exercise was established with a three-way ANOVA (substance × genotype × intensity).Eight participants were genotyped as AA, 18 participants were CA heterozygotes, and 6 participants were CC. There was a main effect of substance (F = 3.348, p = 0.050) on fat oxidation rates during exercise with no genotype effect (F = 0.158, p = 0.959). The post hoc analysis revealed that, in comparison to the placebo, 3 and 6 mg/kg of caffeine increased fat oxidation at 40–50% VO2max in AA (all p < 0.050) and 50–60% VO2max in CA and CC participants (all p < 0.050).Oral intake of 3 and 6 mg/kg of caffeine increased fat oxidation rate during aerobic exercise in individuals with AA, CA and CC genotypes. This suggests that the effect of caffeine to enhance fat oxidation during exercise is not influenced by the CYP1A2 c.-163 A > C polymorphism.The study was registered on clinicaltrials.gov with ID: NCT05975489.Trial registration: The aim of this study was to determine the influence of the CYP1A2 c.-163 A > C (rs762551) polymorphism on the effect of oral caffeine intake on fat oxidation during exercise.Using a pilot randomized, double-blind, crossover, placebo-controlled trial, 32 young and healthy individuals (women = 14, men = 18) performed an incremental test on a cycle ergometer with 3-min stages at workloads from 30 to 70% of maximal oxygen uptake (VO2max). Participants performed this test after the ingestion of (a) placebo; (b) 3 mg/kg of caffeine; (c) 6 mg/kg of caffeine. Fat oxidation rate during exercise was measured by indirect calorimetry. The influence of the CYP1A2 c.-163 A > C polymorphism in the effect of caffeine on fat oxidation rates during exercise was established with a three-way ANOVA (substance × genotype × intensity).Eight participants were genotyped as AA, 18 participants were CA heterozygotes, and 6 participants were CC. There was a main effect of substance (F = 3.348, p = 0.050) on fat oxidation rates during exercise with no genotype effect (F = 0.158, p = 0.959). The post hoc analysis revealed that, in comparison to the placebo, 3 and 6 mg/kg of caffeine increased fat oxidation at 40–50% VO2max in AA (all p < 0.050) and 50–60% VO2max in CA and CC participants (all p < 0.050).Oral intake of 3 and 6 mg/kg of caffeine increased fat oxidation rate during aerobic exercise in individuals with AA, CA and CC genotypes. This suggests that the effect of caffeine to enhance fat oxidation during exercise is not influenced by the CYP1A2 c.-163 A > C polymorphism.The study was registered on clinicaltrials.gov with ID: NCT05975489. [ABSTRACT FROM AUTHOR]

Purpose: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events.Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence’s certainty.From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events.Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting.Methods: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events.Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence’s certainty.From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events.Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting.Results: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events.Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence’s certainty.From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events.Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting.Conclusions: Nut-enriched diets are related to improve lipid and inflammatory biomarkers in meta-analyses in the context of primary cardiovascular prevention. However, primary studies on secondary cardiovascular prevention are scarce and controversial. This systematic review and meta-analysis aimed to evaluate the effect of nut supplementation on lipid and inflammatory profiles in individuals with atherosclerotic cardiovascular disease, and the frequency of adverse events.Six databases were used for research: PubMed, EMBASE, BVS, Cochrane Library, Web of Science, and ClinicalTrials.gov, until February 2023, with no language restrictions. We performed random-effects meta-analyses to compare nut-enriched diets vs. control diets for pre-post intervention changes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system assessed the evidence’s certainty.From the 5187 records identified, eight publications containing data referring to five randomized clinical trials involving 439 participants were included in the final analyses. The nuts evaluated were almonds, pecans, Brazil nuts, and mixed nuts, with doses ranging between 5 g and 85 g (median: 30 g/day). The intervention time varied between 6 and 12 weeks. Compared to nut-free diets, nut intake did not have a statistically significant effect on lipid profile biomarkers, except on the atherogenic index (MD: -0.32 [95% CI -0.58 to -0.06], I2 = 0% - moderate certainty of the evidence). Similarly, there was no effect of nuts on inflammatory profile biomarkers. It was not possible to aggregate data on adverse events.Nut supplementation did not change lipid and inflammatory profiles in the secondary cardiovascular prevention setting. [ABSTRACT FROM AUTHOR]

Purpose: The current study aimed to investigate the effects of legumes inclusion in the hypocaloric dietary approaches to stop hypertension (DASH) diet on fasting plasma glucose (FPG) and cardiometabolic risk factors in overweight and obese patients with type 2 diabetes over 16 weeks. Also, the modulatory effects of rs7903146 variant in the transcription factor 7 like 2 (TCF7L2) gene that is associated with the risk of diabetes, were assessed on these cardiometabolic risk factors. Methods: This study was a randomized controlled trial. Three-hundred participants, aged 30–65 years, whose TCF7L2 rs7903146 genotype was determined, were studied. The participants were randomly assigned to receive either the hypocaloric DASH diet or a hypocaloric legume-based DASH diet. The primary outcome was the difference in FPG change from baseline until the 16-week follow-up between the two dietary interventions. The secondary outcomes were differences in insulin resistance and lipid profile changes between the dietary intervention diets. Results: A reduction in FPG, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) was observed at week 16 in both hypocaloric dietary interventions. Compared to the DASH diet, the legume-based DASH diet decreased the FPG and HOMA-IR. There is no interaction between rs7903146 and intervention diets on glycemic parameters. Conclusion: The DASH diet, enrich in legumes, could improve the glycemic parameters in participants with type 2 diabetes, regardless of having rs7903146 risk or non-risk allele. Registration number of Clinical Trial: Iranian Registry of Clinical Trials (IRCT) (code: IRCT20090203001640N17). [ABSTRACT FROM AUTHOR]

Purpose: The perceived benefits and risks associated with seed oil intake remain controversial, with a limited number of studies investigating the impact of intake on a range of compounds used as cardiometabolic markers. This study aimed to explore the proteomic and cardiometabolic effects of commonly consumed seed oils in the UK, with different fatty acid profiles. Methods: In a parallel randomised control design, healthy adults (n = 84), aged 25–72 with overweight or obesity were randomised to one of three groups: control (habitual diet, CON); 20 mL rapeseed oil per day (RO), or 20 mL sunflower oil per day (SO). Blood, spot urine and anthropometric measures were obtained at 0, 6 and 12 weeks. Proteomic biomarkers analysis was conducted for coronary arterial disease (CAD) and chronic kidney disease (CKD) using capillary electrophoresis coupled to mass spectrometry (CE-MS). Blood lipids, fasting blood glucose, glycative/oxidative stress and inflammatory markers were also analysed. Results: No differences in change between time points were observed between groups for CAD or CKD peptide fingerprint scores. No change was detected within groups for CAD or CKD scores. No detectable differences were observed between groups at week 6 or 12 for the secondary outcomes, except median 8-isoprostane, ~ 50% higher in the SO group after 12-weeks compared to RO and CON groups (p = 0.03). Conclusion: The replacement of habitual fat with either RO or SO for 12 weeks does not lead to an improvement or worsening in cardiovascular health markers in people with overweight or obesity. Trial registration: Trial registration clinicaltrials.gov NCT04867629, retrospectively registered 30/04/2021. [ABSTRACT FROM AUTHOR]

Purpose: Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated. Methods: 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother's blood and cord blood were established. Results: During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy. Conclusions: These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM. [ABSTRACT FROM AUTHOR]

Purpose: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. Insulin resistance and dyslipidemia are linked to PCOS. l-Carnitine supplementation as a management strategy for women with PCOS has been proposed. The effect of l-carnitine supplementation on insulin resistance, sex hormone-binding globulin (SHBG) and lipid profile in overweight/obese women with PCOS was investigated. Methods: This randomized, double-blind, controlled clinical trial, was conducted on 62overweight/obese women with PCOS. Participants were randomly assigned into two groups to receive 1000 mg/day l-carnitine or placebo (1000 mg starch) for 12 weeks. Results: l-Carnitine supplementation compared to the placebo showed a significant improvement in insulin [− 0.7 (− 7.3 to 4.0) vs. 0.7 (− 3.0 to 5.2); P = 0.001], homeostatic model assessment for insulin resistance [− 0.4 (− 1.7 to 1.1) vs. 0.0 (− 0.7 to 1.3); P = 0.002], quantitative insulin sensitivity check index (+ 0.01 ± 0.02 vs. − 0.01 ± 0.01; P = 0.02) and a non-significant change toward improvement in SHBG (+ 11.5 ± 40.2 vs. − 3.2 ± 40.2; P = 0.2). However, there was no significant differences between the two groups in serum levels of fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein-cholesterol and high density lipoprotein cholesterol (P > 0.05). Conclusion: 12-week l-carnitine supplementation in overweight or obese women with PCOS ameliorate insulin resistance, but has no effect on SHBG and lipid profile. Studies with higher dosages and duration of l-carnitine intake are required. The trial was registered on 30 December 2019 at Iranian Registry of Clinical Trials IRCT20191016045131N1. Trial registration: Registered on 30th December 2019 at Iranian Registry of Clinical Trials (IRCT20191016045131N1). [ABSTRACT FROM AUTHOR]

Purpose: Regular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats. Methods: Four-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia. Results: At variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only. Conclusion: Our study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Purpose: To examine the associations of dietary patterns and nutrients with coronary artery calcification (CAC) and pericardial adiposity (PAT) in adults with and without type 1 diabetes. Methods: We conducted a six-year longitudinal analysis of data from Coronary Artery Calcification in Type 1 Diabetes study [n = 1255; T1D: n = 563; non-DM: n = 692] collected at baseline, year 3 and year 6. Participants completed a validated food frequency questionnaire, a physical examination, and fasting (12 h overnight fast) biochemical analyses. CAC and PAT were measured using electron beam computed tomography. Dietary patterns were identified using factor analysis. Generalized estimating equations were used to examine associations of dietary patterns and nutrients with CAC and PAT in models adjusted for traditional cardiovascular risks. Results: The 'starchy veggies, meats and alcohol pattern' was associated with significantly increased risk of CAC presence in all adjusted models; an increasing trend was observed with CAC progression. Increasing intake of dietary proteins and total fats were also associated with higher risk of the presence and/or progression of CAC in adjusted models (all p < 0.05). PAT was positively associated with dietary total fats, and inversely associated with dietary intakes of saturated fats, omega-3 fats and fiber in models adjusted for age, sex, total calories, time, diabetes status, systolic blood pressure, serum lipids and physical activity. Conclusion: Diets high in total fats and proteins, and in meats (processed and red) and alcohol may increase risks of CAC, while saturated fats, omega-3-fats and fiber may be protective against pericardial adiposity as a risk factor for coronary artery disease. ClinicalTrials.gov Identifier: NCT00005754. [ABSTRACT FROM AUTHOR]

Purpose: Dietary guidelines recommend to limit egg consumption to 4 servings per week but the relation between egg intake and health outcomes is still controversial. To evaluate the association of egg consumption and mortality risk in Italian adults and to investigate nutritional factors and serum lipids as potentially explaining such associations. Methods: Longitudinal analysis on 20,562 men and women aged ≥ 35y, free from cardiovascular disease (CVD) and cancer belonging to the Moli-sani Study cohort (enrolled 2005–2010) followed up for a median of 8.2 years. Results: In multivariable-adjusted analysis as compared to low intake (> 0 ≤ 1 egg/week), eating > 4 eggs/week led to an increased risk of all-cause (Hazard ratio [HR] = 1.50; 95%CI 1.13–1.99), CVD (HR = 1.75; 1.07–2.87) and cancer mortality (HR = 1.52; 0.99–2.33). Similarly, an intake of 2–4 eggs/week was associated with higher all-cause (HR = 1.22; 1.01–1.46) and CVD mortality risk (HR = 1.43; 1.03–1.97). An increase of 1 egg per week was associated with higher mortality risk among high-risk individuals, such as those with hypertension and hyperlipidaemia. Dietary cholesterol explained about 43.0% and 39.3% (p values < 0.0001) of the association of eggs with all-cause and CVD mortality, respectively, while serum lipids (e.g., total cholesterol) accounted for a small proportion of egg-mortality relation. Conclusions: Among Italian adults, high egg consumption leads to an increased risk of all-cause and CVD mortality, with the risk being evident even at the recommended intake of 2–4 eggs per week. A substantial part of this association was likely due to the egg contribution to dietary cholesterol. Our findings suggest limiting the consumption of eggs in the diet and these results should be considered in the development of dietary guidelines and updates. [ABSTRACT FROM AUTHOR]

Purpose: Human sirtuins can be a powerful therapeutic target in preventing and treating obesity and age-related diseases. Some dietary components can modulate sirtuins' activity, such as resveratrol. This systematic review aimed to assess whether resveratrol (RSV), without other interventions, can stimulate sirtuins in the treatment of excess weight and its comorbidities. Methods: MEDLINE/Pubmed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were used for search eligible articles. Randomized clinical trials assessing RSV supplementation on changes in the sirtuins' gene expression/protein levels was the primary outcome. Other possible changes in cardiometabolic markers were considered the second outcome. Following PRISMA guidelines and using predefined inclusion and exclusion criteria, two reviewers independently and in parallel screened, assessed the studies' quality, and compiled data. Disagreements were resolved by consensus or consulting a third author. Results: This review included seven randomized control trials. Four articles demonstrated a significant increase in SIRT-1 with different RSV dosages and interventions time. The secondary outcomes showed improvements in insulin sensitivity, lipid profile, metabolic flexibility, total antioxidant capacity, energy expenditure changes, and reduction of ectopic accumulation of fat. Conclusion: Data from RCTs studies showed that RSV supplementation could stimulate SIRT-1 in humans, and therefore contribute to the treatment of excess weight and its comorbidities. However, more research is needed because it was not possible to confirm this effect truly. [PROSPERO registration number: CRD42020205571] [ABSTRACT FROM AUTHOR]

Purpose: The effect of manipulating the fatty acid profile of the diet over generations could affect the susceptibility to develop obesity and metabolic disorders. Although some acute effects were described, the impact of transgenerational continuous supplementation with omega 3 fatty acids on metabolic homeostasis and skeletal muscle metabolic flexibility during a nutritional stress is unknown. Methods: We analyzed the effect of an obesogenic diet in mice after transgenerational supplementation with an omega-3 rich oil (mainly EPA) or a control oil. Young F3 animals received a high fat and high sucrose diet for 4 months. Whole-body biometric data were recorded and lipidomic/transcriptomic adaptations were explored in the skeletal muscle. Results: F3 mice from the lineage supplemented with EPA gained less weight, fat mass, and exhibited better metabolic parameters after the obesogenic diet compared to mice from the control lineage. Transcriptomic exploration of skeletal muscle showed differential regulation of biological processes such as fibrosis, fatty acid catabolism, and inflammation between lineages. These adaptations were associated to subtle lipid remodeling of cellular membranes with an enrichment in phospholipids with omega 3 fatty acid in mice from the EPA lineage. Conclusion: Transgenerational and continuous intake of EPA could help to reduce cardiovascular and metabolic risks related to an unbalanced diet by the modulation of insulin sensitivity, fatty acid metabolism, and fibrosis in skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a chronic disease and the prevalence of it is rapidly increasing. Recently, the use of natural products in chronic diseases such as diabetes has gained more attention. Chlorella, a single-celled green alga, is one of them. There have been some studies on the effects of chlorella supplementation in chronic diseases such as NAFLD, prediabetes, and diabetic mice, but none of them examined the effects of chlorella in patients with T2DM. The present study was designed to evaluate the effects of chlorella supplementation on glycemic control, lipid profile, and anthropometric indices in type 2 diabetic patients. Methods: This study is a double-blind, randomized controlled trial. 84 patients with T2DM assigned into two groups, receiving 1500 mg/day C. vulgaris or placebo for 8 weeks. Anthropometric information, blood pressure, 24-h food intake recall, and blood samples were collected at the beginning and end of the study to determine the changes of FBS, HbA1c, insulin concentration, insulin resistance, and lipid profile. Results: None of the variables investigated in this study showed a significant change after 8 weeks of intervention with C. vulgaris. Conclusion: According to the findings of this study, supplementation with C. vulgaris with a dosage of 1500 mg/day for 8 weeks, does not improve the anthropometric measurements, glycemic status, and lipid profile as well. Thus, it cannot be considered as a complementary therapeutic approach to common medications at this dosage and duration. However, future studies with a higher dosage of C. vulgaris and more prolonged than 8 weeks are needed to be done. [ABSTRACT FROM AUTHOR]

Purpose: Blueberry and cranberry are rich in anthocyanins. The present study was to investigate the effects of anthocyanin extracts from blueberry and cranberry on body weight and gut microbiota. Methods: C57BL/6 J Mice were divided into six groups (n = 9 each) fed one of six diets namely low-fat diet (LFD), high-fat diet (HFD), HFD with the addition of 1% blueberry extract (BL), 2% blueberry extract (BH), 1% cranberry extract (CL), and 2% cranberry extract (CH), respectively. Results: Feeding BL and BH diets significantly decreased body weight gain by 20–23%, total adipose tissue weight by 18–20%, and total liver lipids by 16–18% compared with feeding HFD. Feeding CH diet but not CL diet reduced the body weight by 27%, accompanied by a significant reduction of total plasma cholesterol by 25% and tumor necrosis factor alpha (TNF-α) by 38%. The metagenomic analysis showed that the supplementation of blueberry and cranberry anthocyanin extracts reduced plasma lipopolysaccharide concentration, accompanied by a reduction in the relative abundance of Rikenella and Rikenellaceae. Dietary supplementation of berry anthocyanin extracts promoted the growth of Lachnoclostridium, Roseburia, and Clostridium_innocuum_group in genus level, leading to a greater production of fecal short-chain fatty acids (SCFA). Conclusions: It was concluded that both berry anthocyanins could manage the body weight and favorably modulate the gut microbiota at least in mice. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the effects of vitamin K2 supplementation in the form of menaquinone-7 (MK-7) on glucose, insulin, and lipid metabolism in patients with type 2 diabetes mellitus (T2DM). Methods: In this double-blinded, placebo-controlled, randomized trial, 68 insulin-independent people with diabetes received either 180 µg MK-7 twice a day or placebo for 12 weeks. We assessed fasting plasma glucose (FPG) and insulin concentrations (primary outcomes), glycated hemoglobin (HbA1c), insulin sensitivity indices, and lipid profiles (secondary outcomes) at baseline and end of the trial. Results: At the end of the trial, FPG (effect size (ES) = − 0.68; p-adjusted = 0.031) and HbA1c (ES = − 0.36; p-adjusted = 0.004) were significantly lower in the vitamin K2 group compared with the placebo at the end of the trial. The number of participants achieved the target levels of glycemic control based on FPG, and HbA1c concentrations were significantly higher in the vitamin K2 group compared to the placebo group. Insulin concentrations (ES = − 0.29; p = 0.019) and homeostatic model assessment for insulin resistance (HOMA-IR) significantly decreased in the vitamin K2 group (ES = − 0.29; p = 0.019) compared to baseline, but their values were not significantly different compared to the placebo group at the end of the trial. No significant variation was observed in lipid profiles. Conclusion: Daily intake of 360 µg Vitamin K2 in the form of MK-7 for 12-weeks reduces FPG and HbA1c in patients with T2DM but does not have a lipid-lowering effect. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether high intake of cod or salmon would affect gut microbiota profile, faecal output and serum concentrations of lipids and bile acids. Methods: Seventy-six adults with overweight/obesity with no reported gastrointestinal disease were randomly assigned to consume 750 g/week of either cod or salmon, or to avoid fish intake (Control group) for 8 weeks. Fifteen participants from each group were randomly selected for 72 h faeces collection at baseline and end point for gut microbiota profile analyses using 54 bacterial DNA probes. Food intake was registered, and fasting serum and morning urine were collected at baseline and end point. Results: Sixty-five participants were included in serum and urine analyses, and gut microbiota profile was analysed for 33 participants. Principal component analysis of gut microbiota showed an almost complete separation of the Salmon group from the Control group, with lower counts for bacteria in the Bacteroidetes phylum and the Clostridiales order of the Firmicutes phyla, and higher counts for bacteria in the Selenomonadales order of the Firmicutes phylum. The Cod group showed greater similarity to the Salmon group than to the Control group. Intake of fibres, proteins, fats and carbohydrates, faecal daily mass and output of fat, cholesterol and total bile acids, and serum concentrations of cholesterol, triacylglycerols, non-esterified fatty acids and total bile acids were not altered in the experimental groups. Conclusion: A high intake of cod or salmon fillet modulated gut microbiota but did not affect faecal output or serum concentrations of lipids and total bile acids. Clinical trial registration: This trial was registered at clinicaltrials.gov as NCT02350595. [ABSTRACT FROM AUTHOR]

Purpose: Overweight and obesity are associated with many health problems, including cardiovascular disease (CVD). Evidence from previous studies has shown that extracts from olive leaves rich in olive phenolics are able to positively affect CVD risk factors, such as high blood pressure and dyslipidemia. The aim of this study was to investigate the effect of 8-week olive leaf extract (OLE) administration on blood lipid profiles in overweight/obese subjects with mildly elevated cholesterol levels. Methods: In this randomized, double-blind, placebo-controlled study, 77 healthy adult overweight/obese subjects (aged 56 ± 10 years and BMI 29.0 ± 2.7 kg/m2) with total cholesterol levels of 5.0–8.0 mmol/L (5.9 ± 0.7 mmol/L) were randomly assigned to receive 500 mg of OLE (n = 39) or placebo (n = 38) for 8 weeks. In total, 74 subjects completed the entire study protocol. At baseline, after 4 weeks, and after 8 weeks of supplementation, blood lipid profiles, oxidized low-density lipoprotein (oxLDL), blood pressure, glucose, and insulin levels were assessed. In addition, liver function parameters were measured at baseline and after 8 weeks. Results: OLE supplementation did not significantly affect blood lipid levels after 4 weeks or after 8 weeks compared to placebo (all p > 0.05). For oxLDL, blood pressure, glucose, and insulin levels and liver function parameters, also no statistically significant differences were found between the two intervention groups (all p > 0.05). Conclusions: Blood lipid profiles were not significantly affected by 8 weeks OLE supplementation in overweight/obese subjects with mildly elevated cholesterol levels. Trial registered: The trial has been registered at ClinicalTrials.gov (NCT02990637). [ABSTRACT FROM AUTHOR]

Purpose: Our recent study has reported that whole mung bean showed better beneficial effects on high-fat diet (HFD)-induced obesity and gut microbiota disorders when compared with the decorticated mung bean at the same intervention dose level, suggesting that the mung bean seed coat (MBC) may play a crucial role in its health benefits. This study aims to investigate whether MBC has beneficial benefits on the prevention of HFD-induced obesity and the modulation of gut microbiota in mice when it was supplemented in HFD. Methods: Herein, male C57BL/6 J mice were fed with normal control diet, HFD, and HFD supplemented with MBC (3–6%, w/w) for 12 weeks. The changes in physiological, histological, biochemical parameters, serum endotoxin, proinflammatory cytokines, and gut microbiota composition of mice were determined to assess the ability of MBC to alleviate HFD-induced obesity and modulate gut microbiota disorders in mice. Results: MBC supplementation exhibited significant reductions in the HFD-induced adiposity, fat accumulation, serum lipid levels, lipopolysaccharide, and proinflammatory cytokines concentrations (P < 0.05), which was accompanied by improvements in hepatic steatosis and adipocyte size. Especially, the elevated fasting blood glucose and insulin resistance were also significantly improved by MBC supplementation (P < 0.05). Furthermore, high-throughput sequencing of the 16S rRNA gene revealed that MBC could normalize HFD-induced gut microbiota dysbiosis. MBC not only could promote the bloom of Akkermansia , but also restore several HFD-dependent taxa (Blautia , Ruminiclostridium_9 , Bilophila , and unclassified_f_Ruminococcaceae) back to normal status, co-occurring with the decreases in obesity-related indices. Conclusions: This study provides evidence that MBC may be mainly responsible for the beneficial effects of whole mung bean on preventing the HFD-induced changes, thus enlarging the application value of MBC. [ABSTRACT FROM AUTHOR]

Purpose: Populations malnourished in early life are at increased risk for cardiometabolic diseases. We assessed if improved nutrition predicts cardiometabolic function, as assessed by postprandial biomarker responses. Methods: Participants had been randomized at the village level to receive one of two nutritional supplements as children. At mean age 44 y (range 37–53 years), we obtained plasma samples before and 2 h after a mixed-component meal challenge. We assayed biomarkers including lipids, glycemic measurements, and inflammatory cytokines. We compared postprandial biomarker responses among those who received the improved nutrition intervention from conception through to their second birthday (the first 1000 days) to those with other exposure status, including those who received the improved nutrition intervention at other ages, and those who received the less nutritious supplement. Results: Among 1027 participants (59.4% female), 22.9% were exposed to improved nutrition in the first 1000 days. Insulin increased the most in response to the meal challenge (over twofold), and non-esterified fatty acids decreased the most (by half). Glucose increased postprandial by 11.4% in the exposed group, compared with 15.7% in the other exposure group (p < 0.05), which remained significant after adjusting for confounders (− 4.7%; 95% confidence interval: − 9.3%, − 0.01%). Responses to the prandial challenges for the other biomarkers did not differ by intervention group (all p > 0.05). Conclusion: Early life exposure to improved nutrition was associated with a more favorable postprandial glucose response in this population. We did not observe a difference in overall cardiometabolic responses between the exposure groups. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of Nigella sativa (N.S) oil supplements on CVD risk factors in a crossover design for the first time. Methods: Obese and overweight healthy women were randomized to receive N.S oil (2000 mg/day) and placebo. This intervention period lasted for 8 weeks and separated by a 4-week washout period. An iso-caloric diet was given to every individual throughout the study. Blood pressure, lipid profile, atherogenic indices and liver enzymes were measured. Pkcross procedure was performed for statistical analyses using Stata software. Cohen's d was estimated as effect size for all outcomes to measure the magnitude of the effects. Results: Thirty-nine participants completed the study. Capsules of N.S increased serum high-density lipoprotein cholesterol (Cohen's d = 0.47, P = 0.009), reduced low-density lipoprotein cholesterol (Cohen's d = − 0.33, P = 0.031), reduced TC/HDL-C ratio (as an atherogenic index, Cohen's d = − 0.9, P < 0.001), reduced serum glutamic-oxaloacetic transaminase (Cohen's d = 0− 0.5, P = 0.038) and reduced systolic blood pressure (Cohen's d = − 0.4, P < 0.001). There was no effect on diastolic blood pressure measures (P = 0.96). Conclusion: The overall improvements in cardiovascular disease (CVD) risk factors showed beneficial effects of N.S supplements among adults with obesity to prevent possible cardiovascular diseases. More studies with different designs and in other populations are suggested to clarify the exact effects of N.S as a complementary therapy for modulating CVD risk factors in individuals with overweight and obesity. Trial registration: Iranian Registry of Clinical Trials, IRCT20180528039884N1, Registered on February 15th, 2019. [ABSTRACT FROM AUTHOR]

Purpose: Nonalcoholic fatty liver disease (NAFLD) is currently the leading cause of chronic liver disease in developing countries. The pathogenesis is complex, and there is currently no effective treatment. Betaine is an essential intermediate in choline catabolism and an important component of the methionine cycle. Betaine deficiency is associated with NAFLD severity, and its mechanism needs to be further elaborated. Methods: In this study, an NAFLD mouse model was established by feeding ApoE−/− mice a high-fat diet. The effects of betaine on NAFLD were investigated, including its mechanism. Results: In this study, after treatment with betaine, blood lipid levels and liver damage were significantly decreased in the NAFLD mouse model. The fat infiltration of the liver tissues of high-fat diet (HFD)-fed mice after betaine administration was significantly improved. Betaine treatment significantly upregulated AMP-activated protein kinase (AMPK), fibroblast growth factor 10 (FGF10), and adipose triglyceride lipase (ATGL) protein levels both in vivo and in vitro and suppressed lipid metabolism-related genes. Furthermore, the overexpression of FGF10 increased the protein level of AMPK and decreased lipid accumulation in HepG2 cells. Conclusion: Taken together, the data strongly suggest that betaine significantly prevents high-fat diet-induced NAFLD through the FGF10/AMPK signaling pathway in ApoE−/− mice. [ABSTRACT FROM AUTHOR]

Background: Hesperidin has been reported to have biological activities such as antihypertensive, hypoglycemic, and antioxidant effects. This study investigated whether hesperidin could improve signs of the metabolic syndrome and cardiac function in a high-fat diet (HFD) induced metabolic syndrome (MS) in rats. Methods: Male Sprague–Dawley rats were fed HFD and 15% fructose for 16 weeks and treated with hesperidin (15 or 30 mg/kg, based on signs of MS from a preliminary study) or metformin, a positive control agent, (100 mg/kg) for the final four weeks. Cardiac function, blood pressure, fasting blood glucose, oral glucose tolerance, serum insulin, and lipid profiles were measured. Histomorphometrics of left ventricles, epidydimal fat pads and liver were evaluated. Expressions of phosphorylate insulin receptor substrate1(p-IRS1), p-Akt and GLUT4 in cardiac tissue were determined. Results: Hesperidin and metformin attenuated MS in HFD rats (p < 0.05). The accumulation of visceral fat pads and fatty liver associated with increases in liver lipid contents and liver enzymes were found in MS rats that were alleviated in hesperidin or metformin-treated groups (p < 0.05). Hesperidin and metformin improved cardiac dysfunction and hypertrophy observed in MS rats (p < 0.05). Restoration of the insulin signaling pathway, IRS/Akt/GLUT4 protein expression, was demonstrated in hesperidin and metformin-treated groups (p < 0.05). Hesperidin (30 mg/kg) was more effective than the lower dose. Conclusion: Hesperidin was effective in reducing signs of MS and alterations of LV hypertrophy and function. These beneficial effects on the heart were associated with the restoration of the cardiac insulin signaling pathway in MS rats. [ABSTRACT FROM AUTHOR]

Purpose: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. Methods: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6–9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. Results: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group (− 0.05 vs. 0.00 mmol/L, regression coefficient (β) = − 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (β = − 0.0203, + 47% change in β) and butter-based spreads (β = − 0.0294, + 30% change in β), moderate-to-vigorous physical activity (β = − 0.0268, + 30% change in β), light physical activity (β = − 0.0274, + 29% change in β) and sedentary time (β = − 0.0270, + 30% change in β). The intervention had no effect on other plasma lipids. Conclusion: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. Clinical Trial Registry Number: NCT01803776, ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Purpose: We examined the impact of matrix food structure on post-prandial folate bioavailability (and other macronutrients) in human volunteers using a randomized, controlled, crossover experimental design. Methods: Twelve healthy male volunteers (22.6 ± 0.4 years old) were offered four food models (differing in matrix structure: Custard, Pudding, Sponge cake and Biscuit) to which 1 mg of folic acid was added, according to a randomized, controlled, crossover experimental design. Plasma folates, glucose, insulin, alpha amino nitrogen and triglycerides were measured over the post-prandial period (from T0 to T480 min). Results: Food matrix structure was capable of altering folate plasma availability. The highest folate availability was observed for pudding and to a lesser extent Sponge cake whereas the lowest was for the two matrices presenting extreme rheological properties: Custard (liquid) (P < 0.05 total AUC) and to a lesser extent Biscuit (hard solid) (P < 0.05, AUC 180 min). The analysis of plasma kinetics of appearance of other nutrients/metabolites helps to understand/explain the lower bioavailability of folates in Custard and Biscuit. Conclusion: A least overall efficient bio-accessibility of all macronutrients and folic acid is observed in the gut lumen for Biscuit (delayed/incomplete destructuration of biscuit along the digestive tract). On the contrary, the lower folic acid absorption observed with custard does not fit with the rapid plasma appearance of other nutrients and should require further investigation. [ABSTRACT FROM AUTHOR]

Purpose: Inconsistent evidence exists for greater satiety after medium-chain triglycerides (MCT) or conjugated linoleic acid (CLA) compared to long-chain triglycerides (LCT). Furthermore, the mechanisms are poorly understood and effects in people with a healthy weight and those with overweight/obesity have not been compared. This study aimed to compare appetite responses in these groups and examine the mechanisms behind any differences. Methods: Fifteen participants with healthy weight (BMI: 22.7 ± 1.9 kg·m−2) and fourteen participants with overweight/obesity (BMI: 30.9 ± 3.9 kg·m−2) consumed a breakfast containing either 23.06 g vegetable oil (CON), 25.00 g MCT oil (MCT), or 6.25 g CLA and 16.80 g vegetable oil (CLA). Appetite, peptide YY (PYY), total ghrelin (TG), β-hydroxybutyrate, and gastric emptying (GE) were measured throughout. Energy intake was assessed at an ad libitum lunch and throughout the following ~ 36 h. Results: Neither MCT nor CLA decreased ad libitum intake; however MCT decreased day 1 energy intake (P = 0.031) and the 48-h period (P = 0.005) compared to CON. MCT delayed GE (P ≤ 0.01) compared to CON, whereas CLA did not. PYY and TG concentrations were not different (P = 0.743 and P = 0.188, respectively), but MCT increased β-hydroxybutyrate concentrations compared to CON (P = 0.005) and CLA (P < 0.001). β-hydroxybutyrate concentrations were higher in participants with overweight/obesity (P = 0.009). Conclusion: Consumption of MCT reduces energy intake in the subsequent 48 h, whereas CLA does not. Delayed gastric emptying or increased β-hydroxybutyrate concentrations may mediate this. [ABSTRACT FROM AUTHOR]

Background and aims: Existing evidence on the possible effects of synbiotics on lipid profile is inconclusive. The aim of the present systematic review was to clarify the effects of synbiotics consumption on lipid profile. Methods: A systematic literature search of online databases PubMed, Scopus, ISI Web of science, Cochrane's library and Google Scholar was conducted up to January 2019. Randomized controlled trials (RCTs) investigating the effects of synbiotics on lipid profile in adults were included. The overall effect was presented as weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis model. Results: A total of 23 RCTs with 1338 participants were included. Synbiotic consumption resulted in a significant decrease in plasma concentrations of total cholesterol (WMD = − 10.17 mg/dL; 95% CI − 15.74 to − 4.60; p < 0.001), triglyceride (WMD = − 14.30 mg/dL; 95% CI − 25.32 to − 3.28; p = 0.01), low-density lipoprotein cholesterol (WMD = − 8.32 mg/dL; 95% CI − 13.21 to − 3.43; p < 0.001), and an increase in plasma high-density lipoprotein cholesterol (WMD = 1.3 mg/dL; 95% CI 0.03 to 2.56; p = 0.04) levels compared to control (placebo supplements/control foods/conventional products). The effects are more pronounced when synbiotics supplements are consumed for > 8 weeks. Conclusion: Synbiotic supplements may be beneficial to improve lipid profile, especially when they are consumed for > 8 weeks. [ABSTRACT FROM AUTHOR]