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Aim To gain further insight into intestinal cholesterol homeostasis in dyslipidaemic men with insulin resistance (IR) by examining the impact of treatment with ezetimibe on the expression of key genes involved in cholesterol synthesis and LDL receptor (R)-mediated uptake of lipoproteins. Methods A total of 25 men with dyslipidaemia and IR were recruited to participate in this double-blind, randomized, crossover, placebo-controlled trial. Participants received 10 mg/day ezetimibe or placebo for periods of 12 weeks each. Intestinal gene expression was measured by quantitative PCR in duodenal biopsy samples collected by gastroduodenoscopy at the end of each treatment. Results A total of 20 participants completed the protocol. Treatment with ezetimibe significantly increased intestinal LDLR (+16.2%; P = .01), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoAR; +14.0%; P = .04) and acetyl-Coenzyme A acetyltransferase 2 (ACAT-2) mRNA expression (+12.5%; P = .03). Changes in sterol regulatory element-binding transcription factor 2 (SREBP-2) expression were significantly correlated with changes in HMG-CoAR (r = 0.55; P

BACKGROUND To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. OBJECTIVES We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. DESIGN In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. RESULTS Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046). CONCLUSIONS DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003.

Dairy products are rich sources of an array of fatty acids (FA) that have been shown individually and in certain clusters to exert varying effects on cardiovascular health, for which the circulating lipid profile is a powerful biomarker. Whether the profile of these FA is reflected in blood upon short terms of intake, possibly contributing to the lipid-related health impacts of dairy products, remains to be fully established. The objectives of the present study were to assess a recommended dairy product consumption in relation to circulating FA and lipid profiles, and to evaluate certain FA in dairy fat as potential biomarkers of intake. In a free-living, multi-centre, cross-over design, 124 healthy individuals consumed 3 servings/d of commercial dairy (DAIRY; 1 % fat milk, 1·5 % fat yogurt and 34 % fat cheese) or energy-equivalent control (CONTROL; fruit and vegetable juice, cashews and a cookie) products for 4 weeks each, separated by a 4-week washout period. Plasma FA and serum lipid profiles were assessed by standard methods at the end of each dietary phase. After 4 weeks of intake, plasma levels of FA pentadecanoic acid (15 : 0) and heptadecanoic acid (17 : 0) were higher (0·26v.0·22 % and 0·42v.0·39 % of the total identified FA, respectively) after the DAIRY phase than after the CONTROL phase (PP= 0·04). In conclusion, intake of 3 servings/d of conventional dairy products may modify certain circulating FA and lipid profiles within 4 weeks, where 15 : 0 and 17 : 0 may be potential short-term biomarkers of intake.

Background: Randomized controlled trials specifically designed to assess inflammation-related outcomes in response to dairy consumption are lacking. Objective: We investigated the impact of dairy food consumption on biomarkers of inflammation in healthy men and women with low-grade systemic inflammation. Methods: In a multicenter randomized crossover study, 112 adult men and women with high-sensitivity C-reactive protein (hs-CRP) values >1 mg/L consumed 3s ervings/d of dairy (375 mL low-fat milk, 175 gl ow-fat yogurt, and 30 gr egular-fat cheddar cheese) or energy-matched control (fruit juice, vegetable juice, cashews, and 1 cookie) products as part of prudent 4-wk diets, each separated by a 4- to 8-wk washout period. Serum concentrations of inflammation biomarkers were measured at the beginning and end of each dietary phase. Expression levels of key inflammatory genes and transcription factors in whole blood cells were assessed at the end of each diet by real-time polymerase chain reaction in a random subset of 53 subjects. Results: Analysis of within-diet changes (post- vs. prediet values) showed a significant reduction in hs-CRP concentrations after the control diet (211.7%, P = 0.05) but no change after the dairy diet (27.3%, P = 0.47). As a result, changes in hs-CRP differed between the dairy and control diets (P = 0.04). Both the control and dairy diets similarly reduced interleukin-6 concentrations compared with diet-specific baseline values (217.6% and 219.9%, respectively; P < 0.0001 for both, P = 0.77 for between-diet comparison). No between- or within-diet difference was observed in adiponectin concentrations, and there was also no between-diet difference in the expression of inflammatory genes and transcription factors. Conclusion: Consistent with data from previous work, these results suggest that short-term consumption of a combination of low- and high-fat dairy products as part of a healthy diet has no adverse effects on inflammation. This trial was registered at www.clinicaltrials.gov as NCT01444326. J. Nutr. 144: 1760‐1767, 2014.

Aim: To investigate the effects of sitagliptin therapy on the kinetics of triglyceride-rich lipoprotein (TRL) apolipoprotein (apo)B-48, VLDL apoB-100, apoE and apoC-III in patients with type 2 diabetes. Methods: Twenty-two subjects with type 2 diabetes were recruited in this double-blind crossover study, during which the subjects received sitagliptin (100 mg/day) or placebo for a 6-week period each. At the end of each phase of treatment, the in vivo kinetics of the different apolipoproteins were assessed using a primed-constant infusion of L-[5,5,5-D3]leucine for 12 h, with the participants in a constantly fed state. Results: Sitagliptin therapy significantly reduced fasting plasma triglyceride ( −15.4%, p = 0.03), apoB-48 (−16.3%, p = 0.03) and free fatty acid concentrations (−9.5%, p = 0.04), as well as plasma HbA1c (placebo: 7.0% ± 0.8 vs. sitagliptin: 6.6% ± 0.7, p < 0.0001) and plasma glucose levels (−13.5%, p = 0.001), without any significant effect on insulin levels. Kinetic results showed that treatment with sitagliptin significantly reduced the pool size of TRL apoB-48 by −20.8% (p = 0.03), paralleled by a reduction in the production rate of these particles (−16.0%, p = 0.03). The VLDL apoB-100 pool size was also significantly decreased by sitagliptin therapy ( −9.3%, p = 0.03), mainly because of a reduction in the hepatic secretion of these lipoproteins, although this difference did not reach statistical significance ( −9.2%, p = 0.06). Conclusions: Treatment with sitagliptin for 6 weeks reduced triglyceride-rich apoB-containing lipoprotein levels by reducing the synthesis of these