In vitro dissolution behaviour and absorption in humans of a novel mixed L-lysine salt formulation of EPA and DHA

Introduction: Supplements with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are generally oil-based formulations containing their triacylglycerols, phospholipids or ethyl-esters (EE). Recently, a L-lysine salt of carboxylic EPA and DHA became available (Lys-FFA), which necessitated to study its oral absorption and plasma kinetics in humans. Objectives: The in vitro dissolution characteristics, oral bioavailability and 48 h plasma profiles of EPA and DHA (as triacylglycerides) of Lys-FFA, relative to a commercially available oil-based EE supplement. Methods: Dissociation of the lysine from the FFAs was studied in vitro applying simulated gastric (12 h) and intestinal (3 h) conditions. In an open label, randomized, two-way cross-over design, oral administration of Lys-FFA (500 mg EPA plus 302 mg DHA) versus EE (504 mg EPA plus 378 mg DHA) was studied over 48 h, in eight female volunteers. Plasma profiles of EPA and DHA were described by Area Under the Curve (AUC; 0–12 h), Cmax and Tmax. Results: Dissolution studies with Lys-FFA showed complete dissociation under both conditions. In volunteers Lys-FFA showed rapid absorption and high bioavailability indicated by significant differences in both the AUC0–12hr and Cmax when compared to the EE comparator (p0–12hr which was for EPA 5 times higher with Lys-FFA than with the EE formulation. Conclusion: This first-in-man study of Lys-FFA demonstrated rapid absorption of EPA and DHA and a considerably higher bioavailability compared to an EE supplement under fasting conditions. The release and absorption characteristics from this solid form offer several new options in terms of formulation technology and dosing.</p

Physical activity and sedentary behavior show distinct associations with tissue-specific insulin sensitivity in adults with overweight

The aim of this study is to investigate associations between the physical activity (PA) spectrum (sedentary behavior to exercise) and tissue-specific insulin resistance (IR). Methods: We included 219 participants for analysis (median [IQR]: 61 [55; 67] years, BMI 29.6 [26.9; 32.0] kg/m2; 60% female) with predominant muscle or liver IR, as determined using a 7-point oral glucose tolerance test (OGTT). PA and sedentary behavior were measured objectively (ActivPAL) across 7 days. Context-specific PA was assessed with the Baecke questionnaire. Multiple linear regression models (adjustments include age, sex, BMI, site, season, retirement, and dietary intake) were used to determine associations between the PA spectrum and hepatic insulin resistance index (HIRI), muscle insulin sensitivity index (MISI) and whole-body IR (HOMA-IR, Matsuda index). Results: In fully adjusted models, objectively measured total PA (standardized regression coefficient β = 0.17, p = 0.020), light-intensity PA (β = 0.15, p = 0.045) and moderate-to-vigorous intensity PA (β = 0.13, p = 0.048) were independently associated with Matsuda index, but not HOMA-IR (p > 0.05). A higher questionnaire-derived sport index and leisure index were associated with significantly lower whole-body IR (Matsuda, HOMA-IR) in men but not in women. Results varied across tissues: more time spent sedentary (β = −0.24, p = 0.045) and a higher leisure index (β = 0.14, p = 0.034) were respectively negatively and positively associated with MISI, but not HIRI. A higher sport index was associated with lower HIRI (β = −0.30, p = 0.007, in men only). Conclusion: While we confirm a beneficial association between PA and whole-body IR, our findings indicate that associations between the PA spectrum and IR seem distinct depending on the primary site of insulin resistance (muscle or liver)

International evaluation of circumferential resection margins after rectal cancer resection: insights from the Swedish and Dutch audits

Aim: This study aimed to determine predictive factors for the circumferential resection margin (CRM) within two northern European countries with supposed similarity in providing rectal cancer care. Method: Data for all patients undergoing rectal resection for clinical tumour node metastasis (TNM) stage I–III rectal cancer were extracted from the Swedish ColoRectal Cancer Registry and the Dutch ColoRectal Audit (2011–2015). Separate analyses were performed for cT1–3 and cT4 stage. Predictive factors for the CRM were determined using univariable and multivariable logistic regression analyses. Results: A total of 6444 Swedish and 12 089 Dutch patients were analysed. Over time the number of hospitals treating rectal cancer decreased from 52 to 42 in Sweden, and 82 to 79 in the Netherlands. In the Swedish population, proportions of cT4 stage (17% vs 8%), multivisceral resection (14% vs 7%) and abdominoperineal excision (APR) (37% vs 31%) were higher. The overall proportion of patients with a positive CRM (CRM+) was 7.8% in Sweden and 5.4% in the Netherlands. In both populations with cT1–3 stage disease, common independent risk factors for CRM+ were cT3, APR and multivisceral resection. No common risk factors for CRM+ in cT4 stage disease were found. An independent impact of hospital volume on CRM+ could be demonstrated for the cT1–3 Dutch population. Conclusion: Within two northern European countries with implemented clinical auditing, rectal cancer care might potentially be improved by further optimizing the treatment of distal and locally advanced rectal cancer