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Background Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) offer many health benefits, yet the absorption from standard ethyl ester (EE) formulation requires concurrent intake of a fatty meal. This study aimed to evaluate the absorption of EPA and DHA from a novel omega-3 formulation, Phospholipids + EPA/DHA (PL+), which combines high phospholipdi krill oil (KO) and EE, in comparison to a standard EE product under a low-fat dietary condition in healthy adults. Methods In this randomized, cross-over, single-dose study, the pharmacokinetic profiles of EPA and DHA from PL+ and EE product was assessed. Each product contained approximately 1200 mg EPA+DHA. Participants consumed a single dose of the capsules under a low-fat diet regimen, with plasma samples collected at baseline and over a 72-hour period after dosing. Following a 14-day washout period, participants crossed over to the alternate treatment. Plasma concentrations of EPA, DHA, and combined EPA+DHA were analysed. Results Twelve participants (six women and six men) were included, completed all study visits and were included in the analyses. The participants' mean age was 34.3 years (SD = 12.4), and the mean BMI was 22.6 kg/m² (SD = 3.2). The baseline-corrected incremental area under the curve (iAUC0-12h) for combined EPA+DHA was significantly higher for PL+ (255.5 [SD = 81.4] μg/mL*h) compared to EE (34.2 [SD = 33.4] μg/mL*h; P < 0.001). The treatment ratio of iAUC0-12h for PL+ relative to EE was 10.5 (95 % CI: 6.1 - 18.1; P < 0.001). Similar patterns were observed for iAUC0-24h and iAUC0-72h for combined EPA+DHA, as well as for EPA and DHA individually. Sensitivity analyses by adjusting the minimal difference on dose between products yielded consistent findings. Conclusions The results indicate that PL+ technology significantly enhances the absorption of EPA and DHA compared to standard EE alone in a low-fat dietary condition. These outcomes suggest that the absorption of EE formulations can be significantly improved through combination with high phospholipid krill oil, as evidenced by the performance of the PL+ formulation.

Background: Omega-3 fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are polyunsaturated fatty acids (PUFAs) with notable health benefits. Due to limited physiological production and insufficient dietary supply, external supplementation is important. Objective: This study aimed to compare the pharmacokinetics and bioavailability of EPA and DHA in AvailOm® omega-3-lysine salt (Lys-FFA) versus standard ethyl ester (EE) and triglyceride (TG) formulations after a single oral dose in healthy subjects. Design: A randomised, three-way crossover study was conducted with 21 healthy subjects. Results: Twenty-one subjects (10 men, 11 women) completed the study. The average age was 41.7 years, and the mean body mass index was 23.0 kg/m2. The Lys-FFA formulation showed significantly higher uptake of omega-3 fatty acids (EPA+DHA combined and each individually) compared to EE. Specifically, Lys-FFA had a 9.33-fold (0-12 h) and 8.09-fold (0-24 h) higher bioavailability of EPA+DHA than EE and a 1.57-fold (0-12 h) and 1.44-fold (0-24 h) higher bioavailability than TG. ΔCmax and Tmax also favoured Lys-FFA over EE. Discussion: Under fasting conditions, the absorption of EPA and DHA from EE is limited due to the need for enzymatic cleavage before absorption. This requirement is bypassed with Lys-FFA, which does not need cleavage. Conclusions: The study demonstrates that EPA and DHA lysine salt (Lys-FFA) offers superior bioavailability compared to EE and triglyceride forms, presenting a more effective supplementation option.

The implication of Torquetenovirus (TTV) in ischemic heart disease (IHD) has not been thoroughly explored. This study investigated the association between TTV viremia, pro-inflammatory cytokines, and IHD risk in an aging population. This cross-sectional study included 900 non-IHD subjects and 86 individuals with IHD (aged 55-75 years) selected from the MARK-AGE project. Results were verified in another independent Report-Age cohort, including 94 inpatients with chronic IHD and 111 inpatients with non-IHD (aged 65-96 years). Multivariable logistic regression in the MARK-AGE cohort revealed that male sex, TTV viremia ≥4log, Cu/Zn ratio, diabetes, hypertension, and smoking were significant IHD predictors. Notably, TTV viremia ≥4log independently increased the IHD risk (odds ratio [OR]: 2.51, 95% confidence interval [CI]: 1.42-4.43), confirmed in the Report-Age cohort (OR: 4.90, 95% CI: 2.32-10.39). In a RASIG subgroup, individuals with TTV viremia ≥4 log, both with and without IHD, exhibited increased plasma pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, TNF-α) compared to those with TTV viremia <4 log. No significant difference in cytokine production was observed between IHD patients and non-IHD with TTV viremia ≥4 log. A positive correlation between TTV viremia and DNA methylation estimator of leukocyte telomere length was observed in Report-Age patients. Additionally, IHD Report-Age patients with TTV viremia ≥4 log displayed higher NLR and SIRI index than those with TTV viremia <4 log. In conclusion, a high TTV viremia is associated with an elevated IHD risk in the older population, potentially arising from an augmented pro-inflammatory response and immunosenescence.

Scope: A mixture of (6S)-5-methyltetrahydrofolate-calcium salt ((6S)-5-MTHF-Ca) and folic acid (FA) from multimicronutrient supplements may show a dose-dependent effect on serum folate concentrations. Methods and results: The study compares fasting concentrations of serum folate spices after 8 weeks of either 400 or 800 µg day-1 of 1:1 folate mixture in 172 non-pregnant women. Serum (6S)-5-MTHF concentrations raise from a mean (SD) of 19.1 (13.4) to 73.9 (19.6) nmol L-1 in the 800 µg group and from 17.5 (9.4) to 54.5 (21.1) nmol L-1 in the 400 µg group (p < 0.001 within-group changes). The raise in serum (6S)-5-MTHF is stronger in the 800 µg compared to the 400 µg group (p < 0.001 between-group). The prevalence of FA concentrations ≥0.20 nmol L-1 increases between baseline and week 8 in both groups, but is not different between the groups (p = 0.116). The mean percentage of (6S)-5-MTHF of total serum folate increases in both intervention groups, but is not different between the groups at 8 weeks (95.5 (4.1)% versus 94.4 (5.7)%, p = 0.309). Conclusions: Supplementation of multimicronutrients with 800 µg folate mix for 8 weeks causes higher serum (6S)-5-MTHF concentrations, but not a higher prevalence of detectable FA compares to 400 µg folate.

The predictive value of the susceptibility to oxidation of LDL particles (LDLox) in cardiometabolic risk assessment is incompletely understood. The main objective of the current study was to assess its relationship with other relevant biomarkers and cardiometabolic risk factors from MARK-AGE data. A cross-sectional observational study was carried out on 1089 subjects (528 men and 561 women), aged 40-75 years old, randomly recruited age- and sex-stratified individuals from the general population. A correlation analysis exploring the relationships between LDLox and relevant biomarkers was undertaken, as well as the development and validation of several machine learning algorithms, for estimating the risk of the combined status of high blood pressure and obesity for the MARK-AGE subjects. The machine learning models yielded Area Under the Receiver Operating Characteristic Curve Score ranging 0.783-0.839 for the internal validation, while the external validation resulted in an Under the Receiver Operating Characteristic Curve Score between 0.648 and 0.787, with the variables based on LDLox reaching significant importance within the obtained predictions. The current study offers novel insights regarding the combined effects of LDL oxidation and other ageing markers on cardiometabolic risk. Future studies might be extended on larger patient cohorts, in order to obtain reproducible clinical assessment models.

Background: Collagen hydrolysates (CH) in functional foods and supplements are dietary sources of amino acids (AAs) and di- and tripeptides linked to various health benefits. This study aimed to investigate the single-dose bioavailability of skin- and hide-derived CH from fish, porcine and bovine origin with different molecular weights (bovine 2,000 and 5,000 Da). Methods: A randomised, double-blind crossover clinical study was performed with healthy volunteers assessing the plasma concentration of free and peptide-bound hydroxyproline (Hyp) as well as selected peptides reported to be abundantly present in collagen. Results: The pharmacokinetic endpoints demonstrated comparable uptake of free Hyp from all CH. A higher amount of total compared to free Hyp indicated the uptake of substantial amounts of Hyp-containing di- or tripeptides. Conclusion: Independently of source and molecular weight, all CH yielded relevant plasma concentrations of the investigated metabolites. Larger studies are needed to estimate an ideal level of selected circulating metabolites needed to trigger distinct physiological reactions in target tissues.