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Background: (6S)-5-Methyltetrahydrofolate ((6S)-5-MethylTHF) is the physiological folate form in biological fluids. Salts of (6S)-5-MethylTHF may have advantages compared to folic acid and are increasingly used in foods and supplements. Objective and design: The present study describes the physicochemical properties of the (6S)-5-MethylTHF-2Chol salt as a source of methylfolate with respect to solubility, conductivity, and melting point. The pharmacokinetics of (6S)-5-MethylTHF-2Chol and folic acid were compared in a randomized controlled double-blind cross-over study using a single equimolar oral dose of each of the folate substances. Results: The solubility of the dicholine salt was very high (650 mg/mL in H2O and 40 mg/mL in H2O under acidic conditions). The incremental area under the curve (iAUC0-8h) was significantly higher after the administration of (6S)-5-MethylTHF-2Chol compared to folic acid ([1.64-fold, P < 0.0001] for total folate and 2.56-fold higher for (6S)-5-MethylTHF [P < 0.0001]). Discussion and conclusions: The bioavailability of (6S)-5-MethylTHF-2Chol is higher compared to folic acid. The crystalline structure of (6S)-5-MethylTHF-2Chol and its water solubility are advantageous in terms of stability in nutraceutical products and absorption in the gut. (6S)-5-MethylTHF-2Chol is the source of folate that may enable the development of new applications.

Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35-75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values.

Osteoarthritis (OA) is a prevalent degenerative joint disease, often affecting the elderly, characterized by cartilage degradation and bone remodelling, leading to pain, stiffness, and impaired movement. This 12-week, randomized, double-blind, placebo-controlled pilot study investigated the efficacy of a formulation containing collagen type II, glucosamine hydrochloride and chondroitin sulfate, in alleviating knee OA symptoms in subjects with mild to moderate knee pain. Fifty-four participants were enrolled, with 52 completing the study. Participants were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), performance-based physical function tests and global assessment tests. Results indicated significant improvements in the verum group compared to placebo. KOOS subscales showed improvements in symptoms (8.16%, p < 0.05), sport/recreation (25.25%, p < 0.01), and quality of life (27.66%, p < 0.001). Stiffness improved by 14.68% (p < 0.05) in the verum group. Both groups exhibited significant pain reduction (KOOS pain, p < 0.001 and p < 0.01 for verum and placebo, respectively). Performance-based measures, such as the Chair Stand test, improved significantly in both groups, though other metrics showed no significant differences. The verum group exhibited a linear improvement over 12 weeks, contrasting with the placebo group's initial response and subsequent plateau. SF-36 Physical Component scores improved in both groups (p < 0.05), but mental health scores remained unchanged. Global assessment favoured the verum group, with more participants reporting OA improvement and recommending the product (p < 0.01). Biomarkers hsCRP and COMP showed no significant changes, likely due to sample variability. While the study did not achieve its primary endpoint, the nutritional formulation demonstrated an excellent safety profile and encouraging improvements in patient-reported symptoms and quality of life, warranting larger confirmatory trials.

Heartburn and acid regurgitation are main symptoms of gastro-esophageal reflux, a widespread complaint with a significant impact on quality of life (QoL). Refluthin® for Heartburn chewable tablets (Refluthin) are a symptomatic treatment option containing a combination of an antacid (CaCO3, MgCO3) and a polysaccharide-rich extract with mucoprotective substances from Opuntia ficus-indica cladodes. To investigate performance and safety of Refluthin in the rapid and long lasting relief of heartburn and acid related gastric discomfort under practical use conditions, a prospective, clinical, uncontrolled, open-label study was conducted. Adults with symptomatic heartburn, acid regurgitation, and/or recurrent acid related gastric discomfort took one tablet Refluthin up to four times/day as needed for up to 4 weeks. Endpoints were both time to onset and duration of symptom relief; reflux symptom intensity/frequency; global assessments (QoL, performance, satisfaction, usability, tolerability); and safety. 81/100 participants (81%) responded with a first symptom relief within ≤ 20 min in ≥ 50% of the individual applications. Long lasting effects of > 120 min were reported by 83/100 (83%) participants. Significant reductions in heartburn event frequency and intensity were seen within the 4 weeks of intermittent use (p < 0.0001, respectively). Global assessment results and safety-relevant findings were also favorable. Results thus demonstrated a distinct rapid and long lasting symptom relief after intake of Refluthin, with a safe and easy use. The significant reductions in frequency and intensity of heartburn events over time indicate sustained effects under treatment. These long-term effects might be explainable by soothing and protection of the irritated mucous membrane by Refluthin.

It is widely recognized that dietary polyphenols have a strong tendency to interact with proteins, specifically those rich in proline residues. So far, the impact of a matrix rich in polyphenols, like coffee, on the bioavailability of amino acids (AAs) and bioactive peptides (BAPs) from collagen hydrolysates (CH) has not been elucidated. This study aimed to compare the bioavailability of the signature AAs and BAPs from bovine CH dissolved in coffee in healthy human volunteers. The clinical trial was carried out as randomized, cross-over design. CH were dissolved in water or coffee, respectively, and provided as single dose in a fasting state. The uptake of the CH signature AAs hydroxyproline (Hyp), glycine (Gly) and proline (Pro) and BAPs (Pro-Hyp, Hyp-Gly, Gly-Pro-Hyp) into the bloodstream was followed over a period of 360 min. Plasma concentrations were determined with UPLC-MS/MS. The peak concentrations of the free signature AAs after intake of CH dissolved in water occurred between 60 and 120 min. Notably, there were significant variations in the increase of plasma concentrations over time of Hyp and Pro when CH was dissolved in coffee. However, when considering the uptake of BAPs, the pharmacokinetic endpoints iAUC, ΔCmax, and Tmax demonstrated similarity between water and coffee. This study emphasizes the importance of understanding how different food matrices, such as water vs. coffee, affect the absorption of bioactive compounds from dietary sources, in this case from CH. Ongoing research aims to explore the connection between food matrices, BAPs and human health with the goal of optimizing dietary interventions for promoting overall well-being.

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 products 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 analyzed. 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.