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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.

Aim In case of exocrine pancreatic insufficiency (EPI), the replacement of digestive enzymes with, for example porcine pancreatin or fungal rizoenzymes, is unavoidable under certain conditions. Current guidelines indicate that preparations from porcine pancreas have more advantageous physicochemical properties compared to those from fungi, especially at high bile salt concentrations, and that the latter can, therefore, only be used clinically to a limited extent. Since rizoenzymes are increasingly used in clinical practice, the present in vitro study investigated efficiency of enzymatic activity of rizoenzymes in comparison to pancreatin under various physiological and partly extreme environmental conditions. Materials and Methods The lipolytic properties of two typical preparations containing digestive enzymes from porcine pancreatin and rizoenzymes were compared (same dosage of activity units) at different pH values (pH 3-9), with the addition of different bile salt concentrations (0-15 mmol/L sodium taurocholate). Lipolytic activity was measured by quantifying the fatty acids released from olive oil substrate by liquid chromatography-tandem mass spectrometry after enzymatic digestion. Results For both enzyme preparations, the lipolytic activity maximum was reached at pH 7 with comparable fatty acid conversion rates (57% pancreatin, 58% rizoenzymes). However, in contrast to pancreatin, rizoenzymes were already active for certain fatty acids from pH 3 to 4. At a bile salt concentration up to 10 mmol/L taurocholate, there was an increase in activity of both enzyme preparations (rizoenzymes 69% vs. pancreatin 58% enzymatic conversion). Only at rather unphysiological concentration of 15 mmol/L during EPI, there was a slight decrease in activity (to 56%) for the rizoenzymes. Conclusions Rizoenzymes are an alternative therapeutic option for EPI. Relevant differences between rizoenzymes and pancreatin with regard to lipolytic activity under different physicochemical conditions could not be demonstrated in this study, whereas a potential advantage in favour of rizoenzymes activity at already low pH values was observed.

Inulin and oligofructose are prebiotic dietary fibres which affect gut microbiota and thereby host health. We aimed to demonstrate that 2.5 g/d oligofructose can lead to a significant increase in bifidobacteria thereby contributing to host health. 64 volunteers were randomized to consume 2.5 g/d Orafti® oligofructose or placebo for 14 days followed by a 4 week wash-out period and then crossed-over to the other intervention. Bifidobacteria and affect were assessed at the beginning and end of each intervention period. Furthermore, digestive function was documented daily. Bifidobacterium spp. increased significantly upon 2.5 g/d oligofructose intake compared to placebo (p = 0.016). Furthermore, stool frequency significantly increased during oligofructose compared to placebo (p = 0.0204) intake. With respect to affect, no significant changes were observed. This study is the first to demonstrate a significant increase in bifidobacteria coinciding with increased stool frequency after a very low dose of 2.5 g/d chicory oligofructose.

Recent studies have shown that elevated concentrations of unconjugated bilirubin (UCB) may be a protective host factor against the development of noncommunicable diseases (NCDs), whereas low levels of UCB are associated with the opposite effect. The results of this European study, in which 2,489 samples were tested for their UCB concentration using high-performance liquid chromatography (HPLC) and additional data from the MARK-AGE database were used for analysis, provide further evidence that elevated UCB concentrations are linked to a lower risk of developing NCDs and may act as a predictive marker of biological aging as individuals with elevated UCB concentrations showed favourable outcomes in metabolic health and oxidative-stress-related biomarkers. These findings underline the significance of studying individuals with moderate hyperbilirubinemia and investigate UCB routinely, also in the setting of aging, since this condition affects millions of people worldwide but has been underrepresented in clinical research and practice until now.