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01. August 24

Absorption of bioactive peptides following collagen hydrolysate intake: a randomized, double-blind crossover study in healthy individuals

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 randomized, 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.


Virgilio N, Schön C, Mödinger Y, van der Steen B, Vleminckx S, van Holthoon FL, Kleinnijenhuis AJ, Silva CIF, Prawitt J

Front Nutr. 2024 Aug 1;11:1416643. doi: 10.3389/fnut.2024.1416643

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01. August 24

Characterisation of the lipolytic enzymatic activities of fungal rizoenzymes from Rhizopus oryzae in comparison to pancreatin from pigs

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 favor of rizoenzymes activity at already low pH values was observed.


Schön, C., Wacker, R., Rothe, M., Lipowicz, B. & Iphöfer, A

European Pharmaceutical Journal, 71(1), 2024. 53-60

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16. July 24

Prebiotic effect of oligofructose after 2 weeks supplementation with a low dose: A randomized, double-blind, placebo-controlled, cross-over study

Inulin and oligofructose are prebiotic dietary fibers 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.


Van Harsselaar J, Mödinger Y, Dharsono T, Menzel D, Theis S, Schön C

Journal of Functional Foods. Volume 119. August 2024

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09. June 24

Association between bilirubin and biomarkers of metabolic health and oxidative stress in the MARK-AGE cohort

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 favorable 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.


Schoissengeier V, Maqboul L, Weber D, Grune T, Bürkle A, Moreno-Villaneuva M, Franceschi C, Capri M, Bernhard J, Toussaint O, Debacq-Chainiaux F, Weinberger B, Gonos ES, Sikora E, Dollé M, Jansen E, Slagboom PE, Hervonnen A, Hurme M, Breusing N, Frank J, Bulmer AC, Wagner KH

iScience. 2024 Jun 9;27(7):110234. doi: 10.1016/j.isci.2024.110234. PMID: 39021797; PMCID: PMC11253506

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28. May 24

Oil-Based Curcuminoid Phospholipid Formulation Mimicking Natural Digestion Enhances Oral Bioavailability of Curcuminoids in Healthy Subjects

Curcumin, the fat-soluble active ingredient and major compound of curcuminoids contained in the curcuma root, is known for its physiological low absorption and bioavailability. Various formulations and galenic technologies are currently available on the market. In this study, the product tested was provided as a soft gelatin capsule containing curcuminoids in an oily matrix mixed with phospholipids (oil/phospholipids [PL]-based, no new technologies applied or artificial excipients added). This was intended to improve bioavailability of curcuminoids as well as to mimic the natural digestion process of fat-soluble substances. In particular, the oral bioavailability of curcuminoids in the oil/PL-based formulation was compared with the pure curcuminoids extract alone (reference product), in a randomized, cross-over, single oral dose study design. Twelve healthy subjects were administered 200 mg curcuminoids under fasting conditions. Pharmacokinetic parameters were analyzed from individual concentration–time curves of total curcuminoids, as well as the curcumin metabolite tetrahydrocurcumin (THC). Results showed significantly higher AUC0-8h levels after the intake of the oil/PL-based formulation for total curcuminoids (205.60 vs. 112.50 ng/mL*h, P = .0001) as well as for THC (347.30 vs. 118.90 ng/mL*h, P < .0001) in comparison to the pure curcuminoids extract. Cmax was also significantly higher for both parameters analyzed (total curcuminoids: 47.54 vs. 21.16 ng/mL, P = .0001; THC: 96.69 vs. 29.83 ng/mL, P < .0001). In addition, the uptake kinetic of total curcuminoids was significantly fastened with the oil/PL-based curcuminoids formulation compared with the pure curcuminoids extract (P = .0446). These data suggest an improved impact on curcuminoids uptake of the oil/PL-based formulation and confirms its good tolerability.


Wagner T, Wacker R, Klein T, Kompek A, Schön C

J Med Food. 2024 May;27(5):396-403. doi: 10.1089/jmf.2023.0185

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30. April 24

Synbiotic Bacillus megaterium DSM 32963 and n-3 PUFA Salt Composition Elevates Pro-Resolving Lipid Mediator Levels in Healthy Subjects: A Randomized Controlled Study

Beneficial health effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) are partly attributed to specialized pro-resolving mediators (SPMs), which promote inflammation resolution. Strategies to improve n-3 PUFA conversion to SPMs may, therefore, be useful to treat or prevent chronic inflammatory disorders. Here, we explored a synbiotic strategy to increase circulating SPM precursor levels. Healthy participants (n = 72) received either SynΩ3 (250 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) lysine salts; two billion CFU Bacillus megaterium; n = 23), placebo (n = 24), or fish oil (300 mg EPA plus DHA; N = 25) capsules daily for 28 days in a randomized, double-blind placebo-controlled parallel 3-group design. Biomarkers were assessed at baseline and after 2 and 28 days of intervention. The primary analysis involved the comparison between SynΩ3 and placebo. In addition, SynΩ3 was compared to fish oil. The synbiotic SynΩ3 comprising Bacillus megaterium DSM 32963 and n-3 PUFA salts significantly increased circulating SPM precursor levels, including 18-hydroxy-eicosapentaenoic acid (18-HEPE) plus 5-HEPE, which was not achieved to this extent by fish oil with a similar n-3 PUFA content. Omega-3 indices were increased slightly by both SynΩ3 and fish oil. These findings suggest reconsidering conventional n-3 PUFA supplementation and testing the effectiveness of SynΩ3 particularly in conditions related to inflammation.


Speckmann B, Wagner T, Jordan PM, Werz O, Wilhelm M, Tom Dieck H, Schön C

Nutrients. 2024 Jan 15;16(2):260. doi: 10.3390/nu16020260

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