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© 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance. Methods: A total of 73 children with DS (aged 6-12 years) were randomized. Participants received 0.5% EGCG (10 mg/kg daily dose) or placebo for 6 months with 3 months follow up after treatment discontinuation. Results: In total, 72 children were treated and 66 completed the study. A total of 38 participants were included in theEGCGgroup and 35 in the placebo group. Of 72 treated participants, 62 (86%) had 229 treatment-emergent adverse events (AEs). Of 37 participants in the EGCG group, 13 (35%) had 18 drug-related treatment-emergent AEs and 12 of 35 (34%) from the placebo group had 22 events. In the EGCG group, neither severe AEs nor increase in the incidence of AEs related to safety biomarkers were observed. Cognition and functionality were not improved compared with placebo. Secondary efficacy outcomes in girls point to a need for future work. Conclusion: The use of EGCG is safe and well-tolerated in children with DS, but efficacy results do not support its use in this population. Peer Reviewed Article signat per 26 autors/es: Cécile Cieuta-Walti, Aida Cuenca-Royo, Klaus Langohr, Claire Rakic, Ma Ángeles López-Vílchez, Julián Lirio, Domingo González-Lamuño Leguina, Teresa Bermejo González, Jordi García García, Maria Rimblas Roure, Ana Aldea-Perona, Laura Forcano, Maria Gomis-Gonzalez, Sebastià Videla Cés, Florence Lacaille, Aimé Ravel, Clotilde Mircher, Hervé Walti, Nathalie Janel, Julien Dairou, Marilyne Lévy, Sophie Durand, Mara Dierssen, Silvia Sacco, Rafael de la Torre Fornell, PERSEUS Study Group

Context Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. Objective We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse. Methods Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated. Results An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment. Conclusion These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.

Results from epidemiological studies support the relationship between the consumption of phenolic-rich food and a low incidence of coronary heart disease (1)(2). The lower incidences of coronary heart disease and certain cancers in Mediterranean countries have been associated with diet, of which fruits, vegetables, legumes, and grains are the usual components and the major fat component is olive oil (3). The Mediterranean dietary pattern has been also shown to be effective in secondary prevention of coronary heart disease (4). Virgin olive oil is rich in phenolic compounds with strong antioxidant properties that protect olive oil from autooxidation (5). In addition, olive oil phenolic compounds have been shown to delay in vitro metal-induced and radical-dependent LDL oxidation (6)(7). Among the phenolic compounds in olive oil is tyrosol (4-hydroxyphenylethanol), which is also present in other dietary sources (8)(9) and has mild antioxidant properties (10)(11)(12). However, information on the bioavailability of dietary phenolic compounds in humans is scarce (13)(14). In bioavailability studies of phenolic compounds, one of the main problems is the estimation of the dose administered because these substances can be present in multiple forms in food. In the specific case of olive oil, phenolic compounds may be in the form of glycosides, polymers, and esters (12)(15). To our knowledge, the bioavailability of tyrosol from nonsupplemented dietary sources has not been described previously. Eight healthy volunteers were recruited (five men and three women; age range, 25–52 years). The local ethics committee, CEIC-IMAS (register no. 98/798/I), approved the protocol, and participants signed an informed consent. All volunteers could be considered healthy on the basis of physical examination and standard biochemical and hematological tests. Subjects had an mean weight of 75 ± 13.47 kg (men, 83.2 ± 4.4 kg; women, …