title: A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women-A Randomized Controlled Trial.
abstract: Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40-70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F₂-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women.
authors.affiliation: Department of Nutrition, School of Medicine-WG 48, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA. lynn.kam@case.edu.
authors.forename: Lynn
authors.initials: L
authors.lastname: Cialdella-Kam
authors.affiliation: Human Performance Laboratory, North Carolina Research Campus, Appalachian State University, 600 Laureate Way, Kannapolis, NC 28081, USA. niemandc@appstate.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Nieman
authors.affiliation: Levine Center for Health and Wellness, Queens University of Charlotte, 1900 Selwyn Avenue, Charlotte, NC 28274, USA. knaba@queens.edu.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Knab
authors.affiliation: Department of Health &amp; Exercise Science, Appalachian State University, ASU Box 32071, 111 Rivers Street, 050 Convocation Center, Boone, NC 28608, USA. shanelyra@appstate.edu.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Shanely
authors.affiliation: Human Performance Laboratory, North Carolina Research Campus, Appalachian State University, 600 Laureate Way, Kannapolis, NC 28081, USA. meaneyMP@appstate.edu.
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Meaney
authors.affiliation: North Carolina Research Campus, Dole Nutrition Research Laboratory, Kannapolis, NC 28081, USA. fuxia.jin@dole.com.
authors.forename: Fuxia
authors.initials: F
authors.lastname: Jin
authors.affiliation: Bioinformatics Services Division, North Carolina Research Campus, UNC Charlotte, 600 Laureate Way, Kannapolis, NC 28081, USA. wsha@uncc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.affiliation: Program in Cardiovascular &amp; Metabolic Diseases and Center for Computational Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. sujoy.ghosh@duke-nus.edu.sg.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers; D019587:Dietary Supplements; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008875:Middle Aged; D050177:Overweight / Q000097:blood / Q000378:metabolism*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005395:Fish Oils; D005419:Flavonoids
keywords: dietary supplement; flavonol; genomic profiling; omega-3; quercetin