Tier 4 — mechanistic

Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer

Jeffrey I Zwicker, Benjamin L Schlechter, Jack D Stopa, Howard A Liebman, Anita Aggarwal, Maneka Puligandla, Thomas Caughey, Kenneth A Bauer, Nancy Kuemmerle, Ellice Wong, Ted Wun, Marilyn McLaughlin, Manuel Hidalgo, Donna Neuberg, Bruce Furie, Robert Flaumenhaft, CATIQ Investigators11
JCI insight 2019 4(4):e125851

Bibliography

PubMed
PMID 30652973
PubMed Central
PMC6478409
DOI
10.1172/jci.insight.125851
Funding
Reported funding/support: Quercegen PharmaResearch fundingNational Heart, Lung, and Blood Institutehttps://doi.org/10.13039/100000050U54HL112302National Heart, Lung, and Blood Institutehttps://doi.org/10.13039/100000050see commentsNational Heart, Lung, and Blood Institutehttps://doi.org/10.13039/100000050U01HL143365R35HL135775, T32HL007917
Competing interests
Reported disclosure: JIZ serves as a consultant for Parexel and served on advisory boards for Bayer, Seattle Genetics, and Incyte. TW receives research support and serves on advisory boards for Janssen and Pfizer. RF is a consultant for PlateletDiagnostics. JDS is an employee of Rubius Therapeutics. DN serves as a trustee with stock ownership in Madrigal Pharmaceuticals and receives research funding from Pharmacyclics. HAL reports spousal consulting income from Alexion. MH discloses equity in Champions Oncology and research support and/or honoraria from Celgene, Pfizer, Bioline, Asana, Erytech, Bicycle, Berg, Roche, EMD, Oncomatryx, MedImmune, Bayer, Novartis, Targovax, MSD, and Bioncotech.

Study snapshot

DesignOpen-label phase 2 sequential dose-cohort study
ModelHuman observational research
Sample57 advanced-cancer patients: 28 at 500 mg and 29 at 1,000 mg
InterventionIsoquercetin 500 or 1,000 mg/day
Duration56 days
EndpointsPlatelet or coagulation measurements

What the study showed, in plain terms

Published in 2019, this source examined safety, interactions and special populations. Design: Open-label phase 2 sequential dose-cohort study. Sample/model: 57 advanced-cancer patients: 28 at 500 mg and 29 at 1,000 mg. The exposure or intervention was Isoquercetin 500 or 1,000 mg/day. Follow-up or treatment period: 56 days.

Coagulation biomarkers, including D-dimer at the higher dose, declined. No primary venous-thrombosis events or major hemorrhages were observed.

No randomized comparator. Absence of events in a small cohort does not establish thrombosis prevention, and tumor treatment was not the tested outcome.

Continue with Quercetin Data Center

For topic-level interpretation, read Quercetin Side Effects and Safety: A Practical Guide. This is a related guide; the citation panel separately identifies articles that directly cite this paper.

Key findings

  • Coagulation biomarkers, including D-dimer at the higher dose, declined.
  • No primary venous-thrombosis events or major hemorrhages were observed.
  • The recorded outcome domains were Platelet or coagulation measurements.
  • The exposure was observed rather than assigned as an isolated supplement treatment.

What this study can and cannot tell us

  • No randomized comparator. Absence of events in a small cohort does not establish thrombosis prevention, and tumor treatment was not the tested outcome.
  • Confounding, dietary patterns, illness, medication use and reverse causation can influence an association. Blood or dietary concentrations do not identify the effect of starting a capsule.
  • Source basis: Source check: accessible full text and indexed metadata. Missing method details, funding information or participant denominators are not inferred.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology