{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:09:28Z","timestamp":1791565768247,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ISURA\u2019s research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters\u2014including maximum concentration (Cmax), time to reach Cmax (Tmax), and area under the curve (AUC)\u2014were calculated. Results: Mean AUC0\u201324, Cmax, Tmax, and T\u00bd values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC0\u201324 for glucosamine was modestly higher with rGS (18,300 ng\u00b7h\/mL) than with cGS (12,900 ng\u00b7h\/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng\u00b7h\/mL; cGS: 50,600 ng\u00b7h\/mL), with a geometric mean ratio of 1.39, a delayed Tmax (6\u20138 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS\u2019 pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results.<\/jats:p>","DOI":"10.3390\/nu17152491","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:37:23Z","timestamp":1753861043000},"page":"2491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Does Salt Form Matter? A Pilot Randomized, Double-Blind, Crossover Pharmacokinetic Comparison of Crystalline and Regular Glucosamine Sulfate in Healthy Volunteers"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8843-0650","authenticated-orcid":false,"given":"Chuck","family":"Chang","sequence":"first","affiliation":[{"name":"Clinical Research, ISURA, Burnaby, BC V3N 4S9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afoke","family":"Ibi","sequence":"additional","affiliation":[{"name":"Clinical Research, ISURA, Burnaby, BC V3N 4S9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Research, ISURA, Burnaby, BC V3N 4S9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8118-2683","authenticated-orcid":false,"given":"Min","family":"Du","sequence":"additional","affiliation":[{"name":"Clinical Research, ISURA, Burnaby, BC V3N 4S9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Seok","family":"Roh","sequence":"additional","affiliation":[{"name":"Clinical Research, ISURA, Burnaby, BC V3N 4S9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6125-2277","authenticated-orcid":false,"given":"Robert","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Biology Department, University of British Columbia, Kelowna, BC V1V 1V7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2784-1435","authenticated-orcid":false,"given":"Julia","family":"Solnier","sequence":"additional","affiliation":[{"name":"Clinical Research, ISURA, Burnaby, BC V3N 4S9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/BRS.0b013e31826a0a8d","article-title":"The Effect of Glucosamine Sulfate on the Proliferative Potential and Glycosaminoglycan Synthesis of Nucleus Pulposus Intervertebral Disc Cells","volume":"38","author":"Mavrogonatou","year":"2013","journal-title":"Spine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1054\/mehy.1999.0954","article-title":"Sulfated Glycosaminoglycans and Glucosamine May Synergize in Promoting Synovial Hyaluronic Acid Synthesis","volume":"54","author":"McCarty","year":"2000","journal-title":"Med. 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