Long-Term Selenium-Yeast Supplementation Does Not Affect Bone Turnover Markers: A Randomized Placebo-Controlled Trial

Giorgia Perri*, Tom R. Hill, John C. Mathers, Jennifer S. Walsh, Fatma Gossiel, Kristian Winther, Jacob Frölich, Lars Folkestad, Søren Cold, Richard Eastell

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Abstract

Higher selenium status has been associated with lower bone turnover markers (BTM) in epidemiological studies. However, the long-term impact of selenium supplementation on BTMs has not been studied. We investigated the effects of selenium supplementation on BTMs including osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), collagen type I cross-linked C-telopeptide (CTX), and bone alkaline phosphatase (BALP) in the short (6 months) and long term (5 years). A total of 481 Danish men and women (60–74 years) were randomized to receive placebo-yeast versus 100, 200, or 300 μg selenium as selenium-enriched yeast daily for 5 years. Plasma selenium concentration was measured using inductively coupled plasma mass spectrometry, and BTMs were measured in nonfasted samples at baseline, 6 months, and 5 years. Data were analyzed by ANCOVA to investigate the shape of the dose-response relationships. Covariates included age, body mass index, baseline selenium status, baseline BTM, smoking, alcohol, supplement use, and medication. Plasma selenium concentration (mean 86.5 μg/d at baseline) increased significantly with increasing selenium supplementation to 152.6, 209.1, and 253.7 μg/L after 6 months and remained elevated at 5 years (158.4, 222.4, and 275.9 μg/L for 100, 200, and 300 μg supplemental selenium/d, respectively (p < 0.001)). There was no change in plasma selenium concentration in the placebo-treated group. There was no significant effect of selenium supplementation on OC (6 months p = 0.37; 5 years p = 0.63), PINP (6 months p = 0.37; 5 years p = 0.79), CTX (6 months p = 0.91; 5 years p = 0.58) or BALP (6 months p = 0.17; 5 years p = 0.53). The relatively replete baseline selenium status in the study participants may explain this lack of effect. Testing in more deficient populations may provide further insights into the impact of selenium supplementation on bone health.

OriginalsprogEngelsk
TidsskriftJournal of Bone and Mineral Research
Vol/bind37
Udgave nummer11
Sider (fra-til)2165-2173
ISSN0884-0431
DOI
StatusUdgivet - nov. 2022

Bibliografisk note

Funding Information:
Support for the study came from the Danish Cancer Society; the Research Foundation of the County of Funen; Cypress Systems Inc.; the Danish Veterinary and Food Administration; the Council of Consultant Physicians, Odense University Hospital; the Clinical Experimental Research Foundation at Department of Oncology, Odense University Hospital; K.A Rohde's Foundation; and Dagmar Marshall's Foundation. The selenium and placebo tablets were provided by Pharma Nord ApS, Vejle, Denmark. Immunodiagnostic Systems (Boldon, UK) provided the reagents for the BTMs. We thank The MRC‐Versus Arthritis Centre for Integrated Research into Musculoskeletal Aging (CIMA) ( https://www.cimauk.org/ ) for funding the PhD program of study associated with this research. We also acknowledge the generous donations provided by Cumbria Community Foundation and Beverley Charitable Trust Fund throughout the associated PhD program of study. No funder had any role in the design, analysis, or writing of this article.

Funding Information:
RE received consultancy funding from IDS, Sandoz, Samsung, Haoma Medica, CL Bio, Biocon, Coherus, and Takeda; meeting presentations for Pharmacosmos, Alexion, and Amgen; and grant funding from Roche, Pharmacosmos, and Alexion. JSW received speaker's honoraria from Eli Lilly and Sandoz, grant funding from Alexion, donation of drug from Eli Lilly for clinical studies, and consulting fees from Mereo Biopharma. All other authors state that they have no conflicts of interest.

Funding Information:
We acknowledge Professor Kim Overvad for planning of the DK PRECISE pilot trial, Ann Knoop for inputting the earlier phases, and Peter Schnohr for collecting data from the Copenhagen City Heart Study. Support for the study came from the Danish Cancer Society; the Research Foundation of the County of Funen; Cypress Systems Inc.; the Danish Veterinary and Food Administration; the Council of Consultant Physicians, Odense University Hospital; the Clinical Experimental Research Foundation at Department of Oncology, Odense University Hospital; K.A Rohde's Foundation; and Dagmar Marshall's Foundation. The selenium and placebo tablets were provided by Pharma Nord ApS, Vejle, Denmark. Immunodiagnostic Systems (Boldon, UK) provided the reagents for the BTMs. We thank The MRC-Versus Arthritis Centre for Integrated Research into Musculoskeletal Aging (CIMA) (https://www.cimauk.org/) for funding the PhD program of study associated with this research. We also acknowledge the generous donations provided by Cumbria Community Foundation and Beverley Charitable Trust Fund throughout the associated PhD program of study. No funder had any role in the design, analysis, or writing of this article. Authors’ roles: RE, JSW, FG, LF, JF, and KW designed the research. RE, FG, FC, KW, and SC conducted the research. GP performed statistical analysis. GP, TRH, and JCM wrote the manuscript. GP had primary responsibility for final content. GP, TRH, JCM, FC, KHW, LF, SC, RE, and JSW revised the manuscript. All authors read and approved the final manuscript.

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