Aging Men With Insufficient Vitamin D Have a Higher Mortality Risk: No Added Value of its Free Fractions or Active Form

Dejaeger, Marian; Antonio, Leen; Bouillon, Roger; Moors, Hannes; Wu, Frederick CW; O'Neill, Terence W; Huhtaniemi, Ilpo T; Rastrelli, Giulia; Forti, Gianni; Maggi, Mario; Casanueva, Felipe F; Slowikowska-Hilczer, Jolanta; Punab, Margus; Gielen, Evelien; Tournoy, Jos; Vanderschueren, Dirk

doi:10.1210/clinem/dgab743

Aging Men With Insufficient Vitamin D Have a Higher Mortality Risk: No Added Value of its Free Fractions or Active Form

Author:

Dejaeger, Marian

Antonio, Leen ; Bouillon, Roger ; Moors, Hannes ; Wu, Frederick CW ; O'Neill, Terence W ; Huhtaniemi, Ilpo T ; Rastrelli, Giulia ; Forti, Gianni ; Maggi, Mario ; Casanueva, Felipe F ; Slowikowska-Hilczer, Jolanta ; Punab, Margus ; Gielen, Evelien ; Tournoy, Jos ; Vanderschueren, Dirk

Keywords:

Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, total 25(OH)D, free 25(OH)D, 1, 25(OH)(2)D, DBP, mortality, SERUM 25-HYDROXYVITAMIN D, D-BINDING PROTEIN, PARATHYROID-HORMONE, DISEASE MORTALITY, ALL-CAUSE, 1,25-DIHYDROXYVITAMIN-D, METAANALYSIS, 25(OH)2D, Adult, Aged, Follow-Up Studies, Humans, Male, Middle Aged, Mortality, Prospective Studies, Risk Assessment, Risk Factors, Vitamin D, Vitamin D Deficiency, Vitamin D-Binding Protein, Total 25(OH)D, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine, 3202 Clinical sciences

Abstract:

CONTEXT: Low total 25-hydroxyvitamin D (25(OH)D) has been associated with mortality. Whether vitamin D in its free form or 1,25-dihydroxyvitamin D (1,25(OH)2D), provide any additional information is unclear. OBJECTIVE: To determine what level of 25(OH)D is predictive for mortality and if free 25(OH)D or 1,25(OH) 2 D concentrations have any added value. METHODS: This prospective cohort comprised 1915 community-dwelling men, aged 40 to 79 years. Intervention included determination of association of total and free 25(OH)D and 1,25(OH) 2 D concentrations with survival status. Vitamin D results were grouped into quintiles. For total 25(OH)D, specific cutoff values were also applied. Cox proportional hazard models were used adjusted for center, body mass index, smoking, alcohol, physical activity, season of blood sample, kidney function, and number of comorbidities. RESULTS: A total of 469 (23.5%) men died during a mean follow-up of 12.3 ± 3.4 years. Compared to those with normal vitamin D values (> 30 µg/L), men with a total 25(OH)D of less than 20 µg/L had an increased mortality (hazard ratio [HR] 2.03 [95% CI, 1.39-2.96]; P < .001). Likewise, men in the lowest 3 free 25(OH)D quintiles (< 4.43 ng/L) had a higher mortality risk compared to the highest quintile (HR 2.09 [95% CI, 1.34-3.25]; P < .01). Mortality risks were similar across all 1,25(OH)2D and vitamin D binding protein quintiles. CONCLUSION: Aging men with vitamin D deficiency have a 2-fold increased mortality risk. Determinations of either the free fractions of vitamin D or measurement of its active form offer no additional information on mortality risks.