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

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) 2 D), 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. Design: Prospective cohort. Setting: Community-dwelling men. Participants: 1,915 men, aged 40-79 years. Interventions: Determination of association of total and free 25(OH)D and 1,25(OH) 2 D concentrations with survival status. Main outcome measure: Vitamin D results were grouped into quintiles. For total 25(OH)D, specific cut-off values were also applied. Cox proportional hazard models were used adjusted for centre, BMI, smoking, alcohol, physical activity, season of blood sample, kidney functionand number of comorbidities. Results: 469 (23.5%) men died during a mean follow-up of 12.3±3.4 years. Compared to those with normal vitamin D (>30 µg/L) men with a total 25(OH)D below 20 µg/L had an increased mortality [HR 2.03 (95%CI 1.39-2.96); p<0.001]. Likewise, men in the lowest three free 25(OH)D quintiles (<4.43 ng/L) had a higher mortality risk compared to the highest quintile [HR 2.09 (1.34-3.25); p<0.01]. Mortality risks were similar across all 1,25(OH) 2 D and vitamin D binding protein quintiles. Conclusions: Ageing men with vitamin D deficiency have a twofold 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.