Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO)

Michelle Shardell, Anne R. Cappola, Jack M. Guralnik, Gregory E. Hicks, Stephen B. Kritchevsky, Eleanor M. Simonsick, Luigi Ferrucci, Richard D. Semba, Nancy Chiles Shaffer, Tamara Harris, Gudny Eiriksdottir, Vilmundur Gudnason, Mary Frances Cotch, Eric Orwoll, Kristine E. Ensrud, Peggy M. Cawthon

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


BACKGROUND: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health.

OBJECTIVES: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function.

METHODS: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes.

RESULTS: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets.

CONCLUSIONS: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

Original languageEnglish (US)
Pages (from-to)16-28
Number of pages13
JournalAmerican Journal of Clinical Nutrition
Issue number1
StatePublished - Jul 1 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.


  • extraskeletal health
  • gait speed
  • older adults
  • physical function
  • vitamin D
  • Body Composition
  • United States
  • Humans
  • Vitamin D Deficiency
  • Independent Living
  • Male
  • Sex Factors
  • Aged, 80 and over
  • Female
  • Italy
  • Aged
  • Physical Functional Performance
  • Vitamin D/analogs & derivatives

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Meta-Analysis
  • Research Support, N.I.H., Intramural
  • Journal Article
  • Research Support, N.I.H., Extramural


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