Higher levels of serum 25-OHD were associated with better physical performance but did not predict rate of change in physical performance during follow-up. Our results are consistent with two longitudinal observational studies in postmenopausal women reporting no association between baseline levels of 25-OHD and change in physical performance over ≥3 years of follow-up.15,16
In contrast, two other longitudinal cohort studies reported significant association between baseline levels of serum vitamin D and change in physical performance.14,17
Wicherts et al.14
reported significantly greater 3-year declines in summary performance scores comparing participants with low serum 25-OHD (≤50
nmol/L) to those with high levels (75
nmol/L) in a study including 979 men and women in the Longitudinal Aging Study Amsterdam (LASA). This study did not report results separately for men and women. Another longitudinal study including 656 women in the Rancho Bernardo Study (RBS) reported that women in the lowest 25-OHD quartile (<80
nmol/L) compared to the highest quartile had accelerated rates of decline in the timed up and go test and timed chair-stands over 2.5 years of follow-up.17
These two longitudinal studies reporting a significant association between vitamin D and declines in physical performance differ from our study in terms of the distribution of vitamin D in the population. While the mean level of serum 25-OHD in the LASA population was similar to that in our study (53.9
nmol/L vs. 48.2
nmol/L), the percent of the study population with the highest levels of vitamin D in LASA (≥75
nmol/L) was almost twice the percent in the WHI (18% vs. 11%).14
The mean level of serum 25-OHD in the RBS cohort was much higher than the level in the current study (100.8 vs. 48.2
Perhaps the observed significant association between serum vitamin D and change in functional performance in these two latter trials with greater variability of serum vitamin D suggests that the benefits of vitamin D are observed only among those with greater levels of vitamin D. A small trial (n
=139) of vitamin D-deficient older adults reported a significant improvement in an aggregate measure of functional performance in the intervention group compared to a decline in the control group over a 6-month period.28
However, very large doses of vitamin D such as were administered in that trial may have unintended consequences, such as an increase in falling.29
Further, this follow-up period was very short, and it is not clear if the improvement would be sustained over a longer follow-up period.
Several reasons for the lack of an observed association between serum 25-OHD and change in physical performance in the current study should be considered. There is a lack of agreement about definitive categorizations of 25-OHD deficiency, although the 25-OHD cutoffs used in this study were previously found to be appropriate30
and the trends observed in the current study provide credibility for their use. Current evidence suggests that serum vitamin D levels <50
nmol/L indicate deficiency.30
It is also possible that the specificity of our physical performance tests may have been inadequate to detect the mechanisms by which 25-OHD is thought to affect neuromuscular response, such as by affecting a specific muscle type (e.g., fast twitch or slow twitch fibers), muscle contraction speed, or nerve conduction velocity.11
Error in our measurement of physical performance may have also biased our results toward the null. The physical performance summary score was a construct in which its internal consistency was measured with a Cronbach's alpha value of 0.60, indicating only fair reliability. Removal analysis indicated that of the three measures available for use in this study, grip strength was the least correlated with the total (r
=0.32). Despite its shortcomings, the summary score is important, as it gives a broader measure of physical performance that is not confined to the parameters of a single test. Finally, although all models controlled for baseline characteristics, health status, and physical activity, residual confounding from other factors related to decline in physical performance may still be present.
The WHI is a diverse longitudinal study; however, the results of this substudy, drawing from a sample that was disproportionately white (92%, 510 women), must be interpreted cautiously with respect to the general population. Furthermore, given racial disparities in disability,31
this study may underestimate the influence of serum 25-OHD in relation to change in physical performance.
In this longitudinal, observational study, higher serum 25-OHD was associated with better physical performance but did not predict change in physical performance over the 6-year period. Additional studies in diverse populations, including randomized clinical trials of moderate to high dose vitamin D supplementation, are warranted.