We developed algorithms that explained 31, 22, and 42% of the variance in measured s25(OH)D levels in our black, white, and racially combined populations, respectively. The higher R2 of the combined model indicates that the race variable captures factors not accounted for, nor yet understood. Only age and sun exposure factor were found to have significantly different effects between races. Among blacks, sun exposure had a lesser impact than diet due to diminished cutaneous production of s25(OH)D. For both races, season had a higher impact on changes in s25(OH)D levels than any other factor, even after we included variables for sun exposure.
The difference we found in mean s25(OH)D levels between races is no doubt due in part to the differences in skin tone. Not only is the lighter toned skin of whites capable of greater production of s25(OH)D, cutaneously produced vitamin D3
has been reported to result in more sustained levels of s25(OH)D than does oral dosing of vitamin D2
Decreased production of cutaneous 7 dehydroxy cholesterol with age has been reported in Caucasians with skin type III, the most common skin type in the United States [14
]. This may contribute to the negative association of s25(OH)D levels with age which, in our white cohort, remained after adjustment for sun exposure factor, the only other variable found to decrease with age in sex-adjusted analyses. As in NHANES III reports [9
], we found no association between s25(OH)D and age among blacks, this difference with white subjects being nearly statistically significant (p
For whites, we found a negative association between BMI and s25(OH)D levels which is consistent with the literature [8
]. For blacks, the association in the age and sex-adjusted model disappeared in the multivariate model. In the literature, when only blacks are included in the model, the results vary [4
At first glance, the positive linear association that we found in whites between skin types I to IV and s25(OH)D levels and the curvilinear relationship in blacks appear to conflict with the understanding that the fairer the skin, the higher the conversion of pre-vitamin D to cholecalciferol per unit of UVB radiance [2
]. But photosensitive skin type is determined by the skin’s potential for tanning [44
] while skin color is determined by the amount of melanin in the skin [2
]. Skin types I and II correlate well with skin color, but skin types III and IV can have fair as well as darker tones prior to tanning. We found, along with others [52
], that those with greater ability to tan spend more time in the sunshine (p
= 0.03) explaining the higher levels of s25(OH)D with increasing skin type. That some effect of skin type on s25(OH)D persists after adjustment for sun exposure may be due to residual confounding.
Many studies have reported that s25(OH)D levels are lowest in winter and highest in summer when UV strength is at its peak [4
]. At least one study reported highest levels in the fall [9
]. Our study found levels in whites were lowest and began to rise when UVB intensity began its annual considerable increase in April [40
], continuing past the summer peak of UVB strength until January (). The continued rise through fall may imply a cumulative effect, s25(OH)D continuing to be stored while UVB strength is high, thereafter being released from storage for a time. Additionally, a positive association between amount of body exposed and UV season (p
= 0.004) in whites but not blacks indicates an increasing body exposure among whites during fall, which may explain the continuing rise in their s25(OH)D levels during this time. A similar trend in s25(OH)D levels in blacks occurred 1 and 2 months ahead of the whites (). The earlier start in decreasing s25(OH)D levels in blacks may be explained, at least in part, by the inability of their darker skin to produce vitamin D at the lower intensities of UVB radiation in the fall and by their lack of increased body exposure during that time.
The variables, UV season and erythemal zone which we constructed from maps of UV radiation weighted for erythemal reaction and which included UVA, B, and C were intended to improve the accuracy of season and latitude as surrogates for UVB exposure. While they did produce moderate improvements in R2
, further improvement is likely with the use of recently published maps of UV radiation which have been refined and weighted for pre-vitamin D3
] rather than erythemal reaction in human skin.
Whether our model will allow effective regression calibration remains to be seen in actual trials with disease endpoints. Giovannucci et al. [5
] used this approach to predict colon cancer risk with an R2
for predicting s25(OH)D of 0.28 in a model that included race. Compared to the (unattainable) average of a large number of serum values, using our predictive equations would reduce power by about 50%. However, using a single serum measure without adjustment for its with-in person random error will also result in a 30–40% reduction in power, but in addition, will bias effect estimates toward the null by about 50% [55
There are several limitations to this study including the relative inaccuracy of measuring certain exposure variables. There are the well-known effects of errors in dietary questionnaires [57
]. We did not separate cholecalciferol and ergocalciferol [58
], or account for other vitamin D metabolites found in animal products [60
]. The nutrient database values for vitamin D in foods and supplements are inaccurate, a problem currently being addressed by the Nutrient Data Laboratory [61
As with many questionnaire items, questions for duration of vitamin D-producing sun exposure and amount of body exposed requested ‘usual’, not ‘actual’, exposure times. We could not correct for the variation in strength of UVB that occurs throughout the day. We found neither advantage in separating exposure by time of day, nor weighting midday hours by 2 [46
]. We were also unable to adjust for the point at which cutaneous production of s25(OH)D levels plateau for each individual. Total sun time may have exceeded this point for many, especially those with lighter skin and longer daily sun exposure times.
The dynamics of lag time between UV exposure/vitamin D intake and s25(OH)D levels has not yet been fully elucidated. No calculations were made to differentiate between cutaneous production of vitamin D which results in a more sustained supply of s25(OH)D compared to oral vitamin D [49
]. Reports for the half-life of s25(OH)D vary from 2 weeks to 2 months [58
we obtained in our study compare favorably with other studies on US populations [4
], but are still relatively low. Other factors such as the common genetic variants of vitamin D binding protein which result in as much as a threefold difference in s25(OH)D levels [28
], and others yet unknown, may contribute to this.