Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

Abstract

Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.

Lifestyle and Other Factors Explain One-Half of the Variability in the Serum 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Healthy Adults

“…We may have seen this result because our sample size was very large and we could adjust for many potential confounders. Our results also contrast with studies that reported a significant association between response to supplementation and BMI (27), including a systematic review suggesting that the dose per kilogram of body weight explains 34.5% of the serum response (28). Although BMI affected baseline serum 25(OH)D concentrations, it did not independently affect the serum response to supplementation in our study.…”

“…Although BMI affected baseline serum 25(OH)D concentrations, it did not independently affect the serum response to supplementation in our study. Other studies provide mixed or limited evidence that response to supplementation is associated with calcium intake, estrogen use, and dietary fat (27), but our results supported none of these associations. The inconsistencies seen across studies may reflect small sample sizes, as well as differences in the covariates collected and how they were measured.…”

“…The rs10766197 polymorphism of CYP2R1 was significantly associated with serum response in non-Hispanic whites, but it did not improve the explanatory value (R 2 ) of the multivariable model. Although our model confirmed the findings of others that response to supplementation varies with season of blood collection and baseline serum 25(OH)D concentration (27,42), other aspects of the analysis were unexpected. For example, we found a significantly greater proportional serum 25(OH)D concentration increase from supplementation in women than in men, a finding that, to our knowledge, has not been reported in other trials (5,21,27,43,44).…”

“…The inconsistencies seen across studies may reflect small sample sizes, as well as differences in the covariates collected and how they were measured. Age and race were not associated with response to supplementation in our study or in several others (21,27,(45)(46)(47)(48)(49)(50)(51). Several variables (being female, greater physical activity, wearing long pants and sleeves while outdoors, and personal vitamin D supplement use) contributed significantly to both baseline and response models; this suggests either that these factors are independent determinants of both baseline serum 25(OH)D concentration and response to supplementation, or that they have residual effects in the response model because they are imperfectly represented by baseline serum 25(OH)D concentration, e.g., because of measurement error.…”

“…Many factors are known to be associated with serum 25(OH)D concentrations, including sun exposure, BMI, skin pigmentation, medications, and comorbidities (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), but, to our knowledge, there is limited evidence on a few factors that may affect the magnitude of serum response to cholecalciferol supplementation, e.g., baseline serum 25(OH)D, BMI, age, calcium intake, and season (27,28). The NAM provides intake recommendations by age and sex, but it is unclear whether supplementation should be varied according to vitamin D status, weight, or other factors (7).…”