The impact of seasonality and other determinants on vitamin D concentration in childhood and adulthood: still an unresolved issue

We are thankful to Zostautiene et al. for their comments (1) on our study about the potential association between shorter duration of daylight at birth and vitamin D metabolism later in life in a Southern European country (i.e., Italy) (2). The authors carried out a similar investigation in a Northern European country (i.e., Norway), and concluded that the month of birth had no significant relation with later serum vitamin D concentration. Indeed, some important and valuable issues were raised to explain the differences observed in the two studies. First, we definitely agree that considerable differences exist in both duration and intensity of daylight between Northern and Southern Europe, and the much greater impact of sunlight exposure in Italy may represent a crucial element for explaining our separate findings. It is also remarkable that Norway has proactively established a widespread policy of vitamin D supplementation to infants, whereas in Italy supplementation is virtually inexistent. Therefore, our epidemiological data are seemingly more robust, since the potential bias attributable to an external influence of exogenous vitamin D on the endogenous metabolism of this hormone is clearly lower. Finally, the third issue raised by Zostautiene et al. about seasonality of blood collection is real. In a previous epidemiological study at our latitudes we also showed that the season of blood sampling is an important pre-analytical factor in the assessment of vitamin D status (3), wherein the frequency of subjects with vitamin D deficiency was found to be nearly double in blood samples drawn in winter and spring than in those collected in summer and autumn. Therefore, in order to rule out a potential bias due to blood sampling seasonality in our analysis about the impact of birth season on vitamin D status, we performed an additional multivariate analysis, entering serum vitamin D as dependent variable whereas age, sex, mean duration of daylight at birth and sampling season were entered as independent variables. Interestingly, age and vitamin D concentration remained unrelated, the strength of association between serum vitamin D and both gender and mean duration of daylight already found in our prior analysis was substantially confirmed, whereas a highly significant correlation was also observed between vitamin D status and season of sampling (Table 1).

Table 1 Multivariate analysis obtained by entering serum vitamin D as dependent variable, whereas age, sex, mean duration of daylight at birth and season of sampling were entered as independent variables
Full table

In conclusion, an intriguing scenario emerges combining our data with those of to Zostautiene et al. (1), in that the outcome of many epidemiological studies about vitamin D status may be dependent upon a number of pre-analytical and analytical variables (Table 2), which should always be considered when drawing definitive conclusions about the metabolism of this intriguing hormone in childhood and adulthood (4-6).

Table 2 List of potential confounders of vitamin D status in epidemiological investigations
Full table

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

1. Zostautiene I, Jorde R, Grimnes G. No association between birth season and vitamin D concentration in adults in a North Norwegian population—the Tromsø study. Ann Transl Med 2016;4:20.
2. Lippi G, Bonelli P, Buonocore R, et al. Birth season and vitamin D concentration in adulthood. Ann Transl Med 2015;3:231. [PubMed]
3. Bonelli P, Buonocore R, Aloe R, et al. Blood sampling seasonality as an important preanalytical factor for assessment of vitamin D status. J Med Biochem 2015;34:1-5.
4. Targher G, Pichiri I, Lippi G. Vitamin D, thrombosis, and hemostasis: more than skin deep. Semin Thromb Hemost 2012;38:114-24. [PubMed]
5. Lucas RM, Ponsonby AL, Dear K, et al. Vitamin D status: multifactorial contribution of environment, genes and other factors in healthy Australian adults across a latitude gradient. J Steroid Biochem Mol Biol 2013;136:300-8. [PubMed]
6. Touvier M, Deschasaux M, Montourcy M, et al. Determinants of vitamin D status in Caucasian adults: influence of sun exposure, dietary intake, sociodemographic, lifestyle, anthropometric, and genetic factors. J Invest Dermatol 2015;135:378-88. [PubMed]