Vitamin D levels observed to vary by 20 percent during a day – Feb 2019

25-Hydroxyvitamin D variability within-person due to diurnal rhythm and illness: a case report

Journal of Medical Case Reports volume 13, February 2019
Christine B. French, Sharon L. McDonnell & Reinhold Vieth

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3 days for a person who had been taking 5,000 IU of Vitamin D daily at noon for a year

Note: Portion showing a sick day was removed from this chart

Background
Vitamin D nutrition research requires accurate measures of circulating 25-hydroxyvitamin D. Our objectives were to test whether a diurnal fluctuation in blood-spot concentrations of 25-hydroxyvitamin D can be demonstrated statistically in a single individual, and whether such fluctuation is affected by the pre-dose versus post-dose timing of the blood draw.

Case presentation
The participant in this case study was a generally healthy Caucasian woman in her 40s who has taken 5000 IU vitamin D3 supplement at midday for over 1 year. Each blood sample was drawn individually from a finger prick onto filter paper at morning, midday, or night, on 4 days (three groups of five individual blood samples per collection day). On days 1 and 2, the midday samples were collected approximately 1 hour after the supplement was taken; on days 3 and 4, the midday samples were collected within an hour prior to supplementation (the classical, daily “trough” value for a drug). There was a significant daily pattern of variation in 25-hydroxyvitamin D concentrations (analysis of variance p ≤ 0.02 for 3 of the 4 days): peak midday mean 25-hydroxyvitamin D was approximately 20% higher than in the morning, and approximately 13% higher than in the evening. Trough sampling produced no significant difference in 25-hydroxyvitamin D compared to sampling an hour after the dose. An incidental finding was that acute illness during the study was related to acutely lower 25-hydroxyvitamin D at every sampling time in the day (p < 0.00001).

Conclusions
There was a consistent diurnal variation in 25-hydroxyvitamin D, with the peak at midday. There was no difference between trough versus post-dose blood draws. Acute illness may acutely lower serum 25-hydroxyvitamin D levels. Because within-person, within-day variability in 25-hydroxyvitamin D is approximately 20%, sampling time introduces systematic error in vitamin D nutritional assessment that is bigger than random analytical error or choice of assay method.

References

1. Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab. 2002;87:4952-6.
2. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89:5387-91.
3. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303:1815-22.
4. Ish-Shalom S, Segal E, Salganik T, Raz B, Bromberg IL, Vieth R. Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. J Clin Endocrinol Metab. 2008;93:3430-5.
5. Binkley N, Carter GD. Toward Clarity in Clinical Vitamin D Status Assessment: 25(OH)D Assay Standardization. Endocrinol Metab Clin N Am. 2017;46:885-99.
6. Sempos CT, Betz JM, Camara JE, Carter GD, Cavalier E, Clarke MW, Dowling KG, Durazo-Arvizu RA, Hoofnagle AN, Liu A, Phinney KW, Sarafin K, Wise SA, Coates PM. General Steps to Standardize the Laboratory Measurement of Serum Total 25-Hydroxyvitamin D. J AOAC Int. 2017;100:1230-3.
7. Jones KS, Redmond J, Fulford AJ, Jarjou L, Zhou B, Prentice A, Schoenmakers I. Diurnal rhythms of vitamin D binding protein and total and free vitamin D metabolites. J Steroid Biochem Mol Biol. 2017;172:130-5.
8. Masood T, Kushwaha RS, Singh R, Sailwal S, Pandey H, Varma A, Singh RK, Cornelissen G. Circadian rhythm of serum 25 (OH) vitamin D, calcium and phosphorus levels in the treatment and management of type-2 diabetic patients. Drug DiscovTher. 2015;9:70-4.
9. Institute of Medicine Committee to Review Dietary Reference Intakes for Vitamin D, Calcium. The National Academies Collection: Reports funded by National Institutes of Health. In: Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US) National Academy of Sciences; 2011.
10. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911-30.
11. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69:842-56.
12. Eyles D, Anderson C, Ko P, Jones A, Thomas A, Burne T, et al. A sensitive LC/ MS/MS assay of 25OH vitamin D(3) and 25OH vitamin D(2) in dried blood spots. Clin Chim Acta. 2009;403(1-2):145-51.
13. ZRT Laboratory. Blood Spot Test Specifications 25-Hydroxy Vitamin D2/D3. http://www.zrtlab.com/media/1086/vitamin_d_bs_test_specs.pdf. Accessed 17 Aug 2018.
14. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014;2:76-89.
15. Madden K, Feldman HA, Chun RF, Smith EM, Sullivan RM, Agan AA, Keisling SM, Panoskaltsis-Mortari A, Randolph AG. Critically Ill Children Have Low Vitamin D-Binding Protein, Influencing Bioavailability of Vitamin D. Ann Am Thorac Soc. 2015;12:1654-61.
16. Ghafouri B, Carlsson A, Holmberg S, Thelin A, Tagesson C. Biomarkers of systemic inflammation in farmers with musculoskeletal disorders; a plasma proteomic study. BMC Musculoskelet Disord. 2016;17:206.
17. Delanghe JR, Speeckaert R, Speeckaert MM. Behind the scenes of vitamin D binding protein: more than vitamin D binding. Best Pract Res Clin Endocrinol Metab. 2015;29:773-86.