Diurnal variation of hematology parameters in healthy young males: The Bispebjerg study of diurnal variations

Abstract

Purpose. To evaluate the influence of time of day on the circulating concentrations of 21 hematology parameters. Materials and methods. Venous blood samples were obtained under standardized circumstances from 24 healthy young men every third hour through 24 hours, nine time points in total. At each time point, the level of melatonin, iron, transferrin, transferrin saturation, ferritin, cobalamin, folate, red blood cells and white blood cells was measured. The data were analysed by rhythmometric statistical methods. The biological variations were calculated. Results. Significant oscillation of melatonin (p < 0.0001) with an amplitude (amp) of 19.84 pg/ml and a peak level at 03:34 h confirmed the normal 24-hour rhythms of the participants. Erythrocytes (p < 0.0001, amp = 0.15 × 10¹²/L), hemoglobin (p < 0.0001, amp = 0.29 mmol/L), hematocrit (p < 0.0001, amp = 0.01), iron (p < 0.0001, amp = 4.00μmol/L), transferrin (p = 0.03, amp = 1.41μmol/L), transferrin saturation (p < 0.0001, amp = 6.37%) and folate (p < 0.0001, amp = 1.55nmol/L) oscillated significantly, with gradually falling mean levels through the day to nadir around midnight. Leukocyte count (p < 0.0001, amp = 0.78 × 10⁹/L), neutrophils (p = 0.001, 0.31 × 10⁹/L), eosinophils (p < 0.0001, amp = 0.04 × 10⁹/L), monocytes (p = 0.0009, amp = 0.06 × 10⁹/L), lymphocytes (p < 0.0001, amp = 0.49 × 10⁹/L) oscillated significantly with gradually increasing mean levels through the day peaking at midnight. Iron, leukocytes and hemoglobin had the highest 24 hour oscillations in proportion to the reference intervals of the parameters for healthy young men. Conclusions. Biochemical screenings are biased by diurnal variations, which must be considered when blood concentrations of these parameters are interpreted in the clinical setting.

Key Words::

• Biological clocks
• biorhythms
• circadian rhythm
• chronobiology
• 24-hour rhythm

Acknowledgments

The skilful technical assistance of the laboratory technicians of the department, in particular Lone Hellstrøm, Jannik Pedersen and Anita Hansen is gratefully acknowledged. The study was supported by the Danish Biotechnology Center for Cellular Communication.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.