Oral lactoferrin influences psychological stress in humans: A single-dose administration crossover study

Lactoferrin is a secretory protein with various physiological functions. Bovine lactoferrin has been demonstrated to alleviate psychological stresses in rats, but this effect in humans has not yet been assessed. The present study aimed to investigate the changes in psychological stress markers following a calculation task, with either lactoferrin or a placebo orally administered prior to the task. A total of 16 healthy female college students visited Juntendo University, Inzai, Japan following an overnight fast. Subjects were quietly seated for 15 min to stabilize the respiratory rate at 0.25 Hz (one breath every 4 sec). Then, subjects provided saliva, ingested either lactoferrin (800 mg of lactoferrin + soy milk) or a placebo (soy milk), remained seated for another 15 min with respiration rate at 0.25 Hz, and performed a calculation task. The task comprised two sets of 15-min calculations, with a 5-min interval between sets. Each calculation set consisted of various multiplications and divisions using pairs of three-digit numbers. Following the calculation task, saliva was collected again. Heart rate was also monitored to identify the frequency domain of heart-rate variability. The calculation task resulted in increased activity of salivary amylase, and decreased concentration of chromogranin A for both lactoferrin (P=0.028 and P<0.001, respectively) and placebo (P=0.003 and P<0.001, respectively) treatments. The degrees of changes in these salivary markers were similar between the two treatments. Heart rate variability exhibited an increase in the high-frequency (HF) component (P=0.022) and a decrease in low-frequency (LF)/HF and LF/(LF+HF) ratios (both P<0.001) following the calculation task under the placebo condition, demonstrating an upregulation of parasympathetic and a downregulation of sympathetic nervous activities. These changes in parasympathetic (HF) and sympathetic (LF/HF) activities, however, were alleviated by lactoferrin compared with the placebo (P=0.007 and P=0.026, respectively). Collectively these results suggest that oral lactoferrin may mitigate psychological stress in humans.