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

Abstract

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.

Identification of possible new salivary biomarkers of stress in sheep using a high-resolution quantitative proteomic technique

“…Maekawa et al (2017) reported that the lactoferrin ameliorates corticosterone-related acute stress and hyperglycemia in rats, and its effect, which could be attributed to the activation of the HPA axis. In a recent report performed in human, Shinjo et al (2018) indicated the possible application of lactoferrin in managing psychological stress being able to exert a suppression effect on the changed in parasympathetic and sympathetic activities evoked by the calculation task. Therefore, the pathway of actuation in stress response it could be at both levels (HPA and autonomic nervous system (SNA)).…”

Relationships between Parameters of the Cardiovascular System, Salivary Lactoferrin Level and Body Temperature during a Short-Term Human Whole-Body Exposure to Cold Air

“…Stress-protective effects of lactoferrin administration before stress are known, in particular, the severity of inflammation decreases with subsequent exposure to stress. (20) However, the presence of marginal high basic values of salivary lactoferrin may reflect a pronounced activity of oxidative processes during the development of inflammation in the tissues, which does not allow an adequate vascular and immune response to develop with subsequent exposure to cold and to ensure the preservation of body temperature. Therefore, the focus of vegetative and immune reactions in individuals with a high baseline lactoferrin level (more than 75th percentile)in terms of adaptation and/or maladaptation at low temperatures needs further special study.…”

Maternal Distress and Social Support are Linked to Human Milk Immune Properties

“…Although no such analysis has been published before, experimental studies in rodents and humans suggest a possible physiological base for this association. Single-dose oral administration of bovine LF was found to mitigate the physiological response to experimentally induced psychological stress in rats [60] and humans [61]. Thus, it is possible that in breastfeeding mothers with increased anxiety, LF is preferentially used to alleviate the consequences of higher stress and LF transfer to milk remains low.…”