ß-Eudesmol, an Oxygenized Sesquiterpene, Reduces the Increase in Saliva 3-Methoxy-4-Hydroxyphenylglycol After the "Trier Social Stress Test" in Healthy Humans: A Randomized, Double-Blind, Placebo-Controlled Cross-Over Study.

Hops, the immature inflorescences of the female hop plant (Humulus lupulus L.) are one of the main components of beer and provides flavor and bitterness. ß-Eudesmol, an oxygenated sesquiterpene, is reported to accumulate in a particular hop cultivar. Recently, we revealed that ß-Eudesmol ingestion affected autonomic nerve activity in an animal model. The effect on humans has not been elucidated, therefore, we investigated the effects of ß-Eudesmol on reducing objective and subjective markers related to sympathetic nerve activity after the application of mental stress in healthy participants. Fifty participants (male and female aged 20 to 50 years) were randomly assigned to two groups. Five minutes before taking the Trier Social Stress Test (TSST) as a mental stressor, participants in each group ingested a beverage containing ß-Eudesmol, the active beverage, or a placebo beverage that did not contain ß-Eudesmol. Saliva 3-methoxy-4-hydroxyphenylglycol (MHPG), a major product of noradrenaline breakdown and a representative marker of sympathetic nerve activity, was significantly lower just after the TSST in the active group compared with the placebo group. Saliva cortisol, a marker of the endocrine stress response system, was not significantly different between the two groups. No adverse events related to test beverage ingestion were observed. This is the first experimental evidence of ß-Eudesmol effect for mental stress in human.

Salivary 3-methoxy-4-hydroxyphenylglycol increases after awakening in healthy young adults.

Levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) may reflect central noradrenergic activity. In this study, we investigated salivary MHPG changes after awakening, and explored their relationships with cortisol and peripheral autonomic activity. The participants were 25 college students. Saliva samples were collected on awakening and 30 min after awakening to determine MHPG and cortisol. Ambulatory electrocardiograms were obtained to assess heart rate, cardiac sympathetic index (CSI), and cardiac vagal index (CVI) before and after awakening. MHPG levels increased significantly during the first 30 min after awakening. Similarly, cortisol, heart rate, and CSI increased during the 30 min after awakening, but changes in MHPG did not correlate with changes in cortisol, heart rate, CSI, and CVI during that period. This study demonstrated that salivary MHPG levels increase after awakening, in common with cortisol, heart rate, and cardiac sympathetic activity.

Short sleeping time and psychobiological responses to acute stress.

The aim of this study was to examine the association between self-reported sleeping time and psychobiological stress responses [3-Methoxy-4-hydroxyphenylglycol (MHPG) and Secretory immunoglobulin A (IgA), perceived stress responses]. Thirty seven healthy men and women were recruited, and participants were divided according to the habitual number of hours of sleep as follows: adequate sleepers (AS) (6-8h sleep per night regularly) (N=22) and short sleepers (SS) (less than 5h sleep per night regularly) (N=15). Salivary MHPG, s-IgA and perceived stress were measured at baseline, immediately after task and recovery period. An increase in free-MHPG during the task period was observed in AS although free-MHPG increased only after the task period in SS. The level of s-IgA in both groups significantly increased during the task period, and quickly returned to a basal level during the recovery period. The results show that less than 5h of sleep was associated with different responsiveness to the Stroop color word conflict task compared to sufficient sleep, especially in the NA system.

Synergistic effects of psychological and immune stressors on inflammatory cytokine and sickness responses in humans.

Activation of the innate immune system is commonly accompanied by a set of behavioural, psychological and physiological changes known as 'sickness behaviour'. In animals, infection-related sickness symptoms are significantly increased by exposure to psychosocial stress, suggesting that psychological and immune stressors may operate through similar pathways to induce sickness. We used a double-blind, randomised, placebo-controlled design to examine the effect of acute psychological stress on immune and subjective mood responses to typhoid vaccination in 59 men. Volunteers were assigned to one of four experimental conditions in which they were either injected with typhoid vaccine or saline placebo, and then either rested or completed two challenging behavioural tasks. Typhoid vaccine induced a significant rise in participants' serum levels of interleukin-6 (IL-6) and this response was significantly larger in the stress versus rest conditions. Negative mood increased immediately post-tasks, an effect also more pronounced in the vaccine/stress condition. In the vaccine/stress group, participants with larger IL-6 responses had heightened systolic blood pressure responses to tasks and elevated post-stress salivary levels of the noradrenaline metabolite 3-methoxy-phenyl glycol (MHPG) and cortisol. Our findings suggest that, as seen in animals, psychological and immune stressors may act synergistically to promote inflammation and sickness behaviour in humans.