The relationship between immune fitness and saliva biomarkers of systemic inflammation.

Purpose: It is vital that Immune fitness, i.e., how well the immune system functions and reacts to challenges, can be reliably be examined. The current study aimed to compare immune fitness with assessments of saliva biomarkers of systemic inflammation. Methods: N = 108 healthy young adults (18-30-year-old students of Utrecht University, the Netherlands) participated in the study. A saliva sample was collected for biomarker assessment (Interleukin (IL)-1ß, IL-6, IL-8, IL-10, immunoglobulin A (IgA), and tumor necrosis factor-alpha (TNF-α), and c-reactive protein (CRP). Additionally, a survey was completed to assess immune fitness, mood, mental resilience, and quality of life. The correlations between the biomarker assessments, immune fitness and mood were determined. Results: No significant correlations between immune fitness and biomarkers of systemic inflammation were found. Significant sex differences in correlations with immune fitness were demonstrated for loneliness (significant only in men) and fatigue (significant only in women). For both sexes, immune fitness correlated significantly with anxiety, mental resilience, and quality of life. Conclusion: No significant correlations were found between immune fitness and saliva biomarkers of systemic inflammation. Immune fitness correlated significantly with anxiety, mental resilience, and quality of life. Sex differences were demonstrated in the relation of immune fitness with loneliness and fatigue. Future research should further investigate factors that may influence the relationship between immune fitness, mood, and biomarkers of systemic inflammation, including underlying psychological mechanisms of possible sex differences.

An evening of alcohol consumption negatively impacts next-day immune fitness in both hangover-sensitive drinkers and hangover-resistant drinkers.

BACKGROUND: Survey research found poorer baseline immune fitness for self-reported hangover-sensitive drinkers compared to hangover-resistant drinkers. However, up to now a limited number of clinical studies revealed mixed results regarding the relationship between the concentrations of biomarkers of systemic inflammation in blood or saliva with hangover severity, and could not differentiate between hangover-sensitive drinkers and hangover-resistant drinkers. The aim of this study was to assess immune fitness and saliva biomarkers of systemic inflammation at multiple timepoints following an alcohol day and alcohol-free control day. METHODS: The study had a semi-naturalistic design. In the evening before the test days, participants were not supervised. They could drink ad libitum drinking on the alcohol test day and refrained from drinking alcohol on the control day. Activities and behaviors on the alcohol and control day were reported the follow morning. On both test days, from 09:30 to 15:30, hourly assessments of immune fitness (single-item scale) and overall hangover severity (single-item scale) were made and saliva samples were collected for biomarker assessments. RESULTS: N = 14 hangover-resistant drinkers and n = 15 hangover-sensitive drinkers participated in the study. The amount of alcohol consumed on the alcohol day did not significantly differ between the hangover-resistant group (mean (SD) of 13.5 (7.9) alcoholic drinks) and the hangover-sensitive group (mean (SD) of 12.4 (4.4) alcoholic drinks). All hangover-sensitive drinkers reported having a hangover following the alcohol day (overall hangover severity score 6.1 (on a 0-10 scale) at 09:30, gradually decreasing to 3.3 at 15:30), whereas the hangover-resistant drinkers reported no hangover. On the control day, immune fitness of the hangover-sensitive group was significantly poorer than the hangover-resistant group. On the alcohol day, both groups showed a significant reduction in immune fitness. The effect was evident throughout the day, but significantly more pronounced in the hangover-sensitive group than the hangover-resistant group. No significant differences between the groups were found at any time point on the two test days for saliva concentrations of Interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor (TNF)-α. CONCLUSIONS: Whereas hangover-sensitive drinkers reported a hangover following an alcohol day and hangover-resistant drinkers did not, both groups reported significantly reduced immune fitness throughout the day. However, the reduction in immune fitness among hangover-sensitive drinkers was significantly more pronounced in comparison to the hangover-resistant group.

Predictors of Hangover Frequency and Severity: The Impact of Alcohol Consumption, Mental Resilience, Personality, Lifestyle, Coping and Mood.

Mental resilience is the ability to bounce back from daily life stressors such as divorce or losing a job. Extensive research has demonstrated a negative relationship between mental resilience and alcohol consumption. That is, both the quantity and frequency of alcohol consumption are greater in individuals with lower levels of mental resilience. There has, however, been little scientific attention paid to the relationship between mental resilience and alcohol hangover severity. The objective of this study was to evaluate psychological factors that may impact the frequency and severity of alcohol hangovers, including alcohol intake itself, mental resilience, personality, baseline mood, lifestyle, and coping mechanisms. An online survey was conducted among Dutch adults (N = 153) who had a hangover after their heaviest drinking occasion in the period before the start of the COVID-19 pandemic (15 January to 14 March 2020). Questions were asked about their alcohol consumption and hangover severity on their heaviest drinking occasion. Mental resilience was assessed with the Brief Mental Resilience scale, personality with the Eysenck Personality Questionnaire-Revised Short Scale (EPQ-RSS), mood via single item assessments, and lifestyle and coping with the modified Fantastic Lifestyle Checklist. The partial correlation, corrected for estimated peak blood alcohol concentration (BAC), between mental resilience and hangover severity was not significant (r = 0.010, p = 0.848). Furthermore, no significant correlations were found between hangover severity or frequency and personality and baseline mood. For lifestyle and coping factors, a negative correlation was found between the use of tobacco and toxins (i.e., drugs, medicines, caffeine) and the frequency of experiencing hangovers. Regression analysis revealed that hangover severity after the heaviest drinking occasion (31.2%) was the best predictor of hangover frequency, and that subjective intoxication on the heaviest drinking occasion (38.4%) was the best predictor of next-day hangover severity. Mood, mental resilience, and personality were not relevant predictors of hangover frequency and severity. In conclusion, mental resilience, personality, and baseline mood do not predict hangover frequency and severity.

Epigenome-Wide Association Studies of the Fractional Exhaled Nitric Oxide and Bronchodilator Drug Response in Moderate-to-Severe Pediatric Asthma.

Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10-8 were used to control for false-positive results. The CpG cg12835256 (PLA2G12A) was genome-wide associated with FeNO in blood samples (coefficient= -0.015, p = 2.53 × 10-9) and nominally associated in nasal samples (coefficient = -0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.

Alcohol Consumption, Hangovers, and Smoking among Buenos Aires University Students during the COVID-19 Pandemic.

In Argentina, the 2019 coronavirus disease (COVID-19) pandemic led to serious changes to social interaction, health, economy, and education. Argentina experienced two extensive lockdown periods. University education remained virtual for almost two academic years. The purpose of the present work was to analyze the impact of the COVID-19 lockdowns in Argentina on alcohol consumption, hangover severity and smoking among university students in Buenos Aires. A retrospective online survey was conducted in 2021 among students of the University of Buenos Aires. Participants aged 18-35 years old were asked about the average number of alcoholic drinks and number of drinking days per week, binge drinking occasions, drunkenness, next day hangover severity, number of hangovers per month, and smoking behavior. The results showed that the first and second COVID-19 lockdowns were associated with significant reductions in both weekly alcohol consumption, and hangover severity and subjective intoxication on their heaviest drinking occasions. Males consumed significantly more alcohol than females, and older students (25-35 years old) consumed more alcohol than younger students (18-24 years old). In addition, younger students reduced the number of cigarettes smoked per day during the two lockdown periods while older students exhibited significantly more smoking days per week. In conclusion, the present work in Argentinian students revealed a significant reduction in weekly alcohol consumption, and subjective intoxication and hangover severity on their heaviest drinking occasions during the pandemic lockdown periods.

Unknown safety and efficacy of alcohol hangover treatments puts consumers at risk.

It is important that hangover products are both safe and effective. The aims of the current study were to evaluate (a) the ingredients of currently marketed hangover treatments, (b) whether companies make disease modification claims for these products, and (c) the extent and quality of any independent scientific evidence on their efficacy and safety. Of eighty-two hangover products identified, the most common ingredients were vitamin B, vitamin C, milk thistle extract (silymarin), dihydromyricetin (DHM), and N-acetyl L-cysteine (NAC), often in combination. Fifty-one products (62.2% of the 82 evaluated products) contained one or more vitamins of which the dose exceeded the corresponding daily recommended intake level. For 9 (28.1%) of 32 products that reported the dose of Vitamin B3 and 2 (8.0%) of 25 products that reported the dose of Vitamin B9 the corresponding tolerable upper intake level was exceeded. Further, in many other cases the dose of other ingredients was not reported (e.g., dosages of DHM and NAC were not reported by 59% and 73% of the products containing these ingredients), and corresponding tolerable upper limits are unknown. A review of scientific literature revealed no peer-reviewed human data demonstrating either safety or efficacy of any of the 82 evaluated hangover products. Further, the product name and/or package/insert included explicit disease modification claims in 64.6% of the products. Finally, 45.1% of the products contain NAC as an ingredient. As NAC is registered as a drug by the US Food and Drug Administration (FDA), it is prohibited as an ingredient in dietary supplements or foods. We conclude that, in the interest of consumers, independent research supporting the safety and efficacy of hangover treatments should be a minimum requirement for hangover treatment claims irrespective whether the products are registered as medicinal drugs or dietary supplements.

Immune Responses after Heavy Alcohol Consumption: Cytokine Concentrations in Hangover-Sensitive and Hangover-Resistant Drinkers.

This study investigated immunological changes during an alcohol hangover, and the possible difference between hangover-resistant and hangover-sensitive drinkers in terms of immune reactivity. Using a semi-naturalistic design, N = 36 healthy social drinkers (18 to 30 years old) provided saliva samples on a control day (after drinking no alcohol) and on a post-alcohol day. Hangover severity was rated directly after saliva collection. Cytokine concentrations, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α, and hangover severity were compared between both test days and between hangover-sensitive and -resistant drinkers. Data from N = 35 drinkers (17 hangover-sensitive and 18 hangover-resistant) were included in the statistical analyses. Relative to the control day, there were significant increases in saliva IL-6 and IL-10 concentrations on the post-alcohol day. No significant differences in cytokine concentrations were found between hangover-sensitive and hangover-resistant drinkers, nor did any change in cytokine concentration correlate significantly with hangover severity. In line with previous controlled studies assessing cytokines in blood, the current naturalistic study using saliva samples also demonstrated that the immune system responds to high-level alcohol intake. However, further research is warranted, as, in contrast to previous findings in blood samples, changes in saliva cytokine concentrations did not differ significantly between hangover-sensitive and hangover-resistant drinkers, nor did they correlate significantly with hangover severity.

Does Alcohol Hangover Affect Emotion Regulation Capacity? Evidence From a Naturalistic Cross-Over Study Design.

AIMS: The aim of this study was to investigate the effects of alcohol hangover on emotion regulation. METHODS: Forty-five non-smoking, healthy participants aged between 18 and 30 years completed a lab-based emotion regulation task assessing cognitive reappraisal and an emotion regulation questionnaire (State-Difficulties in Emotion Regulation Scale [S-DERS]) when hungover (morning following a night of heavy drinking) and under a no-hangover condition in a naturalistic, within-subjects design study. RESULTS: Participants reported poorer emotion regulation overall (P < 0.001, d = 0.75), and for the subscales 'Non-Acceptance', 'Modulation' and 'Clarity' (Ps ≤ 0.001, ds ≥ 0.62), but not 'Awareness' on the S-DERS, in the hangover versus the no-hangover condition. Hangover did not impair emotion regulation ability as assessed using the lab-based task (Ps ≥ 0.21, ds ≤ 0.40), but there was a general negative shift in valence ratings (i.e. all images were rated more negatively) in the hangover relative to the no-hangover condition (P < 0.001, d = 1.16). CONCLUSION: These results suggest that emotion regulation in everyday life and emotional reactivity may be adversely affected by alcohol hangover, but some emotion regulation strategies (e.g. deliberate cognitive reappraisal) may be unaffected.

The Inflammatory Response to Alcohol Consumption and Its Role in the Pathology of Alcohol Hangover.

An increasing number of studies are focusing on the inflammatory response to alcohol as a potentially important determinant of hangover severity. In this article, data from two studies were re-evaluated to investigate the relationship between hangover severity and relevant biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol. Hangover severity was significantly and positively correlated with blood concentrations of biomarkers of the inflammatory response to alcohol, in particular, Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP). At 4 h after alcohol consumption, blood ethanol concentration (but not acetaldehyde) was significantly and positively associated with elevated levels of IL-6, suggesting a direct inflammatory effect of ethanol. In addition, biomarkers of oxidative stress, i.e., malondialdehyde and 8-isoprostrane, were significantly correlated with hangover severity, suggesting that oxidative stress also contributes to the inflammatory response. The timing of the assessments suggests initial slow elimination of ethanol in the first hours after alcohol consumption. As a consequence, more ethanol is present in the second half of the night and the next morning, which will elicit more oxidative stress and a more profound inflammatory response. Together, these processes result in more severe hangovers.

The Effects of Alcohol Hangover on Executive Functions.

Recent research has suggested that processes reliant on executive functions are impaired by an alcohol hangover, yet few studies have investigated the effect of hangovers on core executive function processes. Therefore, the current study investigated the effect of hangovers on the three core components of the unity/diversity model of executive functions: the ability to switch attention, update information in working memory, and maintain goals. Thirty-five 18-to-30-year-old non-smoking individuals who reported experiencing a hangover at least once in the previous month participated in this study. They completed tasks measuring switching (number-switching task), updating (n-back task), and goal maintenance (AX Continuous Performance Test, AX-CPT) whilst experiencing a hangover and without a hangover in a 'naturalistic' within-subjects crossover design. Participants made more errors in the switching task (p = 0.019), more errors in both the 1- (p < 0.001) and 2-back (p < 0.001) versions of the n-back, and more errors in the AX-CPT (p = 0.007) tasks when experiencing a hangover, compared to the no-hangover condition. These results suggest that an alcohol hangover impairs core executive function processes that are important for everyday behaviours, such as decision-making, planning, and mental flexibility.

Positive effects of Red Bull® Energy Drink on driving performance during prolonged driving.

BACKGROUND: The purpose of this study was to examine if Red Bull® Energy Drink can counteract sleepiness and driving impairment during prolonged driving. METHODS: Twenty-four healthy volunteers participated in this double-blind placebo-controlled crossover study. After 2 h of highway driving in the STISIM driving simulator, subjects had a 15-min break and consumed Red Bull® Energy Drink (250 ml) or placebo (Red Bull® Energy Drink without the functional ingredients: caffeine, taurine, glucuronolactone, B vitamins (niacin, pantothenic acid, B6, B12), and inositol) before driving for two additional hours. A third condition comprised 4 h of uninterrupted driving. Primary parameter was the standard deviation of lateral position (SDLP), i.e., the weaving of the car. Secondary parameters included SD speed, subjective driving quality, sleepiness, and mental effort to perform the test. RESULTS: No significant differences were observed during the first 2 h of driving. Red Bull® Energy Drink significantly improved driving relative to placebo: SDLP was significantly reduced during the 3rd (p < 0.046) and 4th hour of driving (p < 0.011). Red Bull® Energy Drink significantly reduced the standard deviation of speed (p < 0.004), improved subjective driving quality (p < 0.0001), and reduced mental effort to perform the test (p < 0.024) during the 3rd hour of driving. Subjective sleepiness was significantly decreased during both the 3rd and 4th hour of driving after Red Bull® Energy Drink (p < 0.001 and p < 0.009, respectively). Relative to uninterrupted driving, Red Bull® Energy Drink significantly improved each parameter. CONCLUSION: Red Bull® Energy Drink significantly improves driving performance and reduces driver sleepiness during prolonged highway driving.

The pathology of alcohol hangover.

Research on human subjects analyzing blood and urine samples determined biological correlates that may explain the pathology of alcohol hangover. These analyses showed that concentrations of various hormones, electrolytes, free fatty acids, triglycerides, lactate, ketone bodies, cortisol, and glucose were not significantly correlated with reported alcohol hangover severity. Also, markers of dehydration (e.g., vasopressin) were not significantly related to hangover severity. Some studies report a significant correlation between blood acetaldehyde concentration and hangover severity, but most convincing is the significant relationship between immune factors and hangover severity. The latter is supported by studies showing that hangover severity may be reduced by inhibitors of prostaglandin synthesis. Several factors do not cause alcohol hangover but can aggravate its severity. These include sleep deprivation, smoking, congeners, health status, genetics and individual differences. Future studies should more rigorously study these factors as well as biological correlates to further elucidate the pathology of alcohol hangover.

A psychoneuroimmunological review on cytokines involved in antidepressant treatment response.

OBJECTIVES: The literature exploring the role that cytokine functioning plays in the pathogenesis and treatment of depressive illness is reviewed. The review focuses on the influence of antidepressants on cytokines, and on how treatment response might be affected by genetic variants of cytokines. METHOD: The authors systematically reviewed the scientific literature on the subject over the last 20 years, searching PubMed, PsychInfo, and Cochrane databases. RESULTS: Antidepressants modulate cytokine functioning, and these mechanisms appear to directly influence treatment outcome in depression. Antidepressants appear to normalize serum levels of major inflammatory cytokines, including interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). Antidepressants are postulated to modulate cytokine functioning through their effects on intracellular cyclic adenosyl monophosphate (cAMP), serotonin metabolism, the hypothalamo-pituitary-adrenocortical (HPA) axis or through a direct action on neurogenesis. Preliminary research shows that cytokine genotypes and functioning may be able to help predict antidepressant treatment response. CONCLUSIONS: Current literature demonstrates an association between antidepressant action and cytokine functioning in major depression. Improved understanding of the specific pharmacologic and pharmacogenetic mechanisms is needed. Such knowledge may serve to enhance our understanding of depression, leading to promising new directions in the pathology, nosology, and treatment of depression.