Lisa M. Hernández

Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.

Epidemiologic evidence supports that diets rich in polyphenols promote health and may delay the onset of colon cancer. Cocoa and chocolate products have some of the highest polyphenolic concentrations compared to other polyphenolic food sources. This study tested the hypothesis that a diet including dark chocolate can protect against colon cancer by inhibiting aberrant crypt foci (ACF) formation, downregulating gene expression of inflammatory mediators, and favorably altering cell kinetics. We also investigated whether bloomed dark chocolate retains the antioxidant capacity and protects against colon cancer. Forty-eight rats received either a diet containing control (no chocolate), regular dark chocolate, or bloomed dark chocolate and were injected subcutaneously with saline or azoxymethane. Relative to control, both regular and bloomed dark chocolate diets lowered the total number of ACF (P = 0.022). Chocolate diet-fed animals downregulated transcription levels of COX-2 (P = 0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index (P = 0.001). These results suggest that a diet including dark chocolate can reduce cell proliferation and some gene expression involving inflammation, which may explain the lower number of early preneoplastic lesions. These results provide new insight on polyphenol-rich chocolate foods and colon cancer prevention.

Influence of resistance training combined with daily consumption of an egg-based or bagel-based breakfast on risk factors for chronic diseases in healthy untrained individuals.

Objective: Egg consumption is often discouraged due to cholesterol content; however, recent studies have not demonstrated a clear adverse influence of eggs on blood lipids. Furthermore, exercise training promotes improved lipids and blood pressure. The purpose of the study was to examine the effect of eating an isoenergetic (400 kcal) egg-based (including two eggs per day) versus bagel-based breakfasts, daily, combined with resistance training three times per week, prior to breakfast, on plasma lipids, glucose, insulin, insulin sensitivity and blood pressure in untrained individuals. Methods: Twenty-five healthy adult men and women (18–35 years of age) participated in the twelve week study following random assignment to study groups. Lipids and blood pressure were examined at baseline and after 6 and 12 weeks. Results: Plasma triglycerides (TG) decreased significantly in the egg- based breakfast (EBB) group from baseline to six weeks (p = 0.011) and from six to twelve weeks (p = 0.045). A significant (p = 0.033) decrease in insulin sensitivity was observed in the bagel-based breakfast (BBB) group from zero to six weeks. No significant effects on systolic blood pressure, diastolic blood pressure, total cholesterol, high density lipoprotein- cholesterol or low density lipoprotein cholesterol were detected. Conclusion: Overall, daily breakfasts including two eggs for twelve weeks did not adversely affect lipids during a resistance training program and promoted improvements in plasma TG.

Anabolic hormone profiles in elite military men

We recently characterized the awakening responses and daily profiles of the catabolic stress hormone cortisol in elite military men. Anabolic hormones follow a similar daily pattern and may counteract the catabolic effects of cortisol. This companion report is the first to characterize daily profiles of anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in this population. Overall, the men in this study displayed anabolic hormone profiles comparable to that of healthy, athletic populations. Consistent with the cortisol findings in our prior report, summary parameters of magnitude (hormone output) within the first hour after awakening displayed superior stability versus summary parameters of pattern for both DHEA (r range: 0.77-0.82) and testosterone (r range: 0.62-0.69). Summary parameters of evening function were stable for the two hormones (both p<0.001), while the absolute decrease in testosterone across the day was a stable proxy of diurnal function (p<0.001). Removal of noncompliant subjects did not appreciably affect concentration estimates for either hormone at any time point, nor did it alter the repeatability of any summary parameter. The first of its kind, this report enables accurate estimations of anabolic balance and resultant effects upon health and human performance in this highly resilient yet chronically stressed population.

A genetic risk factor for major depression and suicidal ideation is mitigated by physical activity

We evaluated associations of five candidate polymorphisms (Bcl1 [rs41423247], -2C/G [rs2070951], COMT [rs737865], Val66Met [rs6265], and 5HTTLPR [biallelic and triallelic [5HTTLPR/rs25531]) with probable MDD and suicidal ideation (SI), the effects of physical activity on these endpoints, and whether physical activity attenuates genetic risk in military members (N=736). C carriers who were also less physically active were 3.3 times as likely to meet criteria for probable MDD and 9.6 times as likely to endorse SI as compared to physically active GG carriers. An adequate dose of physical activity diminishes risk of MDD and SI imposed by a genetic predisposition.

Cortisol Awakening Response in Elite Military Men: Summary Parameters, Stability Measurement, and Effect of Compliance

The cortisol awakening response (CAR) holds promise as a clinically important marker of health status. However, CAR research is routinely challenged by its innate complexity, sensitivity to confounds, and methodological inconsistencies. In this unprecedented characterization of CAR in elite military men (N = 58), we established summary parameters, evaluated sampling stability across two consecutive days, and explored the effect of subject compliance. Average salivary cortisol concentrations increased nearly 60% within 30 minutes of waking, followed by a swift recovery to waking values at 60 minutes. Approximately one in six were classified as negative responders (i.e., <0% change from waking to 30-minute postawakening). Three summary parameters of magnitude, as well as three summary parameters of pattern, were computed. Consistent with our hypothesis, summary parameters of magnitude displayed superior stability compared with summary parameters of pattern in the total sample. As expected, compliance with target sampling times was relatively good; average deviations of self-reported morning sampling times in relation to actigraph-derived wake times across both days were within ±5 minutes, and nearly two-thirds of the sample was classified as CAR compliant across both days. Although compliance had equivocal effects on some measures of magnitude, it substantially improved the stability of summary parameters of pattern. The first of its kind, this study established the foundation for a program of CAR research in a profoundly resilient yet chronically stressed population. Building from this, our forthcoming research will evaluate demographic, biobehavioral, and clinical determinants of CAR in this unique population.

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.

The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high < SS/low = L/high < L/low). Thus, 5HTTLPR and prior trauma exposure demonstrated counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings.

Morning Cortisol Is Associated With Stress and Sleep in Elite Military Men: A Brief Report

Introduction Accumulating evidence suggests that trends in salivary cortisol after awakening may be reliable biological predictors of morbidity and mortality. In a sample of elite military men, our lab recently established summary parameters of morning cortisol as well as their stability across 2 d of repeated sampling. Materials and Methods In this follow-on study, we evaluated summary parameters and their relationships to theoretically relevant demographic (i.e., age, body mass index) and biobehavioral correlates (i.e., blood pressure [BP], sleep parameters, fatigue, and perceived stress). Fifty-eight male active duty U.S. Navy SEALs self-collected salivary samples on 2 consecutive, midweek workdays upon waking (WAKE), WAKE+30 min, WAKE+60 min, 4 p.m., and 9 p.m. in a nondeployed, free-living setting. Resting BP was measured manually, and sleep-wake periods were objectively derived using actigraphy. Daily fatigue and perceived stress were measured by self-report. Summary parameters of morning cortisol magnitude (i.e., peak value [Peak], area under the curve in terms of ground [AUCG], and average of morning samples [AVE]) were assessed with respect to each demographic and biobehavioral item via correlational analyses. A subgroup of 29 participants was selected for compliance with salivary sampling in the morning across 2 d. Results Perceived stress was positively associated with Peak (r[27] = 0.437, p < 0.05), AUCG (r[25] = 0.500, p < 0.01), and AVE (r[25] = 0.506, p < 0.01). Total sleep time was also positively associated with Peak (r[26] = 0.378, p < 0.05). There were borderline associations between some summary parameters and diastolic BP, percent sleep, and wake after sleep onset. Age, systolic BP, body mass index, time in bed, sleep efficiency, and fatigue did not associate with morning cortisol. Conclusions Preliminary evidence of morning cortisol summary parameters as biobehavioral indicators was established, and these parameters appeared to associate with stress and sleep in elite military men.

The “yin and yang” of the adrenal and gonadal systems in elite military men

Abstract We recently established daily, free-living profiles of the adrenal hormone cortisol, the (primarily adrenal) anabolic precursor dehydroepiandrosterone (DHEA) and the (primarily gonadal) anabolic hormone testosterone in elite military men. A prevailing view is that adrenal and gonadal systems reciprocally modulate each other; however, recent paradigm shifts prompted the characterization of these systems as parallel, cooperative processes (i.e. the “positive coupling” hypothesis). In this study, we tested the positive coupling hypothesis in 57 elite military men by evaluating associations between adrenal and gonadal biomarkers across the day. Salivary DHEA was moderately and positively coupled with salivary cortisol, as was salivary testosterone. Anabolic processes (i.e. salivary DHEA and testosterone) were also positively and reliably coupled across the day. In multivariate models, salivary DHEA and cortisol combined to account for substantial variance in salivary testosterone concentrations across the day, but this was driven almost exclusively by DHEA. This may reflect choreographed adrenal release of DHEA with testicular and/or adrenal release of testosterone, systemic conversion of DHEA to testosterone, or both. DHEA and testosterone modestly and less robustly predicted cortisol concentrations; this was confined to the morning, and testosterone was the primary predictor. Altogether, top-down co-activation of adrenal and gonadal hormone secretion may complement bottom-up counter-regulatory functions to foster anabolic balance and neuronal survival; hence, the “yin and yang” of adrenal and gonadal systems. This may be an adaptive process that is amplified by stress, competition, and/or dominance hierarchy.

Anabolic hormone profiles in elite military men: Robust associations with age, stress, and fatigue

HighlightsWe evaluated anabolic hormones and biobehavioral health in elite military men.Robust linear associations were observed between testosterone and perceived stress.Lower dehydroepiandrosterone and testosterone associated with higher fatigue.Routine monitoring of anabolic hormones is important in stressed populations. ABSTRACT We recently established stable daily profiles of the anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in 57 elite military men. In this follow‐on study, we explored associations of salivary anabolic hormone profiles with demographic (i.e., age, body mass index [BMI]) and biobehavioral health indices (i.e., blood pressure, sleep, perceived stress, fatigue) via correlational models. Next, nuanced patterns were constructed using quartile splits followed by one‐way analysis of variance and post hoc subgroup comparisons. Both DHEA (r range: −0.33 to −0.49) and testosterone (r range: −0.19 to −0.41) were inversely associated with age. Quartile comparisons revealed that age‐related declines in DHEA were linear, curvilinear, or sigmoidal, depending on the summary parameter of interest. Anabolic hormone profiles did not associate with BMI, blood pressure, or sleep efficiency. Robust linear associations were observed between testosterone and perceived stress (r range: −0.29 to −0.36); concentration‐dependent patterns were less discernible. Lower DHEA (r range: −0.22 to −0.30) and testosterone (r range: −0.22 to −0.36) concentrations associated with higher fatigue. Subsequent quartile comparisons suggested a concentration‐dependent threshold with respect to evening testosterone. Specifically, those individuals within the lowest quartile (≤68.4 pg/mL) endorsed the highest fatigue of the four groups (p = 0.01), while the remaining three groups did not differ from each other. This study not only showed that anabolic hormone profiles have distinctive age trajectories, but are also valuable predictors of stress and fatigue in elite military men. This highlights the importance of routine monitoring of anabolic hormone profiles to sustain and optimize health and readiness in chronically stressed populations.