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A 2 Week Cross-over Intervention with a Low Carbohydrate, High Fat Diet Compared to a High Carbohydrate Diet Attenuates Exercise-Induced Cortisol Response, but Not the Reduction of Exercise Capacity, in Recreational Athletes.
Terink, R, Witkamp, RF, Hopman, MTE, Siebelink, E, Savelkoul, HFJ, Mensink, M
Nutrients. 2021;(1)
Abstract
Low carbohydrate, high fat (LCHF) diets are followed by athletes, but questions remain regarding effects of LCHF on metabolic adaptation, exercise-induced stress, immune function and their time-course. In this cross-over study, 14 recreational male athletes (32.9 ± 8.2 years, VO2max 57.3 ± 5.8 mL/kg/min) followed a two week LCHF diet (<10 En% carbohydrates (CHO), ~75En% Fat) and a two week HC diet (>50 En% CHO), in random order, with a wash-out period of >2 weeks in between. After 2 days and 2 weeks on either diet, participants performed cycle ergometry for 90 min at 60%Wmax. Blood samples for analysis of cortisol, free fatty acids (FFA), glucose and ketones, and saliva samples for immunoglobin A (s-IgA) were collected at different time points before and after exercise. The LCHF diet resulted in higher FFA, higher ketones and lower glucose levels compared to the HC diet (p < 0.05). Exercise-induced cortisol response was higher after 2 days on the LCHF diet (822 ± 215 nmol/L) compared to 2 weeks on the LCHF diet (669 ± 243 nmol/L, p = 0.004) and compared to both test days following the HC diet (609 ± 208 and 555 ± 173 nmol/L, both p < 0.001). Workload was lower, and perceived exertion higher, on the LCHF diet compared to the HC diet on both occasions. A drop in s-IgA following exercise was not seen after 2 days on the LCHF diet, in contrast to the HC diet. In conclusion, the LCHF diet resulted in reduced workload with metabolic effects and a pronounced exercise-induced cortisol response after 2 days. Although indications of adaptation were seen after 2 weeks on the LCHF diet, work output was still lower.
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Association between hair cortisol concentration and dietary intake among normal weight preschool children predisposed to overweight and obesity.
Larsen, SC, Rohde, JF, Olsen, NJ, Händel, MN, Stougaard, M, Fahrenkrug, J, Heitmann, BL
PloS one. 2019;(3):e0213573
Abstract
BACKGROUND The association between chronically elevated cortisol, as measured by hair cortisol concentration (HCC), and dietary intake among children has generally not been explored. Moreover, it is unknown whether there is an association between parental HCC and dietary intake among their children. OBJECTIVE To examine associations between HCC and dietary intake among children, and to explore the association between parental HCC and dietary intake among their children. METHODS We conducted a cross-sectional study based on 296 children predisposed to overweight and obesity who participated in the Healthy Start study. Multiple Linear regression analyses were conducted to assess the association between HCC and total energy intake, macronutrients, fruit and vegetables, added sugar, sugar-sweetened beverages (SSB), and a diet quality index (DQI). RESULTS Among the children, we found that higher HCC was associated with a lower consumption of dietary fat (β: -0.7 g/day [95% CI: -1.3, -0.0] per 100 pg/mg HCC). We found no statistically significant association between HCC and intake of total energy, protein, carbohydrate, fruit and vegetables, added sugar, SSB or DQI. We found no association between parental HCC and intake of total energy, added sugar, selected food groups or DQI among their children. However, stratified analyses showed that paternal HCC was associated with a borderline significant lower total energy intake and significantly lower protein intake, but only among daughters (adjusted β: -42 kcal/day [95% CI: -85, 0] and -2.6 g/day [95% CI: -4.4, -0.8] per 100 pg/mg HCC, respectively). CONCLUSION Among children, chronic stress as measured by HCC may be associated with a lower fat consumption, and paternal HCC may be associated with a lower intake of energy and protein among their daughters. However, the associations observed were weak, and any clinical relevance of these findings remains questionable.
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Characterizing the temporal Dynamics of Melatonin and Cortisol Changes in Response to Nocturnal Light Exposure.
Rahman, SA, Wright, KP, Lockley, SW, Czeisler, CA, Gronfier, C
Scientific reports. 2019;(1):19720
Abstract
We studied the dynamics of melatonin suppression and changes in cortisol levels in humans in response to light exposure at night using high-frequency blood sampling. Twenty-one young healthy participants were randomized to receive either intermittent bright (~9,500 lux) light (IBL), continuous bright light (CBL) or continuous dim (~1 lux) light (VDL) for 6.5 h during the biological night (n = 7 per condition). Melatonin suppression occurred rapidly within the first 5 min and continued until the end of each IBL stimuli (t1/2 = ~13 min). Melatonin recovery occurred more slowly between IBL stimuli (half-maximal recovery rate of ~46 min). Mean melatonin suppression (~40%) and recovery (~50%) were similar across IBL stimuli. Suppression dynamics under CBL were also rapid (t1/2 = ~18 min), with no recovery until the light exposure ended. There was a significant linear increase of cortisol levels between the start and end of each IBL stimulus. Under CBL conditions cortisol showed trimodal changes with an initial linear activating phase, followed by an exponential inhibitory phase, and a final exponential recovery phase. These results show that light exposure at night affects circadian driven hormones differently and that outcomes are influenced by the duration and pattern of light exposure.
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Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.
Skene, DJ, Skornyakov, E, Chowdhury, NR, Gajula, RP, Middleton, B, Satterfield, BC, Porter, KI, Van Dongen, HPA, Gaddameedhi, S
Proceedings of the National Academy of Sciences of the United States of America. 2018;(30):7825-7830
Abstract
Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is essential to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock disturbances may offer new insights. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-shift schedule, compared with a simulated day-shift schedule, were analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhythmicity under constant routine following either or both simulated shift schedules. However, while traditional markers of the circadian clock in the SCN-melatonin, cortisol, and PER3 expression-maintained a stable phase alignment after both schedules, only a few metabolites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine following the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavioral time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circadian clock. Characterization of these metabolite rhythms will provide insight into the underlying mechanisms linking shift work and metabolic disorders.
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A prospective investigation of perceived stress, infertility-related stress, and cortisol levels in women undergoing in vitro fertilization: influence on embryo quality and clinical pregnancy rate.
Cesta, CE, Johansson, ALV, Hreinsson, J, Rodriguez-Wallberg, KA, Olofsson, JI, Holte, J, Wramsby, H, Wramsby, M, Cnattingius, S, Skalkidou, A, et al
Acta obstetricia et gynecologica Scandinavica. 2018;(3):258-268
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Abstract
INTRODUCTION Women undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self-reported perceived and infertility-related stress and cortisol levels were associated with IVF cycle outcomes. MATERIAL AND METHODS A prospective cohort of 485 women receiving fertility treatment was recruited from September 2011 to December 2013 and followed until December 2014. Data were collected by online questionnaire prior to IVF start and from clinical charts. Salivary cortisol levels were measured. Associations between stress and cycle outcomes (clinical pregnancy and indicators of oocyte and embryo quality) were measured by logistic or linear regression, adjusted for age, body mass index, education, smoking, alcohol and caffeine consumption, shiftwork and night work. RESULTS Ultrasound verified pregnancy rate was 26.6% overall per cycle started and 32.9% per embryo transfer. Stress measures were not associated with clinical pregnancy: when compared with the lowest categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest categories of the perceived stress score was 1.04 (95% CI 0.58-1.87), infertility-related stress score was OR = 1.18 (95% CI 0.56-2.47), morning and evening cortisol was OR = 1.18 (95% CI 0.60-2.29) and OR = 0.66 (95% CI 0.34-1.30), respectively. CONCLUSIONS Perceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes. These findings are potentially reassuring to women undergoing fertility treatment with concerns about the influence of stress on their treatment outcome.
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Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study.
Nilsson, AG, Bergthorsdottir, R, Burman, P, Dahlqvist, P, Ekman, B, Engström, BE, Ragnarsson, O, Skrtic, S, Wahlberg, J, Achenbach, H, et al
European journal of endocrinology. 2017;(6):715-725
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OBJECTIVE To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). DESIGN Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. METHODS Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. RESULTS Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). CONCLUSIONS In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.
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Flavour-enhanced cortisol release during gum chewing.
Hasegawa, Y, Tachibana, Y, Ono, T, Kishimoto, H
PloS one. 2017;(4):e0173475
Abstract
There is some evidence to suggest that chewing gum reduces chronic stress. However, it remains controversial how the taste and odour properties of chewing gum influence stress. The present study was designed to investigate this issue in human subjects. Using an enzyme-linked immunosorbent assay, we tested salivary cortisol concentration, which is thought to be a stress marker, in 96 adults who chewed gum with different combinations of taste and odour. Subjects could discriminate between the types of gum without prior information. Salivary cortisol concentrations were highest and lowest for the subjects who chewed the most flavourful gum and the least flavourful gum, respectively. These findings suggest that the salivary cortisol level during gum chewing is not a marker of negative emotions (i.e., stressful conditions) as traditionally considered but, rather, an index of positive emotions that can facilitate biological responses to overcome stressful conditions.
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Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, Phase III pasireotide study.
Findling, JW, Fleseriu, M, Newell-Price, J, Petersenn, S, Pivonello, R, Kandra, A, Pedroncelli, AM, Biller, BM
Endocrine. 2016;(2):516-523
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Measuring salivary cortisol is a simple, convenient and accurate technique with potential value in monitoring patients with hypercortisolism. This analysis reports changes in late-night salivary cortisol (LNSC) during a 12-month, multicentre, Phase III study of patients with Cushing's disease who were randomized to pasireotide 600 or 900 μg sc bid. LNSC assessment was an exploratory objective based on a single, optional measurement at midnight ± 1 h on the same day as one of the 24-h urinary free cortisol (UFC) measurements. Of 162 enrolled patients, baseline LNSC was measured in 93. Sixty-seven patients had levels above the upper limit of normal (ULN); median baseline levels were 19.7 and 20.7 nmol/L in the groups subsequently randomized to 600 μg (n = 40) and 900 μg (n = 27), respectively. Median LNSC levels decreased from baseline to month 12; median changes in patients who had baseline LNSC > ULN in the 600 and 900 μg groups were -13.4 nmol/L (-52.6 %; n = 19) and -11.8 nmol/L (-56.1 %; n = 14), respectively. LNSC normalized at months 6 and 12 in 25/67 (37.3 %) and 13/67 (19.4 %) patients, respectively; 10/25 and 8/13 patients also had normalized UFC, and 7/25 and 4/13 had partial UFC control (UFC > ULN and ≥50 % decrease from baseline). There was a moderate correlation (r = 0.55) on the log scale between individual patient LNSC and UFC values when all time points were pooled. Pasireotide decreased LNSC levels during 12 months of treatment. Salivary cortisol may be a simple, convenient biomarker for assessing treatment response in patients with Cushing's disease.
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Maternal cortisol and stress are associated with birth outcomes, but are not affected by lipid-based nutrient supplements during pregnancy: an analysis of data from a randomized controlled trial in rural Malawi.
Stewart, CP, Oaks, BM, Laugero, KD, Ashorn, U, Harjunmaa, U, Kumwenda, C, Chaima, D, Maleta, K, Ashorn, P, Dewey, KG
BMC pregnancy and childbirth. 2015;:346
Abstract
BACKGROUND Prenatal micronutrient supplements have been found to increase birth weight, but mechanisms for increased growth are poorly understood. Our hypotheses were that 1) women who receive lipid-based nutrient supplements (LNS) during pregnancy would have lower mean salivary cortisol concentration at 28 wk and 36 wk gestation compared to the multiple micronutrient (MMN) and iron-folic acid (IFA) supplement groups and 2) both salivary cortisol and perceived stress during pregnancy would be associated with shorter duration of gestation and smaller size at birth. METHODS Women were enrolled in the trial in early pregnancy and randomized to receive LNS, MMN, or iron-folic acid (IFA) supplements daily throughout pregnancy. At enrollment, 28 wk and 36 wk gestation, saliva samples were collected and their cortisol concentration was measured. Self-report of perceived stress was measured using questionnaires. Gestation duration was indicated by ultrasound dating and newborn anthropometric measurements (weight, length, head circumference) provided indicators of intrauterine growth. RESULTS Of the 1391 women enrolled in the trial, 1372, 906 and 1049 saliva samples were collected from women at baseline, 28 wk and 36 wk, respectively. There were no significant differences in mean cortisol concentrations by intervention group at 28 wk or 36 wk gestation. Cortisol concentrations were negatively associated with duration of gestation (Baseline: β = -0.05, p = 0.039; 36 wk: β = -0.04, p = 0.037) and birth weight (28 wk: β = -0.08, p = 0.035; 36 wk: β = -0.11, p = 0.003) but not associated with length-for-age or head circumference-for-age z-scores. Perceived stress at 36 wk was significantly associated with shorter newborn LAZ (p = 0.001). There were no significant associations with the risk of small for gestational age, preterm birth, or low birth weight. CONCLUSIONS Maternal salivary cortisol concentration was strongly associated with birth weight and duration of gestation in rural Malawi, but these data do not support the hypothesis that LNS provision to pregnant women would influence their salivary cortisol concentrations. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT01239693.
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Displacement of cortisol from human heart by acute administration of a mineralocorticoid receptor antagonist.
Iqbal, J, Andrew, R, Cruden, NL, Kenyon, CJ, Hughes, KA, Newby, DE, Hadoke, PW, Walker, BR
The Journal of clinical endocrinology and metabolism. 2014;(3):915-22
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CONTEXT Mineralocorticoid receptor (MR) antagonists have beneficial effects in patients with heart failure and myocardial infarction, often attributed to blocking aldosterone action in the myocardium. However, binding of aldosterone to MR requires local activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which inactivates cortisol to cortisone and thereby prevents receptor occupancy by cortisol. In vivo activity of 11β-HSD2 and potential occupancy of MR by cortisol in human heart have not been quantified. OBJECTIVE This study aimed to measure in vivo activity of 11β-HSD2 and to establish whether cortisol binds MR in human heart. PARTICIPANTS AND INTERVENTIONS Nine patients without heart failure undergoing diagnostic coronary angiography were infused to steady state with the stable isotope tracers 9,11,12,12-[(2)H]4-cortisol and 1,2-[(2)H]2-cortisone to quantify cortisol and cortisone production. Samples were obtained from the femoral artery and coronary sinus before and for 40 minutes after bolus iv administration of an MR antagonist, potassium canrenoate. Coronary sinus blood flow was measured by venography and Doppler flow wire. RESULTS There was no detectable production of cortisol or cortisone across the myocardium. After potassium canrenoate administration, plasma aldosterone concentrations increased substantially but aldosterone was not detectably released from the myocardium. In contrast, plasma cortisol concentrations did not change in the systemic circulation but tissue-bound cortisol was released transiently from the myocardium after potassium canrenoate administration. CONCLUSIONS Human cardiac 11β-HSD2 activity appears too low to inactivate cortisol to cortisone. Cortisol is displaced acutely from the myocardium by MR antagonists and may contribute to adverse MR activation in human heart.