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1.
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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2.
Association Between Cortisol, Insulin Resistance and Zinc in Obesity: a Mini-Review.
Morais, JBS, Severo, JS, Beserra, JB, de Oiveira, ARS, Cruz, KJC, de Sousa Melo, SR, do Nascimento, GVR, de Macedo, GFS, do Nascimento Marreiro, D
Biological trace element research. 2019;(2):323-330
Abstract
Adipose tissue is considered an endocrine organ and its excess compromises the immune response and the metabolism of hormones and nutrients. Furthermore, visceral fat accumulation contributes to increased cortisol synthesis, which in turn induces metallothionein and Zip14 expression, which are proteins that contribute to reducing plasma zinc levels. Zinc plays a critical role in the secretion and signaling of insulin. Changes in the biochemical parameters of zinc, as observed in individuals who are obese, contribute to the manifestation of related disorders such as insulin resistance. Thus, the purpose of this review is to provide an update on the current information on the relationship between cortisol, zinc, and insulin resistance in obesity. The data in the literature provide evidence that cortisol affects zinc metabolism, and indicate possible repercussions on insulin signaling that might contribute to the development of resistance to the actions of insulin in obesity.
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3.
Patterns of Death in Patients with Sepsis and the Use of Hydrocortisone, Ascorbic Acid, and Thiamine to Prevent These Deaths.
Marik, PE
Surgical infections. 2018;(8):812-820
Abstract
Background: In general, patients with sepsis die from the host response to the infecting pathogen rather than from the infecting pathogen itself. Four patterns of death have been identified in sepsis, namely vasoplegic shock, single-organ respiratory failure (acute respiratory distress syndrome [ARDS]), multi-system organ failure (MSOF), and persistent MSOF with ongoing inflammation and immunosuppression with recurrent infections (persistent inflammation-immunosuppression and catabolism syndrome [PICS]). To improve the outcome of sepsis adjunctive therapies that modulate the immune system have been tested; these therapies that have targeted specific molecules or pathways have universally failed. Conclusion: We propose that the combination of hydrocortisone, intravenous ascorbic acid, and thiamine (HAT therapy), which synergistically targets multiple pathways, restores the dysregulated immune system and organ injury, and reduces the risk of death and organ failure following sepsis.
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4.
Excess Hydrocortisone Hampers Placental Nutrient Uptake Disrupting Cellular Metabolism.
Mateos, RM, Jiménez, G, Álvarez-Gil, C, Visiedo, F, Rivera-Rodríguez, F, Santos-Rosendo, C, Rodriguez-Pareja, A, Perdomo, G, Lechuga-Sancho, AM
BioMed research international. 2018;:5106174
Abstract
Low birth weight increases neonatal morbidity and mortality, and surviving infants have increased risk of metabolic and cardiovascular disturbances later in life, as well as other neurological, psychiatric, and immune complications. A gestational excess of glucocorticoids (GCs) is a well-known cause for fetal growth retardation, but the biological basis for this association remains elusive. Placental growth is closely related to fetal growth. The placenta is the main regulator of nutrient transport to the fetus, resulting from the difference between placental nutrient uptake and the placenta's own metabolism. The aim of this study was to analyze how excess hydrocortisone affects placental glucose and lipid metabolism. Human placenta explants from term physiological pregnancies were cultured for 18 hours under different hydrocortisone concentrations (2.75, 5.5, and 55 mM; 1, 2, and 20 mg/ml). Placental glucose and lipid uptake and the metabolic partitioning of fatty acids were quantified by isotopic techniques, and expression of specific glucose transporter GLUT1 was quantified by western blot. Cell viability was assessed by MTT, immunohistochemistry and caspase activity. We found that excess hydrocortisone impairs glucose uptake and lipoprotein lipase (LPL) activity, coincident with a GC-dose dependent inhibition of fatty acid oxidation and esterification. None of the experimental conditions showed an increased cell death. In conclusion, our results show that GC overexposure exerts a dysfunctional effect on lipid transport and metabolism and glucose uptake in human placental explants. These findings could well be directly related to a reduced placental growth and possibly to a reduced supply of nutrients to the fetus and the consequent fetal growth retardation and metabolic programming.
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5.
Higher DHEAS Levels Associated with Long-Term Practicing of Tai Chi.
Lai, HM, Liu, MSY, Lin, TJ, Tsai, YL, Chien, EJ
The Chinese journal of physiology. 2017;(2):124-130
Abstract
Tai Chi has many benefits for middle-aged/older individuals including improvements to muscle strength and various body lipid components. DHEAS and testosterone have anti-obesity/anti-aging characteristics and also improve libido, vitality and immunity levels. Thus, the aim of the present study was to investigate the differences between middle-aged Tai Chi practitioners (n = 17) and sedentary individuals (n = 17) in terms of leg strength, blood levels of cholesterol, triglyceride, HDL, as well as DHEAS, testosterone and cortisol. Unpaired t-tests were used to identify significant differences between the two groups. There were no significant differences in body composition, leg strength, blood lipid components and testosterone. However, the Tai Chi practitioners had higher levels of DHEAS (P < 0.01) and lower levels of cortisol (P < 0.05). Thus, Tai Chi practitioners have a higher ratio of DHEAS to cortisol, which might have potential benefits in terms of improving an individual’s health-related quality of life during the aging.
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6.
Hydrocortisone and Ascorbic Acid Synergistically Prevent and Repair Lipopolysaccharide-Induced Pulmonary Endothelial Barrier Dysfunction.
Barabutis, N, Khangoora, V, Marik, PE, Catravas, JD
Chest. 2017;(5):954-962
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Abstract
BACKGROUND Sepsis refers to the dysregulated host immune response elicited by microbial infections resulting in life-threatening organ dysfunction. Sepsis represents a medical challenge, since it is associated with a rate of death as high as 60%. Septic shock is strongly associated with vascular dysfunction and elevated pulmonary capillary permeability. We recently reported that the combination of hydrocortisone (HC), ascorbic acid (vitC), and thiamine dramatically improves outcomes and reduces mortality in patients with sepsis. In the present study, we provide experimental evidence in support of the hypothesis that the combination of HC and vitC enhances endothelial barrier function. METHODS Human lung microvascular endothelial cells were exposed to lipopolysaccharide (LPS) in the absence or presence of HC and vitC. RESULTS LPS alone induced profound hyperpermeability, as reflected in decreased values of transendothelial electrical resistance. vitC alone did not exhibit barrier enhancement properties nor did it affect the LPS-induced hyperpermeability. Similarly, HC alone exhibited only a minor barrier-enhancing and protective effect. Conversely, the combination of HC and vitC, either as before or after treatment, dramatically reversed the LPS-induced barrier dysfunction. The barrier-protective effects of HC and vitC were associated with reversal of LPS-induced p53 and phosphorylated cofilin downregulation and LPS-induced RhoA activation and myosin light chain phosphorylation. CONCLUSIONS These data provide a novel mechanism of endothelial barrier protection and suggest one possible pathway that may contribute to the therapeutic effects of HC and vitC in patients with sepsis.
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Effect of cortisol and/or DHEA on THP1-derived macrophages infected with Mycobacterium tuberculosis.
Bongiovanni, B, Mata-Espinosa, D, D'Attilio, L, Leon-Contreras, JC, Marquez-Velasco, R, Bottasso, O, Hernandez-Pando, R, Bay, ML
Tuberculosis (Edinburgh, Scotland). 2015;(5):562-9
Abstract
Tuberculosis (TB) is a major health problem requiring an appropriate cell immune response to be controlled. Macrophages play a central role in the response against Mycobacterium tuberculosis (Mtb). Given our prior studies in which adrenal steroids were found to modify the cellular immune responses from TB patients, it was sensible to analyze the immunomodulatory capability of cortisol and DHEA on macrophages infected with Mtb. The human macrophage-like THP-1 cells were infected with the H37Rv strain of Mtb and treated with Cortisol and DHEA at different doses. We monitored phagocytosis, intracellular-bacterial growth, autophagosoma formation, as well as cytokine gene expression and production. Cultures exposed to cortisol showed a decreased production of IL-1β, TNF-α, with DHEA being unable to modify the pattern of cytokine production or to reverse the cortisol inhibitory effects. Interestingly the intra-macrophagic bacterial burden was found reduced by DHEA treatment. While this effect was not related to a different cytokine pattern, in terms their production or mRNA expression, DHEA treatment did promote autophagy in Mtb-infected macrophages, irrespective of Cortisol presence. In essence, the better control of Mtb load by DHEA-treated macrophages seems to be dependent on an autophagic mechanism. The present results are relevant for two reasons as autophagy is not only important for clearance of mycobacteria but also for the prevention of tissue damage.
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Effects of carbohydrate ingestion on acute leukocyte, cortisol, and interleukin-6 response in high-intensity long-distance running.
Ihalainen, JK, Vuorimaa, T, Puurtinen, R, Hämäläinen, I, Mero, AA
Journal of strength and conditioning research. 2014;(10):2786-92
Abstract
The purpose of this study was to investigate the effect of ingestion of fluids with different carbohydrate concentrations (0, 1.5, and 7%) on the acute immune stress responses after high-intensity long-distance running. Continuous 18- to 20-km run was performed at 75% of maximal oxygen uptake with carbohydrate supplementation (CHO7%, 7% carbohydrate solution) and low-carbohydrate supplementation (lowCHO1.5%, 1.5% carbohydrate solution) in a randomized, double-blind, placebo (PLA) controlled design. Seven recreational runners (4 men and 3 women) completed all 3 trials. Blood was collected at baseline (PRE) and immediately after the run (POST). The running task induced significant (p ≤ 0.05) increases in leukocyte (white blood cells), neutrophil, and interleukin-6 (IL-6) counts in every trial. There was a significant (p ≤ 0.05) increase in cortisol with PLA and lowCHO1.5% but not with CHO7%. Increase in total leukocyte and neutrophil concentration was significantly lower with CHO7% compared with PLA (p ≤ 0.05). Postexercise IL-6 levels were significantly elevated when compared with baseline in all conditions (p ≤ 0.05). Interleukin-6 (IL-6) concentrations did not differ significantly between trials. LowCHO1.5% sport drink did not significantly differ from PLA in measured variables, which indicated that the amount and rate of carbohydrate ingestion (15 g, 10 g·h) in low-carbohydrate sport drink was not enough to significantly protect from the stress induced by high-intensity long-distance running, whereas the ingestion of CHO7% (45 g·h) blunted the significant cortisol response and significantly decreased the leukocyte response.
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Effects of carbohydrate beverage ingestion on the salivary IgA response to intermittent exercise in the heat.
Sari-Sarraf, V, Doran, DA, Clarke, ND, Atkinson, G, Reilly, T
International journal of sports medicine. 2011;(9):659-65
Abstract
The purpose of this study was to establish if provision of CHO altered the mucosal immune and salivary cortisol responses to intermittent exercise in the heat. In a double-blind design, 10 males undertook soccer-specific intermittent exercise on a motorized treadmill on 2 occasions, each over 90 min and separated by 1 week. During CHO and placebo trials, subjects were given either a carbohydrate solution (3 ml · kg (-1) body weight) or placebo drink, 5 min before the commencement of exercise, at 15, 30 min, at half time, 60 and 75 min into exercise. Salivary flow rate increased throughout the placebo trial and decreased throughout the CHO treatment; the difference between conditions neared statistical significance (P=0.055). Neither s-IgA concentration nor s-IgA to osmolality ratio was affected by 2 conditions or differed at any time-point post-exercise (P>0.05). The s-IgA secretion rate increased, s-IgA to protein ratio decreased post-exercise and salivary cortisol decreased 24 h post-exercise (P<0.05) compared to pre-exercise. Carbohydrate supplementation whilst exercising in the heat, does not influence rating of perceived exertion, thermal sensation, salivary flow rate, s-IgA concentration, s-IgA secretion rate, s-IgA to osmolality ratio or s-IgA to protein ratio and salivary cortisol but heart rate was increased.
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Cortisol response to ACTH stimulation correlates with blood interleukin 6 concentration in healthy humans.
Zarković, M, Ignjatović, S, Dajak, M, Cirić, J, Beleslin, B, Savić, S, Stojković, M, Bulat, P, Trbojević, B
European journal of endocrinology. 2008;(5):649-52
Abstract
OBJECTIVE Interleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitary-adrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. DESIGN AND METHODS Basal IL6 concentration was measured and a low dose (1 microg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22-47 years) were included in the study. RESULTS Data are presented as mean+/-S.E.M. Basal IL6 level was 0.84+/-0.10 pg/ml. Basal cortisol was 351.9+/-18.3 nmol/l. Maximal cortisol during synacthen test was 653.0+/-20.6 nmol/l. Maximal cortisol increment was 301.1+/-20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (r=0.63, 95% confidence interval) 0.42-0.83). CONCLUSIONS In our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions.