Publications

Endocrinology of the Physical Activity


June 26, 2021

HORMONES, EXERCISE, FOOD, SLEEP, AND WORK

Eat, train, sleep, work

WHAT YOU EAT, HOW YOU SLEEP AND HOW MUCH YOU WORK INFLUENCE YOUR HORMONE LEVELS AND ABILITY TO RESPOND TO STIMULATIONS. 

Due to the large number of markers evaluated and relatively large number of subjects, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we were able to perform more advanced statistical analyses to detect correlations and predictors. In the EROS-PREDICTORS paper, we determined the how eating, sleeping, and working habit patterns may drive clinical and biochemical behaviors.

Higher carbohydrate intake predicts quicker GH, prolactin, and cortisol responses to an ITT, which helps athletes to have explosive reaction, particularly important for fast, short-duration sports (short-distance running) and stop-and-go sports (ball games).

Estradiol in males was directly predicted by carbohydrate whereas inversely predicted by overall caloric intake. This dual correlation between food and estradiol is an interesting finding, because while the more carbohydrate athletes take, more conversion of testosterone into estradiol they will present, higher overall caloric intake leads to reduction of aromatase activity. This means that while carbohydrate intake enhances estradiol production, too few caloric intake also induces estradiol production possibly as a mechanism of reduction of the anabolic effects of testosterone, since the organism understands too few caloric intake as a sort of ‘starvation’ that must prevent any anabolism. This shows that both how much and what you eat matter.

Muscle recovery speed was directly predicted by any source of caloric intake, rather than protein or carbohydrate alone, which means that the amount you eat right after a training session, not how much of each macronutrient, is what matters at this moment. Important to mention that this was shown to be valid only for the post-training period.

Higher protein intake prevents overall and visceral body fat accumulation and improves hydration, independently of overall caloric intake, which provides additional evidence for the benefits of protein intake.

Visceral fat was directly correlated by overall caloric intake when protein intake was not high, which means that increased caloric intake may increase visceral fat, unless protein intake is high, showing an anti-visceral fat protective effect of protein intake.

We found that the minimum amount of protein intake for athletes to keep healthy, with optimized hormonal and metabolic responses, and to prevent overtraining syndrome (OTS) was 1.6g/kg/day, which can reach as much as 4.5g/kg/day, with additional improvements when protein is increased until this point, without further risks.

To prevent OTS, athletes should eat at least 45kcal/kg/day and 5g/kg/day of carbohydrate. In addition, professional or elite athletes should have lower and less stressful cognitive demands, preferably work for less than 7 hours daily (when sports training is not the profession), and focus on sleep hygiene for better sleep quality.

Although some of these recommendations were intuitive, providing specific numbers and unveiling specific consequences of each inadequate habit may encourage athletes and coaches to adhere to healthy habits since they can now understand what happens to athletes’ bodies when they do not follow recommendations accordingly. 

Links:
https://www.frontiersin.org/articles/10.3389/fendo.2020.00414/full
https://pubmed.ncbi.nlm.nih.gov/32670198/

Cadegiani FA, Kater CE. Eating, Sleep, and Social Patterns as Independent Predictors of Clinical, Metabolic, and Biochemical Behaviors Among Elite Male Athletes: The EROS-PREDICTORS Study. Front Endocrinol (Lausanne). 2020;11:414. Published 2020 Jun 26. doi:10.3389/fendo.2020.00414. 

Study Abstract

Objectives: Physiological hormonal adaptions in athletes and pathological changes that occur in overtraining syndrome among athletes are unclear. The Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study evaluated 117 markers and unveiled novel hormonal and metabolic beneficial adaptive processes in athletes. The objective of the present study was to uncover which modifiable factors predict the behaviors of clinical and biochemical parameters and to understand their mechanisms and outcomes using the parameters evaluated in the EROS study. Methods: We used multivariate linear regression with 39 participants to analyze five independent variables-the modifiable parameters (caloric, carbohydrate, and protein intake, and sleep quality and duration of concurrent cognitive activity) on 37 dependent variables-that were elected among the parameters evaluated in the EROS study. Results: Carbohydrate intake predicted quick hormonal responses to stress and improved explosive responses during exercise. Protein intake predicted improved body composition and metabolism and caloric intake, regardless of the proportion of macronutrients, predicted muscle recovery, and alertness in the morning. Sleep quality predicted improved mood and excessive concurrent cognitive effort in athletes under intense training predicted impaired metabolism and libido. Conclusions: The results support the premise that eating, sleep, and social patterns modulate metabolic and hormonal function, clinical behaviors, and performance status of male athletes, and should be monitored continuously and actively to avoid dysfunctions.

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THE BEAUTIFUL BODY ORCHESTRA IN ATHLETES

Metabolism and physical conditioning

THE INTERPLAY BETWEEN CLINICAL, METABOLIC, AND BIOCHEMICAL BEHAVIORS IN ATHLETES: THE BEAUTIFUL ORCHESTRY OF THE PHYSICALLY CONDITIONED BODY 

The multiple parameters evaluated in the largest study on Overtraining Syndrome (The EROS Study) of different aspects – clinical, biochemical, metabolic, and body-related – allowed further statistical tools to detect how these parameters direct- and indirectly affect the behaviors of other parameters. The findings of these intercorrelations between the discovered markers, and how these could help detect overtraining syndrome, were described in the EROS-CORRELATIONS paper.

Fat mass was inversely correlated with the testosterone:estradiol (T:E) ratio, which means that fat mass likely stimulates the aromatase activity, enhancing the conversion of testosterone into estradiol, and consequently reducing the T:E ratio.

The T:E ratio predicted the measured resting metabolic rate (RMR):predicted RMR ratio and the chest-to-waist circumference rate. These findings mean that the proportion between testosterone and estradiol predicts the metabolic speed, since the measured-to-predicted RMR measures how fast the metabolism is compared to the metabolism expected according to sex, age, and weight, and also predicts the V-shape body, resulted from higher chest-to-waist circumference rate.

GH, cortisol, and prolactin responses were strongly intercorrelated to an insulin tolerance test (ITT), demonstrated a diffuse hypothalamic response to stress stimulations. It means that under any stimulation, GH, cortisol, or prolactin do not respond alone, independent of the other hormonal axes. Either all hormones or none of the hormones respond, not part of them.

Sleep quality was shown to be the most determinant of psychological states. It means that the main determinant of the psychological moods is how well athletes sleep. Not hormonal levels or training patterns. Sleeping is the key for better mood states.

Fat oxidation, level of hydration, and the amount of both body fat and lean masses are intercorrelated. This finding brings multiple meanings: that the more hydrated you are, the more fat you burn and the less edema you present, that lean and fat masses are the major balances of body metabolism and hydration, and are inversely proportioned, and that lean mass directly stimulates fat burning, while the same does not happen with fat mass, i.e., fat mass does not stimulate its burning alone, it tends to preserve instead.

The amplitude of GH, cortisol, and prolactin responses to stimulations, the level of cortisol response to awakening, and the T:E are correlated with energy levels. This means that the main determinants of the energy levels are how much GH, cortisol, and prolactin you release in response to any stimulation, how much cortisol raises when you wake up, and the level of aromatase activity.

However, it is important to mention that estradiol does have beneficial effects on males, including increase of muscle and bone mass, increase of libido, and improvement of mood states. However, for this to happen, it must be accompanied by concurrent increase of testosterone. If estradiol increases due to pathologically exacerbated aromatase activity, that usually occurs in metabolic conditions such as obesity and type 2 diabetes, and now discovered to occur in overtraining syndrome, the resulting testosterone will be lower, leading to decreased T:E effects and bringing more harms than the goods expected for higher estradiol levels.

The understanding of the clinical, metabolic, body, and biochemical interplays helped elucidate the secondary effects of specific behaviors and reinforced previous observations of the influence of sleeping, hormonal environment and balance, and body composition on other clinical and biochemical markers.

Links:
https://www.frontiersin.org/articles/10.3389/fendo.2019.00858/full
https://pubmed.ncbi.nlm.nih.gov/31920971/

Cadegiani FA, Kater CE. Inter-correlations Among Clinical, Metabolic, and Biochemical Parameters and Their Predictive Value in Healthy and Overtrained Male Athletes: The EROS-CORRELATIONS Study. Front Endocrinol (Lausanne). 2019;10:858. Published 2019 Dec 10. doi:10.3389/fendo.2019.00858.   

Study Abstract

Objectives: The Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study identified multiple hormonal and metabolic conditioning processes in athletes, and underlying mechanisms and biomarkers of overtraining syndrome (OTS). The present study's objective was to reveal independent predictors and linear correlations among the parameters evaluated in the EROS study to predict clinical, metabolic, and biochemical behaviors in healthy and OTS-affected male athletes. Methods: We used multivariate linear regression and linear correlation to analyze possible combinations of the 38 parameters evaluated in the EROS study that revealed significant differences between healthy and OTS-affected athletes. Results: The testosterone-to-estradiol (T:E) ratio predicted the measured-to-predicted basal metabolic rate (BMR) ratio; the T:E ratio and total testosterone level were inversely predicted by fat mass and estradiol was not predicted by any of the non-modifiable parameters. Early and late growth hormone, cortisol, and prolactin responses to an insulin tolerance test (ITT) were strongly correlated. Hormonal responses to the ITT were positively correlated with fat oxidation, predicted-to-measured BMR ratio, muscle mass, and vigor, and inversely correlated with fat mass and fatigue. Salivary cortisol 30 min after awakening and the T:E ratio were inversely correlated with fatigue. Tension was inversely correlated with libido and directly correlated with body fat. The predicted-to-measured BMR ratio was correlated with muscle mass and body water, while fat oxidation was directly correlated with muscle mass and inversely correlated with fat mass. Muscle mass was directly correlated with body water, and extracellular water was directly correlated with body fat and inversely correlated with body water and muscle mass. Conclusions: Hypothalamic-pituitary responses to stimulation were diffuse and indistinguishable between the different axes. A late hormonal response to stimulation, increased cortisol after awakening, and the T:E ratio were correlated with vigor and fatigue. The T:E ratio was also correlated with body metabolism and composition, testosterone was predicted by fat mass, and estradiol predicted anger. Hydration status was inversely correlated with edema, and inter-correlations were found among fat oxidation, hydration, and body fat.

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A NEW DISCOVERY: THE ABILITY OF ATHLETES TO GET HORMONALLY CONDITIONED

 

Hormones in athletes

HORMONAL CONDITIONING, THE NOVEL CONDITIONING PROCESS DETECTED IN ATHLETES. 

Conditioning of the cardiovascular and musculoskeletal systems are conditioning processes extensively described in athletes, and have large contributions to the progressive improvement in sports performance.

However, the improvements in explosion, maintenance of the pace for prolonged periods of time, and increased time-to-fatigue could not be fully explained by the currently described conditioning processes.

In the Endocrine and Metabolic Responses to Overtraining Syndrome (EROS) study, because we compared athletes affected by overtraining syndrome (OTS) with both healthy athletes and healthy sedentary, unexpected differences between healthy athletes and non-physically active subjects were detected. We expected that responses to a non-exercise stimulation would be similar under physiological conditions, i.e., that healthy athletes would disclose similar hormonal responses to a non-exercise stimulation test than sedentary, since the stimulation was independent of any physical effort. However, healthy athletes demonstrated a faster, enhanced, and prolonged response of all hormones compared to non-athletes, irrespective of physical activity, and independent of external factors or other systems. This ended up becoming the proof-of-concept of the conditioning of the endocrine glands, particularly the hypothalamus-pituitary axis, that athletes undergo, and that had not been described to date, at least with these characteristics that avoided confounding biases. The conditioning process of the endocrine system may justify some not fully elucidated improvements in performance and health benefits from exercising.

Not only the cardiovascular and musculoskeletal, but also the endocrine system is conditioned in athletes.  

Links:
https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-019-0443-7
https://pubmed.ncbi.nlm.nih.gov/31675953/ 

Cadegiani FA, Kater CE. Enhancement of hypothalamic-pituitary activity in male athletes: evidence of a novel hormonal mechanism of physical conditioning. BMC Endoc Dis. 2019 Nov 1;19(1):117. Published 2019 Nov 1. doi:10.1186/s12902-019-0443-7 

Study Abstract

Background: Exercise is known to induce multiple beneficial conditioning processes. Conversely, although exercise may generate several hormonal effects, an intrinsic hormonal conditioning process has not been reported. In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we observed inherent and independent conditioning processes of the hypothalamic-pituitary axes in athletes. Our objective is to describe the theory of the novel hormonal conditioning mechanism using the findings from the EROS study.

Methods: In this cross-sectional study, we selected 25 healthy athletes (ATL) and 12 non-physically active healthy controls (NPAC), 18-50 years old, males, with BMI 20-30 kg/m2, with similar baseline characteristics, who underwent gold-standard exercise-independent tests: cosyntropin stimulation test (CST) and insulin tolerance test (ITT), to evaluate cortisol response to CST, and ACTH, cortisol, GH, and prolactin responses to an ITT.

Results: Responses to ITT were significantly earlier and higher in ATL than NPAC for cortisol [Mean ± SD: 21.7 ± 3.1 vs 16.9 ± 4.1 μg/dL; p < 0.001], GH [Median (95% CI): 12.73 (1.1-38.1) vs 4.80 (0.33-27.36) μg/L; p = 0.015], and prolactin [24.3 (10.5-67.45) vs 10.50 (6.21-43.44) ng/mL; p = 0.002]. Cortisol response to CST was similar between ATL and NPAC. During ITT, cortisol, GH, and ACTH mean increase in ATL were 52.2, 265.2, and 18.6% higher than NPAC, respectively. Prolactin response was absent in NPAC, while present in ATL.

Conclusions: We found sufficient evidence to propose the existence of a diffuse enhancement of the hypothalamic-pituitary activity in athletes, not restricted to any axis, showing an intrinsic and independent process of "hormonal conditioning" in athletes, similar to those observed in the cardiovascular and neuromuscular systems. This novel conditioning process may be the missing link for understanding the improved responses observed in athletes to harmful situations, traumas, infections, inflammations, and psychiatric conditions.

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SHOULD ATHLETES FOLLOW NORMAL BLOOD LEVELS?

 

Normal ranges of hormones in athletes

REFERENCE RANGE LEVELS OF HORMONES SHOULD BE ADAPTED FOR ATHLETES TO AVOID MISINTERPRETATION 

In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we decided to compare athletes affected by overtraining syndrome (OTS) with both healthy athletes and healthy sedentary, in order to avoid an incomplete interpretation of the findings in OTS. We expected that hormonal levels would be similar or very close between healthy athletes and healthy sedentary, since none of these two groups present any pathological change, and almost nothing had been described in the medical literature until that point.

However, multiple serendipitous findings regarding hormonal conditioning processes were detected by the differences between healthy athletes and sedentary, while the sick athletes had levels similar to sedentary.

This brings a challenge regarding the interpretation of the hormonal exams. First, levels expected for athletes are not necessarily the ones within the reference range. Second, ‘normal’ levels could actually mean a pathological state if found in an athlete, since ‘normal levels’ were the ones found in OTS, not in healthy athletes.

From our study and a systematic review from the literature, we proposed changes in the reference ranges for basal and stimulated hormonal levels, muscular, and metabolic parameters, to be applied to athletes.

Links:
https://academic.oup.com/jes/article/4/Supplement_1/MON-LB311/5833948
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209598/

Reference:
Cadegiani F, Abrao TPC, da Silva PLH, Kater CE. MON-LB305 The “Normal” Hormonal Levels in Athletes: Should Reference Ranges Be Adapted for the Physically Active Population?. J Endocr Soc. 2020;4(Suppl 1):MON-LB305. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2321

Study Abstract

Background:Despite the growing number of physically active subjects, including elite and amateur athletes, little is known regarding metabolic and hormonal chronic adaptations to exercises. While the elucidation of the hormonal and metabolic physiological adaptations to physical activity is of emerging importance, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study have serendipitously unveiled the existence of multiple metabolic and endocrine physiological changes in male athletes, including chronic increase of testosterone with concurrent physiological increase of estradiol, enhanced GH and cortisol responses to stimulations,andincreased catecholamines, basal metabolic rate, fat oxidation, and hydration status. These findings were uncovered due to a novel methodological design in which athletes affected by overtraining syndrome (OTS) were compared to a two control groups, of healthy athletes (ATL) and healthy non-physically active controls (NPAC). Since none of the parameters were directly dependent on exercise or performance, differences between these two groups were unexpected. From the fact that several parameters were shown to be different between ATL and NPAC, we realized that the use of the reference ranges for general population to analyze results in athletes may potentially under- and over-diagnose a wide range of conditions. Our objective is therefore to determine whether athletes should be biochemically evaluated through specific adapted ranges, and propose preliminary adaptations in these ranges. Methods: A systematic review on the literature on endocrine and metabolic adaptations to exercise was performed, as well as a thorough analysis of the seven arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. Results:Multiple reference ranges were shown to be inaccurate for athletes. Among the parameters that should be adapted for athletes, and their respective adaptedranges include: 1. Cortisol response to an insulin stimulation test (ITT) (> 20.5 μg/dL); 2. GH response to an ITT (> 12 μg/L); 3. Prolactin response to an ITT (> 22 ng/mL); 4. Salivary cortisol at 8AM (> 450 ng/dL); 5. Total testosterone (> 450 ng/dL); 6. Estradiol (25-45 pg/mL) - and testosterone-to-estradiol ratio maintained > 13.7; 7. Total nocturnal urinary catecholamines (> 220 μg/12h); 8. Resting lactate (< 1.0 nMol/L); 9. Measured-to-predicted basal metabolic rate (BMR) (> 105%); 10. Fat oxidation (in relation to total BMR) (> 50%); and 11. Hydration status (body water > 62% of total body weight). Conclusion: Analysis of biochemical parameters in athleted should be interpreted with cautious, particularly hormonal and metabolic parameters, once many parameters likely undergo adaptive changes when under physical activity. Preliminary adaptations for the ranges have been proposed.

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HORMONE RESEARCH DESIGNED FOR THE ATHLETE

Guidelines for the research of hormones in athletes

THE FIRST CLINICAL GUIDELINES FOR THE RESEARCH FIELD OF ENDOCRINOLOGY OF PHYSICAL ACTIVITY AND SPORT 

Because of the lack of standardization of the assessment of hormones in studies on athletes, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study employed standardized methods for the large number of basal and stimulated hormones evaluated by the study.

Since the number of physically-active subjects and amateur and professional athletes is increasing continuously, the adapted physiology of the athlete needs better understanding and elucidation of the many questions remained regarding the changes that occur in the endocrine system. Indeed, while adaptations of the cardiovascular and musculoskeletal systems have been extensively described, very few is known regarding the adaptative processes in the hormonal releasing and responses patterns.

The present paper is a summary of which parameters should be measured, how these parameters should be assessed, and a structured characterization of the sports performed, including classification into sports type, intensity, conditioning level, among others, since adaptations may be sports-, intensity-, and conditioning level-specific.

By the standardization of the hormonal and metabolic assessment methods, and structuring of the characterization of the sports and athletes, further head-to-head comparisons will become feasible, and sports will be able to be compared in terms of quantification of the benefits they bring. 

Links:
https://academic.oup.com/jes/article/4/Supplement_1/MON-LB311/5833948?searchresult=1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209438/

Reference:
Cadegiani FA, da Silva PLH. Clinical Guidelines for the Research on the Endocrinology of Physical Activity and Sport. J Endocr Soc. 2020;4(Suppl 1):MON-LB311. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2333. 

Study Abstract

Background: The importance of physical activity has achieved levels that has been recognized by as a major world public health game changer, which positively engaged a growing number of subjects to become physically active. While effects of exercise on cardiovascular and musculoskeletal systems are well described, little is known regarding hormonal adapted physiology in athletes, as well as how to detect and manage endocrine abnormalities in physically active subjects. Methodological issues and inconsistent findings precluded from a structured understanding of the endocrinology physiology of physical activity and sport. The objective of the present guideline is to uniformize the design and assessment methods of further studies in the field, based on standardized hormonal and metabolic parameters, and dynamic testings. Methods: Guidelines were actively searched within endocrinology, sports medicine, and cardiology societies. Systematic search on PubMed and Cochrane databases for the expressions “(name of the parameter or test)” + “exercise” or “athlete(s)” or “sport(s)” or “validation” or “standardization. Guidelines, consensus, statements, original studies, and reviews that standardized, validated, or proposed parameters and tests that could be potentially employed for the research on physical activity and sport were included.Results: Parameters of the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA), growth hormone-insulin-like growth factor-1 (GH-IGF1), and hypothalamic-pituitary-thyroid (HPT) axes, prolactin, renin-angiotensin-aldosterone system (RAAS), catecholamines and adrenal medulla, bone, water, glucose, and lipid metabolism, and adipose tissue and muscle endocrine profile were analyzed and classified according to the level of standardization, feasibility, and potential roles in physical activity and sport, and recommended accordingly. Recommendations on the characterization of the studied population, including eating, sleeping, social, psychological, and training patterns were depicted. Conclusion: The research on the endocrinology of physical activity and sport requires standardization and uniformization regarding the description of baseline and training characteristics, and which parameters and tests should be employed. These improvements will allow the development of a more structured and comprehensive knowledge on the field, based on comparative joint analyses of further researches, that should employ well-established parameters and adequately controlled for confounding variables.

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Hormones, Exercise, Food, Sleep, and Work


June 26, 2021

Eat, train, sleep, work

WHAT YOU EAT, HOW YOU SLEEP AND HOW MUCH YOU WORK INFLUENCE YOUR HORMONE LEVELS AND ABILITY TO RESPOND TO STIMULATIONS. 

Due to the large number of markers evaluated and relatively large number of subjects, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we were able to perform more advanced statistical analyses to detect correlations and predictors. In the EROS-PREDICTORS paper, we determined the how eating, sleeping, and working habit patterns may drive clinical and biochemical behaviors.

Higher carbohydrate intake predicts quicker GH, prolactin, and cortisol responses to an ITT, which helps athletes to have explosive reaction, particularly important for fast, short-duration sports (short-distance running) and stop-and-go sports (ball games).

Estradiol in males was directly predicted by carbohydrate whereas inversely predicted by overall caloric intake. This dual correlation between food and estradiol is an interesting finding, because while the more carbohydrate athletes take, more conversion of testosterone into estradiol they will present, higher overall caloric intake leads to reduction of aromatase activity. This means that while carbohydrate intake enhances estradiol production, too few caloric intake also induces estradiol production possibly as a mechanism of reduction of the anabolic effects of testosterone, since the organism understands too few caloric intake as a sort of ‘starvation’ that must prevent any anabolism. This shows that both how much and what you eat matter.

Muscle recovery speed was directly predicted by any source of caloric intake, rather than protein or carbohydrate alone, which means that the amount you eat right after a training session, not how much of each macronutrient, is what matters at this moment. Important to mention that this was shown to be valid only for the post-training period.

Higher protein intake prevents overall and visceral body fat accumulation and improves hydration, independently of overall caloric intake, which provides additional evidence for the benefits of protein intake.

Visceral fat was directly correlated by overall caloric intake when protein intake was not high, which means that increased caloric intake may increase visceral fat, unless protein intake is high, showing an anti-visceral fat protective effect of protein intake.

We found that the minimum amount of protein intake for athletes to keep healthy, with optimized hormonal and metabolic responses, and to prevent overtraining syndrome (OTS) was 1.6g/kg/day, which can reach as much as 4.5g/kg/day, with additional improvements when protein is increased until this point, without further risks.

To prevent OTS, athletes should eat at least 45kcal/kg/day and 5g/kg/day of carbohydrate. In addition, professional or elite athletes should have lower and less stressful cognitive demands, preferably work for less than 7 hours daily (when sports training is not the profession), and focus on sleep hygiene for better sleep quality.

Although some of these recommendations were intuitive, providing specific numbers and unveiling specific consequences of each inadequate habit may encourage athletes and coaches to adhere to healthy habits since they can now understand what happens to athletes’ bodies when they do not follow recommendations accordingly. 

Links:
https://www.frontiersin.org/articles/10.3389/fendo.2020.00414/full
https://pubmed.ncbi.nlm.nih.gov/32670198/

Cadegiani FA, Kater CE. Eating, Sleep, and Social Patterns as Independent Predictors of Clinical, Metabolic, and Biochemical Behaviors Among Elite Male Athletes: The EROS-PREDICTORS Study. Front Endocrinol (Lausanne). 2020;11:414. Published 2020 Jun 26. doi:10.3389/fendo.2020.00414. 

Study Abstract

Objectives: Physiological hormonal adaptions in athletes and pathological changes that occur in overtraining syndrome among athletes are unclear. The Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study evaluated 117 markers and unveiled novel hormonal and metabolic beneficial adaptive processes in athletes. The objective of the present study was to uncover which modifiable factors predict the behaviors of clinical and biochemical parameters and to understand their mechanisms and outcomes using the parameters evaluated in the EROS study. Methods: We used multivariate linear regression with 39 participants to analyze five independent variables-the modifiable parameters (caloric, carbohydrate, and protein intake, and sleep quality and duration of concurrent cognitive activity) on 37 dependent variables-that were elected among the parameters evaluated in the EROS study. Results: Carbohydrate intake predicted quick hormonal responses to stress and improved explosive responses during exercise. Protein intake predicted improved body composition and metabolism and caloric intake, regardless of the proportion of macronutrients, predicted muscle recovery, and alertness in the morning. Sleep quality predicted improved mood and excessive concurrent cognitive effort in athletes under intense training predicted impaired metabolism and libido. Conclusions: The results support the premise that eating, sleep, and social patterns modulate metabolic and hormonal function, clinical behaviors, and performance status of male athletes, and should be monitored continuously and actively to avoid dysfunctions.

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The Beautiful Active Body Orchestra


June 26, 2021

Metabolism and physical conditioning

THE INTERPLAY BETWEEN CLINICAL, METABOLIC, AND BIOCHEMICAL BEHAVIORS IN ATHLETES: THE BEAUTIFUL ORCHESTRY OF THE PHYSICALLY CONDITIONED BODY 

The multiple parameters evaluated in the largest study on Overtraining Syndrome (The EROS Study) of different aspects – clinical, biochemical, metabolic, and body-related – allowed further statistical tools to detect how these parameters direct- and indirectly affect the behaviors of other parameters. The findings of these intercorrelations between the discovered markers, and how these could help detect overtraining syndrome, were described in the EROS-CORRELATIONS paper.

Fat mass was inversely correlated with the testosterone:estradiol (T:E) ratio, which means that fat mass likely stimulates the aromatase activity, enhancing the conversion of testosterone into estradiol, and consequently reducing the T:E ratio.

The T:E ratio predicted the measured resting metabolic rate (RMR):predicted RMR ratio and the chest-to-waist circumference rate. These findings mean that the proportion between testosterone and estradiol predicts the metabolic speed, since the measured-to-predicted RMR measures how fast the metabolism is compared to the metabolism expected according to sex, age, and weight, and also predicts the V-shape body, resulted from higher chest-to-waist circumference rate.

GH, cortisol, and prolactin responses were strongly intercorrelated to an insulin tolerance test (ITT), demonstrated a diffuse hypothalamic response to stress stimulations. It means that under any stimulation, GH, cortisol, or prolactin do not respond alone, independent of the other hormonal axes. Either all hormones or none of the hormones respond, not part of them.

Sleep quality was shown to be the most determinant of psychological states. It means that the main determinant of the psychological moods is how well athletes sleep. Not hormonal levels or training patterns. Sleeping is the key for better mood states.

Fat oxidation, level of hydration, and the amount of both body fat and lean masses are intercorrelated. This finding brings multiple meanings: that the more hydrated you are, the more fat you burn and the less edema you present, that lean and fat masses are the major balances of body metabolism and hydration, and are inversely proportioned, and that lean mass directly stimulates fat burning, while the same does not happen with fat mass, i.e., fat mass does not stimulate its burning alone, it tends to preserve instead.

The amplitude of GH, cortisol, and prolactin responses to stimulations, the level of cortisol response to awakening, and the T:E are correlated with energy levels. This means that the main determinants of the energy levels are how much GH, cortisol, and prolactin you release in response to any stimulation, how much cortisol raises when you wake up, and the level of aromatase activity.

However, it is important to mention that estradiol does have beneficial effects on males, including increase of muscle and bone mass, increase of libido, and improvement of mood states. However, for this to happen, it must be accompanied by concurrent increase of testosterone. If estradiol increases due to pathologically exacerbated aromatase activity, that usually occurs in metabolic conditions such as obesity and type 2 diabetes, and now discovered to occur in overtraining syndrome, the resulting testosterone will be lower, leading to decreased T:E effects and bringing more harms than the goods expected for higher estradiol levels.

The understanding of the clinical, metabolic, body, and biochemical interplays helped elucidate the secondary effects of specific behaviors and reinforced previous observations of the influence of sleeping, hormonal environment and balance, and body composition on other clinical and biochemical markers.

Links:
https://www.frontiersin.org/articles/10.3389/fendo.2019.00858/full
https://pubmed.ncbi.nlm.nih.gov/31920971/

Cadegiani FA, Kater CE. Inter-correlations Among Clinical, Metabolic, and Biochemical Parameters and Their Predictive Value in Healthy and Overtrained Male Athletes: The EROS-CORRELATIONS Study. Front Endocrinol (Lausanne). 2019;10:858. Published 2019 Dec 10. doi:10.3389/fendo.2019.00858.   

Study Abstract

Objectives: The Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study identified multiple hormonal and metabolic conditioning processes in athletes, and underlying mechanisms and biomarkers of overtraining syndrome (OTS). The present study's objective was to reveal independent predictors and linear correlations among the parameters evaluated in the EROS study to predict clinical, metabolic, and biochemical behaviors in healthy and OTS-affected male athletes. Methods: We used multivariate linear regression and linear correlation to analyze possible combinations of the 38 parameters evaluated in the EROS study that revealed significant differences between healthy and OTS-affected athletes. Results: The testosterone-to-estradiol (T:E) ratio predicted the measured-to-predicted basal metabolic rate (BMR) ratio; the T:E ratio and total testosterone level were inversely predicted by fat mass and estradiol was not predicted by any of the non-modifiable parameters. Early and late growth hormone, cortisol, and prolactin responses to an insulin tolerance test (ITT) were strongly correlated. Hormonal responses to the ITT were positively correlated with fat oxidation, predicted-to-measured BMR ratio, muscle mass, and vigor, and inversely correlated with fat mass and fatigue. Salivary cortisol 30 min after awakening and the T:E ratio were inversely correlated with fatigue. Tension was inversely correlated with libido and directly correlated with body fat. The predicted-to-measured BMR ratio was correlated with muscle mass and body water, while fat oxidation was directly correlated with muscle mass and inversely correlated with fat mass. Muscle mass was directly correlated with body water, and extracellular water was directly correlated with body fat and inversely correlated with body water and muscle mass. Conclusions: Hypothalamic-pituitary responses to stimulation were diffuse and indistinguishable between the different axes. A late hormonal response to stimulation, increased cortisol after awakening, and the T:E ratio were correlated with vigor and fatigue. The T:E ratio was also correlated with body metabolism and composition, testosterone was predicted by fat mass, and estradiol predicted anger. Hydration status was inversely correlated with edema, and inter-correlations were found among fat oxidation, hydration, and body fat.

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A New Discovery: The Ability of Athletes to get Hormonally Conditioned


June 26, 2021

Hormones in athletes

HORMONAL CONDITIONING, THE NOVEL CONDITIONING PROCESS DETECTED IN ATHLETES. 

Conditioning of the cardiovascular and musculoskeletal systems are conditioning processes extensively described in athletes, and have large contributions to the progressive improvement in sports performance.

However, the improvements in explosion, maintenance of the pace for prolonged periods of time, and increased time-to-fatigue could not be fully explained by the currently described conditioning processes.

In the Endocrine and Metabolic Responses to Overtraining Syndrome (EROS) study, because we compared athletes affected by overtraining syndrome (OTS) with both healthy athletes and healthy sedentary, unexpected differences between healthy athletes and non-physically active subjects were detected. We expected that responses to a non-exercise stimulation would be similar under physiological conditions, i.e., that healthy athletes would disclose similar hormonal responses to a non-exercise stimulation test than sedentary, since the stimulation was independent of any physical effort. However, healthy athletes demonstrated a faster, enhanced, and prolonged response of all hormones compared to non-athletes, irrespective of physical activity, and independent of external factors or other systems. This ended up becoming the proof-of-concept of the conditioning of the endocrine glands, particularly the hypothalamus-pituitary axis, that athletes undergo, and that had not been described to date, at least with these characteristics that avoided confounding biases. The conditioning process of the endocrine system may justify some not fully elucidated improvements in performance and health benefits from exercising.

Not only the cardiovascular and musculoskeletal, but also the endocrine system is conditioned in athletes.  

Links:
https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-019-0443-7
https://pubmed.ncbi.nlm.nih.gov/31675953/ 

Cadegiani FA, Kater CE. Enhancement of hypothalamic-pituitary activity in male athletes: evidence of a novel hormonal mechanism of physical conditioning. BMC Endoc Dis. 2019 Nov 1;19(1):117. Published 2019 Nov 1. doi:10.1186/s12902-019-0443-7 

Study Abstract

Background: Exercise is known to induce multiple beneficial conditioning processes. Conversely, although exercise may generate several hormonal effects, an intrinsic hormonal conditioning process has not been reported. In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we observed inherent and independent conditioning processes of the hypothalamic-pituitary axes in athletes. Our objective is to describe the theory of the novel hormonal conditioning mechanism using the findings from the EROS study.

Methods: In this cross-sectional study, we selected 25 healthy athletes (ATL) and 12 non-physically active healthy controls (NPAC), 18-50 years old, males, with BMI 20-30 kg/m2, with similar baseline characteristics, who underwent gold-standard exercise-independent tests: cosyntropin stimulation test (CST) and insulin tolerance test (ITT), to evaluate cortisol response to CST, and ACTH, cortisol, GH, and prolactin responses to an ITT.

Results: Responses to ITT were significantly earlier and higher in ATL than NPAC for cortisol [Mean ± SD: 21.7 ± 3.1 vs 16.9 ± 4.1 μg/dL; p < 0.001], GH [Median (95% CI): 12.73 (1.1-38.1) vs 4.80 (0.33-27.36) μg/L; p = 0.015], and prolactin [24.3 (10.5-67.45) vs 10.50 (6.21-43.44) ng/mL; p = 0.002]. Cortisol response to CST was similar between ATL and NPAC. During ITT, cortisol, GH, and ACTH mean increase in ATL were 52.2, 265.2, and 18.6% higher than NPAC, respectively. Prolactin response was absent in NPAC, while present in ATL.

Conclusions: We found sufficient evidence to propose the existence of a diffuse enhancement of the hypothalamic-pituitary activity in athletes, not restricted to any axis, showing an intrinsic and independent process of "hormonal conditioning" in athletes, similar to those observed in the cardiovascular and neuromuscular systems. This novel conditioning process may be the missing link for understanding the improved responses observed in athletes to harmful situations, traumas, infections, inflammations, and psychiatric conditions.

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Should Athletes Follow Normal Blood Levels?


June 26, 2021

Normal ranges of hormones in athletes

REFERENCE RANGE LEVELS OF HORMONES SHOULD BE ADAPTED FOR ATHLETES TO AVOID MISINTERPRETATION 

In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we decided to compare athletes affected by overtraining syndrome (OTS) with both healthy athletes and healthy sedentary, in order to avoid an incomplete interpretation of the findings in OTS. We expected that hormonal levels would be similar or very close between healthy athletes and healthy sedentary, since none of these two groups present any pathological change, and almost nothing had been described in the medical literature until that point.

However, multiple serendipitous findings regarding hormonal conditioning processes were detected by the differences between healthy athletes and sedentary, while the sick athletes had levels similar to sedentary.

This brings a challenge regarding the interpretation of the hormonal exams. First, levels expected for athletes are not necessarily the ones within the reference range. Second, ‘normal’ levels could actually mean a pathological state if found in an athlete, since ‘normal levels’ were the ones found in OTS, not in healthy athletes.

From our study and a systematic review from the literature, we proposed changes in the reference ranges for basal and stimulated hormonal levels, muscular, and metabolic parameters, to be applied to athletes.

Links:
https://academic.oup.com/jes/article/4/Supplement_1/MON-LB311/5833948
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209598/

Reference:
Cadegiani F, Abrao TPC, da Silva PLH, Kater CE. MON-LB305 The “Normal” Hormonal Levels in Athletes: Should Reference Ranges Be Adapted for the Physically Active Population?. J Endocr Soc. 2020;4(Suppl 1):MON-LB305. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2321

Study Abstract

Background:Despite the growing number of physically active subjects, including elite and amateur athletes, little is known regarding metabolic and hormonal chronic adaptations to exercises. While the elucidation of the hormonal and metabolic physiological adaptations to physical activity is of emerging importance, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study have serendipitously unveiled the existence of multiple metabolic and endocrine physiological changes in male athletes, including chronic increase of testosterone with concurrent physiological increase of estradiol, enhanced GH and cortisol responses to stimulations,andincreased catecholamines, basal metabolic rate, fat oxidation, and hydration status. These findings were uncovered due to a novel methodological design in which athletes affected by overtraining syndrome (OTS) were compared to a two control groups, of healthy athletes (ATL) and healthy non-physically active controls (NPAC). Since none of the parameters were directly dependent on exercise or performance, differences between these two groups were unexpected. From the fact that several parameters were shown to be different between ATL and NPAC, we realized that the use of the reference ranges for general population to analyze results in athletes may potentially under- and over-diagnose a wide range of conditions. Our objective is therefore to determine whether athletes should be biochemically evaluated through specific adapted ranges, and propose preliminary adaptations in these ranges. Methods: A systematic review on the literature on endocrine and metabolic adaptations to exercise was performed, as well as a thorough analysis of the seven arms of the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study. Results:Multiple reference ranges were shown to be inaccurate for athletes. Among the parameters that should be adapted for athletes, and their respective adaptedranges include: 1. Cortisol response to an insulin stimulation test (ITT) (> 20.5 μg/dL); 2. GH response to an ITT (> 12 μg/L); 3. Prolactin response to an ITT (> 22 ng/mL); 4. Salivary cortisol at 8AM (> 450 ng/dL); 5. Total testosterone (> 450 ng/dL); 6. Estradiol (25-45 pg/mL) - and testosterone-to-estradiol ratio maintained > 13.7; 7. Total nocturnal urinary catecholamines (> 220 μg/12h); 8. Resting lactate (< 1.0 nMol/L); 9. Measured-to-predicted basal metabolic rate (BMR) (> 105%); 10. Fat oxidation (in relation to total BMR) (> 50%); and 11. Hydration status (body water > 62% of total body weight). Conclusion: Analysis of biochemical parameters in athleted should be interpreted with cautious, particularly hormonal and metabolic parameters, once many parameters likely undergo adaptive changes when under physical activity. Preliminary adaptations for the ranges have been proposed.

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Hormone Research Designed for the Athlete


June 26, 2021

Guidelines for the research of hormones in athletes

THE FIRST CLINICAL GUIDELINES FOR THE RESEARCH FIELD OF ENDOCRINOLOGY OF PHYSICAL ACTIVITY AND SPORT 

Because of the lack of standardization of the assessment of hormones in studies on athletes, the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study employed standardized methods for the large number of basal and stimulated hormones evaluated by the study.

Since the number of physically-active subjects and amateur and professional athletes is increasing continuously, the adapted physiology of the athlete needs better understanding and elucidation of the many questions remained regarding the changes that occur in the endocrine system. Indeed, while adaptations of the cardiovascular and musculoskeletal systems have been extensively described, very few is known regarding the adaptative processes in the hormonal releasing and responses patterns.

The present paper is a summary of which parameters should be measured, how these parameters should be assessed, and a structured characterization of the sports performed, including classification into sports type, intensity, conditioning level, among others, since adaptations may be sports-, intensity-, and conditioning level-specific.

By the standardization of the hormonal and metabolic assessment methods, and structuring of the characterization of the sports and athletes, further head-to-head comparisons will become feasible, and sports will be able to be compared in terms of quantification of the benefits they bring. 

Links:
https://academic.oup.com/jes/article/4/Supplement_1/MON-LB311/5833948?searchresult=1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209438/

Reference:
Cadegiani FA, da Silva PLH. Clinical Guidelines for the Research on the Endocrinology of Physical Activity and Sport. J Endocr Soc. 2020;4(Suppl 1):MON-LB311. Published 2020 May 8. doi:10.1210/jendso/bvaa046.2333. 

Study Abstract

Background: The importance of physical activity has achieved levels that has been recognized by as a major world public health game changer, which positively engaged a growing number of subjects to become physically active. While effects of exercise on cardiovascular and musculoskeletal systems are well described, little is known regarding hormonal adapted physiology in athletes, as well as how to detect and manage endocrine abnormalities in physically active subjects. Methodological issues and inconsistent findings precluded from a structured understanding of the endocrinology physiology of physical activity and sport. The objective of the present guideline is to uniformize the design and assessment methods of further studies in the field, based on standardized hormonal and metabolic parameters, and dynamic testings. Methods: Guidelines were actively searched within endocrinology, sports medicine, and cardiology societies. Systematic search on PubMed and Cochrane databases for the expressions “(name of the parameter or test)” + “exercise” or “athlete(s)” or “sport(s)” or “validation” or “standardization. Guidelines, consensus, statements, original studies, and reviews that standardized, validated, or proposed parameters and tests that could be potentially employed for the research on physical activity and sport were included.Results: Parameters of the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA), growth hormone-insulin-like growth factor-1 (GH-IGF1), and hypothalamic-pituitary-thyroid (HPT) axes, prolactin, renin-angiotensin-aldosterone system (RAAS), catecholamines and adrenal medulla, bone, water, glucose, and lipid metabolism, and adipose tissue and muscle endocrine profile were analyzed and classified according to the level of standardization, feasibility, and potential roles in physical activity and sport, and recommended accordingly. Recommendations on the characterization of the studied population, including eating, sleeping, social, psychological, and training patterns were depicted. Conclusion: The research on the endocrinology of physical activity and sport requires standardization and uniformization regarding the description of baseline and training characteristics, and which parameters and tests should be employed. These improvements will allow the development of a more structured and comprehensive knowledge on the field, based on comparative joint analyses of further researches, that should employ well-established parameters and adequately controlled for confounding variables.

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