Cumulative Endocrine Dysfunction in Relative Energy Deficiency in Sport (RED-S)

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Unfortunately I continue to see athletes, both male and female, whose health and athletic performance is hampered due to Relative Energy Deficiency in Sports (RED-S). There have been some high profile athletes who have been very open about how RED-S has affected them, alerting younger athletes to potential pitfalls.

Does this issue warrant highlighting? Yes! The athletes I see and those that speak out are only just the tip of the iceberg. In a study of exercising females, half were found to have subtle menstrual hormone disruption such as luteal phase deficit or anovulation. A third were amenorrhoeic, with no periods at all. All women of reproductive age, whether an athlete or not, should have regular periods, otherwise there are potential serious health and performance sequaelae. However studies in both the USA and Australia have revealed that the majority of young exercising women are not aware of the link between menstrual disruption and deleterious, potentially irreversible effects on bone health.

The impact of non-integrated periodisation of training, nutrition and recovery has evolved since the early description of the female athlete triad. The constellation of amenorrhoea, disordered eating and osteoporosis is now considered to be a clinical spectrum. In turn the female athlete triad is part of a much broader picture of RED-S, which includes adverse multi-system effects beyond bone health and is also seen in male athletes.

Although an athlete may appear healthy, what are the underlying Endocrine disruptions occurring in RED-S that ultimately will impede both optimal health and performance to full potential? In general, female exercisers are more susceptible to internal and external perturbations as the female Endocrine system is more finely balanced than in males. Nevertheless, in a study of male athletes, in the short time period after completing a training session, bone turnover was adversely affected, with an increase in markers of resorption relative to formation, if an athlete did not refuel rapidly with protein and carbohydrate. In the now classic research by Loucks, 5 days of manipulated energy restricted availability, via dietary intake and exercise output, caused disruption in LH pulsatility in previously eumenorrhoeic women. From this research and subsequent studies, not only is the reproductive axis disrupted with reduced energy availability, in addition hypothalamus-pituitary-thyroid (decreased T3) and adrenal axes (increased cortisol) and decreased IGF1 due to relative GH resistance are all disrupted. These interactive hormonal dysfunctions occur even before reduction in sex steroids. A recent study demonstrated that beyond the average energy availability over a 24 hour time window, within day energy deficits in terms of duration and magnitude are associated with a greater degree of disruption of Endocrine and metabolic markers, in particular decreased oestradiol and increased cortisol. So consistency of nutrition, not only during a training season but from day to day is vital.

Although energy availability is the crucial factor in the pathophysiology of RED-S, measuring this is not practical for all athletes in terms of accuracy and cost. Clinical menstrual status in female athletes and basic Endocrine markers are proposed as being more reliable and accessible. The Endocrine system is very sensitive to internal and external perturbations, as described above, and presages performance consequences of RED-S, such as injury. An important starting point is for all female athletes is to ask themselves: are my periods regular? This is also a vital question that coaches and parents need to consider for athletes in their care. If the answer is no, then this needs to be assessed, ideally by those with experience in Sports Endocrinology.

Why are these clinical and biochemical markers of Endocrine dysfunction important for athletes? Essentially there are significant health and performance implications for athletes. As outlined in the stories of female athletes, by the time career limiting stress fractures become obvious, typically in early twenties, the Endocrine system has been in disarray for a significant time. Long term, irreversible poor bone health and adverse body composition have been established.

In my opinion, emphasis should be placed on the positive outcome of integrating periodised training, nutrition and recovery to support a functional Endocrine system and therefore optimal health and ability to reach full athletic potential. For example for female athletes, competing in sports where low body mass confers a performance advantage, such as ballet, gymnastics and road cycling, finely tuned neuromuscular skills are essential to reach maximal potential and minimise injury risk. Yet these are the athletes most at risk of developing RED-S, with consequential adverse effects on menstrual cycles, endogenous oestrogen secretion and neuromuscular function.

Rather than reading headlines about the concerning health issues amongst athletes, more guidance for athletes and those working with them, on the warning signs and how to combat RED-S are needed so that athletes can reach their full potential and the headlines become about athlete achievements.

For more discussion on the Endocrine and Metabolic aspects of Sport and Exercise Medicine, all members of multi-disciplinary team working with athletes, including athletes and coaches are welcome to the BASEM Spring Conference

BAsem2018_SpringConf_BJSM

References

Relative Energy Deficiency in Sports (RED-S) Practical considerations for endurance athletes

British middle-distance runner Bobby Clay is struggling with osteoporosis but wants her experience to act as a lesson for fellow young athletes Athletics Weekly 2017

In a special AW report, former English Schools champion Jen Walsh reveals the devastation that the female athlete triad can wreak Athletics Weekly 2017

Optimal Health: Especially Young Athletes! Part 3 – Consequences of Relative Energy Deficiency in Sports BASEM 2017

Prevalence High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures. Human Repro 2010

Energy deficiency, menstrual disturbances, and low bone mass: what do exercising Australian women know about the female athlete triad? Int J Sport Nutr Exerc Metab. 2012

Female adolescent athletes’ awareness of the connection between menstrual status and bone health J Pediatr Adolesc Gynecol. 2011

Optimal health: including female athletes! Part 1 Bones BJSM 2017

Optimal Health: For All Athletes! Part 4 – Mechanisms BASEM 2017

Optimal health: including male athletes! Part 2 Relative Energy Deficiency in sports BJSM 2017

Sports Endocrinology – what does it have to do with performance? BJSM 2017

The Effect of Postexercise Carbohydrate and Protein Ingestion on Bone Metabolism Translational Journal of the American College of Sports Medicine 2017

Luteinizing hormone pulsatility is disrupted at a threshold of energy availability in regularly menstruating women JCEM 2003

Within-day energy deficiency and reproductive function in female endurance athletes Scandinavian Journal of Science and medicine in Sports 2017

Low Energy Availability is Difficult to Assess But Outcomes Have Large Impact on Bone Injury Rates in Elite Distance Athletes Sports Nutrition and Exercise Metabolism 2017

Body Composition for Health and Sports Performance

Reduced Neuromuscular Performance in Amenorrheic Elite Endurance Athletes Medicine & Science in Sports & Exercise 2017

Conferences in Sport/Dance, Exercise Science and Medicine 2018

Conferences for the New Year:

BAsem2018_SpringConf_BJSM

If you are interested in any aspects of Sport/Dance, Exercise and Lifestyle Medicine here are some suggestions:

British Association of Sport and Exercise Medicine Spring Conference 22 March 2018 “Health, Hormones and Human Performance” Covering the Endocrine and Metabolic aspects of Sport, Dance, Exercise Science and Medicine. From the elite athlete to the reluctant exerciser. Aimed at all those members of the multidisciplinary team working with athletes/dancers, plus athletes/dancers and their coaches/teachers.

CPD points awarded from Faculty of Sports and Exercise Medicine FSEM

BASES British Association of Sport and Exercise Sciences CPD awarded

British Journal of Sports Medicine Quality International Education Approved

CPD points from Royal College of Physicians

CPD from REP-S

 

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Why? The balance and timing of exercise, nutrition and recovery is key to optimising health and all aspects of human performance. Intricate network interactions between the Endocrine system and metabolic signalling pathways drive these positive adaptations. However, non-integration of these lifestyle factors can disrupt signalling feedback pathways and predispose to maladaptation and potentially disease states.

What? Discussion, led by experienced clinicians and researchers will cover:

· Key role of Sports Endocrinology in health and performance

· Effects of exercise modalities on body composition and bone health

· Machine learning in interpreting biochemical & metabolomic patterns

· Endocrine & metabolic markers in assessing health & training status

· Gut metabolism in supporting health and performance

· Exercise as crucial lifestyle factor in pre-existing metabolic dysfunction

Who? This conference is relevant to all members of multidisciplinary teams supporting both reluctant exercisers and elite athletes. Medics, researchers, physiologists, physiotherapists, nutritionists, psychologists, coaches, athletes. All welcome.

Health, Hormones and Human Performance will be a conference of interest to all those involved with aspiring and elite athletes, including dancers (National Institute of Dance Medicine and Science NIDMS) and those supporting reluctant exercisers through Lifestyle Medicine.

Latest news from BASEM. Interview with BASEM Today Issue 41 – Winter 2017

 

Wales Exercise Medicine Symposium by Cardiff Sports & Exercise Medicine Society 27/1/18. This includes Dr Peter Brukner, founder of the Olympic Sports Medicine Park in Melbourne, and an afternoon session discussing the female athlete through the lifespan. CPD points applied for from the Royal College of Physicians, the Faculty of Sports and Exercise Medicine, REPs and the Royal College Of General Practitioners.

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Women in Sport and Exercise Conference 2018  13-14 June Organised by The Women in Sport and Exercise Academic Network and attracting British Association of Sport and Exercise Sciences (BASES) CPD points.

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Body Composition for Health and Sports Performance

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Body Composition from DEXA scan

Focusing on changes in body weight and body mass index (BMI) alone, as outcome measures of lifestyle interventions, ignores the beneficial multi-system and psychological effects of lifestyle medicine, in particular exercise. This includes advantageous changes in body composition for health and performance.

Why is body composition important? Because not all weight is equal in terms of tissue composition and distribution. To support optimal health, favourable levels of lean mass  versus fat mass decreases the risk of sarcopenia, associated bone loss and metabolic syndrome. For athletes, high lean mass coupled with low fat mass is related to improved athletic performance, especially in disciplines where strength to weight ratio a major consideration and/or those disciplines such as gymnastics and ballet where an aesthetic component confers a performance advantage.

The range of methods for measuring body composition have advantages and disadvantages in terms of accuracy, accessibility and expense. Although accurate in experienced hands, skin fold measurements are limited to giving a measure of subcutaneous fat. Impedance scales have the advantage of giving a measure of both total and visceral fat percentage, however accuracy is dependent on hydration status, amongst other variable factors. Dual-Energy X-Ray Absorptiometry (DEXA) scan is the “gold standard” for measuring body composition to include bone, lean and fat: both total and visceral. DEXA scan is relatively inexpensive and very low radiation dose compared to traditional X ray or computerised tomography (CT). This method of assessing body composition during training seasons is used by some professional sports teams. The illustration above shows a trained male with total fat in the athletic range. Although simple to measure, BMI does not accurately reflect body composition. All methods of assessing body composition can potentially have role in monitoring changes, for example over training seasons, and trends for individuals rather than relying on the absolute values of metrics measured.

How to go about optimising body composition? Combined exercise and nutritional strategies trigger and reinforce favourable metabolic and Endocrine signalling pathways. The detail of these lifestyle strategies will depend on the clinical context and the objectives of the individual: ranging from a sedentary person trying to improve health and well being, to an athlete aiming to improve sport performance. In all scenarios protein intake is an important factor in supporting lean mass, alongside tailored exercise/training. Temporal considerations for optimising body composition in athletes include the age of the athlete and targeting key competitions during a training cycle and in long term over athletic career. Ultimately optimising body composition has to translate to improved athletic performance for the endurance athlete. So aiming for “high quality weight loss” with retention or even improved lean mass, is more likely to support performance, rather than focusing on fat mass loss in isolation, which may occur in any case as a secondary consequence of integrated periodised training, nutrition and recovery. Striving for weight loss and reduced fat mass without careful monitoring and attention to effects on performance, can run the risk of athletes developing relative energy deficiency in sports (RED-S). Female athletes with functional hypothalamic amenorrhoea have been shown to decreased levels not only of lean and fat mass, but in addition reduced metabolically active brown fat and the associated hormone isirin which promotes fat “browning” and impacts bone mineralisation. In addition, there are differences between male and female athletes to be considered in terms of body composition and cycling performance.

From middle-age, both lean mass and bone mineral density (BMD) decline: sarcopenia and bone health intertwined. In order to mitigate against these changes, resistance exercise is particularly beneficial to stimulate muscle and load the skeleton and for metabolic and cognitive benefits. BMI is particularly misleading as a metric to assess risk of disease in menopausal women. Rather, the finer detail of body composition, for example visceral fat area, is more informative in terms of metabolic and psychological health.

Body composition is a more reliable indicator of health than body weight or BMI. Nevertheless body composition in isolation is not the sole determinant of health and performance. Rather body composition is just one of many multi-system effects mediated by integrated metabolic and Endocrine signalling pathways. These network effects are driven by lifestyle factors including exercise, nutrition and recovery, to determine health and sports performance.

For more discussion and debate on the role of body composition for health and performance BASEM Spring Conference 2018 6 CPD points from FSEM and BJSM approved for international education

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References

Challenging those hard to shift, big fat obesity risks BMJ 2017; 359: j5303 British Journal of Medicine 2017

Lifestyle Choices for optimising health: exercise, nutrition, sleep British Journal of Sport Medicine 2107

One road to Rome: Exercise British Journal of Sport Medicine 2107

Current Status of Body Composition Assessment in Sport Review and Position Statement on Behalf of the Ad Hoc Research Working Group on Body Composition Health and Performance, Under the Auspices of the I.O.C.Medical Commission

International society of sports nutrition position stand: diets and body composition Journal of the International Society of Sports Nutrition 2017
Case-Study: Body Composition Periodization in an Olympic-Level Female Middle-Distance Runner Over a 9-Year Career International Journal of Sport Nutrition and Exercise Metabolism 2017

Body composition assessment of English Premier League soccer players: a comparative DXA analysis of first team, U21 and U18 squads Journal of Sports Sciences

Protein Recommendations for Weight Loss in Elite Athletes: A Focus on Body Composition and Performance International Journal of Sport Nutrition and Exercise Metabolism 2017

Optimal Health: For All Athletes! Part 4 – Mechanisms British Association for Sport and Exercise Medicine 2017

Effect of Chronic Athletic Activity on Brown Fat in Young Women Plos One 2106

Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates Plos One

Kings and Queens of the Mountains Science4Performance

Low bone mineral density in middle-aged women: a red flag for sarcopenia Menopause 2017

Resistance training – an underutilised drug available in everybody’s medicine cabinet BJSM 2017

Benefits of resistance training in physically frail elderly: a systematic review Ageing Clinical and Experimental Research 2017

Is BMI a valid measure of obesity in postmenopausal women? Menopause 2017

Association of visceral fat area with the presence of depressive symptoms in Chinese postmenopausal women with normal glucose tolerance Menopause 2017

 

 

 

Optimising Health and Athletic Performance

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In order to improve sports performance, athletes periodise their training, nutrition and recovery within the context of a training season. For those not in exercise training, these controllable lifestyle factors correspond to exercise, diet and sleep, which require modification during the lifespan. In old money, this was called preventative medicine. Taking this a step further, rather than preventing disease, this proactive, personalised approach optimises health. Health should be a positive combination of physical, mental and social well being, not simply an absence of illness.

Failure to balance these lifestyle factors in an integrated fashion leads to negative outcomes. An athlete may experience maladaptation, rather than the desired adaptations to exercise training. For non-athletes an adverse combination of lifestyle factors can lead to suboptimal health and a predisposition to developing chronic disease.

What are the fundamental pathophysiological mechanisms involved in the aetiology of the clinical spectrum of suboptimal health, suboptimal sports performance and chronic disease?

Inflammation A degree of systemic inflammation and oxidative stress induced by exercise training is required to drive desired adaptations to support improved sport performance. However, prolonged, elevated levels of inflammation have adverse effects on health and underpin many chronic disease states. For example, inflammation is a contributing pathophysiological factor in the development of atherosclerosis and atherothrombosis in cardiovascular disease. What drives this over-response of the inflammatory process? Any combination of adverse lifestyle factors. Adipose tissue has an Endocrine function, releasing a subgroup of cytokines: adipokines which have peripheral and central signalling roles in energy homeostasis and inflammation. In a study of Belgian children, pro-inflammatory energy related biomarkers (high leptin and low adiponectin) were associated with decreased heart rate variability and hence in the long term increased risk of cardiovascular disease. For those with a pre-existing chronic inflammatory condition, response to treatment can be optimised with personalised lifestyle interventions.

Metabolism Non-integrated lifestyle factors can disrupt signalling pathways involved in glucose regulation, which can result in hyperinsulinaeamia and insulin resistance. This is the underlying pathological process in the aetiology of metabolic syndrome and metabolic inflexibility. Non-pharmacological interventions such as exercise and nutrition, synchronised with endogenous circadian rhythms, can improve these signalling pathways associated with insulin sensitivity at the mitochondrial level.

Intriguingly, evidence is emerging of the interaction between osteocalcin and insulin, in other words an Endocrine feedback mechanism linking bone and metabolic health. This is reflected clinically with increased fracture risk found amongst type 2 diabetics (T2DM) with longer duration and higher HbA1C.

Hormone imbalance The hypothalamus is the neuroendocrine gatekeeper of the Endocrine system. Internal feedback and external stimuli are integrated by the hypothalamus to produce an appropriate Endocrine response from the pituitary gland. The pathogenesis of metabolic syndrome involves disruption to the neuroendocrine control of energy homeostasis with resistance to hormones secreted from adipose tissue (leptin) and the stomach (ghrelin). Further evidence for the important network effects between the Endocrine and metabolic systems comes from polycystic ovarian syndrome (PCOS). Although women with this condition typically present to the Endocrine clinic, the underlying aetiology is metabolic dysfunction with insulin resistance disrupting the hypothamic-pituitary-ovarian axis. The same pathophysiology of disrupted metabolic signalling adversely impacting the hypothalamic-pituitary-gonadal axis also applies to males.

In athletes, the exact same signalling pathways and neuroendocrine systems are involved in the development of relative energy deficiency in sports (RED-S) where the underlying aetiology is imbalance in the periodisation of training load, nutrition and recovery.

Gastrointestinal tract In addition to malabsorption issues such as coeliac disease and non-gluten wheat sensitivity, there is emerging evidence that the composition and diversity of the gut microbiota plays a significant role in health. The microbiome of professional athletes differs from sedentary people, especially at a functional metabolic level. Conversely, an adverse gut microbiome is implicated in the pathogenesis of metabolic dysfunction such as obesity and T2DM, via modulation of enteroendocrine hormones regulating appetite centrally and insulin secretion peripherally.

Circadian disregulation As previously discussed, it is not just a question of what but WHEN you eat, sleep and exercise. If there is conflict in the timing of these lifestyle activities with internal biological clocks, then this can disrupt metabolic and endocrine signally. For example, in children curtailed sleep can impact glucose control and insulin sensitivity, predisposing to risk of developing T2DM. Eating too close to the onset of melatonin release in the evening can cause adverse body composition, irrespective of what you eat and activity levels. In those with pre-existing metabolic dysfunction, such as PCOS, timing of meals has an effect on insulin levels and hence reproductive Endocrine function. The immune system displays circadian rhythmicity which integrated with external cues (for example when we eat/exercise/sleep) optimises our immune response. For athletes competing in high intensity races, this may be more favourable in terms of Endocrine and metabolic status in the evening.

Psychology Psychological stress impacts the key pathophysiological mechanisms outlined above: metabolic signalling, inflammation and neuroendocrine regulation, which contribute to Endocrine and metabolic dysfunction. Fortunately stress is a modifiable lifestyle risk factor. In the case of functional hypothalamic amenorrhoea (where nutrition/exercise/sleep are balanced), psychological intervention can reverse this situation.

Conclusion Putting this all together, if the modifiable lifestyle factors of exercise, nutrition, sleep are optimised in terms of composition and timing, this improves metabolic and Endocrine signalling pathways, including neuroendocrine regulation. Preventative Medicine going beyond preventing disease; it optimises health.

BASEM annual conference 22/3/18: Health, Hormones and Human Performance

Presentations

References

Athletic Fatigue: Part 2 Dr N. Keay

From population based norms to personalised medicine: Health, Fitness, Sports Performance Dr N. Keay, British Journal of Sports Medicine 2017

Endocrine system: balance and interplay in response to exercise training Dr N. Keay

Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventions British Journal of Sports Medicine 2017

Longitudinal Associations of Leptin and Adiponectin with Heart Rate Variability in Children Frontiers in Physiology 2017

A Proposal for a Study on Treatment Selection and Lifestyle Recommendations in Chronic Inflammatory Diseases: A Danish Multidisciplinary Collaboration on Prognostic Factors and Personalised Medicine Nutrients 2017

Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals Sports Medicine 2017

Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus Nature Reviews Endocrinology

Insulin and osteocalcin: further evidence for a mutual cross-talk Endocrine 2017

HbA1c levels, diabetes duration linked to fracture risk Endocrine Today 2017

The cellular and molecular bases of leptin and ghrelin resistance in obesity Nature Reviews Endocrinology 2017

Metabolic and Endocrine System Networks Dr N. Keay

Adiponectin and resistin: potential metabolic signals affecting hypothalamo-pituitary gonadal axis in females and males of different species Reproduction 2017

Optimal Health: For All Athletes! Part 4 – Mechanisms Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Ubiquitous Microbiome: impact on health, sport performance and disease Dr N. Keay

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level Gut. BMJ

Interplay between gut microbiota, its metabolites and human metabolism: Dissecting cause from consequence Trends in Food Science & Technology 2016

Temporal considerations in Endocrine/Metabolic interactions Part 1 Dr N. Keay, British Journal of Sports Medicine 2017

Temporal considerations in Endocrine/Metabolic interactions Part 2 Dr N. Keay, British Journal of Sports Medicine 2017

Sleep Duration and Risk of Type 2 Diabetes Paediatrics 2017

Later circadian timing of food intake is associated with increased body fat Am J Clin Nutr. 2017

Effects of caloric intake timing on insulin resistance and hyperandrogenism in lean women with polycystic ovary syndrome Clin Sci (London)

Immunity around the clock Science

Effect of Time of Day on Performance, Hormonal and Metabolic Response during a 1000-M Cycling Time Trial PLOS

Type 2 diabetes mellitus and psychological stress — a modifiable risk factor Nature Reviews Endocrinology 2017

Recovery of ovarian activity in women with functional hypothalamic amenorrhea who were treated with cognitive behaviour therapy Fertil Steril

 

Temporal considerations in Endocrine/Metabolic interactions Part 1

LifeSeasonDay

It is not a simple question of what, but when we eat, sleep and exercise.

The Endocrine system displays temporal variation in release of hormones. Integrating external lifestyle factors with this internal, intrinsic temporal dimension is crucial for supporting metabolic and Endocrine health.

Amplitude and frequency of hormonal secretion display a variety of temporal patterns:

  • Diurnal variation, synchronised with external light/dark. Orchestrated by a specific area of the hypothalamus, the neuroendocrine gatekeeper.
  • Circadian rhythm, roughly 24-25 hours which can vary with season according to duration of release of melatonin from the pineal gland.
  • Infradian rhythms longer than a day, for example lunar month seen in patterns of hypothalamic-pituitary-ovarian axis hormone release during the menstrual cycle.
  • Further changes in these temporal release and feedback patterns occur over a longer timescale during the lifespan.

Hormones influence gene expression and hence protein synthesis over varying timescales outlined above. The control system for hormone release is based on interactive feedback loops. The hypothalamus is the neuroendocrine gatekeeper, which integrates external inputs and internal feedback.  The net result is to maintain intrinsic biological clocks, whilst orchestrating adaptations to internal perturbations stimulated by external factors such as sleep pattern, nutrition and exercise.

Circadian alignment refers to consistent temporal patterns of sleep, nutrition and physical activity. Circadian misalignment affects sleep-architecture and subsequently disturbs the interaction of metabolic and Endocrine health. This includes gut-peptides, glucose-insulin interaction, substrate oxidation, leptin & ghrelin concentrations and hypothalamic-pituitary-adrenal/gonadal-axes. The main stimuli for growth hormone release are sleep and exercise. Growth hormone is essential for supporting favourable body composition. These integrated patterns of environmental factors may have a more pronounced effect on those with a genetic predisposition or during crucial stages of lifespan. For example curtailed sleep during puberty can impact epigenetic factors such as telomere length and thus may predispose to metabolic disruption in later life. Regarding activity levels, there are strong relationships between time spent looking at screens and markers, such as insulin resistance, for risk of developing type 2 diabetes mellitus in children aged 9 to 10 years.

In addition to adverse metabolic effects set in motion by circadian misalignment, bone turnover has also shown to be impacted. Circadian disruption in young men resulted in uncoupling of bone turnover, with decreased formation and unchanged bone resorption as shown by monitoring bone markers. In other words a net negative effect on bone health, which was most pronounced in younger adult males compared with their older counterparts. These examples underline the importance of taking into account changes in endogenous temporal patterns during the lifespan and hence differing responses to external lifestyle changes.

For male and female athletes, integrated periodised training, nutrition and recovery has to be carefully planned over training seasons to support optimal adaptations in Endocrine and metabolic networks to improve performance. Training plans that do not balance these all these elements can result in underperformance, potentially relative energy deficiency in sport and consequences for health in both short and long term.

Part 2 will consider the longer term consequences and interactions of these temporal patterns of lifestyle factors, including seasonal training patterns in male and female athletes, on the intrinsic biochronometry controlling the Endocrine and metabolic networks during lifespan.

For further discussion on Health, Hormones and Human Performance, come to the BASEM annual conference

References

Sports Endocrinology – what does it have to do with performance? Dr N.Keay, British Journal of Sports Medicine 2017

One road to Rome: Metabolic Syndrome, Athletes, Exercise Dr N. Keay

Metabolic and Endocrine System Networks Dr N. Keay

Endocrine system: balance and interplay in response to exercise training Dr N.Keay

Sleep for health and sports performance Dr N.Keay, British Journal of Sports Medicine 2017

Factors Impacting Bone Development Dr N. Keay

Sleep, circadian rhythm and body weight: parallel developments Proc Nutr Soc

Sleep Duration and Telomere Length in Children Journal of Paediatrics 2017

Screen time is associated with adiposity and insulin resistance in children Archives of Disease in Childhood

Circadian disruption may lead to bone loss in healthy men Endocrine today 2017

Successful Ageing Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Clusters of Athletes – A follow on from RED-S blog series to put forward impact of RED-S on athlete underperformance Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Optimal Health: For All Athletes! Part 4 – Mechanisms Dr N. Keay, British Association of Sport and Exercise Medicine 2017

 

 

 

 

One road to Rome: Metabolic Syndrome, Athletes, Exercise

One road to Rome

Metabolic syndrome comprises a cluster of symptoms including: hypertension, dyslipidaemia, fatty liver disease and type 2 diabetes mellitus (T2DM).

The underlying pathological process is insulin resistance which distorts metabolism. Temporal and mechanistic connections have been described between hyperinsulinaemia, obesity and insulin resistance. Insulin levels rise, potentially stimulated by excess intake of refined carbohydrates and in addition the metabolic actions of insulin are attenuated on target tissues such as the liver, skeletal muscle and adipose tissue. At a cellular level, inflammatory changes play a part in this metabolic dis-regulation. Mitochondrial action in skeletal muscle is impaired, compromising the ability to oxidise fat as a substrate, thus resulting in muscle glycolysis and a consequent rise in blood lactate.

Although much attention has been focused on restricting calories and treating elevated lipids with medication (statins), evidence is now emerging that this does not have the anticipated effect of reducing mortality from cardiovascular disease. In addition, it has been proposed that the gut microbiota plays a pivotal role in metabolism, inflammation and immunity.

Metabolic syndrome usually conjures an image of an overweight person with or on the verge of developing T2DM. However there is an interesting group of slim people who are also are at risk of developing metabolic syndrome due to insulin resistance. The majority of women with polycystic ovary syndrome (PCOS) present with menstrual disturbance of some description. However not all display the textbook characteristics of Stein-Leventhal syndrome (overweight, hirsute and with skin problems). There is in fact of spectrum of clinical phenotypes ranging from the overweight to the slim. In all phenotypes of PCOS, the crucial uniting underlying metabolic disturbance is insulin resistance. The degree of insulin resistance has been shown to be related to adverse body composition with increased ratio of whole body fat to lean mass.

Although this confuses the picture somewhat, it also simplifies the approach. In all cases the single most important lifestyle modification is exercise.

Exercise improves metabolic flexibility: the ability to adapt substrate oxidation to substrate availability. Endurance exercise training amongst athletes results in improved fat oxidation and right shift of the lactate tolerance curve. Conversely metabolic inflexibility associated with inactivity is implicated in the development of insulin resistance and metabolic syndrome.

What about nutritional strategies that might improve metabolic flexibility? Ketogenic diets can either be endogenous (carbohydrate restricted intake) or exogenous (ingestion of ketone esters and carbohydrate). Low carbohydrate/high fat diets (terms often used interchangeably with all types of ketogenic diets) have been shown to improve fat oxidation and potentially mitigate cognitive decline in older people.

However, in the case of athletes, the benefits do not necessarily translate to better performance. Despite reports of such diets enhancing fat oxidation and favourable changes in body composition, a recent study demonstrates that this, in isolation, does not translate into improved sport performance. A possible explanation is the oxygen demand of increased oxidation of fat needs to be supported by a higher oxygen supply. The intermediate group of endurance athletes in this study, on the periodised carbohydrate intake, fared better in performance terms. Another recent study confirmed that a ketogenic diet failed to improve the performance of endurance athletes, in spite of improving fat metabolism and body composition. Despite small numbers, this warrants particular mention as the majority of participants were women, who are in general very underrepresented in scientific studies.

In all likelihood, the reason that these type of diets (ketogenic, high fat/low carb: not always well defined!) did not improve sport performance is that only one aspect of metabolism was impacted and quantified. Although fat oxidation, modified via dietary interventions, is certainly an important component of metabolism, the impact on the interactive network effects of the Endocrine system should be evaluated in the broader context of circadian rhythm. For athletes this goes further, to include integrated periodisation of nutrition, training and recovery to optimise performance, throughout the year.

In addition to dietary interventions, medical researchers continue to explore the use of exercise mimetics and metabolic modulators, to address metabolic syndrome. Unfortunately, some have sought their use as a short cut to improved sport performance. Many of these substances appear on the WADA banned list for athletes. However the bottom line is that it is impossible to mimic, either through a dietary or pharmacological intervention, the multi-system, integrated interplay between exercise, metabolism and the Endocrine system.

Only one road to Rome!

Whatever your current level of activity, whether reluctant exerciser or athlete, the path is the same to improve health and performance. This route is exercise, supported with periodised nutrition and recovery. Exercise will automatically set in motion the interactive responses and adaptations of your metabolic and Endocrine systems.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

Insulin action and resistance in obesity and type 2 diabetes Nature Medicine 2017

Inflammation: Why and How Much? Dr N. Keay, British Association of Sport and Exercise Medicine

The cholesterol and calorie hypotheses are both dead — it is time to focus on the real culprit: insulin resistance Clinical Pharmacist 2017

Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus Nature Reviews Endocrinology 2016

The essential role of exercise in the management of type 2 diabetes Cleveland Clinic Journal of Medicine 2017

β cell function and insulin resistance in lean cases with polycystic ovary syndrome Gynecol Endocrinol. 2017

The many faces of polycystic ovary syndrome in Endocrinology. Conference Royal Society of Medicine 2017

Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome Hum Reprod 2014

Sedentary behaviour is a key determinant of metabolic inflexibility Journal of physiology 2017

International society of sports nutrition position stand: diets and body composition J Int Soc Sports Nutr. 2017

A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease Exp Gerontol. 2017

Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers J Physiol. 2017

Ketogenic diet benefits body composition and well-being but not performance in a pilot case study of New Zealand endurance athletes J Int Soc Sports Nutr. 2017

Sports Endocrinology – what does it have to do with performance? Dr N. Keay, British Journal of Sports Medicine 2017

Hormones and Sports Performance

Endocrine system: balance and interplay in response to exercise training

 

Hormones and Sports Performance

WADA

The interactive network effects of the Endocrine system are key in producing effective adaptations to exercise. This in turn results in improved sport performance. Athletes are aware of the crucial role of the Endocrine system in sports performance. Therefore it is not surprising that, on the World Anti-Doping agency (WADA) banned list, the majority of prohibited substances both in and out of competition are hormones, mimetics and hormone and metabolic modulators. In 2013 hormones accounted for 75% of all adverse analytical findings. Use of such substances to enhance performance is not only illegal and against the spirit of sport, but also potentially harmful to the health of the athlete.

Considering some of these prohibited hormones, the usual suspects start with anabolic agents: anabolic androgenic steroids whether these be synthetic derivatives taken exogenously or molecular identical endogenous steroids, including metabolites and isomers, administered exogenously.  In a study recently published in the BJSM, female athletes with free testosterone levels in the highest tertile displayed better performance than those in lowest tertile of up to 4.5% in certain power/anaerobic events such as 400m, 800m, hammer and pole jump. This may be due to associated body composition with increased lean mass and “risk taking” behaviour. In 2015, the Court of Arbitration for Sport ruled that the IAAF should suspend the existing upper limit on female athlete testosterone, of 10nmol/l, because at the time there was insufficient evidence that such levels would improve performance in female athletes. In view of the results of this study, the situation may have to be reviewed. This is clearly an ethical dilemma regarding intersex athletes, whose hyerandrogenism is due to endogenous biological factors.

Next up there are peptide hormones/growth factors/mimetics. As previously discussed, growth hormone (GH) proved a challenging peptide hormone for which to develop a dope test. Firstly what are the “normal” ranges for elites athletes, seeing as exercise and sleep are the two major stimuli for GH release? Furthermore, elite athletes represent a subset of the population, for whom the normal range may differ. Secondly exogenous genetically engineered GH is to all intents and purposes identical to endogenous secreted GH, with a relatively short half life. Hence early on in development of a dope test we realised that downstream markers, particularly of bone turnover would have to be used. This brings the discussion to erythropoietin (EPO). In a similar way to GH and allied releasing factors, increases in key surrogate variables producing performance enhancement are measured. In the case of exogenous EPO these are changes in haemoglobin and haematocrit as recorded in an athletes’ biological passport. A recent study on amateur cyclists given EPO in a double blind randomised placebo controlled trial, reported no improvement in a submaximal field test. Although the effects in elite cyclists would arguably be more relevant, this is not possible for obvious ethical reasons. Nevertheless the effects on elite cyclists during maximal efforts, for example in an attack on a mountainous stage in the Tour de France, would not necessarily correlate to amateurs in submaximal conditions, where there may be other limiting factors to performance. In addition athletes may use supraphysiological dosing regimens (“stacking” or “pyramiding”), not necessarily comparable to those used in clinical studies. In my opinion, apart from potential ergogenic benefits, whatever the degree, the intention to “take a short cut” to improve performance is the issue, not to mention the adverse health sequelae, for example, the study noted a thrombotic tendency with EPO, even in modest doses.

Hormone and metabolic modulators have received attention following the fall from grace of Maria Sharapova. Meldonium which is licensed for use in Baltic countries has beneficial anti-ischaemic effects in cardiovascular, neurological and metabolic disease states. Apparently this drug was use amongst Soviet troops during the war in mountainous Afghanistan. Amongst athletes the intended purpose is to improve endurance exercise performance and recovery post exercise. This is an example where an unfortunate spin off from developing drugs to treat disease states, is that such drugs are also see by some athletes as a short cut to enhance sport performance.

Although thyroxine is not on the banned list, there are certainly arguments that exogenous thyroxine should not be given to athletes, unless there is definitive biochemical evidence that the athlete suffers with hypothyroidism: as defined by criteria for diagnosing this condition with consistently elevated thyroid stimulating hormone (TSH) above the normal range, with paired low T4. Thyroid autoantibodies may also provide extra clinical information. The effect of intense training on the hypothalamic-pituitary-thyroid axis is to slightly suppress both TSH and T4, whilst these remain in the normal range. In this instance medicating with exogenous thyroxine would be to support recovery from training, rather than to legitimately treat a proven medical condition. In a similar way a TUE is only justified for testosterone in pathological disorders of the hypothalamo-pituitary-testicular axis and not for suppressed testosterone as a result of training stress.

Unfortunately supplements are a source of preventable anti-doping rule violations (ADRV) representing up to half of the total ADRVs. Either such supplements have not listed all the contents, or contamination has occurred during manufacture. If an athlete wishes to take supplements, certainly it is advisable only to take reliably tested products. Nevertheless even if an athlete unintentionally ingests prohibited substances, then ultimately they are still liable. If claims of the benefits of such supplements sound too good to be true, they probably are. Ultimately supplements will not win races and there is no substitute for periodised training, nutrition and recovery.

Effectively there is an arms race between would-be doper and medical expertise in Sports Endocrinology. However, freezing samples for potential re-analysis with emerging understanding and technology in the future is an added deterrent for athletes whose intention is to take a short cut to improving sport performance.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

Endocrine system: balance and interplay in response to exercise training

Sports Endocrinology – what does it have to do with performance? Dr N. Keay, British Journal of Sports Medicine 2017

Enhancing Sport Performance: Part 1 Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sport: a double blind, placebo controlled study. Journal of Clinical Endocrinology and Metabolism. 85 (4) 1505-1512. 2000.

From population based norms to personalised medicine: Health, Fitness, Sports Performance  Dr N. Keay, British Journal of Sports Medicine 2017

Enabling Sport Performance: part 2

Enhancing Sports Performance: part 3

World Anti-Doping Agency

Serum androgen levels and their relation to performance in track and field: mass spectrometry results from 2127 observations in male and female elite athletes British Journal of Sports Medicine

Doping Status of DHEA Treatment for Female Athletes with Adrenal Insufficiency Clinical Journal of Sports Medicine 2017

Testosterone treatment and risk of venous thromboembolism: population based case-control study British Medical Journal 2016

Effects of erythropoietin on cycling performance of well trained cyclists: a double-blind, randomised, placebo-controlled trial The Lancet, Haematology 2017

Meldonium use by athletes at the Baku 2015 European Games. Adding data to Ms Maria Sharapova’s failed drug test case British Journal of Sports Medicine 2016

Fatigue, sport performance and hormones..more on the endocrine system  Dr N. Keay, British Journal of Sports Medicine 2017

Australian Sport Anti-Doping Authority

 

Factors Impacting Bone Development

Optimal body mass index (BMI) coupled with favourable body composition of lean mass and visceral fat is associated with accrual of bone mineral density (BMD) and peak bone mass (PBM) which is vital for setting up BMD within normal ranges for adult life.

New research demonstrates that high BMI exerts a negative effect on the accumulation of BMD and bone architecture in young people. This is something of a surprise. Elevated BMI in young people is known to have a deleterious effect on cardio-metabolic health. However, to date the thinking has been that raised BMI would at least mean that weight bearing exercise would be “weighted” and hence favour accumulation of BMD. Rather it is reported that elevated BMI with increased visceral fat results in impaired bone architecture and BMD. Coupled with decreased lean mass, this means less muscle to exert force on the skeleton to promote BMD accumulation. This distorted body composition impairs attainment of PBM.screen-shot-2016-12-01-at-08-29-56

In my research, deficiency of BMD was found to be irreversible later in adult life, despite normalising body weight, shown for those at the other end of the spectrum of BMI. Those with relative energy deficiency in sports (REDs), formally known as the female athlete triad, demonstrated suboptimal BMD correlated with previous duration of low weight, amenorrhea and delayed onset of menarche, many years on despite return to optimal body weight and normal menstrual status.

Adverse body composition with increased deposition of visceral fat is seen in patients with growth hormone (GH) deficiency, for example post pituitary surgery. Interestingly in these young people with high levels of visceral fat, low levels of GH were recorded. The proposed mechanism of suppression of GH secretion in overweight young people has been discussed. Interestingly high levels of leptin are found in overweight youngsters, compared to low levels found my studies of low weight young dancers with menstrual disturbance. In other words, there appears to be feedback between body weight, body composition and the endocrine system. The other disadvantage of high levels of adipose tissue is that fat soluble vitamin D is “fat locked” and unable to support bone mineral accumulation.

Optimal BMI and body composition are factors associated with accrual of BMD and PBM which is vital for setting up BMD within normal ranges for adult life. In those young people with high BMI and disrupted body composition, dietary measures are needed to reduce body weight. Combined with exercise, including resistance and cardiovascular weight bearing forms, to improve body composition and thus bone architecture and BMD accrual.

For further discussion on Endocrine and Metabolic aspects of SEM come to the BASEM annual conference 22/3/18: Health, Hormones and Human Performance

References

Optimal health: including female athletes! Part 1 Bones Dr N. Keay, British Journal Sport Medicine

Optimal Health: Especially Young Athletes! Part 3 – Consequences of Relative Energy Deficiency in Sports Dr N. Keay, British Association Sport and Exercise Medicine

Science Daily

EurekaAlert

Paediatric Reports