metabolic syndrome – Dr Nicky Keay

Health, Hormones and Human Performance Part 2

8 April 2018

Endocrine and Metabolic aspects of Sports and Exercise Medicine are crucial determinants of health and human performance, from reluctant exerciser through to elite athlete and professional dancer. This is what the recent BASEM spring conference set out to demonstrate. The previous blog described functional disruption of Endocrine networks caused by non-integrated periodisation of the three key lifestyle factors of exercise/training, nutrition and recovery/sleep, can lead to adverse effects on health and athletic performance.

Integrated periodisation of exercise, nutrition, recovery for optimisation of health and performance (Keay BJSM 2017)

Grace, aesthetic line and ethereal quality belie the athletic prowess required in ballet. What are the Endocrine, metabolic and bone health consequences for this unique group of athletes? Dr Roger Wolman (Medical Advisor to National Institute for Dance Medicine and Science) returned to the important topic of insufficient energy availability in sport/dance where being lightweight confers a performance advantage, resulting in dysfunction in multiple endocrine axes. Dr Wolman discussed his recent research studies in dancers revealing an intriguing synergistic action between oestrogen and vitamin D, which is itself a steroid hormone. Evidence was presented to demonstrate how being replete in vitamin D has beneficial effects on bone, immunity and muscle function. Thus it is key in preventing injury and supporting health in athletes, with particular relevance in premenarchal and postmenopausal women, who are in relative oestrogen deficient states. This presentation will certainly change my clinical practice and, I am sure, that of many in the audience, in ensuring that athletes/patients are vitamin D replete. This may have to be achieved in the form of strategic use of sports informed vitamin D supplementation, given that even walking naked for 5 hours a day outside during UK winter, would not stimulate enough vitamin D production. Therefore, to the relief of many in the audience, Dr Wolman did not recommend this strategy.

Dr Kate Ackerman (member of RED-S IOC working group) explained why we should all tap into our inner endocrinologist. Sport and Exercise Medicine (SEM) goes far beyond diagnosing and treating injury. Is there any underlying endocrine cause for suboptimal health, performance or injury? Be this an endocrine diagnosis that should not be missed, or a functional endocrine dysfunction due to relative energy deficiency in sports (RED-S). Dr Ackerman explained the importance of the multidisciplinary team in both identifying and supporting an athlete experiencing the consequences of RED-S. New research from Dr Ackerman’s group was presented indicating the effects of RED-S on both health and athletic performance.

Females now have combative roles alongside their male counterparts. What are the implications of this type of intensive exercise training? Dr Julie Greaves (Research Director of the ministerial women in ground close combat research programme) presented insightful research revealing that differences in the geometry of bone in men and women can predispose towards bone stress injury and account for increased incidence in this type of injury in female recruits.

Lunchtime discussion and debate was focused on the determinants of athletic gender, lead by Dr Joanna Harper and Professor Yannis Pitsiladis (International Federation of Sports Medicine). Rather than relying on genetic sex, testosterone concentration was proposed as the criteria for determining whether an athlete competes in male or female events. That testosterone concentration is linked to performance was demonstrated in a study published last year in the BMJ where female athletes in the upper tertile of testosterone were shown to have a performance advantage in certain strength based track and field disciplines. This could potentially be an objective, functional metric used to determine sporting categories for transgender and intersex athletes. The only current uncertainty is how previously high levels of testosterone seen in male, or intersex athletes would have already had an impact on physiology, if this athlete then wished to compete as female and therefore lower testosterone levels with medication.

Nutrition is a key component in optimising health and performance through the Endocrine system. Dr Sophie Killer (English Institute of Sport) explained practical implications for athletes. In a study stimulating a training camp, there were distinct differences between athletes on different regimes of carbohydrate intake in terms of endocrine markers and psychological effects. Those athletes on restricted carbohydrate intake fared worse.

Insulin insensitivity is the underlying pathological process in developing type 2 diabetes mellitus (T2DM) and metabolic syndrome. What is the crucial lifestyle intervention to combat this? Dr Richard Bracken (Swansea University) presented the science behind why and how exercise improves blood glucose control and therefore ultimately risk of developing the macro and microvascular complications of diabetes. T2DM is an increasing health issue in the population, which has to be addressed beyond reaching for the prescription pad for medication. Dr Bracken outlined some effective strategies to encourage the reluctant exerciser to become more active. Having worked myself in NHS diabetic clinics over many years, this was a key presentation at the conference to demonstrate that SEM goes far beyond a relatively small group of elite athletes. Highlighting the crucial role of physical activity in supporting health and performance through optimisation of endocrine networks: uniting the elite athlete and the reluctant exerciser.

One road to Rome — One Road to Rome (BJSM Keay 2017)

Motivate2Move initiative aims to shift the emphasis from treating disease, to preventing disease. Dr Brian Johnson presented the excellent resource for healthcare professionals to encourage, motivate and educate patients in order to consider exercise as an effective and enjoyable way to improve health.

Hormones play a key role in health and human performance, applicable to all levels of exerciser from reluctant exerciser to elite athlete.

FactorsWordCloud4

References

Health, Hormones and Human Performance BASEM Spring Conference

Video of presentation on Endocrine and Metabolic aspects of Sport and Exercise Medicine from BASEM Spring Conference

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

Lifestyle Choices for optimising health: exercise, nutrition, sleep Keay BJSM 2017

One road to Rome: Exercise Keay, BJSM 2017

Health, Hormones and Human Performance Part 1

2 April 2018

How hormones determine health and athletic performance

Endocrine and Metabolic aspects of Sports and Exercise Medicine are crucial determinants of health and human performance, from reluctant exerciser through to elite athlete and professional dancer. This is what I set out to demonstrate as the chair of the recent British Association of Sport and Medicine conference, with insightful presentations from my colleagues whom I had invited to share their research and practical applications of their work. The audience comprised of doctors with interest in sport and exercise medicine, representatives from the dance world, research scientists, nutritionists, physiotherapists, coaches and trainers. In short, all were members of multi-disciplinary teams supporting aspiring athletes. The importance of the conference was reflected in CDP awards from FSEM, BASES, Royal College of Physicians (RCP), REP-S and endorsement for international education from BJSM and National Institute of Dance Medicine and Science (NIDMS).

Exercise is a crucial lifestyle factor in determining health and disease. Yet we see an increasing polarisation in the amount of exercise taken across the general population. At one end of the spectrum, the increasing training loads of elite athletes and professional dancers push the levels of human performance to greater heights. On the other side of the spectrum, rising levels of inactivity, in large swathes of the population, increase the risk of poor health and developing disease states. Which fundamental biological processes and systems link these groups with apparently dichotomous levels of exercise? What determines the outcome of the underlying Endocrine and metabolic network interactions? How can an understanding of these factors help prevent sports injuries and lead to more effective rehabilitation? How can we employ Endocrine markers to predict and provide guidance towards beneficial outcomes for health and human performance?

If you weren’t able to come and participate in the discussion, these are some topics presented. My opening presentation (see video below) set the scene, outlining why having an optimally functioning Endocrine system is fundamental to health and performance. Conversely, functional disruption of Endocrine networks occurs with non integrated periodisation of the three key lifestyle factors of exercise/training, nutrition and recovery/sleep, which can lead to adverse effects on health and athletic performance.

In the case of an imbalance in training load and nutrition, this can manifest as the female athlete triad, which has now evolved into relative energy deficiency in sports (RED-S) in recognition of the fact that Endocrine feedback loops are disrupted across many hormonal axes, not just the reproductive axis. And, significantly, acknowledging the fact that males athletes can also be impacted by insufficient energy availability to meet both training and “housekeeping” energy requirements. Why and how RED-S can affect male athletes, in particular male competitive road cyclists, was discussed, highlighting the need for further research to investigate practical and effective strategies to optimise health and therefore ultimately performance in competition.

A degree of overlap and interplay exists between RED-S (imbalance in nutrition and training load), non functional over-reaching and over-training syndrome (imbalances in training load and recovery). Indeed research evidence was presented suggesting that RED-S increases the risk of developing over-training syndrome. In these situations of functional disruption of the Endocrine networks, underlying Endocrine conditions per se should be excluded. Case studies demonstrated this principle in the diagnosis of RED-S. This is particularly important in the investigation of amenorrhoea. All women of reproductive age, whether athletes or not, should have regular menstruation (apart from when pregnant!), as a barometer of healthy hormones. Indeed, since hormones are essential to drive positive adaptations to exercise, healthy hormones are key in attaining full athletic potential in any athlete/dancer, whether male or female. Evidence was presented from research studies for the role of validated Endocrine markers and clinical menstrual status in females as objective and quantifiable measures of energy availability and hence injury risk in both male and female athletes.

Triumvirate of external factors impacting Endocrine system and hence performance

Alongside training metrics, if female athletes recorded menstrual pattern (as Gwen Jorgensen recently showed on her Training Peaks) and all athletes kept a biological passport of selected Endocrine markers; this could potentially identify at an early stage any imbalances in the triumvirate of training load, nutrition and recovery. Pre-empting development of RED-S or over-training syndrome, supports the maintenance of healthy hormones and hence optimal human performance.

Look out for presentations from speakers which will be uploaded on BASEM website shortly.

References

Video of presentation on the Endocrine and Metabolic Aspects of Sports and Exercise Medicine BASEM conference “Health, Hormones and Human Performance”

Study of hormones, body composition, bone mineral density and performance in competitive male road cyclists Investigation of effective and practical nutrition and off bike exercise interventions

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

Male Athletes: the Bare Bones of Cyclists

16 February 2018

Chris Boardman is an Olympic gold medal winner and world record breaking cyclist. However, he explains in his biography that he retired in his early thirties with weak bones and low testosterone. At the time he was treated with medication aimed at improving his bone strength, but this severely impacted his performance on the bike.

What was the cause of this superlative male athlete’s unhealthy condition that ultimately lead to his retirement? Is this still an issue for male cyclists today? Is it limited to elite professional riders?

Periodisation of key training factors support the Endocrine system to optimise performance

In 2014 the IOC published a description of relative energy deficiency in sports (RED-S), where nutrition intake is insufficient to cover training demands and the basic “housekeeping” activities of the body. This induces an energy-saving mode that impacts health and therefore athletic performance. The female athlete triad had been previously described as the combination of disordered eating, menstrual disruption and impaired bone health. RED-S goes beyond the female athlete triad to include a broader range of impacts on systems other than just the bones and female hormone production. Significantly RED-S includes male athletes. Today, Chris Boardman would be diagnosed with RED-S.

Has this new information improved the identification and support of male athletes at risk of RED-S? In a recent pilot study, 5 out of 10 competitive amateur riders (Category 2 and above) were in the lowest age-matched percentile of body fat and 9 out 10 where in the lowest 6% relative to the population of similar age. Significantly, 7 out of 10 riders had below-average for age bone mineral density (BMD) in the lumbar spine, with two males having bone densities that would be low for an 85 year old.

Why is poor bone health a particular risk for competitive male cyclists? Depending on the type of exercise, beneficial adaptations include mechanical strengthening of specific parts of the skeletal system. For example, assuming good nutrition, runners tend to have strong hips, whereas rowers have more robust spines in terms of BMD and bone microarchitecture. Conversely the non-weight-bearing nature of cycling and the generally lower level of upper-body musculature reduce the mechanical loading forces though the spine: low osteogenic (bone building) stimuli. Although similar to swimming, in the sense that body weight is supported in the water, the major difference between these two forms of exercise is that in cycling, particularly for climbing, low body mass confers a performance advantage. This brings in the additional factor for bone health of potential inadequacies in nutrition and therefore consequences on hormone production.

An optimal balance of training, nutrition and recovery drives beneficial adaptations to exercise throughout the body. The body’s Endocrine system releases hormones that stimulate positive changes, such as the process of improving the efficiency of delivering and utilising oxygen and nutrients to exercising tissues, including the skeletal system. Any imbalances in periodisation between the three inputs of training, nutrition and recovery will compromise health and athletic performance.

Cyclists are at particular risk of insufficient fuelling. This may be an intentional attempt to maintain low body weight, which can lead to healthy eating becoming an unhealthy orthorexic pattern, where vital food groups for endurance sport, such as carbohydrates are excluded. There is also a practical element to fuelling adequately during long rides and refuelling afterwards. Consistency of nutrition throughout the day has been highlighted in a recent study of male endurance athletes where although an average 24 hour intake may be sufficient, if there are any significant deficits during this time, then this is reflected in increased adverse impact on catabolic Endocrine makers. In another study of male athletes if refuelling with carbohydrate and protein after training did not occur promptly, this lead to an increase in bone resorption over formation markers.

Recovery is an essential part of a training schedule, because the adaptations to exercise occur during rest. Sleep, in particular, is a major stimulus for growth hormone release, which drives positive adaptive changes in terms of body composition and bone turnover. Conversely, insufficient recovery time due to a packed schedule of training and work, places extra stresses on the Endocrine system. Getting to bed half an hour earlier than usual every day quickly adds up to an extra night’s sleep.

Does it matter if some areas of the skeleton are weaker than others? Yes, because this increases your risk of fracture, not just if you come off your bike, but also with relatively low force impacts. In the case of runners and triathletes, bone stress injuries are more likely to occur as an early warning sign of impaired bone health due to RED-S. Since low impact forces are absent in cycling, it may take a crash to reveal the strength of a rider’s bones. Studying the list of injuries in elite cyclists there are many fractures, with longer recovery time for vertebral fractures. So potentially cyclists can develop more severe bone health issues than other athletes, before becoming aware of the situation.

If you are a male cyclist, what can you do to prevent issues of bone health and risk of developing RED-S and suboptimal performance on the bike? Watch this space! A study is planned to investigate practical and effective strategies to optimise health and performance on the bike. In meantime there will be more discussion on “Health, Hormones and Human Performance” at the BASEM conference 22 March. All welcome, including athletes and coaches, alongside healthcare professional working with athletes.

References

Mechanisms for optimal health…for all athletes! BJSM 2017

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

Lifestyle Choices for optimising health: exercise, nutrition, sleep BJSM 2017

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

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

Within-day Energy Deficiency and Metabolic Perturbation in Male Endurance Athletes International Journal of Sport Nutrition and Exercise Metabolism 2018

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

Sleep for health and sports performance BJSM 2017

Body Composition for Health and Sports Performance

9 December 2017

Screen Shot 2017-12-02 at 15.03.23 — 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

BAsem2018_SpringConf_BJSM FSEM_CPD_Award Screen Shot 2017-12-12 at 14.47.15

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

20 September 2017

FactorsWordCloud4

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

Ubiquitous Microbiome: impact on health, sport performance and disease

14 August 2017

Microbiome Mitochondria Feedback

The gut microbiome plays a key role in regulating the optimal degree of response to exercise required to stimulate desired adaptive changes.

We have at least as many bacterial cells as human cells in our bodies. We are all familiar with the effects of disturbing the balance of beneficial microbes in our gut. Beyond this, the gut microbiome (the range of microbes, their genetic material and metabolites) is essential for health. An interactive feedback exists between gut microbiota and functional immunity, inflammation, metabolism and neurological function

Sports performance: endurance exercise increases metabolic, oxidative and inflammatory stress, signalled by the release of exerkines from exercising tissue. This signalling network induces adaptive responses mediated via the Endocrine system. Maladaptation to exercise can be due either to an undesirable over-response or an insufficient response.

Intricate interactive feedback links exist between mitochondria and the gut microbiota. In addition to being the power generators of all metabolically active cells, mitochondria produce reactive oxygen species (ROS) and reactive nitrogen species during high intensity exercise. These oxidative stress signals not only mediate adaptive responses to exercise during recovery, but influence gut microbiota by regulating intestinal barrier function and mucosal immune response. Mitochondrial genetic variation could influence mitochondrial function and thus gut microbiota composition and function. Equally, the gut microbiota and its metabolites, such as short chain fatty acids, impact mitochondrial biogenesis, energy production and regulate immune and inflammatory responses in the gut to mitochondrial derived oxidative species. So nutritional strategies to support favourable gut microbiota would potentially support the beneficial effects of the interactions described above to optimise sport performance in athletes.

Conversely, disruption to favourable diversity of the gut microbiota, dysbiosis, is associated with increase in both inflammation and oxidative stress. Not a good situation for either health or sport performance. Alteration to the integrity of the intestinal wall increasing permeability can also be a factor in disrupting the composition of the gut microbiota. The resultant increased antigen load due to bacterial translocation across the gut wall is linked to increased inflammation, oxidative stress and metabolic dysfunction. “Leaky gut” can occur in high level endurance exercise where splanchnic blood flow is diverted away from the gut to exercising tissues for long periods of time, resulting in relative hypo-perfusion and an effective re-perfusion injury on stopping exercise. In the longer term the increased levels of inflammation, oxidative stress and antigen load impair adaptation to exercise and are associated with endocrine dysfunction in chronic disease states, for example autoimmune conditions, metabolic syndrome (type 2 diabetes mellitus, obesity) and depression.

Evidence links the composition of the gut microbiota to changes in circulating metabolites and obesity. For example, low abundance of certain species of gut microbiota reduces levels of circulating amino acid glutamine, which acts as a neurotransmitter precursor. Bariatric surgery is associated with changes in the release of gut hormones regulating food intake behaviour and energy homeostasis. In addition, beneficial changes are seen in the gut microbiota which could directly or indirectly support weight loss, via action on gut hormones.

Metformin is frequency used to improve insulin sensitivity in both type 2 diabetes mellitus and polycystic ovary syndrome. However, the mechanism is poorly understood. There is now evidence that the effect of metformin is mediated via changes in gut microbiota diversity. Transfer of stool from those treated with metformin improves insulin sensitivity in mice. In addition metformin regulates genes in some gut microbiota species that encode metalloproteins or metal transporters, which are know to be effective ligands. The pathophysiology of metabolic syndrome and obesity involves an inflammatory component which is triggered by gut dysbiosis and bacterial translocation, with increased generation of oxidative species. Probiotics have a potential role in regulating the redox status of the host via their metal ion chelating ability and metabolite production, which has an impact on the production of ROS and associated signalling pathways. Prebiotics found in dietary polyphenols promote these actions of favourable gut microbiota, which is of benefit in metabolic syndrome.

Recently it has been postulated that the gut microbiome, apart from playing a crucial role in health and pathogenesis of disease states, also impacts brain development, maturation, function and cognitive processes.

Understanding the role of the gut microbiome on metabolism, inflammation and redox status is very relevant to athletes where an optimal response to exercise training supports adaptations to improve performance, whereas an over or under response in these pathways results in maladaptive responses.

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

Presentations

References

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

Inflammation: Why and How Much? Dr N.Keay, British Association of Sport and Exercise Medicine 2017

The Crosstalk between the Gut Microbiota and Mitochondria during Exercise Front Physiol. 2017

Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities Psychother Psychosom 2017

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention Nature Medicine 2017

Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug Nature Medicine 2017

L’altération de la perméabilité intestinale : chaînon manquant entre dysbiose et inflammation au cours de l’obésité ? Med Sci (Paris)

Antioxidant Properties of Probiotic Bacteria Nutrients 2017

The Impact of Gut Microbiota on Gender-Specific Differences in Immunity Front. Immunol 2017

Commentary: Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome Front. Immunol., 27 July 2017

Gut microbial communities modulating brain development and function Gut Microbes

Temporal considerations in Endocrine/Metabolic interactions Part 2

2 August 2017

LifeSeasonDay

As discussed in the first part of this blog series, the Endocrine system displays temporal variation in release of hormones. Amplitude and frequency of hormonal secretion display a variety of time-related patterns. Integrating external lifestyle factors with this internal, intrinsic temporal dimension is crucial for supporting metabolic and Endocrine health and sport performance.

Circadian misalignment and sedentary lifestyle has been implicated in the increased incidence of metabolic syndrome driven by insulin resistance and associated metabolic inflexibility and decrease in fat oxidation. However, a recent study of overweight individuals, found that increases in fat oxidation from lifestyle intervention, corresponded to different clinical outcomes. Both those who maintained weight loss and those who regained weight displayed increased fat oxidation compared to baseline. How could this be? Increased fat oxidation is only part of the equation in overall fat balance. What adaptations in the metabolic and Endocrine networks were occurring during rest periods? In the case of those that maintained weight loss, increased fat oxidation was reflected in biochemical and physiological adaptations to enable this process. Whereas for those that regained weight in the long term, increased fat oxidation was enabled by increased availability of lipids, indicating increased fat synthesis over degradation.

Clearly there is individual variation in long-term Endocrine and metabolic responses to external factors. Focusing on optimising a single aspect of metabolism in the short term, will not necessarily produce the expected, or desired clinical outcome over a sustained period of time. As previously discussed the single most effective lifestyle change that induces synchronised, beneficial sustained Endocrine and metabolic adaptations is exercise.

It will come as no surprise that focusing on maximising use of a single substrate in metabolism, without integration into a seasonal training plan and consideration of impacts on internal control networks, has not produced the desired outcome of improved performance amongst athletes. Theoretically, increasing fat oxidation will benefit endurance athletes by sparing glycogen use for high intensity efforts. Nutritional ketosis can be endogenous (carbohydrate restricted intake) or exogenous (ingestion of ketone esters and carbohydrate). Low carbohydrate/high fat diets have been shown in numerous studies to increase fat oxidation, however, this was at the expense of effective glucose metabolism required during high intensity efforts. Potentially there could be adverse effects of low carbohydrate intake on gut microbiota and immunity.

This effect was observed even in a study on a short timescale using a blinded, placebo-controlled exogenous ketogenic intervention during a bicycle test, where glycogen was available as a substrate. The proposed mechanism is that although ketogenic diets promote fat oxidation, this down-regulates glucose use, as a respiratory substrate. In addition, fat oxidation carries a higher oxygen demand for a lower yield of ATP, compared to glucose as a substrate in oxidative phosphorylation.

Metabolic flexibility the ability to use a range of substrates according to requirement, is key for health and sport performance. For example, during high intensity phases of an endurance race, carbohydrate will need to be taken on board, so rehearsing what types/timing of such nutrition works best for an individual athlete in some training sessions is important. Equally, some low intensity training sessions with low carbohydrate intake could encourage metabolic flexibility. However, in a recent study “training low” or periodised carbohydrate intake failed to confer a performance advantage. I would suggest that the four week study time frame, which was not integrated into the overall training season plan, is not conclusive as to whether favourable long term Endocrine and metabolic adaptations would occur. A review highlighted seasonal variations in male and female athletes in terms of energy requirements for different training loads and body composition required for phases of training blocks and cycles over a full training season.

Essentially an integrated periodisation of training, nutrition and recovery over a full training season will optimise the desired Endocrine and metabolic adaptations for improved sport-specific performance. The emphasis will vary over the lifespan of the individual. The intricately synchronised sequential Endocrine control of the female menstrual cycle is particularly sensitive to external perturbations of nutrition, exercise and recovery. Unfortunately the majority of research studies focus on male subjects.

In all scenarios, the same fundamental temporal mechanisms are in play. The body seeks to maintain homeostasis: status quo of the internal milieu is the rule. Any external lifestyle factors provoke short term internal responses, which are regulated by longer term Endocrine network responses to result in metabolic and physiological adaptations.

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

References

Temporal considerations in Endocrine/Metabolic interactions Part 1 Dr N. Keay

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

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

Influence of maximal fat oxidation on long-term weight loss maintenance in humans Journal of Applied Physiology 2017

One road to Rome: Metabolic Syndrome, Athletes, Exercise Dr N.Keay 2017

Metabolic and Endocrine System NetworksDr N. Keay 2017

Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males Applied Physiology, Nutrition, and Metabolism 2017

Endocrine system: balance and interplay in response to exercise training Dr N. Keay 2017

No Superior Adaptations to Carbohydrate Periodization in Elite Endurance Athletes Medicine & Science in Sports & Exercise 2017

Total Energy Expenditure, Energy Intake, and Body Composition in Endurance Athletes Across the Training Season: A Systematic Review Sports Medicine – Open 2017

Successful Ageing 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

Metabolic and Endocrine System Networks

24 July 2017

EndoMetaNetworks

What are the most effective strategies to optimise health and performance? There are ever more emerging possibilities, permutations and combinations to chose from.

The simple answer is that the most effective option will depend on your starting point and what you are trying to achieve. In all cases exercise and activity levels are the fundamental basis for health and performance. Regarding nutritional strategies to support effective exercise adaptations, no single component of your dietary intake can be considered in isolation. After all, the metabolic pathways and Endocrine axes in your body work as an interactive network, with an important temporal dimension.

Emerging evidence implicates resistance to the anabolic pancreatic hormone, insulin, as the underlying pathological process in the development of metabolic syndrome. What type of diet might drive or conversely counter this process involving metabolism and the Endocrine system? The standard approach, of calorie restriction and aggressive pharmacological treatment of raised lipids, does not produce the anticipated reduction in cardiovascular mortality. Rather the synergistic effect of a diet high in both fat and carbohydrate induces hypothalamic inflammation and dysfunction in the control system of energy metabolism. The hypothalamus is the neuroendocrine gatekeeper providing the crucial link between internal and external stimuli and homeostasis of the internal milieu through integrated Endocrine responses. Intriguingly there is as an inflammatory component to the pathogenesis of cardiovascular disease.

The interaction between metabolic, Endocrine and inflammatory networks is seen in polycystic ovary syndrome (PCOS). The clinical diagnosis of PCOS relies on two of three diagnostic criteria (menstrual disturbance, hyperandrogenism, ovarian morphology). However, the underlying metabolic disruption for all phenotypes of the condition, from overweight to slim, is insulin resistance. The link between adverse body composition, metabolic and Endocrine dysfunction has recently been described. Adipokines, a class of cytokine, including adiponectin and resistin are produced by adipose tissue and exert an effect on metabolism, including insulin sensitivity and inflammation. Changes in plasma concentrations and/or expression of adipokines are seen in metabolic dysfunction and potentially have direct and indirect effects on the hypothalmic-pituitary-gonadal axis in PCOS.

Further evidence of the crucial interaction between metabolic and Endocrine systems and health was found in a longitudinal study of children, quantifying heart rate variability and the energy and inflammatory related biomarkers leptin (atherogenic) and adiponectin (anti-atherogenic) as potential predictive markers in cardiovascular screening/prevention.

Exogenous hormones impact not only the endogenous Endocrine system, but have metabolic effects. The intended purpose of the combined oral contraceptive pill (OCP) is to suppress ovulation. Another effect on the Endocrine system is to increase production of sex hormone-binding globulin (SHBG), which binds free testosterone. This has a therapeutic effect in the treatment of PCOS to lower elevated testosterone, however this may not be such a desirable effect in female athletes, where higher range testosterone levels as associated with performance advantages in certain power events. In the case of female athletes with relative energy deficiency in sports (RED-S), use of the OCP masks underlying hypothalamic amenorrhoea and is not effective in bone health protection. Further areas where Endocrine manipulation impacts metabolism are an increase in oxidative stress with OCP use and alterations in nutritional requirements due to alteration of absorption of vitamins and minerals such as vitamin B complex and magnesium, which are vital for enzymic processes involved in energy production. Yet an elevation of ferritin as an acute phase reactant is seen. These interactions of Endocrine and metabolic networks are particularly important considerations for the female athlete.

There is no single elixir for health and performance. We are individuals with subtle differences in our genetic and epigenetic make up, including the diversity of our microbiome. Furthermore, the Endocrine and metabolic milieu changes during our lifespan. Personalised health and performance strategies must take account of the complex, intricate interactions between the Endocrine and metabolic networks.

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

References

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

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

Dietary sugars, not lipids, drive hypothalamic inflammation Molecular Metabolism June 2017

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

Longitudinal Associations of Leptin and Adiponectin with Heart Rate Variability in Children Front. Physiol 2017

AKR1C3-mediated adipose androgen generation drives lipotoxicity in women with polycystic ovary syndrome J Clin Endocrinol Metab 2017

Hormones and Sports Performance Dr N. Keay

Mechanisms for optimal health…for all athletes! Dr N. Keay, British Journal of Sport and Exercise Medicine

Oxidative Stress in Female Athletes Using Combined Oral Contraceptives Sports Medicine – Open

Oral contraceptives and changes in nutritional requirements European Review for Medical and Pharmacological Sciences

Inflammation: Why and How Much? Dr N. Keay, British Association of Sport and Exercise Medicine 2017

One road to Rome: Metabolic Syndrome, Athletes, Exercise

20 July 2017

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