Health and Performance during Lifespan: latest research

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Your lifespan depends on genetic and key lifestyle choices

Lifespan is dependent on a range of genetic factors combined with lifestyle choices. For example a recent study reported that an increase in one body mass index unit reduced lifespan by 7 months, whilst 1 year of education increased lifespan by 11 months. Physical activity was shown to be a particularly important lifestyle factor through its action on preventing age-related telomere shortening and thus reducing of cellular ageing by 9 years. Nevertheless, even though males and females have essentially identical genomes, genetic expression differs. This results in different disease susceptibilities and evolutionary selection pressures. More studies involving female participants are required!

Circadian clock

Much evidence is emerging about the importance of paying respect to our internal biological clocks when considering the timing of lifestyle factors such as eating, activity and sleep. For example intermittent fasting, especially during the night, and time restricted eating during the day enables metabolic flexibility. In other words, eating within a daylight time window will support favourable metabolism and body composition. No midnight snacks!

For athletes, even more care needs be given to timing of nutrition to support athletic performance. In the short term there is evidence that rapid refuelling after training with a combination of carbohydrate and protein favours a positive balance of bone turnover that supports bone health and prevents injury in the longer term. Periodised nutrition over a training season, integrated with exercise and recovery, is important in order to benefit from training adaptations and optimise athletic performance.

Protein intake in athletes and non athletes

Recovering from injury can be a frustrating time and some athletes may be tempted to reduce food intake to compensate for reduced training. However, recommendations are to maintain and even increase protein consumption to prevent a loss of lean mass and disruption of metabolic signalling. In the case of combined lifestyle interventions, such as nutrition and exercise aimed at reducing body weight, these should be directed at improving body composition. Adequate protein intake alongside exercise will maintain lean mass in order to minimise the risk of sarcopenia and associated bone loss which can occur during hypocaloric regimes. Good protein intake is important for bone health to support bone mineral density and reduce the risk of osteoporosis and fracture.

Adolescent Athlete

In the young athlete, integrated periodisation of training, nutrition and recovery is of particular importance, not only to support health and performance, but as an injury prevention strategy.  Sufficient sleep and nutrition to match training demands are key.

Differences between circadian phenotype and performance in athletes

For everyone, whether athlete or reluctant exerciser, balancing and timing key lifestyle choices of exercise, nutrition and sleep are key for optimising health and performance. However there are individual differences when it comes to the best time for athletes to perform, according to circadian phenotype/chronotype. In other words personal biological clocks which run on biological time. An individual’s performance can vary by as much as 26% depending on the time of day relative to one’s entrained waking time.

Later in Life

Ageing can be can be confused with loss of fitness and ability to perform activities of daily living. Although a degree of loss of fitness does occur with increasing age, this can be prevented to a certain degree and certainly delayed with physical activity. Exercise attenuates sarcopenia, which supports bone mineral density with the added benefit of improved proprioception, helping to reduce risk of falls and potential fracture; not to mention the psychological benefits of exercise.

 

For more discussion on Health Hormones and Human Performance come to British Association of Sport and Exercise Medicine Spring Conference 

BAsem2018_SpringConf_BJSM

References

Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity Nature Communications 2017

Physical activity and telomere length in U.S. men and women: An NHANES investigation Preventive Medicine 2017

The landscape of sex-differential transcriptome and its consequent selection in human adults BMC Biology 2017

Temporal considerations in Endocrine/Metabolic interactions Part 1 British Journal of Sport and Exercise Medicine, October 2017

Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting Obesity 2017

Temporal considerations in Endocrine/Metabolic interactions Part 2 British Journal of Sport and Exercise Medicine, October 2017

Time-restricted eating may yield moderate weight loss in obesity Endocrine Today 2017

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

Periodized Nutrition for Athletes Sports Medicine 2017

Internal Biological Clocks and Sport Performance British Journal of Sport and Exercise Medicine, October 2017

Nutritional support for injuries requiring reduced activity Sports in Science Exchange 2017

Balance fat and muscle to keep bones healthy, study suggests NTU October 2017

Dietary Protein Intake above the Current RDA and Bone Health: A Systematic Review and Meta-Analysis Journal of the American College of Nutrition 2017

Too little sleep and an unhealthy diet could increase the risk of sustaining a new injury in adolescent elite athletes Scandinavian Journal of Medicine & Science in Sports

Sleep for health and sports performance British Journal of Sport and Exercise Medicine, 2017

The impact of circadian phenotype and time since awakening on diurnal performance in athletes Current Biology

Successful Ageing British Association of Sport and Exercise Medicine 2017

Focus on physical activity can help avoid unnecessary social care BMJ October 2017

Biochemical Pathways of Sarcopenia and Their Modulation by Physical Exercise: A Narrative Review Frontiers in Medicine 2017

 

Lifestyle Choices

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Lifestyle Choices: Exercise, Nutrition, Sleep

Lifestyle factors of exercise, nutrition and sleep are vital for optimising health. In the illustration shown, ideally we should be in the green zone representing a balance between these lifestyle factors. Slipping into the peripheral red zone represents an imbalance: either too much or too little of any of these three elements. In particular exercise is of paramount importance being the most effective way of producing beneficial, multi-system effects mediated via the Endocrine system to optimise health and playing an important role in chronic disease prevention. However, it is not just a matter of what, but when: timing is crucial in integrating lifestyle factors with internal biological clocks. Beyond these guiding principles, personal preference and choice is emerging as being just as important as the lifestyle factor itself.

In a fascinating study, 58 participants were given either a prescribed exercise session, or a choice of exercise. Afterwards the participants were presented with a choice of foods, which they believed was simply as way of thank you for taking part in the exercise study. Post exercise, in those given no choice exercise, higher energy intake of food was consumed with larger proportion of “unhealthy” food compared to choice exercise group. The choice exercise group reported greater value and enjoyment of the exercise session. Thus autonomous choice of exercise not only provides positive reinforcement of exercising, but subsequent food choice is improved.

This concept of facilitating self determination, particularly when it comes to exercise was explored at the the recent annual British Association of Sport and Exercise conference. “Practicalities of intervention design, adherence and motivation” was presented by Dr Carly McKay from Bath University, who described how empowering people to make choices is far more likely to mean they will adhere to those lifestyle options that will optimise health.

What about the optimal timing of exercise which might improve motivation and performance? Well this depends on the context and what you are trying to achieve. In the case of training for competition and competition itself, optimal performance tends to be early evening, providing the most favourable hormonal milieu. Although in theory the morning diurnal release of cortisol might help with exercise, the downside is that this may interfere with blood glucose regulation. Furthermore, focusing on just one hormone in the Endocrine system, rather than the integrated function of the hypothalamic-pituitary axis could be misleading. Although due respect should be paid to internal biological clocks, to prevent circadian misalignment between internal pacemakers and external factors; equally becoming too obsessive about sticking to a rigid schedule would psychologically take away that essential element of choice. Practicality is a very important consideration and a degree of flexibility when planning the timing of exercise. For example, my choice of cardiovascualar exercise is swimming, which I fit in according to work commitments and when public lane swimming is available. Fortunately whilst at the BASEM conference in Bath, these practical conditions were met during the lunch break to take advantage of the 50m pool at Bath University. Pragmatic, not dogmatic when it comes to timing of exercise.

Timing of nutrition post exhaustive exercise is an important factor in supporting bone health. Immediate, rather than delayed refuelling with carbohydrate and protein is more advantageous in the balance of bone turnover markers; favouring formation over resorption. In the longer term, prolonged low energy availability as in the situation of relative energy deficiency in sport (RED-S) has a potentially irreversible adverse effect on bone health. In terms of the timing of meals, not eating too close to going to sleep, ideally 2 hours before melatonin release, is best for metabolic health.

Backing up the lifestyle choices of exercise and nutrition is sleep. Timing, duration and quality of sleep is essential for many aspects of health such as hormonal release of growth hormone, functional immunity and cognitive function. Certainly it is well recognised that shift workers, with circadian misalignment: disturbed sleep patterns relative to intrinsic biological clocks, are more at risk of developing cardio-metabolic disease.

In summary, a prescriptive approach to lifestyle factors could be counter productive. Discussing options and encouraging individuals to make their own informed and personal choices is far more likely to enable that person to take responsibility for their health and adhere to changes in lifestyle that are beneficial for their health. Having worked in hospital based NHS diabetic clinics for many years, I appreciate that supporting reluctant exercisers is not always an easy task. Equally it can be difficult to distinguish between the effects of ageing and loss of fitness. However, this does not mean that this supportive and inclusive approach should be abandoned. Rather, encouraging people to participate in decision making that they feel leads to options that are realistic and beneficial, is the approach most likely to work, especially in the long term.

“If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health.”
— Hippocrates

 

For more discussion on Health Hormones and Human Performance come to British Association of Sport and Exercise Medicine Spring Conference 

BAsem2018_SpringConf_BJSM

References

Presentations

One road to Rome: Exercise Dr N. Keay, British Journal of Sports Medicine 2017

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

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

Internal Biological Clocks and Sport Performance Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Providing Choice in Exercise Influences Food Intake at the Subsequent Meal Medicine & Science in Sports & Exercise October 2017

BASEM/FSEM Annual Conference 2017, Assembly Rooms, Bath

Addiction to Exercise – what distinguishes a healthy level of commitment from exercise addiction? Dr N. Keay, British Journal of Sports Medicine 2017

The Effect of Postexercise Carbohydrate and Protein Ingestion on Bone Metabolism Translational Journal of the American College of Sports Medicine October 2107

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

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

Focus on physical activity can help avoid unnecessary social care British Medical Journal October 2017

Internal Biological Clocks and Sport Performance

A Nobel Prize was awarded this week to researchers who uncovered the molecular mechanisms controlling circadian rhythm: our internal biological clock.

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Circadian Hormone Release

These mechanisms rely on negative feedback loops found in many biological systems where periodicity of gene expression is key, such as the Endocrine system. Internal biological clocks allow for anticipation of the requirements from body systems at different times of the day and the ability to adapt to changes in external lifestyle factors. What is the clinical significance of biochronometers?

The importance of integration of lifestyle factors, such as timing of eating, activity and sleep with our internal biological clocks is revealed in situations of circadian misalignment that lead to suboptimal health and disease states in the longer term.

Consideration of our biochronometers is especially important for athletes in order to synchronise periodised training, nutrition and recovery and thus optimise health and sports performance.

Athletic Performance Performance in a cycle time trial was found to be better in the evening, rather than the morning, proposed to be due to a more favourable endogenous hormonal and metabolic internal milieu. Certainly there were some disgruntled swimmers at an international event, when the usual pattern of morning heats and evenings finals was switched, to accommodate television viewing spectators.

Female athletes: menstrual cycle/training season Women have an extra layer of endogenous biological periodicity in the form of the menstrual cycle controlled by temporal changes of hormone release in the hypothamalmus-pituitary-ovarian Endocrine axis. Changes in external factors of training load, nutrition and recovery are detected by the neuroendocrine gatekeeper, the hypothalamus, which produces an appropriate change in frequency and amplitude of GnRH (gonadotrophin releasing hormone), which in turn impacts the pulsatility of LH (lutenising hormone) release from the pituitary and hence the phases of the menstrual cycle, in particular ovulation. Even short term reduction of energy availability in eumenorrhoeic female athletes can inhibit LH pulsatility frequency and release of other hormones such as IGF1. Disrupted release of sex steroids and IGF1 has a negative effect on bone turnover: increased resorption and decreased formation. Active females have been found more susceptible to reduction in energy availability impacting bone metabolism than their male counterparts.

Another consequence of the phasic nature of the menstrual cycle relating to external factors such as exercise, is that injury risk could be linked to changes in the expression of receptors for for sex steroids oestrogen and progesterone in skeletal muscle. Certainly during pregnancy and the post partum period, relaxin hormone increases the laxity of soft tissues, such as ligaments, and hence maintenance stretching, rather than seeking to increase flexibility, is recommended to prevent injury, .

In order to produce desired temporal adaptive changes in response to exercise training, signalling pathways mediated by reactive oxidative species and inflammatory markers are stimulated in the short term, with supportive Endocrine interactions in the longer term. However, an over-response can impair adaptive changes and impact other biological systems such as the immune system. This maladaptive response could occur as a result of non-integrated periodisation of training, nutrition and recovery in athletes and, in the case of female athletes, oral contraceptive pill use has been implicated, as this effectively imposes a medical menopause, preventing the phasic release of endogenous hormones.

Considering a longer time scale, such as a training season, female athletes were found to have a more significant fall ferritin during than male athletes. Low normal iron does not necessarily correlate to iron deficiency anaemia, but low levels in athletes can impact bone health. Supplementation with vitamin C to improve absorption may help, although iron overload can have deleterious effects. As training intensity increases as the season progresses, six monthly haematological reviews for female athletes were recommended in this study.

Changes in set point feedback Feedback control of the Endocrine system, for example the hypothalamic-pituitary-thyroid axis is dynamic: both anticipatory and adaptive, depending on internal and external inputs. However, presentation of a prolonged stimulus can result in maladaptation in the longer term. For example, disruption of signalling pathways leading to hyperinsulinaemia results in insulin resistance, which represents the underlying pathophysiological mechanism of obesity and the metabolic syndrome. In other words a situation of tachyphylaxis, where prolonged, repeated stimulus over time results in insensitivity to the original stimulus. This also applies to the nature of exercise training over a training season and diets that exclude a major food type: temporal variety is key.

Lifespan (prematurity, ageing) Changes during the lifespan represent an important biochronometer. Premature and small-for-dates babies are at risk of long term metabolic and Endocrine dysfunction, potentially due to intrauterine reprogramming of the hypothalamic-pituitary axis. At the other end of the biological time scale, with advancing age, DNA methylation and changes in epigenetic expression occur. It has been suggested that this age related methylation drift could be delayed with calorie restriction. Melatonin, a key player in intrinsic biological time keeping has been proposed to attenuate bone resorption by reducing relative oxidative stress. This would potentially explain why shift workers with disrupted sleep patterns are reported to be at risk not only of metabolic dysfunction, but also impaired bone health. Disrupted sleep patterns are a concern for athletes, especially those whose training and competition schedule involve frequent international travel across time zones.

In summary, respecting your internal biological clocks and integrating your lifestyle and your training, nutrition and recovery with these intrinsic pacemakers in mind will optimise health and performance.

References

The Nobel Prize in Physiology or Medicine 2017

Circadian clock control of endocrine factors Nat. Rev. Endocrinol

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

Athletic Fatigue: Part 2 Dr N. Keay 2017

Effect of Time of Day on Performance, Hormonal and Metabolic Response during a 1000-M Cycling Time Trial Plos One 2017

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

Effects of reduced energy availability on bone metabolism in women and men Bone 2017

Expression of sex steroid hormone receptors in human skeletal muscle during the menstrual cycle Acta Physiol (Oxf). 2017

Endocrine system: balance and interplay in response to exercise training

Kynurenic acid is reduced in females and oral contraceptive users: Implications for depression Science Direct 2017

Oxidative Stress in Female Athletes Using Combined Oral Contraceptives Sports Medicine

Iron monitoring of male and female rugby sevens players over an international season J Sports Med Phys Fitness. 2017

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming Frontiers in Endocrinology 2017

Stress- and allostasis-induced brain plasticity Annu Rev Med

Optimising Health and Athletic Performance Dr N. Keay 2017

Long-term metabolic risk among children born premature or small for gestational age Nature Reviews Endocrinology 2017

Caloric restriction delays age-related methylation drift Nature Communications 2017

Melatonin at pharmacological concentrations suppresses osteoclastogenesis via the attenuation of intracellular ROS Osteoporosis International 2017

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

 

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

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Performance Implications of RED-S (IOC statement 2014)

Introduction Relative Energy Deficiency in Sport (RED-S) has developed out of the concept of the Female Athlete Triad (menstrual dysfunction, disordered eating and decreased bone mineral density) as it has become apparent that low energy availability, ie not eating enough calories to support training levels, has more widespread adverse impacts on health consequently performance in athletes than previously recognised. RED-S can impact both male and female athletes of all ages – if you are a male athlete, please do not stop reading! Young developing athletes can be at particular risk of RED-S as this represents a time of growth and development, which entails many nutritional demands in addition to those to support training. This represents a time to set up the template for health into adulthood.

Why does RED-S occur? RED-S is particularly prevalent in sports where low body weight confers a performance advantage or for aesthetic reasons. For example: long distance running, triathlon, gymnastics, dance and cycle road racing. However, RED-S could also occur not as an intentional strategy to control body weight, but rather during cycles of increased training load where periodised nutrition has not been synchronised with the increased demand on the body.

What is RED-S? Fundamentally there is a mismatch between food intake (in terms of energy and micronutrients) and the demand for nutrition required to cover expenditure, both for training and for basic “housekeeping” tasks in the body. If there is insufficient energy availability, then the body switches into an energy saving mode. This “go slow” mode has implications for hormone production and metabolic processes, which impacts all systems throughout the body. The reason why RED-S was originally described as the Female Athlete Triad is that in women the “energy saving mode” involves menstrual periods being switched off: a pretty obvious external sign as all women of child bearing age should have periods (apart from when pregnant). Low oestrogen levels have an adverse effect on bone health, resulting in decrease in bone mineral density. This effectively renders young women at increased risk of both soft tissue and bone injury, as seen in post-menopausal women. As described in the IOC statement published 2014 in British Journal of Sports Medicine on RED-S, the Female Athlete Triad is now recognised as just the tip of the iceberg. Disruption of hormone levels does not only adversely impact menstrual periods and bone health. There are knock on effects impacting the immune system, cardiovascular system, muscles, nervous system, gut health and the list goes on. Importantly, this situation is also seen in male athletes: for example, whether or not a sport is weight bearing, which traditionally improves bone health, in RED-S the predominant effect of disrupted hormones is to decrease bone density, leading to increased fracture risk.

What is the significance of RED-S? Do these effects of RED-S matter? Yes: there is a detrimental effect on not only health, but on all elements of sports performance. These include an inability to improve as expected in response to training and increased risk of injury. In the long-term there are potential implications for health with inability to reach peak bone mass for young athletes and at the other end of the scale, irreversible bone loss being seen in retired athletes.

Here is a summary of the potential impact of RED-S:

• Endocrine dysfunction: decreased training response

• Metabolic disruption: decreased endurance performance

• Bone health: increased risk bone stress injuries

• Decreased functional immunity: prone to infection

• Gut malfunction: impaired absorption of nutrients

• Decreased neuromuscular co-ordination: injury risk

• Psychological impact: inability to recognise risk developing RED-S

As you can see, these adverse effects are all relevant to performance in endurance sport.

What to do if you are concerned you may have RED-S?

Health Considerations:

• Women: even if your adult weight is steady, if you are a female athlete of reproductive age whose periods have stopped, then do not ignore this! In the first instance, you need to exclude any other causes (for example polycystic ovary syndrome and other hormone issues) in conjunction with your doctor. Then take a look at how you are eating in line with your training load – see the nutritional considerations section below.

• Men: if you are a male athlete struggling to improve sport performance, then review both your training load and your periodised nutrition and recovery. If the cause is RED-S then do not wait until your sport performance drops or you get injured before taking action. You may also want to consider having your testosterone levels measured to check that these are in the normal range.

Nutritional Considerations: From colleague Jo Scott-Dalgleish BSc (Hons), mBANT, CNHC

• Ensure an adequate energy intake. Use My Fitness Pal or a similar app to track your food intake over the course of week. On any day when you train, if you are consuming fewer than 2500 calories as a male endurance athlete and 2000 calories as a female endurance athlete, your intake is likely to be inadequate as these are the guidelines for the general population. If you are taking in fewer than 2750 calories (male) or 2250 calories (female) on a day when you are training for two hours or more, you are likely to be at increased risk of RED-S. Use this data to learn more about appropriate food choices and serving sizes, and introduce some changes to increase your intake in line with your training load. But I do not suggest using apps like these on a long-term basis as they may encourage an unhealthy obsession with your food intake.

• Focus on nutrient density. Make good quality food choices to help you get enough vitamins and minerals as well as carbohydrates, protein, fat and fibre. Try to eat fresh, minimally processed foods rather than too much packaged food, including 3-5 servings of vegetables and 2-3 pieces of fresh fruit each day.

• Avoid excluding foods, whole food groups or following ‘fad diets’. Unless you have a genuine allergy or a diagnosed medical condition such as coeliac disease or lactose intolerance. Or you have been advised to avoid certain foods by a dietician or other well-qualified nutrition practitioner to help manage a health condition such as Irritable Bowel Syndrome. If you are vegetarian or vegan, see Jo’s blog here for tips on ensuring a well-balanced approach.

• Periodise your carbohydrate intake in line with your training. Increase your intake of starches and sugars (including vegetables and fruit) on your heavier training days. A low daily carbohydrate intake might be in the range of 2-4 g/kg of body weight. This is OK for lower volume training days, but should be increased to 5-8 g/kg when training for 2-3 hours or more in a single day. Again, use an app like My Fitness Pal for a week to help you assess your carbohydrate intake. If you are experiencing RED-S, avoid following approaches like fasted training or low carb-high fat diets (LCHF) due to potential adverse effects on hormones.

• Pay attention to your recovery nutrition. Consuming 15-25g of protein and 45-75g of carbohydrate in the hour after exercise, whether as a snack or as part of a meal will help you to each your energy intake goals, restock your glycogen stores for your next training session and protect lean muscle mass.

Jo Scott-Dalgleish BSc (Hons), mBANT, CNHC, is a registered nutritional therapist specialising in nutrition for endurance sport, based in London. She works with triathletes, distance runners and cyclists to help optimise both their performance and their health through the creation of an individual nutritional plan. For more details, please visit www.endurancesportsnutritionist.co.uk.

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

Presentations

References

Optimal health: including female athletes! Part 1 Bones Dr N. Keay, British Journal of Sport Medicine 2017

Optimal health: including male athletes! Part 2 Relative Energy Deficiency in sports Dr N. Keay, British Journal of Sport Medicine 2017

Optimal Health: Especially Young Athletes! Part 3 – Consequences of Relative Energy Deficiency in Sports Dr N. Keay, British Association of Sport and Exercise Medicine 2017

Mechanisms for optimal health…for all athletes! Dr N. Keay, British Journal of Sport Medicine 2017

The IOC consensus statement: beyond the Female Athlete Triad—Relative Energy Deficiency in Sport (RED-S) British Journal of Sports Medicine 2014

Nutritional considerations for vegetarian endurance athletes Jo Scott-Dalgleish, Endurance Sports Nutrition 2017

 

What has your gut microbiome ever done for you?

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Our body acts as a host to vast array of micro-organisms. Often, we are only aware of these micro-organisms causing unwanted infection: for example when a cut on the skin becomes infected, or we suffer with a bout of infective gastro-intestinal upset. Actually, this perception of the micro-organisms, living both on and inside, only causing unwanted infections is very biased. The microbiome (all the micro-organisms, their genetic material and metabolites produced) plays a vital role in keeping us healthy.

Recent research demonstrates that elite level cyclists host distinct clusters of microbiome communities when compared to controls which contribute to more effective metabolic pathways.

The gut microbiota consist of the range of micro-organisms living in our gut, mainly the colon. Recent research reveals that the diversity and functions of the gut microbiota have far reaching impact on health. For example, there is an important interaction between these micro-organisms and mitochondria, which are the organelles in cells responsible for producing energy. This cross talk is of particular consideration for athletes who seek to optimise energy production for training and competition. The gut microbiota also interact with the immune system and central nervous system function, including behaviour. There is evidence that the gut microbiota even influences brain development.

Microbiome Mitochondria Feedback

On the other side of the coin, any disruption in the beneficial types of gut microbiota have been linked to chronic disease states including obesity, metabolic syndrome and mental health issues. What causes imbalances in gut microbiota to produce such problems? A possible aetiology is a poorly balanced diet, or the side effect of medication which does not support the growth and function of beneficial bacteria. Rather an overgrowth of potentially harmful bacteria is favoured: dysbiosis. In athletes there is a condition know as “leaky gut” which can result from endurance training. In this scenario, blood is diverted away from the gut during exercise to the exercising muscles. After stopping exercise, blood flow is restored to the gut resulting in a mild reperfusion injury. This results in a slightly “leaky gut” so that unwanted bacteria in the gut are able to pass into the body and provoke an inflammatory response. Equally this situation can also mean desirable nutrients in the gut as less well absorbed. Although a degree of inflammatory response supports desirable adaptations to exercise, clearly an over-response will be counter productive to improving sports performance.

The gut microbiota have been reported to regulate immune function. Athletes in heavy training can experience suppressed functional immunity so any strategies to support the gut microbiota will potentially be beneficial in preventing infection.

What can you do to support a beneficial gut microbiota to support health and sport performance?

  • Try to include at least one fermented food source in your diet every day to boost your probiotic bacteria. Try sourdough bread, yogurt, kefir (similar to yogurt), sauerkraut, kimchi (Korean fermented vegetables), tempeh and miso (fermented soya products) and kombucha (fermented teas). These products can be found in health food shops and are becoming more widely available in some supermarkets and lunch places.
  • Regularly eat pre-biotic foods like garlic, onion, leeks, chickpeas, beans and lentils. These provide fuel for your probiotic bacteria, enabling them to proliferate.
  • Have adequate fibre in your diet from a wide variety of plant foods: eg wholegrains, legumes, vegetables, fruits, nuts, seeds. Dietary fibre is fermented by your probiotic bacteria to produce short chain fatty acids (SCFAs) which play a key role in keeping your gut healthy.
  • Consume foods and drinks rich in polyphenols: eg berries, green tea, coffee, black tea, red wine, dark chocolate, apples. Polyphenols, found in many plant foods, have been shown to help increase probiotic bacteria in the gut.
  • Take a good quality, multi-species probiotic supplement during winter, heavy training blocks and when travelling abroad, especially for races. To find out more about the potential benefits of probiotic supplementation for athletes, see this blog by nutritional therapist Jo Scott-Dalgleish: http://www.endurancesportsnutritionist.co.uk/blog/probiotics-guide-endurance-athlete/

To find out more about the interaction between Health, Hormones and Human Performance come to the British Association of Sport and Exercise Medicine annual conference

References

Community characteristics of the gut microbiomes of competitive cyclists Microbiome August 2017

Ubiquitous Microbiome: impact on health, sport performance and disease

Endocrine system: balance and interplay in response to exercise training

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

Temporal considerations in Endocrine/Metabolic interactions Part 2

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

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

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 Sport and Exercise Medicine

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

 

 

Fatigue, Sport Performance and Hormones…

How do you feel on Monday morning, when the alarm wakes you at 7am with a day of work ahead after the weekend? A bit tired, slightly lethargic, sluggish, maybe a little bit down, perhaps a few regrets about somewhat too much alcohol/food over weekend, frustrated that the exercise training schedule didn’t go according to plan?sleep

There are many causes of fatigue and sport underperformance: Endocrine, immunological, infective, metabolic, haematological, nutritional, digestive, neoplastic….. The adrenal gland in the Endocrine system in particular has come in for some bad press recently.

Adrenal woes

Undoubtedly the adrenal glands have a case to answer. Situated above the kidneys these Endocrine glands produce glucocorticoids, mineralocorticoids, androgens from the adrenal cortex and from the adrenal medulla adrenaline. Glucocorticoids (e.g. cortisol) have a metabolic function to maintain energy homeostasis and an immune function to suppress inflammation. Mineralocorticoids (e.g. aldosterone) maintain electrolyte and water balance. As mineralocorticoids and glucocorticoids are similar biological steroid molecules, there is some degree of overlap in their actions.

Addison’s disease and Cushing’s disease are serious medical conditions, corresponding respectively to under or over production by the adrenal glands of steroid hormones. Someone presenting in Addisonian crisis is a medical emergency requiring resuscitation with intravenous hydrocortisone and fluids. Conversely those with Cushing’s can present with hypertension and elevated blood glucose. Yet, apart from in the extremes of these disease states, cortisol metrics do not correlate with clinical symptoms. This is one reason why it is unwise and potentially dangerous to stimulate cortisol production based on clinical symptoms. Inappropriate exogenous steroid intake can suppress normal endogenous production and reduce the ability to respond normally to “stress” situations, such as infection. This is why the prescription of steroids, for example to reduce inflammation in autoimmune disease, is always given in a course of reducing dose and a steroid alert card has to be carried. Athletes should also be aware that exogenous steroid intake is a doping offence.

However, what is the “normal” concentration for cortisol? Well, for a start, it depends what time of day a sample is taken, as cortisol is produced in a circadian rhythm, with highest values in the morning on waking and lowest levels about 2/3am. Nor is this temporal periodicity of production the only variable, there are considerations such as tissue responsiveness and metabolism (break down) of the hormone. On top of these variables there are other inputs to the feedback control mechanism, which can in turn influence these variables. In other words, focusing on the steroid hormone production of the adrenal gland in isolation, could overlook underlying hypothamalmic-pituitary-adrenal (H-P-A) axis dysfunction and indeed wider issues.

Much maligned thyroid

That is not end of the possible causes of fatigue and sport underperformance: the H-P-A axis is just one of many interrelated, interacting Endocrine systems. There are many neuroendocrine inputs to the hypothalamus, the gate keeper of the control of the Endocrine system. Furthermore there are network interaction effects between the various Endocrine control feedback loops. For example cortisol towards the top end of “normal” range can impede the conversion at the tissue level of thyroxine (T4) to the more active triiodothyronine (T3) by enzymes which require selenium to function. Rather T4 can be converted to reverse T3 which is biologically inactive, but blocks the receptors for T3 and thus impair its action. This in turn can interfere with the feedback loop controlling thyroid function (hypothalamic-pituitary-thyroid axis). The physiological ratio of T4 to T3 is 14:1, which is why supplementation with desiccated thyroid is not advisable with ratio of 4:1. There are other processes which can crucially interfere with this peripheral conversion of T4 to T3, such as inflammation and gut dysbiosis, which can occur as result of strenuous exercise training. So what might appear to be a primary thyroid dysfunction can have an apparently unrelated underlying cause. Indeed amongst highly trained athletes thyroid function can show an unusual pattern, with both thyroid stimulating hormone (TSH) and T4 at low end of the “normal “range, thought to be due to resetting of the hypothalamic-pituitary control signalling system. This highlights that the “normal” range for many hormones comprises subsets of the population and in the case of TSH, the “normal” range is not age adjusted, despite TSH increasing with age. As described by Dr Boelaert at recent conferences, there is certainly no medical justification for reports of some athletes in the USA being given thyroxine with TSH>2 (when the normal range is 0.5-5mU/l). Although thyroxine is not on the banned list for athletes, it could have potentially serious implications for health due to its impact on the Endocrine system as a whole.

Endocrine system interactions

SportsEndocrinologyWordCloud

Symptoms of fatigue are common to many clinical conditions, not just dysfunction in an Endocrine control axis in isolation, nor even the network interactive effects of the Endocrine system in isolation. For example, the impact of nutrition relative to training load produces a spectrum of clinical pictures and Endocrine disturbances seen in Relative Energy Deficiency in Sport (RED-S) in terms of health and sport performance.

Underlying mechanisms of Endocrine dysfunction

There may be predisposing factors in developing any clinical syndrome, the usual suspects being inflammation: whether infective, dysbioses, autoimmune; nutritional status linked with endocrine status;  training load with inadequate periodised recovery to name a few….

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

From population based norms to personalised medicine: Health, Fitness, Sports Performance British Journal of Sport Medicine 2017

Sports Endocrinology – what does it have to do with performance? British Journal of Sport Medicine 2017

Advanced Medicine Conference, Royal College of Physicians, London 13-16 February 2017, Endocrine session: Dr Kristien Boelaert, Dr Helen Simpson, Professor Rebecca Reynolds

Subclinical hypothydroidism in athletes. Lecture by Dr Kristeien Boelaert, British Association of Sport and Exercise Medicine Spring Conference 2014. The Fatigued Athlete

Sport Performance and RED-S, insights from recent Annual Sport and Exercise Medicine and Innovations in Sport and Exercise Nutrition Conferences British Journal of Sport Medicine 2017

Relative Energy Deficiency in Sport CPD module British Association of Sport and Exercise Medicine 2017

Sleep for health and sports performance British Journal of Sport Medicine 2017

Inflammation: why and how much? British Association of Sport and Exercise Medicine 2017

Clusters of athletes British Association of Sport and Exercise Medicine 2017

Enhancing Sport Performance: Part 1 British Association of Sport and Exercise Medicine 2017

Balance of recovery and adaptation for sports performance British Association of Sport and Exercise Medicine 2017

Annual Sport and Exercise Medicine Conference, London 8/3/17 Gut Dysbiosis, Dr Ese Stacey

Adrenal fatigue does not exist: a systematic review BMC Endocrine Disorders. 2016; 16(1): 48.

A Controversy Continues: Combination Treatment for Hypothyroidism Endocrine News, Endocrine Society April 2017

Inflammation: why and how much?

Inflammation: optimal or overreaction

Systemic autoimmune disease is a chronic overreaction of the inflammatory system. Exercise training is structured to provoke the optimal level of inflammation for adaptation to facilitate sport performance. This blog describes some of the recent significant advances in the understanding of the underlying mechanisms of inflammation and its interactions with the endocrine system, immunity and the microbiome, in relation to autoimmune disease. Applying this knowledge to the adaptive inflammatory effects of training in sport represents a potentially hugely beneficial area of future research.

The ubiquitous microbiomea-muciniphila-233x300

There has been much discussion on the key role of the microbiome, eloquently described by Professor Tim Spector, Professor of Genetic Epidemiology, King’s College, London at recent conferences at the Royal Society of Medicine and The Royal College of Physicians. The microbiome is the DNA of all the microbes in our body. The diversity of the microbiota community in the gut wall of the colon appears to have the most profound effects in terms of disease prediction and indeed a better indicator of developing autoimmune conditions (such as inflammatory bowel disease and rheumatoid arthritis) and metabolic conditions (such as obesity and diabetes mellitus) than our own DNA. So how does the diversity of the gut microbiome have such a profound impact?

It appears that in order to promote diversity of the gut micobiota, prebiotics such as inulin found in fibrous foods should be ingested and then “fertilised” with probiotics found in fermented foods. Enhancing the diversity of the gut microbiome supports the production of short-chain fatty acids which have far reaching influences on epigenetic and immune regulation, the brain, gut hormones and the liver. Furthermore, the diurnal rhythmic movement of the gut microbiota have been shown to regulate host circadian epigenetic, transcriptional and metabolite oscillations which impacts host physiology and disease susceptibility.

In inflammatory conditions such as autoimmune disease, a decrease in the diversity of “good” microbiota has been described. Furthermore, if a decrease in beneficial microbiota is the primary event, then this can lead to an increase in the likelihood of developing autoimmune disease. What is the mechanism of this dynamic interaction between the microbiome and immunity?

Immunity and inflammation

In recent research, the protein receptor marker of microbiota in the gut has been shown to modulate intestinal serotonin transporter activity. Serotonin (5-hydroxytryptamine 5-HT) has shown to be an essential intestinal physiological neuromodulator that is also involved in inflammatory bowel disease. In addition, an increase in inflammatory cytokines such as interleukin 6 and tumour necrosis factor alpha, is know to be associated with low levels of cerebral serotonin and dopamine. The causal link between disrupted immune function and increased inflammation, as in autoimmune disease, is an unfavourable microbiome. Development of autoimmune disease is often multifactorial, for example,  a change in the microbiome might trigger gene expression with adverse effects. Indeed gene expression (independent of sex steroids) has been shown to account for increased prevalence of autoimmune disease in women.

Depression of serotonin levels

Low levels of the neurotransmitter serotonin are know to be linked to depression. Hence prescription of selective serotonin uptake inhibitors to those suffering with depression. However recent research has now revealed a dynamic interaction between peripheral and cerebral effects of the microbiome on immunity and mood, mediated via the circadian release of key hormones such as serotonin. Serotonin is synthesised from precursor tryptophan in the gastrointestinal tract and central nervous system. Low mood in autoimmune disease could be due to psychological factors: knowing that this is a chronic condition with reduced life expectancy. Reduced serotonin, may be a further biochemical reason. Potentially lack of sleep due to pain in autoimmune disease would also suppress serotonin levels.

Applications for microbiome/immunity/inflammation interactions

How will these findings from recent research help in optimising inflammatory mediated adaptations to exercise training and support the understanding and treatment of autoimmune disease? It has been suggested that serotonin could be a treatment for rheumatoid arthritis, as 5HT appears to have a peripheral immuno-regulatoty role in the pathophysiology of this autoimmune disease. Optimising the microbiome, with prebiotics and probiotics, may improve disease activity and improve response to treatment with biologics.

Is the nature of an autoimmune disease such as rheumatoid arthritis (RA) changing? Deformed hands with swollen joints were a perennial favourite for medical examinations. However as described recently at a conference at Royal College of Physicians, although joint destruction is still a feature of RA, this seems to be accompanied by less joint swelling and involvement of greater range of joints. Are the triggers changing rather than a change in the nature of disease? How do nutrition and medication impact the microbiome?

For athletes, apart from periodising energy requirements and micronutrients to support training, encouraging a diverse microbiome will potentially support adaptive changes to training.

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

Balance of recovery and adaptation for sports performance. Dr N. Keay, British Association of Sports and Exercise Medicine

Sleep for health and sports performance. Dr N. Keay, British Journal of Sport and Exercise Medicine

Conference Royal Society of Medicine. “Food: the good, the bad and the ugly” 1/2/17

“Food, microbes and health” Professor Tim Spector, Professor of Genetic Epidemiology, King’s College, London

“Nutrition and the gut: food as trigger for disease; food as medicine” Dr Charlie Lees, Chair Scottish Society of Gastroenterology IBD Interest Group. European Crohn’s and Colitis Organisation Committe

“Nutrition and its effect on the immune system” Dr Liam O’Mahony, Head of Molecular Immunology, swiss Institute of Allergy and Asthma Research

Advanced Medicine Conference. Royal College of Physicians 13-16 February 2017

” The gut microbiome clinical and physiological tolerance” Professor Tim Spector, Professor of Genetic Epidemiology, King’s College, London

“Rheumatoid arthritis-ensuring everyone gets the best treatment” Dr Neil Snowden

Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations Cell Volume 167, Issue 6, p1495–1510.e12, 1 December 2016

Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation. Eva Latorre , Elena Layunta, Laura Grasa, Marta Castro, Julián Pardo, Fernando Gomollón, Ana I. Alcalde †, José E. Mesonero. Published: December 29, 2016

A gene network regulated by the transcription factor VGLL3 as a promoter of sex-biased autoimmune diseases. Yun Liang, Lam C Tsoi, Xianying Xing, Maria A Beamer, William R Swindell, Mrinal K Sarkar, Celine C Berthier, Philip E Stuart, Paul W Harms, Rajan P Nair, James T Elder, John J Voorhees, J Michelle Kahlenberg & Johann E Gudjonsson
Nature Immunology 18, 152–160 (2017)

Serotonin Is Involved in Autoimmune Arthritis through Th17 Immunity and Bone Resorption. Yasmine Chabbi-Achengli, Tereza Coman, Corinne Collet, Jacques Callebert, Michelangelo Corcelli, Hilène Lin, Rachel Rignault, Michel Dy, Marie-Christine de Vernejoul, Francine Côté. The American Journal of Pathology. April 2016 Volume 186, Issue 4, Pages 927–937