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

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

 

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

EnergyBalance

Introduction Relative Energy Deficiency in Sport (RED-S) has evolved from the previously described Female Athlete Triad (menstrual dysfunction, disordered eating and decreased bone mineral density). The reason for the development of this clinical model of RED-S is that it has become apparent that low energy availability, ie not eating enough calories to support the combined energy demands of health and training, has more widespread adverse impacts on health and consequently performance in athletes and dancers than previously recognised. Furthermore, the RED-S model includes both male and female athletes– so if you are a male athlete, please do not stop reading! Low energy availability can impact male and female exercises of all levels and of all ages. 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 of exercise training and for basic “housekeeping” tasks in the body to maintain health. 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 and updated 2018 in British Journal of Sports Medicine , 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, it is recognised that this situation is also seen in male athletes: low energy availability resulting in adverse health and performance consequences. Although exercise/dance is known to have many beneficial effects on health, all these beneficial effects are negated by low energy availability. 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.

Male cyclists Road cyclists are doubly at risk of the detrimental effects of RED-S on bone health. Performing a non-weight bearing form of exercise deprives the skeleton of the positive effect of mechanical skeletal loading on bone health. Furthermore being low body weight is a performance advantage for road cyclists when it comes to riding up hills/mountains in order to produce higher Watts/Kg over 60 minutes (60 minute functional threshold power FTP). This puts cyclists at risk of developing low energy availability, endocrine dysfunction and consequent impairment of bone health. In weight bearing sport the warning sign of suboptimal bone health if often stress fracture. This will be absent in cyclists. Hence low energy availability may go unrecognised until a bike fall results in serious fracture and indeed fractures appears as the most common type of injury amongst cyclists. Furthermore, the lumbar spine is recognised as the site most susceptible to endocrine dysfunction in RED-S. Vertebral fracture is recorded as the type of fracture in cyclists requiring the longest time off the bike. In a recent study, it was found that the factor most indicative of 60 minute FTP, was training load and NOT low body fat. Furthermore, training in low energy availability state will not result in the expected 60 minute FTP performance. So far more effective to train with sufficient nutrition on board, rather than restricting intake which will render training less effective.

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

It is important to consider whether the energy deficiency that you are experiencing is intentional or unintentional.

Intentional: you may be deliberately restricting your calorie intake to lose weight and body fat, although you are already a healthy weight, as you believe this will improve your power-to-weight ratio or run speed.

  • If you are trying to lose weight – or anxious about gaining weight – and experiencing issues with hormones (such as missing your periods or not experiencing morning erections) or bone health (such as getting a stress fracture) or finding that your performance is declining rather than improving, it may be time to seek support.
  • This is particularly important if your eating patterns have become disordered, eg exclusion of multiple food groups, binge eating and/or purging, or deliberately avoiding social situations around food.
  • Please visit the resources section of an excellent campaign website that has been put together to help athletes talk more openly about their experiences with food, disordered eating and RED-S and find help: https://trainbrave.org/resources/.
  • Another great resource to learn more about RED-S and how it can adversely affect your health is http://health4performance.co.uk/athlete-dancer/

Unintentional: eating fewer calories than your body needs when you are training hard is common in endurance athletes and often not deliberate.

  • You may not yet be experiencing the symptoms of RED-S outlined as above, but you are greatly at risk of doing so if you continue to under-eat relative to your training over a period of months or years.
  • You do not need to be losing weight to be energy deficient, as your body’s metabolism adjusts to a lower intake but compromises on other functions while your weight stays the same. For example, you may experience constipation or bloating due to slowed digestive function. Here are some tips to help you meet your energy needs.

Here are some tips to help you to better manage your energy intake if you are at unintentional risk of RED-S.

  • Track your food intake vs energy expenditure for a short period. Use My Fitness Pal or a similar app to track these daily 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 after taking your energy expenditure through training into account, your intake is likely to be inadequate as these are the guidelines for the general population. 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.
    • 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. This would include use of sports nutrition products like bars, gels and sports drinks during training. Again, use an app like My Fitness Pal for a week to help you assess your carbohydrate intake.
  • 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.
  • 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 my blog here [link to https://www.endurancesportsnutritionist.co.uk/blog/vegan-diets-guide-endurance-athlete/] for tips on ensuring a well-balanced approach.
  • 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.

If you are experiencing relative energy deficiency, avoid following approaches like fasted training, where the training benefits are likely to be outweighed by the pitfalls of inadequate calorie intake. I also suggest avoiding low carb-high fat diets (LCHF) due to potential adverse effects on thyroid hormones, particularly T3, which may slow down metabolism and impact on performance. It can also be difficult to obtain adequate calories from these types of diets due to the near exclusion of a whole food group – which is why they may be very effective for weight loss in people who are overweight – and the lack of carbohydrate may harm performance through a loss of metabolic flexibility, ie ability to utilise carbohydrate as fuel when required for high intensity efforts.

Conferences in Sport/Dance, Exercise Science and Medicine 2018

References

Raising Awareness of RED-S in Male and Female Athletes and Dancers Dr N. Keay, British Journal of Sport Medicine 2018

2018 UPDATE: Relative Energy Deficiency in Sport (RED-S) Dr N. Keay, British Journal of Sport Medicine 2018

Low energy availability assessed by a sport-specific questionnaire and clinical interview indicative of bone health, endocrine profile and cycling performance in competitive male cyclists. Keay N, Francis G, Hind K. BMJ Open Sport & Exercise Medicine 2018

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

 

Athletic Fatigue: Part 2

A degree of athletic fatigue following a training session, as described in part 1, is required to set in motion mechanisms to drive beneficial adaptations to exercise. At what point does this process of functional over-reaching tip into non-functional over-reaching denoted by failure to improve sports performance? Or further still along the spectrum and time scale, the chronic situation of overtraining and decrease in performance? Is this a matter of time scale, or degree, or both?

Slide1
Integrated Periodisation of Training Load, Nutrition and Recovery keeps an individual on the green plateau, avoiding descent into the red zone, due to an excess or deficiency

Determining the tipping point between these fatigue situations is important for health and performance. A first step is always to exclude underlying organic disease states, be these of Endocrine, systemic inflammatory or infective aetiologies. Thereafter the crucial step is to assess whether the periodisation of training, nutrition and recovery are integrated over a training block and in the longer term over a training season.

What about the application of Endocrine markers to monitor training load? Although the recent studies described below are more applicable to research scenarios, they give some interesting insights into the interactive networks effects of the Endocrine system and the multifactorial nature of fatigue amongst individual athletes.

In the short term, during a 2 day rowing competition, increases in wakening salivary cortisol were noted followed by return towards baseline in subsequent 2 day recovery. Despite individual variability with salivary cortisol measurement, this does at least offer a noninvasive way to adjust training loads around competition time for elite athletes.

Over an 11 day stimulated training camp and recovery during the sport specific preparatory phase of the training season, blood metabolic and Endocrine markers were measured. In the case of an endurance based training camp in cyclists, a significant increase in urea (due to protein breakdown associated with high energy demand training) and decrease in insulin-like growth factor 1 (IGF1) from baseline were noted. Whereas for the strength-based athletes for ball sports, an increase in creatine kinase (CK) was seen, as a result of muscle damage. This study demonstrates how different markers of fatigue are specific to sport discipline and mode of training. Large inter-individual variability existed between the degree of change in markers and degree of fatigue.

In the longer term, for the case of overtraining syndrome potential Endocrine markers have been reviewed. Whilst basal levels of most measured hormones remained stable, a blunted submaximal exercise response of growth hormone (GH), prolactin and ACTH could be indicative of developing overtraining syndrome. Whilst this review is interesting, dynamic testing is not a practical approach and these findings are not specific to over training. Rather this blunted dynamic exercise response would indicate relative suppression of the neuroendocrine hypothalamic-pituitary axis which could potentially involve other stressors such as inadequate sleep or poor nutrition. Although basal levels may lie “within the normal range”, if both pituitary derived stimulating hormone and end endocrine gland hormone concentrations fall in the lower end of the normal ranges (eg low end of range TSH and T4) this is consistent with mild hypothalamic suppression observed over the range of training and fatigue conditions (functional/non-functional and overtraining) and/or Relative Energy Deficiency in Sports (RED-S).

Although the studies above are of research interest, non invasive monitoring, specific to an athlete is more practical for monitoring the effects of training. Several useful easily measurable metrics can give clues: resting heart rate, heart rate variability, power output. Tools on Strava and Training Peaks provide practical insights in monitoring training effectiveness via these metrics. A range of mobile apps makes it ever easier to augment a personal training log to include these training metrics, along with feel, sleep and nutrition. Such a log provides feedback on health and fitness for the individual athlete, in order to personalise training plans. Certainly adding the results from any standard basal blood tests will also help add to the picture, along the lines of building a longitudinal personal biological passport. After all, “normal ranges” are based on the general population, of which top level athletes may represent a subgroup. The more personalised the metics recorded over a long time scale, the more sensitive and useful the process to guide improvement in sport performance.

Context is key when considering athletic fatigue: temporal considerations and individual variation. Certainly the interactive network effects of the Endocrine system are important in determining the degree of adaptation to exercise and therefore sports performance. However the Endocrine system acts in conjunction with many other systems (metabolic, immune and inflammatory), in determining the effectiveness of training in improving sports performance. So it is not surprising that one metric or marker in isolation is not predictive of fatigue status in individual athletes.

For more discussion on Health, Hormones and Human Performance come to the British Association of Sport and Exercise Medicine annual conference

Presentations

References

Athletic Fatigue: Part 1

Endocrine system: balance and interplay in response to exercise training

Temporal considerations in Endocrine/Metabolic interactions Part 1

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

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

Capturing effort and recovery: reactive and recuperative cortisol responses to competition in well-trained rowers British Journal of Sports Medicine

Blood-Borne Markers of Fatigue in Competitive Athletes – Results from Simulated Training Camps Plos One

Hormonal aspects of overtraining syndrome: a systematic review BMC Sports Science, Medicine and Rehabilitation 2017

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

Strava Fitness and Freshness Science4Performance 2017

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

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

What has your gut microbiome ever done for you?

a-muciniphila-233x300

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

Athletic Fatigue: Part 1

Interpreting athletic fatigue is not easy. Consideration has to be given to context and time scale. What are the markers and metrics that can help identify where an athlete lies in the optimal balance between training, recovery and nutrition which support beneficial adaptations to exercise whilst avoiding the pitfalls of fatigue and maladaptation? This blog will discuss the mechanisms of athletic fatigue in the short term.

Screen Shot 2017-08-30 at 09.17.58
Proposed causes of fatigue dependent on duration and intensity of training session

In the short term, during an endurance training session or race, the temporal sequence of athletic fatigue depends on duration and intensity. It is proposed that below lactate threshold (LT1), a central mechanism governs: increasing central motor drive is required to maintain skeletal muscular power output until neuromuscular fatigue cannot be overcome. From lactate threshold (LT1) to lactate turn point (LT2), a combination of central and peripheral factors (such as glycogen depletion) are thought to underpin fatigue. During high intensity efforts, above LT2 (which correspond to efforts at critical power), accumulation of peripheral metabolites and inability to restore homeostasis predominate in causing fatigue and ultimately inability to continue, leading to “task failure”. Of course there is a continuum and interaction of the mechanisms determining this power-duration relationship. As glycogen stores deplete this impacts muscle contractility by impairing release of calcium from the sarcoplasmic reticulum in skeletal muscle. Accumulation of metabolites could stimulate inhibitory afferent feedback to central motor drive for muscle contraction, combined with decrease in blood glucose impacting central nervous system (CNS) function.

Even if you are a keen athlete, it may not be possible to perform a lactate tolerance or VO2 max test under lab conditions. However a range of metrics, such as heart rate and power output, can be readily collected using personalised monitoring devices and then analysed. These metrics are related to physiological markers. For example heart rate and power output are surrogate markers of plasma lactate concentration and thus can be used to determine training zones.

A training session needs to provoke a degree of training stress, reflected by some short term fatigue, to set in motion adaptations to exercise. At a cellular level this includes oxidative stress and exerkines released by exercising tissues, backed up by Endocrine responses that continue to take effect after completing training during recovery and sleep. Repeated bouts of exercise training, followed by adequate recovery, result in a stepwise increase in fitness. Adequate periodised nutrition to match variations in demand from training also need to be factored in to prevent the Endocrine system dysfunction seen in Relative Energy Deficiency in Sports (RED-S), which impairs Endocrine response to training and sports performance. Integrated periodisation of training/recovery/nutrition is essential to support beneficial multi-system adaptations to exercise on a day to day time scale, over successive training blocks and encompassing the whole training and competition season. Psychological aspects cannot be underestimated. At what point does motivation become obsession?

In Part 2 the causes of athletic fatigue over a longer time scale will be discussed, from training blocks to encompassing whole season.

For more discussion on Health, Hormones and Human Performance come to the British Association of Sport and Exercise Medicine annual conference

Presentations

References

Endocrine system: balance and interplay in response to exercise training

Power–duration relationship: Physiology, fatigue, and the limits of human performance European Journal of Sport Science 2016

Strava Ride Statistics Science4Performance 2017

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

Relative Energy Deficiency in Sports (RED-S) Practical Considerations for Endurance Athletes

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

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

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

 

 

Ubiquitous Microbiome: impact on health, sport performance and disease

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

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

 

 

 

Temporal considerations in Endocrine/Metabolic interactions Part 1

LifeSeasonDay

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

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

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

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

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

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

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

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

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

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

References

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

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

Metabolic and Endocrine System Networks Dr N. Keay

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

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

Factors Impacting Bone Development Dr N. Keay

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

Sleep Duration and Telomere Length in Children Journal of Paediatrics 2017

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

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

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

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

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

 

 

 

 

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