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

 

 

Sleep for Health and Sports Performance

“Sleep.. chief nourisher in life’s feast,” Macbeth.

In my blog for British Association of Sport and Exercise Medicine, I described improving sport performance by balancing the adaptive changes induced by training together with the recovery strategies to facilitate this, both in the short and long term.  alec0120-12x17

A recovery strategy which is vital in supporting both health and sport performance, during all stages of the training cycle is sleep.

Sufficient sleep is especially important in young athletes for growth and development and in order to support adaptive changes stimulated by training and to prevent injury. Amongst teenage athletes, studies have shown that a lack of sleep is associated with higher incidence of injury. This may be partly due to impaired proprioception associated with reduced sleep. Sleep is vital for consolidating neurological function and protein synthesis, for example in skeletal muscle. Sleep and exercise are both stimuli for growth hormone release from the anterior pituitary, which mediates some of these adaptive effects.

Lack of sleep can also interfere with functioning of the immune system due to disruption of the circadian rhythm of secretion in key areas of the Endocrine system. Athletes in heavy training, with high “stress” loads and associated elevated cortisol can also experience functional immunosuppression. So a combination of high training load and insufficient sleep can compound to disrupt efficient functioning of the immune system and render athletes more susceptible to illness and so inability to train, adapt and recover effectively.  Lack of sleep disrupts carbohydrate metabolism and recently found to suppress expression of genes regulating cholesterol transport. In overreaching training, lack of sleep could be either a cause or a symptom of insufficient recovery. Certainly sleep deprivation impairs exercise performance capacity (especially aerobic exercise) although whether this is due to a psychological, physical or combination effect is not certain.

Sufficient sleep quality and quantity is required for cognitive function, motor learning, and memory consolidation. All skills that are important for sports performance, especially in young people where there is greater degree of neuroplasticity with potential to develop neuromuscular skills. In a fascinating recorded lecture delivered by Professor Jim Horne at the Royal Society of Medicine, the effects of prolonged wakefulness were described. Apart from slowing reaction time, the executive function of the prefrontal cortex involved in critical decision making is impaired. Important consequences not only for athletes, but for doctors, especially for those of us familiar with the on call system in hospitals back in the bad old days. Sleep pattern pre and post concussive events in teenage athletes is found to be related to degree and duration of concussive symptoms post injury. The explanation of how sleep deprivation can cause these functional effects on the brain has been suggested in a study where subtle changes in cerebral neuronal structural properties were recorded. It is not known whether these changes have long term effects.

So given that sleep is essential not only for health and fitness, but to support sports performance, what strategies to maximise this vital recovery process? Use of electronic devices shortly before bedtime suppresses secretion of melatonin (neurotransmitter and hormone), which is a situation not conducive for sleep. Tryptophan is an amino acid precursor in the synthesis of melatonin and serotonin (neurotransmitter) both of which promote sleep. Recent research demonstrates that protein intake before bed can support skeletal and muscle adaptation from exercise and also recovery from tendon injury. Conversely there is recent report that low levels of serotonin synthesis may contribute to the pathogenesis of autoimmune inflammatory disease such as rheumatoid arthritis. This highlights the subtle balance between degree of change required for positive adaptation and a negative over-response, as in inflammatory conditions. This balance is different for each individual, depending on the clinical setting. So maybe time to revisit the warm milky drink before bed? Like any recovery strategy, sleep can also be periodised to support exercise training, with well structured napping during the day as described by Dr Hannah Macleod, member of gold winning Olympic Hockey team.

In conclusion, when you are planning your training cycle, don’t forget that periodised recovery to compliment your schedule should be factored in, with sleep a priority recovery and adaptation strategy.

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 Sport and Exercise Medicine

Sleep, Injury and Performance

Keay N. The effects of growth hormone misuse/abuse. Use and abuse of hormonal agents: Sport 1999. Vol 7, no 3, 11-12.

Wallace J, Cuneo R, Keay N, Sonksen P. Responses of markers of bone and collagen turover to exercise, growth hormone (GH) administration and GH withdrawal in trained adult males. Journal of Endocrinology and Metabolism 2000. 85 (1): 124-33.

Sleep and sporting performance

Young people: neuromuscular skills for sports performance

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

“Sleepiness and critical decision making”. Recorded lecture Professor Jim Horne, Royal Society of Medicine 16/11/16

What Does Sleep Deprivation Actually Do To The Brain?

Pre-Sleep Protein Ingestion to Improve the Skeletal Muscle Adaptive Response to Exercise Training

Exercise and fitness in young people – what factors contribute to long term health? Dr N. Keay, British Journal of Sports Medicine

Serotonin Synthesis Enzyme Lack Linked With Rheumatoid Arthritis

“Science in Elite Sport” Dr Hannah Macleod, University of Roehampton, 6/12/16

Balance of Recovery and Adaptation for Sport Performance

There has been much recent discussion about the optimal balance of recovery strategies to enable effective return to training, and adaptive processes which occur as the result of training to improve sporting performance.

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I have been reading the scientific reports to try and gain an understanding of this balance between recovery and adaptation. However, my investigations were put into context after attending two fascinating meetings last week where insightful talks were given by Dr Hannah Macleod Olympic gold medallist and presentations at the King’s Sport and Exercise Medicine Conference.

The scientific principle behind exercise training, of any sort, is that improvement in exercise performance follows from the cycle of overload exercise, followed by recovery phase during which adaptive changes occur in musculoskeletal, cardiovascular, metabolic and neurological systems to improve exercise performance capacity. If sufficient recovery is not taken before next training session, then rather than a progressive stepwise upward improvement in performance capacity, a downward progression occurs. In order to avoid this overreaching and overtraining scenario, rather to improve performance, training cycle as described by Dr Macleod often consists of 3 weeks “on”, followed by “rest” week together with well structured napping.

Theoretically, if the amount of recovery needed could be shortened, then more training could be done and thus potentially more adaptive advantages gained. However, by shortening recovery time with various strategies, this might actually curtail and reduce the very adaptive changes being sought. Considering recovery and adaptive responses of skeletal muscle to exercise, there are recent apparently contradictory reports on the benefits of ice baths. To ice bath or not to? Certainly for muscle injury RICE (rest, ice, compression, elevation) regime is well established. Does the same apply for skeletal muscle recovery and adaptation post exercise? The most recent study on 9 non-elite athletic males revealed that post resistance exercise there was no difference in the inflammatory markers or cellular stress markers in skeletal muscle whether recovery was either active or with cold water immersion. Nevertheless a previous study 2015 by the same group had reported attenuated gains in muscle mass and strength with cold water immersion recovery during 3 months of resistance training in 24 non-elite athletic males. The main issue seems to be that it all depends on the part of the long term training cycle and the type of sport in which the athlete is involved. For example, during pre-season training, where long term adaptations are being sought, then an ice bath might potentially attenuate adaptive responses gained from strength training. On the other hand, in the acute clinical setting, post match in a multi-day competition, an ice bath may be of benefit during the course of this competition period. Certainly Dr Macleod described having a compressive ice system on the team bus post match during the Olympics in Rio where 8 matches were played over 14 days. So recovery, especially from any impact injuries, was far more important than considerations of longer term performance in resistance training post Olympics. Not to mention the psychological beneficial effect to athletes with reduced perception of fatigue and muscle soreness and feeling in control of all factors possible.

Finally I would also suggest that just as there is variation between individuals in the positive adaptive responses to exercise, probably genetically determined, there may also be individual variation in the extent and benefits of recovery strategies. For example, in a clinical setting, an over-response of the inflammatory pathways can actually cause harm, such as in autoimmune disease. Another point is that I have restricted this blog to discuss cellular responses of skeletal muscle to resistance exercise and competition. Clearly there are other mechanisms involved in exercise training adaptations such as the neuroendocrine system, together with other types of exercise training and other recovery strategies.

In conclusion, just as training is periodised, it would appear that recovery strategies should also be periodised in conjunction with the phase of the training /competition cycle and type of sport. Apart from the scientific rational, the psychological aspects for athletes also has to be considered.

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

“Science in Elite Sport” talk by Dr Hannah Macleod at University of Roehampton 6/12/16

“Assessing the field of play” King’s Sport and Exercise Medicine Conference, Guy’s Hospital 5/12/16

Inflammation: why and how much? Dr N. Keay, British Association of Sport and exercise Medicine 2017

Endocrine system: balance and interplay in response to exercise training

Rapid recovery versus long term adaptation

Cold water therapy and bad journalism

Do post-work out ice bath help with recovery of sore muscles?

The Use of Cryotherapy in Sports Injuries

The effects of cold water immersion and active recovery on inflammation and cell stress responses in human skeletal muscle after resistance exercise

Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training

Enabling Sport Performance: part 2

Medical perspective on Therapeutic Use Exemptions: TUEs

As described in part 1 of this series of blogs I was on the international medical research team investigating the development of a test for identifying athletes doping with growth hormone. This experience helped form my view on the interaction of medicine and sport performance.

Over the next few days the results of anti-doping study will be presented at the International Federation Forum, with one of the discussions being “Medication Abuse in Elite Sport: the Epidemic!”

As doctors, our primary objective is to treat medical conditions in the most effective manner. It would not be ethical to withhold treatment to certain groups of patients, such as elite athletes. Therefore, where the prescribed medication for the treatment of a legitimate medical condition is on the prohibited list issued by the World Anti-Doping Agency (WADA), a TUE should be sought. After all elite athletes are just as likely to become ill as the general population, if not more so with functional immunosuppression due to training loads and possible energy deficient states.

In my opinion, the use of TUEs in the case of preventative treatment appears to be where the main discussion is centred. The athlete might not be acutely unwell, but may have a chronic condition, which can flare in an acute manner especially where there are known triggers. For example in the general population it is better medical practice to offer prophylactic treatment to a known asthmatic in order to decrease the risk of having an acute asthma attack, rather than waiting to treat an acute attack. Following on this argument, there is a case for offering elite athletes preventative treatment, rather than running the risk of an acute exacerbation requiring urgent treatment in difficult circumstances, for example in the middle of a race where access to required urgent treatment might be problematic. A view has been expressed that athletes with severe asthma have no place in performance sport and the paralympics would be more appropriate. Maybe this view is too extreme, after all exercise is recommended as a supportive strategy for asthma. Successful swimmers such as Thorpedo (Ian Thorpe) overcame both asthma and a reported allergy to chlorine to win Olympic and World titles.

In my opinion, the concept of TUEs for prevention of acute exacerbations of documented chronic conditions is valid. However, the issue seems to be the exact nature of such prophylatic treatment. Ideally the minimum dose of a medcation with the least potential performance enhancing qualities should be preferred. This has to be balanced against the most effective treatment for the specific documented medical condition of the individual athlete. Ultimately the athlete should be at neither disadvantage nor advantage due to a chronic, treatable medical condition.

Canadian law professor and sports lawyer Dr Richard Mc Laren (who conducted investigation into Russian state-sponsored doping) suggested that to investigate potential abuse of TUE system, frequency of certain medications being used in specific sports would need to be quantified.

In the meantime this vexed issued is being discussed at the Association of Summer Olympic International Federations (ASOIF) 9-11 November.

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

Enhancing sport performance: part 1 Dr N. Keay, British Association of Sport and Exercise Medicine

Relative Energy Deficiency in Sport Dr N. Keay, British Association of Sport and Exercise Medicine

WADA World Anti-Doping Agency

UKAD UK Anti-Doping

Enhancing Sport Performance: part 1

The good, the bad and the ugly

A medical perspective on clean athletes, dopers and abuse of the system

When I worked with the international medical research team investigating a method for detecting athletes doping with growth hormone (GH), I was struck by the co-operation of the medical teams and the athletes supporting this research in various countries. This project was supported by the International Olympic Committee and the drug companies manufacturing growth hormone who did not want to see this product mis-used.

growthhormone

Why would athletes seek to dope with GH? GH alters body composition by increasing lean mass and decreasing fat mass, a potential advantage for power sports. In addition to this anabolic effect, GH is potentially advantageous to physiology and metabolism in endurance sport by increasing use of lipid over glycogen as a substrate. However there are serious side effects of elevated GH levels as seen in patients suffering with acromegaly: including increased risk of diabetes mellitus, hypertension and cancer.

One of the challenges we encountered in developing a dope test for GH was that endogenously secreted growth hormone was virtually identical to the manufactured product. In addition, this peptide hormone is released episodically in a pulsatile manner and has a short plasma half life. So early on it was realised that direct measurement of growth hormone was not a reliable option, rather quantification of indirect plasma markers would be required. In turn that meant investigating the pharmacokinetic properties of these markers in exercising people.

So far so good. However what are the “normal” ranges for growth hormone and these secondary markers in elite athletes? The ranges used in the usual clinical hospital setting may not be accurate as exercise is a major stimulus for growth hormone release. Part of the reason elite athletes are better than amateur athletes is that they may have slightly different physiology and/or genetically determined physiology that responds more rapidly to training than the rest of us. So the first step was establishing what normal ranges are for growth hormone and its associated markers in elite athletes. Cue trips to Manchester velodrome with portable centrifuges, taking blood from Olympic medal winning rowers at the British Olympic Park and numerous evenings performing VO2 max tests on athletes.

Throughout this research I was struck by the desire of the elite athletes to participate in a study that would identify cheats, allowing them, as clean athletes, to compete on a level playing field. This gave those of us in medical research team extra incentive to come up with the most reliable and robust test possible. Nevertheless, we were aware that an arms race was taking place, with the dopers trying equally hard to cheat our test. Ultimately, however scientifically robust a test may be, it will not succeed if there is manipulation of the samples provided. This is what makes the alleged systemic abuse of the process so ugly.

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

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

From population based norms to personalised medicine: Health, Fitness, Sports Performance Dr N.Keay, British Journal of Sport Medicine 22/2/17

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

Wallace J, Cuneo R, Keay N, Sonksen P. Responses of markers of bone and collagen turover to exercise, growth hormone (GH) administration and GH withdrawal in trained adult males. Journal of Endocrinology and Metabolism 2000. 85 (1): 124-33

Keay N. The effects of growth hormone misuse/abuse. Use and abuse of hormonal agents: Sport 1999. Vol 7, no 3, 11-12

Wallace J, Cuneo R, Baxter R, Orskov H, Keay N, Sonksen P. Responses of the growth hormone (GH) and insulin-like factor axis to exercise,GH administration and GH withdrawal in trained adult males: a potential test for GH abuse in sport. Journal of Endocrinology and Metabolism 1999. 84 (10): 3591-601

Keay N, Logobardi S, Ehrnborg C, Cittadini A, Rosen T, Healy ML, Dall R, Bassett E, Pentecost C, Powrie J, Boroujerdi M, Jorgensen JOL, Sacca L. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential usefulness as in the detection of GH abuse in sport: a double blind, placebo controlled study. Endocrine Society Conference 1999

Wallace J, Cuneo R, Keay N. Bone markers and growth hormone abuse in athletes. Growth hormone and IGF Research, vol 8: 4: 348

Cuneo R, Wallace J, Keay N. Use of bone markers to detect growth hormone abuse in sport. Proceedings of Annual Scientific Meeting, Endocrine Society of Australia. August 1998, vol 41, p55

Enabling Sport Performance: part 2

Enhancing sports performance: part 3