Metabolic and Endocrine System Networks


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


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



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


As discussed in my previous blog Optimal health: including female athletes! Part 1 Bones, the female athlete triad is well described since 1984. The triad comprises disordered eating, amenorrhoea and reduced bone mineral density (BMD). What was uncertain was whether this was a reversible training effect. My study of professional retired pre-menopausal female dancers demonstrated that such bone loss is irreversible, despite resumption of menses. Furthermore, low body weight, independent of amenorrhoea, causes BMD loss. A few female athletes in my subsequent longitudinal study of professional dancers in the English National Ballet company were “robust” and continued to menstruate, in spite of low body weight. However this could have involved anovulatory cycles and therefore low oestrogen. One parameter cannot be considered in isolation.

Furthermore, it has become apparent that the female athlete triad is just part of a much larger picture, known as Relative Energy Deficiency in sport (RED-S). The fundamental issue is that of energy deficiency caused by a mismatch of energy intake and energy expenditure from exercise training. Quality of diet, including micronutrients is also important.

If you are a male athlete, you may be thinking that this is all just a problem for female counterparts? No. Male athletes can also develop RED-S, especially in sports where low body weight confers a sport performance advantage, for example long-distance runners and road cyclists (especially climbers). In a fascinating lecture, Professor Jorum Sundgot-Borgen from the Department of Sport Medicine, at the Norwegian School of Sport and Exercise Science, described the occurrence in male ski jumpers.

This energy deficient state in RED-S in both female and male athletes produces a cascade, network effect on multiple systems: immune, cardiovascular, endocrine, metabolic and haematological effects. Clearly suboptimal functioning in these key areas has implications for current physical and psychological health of athletes and therefore their sport performance. The psychological element is of note as this may be both cause and effect of RED-S. After all in order to be a successful, especially in sport, a high level of motivation, bordering on obsession, is required. Although athletes with RED-S may not fall into a defined clinical disease state, they demonstrate a subclinical condition that impacts health. Performance implications include decreased training response with reduced endurance, muscle strength and glycogen storage, alongside an increased risk of injury, probably due to impaired adaptive response to training and a decrease in co-ordination and concentration. Psychological sequelae include depression and irritability.

Some features of RED-S may be lead to irreversible health issues in the future, as seen in the case of athletic hypothalamic amenorrhoea in female athletes with permanent loss of BMD. In both male and female athletes low energy density diet relative to energy expenditure with training results in low levels of insulin like growth factor 1 (IGF-1) and sex steroid hormones which impair not only sport performance but bone microarchitecture and mineralisation. Although hypothalamic suppression in females is manifest by lack of menstruation, there is no such obvious clinical sign in males, who may nevertheless also be experiencing suppression of the hypothalamic-pituitary-gonadal axis. It has been shown that oestradiol is the key sex steroid hormone in promoting bone mineralisation: for both male and female. In males testosterone is aromatised to oestradiol which in turn acts on bone. As the same mechanisms are involved in the aetiology and effects of RED-S, then the long term consequences will most likely be the same for both female and male athletes.

In my next blog I will explore the consequences of RED-S in young athletes and delve into the Endocrine mechanisms involved in the aetiology and multi-system outcomes for male and female athletes of all ages.

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


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

Keay N, Fogelman I, Blake G. Bone mineral density in professional female dancers. British Journal of Sports Medicine, vol 31 no2, 143-7, June 1997.

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

Relative Energy Deficiency in sport (REDs) Lecture by Professor Jorum Sundgot-Borgen, IOC working group on female athlete triad and IOC working group on body composition, health and performance. BAEM Spring Conference 2015.

Mountjoy M, Sundgot-Borgen J, Burke L, Carter S, Constantini N, Lebrun C, Meyer N, Sherman R, Steffen K, Budgett R, Ljungqvist A. The IOC consensus statement: beyond the Female Athlete Triad-Relative Energy Deficiency in Sport (RED-S).Br J Sports Med. 2014 Apr;48(7):491-7.

Margo Mountjoy, IOC Medical Commission Games Group. Relative Energy Deficiency in Sport. Aspetar Sports Medicine Journal.