ketogenic diet – Dr Nicky Keay

Temporal considerations in Endocrine/Metabolic interactions Part 2

2 August 2017

LifeSeasonDay

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

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

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

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

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

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

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

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

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

References

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

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

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

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

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

Metabolic and Endocrine System NetworksDr N. Keay 2017

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

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

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

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

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

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

One road to Rome: Metabolic Syndrome, Athletes, Exercise

20 July 2017

One road to Rome

Metabolic syndrome comprises a cluster of symptoms including: hypertension, dyslipidaemia, fatty liver disease and type 2 diabetes mellitus (T2DM).

The underlying pathological process is insulin resistance which distorts metabolism. Temporal and mechanistic connections have been described between hyperinsulinaemia, obesity and insulin resistance. Insulin levels rise, potentially stimulated by excess intake of refined carbohydrates and in addition the metabolic actions of insulin are attenuated on target tissues such as the liver, skeletal muscle and adipose tissue. At a cellular level, inflammatory changes play a part in this metabolic dis-regulation. Mitochondrial action in skeletal muscle is impaired, compromising the ability to oxidise fat as a substrate, thus resulting in muscle glycolysis and a consequent rise in blood lactate.

Although much attention has been focused on restricting calories and treating elevated lipids with medication (statins), evidence is now emerging that this does not have the anticipated effect of reducing mortality from cardiovascular disease. In addition, it has been proposed that the gut microbiota plays a pivotal role in metabolism, inflammation and immunity.

Metabolic syndrome usually conjures an image of an overweight person with or on the verge of developing T2DM. However there is an interesting group of slim people who are also are at risk of developing metabolic syndrome due to insulin resistance. The majority of women with polycystic ovary syndrome (PCOS) present with menstrual disturbance of some description. However not all display the textbook characteristics of Stein-Leventhal syndrome (overweight, hirsute and with skin problems). There is in fact of spectrum of clinical phenotypes ranging from the overweight to the slim. In all phenotypes of PCOS, the crucial uniting underlying metabolic disturbance is insulin resistance. The degree of insulin resistance has been shown to be related to adverse body composition with increased ratio of whole body fat to lean mass.

Although this confuses the picture somewhat, it also simplifies the approach. In all cases the single most important lifestyle modification is exercise.

Exercise improves metabolic flexibility: the ability to adapt substrate oxidation to substrate availability. Endurance exercise training amongst athletes results in improved fat oxidation and right shift of the lactate tolerance curve. Conversely metabolic inflexibility associated with inactivity is implicated in the development of insulin resistance and metabolic syndrome.

What about nutritional strategies that might improve metabolic flexibility? Ketogenic diets can either be endogenous (carbohydrate restricted intake) or exogenous (ingestion of ketone esters and carbohydrate). Low carbohydrate/high fat diets (terms often used interchangeably with all types of ketogenic diets) have been shown to improve fat oxidation and potentially mitigate cognitive decline in older people.

However, in the case of athletes, the benefits do not necessarily translate to better performance. Despite reports of such diets enhancing fat oxidation and favourable changes in body composition, a recent study demonstrates that this, in isolation, does not translate into improved sport performance. A possible explanation is the oxygen demand of increased oxidation of fat needs to be supported by a higher oxygen supply. The intermediate group of endurance athletes in this study, on the periodised carbohydrate intake, fared better in performance terms. Another recent study confirmed that a ketogenic diet failed to improve the performance of endurance athletes, in spite of improving fat metabolism and body composition. Despite small numbers, this warrants particular mention as the majority of participants were women, who are in general very underrepresented in scientific studies.

In all likelihood, the reason that these type of diets (ketogenic, high fat/low carb: not always well defined!) did not improve sport performance is that only one aspect of metabolism was impacted and quantified. Although fat oxidation, modified via dietary interventions, is certainly an important component of metabolism, the impact on the interactive network effects of the Endocrine system should be evaluated in the broader context of circadian rhythm. For athletes this goes further, to include integrated periodisation of nutrition, training and recovery to optimise performance, throughout the year.

In addition to dietary interventions, medical researchers continue to explore the use of exercise mimetics and metabolic modulators, to address metabolic syndrome. Unfortunately, some have sought their use as a short cut to improved sport performance. Many of these substances appear on the WADA banned list for athletes. However the bottom line is that it is impossible to mimic, either through a dietary or pharmacological intervention, the multi-system, integrated interplay between exercise, metabolism and the Endocrine system.

Only one road to Rome!

Whatever your current level of activity, whether reluctant exerciser or athlete, the path is the same to improve health and performance. This route is exercise, supported with periodised nutrition and recovery. Exercise will automatically set in motion the interactive responses and adaptations of your metabolic and Endocrine systems.

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

References

Insulin action and resistance in obesity and type 2 diabetes Nature Medicine 2017

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

The cholesterol and calorie hypotheses are both dead — it is time to focus on the real culprit: insulin resistance Clinical Pharmacist 2017

Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus Nature Reviews Endocrinology 2016

The essential role of exercise in the management of type 2 diabetes Cleveland Clinic Journal of Medicine 2017

β cell function and insulin resistance in lean cases with polycystic ovary syndrome Gynecol Endocrinol. 2017

The many faces of polycystic ovary syndrome in Endocrinology. Conference Royal Society of Medicine 2017

Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome Hum Reprod 2014

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

International society of sports nutrition position stand: diets and body composition J Int Soc Sports Nutr. 2017