Cortisol and the stress response

Cortisol, a steroid hormone produced by the adrenal gland, plays a key role in mobilizing the body’s resources to cope with stressful challenges, including the challenge of running. Among its many roles is the regulation of blood glucose. When demands are high, cortisol acts to conserve glucose for the brain by minimizing uptake of glucose into other tissues and by promoting the production of glucose in the liver.   Because healing is not a priority when dealing with an acute challenge, cortisol suppresses inflammation and the immune system. In a healthy person, cortisol levels return to normal over a time scale of 30-60 minutes after the stress resolves. However if the transient surge of cortisol required to deal with acute stress is not switched off, cortisol inhibits healing by suppressing the formation of collagen while promoting breakdown of protein, thereby damaging many tissues of the body.

Recent evidence from a study by Skoluda and colleagues indicates that endurance athletes tend to have persistently high levels of cortisol. This increases in proportion to training volume. Thus the regulation of cortisol is potentially of great importance not only for ensuring that an athlete obtains benefits from training, but also for long term health.

The relationship between cortisol and inflammation is complex. In the short term cortisol suppresses inflammation, but sustained elevation of cortisol can lead to a suppression of the receptors that mediate the effects of cortisol on body tissues, and consequently, sustained elevation of cortisol can actually promote chronic inflammation which in turn damages tissues by laying down non-functional fibrous tissue as described in my recent post.

Although excessive cortisol is harmful, reduced ability to generate cortisol when required can be even more harmful. Addison’s disease, a rare condition in which the adrenal gland is damaged by autoimmune attack, is characterised by non-specific symptoms such as weakness and fatigue, and can be result in fatal inability to respond to stress. There is some evidence that sustained stress can reduce the capacity of the adrenal glands to produce cortisol when required, though the concept of adrenal fatigue, popularized by some alternative-medicine practitioners, remains an ill-defined entity.

Cortisol production is regulated by a feedback mechanism that takes account of information about the overall metabolic state of the body. This feedback system acts via the hypothalamo-pituitary-adrenal axis (HPA). The release of cortisol from the adrenal glands is stimulated by a hormone, ACTH, that is produced in the pituitary gland. The release of ACTH is in turn stimulated by a hormone, corticotrophin releasing factor, that is secreted by the hypothalamus. Information about the state of the body is funnelled via the amygdala and hippocampus in the temporal lobe of the brain, to the hypothalamus. This complex feedback system allows a diverse array of neural and hormonal signals to control cortisol release in a way that balances the catabolic effects of cortisol, promoting tissues breakdown, with the anabolic effects of other hormones, such as DHEA (a steroid hormone produced in the adrenal glands) and growth hormone, produced in the pituitary gland, that play a role in promoting the repair and strengthening of damaged tissues.  Thus many complex, interacting processes are involved in ensuring the optimal balance between mobilising body resources to deal with acute challenge and subsequent healing. Factors such as levels of ongoing stress from life circumstances and age contribute to the balance.

 Strategies for optimising the stress response

In summary, an athlete requires healthy adrenal glands which can generate enough cortisol to meet the challenge of stress but then to switch off cortisol production to promote recovery. The simple principle is that for optimum training benefit and long term health, we need to avoid excessive stress. However, the best way of achieving this is likely to determined by individual’s genes and life circumstances. While each individual has to find what works for him or her, there are several issues likely to be relevant to most athletes.

1)      Avoiding over-training. As demonstrated by Skoluda, the sustained excess of cortisol is greater in those who train more. Both volume and intensity matter though it is noteworthy that prolonged duration of exercise promotes increase in cortisol, whereas high intensity promotes hormones such as growth hormone and anabolic steroid hormones that promote strengthening of tissues. Consistent with this, some evidence indicates that the over-training syndrome is more strongly linked to high volume training than to high intensity training.

2)      Recovery from training and racing is crucial.   Not only does inadequate recovery increase the risk of persisting inflammation (as discussed in my previous post) but it impedes the transition from the cortisol induced catabolic state to the anabolic state required to rebuild and strengthen body tissues. This raises the major question of how best to determine if recovery is adequate. Subjective indices such as the Profile of Mood States, and autonomic measures such as resting heart rate and heart rate variability provide a guide, but no single test provides the full answer.  This is an issue I will return to again in the near future.

3)      Resistance training promotes the release of anabolic hormones and has many other beneficial effects on metabolism including increased sensitively to insulin. The major metabolic benefits of resistance training can be achieved by two 15 minute sessions per week.

4)      Life-stress and relaxation. Many of us have relatively limited control over the pressures of work and other responsibilities. However the way we react to these pressures is largely under our own control. Sleep plays a cardinal role. During sleep, cortisol levels fall while release of growth hormone is promoted. During our waking hours we can do a great deal to minimise stress. In recent years, the practice of Mindfulness has been proven to be effective in treating clinical disorders including anxiety and depression. It is a technique derived from Eastern meditative practices in which the aim is cultivation of a calm, non-judgmental awareness of one’s present physical and mental state.   Accumulating evidence indicates that this mental state is the optimum state for individuals such as US Navy Seals for whom remaining calm and focussed under intense pressure is crucial. Some studies show that Mindfulness lowers cortisol levels, while other studies have found evidence of beneficial reduction in stress and improved sleep but did not observe significant reduction of cortisol levels. Mindfulness is a knack that can be acquired by practice. Although the evidence for its effectiveness is still preliminary, my own experience is that it is effective in lowering mental and physical tension. I practice it at any time when I feel pressure is building, and also experiment with employing it while running to promote a constructive focussed mental state.

5)      Fuelling before and during training is a debateable topic. Some evidence indicates that training in a fasting state leads to improved endurance performance, perhaps mediated by the development of increased capacity to utilise fat as fuel, but overall the studies have yielded mixed results, as I have discussed in a previous post. I suspect this is because training in a fasted state also promotes increased cortisol levels that might be harmful. I have made appreciable gains in fitness in the past following training in a fasted state, but suffered one of the few serious muscle strains I have ever experienced after three weeks of high volume training predominantly in a fasted state.   This is mere anecdote, but when combined with the mixed evidence from scientific studies, leads me to conclude that training in a fasted state should be done cautiously, ensuring that overall stress levels are not excessive.

6)      Long term nutrition.  In light of the mechanism by which the hypothalamo-pituitary axis (HPA) adjusts cortisol levels in order to maintain metabolic homeostasis, it would be expected that a diet that promotes healthy energy metabolism would also be expected to promote healthy regulation of cortisol. As discussed in several of my recent posts, there is growing evidence that a Mediterranean diet promotes healthy metabolism. In accord with this, the available evidence indicates that a Mediterranean diet does promote healthy regulation of cortisol. For example a study of Spanish women found that those who chose a dietary pattern closer to the Mediterranean diet, with high mono-unsaturated fatty acid intake, showed more stable regulation of cortisol by the HPA.

 Conclusions

The evidence obtaind by Skoluda indicating that endurance athletes suffer sustained elevation of cortisol suggests that taking steps to maintain healthy regulation of cortisol is likely to result not only in a better response to endurance training but also in better long term health. This might be achieved by avoidance of over-training, ensuing good recovery, incorporation of some resistance training into the schedule and a number of life-style adaptations including adequate sleep, stress reduction via strategies such as Mindfulness, and a healthy diet, such as the Mediterranean diet.

9 Responses to “Cortisol and the stress response”

  1. Seth Leon Says:

    Thank you Canute for this informative post on a fascinating, important, and I think not yet fully understood topic.

    If you are not yet familiar, I think you would find the of Robert Saplosky and Bruce McEwen of related importance to this topic. Saplosky has done a great deal of research on chronic stress, much of it with baboons in their natural environment. McEwen has put forth a theory of stress and adaptation with a focus on allostatsis rather than the typical emphasis on homeostasis.

    We know that with increasing age or over-exposure to chronic stress the ability of the stress response system to flexibly turn off and on in response to stressors becomes dampened. Paradoxically exercise is the best known way to maintain a healthy stress response system as we age. Obviously their is a threshold where the positive (eustress as coined by Hans Selye) stress of exercise can lead to systemic distress in excess. I am sure that threshold varies by individual and itself changes over time in response to activity. I think we need a lot research in learning how to find the optimum balance of physical stress that allows for safely increasining the eustress threshold without treading into lasting systemic distress.

    Thanks again :)

    • canute1 Says:

      Seth,
      Thanks for your comment. I agree that the concept of allostasis is important. Somewhat paradoxically, we can best achieve overall stability of metabolism (homeostasis) by experiencing challenges that produce departure from equilibrium, just as we can avoid being caught flat-footed by gently rocking back and forth. Consequently, exercise, which entails departure from equilibrium, generally promotes good health. However, my focus in recent posts has been on why some endurance athletes suffer ill-health in contrast to the usual trend towards enhanced health. It seems to me the important question for any endurance athlete who wishes to push themselves near to their limits is identifying the causes of adverse outcome. I suspect that sustained excess cortisol is likely to be an important factor. But as you say, we still have a lot to learn.

  2. Seth Leon Says:

    Yes, I’m sure cortisol plays a role, leading to postive adaptation in certain doses and maladaptive at at certain thresholds. I am just wondering if we think about the idea of pushing the boundaries of our ‘limits’ in the wrong way. Obviously those elite athletes competing at the extreme have to push themselves really hard. What is it however that separates an optimum stress stimulas/recovery from true over-training. We know that well timed short-term over-reaching leads to good performance after a taper period. That approach does flirt with over-training if any part of that formula is misjudged. I am most interested in the long term how we might move the stimulas/recovery relationship in a progressive direction that gradually allows adaptation to greater stimulas with less recovery time as fitness improves without having to periodically flirt on the extreme boundary. This is more alligned with the middle-way that I find tends to produce steady progress regardless of field when the various factors are well understood.

    • canute1 Says:

      Seth
      Thanks for those thoughts

      Much anedotal evidecne indicates that we can adapt to cope with a greater training volume. At present the accepted way of doing this is by gradual increase in training volume. This is not only supported by anecdotal evidence but make sense insofar as stronger body tissues are less likely to breakdown when stressed and therefore illness likely to generate cytokines that mediate excessive inflammation.

      It seems very likely that genes, life-style and training history all contribute to how well an athlete recovers from training. In my experience, the difference between individuals in ability to tolerate heavy training is one of the main factors predicting long term success as an endurance athlete. While we can do little about our genes, we do have some ability to influence our life-style and training history. Some of the things we can have been recognised for many years: adequate sleep, good diet; recovery from racing and training. The interesting challenge is whether we can discover how to adjust the balance between catabolism and anabolism more effectively taking account of our individual strengths and weaknesses. I agree it would be preferable to find a way that does not require repeatedly pushing ourselves to the edge of over-training.

      Athletes such as Ed Whitlock appears to have found a strategy that works for him without repeatedly flirting with the threshold of over-training, though from what I know of his approach, he appears to monitor his well-being quite carefully.

      I have focussed on cortisol because it plays a key role in the balance between catabolism and anabolism. However, in recent years the science of cellular signalling has revealed many other molecules that play a role. Cortisol is not the only factor but I think that it is the one whose role is best understood, and therefore regulating cortisol is a good place to start. However, it might well be that a comprehensive assessment of overall wellbeing is actually a more reliable way to monitor the situation, as over-all wellbeing might be more sensitive to the state of the multiple interacting signalling systems.

  3. Seth Leon Says:

    Thanks again for your thoughtful and informative reply which is consistent with my understanding and experience.

    We as humans I think tend to look for and find comfort in simple answers to complex patterns. It would be nice if there were one simple indicator of well-being that could inform ideal activity and recovery decisions. For awhile I was looking to HRV as that indicator, and I do think it sensitive to many aspects of well-being. Unfortunately I think it tends to over-sensitive to some aspect that are not overly important to over-training and somewhat insensitive to others (mostly those connected to volume of training which cortisol might better capture).

    Your choice of cortisol is interesting to me, and it would be nice if there were a non-invasive bio marker that could accurately monitor levels. Do you know of any work in this area?

    Recently I purchased a new Suunto Ambit 2r watch. I am somewhat intrigued by the research they have put into objectively measuring training sessions with estimates such as EPOC (excess post exercise recovery), peek training effect, and estimated recovery time. They also have an APP development option. I have just developed an APP that calculates an estimated marathon pace in decimal minutes per mile by means of a Daniels vdot conversion from a sub-maximal running effort. My though is that this will be very useful for monitoring fitness over time. The app does not take into account elevation change or temperature. I wanted to include those factors but the code was to long for ambit 2R compatibility. Thus it is best to evaluate the estimated vdot and marathon pace results from a lap on flat terrain in moderate or cool weather. Temperature will only be a minor factor in the first few miles. Values become fairly accurate after a steady state HR is achieved. You need also to have entered an accurate maximum HR for this app to produce accurate estimates. The estimates should be reasonably accurate at running intensities below lactate threshold. So far I am finding them to be relatively stable regardless of pace between say 65 and 88% of heart rate max.

    It can also be used on race day to evaluate appropriate pacing. If I would have followed the data from this formula in setting a pace for my recent marathon (which I ran after 10 days of being sick and with a chest cold), I would have had better pacing a better time, and a much more pleasant experience overall.

    My thinking right now is that the various data from recent training sessions and training session trends will be most informative although I am still collecting HRV data. Of course I try to do all the basic stuff you recommend regarding sleep, diet, etc…. This cycle I want to add some more resistance training.

    Thanks again for all your informative posts.

    • canute1 Says:

      Seth,
      I agree that it is unreasonable to expect a single measurement to cover all aspects of well-being, though I should be noted that the regulation of cortisol is coupled to the regulation of HRV, such that increase in cortisol tends to be accompanied by reduced HRV. However consistent with your concern about excessive sensitive of HRV, instantaneous values of both cortisol and HRV fluctuate in response to many circumstances, so I do not think that a single measure of either at one time point is likely to provide a good measure of ‘well-being’ . Measurement of cortisol in hair might give a fairly good estimate of sustained levels over a period of weeks or months but that provides little guidance for day by day adjustment sin training.

      I am interested in assessing training stress by measures such as EPOC, though I think the original concept based on an accumulated oxygen debt is not very useful. I do not know how the Suunto Ambit 2r computes it, but when I last looked into EPOC it appeared to me that it under-estimates the training effects of very low intensity training.
      .
      I find that using Daniels formula to predict race performance based on HR measured during submaximal running usually works very well for me, though as you say, the accuracy of the prediction does depend on having an accurate estimate of HRmax and also on having developed endurance adequate for the relevant race distance.

      I plan to do a another post that discusses the topic of measurements might best indicate training load, chronic stress and fitness, in the near future.

  4. Seth Leon Says:

    Hi again,

    Suunto Peak EPOC measures do underestimate the effect of long slow endurance runs ( or other types of long slow endurance training). It seems to serve more as an intensity peak measure.

    They also however have a recovery measure (in HR units) that seems to do a good job of taking into account the duration of a training event. As an example, after my recent marathon the recommended recovery time based on my HR profile from the race was 120 HRs. On my short hilly 2.5 mile commute run with a backpack to work I get a recommended recovery of 5 HRs.

    I need to look at how this recovery measure is calculated, but it seems to be their attempt to provide a more comprehensive recovery index that incorporates the data with duration.

    I will be watching how this corresponds with HRV data as I develop a large enough data sample.

  5. canute1 Says:

    Thanks. I look forward to hearing more about your experience with the Suunto Ambit recovery measure

  6. Lessons from enduring masters marathoners | Canute's Efficient Running Site Says:

    […] regarding over-training including the role of cortisol on several occasions previously (e.g. here and here). In summary, effective training achieves it benefit by stressing the body in a way that […]

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