Number 5 – Just because you can measure something does not mean you should?

March 6, 2017

OK, after stepping out of my comfort zone last week to discuss some aspects of nutritional behaviour change I am back on my “home ground” this week. I spend quite a lot of my time these days reviewing papers and abstracts and I am becoming increasingly aware that one thing that is really letting our discipline of sports science down is the continued use of inappropriate assays and then reliance on these assays to try and interpret data and/or treat “conditions”. I have been giving some thought as to why we continue to use these assays despite the known limitations and I think it comes down to 3 main reasons:

  1. We have been conned by good sales people into believing these assays do have some merit (e.g. we believe that Total Antioxidant Capacity is capable of measuring the total antioxidant capacity when it clearly cannot). We have been sold the sport nutrition equivalent of snake oil!
  2. We fall into the trap of thinking that measuring “something” is better than measuring “nothing” (e.g. we want a quantitative marker of muscle soreness, we don’t have one so we measure CK anyway as there is “nothing better”). I hear this a lot.
  3. There is huge pressure in the applied world to be “cutting edge” and innovative and these fancy measures help practitioners to look to the squad (and gaffer) that they are ahead of the game (i.e. food allergy tests). When in reality they have introduced snake oil into their practice.

Above – One of our key roles as a sport nutritionist it to protect our athletes and other support staff from the snake oil salesmen. This is easier said than done though as often we are not the key decision maker on such things. It is important however that we stay true to our beliefs and at worst work within our own non-negotiables.

At first you may be asking is it really important that we do not engage in this pseudo-science – but what about when these measures result in such flawed data that interpretation is not just useless but results in inappropriate (perhaps detrimental) advice being given to your athletes. Or from a research perspective, the measures are so bad that this results in many years of resultant pointless research that only serves to confuse our field? In these instances, surely measuring nothing is better than the alternate?

Although sport science is a relatively new discipline, we must remember that the parent disciplines that make up the various components of sport science have been researching this for many more years, and as such we should never be scared of going to experts in the parent discipline for advice and guidance. I was very fortunate that I spent 6 years working in Professor Malcolm Jackson’s and Professor Anne McArdle’s free radical research group in the department of medicine at Liverpool University, prior to returning to sport science and they are now my go to people whenever I have a problem in this area. So, I guess there is no better place to start this blog by looking at the misuse of techniques to measure free radicals in an exercise setting and how this is problematic for sport nutritionists.

 

Oxidative stress is terrible so we should stop it – or is it?

Oxidative stress is defined as “an imbalance between the oxidants (reactive species) and antioxidants in favour of the former resulting in damage”. This was first defined by Helmut Siess in the 1985 (I was fortunate to once hit a few balls on the driving range with Helmut and I am delighted to say that his science is far superior to his golf). However, many people working on free radicals in exercise often fail to appreciate the second part of this definition – “resulting in damage”. As such, the applied world has been led to believe that any change in the oxidant : antioxidant relationship is a bad thing and thus we must do whatever we can to prevent this. And since we now know that reactive species are also extremely important signals for adaptation, including mitochondrial biogenesis, this initial naivety as to the complexity of the role of them is potentially deleterious to subsequent performance. Perhaps many hours of intense training have been compromised by blocking the very signals we are trying to activate?

As well as not fully understanding the role of reactive species, many practitioners and sport scientists fail to appreciate the complexity of measuring them. The key problem with measuring reactive species is their incredibly short half-life. For example, the superoxide anion radical has a ½ life of 0.000001 seconds whilst the hydroxyl radical has a ½ life of 0.000000000001 seconds. Imagine how hard it is to measure something that stays around that long!

We are also interested in reactive species in site specific situations, i.e. we often want to know what is going on in skeletal muscle not blood. Even if we can look in the muscle by taking biopsies, we need to know what is going on in the nucleus compared with the cytosol as this has very different effects. I mentioned earlier my former boss Prof Malcolm Jackson. Malcolm has spent most of his career developing some really neat techniques to assess oxidants and antioxidants (see image below). Most recently he has developed techniques that involves real-time imaging of isolated muscle fibers by loading the muscle with specific probes that react with specific reactive species. Such techniques are giving us fantastic insights into the role of oxidants and antioxidants following exercise however unfortunately blood measures will never be able to do this and are only leading to further confusion.

Above – Confocal microspcopy image of a muscle fibre and its neuromuscular junctions (NMJ) from the anterior tibialis muscle following transfection with cytoHyPer (a probe specifically designed to detect the reactive species Hydrogen Peroxide). This probe fluoresces green when loaded with the probe and Hydrogen Peroxide is being produced during muscle contractions. The image is courtesy of Dr Aphrodite Vasilaki, a world class free radical researcher (and great friend of mine) working at The University of Liverpool. Dr Vasilaki was my lab mentor during my days at the University of Liverpool.

Given we know the biological importance of reactive species there is of course huge interest in them and a desire to measure them despite the fact the science is not there yet and as a consequence, there are currently many terrible assays being used, some of these in professional sport, that quite frankly tell us absolutely nothing! One of the most common assays is the assessment of “Total Antioxidant Capacity” or TAC. There are many variations of this assay but all suffer from the same flawed logic (for a great short review please read this from Helmut Sies). It is not surprising why people think that measuring the total antioxidant capacity would be a good idea (given the name of the assay) however in reality TAC cannot measure either the true or total antioxidant capacity at all! Some (certainly not all) of the problems with this assay are:

  1. It is non-physiological. The test involves creating an artificial reaction out of the body and is thus influenced heavily by atmospheric oxygen.
  2. The test involves using a radical to generate a reaction and then measuring the defence capability of the blood. However, protection from one radical does not mean protection against another radical and the body sees many differing radicals constantly.
  3. Exercise increases urate (elevated purine metabolism) which is one of the main things TAC is measuring. So this gives an artificial post exercise value.
  4. The assay mainly measures small molecule antioxidant compounds (e.g. vitamin C) rather than antioxidant enzymes, whereas the majority of radical scavenging in vivo is by antioxidant enzymes.

The very best specialist free radical journals such as ‘Free Radical Biology and Medicine’ and ‘Free Radical Research’, will not publish articles that use TAC as an assay. Surely as sports scientists this tells us something that by using such assays all we are doing is confusing an already confused field.

There are other equally poor measures (such as TBARS) but I will not get into all of them in this short blog. What I will say is that there is no assay available to date that is useful in an applied exercise setting that can have any practical implications for athletes. So, for now, let the researchers try to develop better assays (if this is at all possible) but please do not waste time and effort trying to measure these in exercising athletes and then use the data to inform practice. This will for sure do more harm than good.

Above – My PhD studies were largely focussed on measuring CK and blood markers of free radical production following muscle damaging exercise (the right side of this pic is an EPR spectroscopy used in this study). It was during this time that I quickly realised that 1. CK did not really correlate with anything (some of the subjects who could hardly walk had really low CK where some who were fine had values through the roof) and 2. Trying to measure something in blood than has a ½ life of between 0.000001 and 0.000000000001 seconds and relate this to what is happening in muscle is impossible! Especially when you expose it to atmospheric oxygen which will be far different to what it ever sees in the body.

 

Creatine Kinase – at best an “on/off” switch so why are we using it to quantify damage?

Accurate measurement of exercise-induced muscle damage is of considerable interest to the sport nutritionist (and the rest of the sport science support team for that matter). Quite simply, if someone had an accurate measure that could determine injury and readiness to train they would have found the sport nutrition equivalent of “Charlies Golden Ticket”. Unfortunately to date we have not got such an assay and therefore the search continues (actually we have some nice data on a IL, 6, 8 and 10 but this is very early data). And despite what some people may tell us, I can assure you CK is certainly not the ‘golden ticket’.

In my opinion, in both sport science research and applied practice, the main reason we measure CK is that “we have nothing better”. But is this really a good enough reason to use it? It also fits into the category of looking ‘sciencey’ and thus being an easy sell to the gaffer – but if we look at what it can and can’t do it really does not make any sense to waste our money and time measuring it.

The release of CK from skeletal muscle does reflect some degree of structural damage to the muscle, however we have known for many years (Friden and Lieber, 2001) that CK is actually a very poor predictor of the extent of muscle damage and/or loss of muscle function. We can make an argument that a raised CK suggests there has been some damage but what we cannot say is that the greater the CK value the greater the damage. However, I am very aware that this is precisely how teams are using it. Teams even use CK to make sure that the session was tough enough!! Friden and Lieber, 2001 described the use of CK as a binary measure – i.e. there is or there is not damage. I could tell you after a rugby game there will be some damage without having to bleed the players, (and even after a football game due to the many eccentric contractions), so as far as I can see there really is no case to measure this post game.

Why is CK such a poor marker? Actually, there are many reasons:

  1. There are many injured fibers that show structural abnormalities which do not necessarily contribute to the CK pool we measure.
  2. Measurement of CK will be temporal and could indicate appearance as well as clearance.
  3. Studies have shown substantial variation between research subjects following running exercise despite similar soreness and similar loss of MVC
  4. Histology studies do not support a relationship between damage and CK
  5. The time sequence of peak CK in blood and peak loss of muscle function are very different.

If we do rely on CK to quantify damage, we are in danger of reducing a training load when in fact there is no problem or the opposite, asking someone to train hard when in fact there is substantial soreness and damage. Given that we cannot have any trust in CK’s ability to quantify the extent of damage then does it have any place in the applied environment? For now, I would suggest that, at best, in research we could use CK to prove that a protocol was damaging but unless I am missing something I am not sure how in sport this is any better than the old fashioned techniques of asking the players how do they feel?

Above – a great paper well worth a read on CK and muscle function.

 

Above – Electron microscopy image showing undamaged muscle left and damaged muscle right. In the damaged muscle clearly see disruption, z line streaming etc however we know that the relationship between this and CK is very poor to say the least. If what we really want to know is “is my player ready to train today” surely simple assessments of soreness (0-10 scale) and/or accurate muscle function assessments are what we need? I would argue that CK is far less useful than any of these.

 

You have a food intolerance so change your diet – or do you?

One test that is gaining far too much momentum in professional sport over the last few years is the usage of IgG food allergy tests. This drives me insane. I actually think I need to write an entire blog on allergy tests but for now the simple take home message is that these DIY allergy test kits have no scientific credibility and should not be used to diagnose intolerances. It is, however, far too simple of a sell to the unaware athlete and as such they can get excellent buy in from players. Think of this scenario. “Hi player X, it’s actually not your fault that your body composition is not where it should be, you probably have some allergies, let me test them for you”. Immediately the player now has an excuse why they are not in the shape, they love you, and they want to commit to your way of helping them. In reality they are probably out of shape as they eat too much. You then perform an allergy test, which will invariably result in several “allergies”. Often this allergy involves gluten and/or dairy which when the athlete removes from the diet can result in weight loss (they have reduced their calorie intake). Suddenly, the entire squad now want an allergy test and before you know it they all have “allergies” that need careful handling. However in reality none of them actually have problems and it is the kit itself that has created the confusion.

Please don’t get me wrong, some people do have allergies and as a sport nutritionist, if we suspect this we must refer onto a specialist. The BDA have a great fact sheet on food allergies which covers some common tests used to correctly assess allergies and is well worth a read. The problem with the DIY home kit IgG tests is that they do not assess if there is a problem but rather, they simply measure a physiological response to the exposure to food.

But are there any downsides to wrongful diagnosis of allergies, i.e. does it matter if we tell someone they have an allergy even if they don’t if this results in some behaviour change and improvement in body composition? How can I word this simply: YES! Let me say it again in case you are getting bored now and skimming this. YES it does matter, it really does matter. There are many problems with this approach:

  1. The athletes could end up removing food groups from a diet (such as dairy) and do more harm than good if the key nutrients in this food group are not replaced.
  2. Some alternates are simply not as good as what we have removed (for example soya protein versus whey protein) and in thinking we are helping we are hindering the athlete. My first rule of practice is do no harm and this clearly breaks this one.
  3. People with genuine allergies need to be taken seriously. If we go around telling people we have slight allergies this may not be taken seriously and in the end restaurants, cafes etc could become lazy – this could be fatal for genuine sufferers.
  4. In a team environment, it can be easy to remove the “allergens” from the entire menu to make sure this allergen is not in the system and as such the rest of the team could suffer.
  5. These kits are not cheap and that money could be spent much wiser, for example improving the food provision for the team.
  6. It can create lots of confusion. I have heard of athletes who have been told they are “allergic” to milk but have drank it all their life. So now they have to either ignore their support staff or remove food that they have had great benefits from all their career. If we have symptom free athletes why are we looking for problems?

My ultimate advice on food allergies is to assess symptoms and use this to drive interventions rather than let a test dictate the problem. If you do have an athlete that you suspect has a problem – refer on. I’ve see good results from a low FODMAP approach on IBS symptoms so it’s a good idea when looking for someone to refer to check that they are FODMAP trained. But please remember that genuine allergies are a real problem and we must refer to someone fully trained in this.

In summary, it is crucial that as sport nutritionists we have a great “bull-shit” detector, not only when it comes to products/supplements that we are constantly asked to use with our athletes, but perhaps more importantly on the tests that have been used to validate such products. In this blog, I have picked 3 common tests but there are many more that require this level of scrutiny before we commit to using them. I encourage everyone to try and read the original research themselves rather than rely on 3rd hand information (often from a salesperson) and where possible speak to the world-experts in this field. I also encourage fellow sport scientists to engage with the parent discipline to ensure we maintain the scientific credibility of our field – I’m afraid at present we are in danger of losing credibility based on our reliance on poor techniques. With email and social media, it is no longer hard to ask the real experts and in doing so you may find that you end up measuring less which could ultimately improve performance far better than it would if you had used that expensive test. I often say to colleagues that we should “measure less and do more”. Let’s pick the measures that we are confident have some value and make sure that every single thing we measure has a plan of action that we can relate back to our athlete. After all, surely that’s why we are measuring things in the first place?

 Sorry, this was meant to be a short one but once again I got carried away. Promise blog 6 will be a lot shorter!!

Until the next Close Encounter of the Nutritional Kind

 Take care,

 Graeme

 

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