Monday, 20 July 2015

Wheatgrass juice, Channel 4, and blood oxygen – the data says no!

I just did a piece for Channel 4 on their superfoods program (http://www.channel4.com/programmes/superfoods-the-real-story). It was looking into the claim that wheatgrass juice improved blood oxygen content; allegedly this works by increasing the amount of haemoglobin as haem and chlorophyll look so similar. My incredulity contrasted with the health food expert who supplied the wheatgrass enema to the presenter. The expert said there was a lot of scientific evidence that supported her view. There was not time in the program to give the full account for the reasons for my incredulity so I thought it worth expanding a bit here in case anyone is interested.
·      Haem is an iron porphyrin and chlorophyll is a magnesium chlorin. Superficially haem and chlorophyll appear similar in chemical structure – one of the ideas that led to Charles Schnabel in the 1930s suggesting wheatgrass could be a superfood. Proponents today suggest it can increase the amount of haemoglobin in the blood. However, in the 1930s the structure of proteins was not known. Not only does chlorophyll contain magnesium rather than iron at its centre, but it has a long organic side chain. Even if you could replace the magnesium with iron, you could not put the iron-chlorin into the haemoglobin structure. It just won’t fit.
·      So maybe the chlorophyll provides building blocks to help us make more haem? In this case wheatgrass juice might increase haemoglobin by an indirect mechanism? There are a number of problems with this idea. First there is no evidence that we absorb chlorophyll, whether taken orally or rectally. Even if we did absorb chlorophyll, we cannot convert a chlorin into a haem. The pathways are linked metabolically; plants make haem and chlorophyll from the same organic starting materials. But we have don’t have the enzymes to make this conversion. 
·      In contrast to chlorophyll, we do absorb haem quite efficiently. But we immediately break it down for its iron content, throwing away the porphyrin cofactor. The result. If you want dietary iron, eat black pudding not wheatgrass juice.
·      Still maybe there is an unknown mechanism for the wheatgrass effect? Is there any science that supports the effect of wheatgrass juice increasing blood oxygen content? If there was good human trial data then we could search for a mechanism. After all gut bacteria are increasingly seen as important to health. Maybe feeding our gut chlorophyll has an effect on the body, even if none of that chlorophyll is absorbed? The problem is that there is no good scientific evidence in human studies of any blood oxygen, health benefit or sports performance effects. I looked hard and could find only a very few papers.  The first [1] is full of flaws and, as far as I can see not peer reviewed. However, let’s assume the study was well conducted. The effects observed (0.26% increase in arterial blood oxygen saturation) would have no significant physiological benefit; indeed there was no performance boost reported in this paper.
·      If wheatgrass juice really did increase the number of red blood cells it would be a godsend for many patients who have anaemia. Who needs epo or blood transfusions if you can just eat crushed grass? Two papers looked at this effect. The first, a small pilot study [2], suggested that consuming about 100 mL of wheat grass juice daily could reduce the need for blood transfusions in patients with thalassemia major. However, a later, larger study contradicted this [3]. Neither study was randomised or blinded.
·      Lest I be accused of being a complete cynic there is one study published that holds some promise. In a small double blinded, placebo controlled trial in ulcerative colitis (inflammatory bowel disease), wwheatgrass seemed to have some beneficial effects [4]. This study was conducted in 2002 and, as far as I can tell, has not been followed up. But at least it has the benefit of not straining credulity – the chlorophyll is suggesting to act where we know it goes – the gut.
In short wheatgrass juice is no superfood. At least not when it comes to increasing the number of red blood cells. There is no reason for WADA to put it on the sporting banned list or develop chlorophyll anti-doping tests.



Epo and doping accusations in the Tour de France – the numbers never lie (or do they?)


I was struck by the vehemance of the current anti-Froome accusations. So I thought I would add my tuppence worth to this story. First let me nail my colours to the mast. I have a lot of sympathy with Sir Dave Brailsford when he says “"It is not possible to prove a negative. I can't," [1]. 
Sir Dave is referring to the well-known fallacy in formal logic known as an argumentum ad ignorantiam or “appeal to ignorance”. This poses that “something is true only because it has not been proved false, or that something is false only because it has not been proved true”.
Now there are some cases where versions of this argument are used by philosophers (inductive logic relies on it in part). Indeed you cannot prove any future event true or false until it has happened. Prehistoric man with no knowledge of physics or astronomy had no definite “proof” that the sun would rise tomorrow or that walking off a cliff would result in a fatal fall. However, enough evidence had accumulated from previous life experiences to make these perfectly reasonable assumptions. Indeed it would be impossible for us to live our lives without making these kind of inductive “leaps of faith” every day.
Something ought to go without saying given the scientific literature, but clearly it needs repeating ad infinitum. Doping allegations based purely on performance (in this case speed or power data) fall well short of the strong evidence required for inductive reasoning. Power/time data alone can never prove someone is doping, or even make it probable. If you doubt this please take time to read carefully the recent article by Hein FM Lodewijkx “The Epo Fable in Professional Cycling: Facts, Fallacies and Fabrications” [2].
Not that the Lodewijkx review does not prove that epo does not improve performance; in fact it is careful not to say this.  Times have continually improved in the Tour and doping could be one of many factors that can affect racing times. The devil is in the scientific detail. But it does make salutary reading for people who assume that numbers alone are a reason for crying foul.
One thing that is needed is a proper randomized trail in elite cyclists testing whether epo doping “works”. Crucially, it should include accounting for the likely strong placebo effect (as everyone “knows” epo works – see my previous blog). The definitive study would include giving cyclists epo when they were told they were getting placebo. This kind of approach has been very successful in studies comparing drug and placebo effects on performance following caffeine administration [3]. However, significant ethical issues would need to be overcome before any epo study could start. Worse still cyclists would need to volunteer for a “ban” so it also need an end of career altruistic act.
If such a study were performed, my suspicion is that it would show that epo microdosing is no more effective than a strong placebo. I suspect blood transfusions or high dose epo would outperform placebo, but I doubt those more severe studies could be done. Still I don’t “know” these answers – as a scientist I just want the studies to be done (ethics permitting) to find out!