An imperfect (Q) ten

This has been another of those fortnights of “deja-vu all over again” (in baseball legend Yogi_Berra’s famous phrase), as the newspapers have been full of plugs for “Miracle Supplement” Coenzyme_Q10.

Boots are having a big marketing push for their latest formulation of CoQ10, claiming that it will give you lots of energy, and even offering “your money back if not satisfied” (Boots apparently have confidence in the power of wishful thinking and the placebo effect).

Boots’ press release and promo campaign seems to have generated the usual crop of dim features in the “Health and Beauty” or “Lifestyle” sections of several of the UK national papers. Most of these features, as both Ben Goldacre and David Colquhoun have deconstructed, revolve about deliberate overuse of that misunderstood word, and favourite Alt Health trope, “energy”.

[The mention of “Energy” is, of course, a surefire stand-by for a good dose of health page waffle. The very word drips waffle, and probably scores you a Canard or two on the Quackometer. Wikipedia lists a bunch of usages for “energy”. It is no accident that half of them relate to favourite Alt Health Woo-themes like “spirituality”.]

If you are especially unlucky, your newspaper may have leavened the energy-waffle with what we call a “Media doc filler”, or “MDF” for short. For those that are unfamiliar with this genre of newspaper space-filling, an MDF often accompanies a feature on a new supplement , or heavily marketed medicine, and goes something like this:

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NanoNutri LipoBalls – A Doctor Writes:

“As a national newspaper doctor I am frequently asked by the nice chaps and chap-ettes on the “Nutrition and Health“ pages: “can we have a quick 300 words to pad out this press release – sorry, story – about some expensive supplement?”

My answer is always “Only if it will help tackle my low financial energy levels, sunshine”. And aren’t low energy levels something we all increasingly suffer from in today’s non-stop energy-sapping 24-hr world?

It is amazing these days how often my patients seem to wish they had more energy.

I don’t know how many times I have heard a patient say to me “I feel worn out, doctor”. To which I usually respond: “That sounds very much like what we doctors call an “Energy Deficiency” – fifty pounds, thank you, pay the receptionist on your way out. Next!”

Twenty thousand or so years ago, a quick sabre-toothed tiger hunt would have left primitive man with a huge appetite, but after a haunch of roast mammoth and 12 hrs solid sleep he would have been ready for anything. However, nowadays we work so much we hardly have time to eat, or to sleep more than five hrs a night – and when we do eat it’s more likely to be a hurried prawn sandwich than mammoth supreme.

Faced with that, who couldn’t do with a bit of a pick-me-up? And new NanoNutri LipoBalls® are formulated with EnergyNano’s patented Fast Liposome Intra-Mitochondrial Formula Liquid-energy AntioxidantMax technology, or “FLIM-FLAM” for short, to get extra-fast to the parts other Energy supplements cannot reach.

So how were the results? Well, within a few days of first encountering NanoNutri LipoBalls®, things were certainly looking up. Having banked a pleasingly large cheque, I found that my energy levels had been dramatically improved. A spring had returned to my step, a twinkle to my eye, and a satisfying bulge to my wallet.

(Is that enough?)

A Doctor”

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Now, while I may have been mysteriously “channeling” Private Eye’s fictional Dr Utterfraud here, I am not exaggerating by all that much. If you don’t believe me, read this.

Where does all this hype come from? Well, you can find plenty about CoQ10 and what it does on Wikipedia, but a brief summary would be that it is a chemical substance that is important for how your mitochondria work. Mitochondria are your cells’ “powerhouses”, converting chemical energy (substrates, a posh biochemical word for “fuel substances”) into carbon dioxide and water, with the concomitant production of the cell’s “energy currency” molecule ATP.

 

Here you see the beauty of the CoQ10 sales spin. The description above mentions energy – here in its scientific sense. So voila – mention that CoQ10 helps produce “energy” and it is an instant sell. Everyone would like to have more “energy” (in its non-scientific sense of “get up and go”, the sort that parents wonder at in their small children while bemoaning that they don’t have themselves).

All you have to do is plant in peoples’ minds the two ideas that:

 

1. CoQ10 has something to do with energy (true)

2. Energy (scientific sense) = energy (vernacular sense) (false)

 

and the result is Ker-chinggg – cash registers jingle.

Now, an interesting aspect of the current “Q10 buzz” is that CoQ10 was discovered fifty years ago. It is not new. And it has been around, as a supplement, for at least 15 and probably closer to 25 years. Very “Not new”, in fact. And it has been tried as a therapy or “performance enhancer” in all sorts of studies – on various diseases, from receding gums to cardiovascular problems to Alzheimer’s, on exercise tolerance and performance etc etc.

So what were the results of these studies? Did they show Q10 was the miracle supplement the current crop of stories seem to be claiming?

The answer is “No”. The studies are inconsistent, with the usual problem of small sample size and lack of “blinding”. But the scientific / medical consensus, which you can find a good summary of here, is that there is basically no indication to take CoQ10 even if you are ill, let alone if you are well.

This is actually an object lesson in the different kinds of evidence that one can have for therapies, including pills, and why some types of evidence are more reliable than others. The “hierarcy” of evidence often used nowadays to decide if treatments can be viewed as actually working (and hence can be recommended for widespread adoption as part of medicine), is shown below. This hierarchy allots higher “levels” (essentially “greater reliability”) of evidence to randomized controlled trials (RCTs), and the highest level of all to “Systematic review (with homogeneity) of RCTs”. This last means when you look systematically at all the RCTs together, if you find that the treatment is consistently coming out as effective then it is a very good bet that it really works.

Various other kinds of studies are less convincing than this – a single, but good trial scores grade 1b, a not-so-well-done RCT scores grade 2b.

Figure: Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2001)

(via Dr Kimball Attwood’s wonderful post on evidence based medicine and Alternative medicine here)

Level	Therapy/Prevention, Aetiology/Harm
1a	Systematic Review (with homogeneity*) of RCTs
1b	Individual RCT (with narrow Confidence Interval‡)
1c	All or none§
2a	SR (with homogeneity*) of cohort studies
2b	Individual cohort study (including low quality RCT; e.g., <80% follow-up)
2c	“Outcomes” Research; Ecological studies
3a	SR (with homogeneity*) of case-control studies
3b	Individual Case-Control Study
4	Case-series (and poor quality cohort and case-control studies§§)
5	Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”

Studies which have designs OTHER than a randomized controlled trial score lower. In particular, studies whose design means they tend to be relatively UNreliable (often because they are contaminated by ”expectancy_effects”, by selection_bias relating to the participants, or by regression_toward_the_mean) are down in grade 4. Here the way the trials is done is often “give people the pill, with no control group and no placebo, and then ask if they think taking it made them feel better”.

The similarity between this last one and a “money back guarantee” if you didn’t think Q10 supplements gave you more energy is not a coincidence.

Finally, the idea that “because this works in a dish it will work in people”, much used to plug Alternative medicines, is down at grade 5, as is another familiar one, “this works because this or that expert guru says it does, regardless of the lack of any critical appraisal of the evidence to back it up”.

The talking-up of CoQ10 in leaflets, and on websites, and now in the papers, is mostly a fancy example of the “because it works in a dish” (level 5) argument down at the bottom of the pile. And most of the existing CoQ10 trials in humans, which some of the stories refer to en passant, are down at grade 4. Reviews of the trial evidence on CoQ10 tend to be (at best) in grade 3a, since the trials usually lack “homogeneity” (i.e. the results are inconsistent).

The upshot is that Q10 would not get licenced for use as a medicine in any common condition, because the evidence that it produces benefits simply is not good enough. The only exceptions, thus far, are very rare, mostly genetic, and specifically mitochondrial diseases.

 

Repeat: For all the other stuff, the evidence simply is not there.

Incidentally, this is true even if you take something where there seems to be a really appealingly plausible scientific rationale for using CoQ10 (grade 5). The best-known example is probably in people taking statins. Your cells make their own CoQ10 – another reason why the need for supplements is very dubious – and the biosynthetic pathway leading to CoQ10 is “shared” (part of it) with cholesterol biosynthesis. Hence the common website claim that if you are taking cholesterol-lowering statins (which partially inhibit a key enzyme in the pathway) then you “need” to supplement your CoQ10.

Sounds plausible. However, it turns out that the trial evidence is not running in favour of CoQ10 supplementation even when people are taking statins, and even in the subgroup of people on statins who have symptoms suggestive of statin side effects (Coracle has written about this at length). So if CoQ10 were to be marketed as a medicine for this statin setting there would not be nearly enough evidence to approve it. This points up – again – the difference between the efficacy standards required for drugs (there are some) and supplements (there aren’t any).

Of course, if there isn’t convincing evidence that CoQ10 makes a difference even in a situation where using it might seem biochemically highly “plausible”, you can bet your mortgage there is bugger all reason for normal people to take it on the off chance that it will do something. Apart from making the supplement peddlers considerably richer,

But…. To keep repeating the obvious, you don’t need any evidence to market a supplement. You only need to show that it doesn’t seem to be toxic.

 

Plus ca change, plus c’est la meme chose

Getting back to “déjà vu all over again”, the CoQ10 thing prompted me to have a dig through my own files. Back in the mid 1990s – about 1995 or 96, I think – I remember seeing a big display of CoQ10 pills in Boots. (Yes, amazingly they already sold them back then). As a ”recovering Biochemist”, this piqued my interest, so a year or two later I started setting medical student dissertation topics (i.e. reviews of the scientific literature) about supplements and alternative remedies.

Which leads me to this: lurking in my files is a dissertation a first year medical student wrote for me back in 1999 (sic) on:

 

“Coenzyme Q10: snake oil or medicine?”

[The student would have graduated in 2003 and is now, I guess, a junior doctor]

A couple of sample quotations:

”While some adverts for CoQ10 make use of anecdotal evidence from individuals testifying to “the miracle of Q10”, others make weightier-sounding allusions to scientific studies. But to what extent are claims made by the supplement industry upheld by scientific studies?”

A question Dr Thomas Stuttaford, Boots, and various health page journalists appear to have forgotten how to formulate. The answer, as we have already seen above, is “Not very much, if at all”.

Another bit from the student’s work discussing the “lifestyle-enhancing” claims for Q10:

”…What constitutes “normal” levels [of CoQ10] is of course open to debate. While no frank CoQ10 deficiency has yet been described, Folkers claims that suboptimal levels of CoQ10 are universal. There is, however, little current evidence to suggest that CoQ10 supplementation benefits the healthy individual.

Despite this, many people do take CoQ10, seemingly unconcerned about the lack of scientific evidence to support the anti-ageing, energy-boosting, flab-fighting, brain-stimulating and sex-life enhancing claims the adverts boast.

Adverts on the Internet may allude to scientific studies but generally fail to provide references and information is sometimes presented in a misleading way. They generally use a didactic tone and sometimes warp information to [persuade people] to buy their product, as demonstrated by the following advert:

”The body’s levels of CoQ10 decline with age; therefore it is necessary to supplement the diet. Food does not contain significant amounts of CoQ10 and the body des not produce enough CoQ10 on its own, so supplementation is imperative in order to have adequate amounts of it” (Emphasis added).

[Furthermore], findings of low levels of CoQ10 in disease states do not necessarily imply that low levels will lead to these diseases, as some adverts claim.

All [this] renders consumers vulnerable, all the more worrying since direct-to-consumer advertising of [nutriceutical] products is now big business. …”

 

Hmmm. Now, it is fair to say this was a bright student, even by the normal bright standards of first year medics. But… armed with essentially A level-plus-a-bit scientific knowledge, a first-rate brain, and a questioning mindset, s/he could see through the claims of the supplement peddlers. So one might expect that Boots’ “panel of experts”, Ann Walker PhD, and even Dr Stuttaford ought to be able to take a slightly more balanced view.

 

…If they wanted to.

And there’s the catch.

If they wanted to.

 

Boots, remember, are trying to sell you something. So is Ann Walker. Why should a seller tell the truth if spin sells better? And Dr Stuttaford is making a living cranking out re-worded press release bumpf.

Plus – there is nothing to stop them. Provided they avoid making directly and demonstrably false claims – as opposed to writing ambiguous things that will merely encourage readers to draw obvious but erroneous conclusions – they can say what they like.

As ever, caveat emptor. And that means you.

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