Holford Watch: Patrick Holford, nutritionism and bad science

Today, the ASA have ruled against Health Products for Life (HPFL): a supplement company that Professor Patrick Holford (Head of Science and Education at Biocare) sold to Biocare, and which has a website - and sells pills - with a picture of Holford’s face on. Holford is beginning to amass a collection of ASA rulings both for his own offerings and those for products that he endorses. (more…)

In the run-up to the new year, Prof Patrick Holford of Teesside University has been promoting his “9-Day Liver Detox”. More on that later, but I thought it would be nice to start with some holistic health advice - advice that treats the whole person, instead of just targeting particular symptoms or organs in isolation. As Andrew Wadge (the FSA’s chief scientist) notes on his blog, if you have overindulged over the holidays there are better options than ‘detox’ pills and diets:

First, drink a glass or two of water (tap is fine, cheaper and more sustainable than bottled); second, get a little exercise - maybe a walk in the park - and third, enjoy some nice home-cooked food. There’s a lot of nonsense talked about ‘detoxing’ and most people seem to forget that we are born with a built-in detox mechanism. It’s called the liver. So my advice would be to ditch the detox diets and supplements and buy yourself something nice with the money you’ve saved.

Sounds fair enough to me. But, then, Holford offers an ‘alternative’ approach (more…)

1A slight interruption to your usual service here, while Holford Watch participates in the Ann Walker blog festival. To cut a long story short, UCL was “recently contacted by Dr Alan Lakin on behalf of his wife, herbal medicine practitioner Dr Ann Walker, in relation to comments made about her, on a websitehosted by UCL, by Professor Colquhoun, a distinguished UCL pharmacologist”. In response to Lakin’s contact, UCL forced Colquhoun to move his excellent blog temporarily, though after legal advice was taken I’m pleased to say it should be reinstated at UCL pretty soon.

However, this shouldn’t be the end of the affair. As Ben Goldacre puts it:

There is a more serious issue in the background, however. It strikes me that there is a sizeable cohort of people who sell themselves and their wares by making scientific claims, but then use bullying and legal threats when their claims and ideas are criticised. This to me is completely unacceptable. I suspect that in the case of Dr Lakin and Dr Walker their efforts in this case may backfire, and a great deal more attention will now fall on their work…Are we about to see a festival of Ann Walker?

I certainly hope that we’re going to see a festival of Ann Walker - to defend the freedom of bloggers to write and to criticise. Already, the excellent Science Punk and Quackometer blogs have began to look at Walker’s work. My own modest contribution is below - hopefully, many more will follow. If you’re contributing to the festival, let me know (you can e-mail me through my blogger profile) and I’ll add a link to you here.

Writing on HealthSpan’s site (where ginkgo biloba pills are sold) Ann Walker argues that

More evidence exists for the beneficial effect of ginkgo on mental function than for any herb for any body condition. Indeed, ginkgo is the most well-established herbal treatment for Alzheimer’s disease….The number of double-blind, placebo-controlled human studies on the effects of ginkgo on mental health now exceed 50. The authors of the influential Cochrane review (2002), while calling for further studies, added: ‘Overall there is promising evidence of improvement in cognition and function associated with it’.

These are bold claims. Holford, similarly, argues that ginkgo is a “proven brain booster…A review of all the studies up to 2002 concluded that there is ‘promising evidence of improvement in cognition and function with ginkgo’”*. Unfortunately, their interpretation of the evidence is somewhat selective.

Walker has, on occasion, spoken for HSIS (an “educational” body funded by The Boots Company PLC, Bayer PLC, Perrigo, Seven Seas Ltd and Wyeth Consumer Healthcare), and been very critical of some studies that have argued against the benefits of supplement pills. For example, responding to a high quality JAMA meta-analysis of antioxidant supplements (which found that some actually increase mortality) Walker argues that “The results of these mixed-sample metaanalyses are worthless”. Clearly, then, one would expect Walker to demand a high standard of evidence before recommending any pills.

As noted above, Walker and Holford both sing the praises of Gingko, quoting part of the conclusion of a Cochrane meta-analysis to do so. However, it’s worth quoting the conclusion of this meta-analysis at more length, to get a fuller picture of the evidence:

Many of the early trials used unsatisfactory methods, were small, and we cannot exclude publication bias. Overall there is promising evidence of improvement in cognition and function associated with Ginkgo. However, the three more modern trials show inconsistent results. Our view is that there is need for a large trial using modern methodology and permitting an intention-to-treat analysis to provide robust estimates of the size and mechanism of any treatment effects.

This sounds a lot less positive than Holford’s and Walker’s summary of the review. In effect, this review concludes that - while further trials would be useful - the current evidence base for the use of ginkgo to treat cognitive decline is poor. Therefore, Walker not only uses a meta-analysis here (having been so critical of the JAMA meta-analysis) but Holford and Walker’s interpretation of the meta-analysis is very problematic.

To make matters worse, a February 2007 Cochrane Review of the evidence re. ginkgo and cognitive impairment found that

There is no convincing evidence that Ginkgo biloba is efficacious for dementia and cognitive impairment. Many of the early trials used unsatisfactory methods, were small, and publication bias cannot be excluded. Overall, evidence that Ginkgo has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unconvincing. Two of the best most recent trials, which are also among the largest trials, found no difference between placebo and Ginkgo.

To be blunt, it looks like the trials on ginkgo that Walker so welcomed have been useful - and showed that it doesn’t help with cognitive impairment. The above quotes from Walker come from a 2004 article. However, given Walker’s obvious concern with the way that scientific articles - such as the JAMA review of antioxidant supplements - can mislead the public, it’s a shame that she hasn’t managed update her HealthSpan article in the light of the new evidence (Walker has posted two new articles February 2007).

Likewise, Holford’s book may have been in press before the newer Cochrane review came out. However, one would hope that future editions will be revised to take this into account. Moreover, given that Holford is keen that people do not waste money on supplements, one would hope that he will add an appropriate warning to the ginkgo pills sold by Health Products for Life - to make sure that customers don’t waste money by buying this as a treatment for cognitive decline.

*New Optimum Nutrition for the Mind (Piatkus, 2007 Edition), p395.

Just a quick post to note that, after Holford Watch advice, Health Products for Life have added a warning to the description of their folic acid pills. The new warning reads that “Folic Acid is recommended to be taken alongside a B complex or multivitamin providing 10mcg or more of B12. This is because folic acid can mask the symptonms [sic] of B12 deficiency. The elderly may need more than this level - best determined by a homocysteine or B12 blood test.”

While I still have a number of concerns about Health Products for Life, clearly this additional warning is something to welcome. I’m grateful to Patrick Holford for putting this warning in place.

Holford has e-mailed me about folic acid fortification - objecting to some of the content of this post - and I’d therefore like to explain my position in more detail. I’m grateful to Holford for raising some interesting points, and will take this opportunity to respond to a few of them:

• Holford argues that problems are “already occurring in the US where flour is fortified with folate at half the level proposed for the UK”. This is, technically, correct - the FSA plans to fortify UK bread flour with higher levels of folic acid than is mandatory in the US. However, the FDA insists that a wider range of US staple foods (e.g. rice and grits) are also fortified - meaning that the average folic acid intake in the US increased by 215-240mcg/day following mandatory fortification. It is estimated that fortifying UK bread flour as planned by the FSA will lead to the average folic acid intake by c. 78mcg/day [PDF file, p.7]*.
• Holford argues that there is “no reason for us not to expect [similar problems] in Britain”. However, given that the FSA’s plans will increase UK folic acid consumption by just over 1/3 of what was achieved by compulsory fortification in the US, there is a very good reason to expect that any problems will be less pronounced.
• Holford argues that “[t]he real issue we have to deal with is how to educate and nourish young women.” Certainly, this is important - there have been problems getting across the message that women who are (trying to become) pregnant should generally supplement with folic acid. However, I’m sure that Holford would agree that good nutrition is important for other groups, too. I’d also argue that folate consumption is valuable for the general population, as it may be linked to a reduced risk of cardiovascular disease and cancer (and a good folate intake is definitely important for older women with higher-risk pregnancies). While greens do not oxygenate your blood, the fact that some are a good source of folate is therefore another good reason to eat your greens.
  Holford states that “I do not recommend and continue to be opposed to folate supplementation on its own to any individual or group at risk of B12 deficiency”. I’m glad to hear this - it seems a pretty sensible position on folate supplementation. I would, however, suggest that Holford makes the risks of this clear on his website and web-store: I have e-mailed him to advise that he does so.
• Holford argues that I mis-represent Morris et al’s AJCN paper. I fail to see how this is the case: I note, pretty uncontroversially I would think, that the paper finds that “high folic acid intake combined with inadequate B12 intake is related to cognitive impairment in older people”. To be very precise, the Morris et al paper concludes that “In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment.” All the evidence suggests that eating more folate will - at least to a point - increase your serum folate level. An increase of c. 78mcg/day in folic acid consumption (caused by fortification) will not, in itself, lead to high folic acid consumption and will not in itself lead to high serum folate levels. My argument that “it is very unlikely the modest supplementation supported by the FSA is going to be a significant problem in itself” is therefore correct, and is also perfectly compatible with a reasonable interpretation of the Morris et all paper.
• Holford argues that the problems caused by high folic acid consumption have “nothing to do with the source of folate, whether from diet, fortification or supplements, but to blood levels”. I’d note that the Morris et al paper focused on blood levels of folate - and was therefore only likely to show those risks/benefits associated with different blood levels. I’d acknowledge that there are certain risks associated with high serum folate levels - whatever way these are achieved. However, supplement use can play a very significant part in high folate intake levels: for example, Mulligan et al’s recent article has found (albeit in a relatively small sample) that 94% of the over-60s in their sample group with high folate intake used supplements. There’s an obvious link between eating lots of folate and high serum folate levels - supplements provide an easy means of eating lots of folate.

There are a few more issues around this which I might go into later - but this post is already a bit too long. At any rate, I hope it’s clear from the above why I would stand by my criticisms of the Guardian article on folate fortification. As John Nichols of the Royal College of General Practitioners puts it, I would acknowledge that “[t]here may be a case to be made against folic-acid fortification of bread and flour, but the stream of misinformation in [the Guardian] article is not it”.

* I haven’t had time to check these figures, but they seem about right and the FSA is clearly a reliable source.

11Joanna Blythman was writing in Friday’s Guardian, discussing concerns about plans FDA to fortify UK bread with folic acid11. Discussing it badly. Really, really badly. And - to add to the excitement - using Patrick Holford as a source. I’m going to look at the article - and Holford’s contribution here.

I thought the article was so bad that I wrote a letter to the Guardian criticising it. And - credit where credit’s due - the Guardian has published the letter today. Read my letter here22 (along with an excellent letter from John Nichols of the Royal College of General Practitioners).

Naturally, I’m grateful that the Guardian published the letter - but there are more problems with the article than I could fit into a single letter to the paper (and - while whoever was editing the letter did a good job on it - they did edit out a little of what I had to say). I’ve also been in touch with Holford since the publication of the article (and since after I wrote the letter) and he’s kindly clarified a few of his points. I’m therefore going to use this post to outline some of the problems with Holford’s position, and to go into more detail about some of the points raised in my letter.

Firstly, if the Guardian wants to run an article on adding ‘chemicals’ to our food, it might help if they made sure that their writers know what a ‘chemical’ is. The article certainly appears confused about this (rather central) point: for example, Blythman refers to adding the “controversial chemical” flouride to our water supply.

My God! Chemicals in water! Next you’ll be telling me that there’s hydrogen in there, or even - shudder - dihydrogen monoxide33. One would hope that someone writing for The Guardian would know that water is a chemical (H2O) and that without access to such chemicals we would all die pretty quickly. We need chemicals all the time, not just daily.

Looking for a good source to quote on folic acid and fortification, Blythman chose to quote Holford - listing him as a “nutritionist”. I know Holford doesn’t have any accredited university degrees in nutrition - but ‘nutritionist’ isn’t a accredited title (I could quite legally market the duck in my local park as a ‘nutritionist’) so I’ll let that pass. However, Holford does have a number of competing interests in this area and it would have been appropriate to at least mention this - so that readers could take this into account when judging Holford’s statements. Especially given that Blythman has written at length44 about the distorting effects of the commercial interests of the supermarkets, it’s surprising that she doesn’t think that Holford’s commercial interests are worth mentioning.

Of course, if Holford’s science was sound then his commercial interests wouldn’t be so…well…interesting. However, I’ve got real problems with his arguments - problems which are exacerbated by the fact the Holford’s Health Products for Life makes money from selling folic acid supplements.

In the article, Holford argues that “We already know that folic acid, given without B12, is creating problems for the elderly…And that’s at half the amount that the FSA is proposing to add to British flour.” However, the FSA is proposing55 [PDF file; see p7] to add folic acid to our flour at pretty low levels: 300mcg/100g of flour; after the cooking of bread is taken into account, this “will increase the average folic acid intake of the population by about 78[mcg/day]“.

A high folic acid intake can mask the symptoms of B12 deficiency - something which, as Holford is right to note, is a particular problem for older people. However, the Scientific Advisory Committee on Nutrition has found that66 [PDF file; see p.53] “folic acid intakes up to 1mg/day are not associated with delayed diagnosis of vitamin B12 deficiency in older people.” The American Journal of Clinical Nutrition has found77 that high folic acid intake combined with inadequate B12 intake is related to cognitive impairment in older people (although good folic acid intake, alongside good B12 intake, brings cognitive benefits). However, although David Smith (writing in the same journal) urges caution88, it is very unlikely the modest supplementation supported by the FSA is going to be a significant problem in itself.

This is where Holford’s commercial interests become interesting. The SACN report99 argues that, at current levels of consumption, fortification of bread will increase “the number of people aged 65 years and over with low vitamin B12 status consuming more than 1mg/day of folic acid.” Supplement pills will play a key role here - anyone who wanted to shovel down enough (unfortified) food to eat 1mg of folic acid every day would need the constitution of an ox and a freakish love of spinach. An obvious way to avoid this risk is therefore for people to take fewer supplements. One likely consequence of the move to fortify bread flour is thus more prominent warnings about the need to avoid over-supplementation.

Holford’s Health Products for Life sells1010 folic acid pills (without B12). Holford advises that some people seeking to reduce their risk of Alzheimer’s should supplement with 2mg of folic acid per day1111. This is despite the fact that the Expert Group on Vitamins and Minerals has set1212 [PDF file] a safe Upper Limit (UL) for folic acid supplementation of 1mg/day (though a few groups - e.g. women with high risk pregnancies - may be advised to take more). 2mg/day is, however, not advisable for most of us.

So - Holford is quoted in a Guardian article emphasising the dangers of bread fortification (which could have a negative impact on Health Products for Life sales) but not even mentioning the much more significant risks from folic acid supplementation (Holford has a commercial interest in selling folic acid). Of course, one can’t know why Holford gives the advice he does - and had he given a balanced assessment of the evidence, I would not even need to be asking about him making money from pill sales. However, the rather skewed advice he was quoted giving does appear to serve his commercial interests surprisingly well - and I would therefore argue that the Guardian article should have made his commercial interests clear, in order to allow readers to decide for themselves whether they are relevant.

A note on measurement
1g = 1000 mg (milligrams) = 1,000,000 mcg (micrograms)

Ben Goldacre’s Bad Science column today offers a biting critique of the ’science’ behind the QLink pendants advertised in Holford’s Health Products for Life catalogue. The QLink is sold as protecting against EMR - if you’re worried about EMR, read what Le Canard Noir has to say about it. Focusing on the QLink, though, Goldacre finds that they don’t do anything useful: they don’t emit any interesting ‘frequencies’, and they contain a “coil connected to nothing. And a zero-ohm resistor, which costs half a penny, and is connected to nothing.” This was advertised for £69.99; well, some people think they look nice…

On top of advertising QLink in the Health Products for Life catalogue, Holford gives a glowing testimonial [1] for the pendant:

There are many gadgets out there promising to protect you from electromagnetic radiation and give your energy a boost. I’ve investigated many and didn’t find any stacked up. The one exception is QLink. The scientific proof is deeply impressive.

OK, so Holford finds the ’scientific proof’ that a ‘coil connected to nothing…And a zero-ohm resistor” can boost energy and protect against EMR ‘deeply impressive’. Oh well. What I’ve quoted above might be embarrassing - but the testimonial from Holford gets more toe-curling as it goes on:

After researching all the products available that claim to combat EMR, I’ve finally found one where the science stacks up: QLink. This revolutionary pendant provides continuous support against EMR via a microchip which resonates at the same frequencies as the body’s own energetic field. This so-called Sympathetic Resonance Technology works along the same principles as acupuncture – but
without the needles!

Firstly, Goldacre found that the QLink does not contain a microchip. Apparently, finding “deeply impressive…scientific proof” for a product’s efficacy doesn’t include making that the product contains what you say it does. And I’m not sure how having a copper coil and disconnected 0ohm resistor hanging from your neck works on the same principle as having needles stuck in you during a course of acupuncture. I’d like to know, though! - I’m due to give blood sometime soon, and strapping a copper coil to my wrist sounds much more fun than having a needle inserted in to drain the blood out [2].

Anyway, I really ought to think of a witty way to end this post, but I don’t think I can be bothered. It’s late, and I’m knackered; now if only I could find something to resonate sufficiently sympathetically…

[1] UPDATE: I’ve linked to the google cache of this page because, within minutes of me posting this, the original page was no longer available. Almost enough to make you paranoid…

[2] Seriously, though, if you haven’t given blood before, don’t let me whining about a little needle put you off. It really isn’t particularly painful, and I’m a wimp…

I’ve previously blogged about Holford’s rapid response on the BMJ website failing to declare his ‘competing interests’. David Colquhoun responds to Holford, arguing that Holford “[b]eing the sole shareholder in Health Products for Life might be thought of by the sceptical as constituting a rather large financial interest in promotion of nutritional supplements”.

Rather than apologising, though, Holford has submitted a second rapid response which argues that “I was pointing out that the scientific data for turmeric – found in curry - having a beneficial effect was substantial…Since I don’t run an Indian restaurant I didn’t feel there were any conflicts involved in recommending curry.”

Sounds fair enough. Well, it would be, except Holford’s HealthProductsForLife sells curcumin (turmeric extract) supplements. Holford’s initial rapid response stated that “1834 studies are cited in PubMed on turmeric or curcumin, thought to be the active ingredient in this spice, many of which demonstrate clear anti-inflammatory and immune enhancing properties, 648 of which relate specifically, and consistently, to it’s anti-cancer properties.” HealthProductsForLife therefore sells the product which Holford claims has been shown to have anti-inflammatory, immune-enhancing and anti-cancer properties’. Sounds like a competing interest to me.

One more thing to note - Holford also attacks Prof Colquhoun, arguing that Colquhoun “has so far not felt it relevant to mention his own competing interests and financial involvements with the pharmaceutical industry”. Now, this might lead one to believe that Colquhoun is hiding his interests in the evil pharmaceutical industry - in order to have a go at a poor nutritionist. However, Colquhoun didn’t declare any competing interests because, um, he doesn’t have any (unlike Holford). Colquhoun’s “research has never been funded by the drug industry, but always by the Medical Research Council or by the Wellcome Trust“. Oops.