Lazy and irrelevant research used to smear vitamins as dangerous. Not again!

By Jerome Burne

Yet another round of media stories this week picking up on an “expert’s” claim that vitamins are ineffective and dangerous. They are the medical equivalent of blaming immigrants or single mothers for various social ills; scare stories that spin the data and draw totally unjustified conclusions.

The Guardian version opened with this claim: ‘… over-the-counter multivitamins do “more harm than good” and can increase the risk of developing cancer and heart disease ’ and went on to say that a study reviewing trials involving thousands of patients showed that those taking extra vitamins and minerals ‘were more likely to have health problems.’

A little bit of digging revealed just how misleading that opening was. There was no information about a new trial. What had happened was that a researcher from Colorado University had given a talk at a cancer conference over the weekend which quoted the results of three trials, one dating back to 1996. Each had involved giving a larger than usual amount of a single vitamin to patients in clinical trials.

Political point scoring rather than science

So this had nothing to say about “over-the-counter multivitamins”, because by definition you can’t take a larger amount of a single vitamin by using a multi-vitamin. It also came from Professor Tim Byers, a man who has made a career out of attacking vitamins for prevention. In a paper published in 2010, for example, (Am J Epidemiol. 2010 July 1; 172(1): 1–3) he made exactly the same point: ‘We now know that taking vitamins in supernutritional doses can cause serious harm’.

This is a typical example of the broad-brush statements that are dotted through supplement attacks. There are of course example of high doses causing harm but there are also examples of benefit such as very high doses of B-vitamins reducing brain shrinkage is patients starting to develop cognitive problems or high supplement of vitamin D in cases of serious deficiency.

That’s why the attacks by Byers and others belong in the realm of political point scoring rather than being part of any genuine scientific attempt to assess the benefits and risks of vitamins. His professional field is cancer prevention yet he ignores the details of the research he relies on as well as research that doesn’t support his charge.

Gathering ammunition not scientific data

For example one of the studies he relied on involved giving a large amount of folic acid (1gram – five times the RDA) to patients, who had already had a precancerous polyp removed from their colon, to see if it could prevent more developing. It didn’t. Now that could be treated as useful information. If further trials support it that means advice should be given not to use folic acid to treat people with polyps. Instead he uses it as ammunition against supplements in general

In his talk he claims that ‘some people actually got more cancer while on the vitamins’ and then refers to this study. In fact if you look at the original study it says: ‘Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.’

So the study he relies on to show a cancer risk specifically says it doesn’t show a cancer risk. It’s true that there’s evidence linking folic acid with cancer – is it a risk here? Not according to a study in the Lancet in 2013 which looked at data on nearly 50,000 people and concluded: ‘Folic acid supplements are not linked to an increased cancer risk when taken for up to 5 years.’

Vitamin and risk of lung cancer

Professor Byers’ second exhibit is a trial that has long been used to claim that vitamins are dangerous, but it also tells you nothing about multi-vitamin risk and makes the cancer link look simple when it isn’t. This is what the Guardian said: ‘Taking more than the recommended dosage beta carotene was found to increase the risk of developing lung cancer and heart disease by up to 20%.

The original paper, published in 1996, was an attempt to see if beta-carotene together with a form of vitamin A could reduce the risk of developing lung cancer in long-term heavy smokers with significant lung damage. So not relevant to anyone taking over-the counter multi-vits. The dose used was certainly high -30mg beta carotene, when non-randomised trials have found benefit with 7-8 mg.

The headline ‘20% raised risk’ certainly sounds alarming but it’s misleading.

Buried in the body of the paper, but not mentioned in the abstract or, of course, in Byers’ talk, was this finding: the raised risk of cancer only occurred among those who continued to smoke [my italics]. If you gave up smoking and took the vitamin, your risk of cancer went down by 20%. So an equally valid take-away message from the study would be – don’t smoke and take very high doses of these vitamins.

A follow up study discovered something else important about the combination the vitamin treatment and a raised cancer risk. The conclusion read: ‘… excess risks of lung cancer were restricted primarily to females.’ Another bit of information that could either be used to condemn vitamins or could be seen as valuable information for anyone using vitamins in an informed way.

No cancer risk with the vitamin

Except that a study published only last week made the situation even more complicated. A 20 year study found that the higher your level of various forms of carotene in your blood (lycopene and a-carotene as well as beta-carotene) the lower your risk of breast cancer.  The conclusion read: ‘Woman with high plasma carotenoids were at reduced breast cancer risk particularly for more aggressive and ultimately fatal disease.’

So lots of questions and one message: don’t give women who smoke heavily very high doses of beta-carotene and a synthetic form of vitamin A.

The final paper Byers’ warning relies on, is a large lengthy study of 35,000 men at risk of prostate cancer that’s been running for nearly fifteen years. Called SELECT it’s designed to see if vitamin E and selenium, together or alone, can reduce their risk. By 2011 results showed that the vitamin E didn’t reduce risk but pushed it up by 17%.

So a slam dunk for vitamin dangers? Not necessarily. Again what are missing are various crucial details. One is that the study used synthetic vitamin E. While natural vitamin E comes in eight varieties, the synthetic version only has a single form (alpha-tocopherol). Worse, it blocks the others and no nutritionist would recommend it. More research last year (2014) made the situation a clearer but more complicated.

Avoid a selenium supplement if your levels are high

Older men taking either synthetic vitamin E on its own or selenium (also a synthetic version) on its own were found to double the risk of prostate cancer. Your risk from selenium supplement risk went up even further if you already had a high level of the mineral in your system before you started supplementing.

However the raised risk of taking Vitamin E only applied to those who had low levels of selenium at the start. People have quite high levels of selenium in the USA because food is fortified with it, unlike the UK.

So rather than the crude message – vitamin E causes cancer – the sensible take away messages from this mammoth study are: avoid synthetic vitamin E, take natural vitamin E at lower doses, but have your selenium level checked first and don’t take high doses of selenium if your levels are already high.

What’s causing supplement scaremongering?

Again a trial is being used to make a political medical point rather than to provide any accurate or useful information about vitamins. Anyone informed about vitamins knows they are neither ineffective nor dangerous used properly.

A competent practitioner would start by finding out what minerals and vitamins you were deficient in and what you were eating and how you were living and aim to bring them all into a healthy balanced state. That is the kind of approach that should be tested in trials run by knowledgeable researchers – not with trials that use large doses of synthetic vitamins without taking any notice of the needs of individual patients.

So what is driving this supplement scaremongering and why does one in three Britons take some form of dietary supplement?

The drug danger we all face

The two are almost certainly related. The same day as Byers’ warning was widely reported, another warning was issued and virtually ignored.  It came from the University of Dundee, which warned that the number of adults in a region of Scotland getting more than five drugs had doubled over the past fifteen years to 20% and that the number getting more than ten drugs had tripled to nearly 6%.

‘Drugs can significantly improve a range of health outcomes,’ says the lead researcher Professor Bruce Guthrie, of the University of Dundee, ‘but they can also cause considerable harm – approximately 6.5 per cent of all emergency hospital admissions are attributable to adverse drug events and at least half of these are judged preventable.’

Multiple drug use, known as polypharmacy, greatly increases your chance of having problems anyway but making things even worse are certain drugs that are known to have potentially serious interactions. Currently one in eight adults is on these drugs and among elderly people the situation is worse still. ‘In 2010 44% of people over 70 were prescribed drugs with potentially serious interactions,’ said Guthrie. The numbers have almost certainly gone up since then.

You could be on ten or more drugs by 70

Polypharmacy is the inevitable result of a system that relies almost exclusively on drugs to deal with the epidemic of chronic diseases we are facing and it is clearly far more dangerous than anything caused by vitamins.

However polypharmacy and its very real risks is looming for baby boomers; unsurprisingly many want a better way to maintain their health. What’s needed is a professional program of preventative medicine and supplements would play valuable part in that. However implementing it will require major changes in the way medicine is practised.

Such change in any profession is always vigorously resisted, sometimes with misleading use of data. The energy industry’s fight against the changes needed to deal with the challenges of global warming is one example.

Jerome Burne

Jerome Burne

Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “10 Secrets of Healthy Ageing” was written with nutritionist Patrick Holford. He blogs at “Body of Evidence” – jeromeburne.com. 2015: Finalist for 'Blogger of the Year' award from Medical Journalists' Association.

8 Comments

  • Scientists and mathematicians know very well that in linear systems it is impossible to maximize more than one variable at a time. It may be stretching the analogy a bit, but surely you cannot run a health system to maximize both patient health and drug firm profits? You can worship either God or Mammon – pick exactly one.

    • Editorial

      Don’t think it has to be either or. We already have lots of examples of public private partnerships of varying effectiveness – railways, prison service, roads and of course NHS. Problem is that when it comes to dealing with chronic diseases and keeping people healthy the public side is something of a sleeping partner.

      A vivid example of how disastrous and absurd relying solely on the profit motive to keep us healthy is the mess we are in with antibiotics. There are something like two in the pipeline because, despite rapidly rising resistance to a variety of front-line antibiotics, they are not profitable enough – they cure people quickly – for the companies to invest in producing them. On the other hand there are hundreds (I have no figures but it is a lot) of new cancer drugs coming along all costing a vast amount. That surely is not a sane allocation of resources. Disease prevention is a public good and we can make political decisions about its funding

  • Supplement scaremongering?

    I work as a GP and for the sake of balance have a few problems with supplements I’d like to share.

    I wonder if on finding say a deficiency of the vitamin folic acid its better to take this as a great opportunity to investigate a better overall diet for my patient rather than prescribe a supplement. After all if one vitamin is low it’s perhaps fair to assume that the dietary cause could encompass other, as yet undetected deficiencies that a better diet could remedy.
    If I prescribe one supplement some patients become understandably anxious about others; what about zinc, magnesium or selenium?? Starting a ghastly fandango of tests, long waits for results and then they begin to wonder ‘did we test for Iodine?’
    As part of the anxiety about ‘the best supplements ’ patients often bring me bottles they have paid a lot of money for, to ask if their complex ingredients are safe ? Which is difficult, as being honest I often have no idea!
    I do prescribe supplements, but see them as potentially undermining patient independence and confidence. The way they are advertised concerns me too; do I detect shades of Big-Pharma?
    Dr David Unwin

    • Editorial

      For various reasons several of the comments on the post on vitamins were sent directly to me when I feel they more properly belong as posts on the site. So I am adding them a responses to Dr Unwin’s comment although that isn’t strictly correct. This is from long time vitamin D campaigner Dr Oliver Gillie.

      I think that David Unwin’s story is very helpful. What we do and say must depend on where we are speaking from. As science journalists we can explain about diets and supplements possibly more easily in print than in a inevitably time limited consultation.

      For example, we can say that children/people who eat few vegetables should think of taking folic acid. And sometimes we need to say: Don’t bother your GP with this he is a busy man just go and do it – there is no downside. Parents and children can get into complicated eating issues where the child is refusing, for example, vegetables. That is a good reason to give the child folic acid and if the child is being difficult you may have to do it surreptitiously. Eventually a way may be found round the rejection of vegetables/fruit and then folic acid may be stopped

      • Editorial

        Dr Oliver Gillie also sent another email to me in response to the vitamin article. His grip on Vitamin D research is hugely impressive so if he says the that much of the research claiming to discredit Vitamin D is unreliable and biased I’m listening

        Errors in understanding of vitamins

        Jerome mentions studies of when vitamins don’t work having big errors or distortions. I attach an article of mine published in a learned journal, no less, which explains exactly this. It is about an article in the Lancet which attempts to rubbish vitamin D but they made a fundamental error of scientific reasoning (see abstract below – please email me for a full copy). The scientists who wrote it are supported by an institute in France that gets most of its money from the pharmaceutical industry.

        I have been writing about vitamin D for about 11 years now – academic and popular articles – one from the Telegraph is attached. Some 30,000 learned articles on vitamin D have been published in the last 10 years or so. Keeping up is difficult and entering the subject as a naïve (i.e. not previously exposed to the subject) you will certainly find it very difficult. The Guardian recently had an article on vitamin D which was perfectly competent but extremely conservative because the writer, new to the subject, had gone to the apparently safe conservative sources and exercised professional skepticism. But we seldom have complete proof of all we want and so in science reporting knowing what is reasonable to believe is as important as recognizing proof.

        Science writing often involves a judgement call and that is very difficult if you have little previous knowledge of the subject. It seems obvious to the unschooled that the sun travels round the world and it is easy to make that sort of mistake if you do not know the subject – that is why science reporting is so demanding.

        We get most of vitamin D from the sun. What we get from food can provide only about 5% of the optimum dose. Most of us are deficient and vitamin mixtures all contain too low a dose of vitamin D to make a substantial difference. This is important because we live at the extreme of latitude where white skin has evolved to absorb more sun and people in the Uk with dark skins need extra vitamin D even more than native whites.

        But very few of us have outdoor lives these days as our ancestors did. We live indoors and spend a lot of time in front of screens. We have been wrongly advised to avoid the sun and over-dose on sun-cream – yes science journalists must take it on themselves to correct advice from so called experts (dermatologists) who have overlooked important facts. Air pollution absorbs UVB. We need to go out two hours round midday and wear shorts and short sleeves to get the benefit of sunshine – how many of us can do that? The majority of people in the UK get insufficient vitamin D and some 10% are frankly deficient. An awful lot of disease follows on from that.

        I have droned on long enough – but I want to support Jerome. There is a serious issue here and science journalists need to engage with it.


        Public Health Nutrition: 2015

        Controlled trials of vitamin D, causality and type 2 statistical error

        OIiver Gillie*
        Health Research Forum, 68 Whitehall Park, London N19 3TN, UK

        Abstract
        Two recent studies published in The Lancet (Autier et al. (2013) Lancet Diabetes
        Endocrinol 2, 76–89 and Bolland et al. (2014) Lancet Diabetes Endocrinol 2,
        307–320) have concluded that low levels of vitamin D are not a cause but a
        consequence of ill health brought about by reduced exposure to the sun, an
        association known as ‘reverse causality’. The scientific evidence and reasoning for
        these conclusions are examined here and found to be faulty. A null result in a
        clinical trial of vitamin D in adults need not lead to a conclusion of reverse
        causation when low vitamin D is found in observational studies of the same
        disease earlier in life. To assume an explanation of reverse causality has close
        similarities with type 2 statistical error.
        For example, a null result in providing vitamin D for treatment of adult bones
        that are deformed in the pattern of the rachitic rosary would not alter the
        observation that lack of vitamin D can cause rickets in childhood and may have
        lasting consequences if not cured with vitamin D. Other examples of diseases
        considered on a lifetime basis from conception to adulthood are used to further
        illustrate the issue, which is evidently not obvious and is far from trivial.
        It is concluded that deficiency of vitamin D in cohort studies, especially at
        critical times such as pregnancy and early life, can be the cause of a number of
        important diseases. Denial of the possible benefits of vitamin D, as suggested by
        insistent interpretation of studies with reverse causation, may lead to serious
        harms, some of which are listed.

    • Editorial

      And here is another response to Dr Unwin which was sent directly to me and which I feel deserves wider exposure.
      It comes from Dr Malcolm Kendrick who is an impressive campaigner for greater transparency and clarity in the way drugs are marketed and promoted.

      David,
      I agree with your point about bias. However, bias works in two directions. It works for pharmaceutical products and against anything that is not a pharmaceutical product. The reason for this is simple. It is called money. If you can find a cheap alternative to a pharmaceutical product e.g. a vitamin you cannot afford to run a phase III clinical trial because you cannot patent a vitamin, so any money you spent on a trial would be a complete waste of money as everyone else could immediately use your evidence to sell their own vitamins (far cheaper than you, because you spent $100m on a clinical study).
      I was listening to a neurology professor in the UK who has found that IL2 (interleukin 2) reduces brain tissue damage post-stroke by up to 50%. The team cannot get funding to do a clinical trials because IL2 cannot be patented. End of IL2.
      So, there will never, ever, be a large scale controlled study on vitamins done. The evidence will therefore be ‘poor’ and that is that.
      My own view on vitamins is that…. they are vital. It is exceedingly difficult to overdose on them, but you can if you really try hard. The ‘healthy’ levels are mostly unknown, and were established in the distant past when many people had true, deadly, deficiencies e.g. pellagra, rickets, scurvy. The range for vitamin B12 was established on 7 patients in 1947, all of whom had pernicious anaemia and has never been changed since then. I don’t think we have any idea what optimal may actually be, for any vitamin.
      Most of the research on vitamins has been rubbished, usually by those who have a clear pharma interest. Vitamins have been accused of causing cancer – on the flimsiest of evidence. Any research that shows benefit e.g. Pauling’s work of vitamin C in CHD, the Oxford groups work on Vitamin B in Alzheimer’s has immediately been attacked and…refuted. The industry is behind all the moves to limit the sale of vitamins to the public.
      So, yes, I agree with bias, and I know how it works. I think too many of those who are vehemently pro-vitamin are ‘not tightly wrapped’ and do themselves no favours by ranting and raving. However, you are exceedingly unlikely to do yourself any harm taking vitamins. If you are deficient, or at the low end of ‘normal’ you could to yourself a great deal of good by taking them. The impact of vitamin D on reducing cancer risk (although vitamin D is actually a hormone, not a vitamin), is very compelling, and the bias in this area can be traced to the great powerful force known as pharmaceutical company money.
      Regards
      Malcolm

    • Editorial

      A response from Rufus Greenbaum who has spend a lot of time investigating B vitamins and is impressed with their benefits.

      Dear David,

      If you don’t measure something you will never know if it is working or not

      Measure Homocysteine. If you find it is high, take specific high strength B-vitamins. When you measure it again you will find that Homocysteine has reduced
      - so that set of vitamins worked !

      Why do doctors prescribe Vitamin B12 ?

      Why do cardiologists prescribe Magnesium ?

      What are the effects on the Krebs cycle of these vitamins ?
      - B1, B2, B3, B5, B6, B12, C
      - plus zinc, magnesium, iron, CoQ10, copper & sulphur
      - I realise that we should receive these from our food, but a multi-vitamin helps boost all of these to effective levels

      Read the first 2 books in my Reading List attached and you see many examples of how vitamins & minerals work
      - improve endothelial function
      - deliver nutrients to the brain
      - improve sleep
      - improve digestion
      - optimise hormones
      - reduce inflammation

      Review http://www.vitamindwiki.com
      – check the 80 illnesses where Vitamin D has an impact
      - check the 55 illnesses where Vitamin D has been proven by RCT to prevent or treat the illness
      - if nothing else, improve muscle strength in the elderly

      I realise that there is not a single test for effective age, so I do many different tests where I compare my results to a large cohort
      Partly as a result of taking a carefully selected set of vitamins, minerals and supplements and testing the levels my “Metabolism Age” is 50-55, but I am actually 73

      So something is working for me !

      Regards,

      Rufus Greenbaum

    • Editorial

      Obhi Chatterjee is a one-time statistician, so better able than most to spot what is being done to the numbers in clinical trials, whose personal life has lead him to look closely at the cost/benefit ratio of vitamins.

      Like David, I never believed in vitamin supplementation. That was until I started to research what might have caused my father’s frontotemporal dementia. Now 81, he is only on food-state vitamin and mineral supplements (and has been for two years) – basically those in which his ill-advised low fat diet and prescription drugs had left him deficient after many years.

      Here was a trial which reversed Alzheimer’s using a combination of diet and supplements: http://newsroom.ucla.edu/releases/memory-loss-associated-with-alzheimers-reversed-for-first-time . The treatment protocol is similar to the one my father has been following.

      As a former statistician, I have been dismayed to see how seemingly credible clinical trials have been designed and analysed. There seems to have been clear bias to enhance the positive effects of drugs and undermine the credibility of supplements (eg by using low doses and non-food state supplements). That includes suppression of inconvenient trial outcomes and adverse effects.

      Last month’s paper illustrating how statins cause atherosclerosis and heart failure focused on the pharmacological effects of the deficiencies they cause, including vitamin K2 and selenium. It also included the following observation:

      Since the introduction of statins to clinical medicine in 1987, several kinds of statins were reported to be effective in lowering LDL-C and also preventing CHD events (mostly in 1990s). However, unfair and unethical problems were associ- ated with clinical trials reported by industry-supported scien- tists, and new penal regulations on clinical trials came into effect in 2004 [The EU Clinical Trials Regulation]. After 2004–2005, all clinical trials, per- formed by scientists relatively free of conflict of interest with pharmaceutical industries, reported that statins were effective in lowering LDL-C but no significant beneficial effects were observed for the prevention of CHD (FIGURE 1). Currently, the majority of scientists continue to claim that statins are effective in preventing CHD, but these claims are based on meta- analyses of reports, including those published before the EU regulation (mostly in 1990s).

      The importance of the gut in brain health is the subject of Dr David Perlmutter’s book Brain Maker, which is published today. I look forward to reading it. His previous book Grain Brain was very well-referenced. At least, I found it a lot more convincing than clinical trial analyses hyping ‘relative risk’ – a highly volatile and unreliable statistic.

      Best wishes

      Obhi

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