Anti-oxidants and Supplementation: Not As Straightforward As It Is Made Out To Be

Former Visiting Professor Patrick Holford is Head of Science and Education at Biocare and both he and several other media nutritionists have a relationship with anti-oxidant supplements that mirrors the behaviour of Margaret Thatcher and her Cabinet. She slapped them around (metaphorically), she promised them some huge benefits but didn’t deliver them, she occasionally humiliated them and, through it all, she inspired devotion right up until the coup that followed a groundswell of grumblings that no matter what Those Up Top thought, things were not working so well for Everybody Else.

Well, the coup against anti-oxidant supplements hasn’t happened but there is a definite groundswell of grumblings and scientific evidence that indicates that anti-oxidant supplementation is not delivering the promised benefits. Lisa Melton gave a good overview of the gulf between the hype and reality of anti-oxidants: The antioxidant myth: a medical fairy tale. More recently, Professor Tom Sanders gave the Burke Lecture (pdf) in which he briefly summarised the state of play for the outcomes of trials that tested the antioxidant hypothesis.[1]
The Cochrane Review of anti-oxidant supplements (pdf) reported that there was no reduction in mortality associated with them (there was some manufactured controversy around these findings).

There was a prima facie case for testing anti-oxidant supplementation for potential health benefits. If free radicals caused damage then it was logical that anti-oxidants that mopped up the damage could be nothing but beneficial and protective. Dolphins – good. Big Pharma – bad. Anti-oxidants – good. Free radicals – bad. Ben Goldacre identifies the anti-oxidant story as being at the heart of nutritionism. However, sometimes, the obvious inference just doesn’t work out when it is subjected to clinical testing.[2]

Gimpy and Dr Aust have commented about anti-oxidant supplementation and its putative benefits on Dr John Briffa on testing for food sensitivity: applied kinesiology, dowsing and IgG tests. There is a dearth of clinical evidence to support the use of supplements in a well-nourished, general population without evidence of clinical deficiencies or particular exceptions and needs (e.g., pregnant women or women of child-bearing age may be advised to supplement folic acid; people who need vitamin D supplements because they have little sun exposure and have insufficient dietary sources etc.). For anti-oxidant supplementation in particular, the clinical picture is for no evidence of benefit with some possible exceptions that might need further research[3] (as shown by the results of the Cochrane Review).

But, what about special groups of people? People who are ill and may have substantial nutritional deficiencies because of the nature of the illness? Say, loss of appetite and impaired ability to digest food as a consequence of some forms of cancer. Would they benefit from some anti-oxidant supplementation during treatment? Even here, the evidence is mixed at best. Liz Savage sums up the situation in Antioxidant Supplements May Lessen Benefit of Radiation and Chemotherapy.

Radiation and many chemotherapy agents work to kill cells by inducing free radicals that damage DNA and proteins. Therefore, there is a possibility that taking antioxidant supplements, such as vitamin E or β-carotene, may interfere with the therapies and reduce their anticancer activity. On the other hand, some investigators hypothesize that antioxidant supplementation may protect healthy tissues and reduce the side effects of treatment. Despite two decades of research into this question, no clear answer has appeared.

She discusses the work of Lawenda et al. who carried out a review and conclude:

On the basis of our review of the published randomized clinical trials, we conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.

OK, but are there groups of people, somewhere between healthy and those with cancer, who might benefit from supplements even if they are not specifically anti-oxidants? What about all the recent excitement about the sunshine vitamin?

The evidence is indirect, sparse and conflicted. Mucci and Spiegelman outline the optimism for the protective benefits of vitamin D but the disappointing results to date in some areas of investigation: Vitamin D and Prostate Cancer Risk—A Less Sunny Outlook? The best conclusion that they can offer is:

The absence of a link between vitamin D and prostate cancer risk, even if ultimately confirmed, should not be misinterpreted as evidence against other well-documented health benefits of vitamin D. The weight of evidence does suggest that increased vitamin D levels—from diet, supplementation, or sun exposure—are likely to have a modest beneficial effect on the overall burden of chronic disease in the United States and other epidemiologically similar countries.

There are particular demographics or groups of people who benefit from supplementation. However, there is currently scant clinical support for the supplementation of the general, well-nourished population without any additional clinical needs.[4]

Despite the lack of clinical support, various nutritionists continue to promote anti-oxidants as anti-disease and anti-ageing agents. Worse still, they promote them as having strong clinical evidence. Adults are free to spend their money on what they want – including substances and activities that are demonstrably harmful. If they know what they are doing, then that is their choice. However, rather like ‘MPs and their cash for questions’, it should not be acceptable for nutritionists or manufacturers to distort the clinical evidence to persuade adults that they need to purchase these products as prophylactics against disease or as a means of retarding the ageing process.[5]

Anti-oxidants held out the promise a clean sweep of all those pesky free radicals but are failing to deliver concrete benefits. After almost 30 years there is still scant decent evidence in favour of general or specific supplementation for the general population. However, despite the groundswell of evidence, the acolytes of the anti-oxidant story refuse to modify their beliefs and keep the faith. For how much longer?


[1] Sanders argues that although there are parts of the world where dietary insufficiency means that the population is deficient in several essential nutrients such as vitamin A, this is rarely the case for the general population in the UK or other affluent countries.

[C]ocktails of vitamin A, beta-carotene and antioxidant vitamins such as vitamin C and vitamin E are touted as protecting adults against ageing, cancer and heart disease. A quick search of the internet shows that most of the sites offering dietary supplements are peppered with health claims for the benefits of these supplements for adults. However, a number of large scale randomized controlled trials have failed to answer the question whether these supplements help to prevent cancer in affluent populations. The Alpha-Tocopherol-Beta-Carotene Study (5) was carried out to investigate if the taking the supplements over a five year period lowered risk of developing lung cancer with a placebo supplement. Instead of decreasing risk as was expected, the antioxidant supplements substantially increased risk of getting lung cancer and dying. A second study called the Carotene and Retinol Efficacy Trial (9) which was designed to test if giving supplements to smokers and asbestos workers would reduce their risk of developing cancer, also found that the supplement increased risk of lung cancer and death. Regulatory authorities subsequently stopped further trials using vitamin A because there was clear evidence of harm. The World Cancer Research Fund in its recent report on diet and cancer (6) reviewed all the studies and advised people not to take vitamin A or antioxidant supplements to prevent cancer but to get their nourishment from food.

Whether antioxidants protect against cardiovascular disease has also been tested in several large trials. One of the largest is a UK study (11) where about twenty thousand subjects received a cocktail of supplements or a placebo. The study had was run-in what is called a factorial design where half of the subjects of each groups also got a cholesterol lowering drug called a statin or a placebo. The study showed a huge benefit from taking the statin (12) in terms of decreasing risk of death, heart disease, and stroke and death from all causes but did not show any benefit from the antioxidant supplements. There was no evidence of any protection from cardiovascular disease but there was a trend for the subjects to do worse on the supplements than on the placebo. [pg. 6 of pdf]

[2] E.g., giving a blood transfusion after cardiac surgery seemed to be commonsense. However, clinical testing discredited the practice and revealed that it was linked with a higher risk of ischaemic events, leading to higher rates of kidney impairment, strokes, and heart attacks.
[3] Vicki Brower in An Apple a Day May Be Safer Than Vitamins reports that:

Several new reports, including a commentary in this issue of the Journal (p. 773–778), are raising concerns about the safety and efficacy of vitamin and mineral supplements in healthy individuals and cancer patients and survivors. Some experts see a need for further studies, whereas others say that there are sufficient negative data to stop vitamin trials altogether.

[4] For social and climate reasons, supplementation with vitamin D may be an exception to this for some groups. Vitamin D: New way to treat heart failure?
[5] Related to this point, the Unfair Commercial Practices Directive (pdf) has some thought-provoking sections. E.g., Clause 17 of the 31 banned practices makes it illegal to make a false medical claim for a product or service which may curb the claims that manufacturers can make but it is unclear whether there is still a loophole that allows independent organisations or charities to say what they wish. However, where a charity or organisation is charging money for an endorsement, it is not established whether this changes the picture.
Clause 7.12 makes an offense of “misleading omissions”. – e.g., a nutritional therapist who fails to mention that research has shown that there is no evidence-base for a particular blood test where the omitted information would result in the “average consumer” acting differently – i.e., not purchasing the test. Maybe this might apply to omitting to inform consumers that there is no evidence-base for particular supplementation.
Clauses 14.35 to 14.37 apply to “vulnerable consumers”, and places an obligation traders to take particular care with products aimed at this group. E.g., a nutritional therapist who claims that a food supplement might benefit people with mental health problems might find themselves crossing the boundary of the acceptable. This might be policed more rigorously for claims involving vulnerable child populations.
The Nutrition and Health Claims regulations substantially limit the claims that can be made without verification. However, enforcement relies upon the willingness to intervene of already over-stretched Trading Standards departments.



Filed under antioxidants, cancer, patrick holford, supplements

3 responses to “Anti-oxidants and Supplementation: Not As Straightforward As It Is Made Out To Be

  1. Claire

    OT, apologies, but saw this on the BBC website about a court in South Africa ruling against Matthias Rath et al in the context of unauthorised vitamin trials in AIDS –

  2. nospin

    Why are there no official trials of vitamins and their effect on AIDS patients


  3. There are such trials, this one looks at the effects of micronutrient supplementation for people with TB, both with and without HIV+ status. If you run a search of
    aids vitamin
    aids vitamins
    in the PubMed database, you will be able to find some trials.

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