/ 2 January 2014

The jury is out on antioxidants

Your local pharmacy probably has an aisle labelled "vitamins and supplements", with several shelves offering brightly coloured boxes and bottles, accompanied by pictures of smiling, contented families.

Professional-looking models will declare, on expertly designed pamphlets, that these vitamins and supplements will prevent cancer, reverse ageing and keep the common cold at bay. There may even be a helpful employee to help you to select the best multivitamin for your family.

The reasons for stocking and promoting these products may be many but it is worth noting that the global vitamin and supplement industry is very profitable, valued at up to $68-billion a year.

One line of supplements will probably stand out on most of the boxes or package inserts. It will claim that the products contain "antioxidants", a label worn like a badge of honour.

For example, when visiting your local Dis-Chem, look for Solal Technologies's Aces Plus, labelled as an antioxidant with "complete free radical protection". Or take Patrick Holford's BioCare AGE Antioxidant, which helpfully adds that "antioxidants protect our bodies from free radicals in the environment".

Another example is Dis-Chem's own Multivit Supreme, which purports to contain several antioxidants, or Clicks's Apple Cider with Green Tea Weight Loss Support, which claims to "increase antioxidant levels".

What are antioxidants?
Antioxidants is a name given to molecules that prevent oxidation. These molecules occur in several food types, in the form of vitamins A, C and E, betacarotene and selenium (among many others), and are also produced by the human body. Eating a diet containing a variety of foods (fruits, vegetables, grains, poultry and fish) will probably provide your body with the dietary antioxidants it needs.

The use of vitamin supplements (some of which are antioxidants) is necessary in specific instances, such as during pregnancy, for special diets and with certain childhood conditions, and should be taken after consulting your healthcare provider.

But in the past few decades, an industry has formed around the idea that taking extra antioxidants (often in the form of supplement pills) is unreservedly good for you, even if you are healthy.

Paul Offit, a paediatric specialist in infectious diseases and co-developer of the RotaTeq vaccine, in his book, Do You Believe in Magic? The Sense and Nonsense of Alternative Medicine, published last year, breaks it down for the layman: "Antioxidation vs oxidation has been billed a contest between good and evil … One consequence of oxidation is the generation of electron scavengers called free radicals (evil)."

Having introduced the villain, he expounds on its mischief, which includes damage to "DNA, cell membranes and the lining of arteries", and explains that, therefore, free radicals have been linked to "ageing, cancer and heart disease".

Offit says that our bodies produce the "good guys", the antioxidants.

From his explanation, the solution to combating the effects of time seems obvious – supplemental antioxidant intake. And this is exactly what scientists have been trying to show. But Ben Goldacre, a doctor, epidemiologist and journalist, says in his 2008 book Bad Science: "I think you'll find that it's a bit more complicated than that."

The Cochrane Collaboration is an international organisation that reviews all data on an issue and creates meta-analyses – pooled summaries on the results of all available, relevant research. In 2012, echo­ing the findings of earlier clinical trials on people reported in 2004 and 2005, the organisation issued a meta-analysis on antioxidant supplementation, as studied in 78 randomised clinical trials.

It found that adult patients who were given the antioxidants beta-carotene and vitamins A and E were up to 1.03 to 1.04 times (that is, 3% to 4%) more likely to die than controls who received either a placebo (a dummy pill) or nothing at all. Vitamin C and selenium were not found to increase the number of deaths recorded, but did not prolong life either.

The researchers were unambiguous: "The current evidence does not support the use of antioxidant supplements in the general population or in patients with various diseases."

They concluded that "antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing".

The reasons for these surprising findings may be difficult to determine. It has been dubbed the "antioxidant paradox" by researchers.

"The most likely explanation is that free radicals are not as evil as advertised. People need free radicals to kill bacteria and eliminate new cancer cells," Offit says.

"But when people take large doses of antioxidants, the balance between free-radical production and destruction might tip too much in one direction, causing an unnatural state in which the immune system is less able to kill harmful invaders."

Contesting the findings
When asked for comment, Dis-Chem officials referred the Mail & Guardian to Peter Hill, a pharmacist with a PhD in patient self-care. Hill is also the head of Met-S Care, a South African-based programme that offers services to sufferers of metabolic syndrome.

He said that the study does not state whether antioxidants "positively impact on disease prevention" and that the study's use of death as an outcome is a sign that it was "designed to fail".

The M&G contacted the editorial staff of Quackdown.info, a Cape Town-based website that is a joint project of the Treatment Action Campaign and the Community Media Trust. Quackdown's goal is to "[help] people make informed choices about healthcare".

One of its co-founders, Nathan Geffen, said that "mortality is the most compelling clinical endpoint you can have in a clinical trial. The problem is that it's impossible for most trials to measure mortality. But that the Cochrane reviewers examined trials that included mortality allowed them to consider this, the most important clinical endpoint."

In Do You Believe in Magic? Offit cites the example of Vioxx, a new anti-inflammatory drug that effectively treated inflammation with few side effects on the gastrointestinal system. By monitoring deaths in trials, it was found that patients who were taking Vioxx were more likely to suffer heart attacks, strokes and subsequent death. Due to this unforeseen finding, Vioxx was removed from the market.

Having established that none of the antioxidants studied had a prolonging effect on life at all, the Cochrane reviewers are obtaining the safety profiles of betacarotene and vitamins A and E relating to deaths, and it would seem that these substances have the potential to cause harm.

But Hill also questioned the fact that only 78 studies were used for the review, when a search on research aggregator Pubmed produced 369 728 results.

Geffen said: "[The] Cochrane studies use a rigorous methodology, considered by many to be the gold standard of evidence-based medicine. Only high-quality, controlled studies are included. Large, properly conducted, randomised, controlled studies reduce the risk of confounding [evidence]. One of the points of the Cochrane studies is to assess [this factor]."

Hill is not the first to contest the results of the review. Patrick Holford, well-known supplement promoter from the United Kingdom and self-styled nutritionist, said in an interview with the London Times that he believes the "review is part of a conspiracy by the medical establishment to undermine the advance of the nutritional route to better health".

Dis-Chem director Stan Goetsch said: "We believe that the question around the effectiveness [or] concept of antioxidants is inconclusive but, if any products on our shelves are found to be unsafe, they will be removed immediately."

He also said that Dis-Chem is "very cognisant of the unsubstantiated and often irresponsible claims made on the labels of many nutraceutical products and we have employed a full-time specialist that is taking up this issue directly with all of our present suppliers to ensure compliance with all laid-down guidelines".

Harris Steinman, also from Quack­down, pointed out that the term "nutraceutical" is not legally defined and its regulation has not yet been determined. According to him, guidelines on vitamin supplements will have to come from the Medicines Control Council (MCC).

In 2008, it was reported that the MCC was dealing with a seven-year drug registration backlog. A 2010 report by a task team set up to deal with the backlog and other administrative issues reported that, despite changes, there remained "fundamental process problems".

Koot Kotze was an intern at Bhekisisa when he wrote this article. He is studying towards an MBChB.