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Vitamin E and lung cancer risk

Monday 3 March 2008

“Vitamin E supplements 'could cause up to 27 per cent increase in lung cancer’”, according to a news story in the Daily Mail . Several other news sources report a study of more than 77,000 people that found a “slight but significant increase” in lung cancer risk with a moderate to high intake of vitamin E supplements. The reports also say the study sounded a similar warning for beta-carotene supplements.

The study behind the news report looked at the use of supplemental vitamins (multivitamins, vitamin C, vitamin E and folate) and new cases of lung cancer. Overall, the study found no protective effect of supplements on lung cancer. It also found a barely significant increase in risk of lung cancer associated with vitamin E supplementation. The increased risk was small – a five per cent increase in risk for every 100mg of vitamin E taken per day over 10 years – and this translated to a small increase in the participants with lung cancer.

By far the largest predictor of lung cancer from this large study was smoking, with most cases occurring in current or past smokers.

Where did the story come from?

Dr Christopher Slatore and colleagues from the University of Washington, the VA Puget Sound Health Care System, the University of North Carolina at Chapel Hill, and the Fred Hutchinson Research Centre, Seattle carried out the research. The research was supported by a grant from the National Cancer Institute.

The study was published in the peer-reviewed: The American Journal of Respiratory and Critical Care Medicine.

What kind of scientific study was this?

In this cohort study, the researchers aimed to investigate the links between supplemental multivitamin use, vitamin, C, E and folate, and incidence of lung cancer.

This study - the VITAL study (VITamins And Lifestyle) - was set up to examine the effects of long term supplement use on lung cancer in people aged between 50 and 76 in Washington state.

The researchers mailed 364,418 questionnaires between October 2000–December 2002 asking about medical history, cancer risk, supplement use and diet. Responses were obtained from 21.3% of those sent the questionnaire and this provided 77,719 people for analysis.

The questionnaire asked the participants about their supplement and vitamin use in the 10 years leading up to the start of the study. Supplement intake was classified as current, past, or never used, with specific details about the extent of use (e.g. dose per day, per week etc.). From this data, the researchers calculated the amount of multivitamins taken over 10 years, and the quantities of individual vitamins by looking at those contained in multivitamins (estimated from a reference manual) and from individual supplement tablets.

The researchers also examined other factors that could have an effect on lung cancer risk, such as smoking (years and number of cigarettes per day), age, sex, past cancer history, family history, airways disease, ethnicity, education, marital status, BMI and diet. They carried out statistical analysis of relationships between lung cancer and supplement use allowing for age, sex and smoking. They tested whether any of the other factors were affecting any observed link between these relationships and took into account those that were in their final analysis.

The participants were monitored to see if they developed lung cancer. For this, the researchers used a cancer registry called SEER, which, they said, contains accurate and complete information on cancer and lung cancer histology. The researchers excluded people who had already been diagnosed with lung cancer at the beginning of the study, those whose cancer was only diagnosed after they had died, and those who had relevant data missing. The participants were followed up until they withdrew from the study, moved out of the catchment area, died, or when the study terminated in December 2005.

What were the results of the study?

The analysis included 77,126 subjects who were followed for an average of four years. Of these, 521 developed lung cancer with most cases occurring in current or previous smokers. Few cases developed in people who had never smoked.

There was no link between risk of lung cancer and use of multivitamins, vitamin C, or folate, at any dosage for 10 years. The participants’ age, sex and smoking status were taken into account.

When the researchers looked at vitamin E alone, they found a minimal link to lung cancer (all lung cancers) – with a five per cent increase in risk with every 100mg increase in dose of vitamin E taken per day over 10 years. This result was only just statistically significant.

When the researchers looked at risk for different types of lung cancer, they found that vitamin E was associated with an increased risk in non-small cell lung cancer (the most common type). They say that this amounted to a “28% increased risk of lung cancer at a dose of 400mg/day for 10 years”.

Looking at risk of cancer by vitamin use and dividing people into categories of current and ex-smokers, they only found statistical significance between lung cancer and highest dose vitamin E in current smokers.

What interpretations did the researchers draw from these results?

The researchers concluded that no supplement protected against lung cancer; however, vitamin E was associated with a small increase in risk, especially in smokers.

What does the NHS Knowledge Service make of this study?

This study looked for associations between lung cancer risk and supplement use in a large number of people. However, the links between vitamin E and lung cancer should be considered in context:

  • The researchers found no protective effect of any type of vitamin for lung cancer.
  • The increased risk from vitamin E overall was quite small - a five per cent increase per 100mg per day – and was of borderline statistical significance.
  • The researchers report that the risk was  “largely confined to current smokers” with minimal cases occurring in non-smokers.
  • There may have been errors in the participants’ 10-year history of vitamin use. The usage was estimated by the participants themselves and it is possible that their vitamin use may have been inconsistent over that time period. Likewise, the researchers may have introduced inaccuracies when they estimated the amount of each individual vitamin contained in multivitamin tablets.
  • Although there was an increased risk associated with vitamin E, it cannot be assumed that it was caused by the supplement itself. There could be other reasons causing the increase in risk that have not been taken into account.
  • The results cannot be reliably generalised outside of the predominantly white, US population from which the data was obtained. The researchers also point out that the study had a smaller proportion of current smokers than is present within the actual US population as a whole.

Sir Muir Gray adds…

I see no evidence of vitamin E deficiency in England and so therefore no need for taking extra vitamin E.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Vitamin E linked to lung cancer.

BBC News, 29 February 2008

Vitamin E supplements 'could cause up to 27 per cent increase in lung cancer'.

Daily Mail, 29 February 2008

Links to the science

Tim Byers.

Nutrition and Lung Cancer: Lessons from the Differing Effects of Foods and Supplements.

Am J Respir Crit Care Med. 2008; 177: 470-471