US researchers studying the effect of beta carotene, vitamin C and vitamin E, either singly or in combination, on over 7,000 women found the supplements did not reduce their risk of getting cancer compared to women who did not take the supplements. However an expert who reviewed the study said that while the overall message was there was no link, it uncovered some interesting evidence that should not be overlooked.

The randomized, double-blind, placebo-controlled study was the work of researchers from Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts and is published in the 30 December Advance Access online issue of the Journal of the National Cancer Institute.

A number of observational studies have suggested it is likely that diets high in fruit and vegetables, both rich sources of vitamins (also called antioxidants), prevent cancer. But randomized trials have mostly failed to establish a significant link between the use of antioxidants and cancer risk, wrote the authors in their background material.

For this study, the researchers examined data on 7,627 women who were cancer-free at the start of the study. They were part of a cohort of over 8,000 taking part in the Women’s Antioxidant Cardiovascular Study where all participants had been randomly assigned to take either vitamin C (500 mg of ascorbic acid daily), natural source vitamin E (600 IU of {alpha}-tocopherol every other day), beta-carotene (50 mg every other day), all three supplements, or placebo.

They consulted hospital reports and the National Death Index to get details of cancer diagnoses (including specific site of tumor), and deaths, and analysed the results using advanced statistical tools to assess the relative risks of common cancers associated with the use of the supplements, either individually or in combination. They also tried to establish if cancer risk was affected by how long the supplements were taken for.

The results showed that:

  • Over an average 9.4 years of treatment, 624 women developed incident invasive cancer and 176 women died from cancer.
  • There were no statistically significant links between antioxidant use and total cancer incidence.
  • The relative risks (RR) compared to placebo were: vitamin C group RR was 1.11 (95% confidence interval [CI] = 0.95 to 1.30); vitamin E group RR was 0.93 (95% CI = 0.79 to 1.09); beta carotene group RR was 1.00 (95% CI = 0.85 to 1.17).
  • There were also no significant links between antioxidant use and cancer mortality.
  • Again, compared to placebo, the RRs were for vitamin C 1.28 (95% CI = 0.95 to 1.73), for vitamin E 0.87 (95% CI = 0.65 to 1.17) and for beta carotene 0.84 (95% CI = 0.62 to 1.13).
  • None of the antioxidants showed a significant link with cancer incidence and death with longer use.
  • Combined use of the three antioxidants also had no significant effect on these two outcomes.

Note that a relative risk of 1.00 compared to placebo means the risk is the same, so 0.95 is slightly lower and 1.05 is slightly higher. Confidence Intervals (CI) are a statistician’s way of showing how much confidence one should have in the calculated relative risk, in the sense that a 95% CI of 0.65 to 1.17 means that if you were to run the same “experiment” 100 times, there is a 95 per cent chance that you would get a result in this range.

The researchers concluded that:

“Supplementation with vitamin C, vitamin E, or beta carotene offers no overall benefits in the primary prevention of total cancer incidence or cancer mortality.”

They wrote that the trial showed:

“Neither duration of treatment nor combination of the three antioxidant supplements had effects on overall fatal or nonfatal cancer events.”

“Thus, our results are in agreement with a recent review of randomized trials indicating that total mortality was not affected by duration of supplementation and single or combined antioxidant regimens,” added the researchers.

An accompanying editorial by Dr Demetrius Albanes of the National Cancer Institute, reviewed data from previous randomized controlled trials that examined supplement use and cancer incidence.

Albanes wrote that while this particular study reports there is no link between supplement use and lowering of cancer risk, the results contain valuable information. For example, there was a trend for reduced colon cancer incidence with use of vitamin E, which confirms findings in other studies.

Also, this study linked beta carotene use to a “modest excess” of lung cancer, which is also consistent with other reports, wrote Albanes, who concluded that:

“Null trials or those with unexpected outcomes should not, however, be viewed as failures; they have and will continue to shed light on the causes of cancer and help us discover the means for its prevention.”

“Vitamins C and E and Beta Carotene Supplementation and Cancer Risk: A Randomized Controlled Trial.”
Jennifer Lin , Nancy R. Cook , Christine Albert , Elaine Zaharris , J. Michael Gaziano , Martin Van Denburgh , Julie E. Buring , and JoAnn E. Manson.
Journal of the National Cancer Institute Advance Access published on December 30, 2008.
DOI 10.1093/jnci/djn438.

Click here for Abstract.

Sources: Journal abstract, Journal of the National Cancer Institute.

Written by: Catharine Paddock, PhD