Long-term use of vitamins C and E supplements does not increase cancer risk, new analysis from Harvard researchers shows.
This new data directly contrasts with recent findings, notably the controversial SELECT trial, that have raised questions about supplementation use and their effects on cancer.
The present Harvard analysis, a post trial follow-up of the Physicians' Health Study II (PHS II), revealed that vitamin E supplementation every other day and daily vitamin C supplementation had no effect on total cancers, the incidence of prostate cancer and other site-specific cancers.
The researchers also found no modification of the treatment effect by participant baseline characteristics, concurrent randomised treatment, or duration of follow-up time.
PHS II ended in 2007 and the post trial follow-up period was 3.8 years beyond 8 years of intervention.
"Because of the long developing period for many cancers, continued post trial follow-up is necessary in cancer prevention trials to assess long-term treatment effects, either beneficial or harmful, that may emerge after the intervention ends," the Harvard authors wrote in the American Journal of Clinical Nutrition.
"The findings confirm our initial trial results and indicate that vitamin E and C supplement use has no immediate or long-term effects on cancer risk," the authors wrote.
Vitamin E and cancer risk
The aforementioned SELECT trial which tested vitamin E supplementation of 400 IU/d on the prevention of prostate cancer, reported that men randomised to take active vitamin E developed significantly more prostate cancer compared with placebo during the post trial follow-up.
The promising results from new analysis from PHS II add weight to other strong evidence supporting the safety of long-term supplement use - and, they also revealed an unexpected benefit associated with daily vitamin C supplementation.
Vitamin C and colorectal cancer: "intriguing finding"
Interestingly, the Harvard researchers found a significant reduction in colorectal cancer with active vitamin C supplementation. During the intervention period, daily vitamin C supplementation was associated with a 21% reduction in colorectal cancer, yet during the post trial follow-up this increased to a 46% reduction.
The study authors noted that the finding was "intriguing" and argued that it suggests a possible late effect.
"These findings warrant additional studies to confirm or refute and highlight the importance of continued posttrial observation to detect any potential latent effects for vitamin C and other nutritional interventions," the authors added.
About The Physicians' Health Study II
PHS II was a randomised controlled trial of 14,641 US male physicians that began in 1997. It aimed to test the balance of benefits and risks of vitamin E, vitamin C and a multivitamin for primary prevention of cardiovascular disease, cancer, age-related eye disease, and cognitive decline.
In the vitamin C and vitamin E components, patients were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The findings were published in the Journal of the American Medical Association in 2009.
In the multivitamin component, patients took a daily multivitamin or placebo. This component ended in 2011 and the results, published in the Journal of the American Medical Association, showed an 8% reduction in the risk of total cancer.
Wang L, Sesso HD, Glynn RJ, Christen WG, Bubes V, Manson JE, Buring JE, Gaziano JM. Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial. First published July 9, 2014, doi: 10.3945/ajcn.114.085480 Am J ClinNutr September 2014 ajcn.085480
Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2008 Nov 12;300(18):2123-33. doi: 10.1001/jama.2008.600. Epub 2008 Nov 9.
Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. The Physicians' Health Study II Randomized Controlled Trial. JAMA. 2012;308(18):1871-1880. doi:10.1001/jama.2012.14641.
Dunn BK, Richmond ES, Minasian LM, Ryan AM, Ford LG.A nutrient approach to prostate cancer prevention: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). Nutr Cancer. 2010;62(7):896-918. doi: 10.1080/01635581.2010.509833.