Rapid Review Alert February 15, 2012
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 In EPA & DHA Research
Background: To advance knowledge about the cancer chemopreventive potential of individual nutrients, we investigated the effects of B vitamin and/or ω-3 fatty acid supplements on cancer outcomes among survivors of cardiovascular disease.

Methods: This was an ancillary study of the Supplementation With Folate, Vitamins B6 and B12 and/or Omega-3 Fatty Acids (SU.FOL.OM3) secondary prevention trial (2003-2009). In all, 2501 individuals aged 45 to 80 years were randomized in a 2 x 2 factorial design to one of the following 4 daily supplementation groups: (1) 5 methyltetrahydrofolate (0.56 mg), pyridoxine hydrochloride (vitamin B6; 3 mg) and cyanocobalamin (vitamin B12; 0.02 mg); (2) eicosapentaenoic and docosahexaenoic acid (600 mg) in a 2:1 ratio; (3) B vitamins and ω-3 fatty acids; or (4) placebo. Overall and sex-specific hazard ratios (HRs) and 95% CIs regarding the cancer outcomes were estimated with Cox proportional hazards models.

Results: After 5 years of supplementation, incident cancer was validated in 7.0% of the sample (145 events in men and 29 in women), and death from cancer occurred in 2.3% of the sample. There was no association between cancer outcomes and supplementation with B vitamins (HR, 1.15 [95% CI, 0.85-1.55]) and/or ω-3 fatty acids (HR, 1.17 [95% CI, 0.87-1.58]). There was a statistically significant interaction of treatment by sex, with no effect of treatment on cancer risk among men and increased cancer risk among women for ω-3 fatty acid supplementation (HR, 3.02 [95% CI, 1.33-6.89]).

Authors’ Conclusion: We found no beneficial effects of supplementation with relatively low doses of B vitamins and/or ω-3 fatty acids on cancer outcomes in individuals with prior cardiovascular disease.
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Omega-3s & Cancer

Review of:
Andreeva VA Touvier M Kesse-Guyout E Julia C Galan P and Hercherb S (published online February 13, 2012). B Vitamin and/or
ω-3 Fatty Acid Supplementation and Cancer. Arch Intern Med doi: 10.1001/archinternmed.2011.1450.

Take-Home Message

  • This study supports neither low-dose (600 mg EPA + DHA) supplementation for cancer prevention in individuals with prior cardiovascular disease nor the misleading popular press reports of cancer promotion. While it is biologically plausible that long-chain omega-3 fatty acids protect against cancer, the evidence is equivocal. See the World Cancer Research Fund/American Institute for Cancer Research report for an exhaustive review of the literature.
  • This study does not support a change in eating habits or dietary supplement use. One must consider the totality of the available scientific evidence. The cardiovascular benefits associated with the long-chain omega-3 fatty acids are well-documented, in healthy populations, as well as in the majority of populations with pre-existing cardiovascular ailments. 

What Else Should You Know?

  • Regarding the lack of beneficial effects of EPA & DHA on cancer incidence, according to the authors, “an argument has been extended that the critical period for dietary exposure to these nutrients may be during childhood or early adulthood.” If this is true, then the reported study overshot the window of opportunity.
  • A recent study reported that higher intakes of the long-chain omega-3s are associated with a lower risk of adenomatous polyps in women (Murff et al., 2012).
  • The long-chain omega-3s have been shown to reduce the effects of cancer-related cachexia (Colomer et al., 2007).
  • There are a multitude of studies demonstrating increased effectiveness of anticancer agents by long-chain omega-3s. One such study is Bougnoux et al., 2009.
  • With respect to the results from the primary analysis reported back in 2010, the most likely reason the long-chain omega-3s did not prevent major cardiovascular events in patients with pre-existing cardiovascular disease is that the dose was too low (600 mg EPA + DHA). Consider that the American Heart Association recommends 1 g/day of EPA+DHA for individuals with coronary heart disease.  

Study Limitations

  • The results in the present publication represent ancillary data analyses of a secondary outcome. In essence this was a fishing expedition. Results from appropriate secondary analyses should be used to design future experiments, not draw conclusions. In addition, the results should not be used as a “standard of care” for either patients or the general healthy population.
  • The population studied was not selected for the presence or absence of any factors related to cancer risk, cancer history, etc… Even studies involving populations accounting for these factors are difficult to interpret if they relate to incidence of cancer as a single disease.
  • Fish intake was not tracked; therefore, there’s no way to know what the long-chain omega-3 intake differences were between groups.
  • Even if EPA & DHA are beneficial for cancer prevention, the effect is unlikely to be observed within a five year window. Using an older population increases the likelihood that some subjects have undiagnosed cancer. A younger population needs to be studied for a longer duration in order to see an effect. 

Suggested Citation

Global Organization for EPA and DHA Omega-3s (2012). Omega-3s & Cancer [Peer commentary on the paper “B Vitamin and/or ω-3 Fatty Acid Supplementation and Cancer” by Andreeva VA Touvier M Kesse-Guyout E Julia C Galan P and Hercherb S (published online February 13, 2012). Arch Intern Med doi: 10.1001/archinternmed.2011.1450.].


Bougnoux P Hajjaji N Ferrasson MN Giraudeau B Couet C Le Floch O (2009). Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer 101:1978-1985.
Colomer R Moreno-Nogueira JM García-Luna PP García-Peris P García-de-Lorenzo A Zarazaga A Quecedo L del Llano J Usán L and Casimiro C (2007). N-3 fatty acids, cancer and cachexia: a systematic review of the literature. Br J Nutr 97:823-831.
Galan P Kesse-Guyot E Czernichow S Briancon S Blacher and J Hercberg S for the SU.FOL.OM3 Collaborative Group (2010). Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomized placebo controlled trial. BMJ 2010;341:c6273 doi:10.1136/bmj.c6273.
Murff HJ Shrubsole MJ Cai Q Smalley WE Dai Q Milne GL Ness RM and Zheng W [Epub ahead of print January 25, 2012]. Dietary intake of PUFAs and colorectal polyp risk. Am J Clin Nutr. doi: 10.3945/ajcn.111.024000.
World Cancer Research Fund / American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR, 2007. http://www.dietandcancerreport.org/cancer_resource_center/downloads/Second_Expert_Report_full.pdf




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