Context:

Clinical trials and observational studies report differing effects of omega-3 fatty acids on cancer.

Objectives:

To assess the effect of omega-3 fatty acids on 1) tumor incidence 2) clinical outcomes after cancer treatment, and 3) tumor behavior.

Data Sources:

We searched computerized databases to identify potentially relevant studies and contacted industry experts for unpublished data.

Study Selection:

Tumor incidence and outcomes after cancer treatment. We screened 4,834 titles, reviewed 356 articles, and included 52 articles in our review. For tumor incidence, we restricted to prospective cohort studies in humans, and for clinical outcomes after cancer treatment, we restricted to randomized controlled trials (RCTs); We had no language restrictions.

Tumor behavior. We screened 366 titles, reviewed 82 articles, and included 27 articles in our review. For tumor behavior, we restricted to review articles and meta-analyses of animal studies and cell culture studies in humans and animals. We had no language restrictions.

Data Extraction:

We abstracted data on study design, study population, and outcomes; source, amount, and duration of omega-3 fatty acid consumption; and randomization, dropouts, blinding, and allocation for RCTs.

Data Synthesis:

Tumor incidence. Across 19 cohorts for 11 different types of cancer and using up to 5 different ways to categorize omega-3 fatty acid consumption, 44 estimates of the association between omega-3 fatty acid consumption were reported. Among these, only six were statistically significant. Significant associations between omega-3 consumption (in the form of both fish and alpha-linolenic acid) and cancer risk were reported for breast cancer in two studies; for lung cancer in two; for prostate cancer in one; and for skin cancer in one. For breast cancer one significant estimate was for increased risk and one was for decreased risk; five other estimates did not show a significant association. For lung cancer one of the significant associations was for increased cancer risk, the other was for decreased risk and four other estimates were not significant. Only one study assessed skin cancer risk.

Cancer treatment. We identified 19 studies from which the effect of omega-3 fatty acids on clinical outcomes after cancer therapy could be ascertained, all of which pertained to patients who had undergone cancer surgery for upper gastrointestinal malignancies. We did not identify any studies that assessed the effects of omega-3 fatty acids on clinical outcomes after chemotherapy or radiation treatment. Among the identified studies, the effect of omega-3 fatty acids alone could be ascertained from six studies; the effect of omega-3 fatty acids given in combination with arginine and RNA could be ascertained from 13. Effects on post-operative complications were described in 14, on hospital length of stay in 13, on mortality in ten, on nutritional parameters in 11, and on weight in three. In pooled analyses, omega-3 fatty acids had no effect compared to placebo on post-operative complications, hospital length of stay, nutritional parameters, or mortality.

Relative to a standard enteral diet, omega-3 fatty acids in combination with arginine and RNA were associated with a reduced risk of postoperative complications (RR 0.51, 95%CI 0.40, 0.64) and reduced length of hospital stay (pooled mean difference -3.33 days, 95%CI -4.29, -2.38). Among nine studies that assessed the effect on nutritional parameters omega-3 plus arginine and RNA, prealbumin was significantly higher in the omega-3 + arginine + RNA group in three studies, but not different in three others; mean nitrogen intake was significantly higher in one study but not in another. No significant differences were found for mean caloric intake, mean albumin, or mean transferrin.

Although the combination of omega-3 fatty acids, arginine, and RNA are associated with a reduced risk of post-operative complications and reduced length of hospital stay, it is not possible to ascertain whether these effects are due to omega-3 fatty acids, arginine, RNA, or a combination of these.

Tumor behavior. We evaluated 27 reviews of studies on animals or cell culture models that described the effects of tumor growth, differentiation or apoptosis. Although much of the evidence favored a role for n-3 dietary enrichment in the inhibition or prevention of tumor growth, at least in some animal models, the quality of the reviews is not sufficient to permit strong conclusions to be drawn.

Conclusions:

In a large body of literature spanning numerous cohorts from many countries and with different demographic characteristics, the evidence does not suggest a significant association between omega-3 fatty acids and cancer incidence. In a small body of literature, there is no significant association between omega-3 fatty acids and clinical outcomes after tumor surgery. Although the combination of omega-3 fatty acids, arginine, and RNA are associated with a reduced risk of post-operative complications and reduced length of hospital stay, it is not possible to ascertain whether these effects are due to omega-3 fatty acids, arginine, RNA, or a combination of these. Although a large, but heterogeneous, body of literature suggests that omega-3 dietary enrichment may play a favorable role in the inhibition or prevention of tumor growth in some animal models, the quality of the reviews is not sufficient to permit strong conclusions to be drawn.