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Background The relationship between long-chain omega-3 (LCn3), alpha-linolenic acid (ALA), omega-6 and total polyunsaturated fatty acid (PUFA) intakes and cancer risk is unclear. Methods We searched Medline, Embase, CENTRAL and trials registries for RCTs comparing higher with lower LCn3, ALA, omega-6 and/or total PUFA, that assessed cancers over ≥12 months. Random-effects meta-analyses, sensitivity analyses, subgrouping, risk of bias and GRADE were used. Results We included 47 RCTs (108,194 participants). Increasing LCn3 has little or no effect on cancer diagnosis (RR1.02, 95% CI 0.98–1.07), cancer death (RR0.97, 95% CI 0.90–1.06) or breast cancer diagnosis (RR1.03, 95% CI 0.89–1.20); increasing ALA has little or no effect on cancer death (all high/moderate-quality evidence). Increasing LCn3 (NNTH 334, RR1.10, 95% CI 0.97–1.24) and ALA (NNTH 334, RR1.30, 95% CI 0.72–2.32) may slightly increase prostate cancer risk; increasing total PUFA may slightly increase risk of cancer diagnosis (NNTH 125, RR1.19, 95% CI 0.99–1.42) and cancer death (NNTH 500, RR1.10, 95% CI 0.48–2.49) but total PUFA doses were very high in some trials. Conclusions The most extensive systematic review to assess the effects of increasing PUFAs on cancer risk found increasing total PUFA may very slightly increase cancer risk, offset by small protective effects on cardiovascular diseases.

This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity.