Effect of Alpha Linolenic Acid Supplementation on Serum Prostate Specific Antigen (PSA) Results from the Alpha Omega Trial

Alpha linolenic acid (ALA) is the major omega 3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer. The Alpha Omega Trial was a double blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 262 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60 to 80 years with an initial PSA concentration ,4 ng per mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T  tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut off point greater than 4 ng per mL). Mean serum PSA increased by 0.42 ng per mL on placebo (n  of  815) and by 0.52 ng per mL on ALA (n  of 807), a difference of 0.10 (95  confidence interval: -0.02 to 0.22) ng per mL (P of 0•12). The odds ratio for PSA rising above 4 ng per mL on ALA versus placebo was 1.15 (95 CI: 0.84-1.58). An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from -0.02 to 0.22 ng per mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer. (Authors abstract)

Observational studies suggest that an increased intake of alpha linolenic acid is associated with a moderately lower risk of cardiovascular disease.  In contrast, a higher intake of alpha linolenic acid has also been suggested to be associated with a higher risk of prostate cancer. Two meta analyses that included both prospective and case control studies found that higher intakes of alpha linolenic acid and higher levels in blood and adipose tissue were associated with increased risk of prostate cancer. The association of ALA with prostate cancer is not clear. The Alpha Omega Trial was a double-blind placebo-controlled trial in 60 to 80 year old patients with a history of myocardial infarction who received moderate additional amounts of omega 3 fatty acids for the prevention of recurrent cardiovascular diseases. The incidence of prostate cancer was monitored as a potential adverse effect in this study.   ALA supplementation was not related to the incidence of prostate cancer. However, there were only 42 incident prostate cancer cases and thus the power to detect an effect was low.  Serum concentrations of prostate specific antigen (PSA), a serine protease produced by prostatic epithelial cells, are often elevated in men with prostate cancer. High concentrations may predict long term increases in prostate cancer incidence and mortality.  Supplementation with an additional amount of 2 gram ALA per day during 40 months increased serum PSA concentrations of older post myocardial infarction patients by 0.10 ng per mL. However, the 95 per cent  confidence interval ranged from 20.02 to 0.22 mg per mL. Effects of ALA supplementation on PSA velocity and on the combined endpoint of prostate cancer and a PSA level above 4 ng per mL were in the direction of a raising effect, but the confidence intervals were wide and all included. This is the first large scale clinical trial that investigated the effect of ALA on serum PSA.
Although patients with prostate cancer are quite different from this population and the study was small it should be noted that they did not show an effect on PSA and even showed a reduction in prostate cancer proliferation rates. The present study suggests that an additional amount of 2 g ALA per day may increase serum PSA, but it is unclear if and how ALA could influence prostate carcinogenesis.  In conclusion, an additional amount of 2 g ALA per day did increase the PSA concentration by 0.1 ng per mL, but the confidence interval ranged from a nil finding to a clinically meaningful effect. More research is needed to find out whether ALA influences the serum PSA level and the risk of prostate cancer and which levels of ALA intake are optimal for human health. (Editors comments)