Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA): results from the alpha omega trial

Abstract

Background: 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.

Methods: The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452) 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 2×2 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 60-80 years with an initial PSA concentration <4 ng/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: >4 ng/mL).

Findings: Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: -0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84-1.58).

Interpretation: 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/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.

Trial registration information: ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452.

Figure 1. Participant flow for the study on effect of alpha linolenic acid (ALA) supplementation on PSA in post myocardial patients in the Alpha Omega Trial.

Figure 2. Alpha linolenic acid (ALA) concentrations in plasma cholesteryl esters at baseline, after 20 months and after 40 months, in random samples of post-MI patients, according to treatment group.

Geometric mean values (expressed as mass percentage) on a logarithmic scale are given, with error bars indicating standard errors. After 20 and 40 months, ALA supplementation in the margarine increased serum ALA by 64·7% and 66·9% as compared with placebo. *P<0·001 for group difference at that time point, obtained by t-test for independent samples.

Figure 3. Effect of ALA supplementation on prostate specific antigen (PSA) concentrations (ng/mL) of 1622 male patients.

Values are means (95% confidence interval). ALA = alpha linolenic acid, EPA = eicosapentanoic acid = EPA, DHA = docosahexanoic acid. For the two comparisons of ALA vs. placebo the test of heterogeneity was non-significant (Q-value 0.054; I-squared 0.000; P = 0.82), similar to the comparisons of EPA-DHA vs. placebo (Q-value 0.052; I-squared 0.000; P = 0.82).