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

PLoS One. 2013 Dec 11;8(12):e81519. doi: 10.1371/journal.pone.0081519. eCollection 2013.


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.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage
  • Double-Blind Method
  • Eicosapentaenoic Acid / administration & dosage
  • Humans
  • Logistic Models
  • Male
  • Margarine
  • Middle Aged
  • Myocardial Infarction / physiopathology
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate-Specific Antigen / blood*
  • alpha-Linolenic Acid / administration & dosage*


  • alpha-Linolenic Acid
  • Docosahexaenoic Acids
  • Margarine
  • Eicosapentaenoic Acid
  • Prostate-Specific Antigen

Associated data

  • ClinicalTrials.gov/NCT00127452

Grants and funding

Financial support was obtained from The Netherlands Heart Foundation, the National Institutes of Health (NIH), and Unilever Research and Development. The grant of The Netherlands Heart Foundation covered baseline examinations and mortality follow-up. The NIH grant covered mid-term and final examinations and the verification of nonfatal cardiovascular events. Unilever provided an unrestricted grant for distribution of trial margarines to the patients. Martijn B Katan and Daan Kromhout were supported by an Academy Professorship award of the Royal Netherlands Academy of Arts and Sciences. The funding organizations had no role in the design of the study, data collection, data analysis, interpretation, writing of the report, or the decision to submit.