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

Abstract

BackgroundAlpha 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.MethodsThe 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).FindingsMean 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).InterpretationAn 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 informationClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452.

Dietary Factors and Supplements Influencing Prostate-Specific Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Analysis Review Based on Randomized Controlled Trials

“…Similarly, a cross-over, 6-month lower-dose walnut supplementation (35 g/d) with a 4-week washout interval, failed to reduce PSA among middle-aged men [ 199 ]. Similarly, the Alpha Omega trial [ 200 ] failed to demonstrate differences in the PSA concentrations of older adults with a history of myocardial infarction following 40 months of margarine spread-based α-linolenic acid (ALA) supplementation compared with placebo. When men were randomized to receiving EPA (2.4 g/d) for 12 weeks, or no intervention in the “Study of EPA Effects on Prostate Cancer” (SEEPC) [ 201 ], no differences in PSA response were recorded.…”

Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease

“…Forty-nine trials, including 24,272 randomised participants, met the inclusion criteria. Trials ranged in size from 36 randomised participants (Rossing 1996) to 4997 randomised participants (PREDIMED 2013), with 15 trials randomising at least 250 participants (AlphaOmega -ALA;Bates 1989;DART fat 1989;EPIC-1 2008;EPIC-2 2008;EPOCH 2011;FAAT -Leaf 2005;MRC 1968;NDHS Open 1st 1968;ORL 2013;PREDIMED 2013;Sydney Diet-Heart 1978;Veterans Admin 1969;WAHA -Ros 2016;WINS 2006).…”

Nutrition, dietary interventions and prostate cancer: the latest evidence

“…Despite the promise of omega-3 fatty acids, not all studies agree. Supplementing 2 g alpha-linolenic acid (ALA) per day for 40 months in 1,622 men with PSA <4 ng/ml did not change their PSA [ 72 ]. However, another study found that a high blood serum n-3 PUFA and docosapentaenoic acid (DPA) was associated with reduced total PCa risk while high serum EPA and docosahexaenoic acid (DHA) was possibly associated with increased high-grade PCa risk [ 73 ].…”