Trial DesignEffect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: Design and baseline characteristics of the Alpha Omega Trial
Section snippets
Study design
The Alpha Omega Trial is a multicenter, double-blind, placebo-controlled trial with a parallel 2 × 2 factorial design resulting in 4 treatment groups (Figure 1). Subjects were enrolled in the trial from April 2002 to December 2006 and randomly assigned to different margarine spreads that provided low doses of n-3 fatty acids or placebo (described in more detail below), for a period of 40 months. Dosages are comparable to the Recommended Dietary Intakes for these n-3 fatty acids, namely
Results—Baseline characteristics of the cohort
Baseline characteristics of the cohort of the Alpha Omega Trial are shown in Table V. The cohort included 3,783 men (78%) and 1,054 women (22%), and most subjects (98.6%) were white. Subjects were on average 69 years old. Ten randomized patients did not meet the inclusion criterion for age, that is, one subject was aged 58 and 9 subjects were aged 59 at entry. The median period between the last MI and entry into the study was 3.7 years (Q1-Q3 1.7-6.3 years). For >90% of the subjects, a verified
Discussion
The Alpha Omega Trial is the first food-based double-blind intervention study in which low doses of n-3 fatty acids (ie, intakes within the normal dietary range) are studied in relation to fatal and nonfatal CVD. The n-3 fatty acids were administered through enriched margarine spreads. Trials of low doses of n-3 fatty acids are still feasible in the Netherlands because n-3 enriched foods are only now entering the market and dietary supplements are not widely consumed. Furthermore, Dutch people
Disclosures
Funding sources: Netherlands Heart Foundation (grant no. 2000T401), US National Institutes of Health (NIH/NHLBI and ODS, grant no. R01HL-076200) and Unilever R&D, Vlaardingen.
Author contributions: JMG coordinated the Alpha Omega Trial, contributed to the design of the study, obtained funding and drafted the manuscript; EJG contributed to the design of the study and provided medical supervision of the Alpha Omega Trial; EGS contributed to the design of the study and cosupervised the data
Acknowledgements
The authors express their gratitude to Eveline Waterham, Janny Heijstee, Marianne Pluigers, and Lucy Okma for their valuable contribution to data collection and administrative support. We thank Betty van der Struijs and Pieter Versloot for fatty acid analyses and Els Siebelink for processing of dietary data. Herbert van de Heuvel (LOF B.V., Egmond aan den Hoef) and Nicolette Mak (Valid Express, Amsterdam) are gratefully acknowledged for margarine distribution.
References (29)
- et al.
lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis
Lancet
(2007) - et al.
Dietary α-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk. A meta-analysis
J Nutr
(2004) - et al.
n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review
Am J Clin Nutr
(2006) - et al.
Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids
J Nutr
(2009) - et al.
Relative and biomarker-based validity of a food-frequency questionnaire estimating intake of fats and cholesterol
Am J Clin Nutr
(1993) - et al.
Validity of the physical activity scale for the elderly (PASE): according to energy expenditure assessed by the doubly labeled water method
J Clin Epidemiol
(1997) - et al.
“Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975) - et al.
Fatty acid composition of serum cholesteryl esters and erythrocyte membranes as indicators of linoleic acid intake in man
Am J Clin Nutr
(1989) - et al.
Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART)
Lancet
(1989) - et al.
Fatty acid composition of the plasma lipids in Greenland Eskimos
Am J Clin Nutr
(1975)
The inverse relation between fish consumption and 20-year mortality from coronary heart disease
N Eng J Med
Accumulated evidence on fish consumption and coronary heart disease mortality. A meta-analysis of cohort studies
Circulation
Fish intake, contaminants, and human health: evaluating the risks and the benefits
JAMA
Effect of fish oil on arrhythmias and mortality: systematic review
BMJ
Cited by (0)
Clinical trial registration: ClinicalTrials.gov no. NCT00127452.
- d
Members of the Alpha Omega Trial Group are listed in Appendix B.