Heart & Health Study
Condition: Heart Disease
MeSH terms: Heart Diseases
Study type: Interventional

Summary: 
      We hope to learn more about why certain people have higher levels of the 5-LO protein and
      whether taking fish oil supplements gives such individuals greater protection than others
      against cardiovascular disease. The 5-LO protein is important in the development of heart
      disease because it converts a type of oil from meat into a compound that can cause
      inflammation in blood vessels. This inflammation is a major cause of heart disease.

      Researchers think that people with higher levels of a protein called 5-LO in their white
      blood cells may have a healthier response to using fish oil supplements than do people with
      lower levels of this protein.
    

Detailed description: 
      Fish oil supplements will be given to subjects with different variants in the promoter region
      of the arachidonate 5-lipoxygenase (ALOX5) gene and outcome measures will be evaluated after
      6 wk of supplementation. These outcomes include ALOX5 protein levels (also called
      5-lipoxygenase, or 5-LO), leukotriene levels, markers of inflammation, and blood lipids. The
      5-LO enzyme converts arachidonic acid (AA) to leukotrienes that promote inflammation.
      Subjects with different promoter variants are hypothesized to have different basal or
      stimulated levels of 5-LO expression. Preliminary data suggests that subjects with a promoter
      variant that causes increased 5-LO expression also may have a "better" anti-inflammatory or
      lipid-lowering response to fish oil supplements. The homozygous variant genotype is much more
      common in African Americans than other groups thus we propose to conduct the study in African
      Americans. The fish oil eicosapentaenoic acid (EPA) competitively inhibits conversion of AA
      to pro-inflammatory 4-series leukotrienes.

      The grant proposes to conduct a community-based, double-masked, randomized,
      placebo-controlled trial; n = 15/group, total = 166 (genotypes 44 will have n = 8). The
      intervention group will receive 5.0 g/d fish oil concentrate (3.0 g/d EPA + DHA) for 6 wk.
      The study will be conducted in Oakland, Davis, and Sacramento, California where African
      Americans 20 - 59 y of age without serious chronic disease will be recruited.

      A recent observational study indicates that subjects with a variant allele for ALOX5 may be
      at greater risk for cardiovascular disease and, at the same time, may derive a greater
      benefit from omega-3 fatty acid supplements than do subjects homozygous for the common
      allele. The variant alleles are less common in the white population (18%) than in the black
      population (52%). Since African Americans have a higher prevalence of cardiovascular disease
      and of the ALOX5 variant alleles, as shown in epidemiologic studies, they may have a greater
      benefit from omega-3 supplementation in the reduction of inflammation and cardiovascular risk
      factors. Recruitment will be conducted through the community service, Ethnic Health Institute
      (EHI), of Alta Bates Summit Medical Center in conjunction with UCD, and outreach efforts from
      the USDA, ARS, Western Human Nutrition Research Center (WHNRC) at UC Davis. We will determine
      if subjects with one or two variant ALOX5 alleles have higher ALOX5 gene expression, higher
      production of AA-derived leukotrienes, and a better response to omega-3 supplements than do
      subjects homozygous for the common allele.
    

Intervention name(s): Fish Oil; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): capsules, 5.0 g/d fish oil concentrate (3.0 g/d EPA + DHA), 6 weeks; capsule, 5.0 g/d corn/soybean oil (50/50 mixture), 6 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: ALOX5; 5-lipoxygenase; Heart Disease; Blacks