Suppression of Postprandial Monocyte Activation by Blueberries or Docosahexaenoic Acid in Humans
Condition: Inflammation
MeSH terms: Inflammation
Study type: Interventional

Summary: 
      The overall goal of the research study is to determine whether a high-fat meal causes
      postprandial (after meal) inflammation, and whether eating n-3 polyunsaturated fatty acids
      (PUFAs) or blueberries that are rich in anti-inflammatory polyphenols suppress the
      inflammation in healthy people.
    

Detailed description: 
      Chronic inflammation is one of the key etiological conditions associated with the development
      and progression of chronic diseases including Alzheimer's disease, atherosclerotic
      cardiovascular disease, insulin resistance, obesity and cancer. The causes of chronic
      inflammation and the role of diet in suppressing inflammation are challenging research
      questions. Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs),
      nucleotide-binding oligomerization domain proteins (NODs), and the inflammasome expressed in
      innate immune cells can be activated by a variety of endogenous molecules derived from tissue
      injury and diet (in particular saturated fatty acids), eliciting inflammation. Dysregulated
      induction of PRR-mediated inflammation is known to promote the development of chronic
      diseases. Previous studies showed that saturated fatty acids can activate toll-like receptor
      4 (TLR4) and nucleotide-binding oligomerization domain 2 (NOD2) mediated signaling pathways,
      whereas, docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, and certain
      polyphenols (quercetin, luteolin, Epigallocatechin gallate (EGCG), resveratrol) rich in
      certain fruits and vegetables inhibit TLR4 or NOD2-mediated inflammation. In addition,
      numerous studies have demonstrated that TLR4 knockout mice were protected from high saturated
      fat diet-induced inflammation and insulin resistance, suggesting that high fat diet-induced
      inflammation and insulin resistance are at least partly mediated through the activation of
      TLR4. Direct evidence of saturated fatty acids derived from a high fat meal activating PRRs
      in humans has not been demonstrated. Thus, the investigators propose to determine whether
      saturated fatty acids derived from a high saturated fat meal activate blood monocytes through
      PRRs and whether dietary DHA and freeze-dried blueberry powder can suppress high saturated
      fat meal-induced inflammation by inhibiting PRR activation.

      The experimental procedures and the study activities will last for approximately 9 weeks.
      There will be three test days, scheduled 4 weeks apart. On the test days there will be four
      blood draws (one fasting blood draw and three postprandial blood draws at 1-hour, 3-hour and
      6-hour after breakfast, respectively). Three endothelial function measurements (EndoPAT) will
      be carried out each test day. A pre-test dinner meal will be provided to the subject to eat
      the night before each test day. Subjects will be asked to follow and record a low antioxidant
      and polyphenol diet of their own choosing for 3 days prior to each test day. This includes
      minimizing tea, wine, coffee, chocolate, fruits, vegetables, whole grains, soy, herbs,
      spices, condiments, and fatty fish. All volunteers will participate in all test days,
      receiving in randomize cross-over fashion the following treatments:

      A. High saturated fat diet, placebo powder, sunflower oil. B. High saturated fat diet,
      blueberry powder, sunflower oil. C. High saturated fat diet, placebo powder, DHA.

      The high saturated fat meal will be identical in all treatments and may contain tortilla,
      cheddar cheese, beef sausage, scrambled eggs, and a smoothie style drink containing sugar,
      vanilla extract, oil, whole milk yogurt and the ingredients for masking treatments. The
      placebo powder may contain Beneprotein® (Nestlé Nutrition), Benefiber® (Novartis), oil,
      sugar, artificial food-grade blueberry flavor, and artificial food-grade blue and red colors.
      The blueberry powder (equivalent to four 1/2 cup servings) will be obtained from the U.S.
      Highbush Blueberry Council (Folsom, CA). The DHA will be obtained from Martek Biosciences.
      Blueberry or placebo powder and the DHA or sunflower oil will be combined into a blueberry
      flavored smoothie style drink. Neither the study subjects or the investigators will know
      which treatment is provided on which test day.
    

Intervention name(s): High saturated fat meal, placebo powder and sunflower oil; High saturated fat meal, blueberry powder and sunflower oil; High saturated fat meal, placebo powder and DHA
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): High saturated fat meal with a blueberry flavored shake and sunflower oil; High saturated fat meal with blueberry powder shake and sunflower oil; High saturated fat meal with a blueberry flavored shake and DHA
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: n-3 polyunsaturated fatty acids; blueberries