Effects of Walnuts on Central Blood Pressure, Arterial Stiffness Indices, Lipoproteins, and Other CVD Risk Factors
Condition: Cardiovascular Disease
MeSH terms: Cardiovascular Diseases
Study type: Interventional

Summary: 
      This study will evaluate the effects of walnut-derived ALA and bioactives on multiple CVD
      risk factors, including central blood pressure, arterial stiffness indices, inflammatory
      markers, urinary isoprostanes, vascular adhesion markers, and changes in lipids and
      lipoproteins. Gut microbiome changes due to walnut consumption will also be assessed using
      the 16S rRNA gene.
    

Detailed description: 
      Diets containing nuts likely reduce cardiovascular disease (CVD) risk but the mechanisms
      remain poorly defined. Walnuts contain substantial amounts of polyunsaturated fatty acids
      (PUFAs), particularly alpha-linolenic acid (ALA), and are a rich source of bioactives. Many
      vegetable oils are high in PUFAs but most lack ALA and do not provide the same complement of
      bioactive compounds as walnuts. ALA is thought to improve cardiovascular health by modulating
      circulating lipid concentrations, altering membrane structure/function by enhancing the total
      ω-3 fatty acid content of cell membrane phospholipids, and reducing inflammatory reactions by
      inhibiting production of arachidonic acid-derived eicosanoids. Consumption of walnuts has
      consistently been shown to improve blood lipids/lipoproteins and vascular health. However,
      there remains much debate over what is the preferable replacement for saturated fat in the
      diet. Because of the ALA and bioactives that they provide, walnuts may confer specific CVD
      benefits. To study the effects of walnuts, in terms of both their ALA content and bioactive
      compounds, we will compare two test diets (one containing walnuts and one matched for PUFA
      and ALA content but devoid of walnuts and their bioactives) to a control diet matched for
      macronutrient and linoleic acid (LA) content but providing oleic acid in place of ALA. This
      diet design will provide information about how walnuts affect the selected endpoints of
      interest due to their bioactives as well as their ALA content, and whether walnut ALA is a
      superior substitute for dietary saturated fat compared to oleic acid.

      Feeding protocol and study treatments:

      This study is designed as a double-blind, 3-period, randomized, cross-over controlled feeding
      study. Prior to randomization, participants will complete a two week run-in on a standard
      Western diet. Each diet period treatment phase will be 6 weeks in duration, separated by
      2-week washout periods. The three test diets are: 1) a walnut diet (WD; providing ~2.0 oz of
      walnuts per day); 2) a matched walnut control diet (WCD) that will provide the same fatty
      acid profile as the walnut diet, but will not contain walnuts (and their bioactives); and 3)
      a low ALA diet (LAD) with a similar macronutrient (and linoleic acid) composition as the WD
      and WCD, but using oleic acid to replace ALA. Study diets will be prepared in a metabolic
      kitchen, with three isocaloric meals and a snack provided each day, based on a 7-day rotating
      menu cycle. Participants will be instructed to consume only the prepared foods and limit
      their intake of alcohol to 2 drinks/week and caffeinated calorie-free beverages to 40 ounces
      (5 drinks) per day. Diets will be planned for every subject according to his/her energy
      requirements and will be nutritionally adequate. This diet design will permit the WD to be
      compared with the WCD and LAD and, thereby, allow us to ascertain the specific effects that
      walnuts and their bioactive components (including and beyond ALA) may have on CVD risk
      factors and artery health.
    

Intervention name(s): Walnut Diet; Walnut Control Diet; Low ALA Diet
Intervention type(s): Other; Other; Other
Intervention description(s): 2 oz. walnuts/day (2-3% of total calories from ALA); 2-3% ALA but no walnuts provided; ALA replaced by oleic acid
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other