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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
46
2 oz. walnuts/day (2-3% of total calories from ALA)
2-3% ALA but no walnuts provided
ALA replaced by oleic acid
Penn State University
University Park, Pennsylvania, United States
Change from baseline in central blood pressure at the end of diet period 1 (week 6), end of diet period 2 (week 14), and end of diet period 3 (week 22)
Time frame: End of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in 24-hour ambulatory blood pressure
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in indices of arterial stiffness (pulse wave velocity)
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in lipoprotein particle size
The VAP© Test provides a direct measure of the following lipid and lipoprotein classes and subclasses: LDL, Lp(a), IDL, LDL1, LDL2, LDL3, LDL4, HDL, HDL2, HDL3, VLDL, VLDL1+2, VLDL3, TC, TG, Non-HDL, Remnant Lipoproteins, ApoB100, and ApoA1
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6)
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in the composition of the gut microbiome
This will be assessed via sequencing of microbial 16S rRNA from fecal samples.
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in serum C-reactive protein
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
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Change in serum glucose
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in serum insulin
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in urinary F2α-isoprostanes
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in lipid/lipoprotein profile
Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in heart rate variability
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Change in vascular adhesion markers (VCAM and ICAM)
Time frame: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)