Effects of Walnuts on Central Blood Pressure, Arterial Stiffness Indices, Lipoproteins, and Other CVD Risk Factors

Cardiovascular Disease Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02210767
• Other study ID #: PKE ALA
• Status: Completed
• Phase: N/A
• Start date: August 2014
• Est. completion date: April 2018

Study information

• Verified date: August 2023
• Source: Penn State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

Inclusion Criteria:

• Aged 30-65 years

• BMI greater than 25 and less than or equal to 40 kg/m2

• Non-smokers

• TG < 350 mg/dL

• LDL-C between the 25-95th percentile from NHANES:

• Males: 105-194 mg/dL

• Females: 98-190 mg/dL

• Stage I hypertension:

• SBP > 120 mmHg and/or DBP > 80 mmHg

• SBP < 160 mmHg and DBP < 100 mmHg

• Free of established CVD, stroke, diabetes, liver, kidney or autoimmune disease.

Exclusion Criteria:

• Elevated BP (SBP =160 mmHg OR DBP = 100 mmHg)

• A history of myocardial infarction, stroke, diabetes mellitus, liver disease, inflammatory disease, kidney disease, and/or thyroid disease (unless controlled on medication).

• Blood pressure or cholesterol-lowering medication use

• Refusal to discontinue intake of putative cholesterol-lowering supplements (psyllium, fish oil capsules, soy lecithin, niacin, fiber, flax, and phytoestrogens).

• Vegetarianism or other dietary practices that are inconsistent with the test diets

• Nut allergies (Other food allergies will be reviewed on a case-by-case basis)

• Refusal to discontinue nutritional supplements, herbs, vitamins or NSAID's

• Latex allergy

• Pregnant or lactating females

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Other:
• Walnut Diet
2 oz. walnuts/day (2-3% of total calories from ALA)
• Walnut Control Diet
2-3% ALA but no walnuts provided
• Low ALA Diet
ALA replaced by oleic acid

Locations

Country	Name	City	State
United States	Penn State University	University Park	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Penn State University	California Walnut Commission

Country where clinical trial is conducted

United States, 

References & Publications (7)

Banel DK, Hu FB. Effects of walnut consumption on blood lipids and other cardiovascular risk factors: a meta-analysis and systematic review. Am J Clin Nutr. 2009 Jul;90(1):56-63. doi: 10.3945/ajcn.2009.27457. Epub 2009 May 20. — View Citation

Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L,Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279-1290.

McGuire S. U.S. Department of Agriculture and U.S. Department of Health and Human Services, Dietary Guidelines for Americans, 2010. 7th Edition, Washington, DC: U.S. Government Printing Office, January 2011. Adv Nutr. 2011 May;2(3):293-4. doi: 10.3945/an.111.000430. Epub 2011 Apr 30. No abstract available. — View Citation

Sabate J, Fraser GE, Burke K, Knutsen SF, Bennett H, Lindsted KD. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med. 1993 Mar 4;328(9):603-7. doi: 10.1056/NEJM199303043280902. — View Citation

West SG, Krick AL, Klein LC, Zhao G, Wojtowicz TF, McGuiness M, Bagshaw DM, Wagner P, Ceballos RM, Holub BJ, Kris-Etherton PM. Effects of diets high in walnuts and flax oil on hemodynamic responses to stress and vascular endothelial function. J Am Coll Nutr. 2010 Dec;29(6):595-603. doi: 10.1080/07315724.2010.10719898. — View Citation

Zhang J, Grieger JA, Kris-Etherton PM, Thompson JT, Gillies PJ, Fleming JA, Vanden Heuvel JP. Walnut oil increases cholesterol efflux through inhibition of stearoyl CoA desaturase 1 in THP-1 macrophage-derived foam cells. Nutr Metab (Lond). 2011 Aug 26;8:61. doi: 10.1186/1743-7075-8-61. — View Citation

Zhao G, Etherton TD, Martin KR, West SG, Gillies PJ, Kris-Etherton PM. Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr. 2004 Nov;134(11):2991-7. doi: 10.1093/jn/134.11.2991. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		End of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in 24-hour ambulatory blood pressure		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in indices of arterial stiffness (pulse wave velocity)		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	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	Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6)		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in the composition of the gut microbiome	This will be assessed via sequencing of microbial 16S rRNA from fecal samples.	Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in serum C-reactive protein		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in serum glucose		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in serum insulin		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in urinary F2a-isoprostanes		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in lipid/lipoprotein profile	Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides	Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in heart rate variability		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)
Secondary	Change in vascular adhesion markers (VCAM and ICAM)		Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)