Postprandial Effects of Walnut Components Versus Whole Walnuts on Cardiovascular Disease (CVD) Risk Reduction

NCT00938340 | Completed Results DMC

• 1 other identifier: PKE 102
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the acute, postprandial effects and mechanism of action of various walnut components (separated nut skins, de-fatted nut meat, nut oil) versus whole walnuts on oxidative stress, inflammation and measures of platelet and endothelial function in healthy adults with moderately elevated cholesterol levels.

Conditions

Cardiovascular Disease

Keywords

Cardiovascular Disease

Outcome Measures

Primary Outcomes (8)

• Main Effect of Treatment on the Ferric Reducing Antioxidant Potential (FRAP) Changes in Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. A baseline (0 min) fasting blood sample was collected. Participants then had 15 min to consume 1 of the 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and FRAP was measured at 0, 60, 120, 240, and 360 min. The FRAP assay was used to determine the reducing ability of plasma in a redox-linked colorimetric reaction. Plasma was incubated with the FRAP reagent at room temperature for 1 h and the absorbance at 593 nm was then recorded. Trolox was used as a reference to construct a standard curve to calculate the FRAP value of the samples. The FRAP assay measures lipophilic and hydrophilic antioxidants (total antioxidant capacity), both of which are present in walnuts.

  AUC values were calculated with the trapezoidal rule, using the respective fasting baseline value as the line of reference. Measured at 0 to 360 min (baseline to 360min post meal) for each of the 4 walnut treatments.

• Main Effect of Treatment by Timepoint on the Ferric Reducing Antioxidant Potential (FRAP) Changes in Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. A baseline (0 min) blood sample was collected. Participants then had 15 min to consume 1 of 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and FRAP was measured at 0, 60, 120, 240, and 360 min. The FRAP assay was used to determine the reducing ability of plasma in a redox-linked colorimetric reaction. Plasma was incubated with the FRAP reagent at room temperature for 1 h and the absorbance at 593 nm was then recorded. Trolox was used as a reference to construct a standard curve to calculate the FRAP value of the samples. The FRAP assay measures lipophilic and hydrophilic antioxidants (total antioxidant capacity), both of which are present in walnuts. Several blood samples (n=3) could not be obtained/measured (walnut skin group at 360 min, walnut oil group at 120 min, whole walnut group at 240 min).

  Change from baseline for each timepoint (60, 120, 240, 360 min)

• Main Effect of Treatment on the Changes in Total Thiol Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. A baseline (0 min) fasting blood sample was collected. Participants then had 15 min to consume 1 of the 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and total thiols measured at 0, 60, 120, 240, and 360 min. Total thiols in plasma were determined by the following methods: an aliquot of EDTA plasma was mixed with Tris-EDTA buffer, followed by addition of 10 mmol/L 2,2-dithiobisnitrobenzoic acid and methanol. After incubation at room temperature for 15 min and centrifugation, the absorbance of the supernatant was measured at 412 nm.

  AUC values were calculated with the trapezoidal rule, using the respective fasting baseline value as the line of reference. Measured at 0 to 360 min (baseline to 360min post meal) for each of the 4 walnut treatments.

• Main Effect of Treatment by Timepoint on Total Thiol Changes in Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. A baseline (0 min) fasting blood sample was collected. Participants then had 15 min to consume 1 of the 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and total thiols measured at 0, 60, 120, 240, and 360 min. Total thiols in plasma were determined by the following methods: an aliquot of EDTA plasma was mixed with Tris-EDTA buffer, followed by addition of 10 mmol/L 2,2-dithiobisnitrobenzoic acid and methanol. After incubation at room temperature for 15 min and centrifugation, the absorbance of the supernatant was measured at 412 nm. Several blood samples (n=3) could not be obtained/measured (walnut skin group at 360 min, walnut oil group at 120 min, whole walnut group at 240 min).

  Change from baseline for each timepoint (60, 120, 240, 360 min)

• Main Effect of Treatment on the Changes in Malondialdehyde (MDA) Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. A baseline (0 min) fasting blood sample was collected. Participants then had 15 min to consume 1 of the 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and MDA measured at 0, 60, 120, 240, and 360 min. Plasma MDA was measured by an Agilent 1100 HPLC system with fluorometric detection.

  AUC values were calculated with the trapezoidal rule, using the respective fasting baseline value as the line of reference. Measured at 0 to 360 min (baseline to 360min post meal) for each of the 4 walnut treatments.

• Main Effect of Treatment by Timepoint on Malondialdehyde (MDA) Changes in Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the clinic after a 12-h overnight fast. A baseline (0 min) blood sample was collected. Participants then had 15 min to consume 1 of the 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and MDA measured at 0, 60, 120, 240, and 360 min. Plasma MDA was measured by an Agilent 1100 HPLC system with fluorometric detection. Several blood samples (n=2) could not be obtained (walnut oil group at 120 min and whole walnut group at 240 min).

  Change from baseline for each timepoint (60, 120, 240, 360 min)

• Main Effect of Treatment on the Changes in C-reactive Protein (CRP) Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. A baseline (0 min) fasting blood sample was collected. Participants then had 15 min to consume 1 of the 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and CRP measured at 0, 60, 120, 240, and 360 min. Serum CRP was measured by latex-enhanced immunonephelometry.

  AUC values were calculated with the trapezoidal rule, using the respective fasting baseline value as the line of reference. Measured at 0 to 360 min (baseline to 360min post meal) for each of the 4 walnut treatments.

• Main Effect of Treatment by Timepoint on C-reactive Protein (CRP) Changes in Response to 4 Walnut Treatments

  On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. A baseline (0 min) fasting blood sample was collected. Participants then had 15 min to consume 1 of the 4 walnut test meals. Blood samples (∼30 mL) were subsequently taken at 30, 60, 120, 240, and 360 min following the meal and CRP measured at 0, 60, 120, 240, and 360 min. Serum CRP was measured by latex-enhanced immunonephelometry. Several blood samples (n=3) could not be obtained/measured (walnut oil/120 min, whole walnut/240 min, and walnut skin/360 min).

  Change from baseline for each timepoint (60, 120, 240, 360 min)

Secondary Outcomes (7)

• Main Effect of Treatment on Reactive Hyperemia Index (RHI) Changes in Response to 4 Walnut Treatments

  Change from baseline at 240 min

• Main Effect of Treatment on Framingham Reactive Hyperemia Index (fRHI) Changes in Response to 4 Walnut Treatments

  Change from baseline at 240 min

• Main Effect of Treatment on Heart Rate (HR) Changes in Response to 4 Walnut Treatments

  Change from baseline at 240 min

• Main Effect of Treatment on Augmentation Index (AI) Changes in Response to 4 Walnut Treatments

  Change from baseline at 240 min

• Main Effect of Treatment on Augmentation Index Standardized to a Heart Rate of 75 Beats/Min (AI_75) Changes in Response to 4 Walnut Treatments

  Change from baseline at 240 min

Study Arms (4)

Whole walnut

EXPERIMENTAL

85g whole walnuts, ground, incorporated into inert food carrier

Dietary Supplement: Whole walnut

Walnut "meat"

EXPERIMENTAL

Separated, ground walnut de-fatted nut meat incorporated into inert food carrier

Dietary Supplement: Walnut "meat"

Walnut oil

EXPERIMENTAL

Walnut oil extracted from nut meat and incorporated into inert food carrier

Dietary Supplement: Walnut Oil

Walnut skins

EXPERIMENTAL

Separated, ground walnut skins incorporated into inert food carrier

Dietary Supplement: Walnut Skins

Interventions

Walnut "meat" DIETARY_SUPPLEMENT

Separated, ground walnut de-fatted nut meat incorporated into inert food carrier

Walnut "meat"

Walnut Oil DIETARY_SUPPLEMENT

Walnut oil extracted from nut meat and incorporated into inert food carrier

Walnut oil

Walnut Skins DIETARY_SUPPLEMENT

Separated, ground walnut skins incorporated into inert food carrier

Walnut skins

Whole walnut DIETARY_SUPPLEMENT

85g whole walnuts, ground, incorporated into inert food carrier

Whole walnut

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 21 - 60 years
• Body mass index 25-39 kg/m2
• LDL cholesterol \>110 mg/dL
• \<95 percentile for age and gender for both (based on NHANES data)
• TG \< 350 mg/dL

You may not qualify if:

• High alcohol consumption \> 21 units/week (female subjects) or \> 28 units/week (male subjects)
• Intake of vitamin and mineral supplements within the past 3 weeks or unwillingness to discontinue for 3 weeks prior to screening and for entire study.
• Use of prescription cholesterol-lowering or blood pressure-lowering medications during the study
• Intake of other putative cholesterol-lowering supplements (excl. psyllium, fish oil capsules, soy lecithin, phytoestrogens)
• Intake of anti-inflammatory medications (containing aspirin or NSAIDS) on a regular basis or if an acute intake, within 48 hours of a test day
• Diabetes, liver, kidney, thyroid (unless controlled and stable on replacement medication) or other endocrine disorders from self-reported medical history
• Treatment with drugs acting on the gut, such as ezetimibe, bile acid-binding resins, orlistat
• Dietary restrictions such as a medically prescribed diet, or a slimming diet prior to or during the trial
• Weight loss or gain of 10% body weight or more during a period of 6 months before pre-study examination.
• Blood/plasma donation for reason(s) other than the present study prior to the study (1 month for a male subject or 2 months for a female subject), or during the study
• Lactation 6 weeks before the start of and during study, pregnant or wishing to become pregnant 3 months before or during the study

Sponsors & Collaborators

• Penn State University: lead
• California Walnut Commission: collaborator

Study Sites (1)

Penn State General Clinical Research Center

University Park, Pennsylvania, 16802, United States

Location

Related Publications (2)

• Berryman CE, Grieger JA, West SG, Chen CY, Blumberg JB, Rothblat GH, Sankaranarayanan S, Kris-Etherton PM. Acute consumption of walnuts and walnut components differentially affect postprandial lipemia, endothelial function, oxidative stress, and cholesterol efflux in humans with mild hypercholesterolemia. J Nutr. 2013 Jun;143(6):788-94. doi: 10.3945/jn.112.170993. Epub 2013 Apr 24.

  PMID: 23616506 DERIVED

• 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.

  PMID: 21871057 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Results Point of Contact

• Title: Penny Kris-Etherton
• Organization: Penn State University

pmk3@psu.edu

Study Officials

• Penny M Kris-Etherton, PhD

  Penn State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2009
• First Posted: July 13, 2009
• Study Start: August 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: May 1, 2009
• Last Updated: August 21, 2023
• Results First Posted: October 29, 2018

Record last verified: 2023-08

Locations

US (1)