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

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ClinicalTrials.gov Identifier: NCT00938340
Recruitment Status : Completed
First Posted : July 13, 2009
Results First Posted : October 29, 2018
Last Update Posted : October 29, 2018
Sponsor:
Collaborator:
California Walnut Commission
Information provided by (Responsible Party):
Penny Kris-Etherton, Penn State University

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.

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Dietary Supplement: Walnut "meat" Dietary Supplement: Walnut Oil Dietary Supplement: Walnut Skins Dietary Supplement: Whole walnut Not Applicable

Detailed Description:
Walnuts contain high contents of polyunsaturated fatty acids (PUFA), particularly linoleic acid and linolenic acid. The high PUFA content has been suggested to reduce CVD risk through decreasing total and LDL-cholesterol concentrations, and increasing HDL-C concentrations. In addition, walnuts are rich in substances such as ellagic acid (a polyphenol), antioxidants, vitamin E, fiber, essential fatty acids, flavanoids, and phenolic acids. Polyphenolic compounds are believed to have multiple biological effects influencing oxidative stress, platelet function, inflammation, and cancer initiation and propagation. There is interest in identifying foods with these and other favorable compounds to test their efficacy in real world settings to further understand their role in the human diet. Despite positive benefits found in consumption of the walnuts, it is not known which specific component of the walnut (i.e., whole walnut, walnut skin, defatted walnut, or walnut oil) is most beneficial to health. The investigators hypothesize that maximum improvements in oxidative stress, inflammatory markers, platelet and endothelial function will be observed following consumption of the whole nut versus isolated walnut components, thereby leading to a recommendation to consume walnuts. In addition, results from the research proposed will provide new information about the antioxidant, inflammatory, platelet activity and endothelial effects of the different walnut components and the synergistic effects these components have in the postprandial state.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Postprandial Effects of Walnut Components vs Whole Walnuts on Oxidative Stress, Inflammation, Platelet Function, and Endothelial Function in Volunteers With Moderate Hypercholesterolemia
Study Start Date : August 2007
Actual Primary Completion Date : February 2009
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Whole walnut
85g whole walnuts, ground, incorporated into inert food carrier
Dietary Supplement: Whole walnut
85g whole walnuts, ground, incorporated into inert food carrier

Experimental: Walnut "meat"
Separated, ground walnut de-fatted nut meat incorporated into inert food carrier
Dietary Supplement: Walnut "meat"
Separated, ground walnut de-fatted nut meat incorporated into inert food carrier

Experimental: Walnut oil
Walnut oil extracted from nut meat and incorporated into inert food carrier
Dietary Supplement: Walnut Oil
Walnut oil extracted from nut meat and incorporated into inert food carrier

Experimental: Walnut skins
Separated, ground walnut skins incorporated into inert food carrier
Dietary Supplement: Walnut Skins
Separated, ground walnut skins incorporated into inert food carrier




Primary Outcome Measures :
  1. Main Effect of Treatment on the Ferric Reducing Antioxidant Potential (FRAP) Changes in Response to 4 Walnut Treatments [ Time Frame: 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. ]
    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.

  2. Main Effect of Treatment by Timepoint on the Ferric Reducing Antioxidant Potential (FRAP) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline for each timepoint (60, 120, 240, 360 min) ]
    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).

  3. Main Effect of Treatment on the Changes in Total Thiol Response to 4 Walnut Treatments [ Time Frame: 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. ]
    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.

  4. Main Effect of Treatment by Timepoint on Total Thiol Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline for each timepoint (60, 120, 240, 360 min) ]
    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).

  5. Main Effect of Treatment on the Changes in Malondialdehyde (MDA) Response to 4 Walnut Treatments [ Time Frame: 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. ]
    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.

  6. Main Effect of Treatment by Timepoint on Malondialdehyde (MDA) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline for each timepoint (60, 120, 240, 360 min) ]
    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).

  7. Main Effect of Treatment on the Changes in C-reactive Protein (CRP) Response to 4 Walnut Treatments [ Time Frame: 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. ]
    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.

  8. Main Effect of Treatment by Timepoint on C-reactive Protein (CRP) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline for each timepoint (60, 120, 240, 360 min) ]
    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).


Secondary Outcome Measures :
  1. Main Effect of Treatment on Reactive Hyperemia Index (RHI) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline at 240 min ]
    On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. At baseline the endothelial function test was performed using pulse amplitude tonometry (PAT) (Itamar Medical). Participants then had 15 min to consume 1 of the 4 walnut test meals. The endothelial function test was performed again at 240 min postmeal. RHI was calculated as the ratio of the average pulse wave amplitude during hyperemia (60 to 120 s of the post occlusion period) to the average pulse wave amplitude during baseline in the occluded hand divided by the same values in the control hand and then multiplied by a baseline correction factor. No endothelial function test data available for one participant within the walnut oil group and one within the defatted walnut nutmeat group.

  2. Main Effect of Treatment on Framingham Reactive Hyperemia Index (fRHI) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline at 240 min ]
    On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. At baseline the endothelial function test was performed using pulse amplitude tonometry (PAT) (Itamar Medical). Participants then had 15 min to consume 1 of the 4 walnut test meals. The endothelial function test was performed again at 240 min postmeal. fRHI is an alternative calculation derived from the same raw data (as RHI) and differs in that it uses the period from 90 to 120 s of postocclusion hyperemia, does not incorporate a baseline correction factor, and has a natural log transformation applied to the resulting ratio. No endothelial function test data available for one participant within the walnut oil group and one within the defatted walnut nutmeat group.

  3. Main Effect of Treatment on Heart Rate (HR) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline at 240 min ]
    On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. At baseline the endothelial function test was performed using pulse amplitude tonometry (PAT) (Itamar Medical). Participants then had 15 min to consume 1 of the 4 walnut test meals. The endothelial function test was performed again at 240 min postmeal. No endothelial function test data available for one participant within the walnut oil group and one within the defatted walnut nutmeat group.

  4. Main Effect of Treatment on Augmentation Index (AI) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline at 240 min ]
    On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. At baseline the endothelial function test was performed using pulse amplitude tonometry (PAT) (Itamar Medical). Participants then had 15 min to consume 1 of the 4 walnut test meals. The endothelial function test was performed again at 240 min postmeal. AI is a measure of vascular stiffness (pulse wave reflection) that is calculated from the shape of the pulse wave recorded during baseline. No endothelial function test data was available for one participant within the walnut oil group and one within the defatted walnut nutmeat group.

  5. 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 [ Time Frame: Change from baseline at 240 min ]
    On the day of each test, participants arrived at the General Clinical Research Center after a 12-h overnight fast. At baseline the endothelial function test was performed using pulse amplitude tonometry (PAT) (Itamar Medical). Participants then had 15 min to consume 1 of the 4 walnut test meals. The endothelial function test was performed again at 240 min postmeal. AI is a measure of vascular stiffness (pulse wave reflection) that is calculated from the shape of the pulse wave recorded during baseline. AI can be adjusted to a heart rate of 75 beats/min (AI_75) to correct for the independent effect of heart rate on this measure.No endothelial function test data was available for one participant within the walnut oil group and one within the defatted walnut nutmeat group.

  6. Main Effect of Treatment on the Triglyceride (TG) Changes in Response to 4 Walnut Treatments [ Time Frame: 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. ]
    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 TG was measured at 0, 30, 60, 120, 240, and 360 min. TG were determined by standard colorimetric and enzymatic procedures with commercially available kits (Alfa Wassermann).

  7. Main Effect of Treatment by Timepoint on Triglyceride (TG) Changes in Response to 4 Walnut Treatments [ Time Frame: Change from baseline for each timepoint (30, 60, 120, 240, 360 min) ]
    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 TG was measured at 0, 30, 60, 120, 240, and 360 min. TG were determined by standard colorimetric and enzymatic procedures with commercially available kits (Alfa Wassermann). Several blood samples (n=4) could not be obtained/measured [walnut skin group at 360 min (n=1), walnut oil group at 120 min (n=2), whole walnut group at 240 min(n=1)].



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00938340


Locations
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United States, Pennsylvania
Penn State General Clinical Research Center
University Park, Pennsylvania, United States, 16802
Sponsors and Collaborators
Penn State University
California Walnut Commission
Investigators
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Principal Investigator: Penny M Kris-Etherton, PhD Penn State University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Penny Kris-Etherton, Distinguished Professor of Nutrition, Penn State University
ClinicalTrials.gov Identifier: NCT00938340     History of Changes
Other Study ID Numbers: PKE 102
First Posted: July 13, 2009    Key Record Dates
Results First Posted: October 29, 2018
Last Update Posted: October 29, 2018
Last Verified: February 2018
Keywords provided by Penny Kris-Etherton, Penn State University:
Cardiovascular Disease
Additional relevant MeSH terms:
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Cardiovascular Diseases