Cardiovascular DiseaseNCT00938340

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

A study testing Walnut "meat", Walnut Oil and Walnut Skins in people with Cardiovascular Disease, run by Penn State University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 21 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Cardiovascular Disease
What is being tested?: Walnut "meat", Walnut Oil and Walnut Skins
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteUnited States
Study dates: Aug 2007to May 2009
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

United States1 site

Penn State General Clinical Research Center
University Park, Pennsylvania, 16802

Other trials in United States

About this study

Official title: Postprandial Effects of Walnut Components vs Whole Walnuts on Oxidative Stress, Inflammation, Platelet Function, and Endothelial Function in Volunteers With Moderate Hypercholesterolemia

Read the 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.

Conditions: Cardiovascular Disease
Being tested: Walnut "meat", Walnut Oil, Walnut Skins, Whole walnut
Keywords: Cardiovascular Disease
Medical subject headings: Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Walnut "meat"Dietary supplement
Separated, ground walnut de-fatted nut meat incorporated into inert food carrier
Walnut OilDietary supplement
Walnut oil extracted from nut meat and incorporated into inert food carrier
Walnut SkinsDietary supplement
Separated, ground walnut skins incorporated into inert food carrier
Whole walnutDietary supplement
85g whole walnuts, ground, incorporated into inert food carrier

Study groups in NCT00938340
Study group	Role	What they receive
Whole walnut	Experimental	85g whole walnuts, ground, incorporated into inert food carrier Receives: Dietary Supplement: Whole walnut
Walnut "meat"	Experimental	Separated, ground walnut de-fatted nut meat incorporated into inert food carrier Receives: Dietary Supplement: Walnut "meat"
Walnut oil	Experimental	Walnut oil extracted from nut meat and incorporated into inert food carrier Receives: Dietary Supplement: Walnut Oil
Walnut skins	Experimental	Separated, ground walnut skins incorporated into inert food carrier Receives: Dietary Supplement: Walnut Skins

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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
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.
Measured: Change from baseline at 240 min
Main Effect of Treatment on Framingham Reactive Hyperemia Index (fRHI) 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. 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.
Measured: Change from baseline at 240 min
Main Effect of Treatment on Heart Rate (HR) 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. 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.
Measured: Change from baseline at 240 min
Main Effect of Treatment on Augmentation Index (AI) 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. 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.
Measured: 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
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.
Measured: Change from baseline at 240 min
Main Effect of Treatment on the Triglyceride (TG) 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 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).
Measured: 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 Triglyceride (TG) 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 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)].
Measured: Change from baseline for each timepoint (30, 60, 120, 240, 360 min)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2007May 2009

First posted13 Jul 2009 (estimated)
Study startAug 2007
Primary completionFeb 2009
Study completionMay 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
More trials run by Penn State UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00938340
Sponsor's protocol ID: PKE 102
Status last verified: Aug 2023
First submitted: 18 Jun 2009
Last updated: 21 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 23616506
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.
PubMed 21871057

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Postprandial Effects of Walnut Components vs Whole Walnuts on Oxidative Stress, Inflammation, Platelet Function, and Endothelial Function in Volunteers With Moderate Hypercholesterolemia
ClinicalTrials.gov ID: NCT00938340
Acronym / sponsor ID: PKE 102
Conditions: Cardiovascular Disease
Keywords: Cardiovascular Disease
Study type: Interventional
Recruitment status: Completed
Enrolment: 20 participants (actual)
Lead sponsor: Penn State UniversityUniversity, hospital or other
Collaborators: California Walnut Commission
Study start: Aug 2007
Primary completion: Feb 2009 (actual)
Study completion: May 2009 (actual)
First posted: 13 Jul 2009 (estimated)
Results: Posted 29 Oct 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Whole walnut	Experimental	Dietary Supplement: Whole walnut85g whole walnuts, ground, incorporated into inert food carrier
Walnut "meat"	Experimental	Dietary Supplement: Walnut "meat"Separated, ground walnut de-fatted nut meat incorporated into inert food carrier
Walnut oil	Experimental	Dietary Supplement: Walnut OilWalnut oil extracted from nut meat and incorporated into inert food carrier
Walnut skins	Experimental	Dietary Supplement: Walnut SkinsSeparated, ground walnut skins incorporated into inert food carrier

Who may qualify

Ages: 21 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Walnut "meat"Separated, ground walnut de-fatted nut meat incorporated into inert food carrier	Dietary supplement	Walnut "meat"
Walnut OilWalnut oil extracted from nut meat and incorporated into inert food carrier	Dietary supplement	Walnut oil
Walnut SkinsSeparated, ground walnut skins incorporated into inert food carrier	Dietary supplement	Walnut skins
Whole walnut85g whole walnuts, ground, incorporated into inert food carrier	Dietary supplement	Whole walnut

Primary outcome

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.
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).
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.
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).
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.
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).
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.
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).

7 secondary outcomes

Main Effect of Treatment on Reactive Hyperemia Index (RHI) Changes in Response to 4 Walnut Treatments
Time frame: Change from baseline at 240 min
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
Main Effect of Treatment on Heart Rate (HR) Changes in Response to 4 Walnut Treatments
Time frame: Change from baseline at 240 min
Main Effect of Treatment on Augmentation Index (AI) Changes in Response to 4 Walnut Treatments
Time frame: 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
Time frame: Change from baseline at 240 min
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.
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)

Results and safety

Results posted to the registry on 29 Oct 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Walnut Intervention	20	15

Primary outcome: 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.. Least squares mean (Standard Error). Unit: umol Trolox equivalents (TE)*min/L

Measure	Whole Walnut (85 g) n = 15	Walnut Skins (5.6 g) n = 15	Walnut Oil (51 g) n = 15	Defatted Walnut Nutmeat (34 g) n = 15
Value	-26 (46)	28 (47)	9 (47)	-135 (51)

Whole Walnut (85 g) vs Walnut Skins (5.6 g) vs Walnut Oil (51 g) vs Defatted Walnut Nutmeat (34 g): p <0.01, Mixed Models Analysis
Whole Walnut (85 g) vs Walnut Skins (5.6 g): p = 0.15, Mixed Models Analysis
Whole Walnut (85 g) vs Walnut Oil (51 g): p = 0.35, Mixed Models Analysis

Population analysed: All participants who completed each of the 4 treatment arms

Primary outcome: 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). Least squares mean (Standard Error). Unit: umol Trolox equivalents (TE)/L

Measure	Whole Walnut (60 Min) n = 15	Whole Walnut (120 Min) n = 15	Whole Walnut (240 Min) n = 14	Whole Walnut (360 Min) n = 15	Walnut Skins (60 Min) n = 15	Walnut Skins (120 Min) n = 15	Walnut Skins (240 Min) n = 15	Walnut Skins (360 Min) n = 14	Walnut Oil (60 Min) n = 15	Walnut Oil (120 Min) n = 14	Walnut Oil (240 Min) n = 15	Walnut Oil (360 Min) n = 15	Defatted Walnut Nutmeat (60 Min) n = 15	Defatted Walnut Nutmeat (120 Min) n = 15	Defatted Walnut Nutmeat (240 Min) n = 15	Defatted Walnut Nutmeat (360 Min) n = 15
Value	69 (63)	-34 (63)	-65 (64)	-75 (63)	-4 (64)	10 (64)	7 (64)	98 (65)	-10 (64)	5 (65)	53 (64)	-13 (64)	-139 (66)	-92 (66)	-175 (66)	-134 (66)

Whole Walnut (60 Min) vs Whole Walnut (120 Min) vs Whole Walnut (240 Min) vs Whole Walnut (360 Min) vs Walnut Skins (60 Min) vs Walnut Skins (120 Min) vs Walnut Skins (240 Min) vs Walnut Skins (360 Min) vs Walnut Oil (60 Min) vs Walnut Oil (120 Min) vs Walnut Oil (240 Min) vs Walnut Oil (360 Min) vs Defatted Walnut Nutmeat (60 Min) vs Defatted Walnut Nutmeat (120 Min) vs Defatted Walnut Nutmeat (240 Min) vs Defatted Walnut Nutmeat (360 Min): p = 0.15, Mixed Models Analysis

Primary outcome: Main Effect of Treatment on the Changes in Total Thiol Response to 4 Walnut Treatments

Measure	Whole Walnut (85 g) n = 15	Walnut Skins (5.6 g) n = 15	Walnut Oil (51 g) n = 15	Defatted Walnut Nutmeat (34 g) n = 15
Value	0.024 (0.014)	0.010 (0.015)	0.011 (0.014)	0.026 (0.017)

Whole Walnut (85 g) vs Walnut Skins (5.6 g) vs Walnut Oil (51 g) vs Defatted Walnut Nutmeat (34 g): p = 0.79, Mixed Models Analysis

Population analysed: All participants who completed each of the 4 treatment arms

Primary outcome: 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). Least squares mean (Standard Error). Unit: mmol/L

Measure	Whole Walnut (60 Min) n = 15	Whole Walnut (120 Min) n = 15	Whole Walnut (240 Min) n = 14	Whole Walnut (360 Min) n = 15	Walnut Skins (60 Min) n = 15	Walnut Skins (120 Min) n = 15	Walnut Skins (240 Min) n = 15	Walnut Skins (360 Min) n = 14	Walnut Oil (60 Min) n = 15	Walnut Oil (120 Min) n = 14	Walnut Oil (240 Min) n = 15	Walnut Oil (360 Min) n = 15	Defatted Walnut Nutmeat (60 Min) n = 15	Defatted Walnut Nutmeat (120 Min) n = 15	Defatted Walnut Nutmeat (240 Min) n = 15	Defatted Walnut Nutmeat (360 Min) n = 15
Value	0.051 (0.017)	0.035 (0.017)	0.001 (0.021)	0.010 (0.022)	0.018 (0.018)	-0.004 (0.018)	0.005 (0.021)	0.019 (0.023)	0.022 (0.017)	0.029 (0.018)	0.003 (0.020)	-0.010 (0.023)	0.038 (0.019)	0.037 (0.020)	0.022 (0.022)	0.008 (0.024)

Whole Walnut (60 Min) vs Whole Walnut (120 Min) vs Whole Walnut (240 Min) vs Whole Walnut (360 Min) vs Walnut Skins (60 Min) vs Walnut Skins (120 Min) vs Walnut Skins (240 Min) vs Walnut Skins (360 Min) vs Walnut Oil (60 Min) vs Walnut Oil (120 Min) vs Walnut Oil (240 Min) vs Walnut Oil (360 Min) vs Defatted Walnut Nutmeat (60 Min) vs Defatted Walnut Nutmeat (120 Min) vs Defatted Walnut Nutmeat (240 Min) vs Defatted Walnut Nutmeat (360 Min): p = 0.53, Mixed Models Analysis

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: During the intervention (0 to 360 min). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Walnut Oil	0 of 15 (0%)	9 of 15 (60%)	Not reported
Whole Walnut	0 of 15 (0%)	0 of 15 (0%)	Not reported
Walnut Skins	0 of 15 (0%)	0 of 15 (0%)	Not reported
Defatted Walnut Nutmeat	0 of 15 (0%)	0 of 15 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23616506Berryman 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.
Derived from this study: PubMed 21871057Zhang 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Penny M Kris-Etherton, PhD principal investigator

Penn State University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Walnut "meat", Walnut Oil and Walnut Skins in people with Cardiovascular Disease, run by Penn State University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00938340, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.