Clinical trial NCT00938340: Postprandial Effects of Walnut Components Versus Whole Walnuts on Cardiovascular Disease (CVD) Risk Reduction
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Disease
Keywords: Cardiovascular Disease
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: California Walnut Commission
First posted: 2009-07-13
Enrollment: 20
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Main Effect of Treatment on the Ferric Reducing Antioxidant Potential (FRAP) Changes in Response to 4 Walnut Treatments
timeFrame: 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.
measure: Main Effect of Treatment by Timepoint on the Ferric Reducing Antioxidant Potential (FRAP) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline for each timepoint (60, 120, 240, 360 min)
measure: Main Effect of Treatment on the Changes in Total Thiol Response to 4 Walnut Treatments
timeFrame: 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.
measure: Main Effect of Treatment by Timepoint on Total Thiol Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline for each timepoint (60, 120, 240, 360 min)
measure: Main Effect of Treatment on the Changes in Malondialdehyde (MDA) Response to 4 Walnut Treatments
timeFrame: 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.
measure: Main Effect of Treatment by Timepoint on Malondialdehyde (MDA) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline for each timepoint (60, 120, 240, 360 min)
measure: Main Effect of Treatment on the Changes in C-reactive Protein (CRP) Response to 4 Walnut Treatments
timeFrame: 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.
measure: Main Effect of Treatment by Timepoint on C-reactive Protein (CRP) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline for each timepoint (60, 120, 240, 360 min)
Secondary outcomes:
measure: Main Effect of Treatment on Reactive Hyperemia Index (RHI) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline at 240 min
measure: Main Effect of Treatment on Framingham Reactive Hyperemia Index (fRHI) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline at 240 min
measure: Main Effect of Treatment on Heart Rate (HR) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline at 240 min
measure: Main Effect of Treatment on Augmentation Index (AI) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline at 240 min
measure: 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
timeFrame: Change from baseline at 240 min
measure: Main Effect of Treatment on the Triglyceride (TG) Changes in Response to 4 Walnut Treatments
timeFrame: 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.
measure: Main Effect of Treatment by Timepoint on Triglyceride (TG) Changes in Response to 4 Walnut Treatments
timeFrame: Change from baseline for each timepoint (30, 60, 120, 240, 360 min)
Other outcomes:
Locations:
city: University Park
country: United States
facility: Penn State General Clinical Research Center
state: Pennsylvania
Study officials:
affiliation: Penn State University
name: Penny M Kris-Etherton, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.