Effects of Walnuts on Endothelial Function in Overweight Adults With at Least One Factor of Metabolic Syndrome (Walnut2)

Effects of Walnuts on Endothelial Function in Overweight Adults With at Least One Factor of Metabolic Syndrome: A Randomized, Controlled, Cross-Over Trial

The purpose of this study is to examine the effects of walnut consumption on endothelial function and lipid markers in overweight patients with at least one factor of metabolic syndrome as compared to the control group.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Walnut Supplementation; Dietary supplement: No walnut supplementation

Detailed Description

The prevalence of obesity in both adults and children in the United States has increased significantly over the past 50 years. More than 66% of adults in the US are now overweight or obese and at least 17% of children in the population at large are now considered overweight.Obesity may be a factor predisposing patients to a myriad of comorbidities that increase the associated mortality rate.Several large prospective trials have documented that obesity is an independent risk factor for mortality from cardiovascular disease (CVD). Considering the major metabolic and biochemical changes that occur in obesity, such as atherogenic dyslipidemia, insulin resistance and hyperinsulinemia, endothelial dysfunction, and chronic inflammatory and prothrombotic states, obesity plays a role in the pathogenesis of systemic atherosclerosis and its clinical complications.

Walnuts are rich in alpha-linolenic acid, an essential omega-3 fatty acid, L-arginine and antioxidants. Polyunsaturated fatty acids and antioxidants have anti-oxidative effects and are thought to help preserve the endothelium's capacity to generate nitric oxide (NO), which acts to promote vasodilation, stabilize platelets, and promote the anti-inflammatory abilities of the endothelium. Evidence of this anticipated effect would have implications for strategies to prevent or retard type 2 diabetes mellitus and cardiovascular disease. Endothelial function testing using high frequency ultrasound imaging of the brachial artery to assess endothelium-dependent flow-mediated dilatation (FMD) offers a non-invasive, uniquely valuable means of assessing aggregated influences on cardiac risk by gauging a physiologic response of the vascular endothelium. Proposed, therefore, is a randomized, controlled, cross-over clinical trial, to assess the effects of walnuts on endothelial function in overweight adults with elevated waist circumference and at least one risk factor of metabolic syndrome.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Derby, Connecticut, United States, 06418
      • Yale-Griffin Prevention Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female age 25-75 years
• Non-smoker
• Overweight (BMI ≥ 25) with central adiposity as indicated by waist circumference (102 cm. in men / 88 cm. in women)

• Meet one risk factor of the metabolic syndrome.

  • blood pressure > 130/85 or taking antihypertensive medication

    • fasting plasma glucose (FPG) >100 mg/dL (6.1 mmol/L)
    • fasting serum triglycerides level (TG) > 150 mg/dL (1.69 mmol/L)
    • fasting high-density lipoprotein (HDL) cholesterol < 40 mg/dL (1.04 mmol/L)in men, and < 50 mg/dL (1.29 mmol/L) in women.

Exclusion Criteria:

• Anticipated inability to complete or comply with study protocol
• Use of lipid-lowering or antihypertensive medications or aspirin unless stable on medication for at least 3 months and willing to refrain from taking medication for 12 hours prior to EF scanning
• Preexisting cardiovascular disease (including symptomatic coronary artery disease (CAD), myocardial infarction, angina pectoris, anginal equivalent, peripheral vascular disease, congestive heart failure, carotid stenosis)
• Severe hypertension (systolic blood pressure >180mmHg or diastolic blood pressure >105mmHg), even if well-controlled by medication.
• Diagnosed diabetes mellitus
• Regular use of multivitamins, Vitamin C, Vitamin E, fish oil, flax seed oil, omega-3 fatty acids, CoQ10, fiber supplements, garlic pills, arginine, red yeast rice, and any kind of antioxidant and unwillingness to discontinue supplementation for at least 4 weeks prior to study initiation and for study duration
• Allergic to walnuts or any other nuts
• Diagnosed eating disorder
• On any specific diet, weight control diet, vegan diet
• Any rheumatologic disease requiring regular use of NSAIDs or alternative medications
• Regular use of fiber supplements
• Regular use of vasoactive medication (including glucocorticoids, antineoplastic agents, psychoactive agents, or bronchodilators), and anticoagulant drugs (including Coumadin, plavix )
• Diagnosed sleep apnea
• Substance abuse (chronic alcoholism, other chemical dependency)
• Any unstable medical condition that would limit the ability of a subject to participate fully in the trial (e.g., cancer, AIDS, tuberculosis, psychotic disorder)
• Current or impending pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Walnut Supplementation; Eight weeks with walnut supplementation to an ad lib diet	Dietary supplement: Walnut Supplementation; Eight weeks of walnut supplementation
Placebo Comparator: 2; Eight weeks ad lib diet without walnut supplementation	Dietary supplement: No walnut supplementation; Eight weeks without walnut supplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial function	Brachial artery flow mediated dilation (FMD)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waist circumference		8 weeks
Blood pressure		8 weeks
Weight		8 weeks
Fasting blood glucose		8 weeks
Fasting lipid panel	Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglyceride level, cholesterol / high density lipoprotein cholesterol ratio	8 weeks
Fasting insulin		8 weeks

Collaborators and Investigators

• Sponsor: Griffin Hospital
• Collaborators: California Walnut Commission

Publications and helpful links

General Publications

• Katz DL, Davidhi A, Ma Y, Kavak Y, Bifulco L, Njike VY. Effects of walnuts on endothelial function in overweight adults with visceral obesity: a randomized, controlled, crossover trial. J Am Coll Nutr. 2012 Dec;31(6):415-23. doi: 10.1080/07315724.2012.10720468.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: August 9, 2011
• First Posted (Estimate): August 10, 2011

Study Record Updates

• Last Update Posted (Actual): August 2, 2019
• Last Update Submitted That Met QC Criteria: July 31, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: obesity; endothelial function; walnuts
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Body Weight; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Overweight
• Other Study ID Numbers: 2009-15