Efficacy of Nuts in Obese Children.

Efficacy of Walnuts and Hazelnuts on the Modification of the Lipid Content of Erythrocyte Membranes in Obese Children. A Randomised Controlled Trial.

Obesity is a problem of ever-growing importance, especially in industrialized countries, both in adults and in the pediatric population. Children and obese adolescents, like adults, have an increased risk, compared with normal-weight peers, to develop metabolic syndrome and atherosclerotic disease, pathophysiological basis of cardiovascular events. Alteration of the elastic properties of the arteries has been described previously in obese children and adolescents and is considered an initial marker of atherosclerotic vascular damage. The determination of the indices of arterial stiffness (PWV, Pulse Wave Velocity; AI, Augmentation Index, SI, Stiffness Index) is possible through techniques currently used for the determination of vascular function even in children.

Nuts and hazelnuts are rich in potentially beneficial substances including unsaturated fatty acids, especially omega-6 (present in both) and omega-3 (present only in nuts), Several clinical trials have already shown in adults a potential beneficial effect of the addition of different types of nuts (walnuts, hazelnuts, cashews, pistachios, etc.) on the characteristics of the metabolic syndrome also through their possible antioxidant effect and vasoactive. In children, some epidemiological studies have associated with a higher consumption of nuts reduced risk of hypertension, dyslipidemia, obesity and fasting glucose. The study will be conducted with a randomized design with two arms in parallel with blinded operator. The main objective of this study is to assess the efficacy of 15 grams of nuts and 15 grams of nuts a day in addition to a low calorie diet on the content of erythrocyte membranes of alpha-linolenic acid three months after the beginning of the trial in a group of obese children. Secondary objectives are to evaluate the efficacy of walnuts and hazelnuts in improving the systolic and/or diastolic blood pressure values, lipid profile, glucose and fasting insulin, vascular function.

Study Overview

• Status: Terminated
• Conditions: Child Obesity
• Intervention / Treatment: Dietary supplement: wNUTS, low-caloric diet plus nuts; Other: w/oNUTS, low-caloric diet without nuts

Detailed Description

Obesity is a problem of ever-growing importance, especially in industrialized countries, widespread both in adults and in the pediatric population.

Children and obese adolescents, like adults, have an increased risk, compared with normal-weight peers, to develop high blood pressure, insulin resistance, diabetes, hyperlipidemia, fatty liver disease and the resulting long-term complications. This cluster of metabolic and hemodynamic risk factors, which is known as metabolic syndrome, greatly increases the risk of cardiovascular events in adults. Cardiovascular disease is the leading cause of mortality and morbidity in developed countries and are becoming even in developing countries. Atherosclerotic disease is the pathophysiological basis of cardiovascular events. Atherosclerosis is a multifactorial disease whose early stages of subclinical damage are documented much earlier in cardiovascular events with non-invasive tests. The determination of the indices of arterial stiffness (PWV, Pulse Wave Velocity; AI, Augmentation Index, SI, Stiffness Index) is possible through techniques currently used for the determination of vascular function even in children. The alteration of the elastic properties of the arteries has been described previously in obese children and adolescents and is considered initial marker atherosclerotic vascular damage. Fats particularly saturated fats, without adequate intake of polyunsaturated fat, may facilitate the development of obesity.

The consumption of some specific foods including dried fruit (in a broad sense including walnuts, hazelnuts, almonds, cashews, etc.) within a reduced calorie diet is considered to be a promising approach in the prevention and care of the different components of the metabolic syndrome. The nuts and hazelnuts are rich in potentially beneficial substances including unsaturated fatty acids, especially omega-6 (present in both) and omega-3 (present only in nuts), L-arginine, fiber, minerals, vitamin E, fitosetrols and polyphenols.

Several clinical trials have already shown in adults a potential beneficial effect of the addition of different types of nuts (walnuts, hazelnuts, cashews, pistachios, etc.) on the characteristics of the metabolic syndrome also through their possible antioxidant and vasoactive effect .

In children, some epidemiological studies have associated a higher consumption of nuts with reduced risk of hypertension, dyslipidemia, obesity and fasting glucose alteration.

Our group conducted a study in obese children observing an inverse relationship between omega-6 polyunsaturated fatty acids, contained in large amounts in walnuts, and certain features of metabolic syndrome, such as waist circumference, triglycerides, fasting insulin, systolic blood pressure of 24-hours, suggesting a possible beneficial effect. The project was financed by health ministry and included also the present Protocol ("Obesity, hypertension and subclinical vascular damage in children: the role of dietary factors and lipid mediators. An epidemiological and translational study. "Project Code: GR-2011-02349630).

From arachidonic acid, the main omega-6 type polyunsaturated fatty acids (PUFA), certain metabolites are produced via cytochrome P450 which have vasoactive and natriuretic effect: 20-Hydroxyeicosatetraenoic acid (20-HETE), the epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs). From numerous studies in animal models and some human studies, it is known that these metabolites via cytochrome P450 may be involved both in the homeostasis of blood pressure pressure and in the development of hypertension. In particular, plasmatic 20-HETE has a vasoconstrictor effect while EETs are vasodilators; both exert renal natriuretic effect. Our study intends to verify if in a group of obese children, a low-calorie diet that contains a portion of walnuts and hazelnuts, can change the content of polyunsaturated fatty acids in erythrocyte membranes, particularly alpha-linolenic acid. This could result in possible beneficial effects on the characteristics of the metabolic syndrome in obese children, like an improvement of waist circumference, blood pressure, HDL cholesterol, triglycerides and blood sugar. Our study also intends to acquire information on the effect of the addition of walnuts and hazelnuts and the metabolites of polyunsaturated fatty acids omega-3 and omega-6 metabolized by cytochrome P450 that derives from these nuts in change vessel elasticity.

2. STUDY DESIGN The study will be conducted with a randomized design (two arms in parallel with blinded operator). Doctors in charge of vascular measurements and laboratory technicians will not know which of the two groups analyzed will only have taken the low-calorie diet and who will have assumed the low-calorie diet with walnuts and hazelnuts.

3. PURPOSE OF THE STUDY

The main objective of this study is to assess the efficacy of 15 grams of nuts and 15 grams of nuts a day in addition to a low calorie diet, in modifying the content of of alpha-linolenic acid in erythrocyte membranes evalutated three months after the beginning of the assumption in a group of obese children.

Secondary objectives are:

To evaluate the efficacy of walnuts and hazelnuts in improving in obese children:

• the systolic and/or diastolic blood pressure values;
• metabolic disorders (in particular of the lipid profile: LDL, HDL, triglycerides, and glucose: glucose and fasting insulin);
• vascular function measured by tonometry (PWV and PWA), and ultrasonography (carotid distensibility).
• the modifications of the profile of eicosanoids via CYP450 in plasma and urine

To evaluate:

- the relationship between intake of nuts and hazelnuts, fatty acid profile of erythrocyte membranes and eicosanoids via CYP450, the components of the metabolic syndrome including the blood pressure and vascular elasticity.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • VR
    • Verona, VR, Italy, 37134
      • AOUI Verona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• obese subjects (BMI ≥ 95th percentile for age and sex; reference tables for WHO BMI);
• Aged between 6 and 17 years;
• Signature applied in the informed consent by both parents and consent of the child

Exclusion Criteria:

• chronic liver diseases (hepatitis, cirrhosis).
• Chronic renal failure (serum creatinine> 1.2 mg / dL).
• Malignancies.
• Diabetes (fasting blood glucose ≥ 126 mg / dl or therapy with oral hypoglycemic drugs or insulin).
• cholesterol-lowering or antihypertensive terapy.
• Notes allergies to nuts or hazelnuts or food intolerance to nuts and/or hazelnuts.
• Treatment of less than 6 weeks with any medication which can interfere with fecal microbiota (particularly antibiotics or laxatives).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: wNUTS, low-caloric diet plus nuts; low-caloric diet personalized on single children's requirements plus nuts (15g hazelnuts+15g nuts without shell) for 3 months.	Dietary supplement: wNUTS, low-caloric diet plus nuts; 15g of nuts and 15g of hazelnuts in association with low caloric diet; Other: w/oNUTS, low-caloric diet without nuts; low caloric diet
Other: w/oNUTS, low-caloric diet without nuts; low-caloric diet personalized on single children's requirements plus nuts (15g hazelnuts+15g nuts without shell) for 3 months.	Other: w/oNUTS, low-caloric diet without nuts; low caloric diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALA change	Primary outcome is to compare percentage of fatty acids in erythrocyte membranes (in particular alpha-linolenic acid, ALA) with the content of other membrane-bound fatty acids. It will be compared in the two groups the ALA delta (delta%) between measurement at baseline compared to post-treatment (ie, after 3 months of treatment).	baseline compared to post-treatment (ie, after 3 months of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LA change	to compare percentage of fatty acids in erythrocyte membranes (in particular linoleic acid, LA) with the content of other membrane-bound fatty acids. It will be compared in the two groups the ALA delta (delta%) between measurement at baseline compared to post-treatment (ie, after 3 months of treatment).	baseline compared to post-treatment (ie, after 3 months of treatment)
ABPM change	To compare ambulatory blood pressure (mmHg) measured by validated devices (A&D TM-2430; in the week preceding the beginning of the assumption of diet plus or minus nuts/hazelnuts) and after 3 months from randomization in the two arms.	baseline compared to post-treatment (ie, after 3 months of treatment)
OFFICE BLOOD PRESSURE change	To compare mean arterial pressure obtained during the medical examination (mmHg) by oscillometric validated device in children (Omron 705 IT; average of three measurements) prior to randomization and after 3 months of diet intake plus or minus nuts/hazelnuts.	baseline compared to post-treatment (ie, after 3 months of treatment)
HDL-cholesterol change	To compare HDL-cholesterol	baseline compared to post-treatment (ie, after 3 months of treatment)
triglycerides change	To compare triglycerides	baseline compared to post-treatment (ie, after 3 months of treatment)
glucose change	To compare plasma glucose	baseline compared to post-treatment (ie, after 3 months of treatment)
WAIST CIRCUMFERENCE change	To compare waist circumference change in the 2 arms prior to randomization and after 3 months of diet intake plus or minus nuts/hazelnuts.	baseline compared to post-treatment (ie, after 3 months of treatment)
WEIGHT change	To compare weight change in the 2 arms prior to randomization and after 3 months of diet intake plus or minus nuts/hazelnuts.	baseline compared to post-treatment (ie, after 3 months of treatment)
PWA (Augmentation Index; AIx) change	To compare AIx change as measured by pulse wave analysis (PWA) by SphygmoCor XCEL and in the 2 arms prior to randomization and after 3 months of diet intake plus or minus nuts/hazelnuts.	baseline compared to post-treatment (ie, after 3 months of treatment)
cfPWV change	To compare carotid femoral pulse wave velocity (PWV) change measured by tonometer (SphygmoCor XCEL) in the 2 arms prior to randomization and after 3 months of diet intake plus or minus nuts/hazelnuts.	baseline compared to post-treatment (ie, after 3 months of treatment)
carotid distensibility (cDC) change	To compare cDC change measured by ultrasound in the 2 arms prior to randomization and after 3 months of diet intake plus or minus nuts/hazelnuts.	baseline compared to post-treatment (ie, after 3 months of treatment)
plasma EETs change	To compare plasma epoxyeicosatrienoic acids, metabolites of arachidonic acid vis CYP450	baseline compared to post-treatment (ie, after 3 months of treatment)
plasma DHETs change	To compare plasma dihydroxyeicosatrienoic acids, metabolites of EETs via sEH	baseline compared to post-treatment (ie, after 3 months of treatment)
urine DHETs change	To compare urine dihydroxyeicosatrienoic acids, metabolites of EETs via sEH	baseline compared to post-treatment (ie, after 3 months of treatment)
plasma 20-HETE change	To compare plasma 20-hydroxyeicosatetraenoic acids, metabolites of arachidonic acid via CYP450	baseline compared to post-treatment (ie, after 3 months of treatment)
urine 20-HETE change	To compare urine 20-hydroxyeicosatetraenoic acids, metabolites of arachidonic acid via CYP450	baseline compared to post-treatment (ie, after 3 months of treatment)
plasma EEQs change	To compare plasma epoxyeicosatetraenoic acids, metabolites of eicosapentaenoic acid via CYP450	baseline compared to post-treatment (ie, after 3 months of treatment)
plasma EDPs change	To compare plasma epoxydocosapentaenoic acids, metabolites of docosahexaenoic acid via CYP450	baseline compared to post-treatment (ie, after 3 months of treatment)
MICROBIOTA change	To compare profile of the faecal microbiota by metagenomic of the gene sequences coding for the 16S rRNA prior to randomization and after 3 months of diet intake plus or minus nuts/hazelnuts.	baseline compared to post-treatment (ie, after 3 months of treatment)

Collaborators and Investigators

• Sponsor: Universita di Verona
• Investigators: Principal Investigator: Cristiano Fava, professor, Universita di Verona

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): May 18, 2022
• Study Completion (Actual): May 18, 2022

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: obesity, children, nuts,
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity
• Other Study ID Numbers: VRINoci

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No