The Effects of Orange Juice on Plasma Lipids

Study Overview
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Brief Summary
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The aim of this study is primarily to investigate the ability of antioxidants found in orange juice (OJ) to improve the serum lipid profile. Overweight or mildly obese men, who are otherwise healthy, but with elevated serum total cholesterol concentration will be recruited. The time commitment for subjects is  14wks. Subjects will attend the laboratory on 5 occasions after fasting from midnight. The 1st is a medical screening. Laboratory visits 2 & 5 will take  90min and will be separated by 3 months, during which time subjects will consume 250ml of an orange drink (either OJ or an orange flavoured control drink) once a day. During visits 2 & 5, subjects will have a scan to assess their %body fat using a low-dose x-ray machine, a 20ml blood sample taken and a small sample of fat tissue (about the size of a haricot bean)taken from underneath the skin of the belly. Subjects will record their food intake for 3-days in weeks 3, 7 and 11 of consuming the drink, and come to the lab for visits 3&4 during weeks 4&8. Laboratory visits 3&4 repeat measurements taken in the 1st (screening) visit.

Detailed Description
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Background: Overweight and mild obesity are associated with insulin resistance and mild elevations in lipid risk factors which are not usually sufficiently abnormal to merit treatment. Such people are encouraged to lose weight to reduce their risk of progressing to type 2 diabetes and coronary heart disease, but there is clearly a potential role for dietary modifications to maximize any potential benefit of this weight loss. Flavonoids are known to have vascular effects which might enhance substrate delivery to metabolically active tissues, and thus improve insulin sensitivity. Moreover, there is much interest in the potentially beneficial effect of flavonoids on serum lipid profile. There are many different dietary sources of flavonoids, with fruits such as apples, berries and citrus being rich sources. However, some researchers have expressed concern that a high dietary intake of 100% juice may contribute to the development of insulin resistance, obesity and the Metabolic Syndrome (Bazzano, Li et al. 2008), although this is not universally accepted (Fujioka, Greenway et al. 2006; O'Neil and Nicklas 2008). To date, there have been no studies investigating the effects of citrus fruits on indices of cardio-metabolic health in people who are presently healthy but are at risk of developing some features of the Metabolic Syndrome. Aims: To investigate the effects of orange juice (OJ) intake on appetite hormones, blood pressure and plasma lipids. In addition we aim to investigate any gene expression changes associated with OJ consumption, in particular in adipose tissue. Experimental protocol and methods: Overweight or obese men (BMI 27-35), who are otherwise healthy, will be recruited onto the study. They will attend the 'David Greenfield Human Physiology' laboratories on 5 convenient mornings, following an overnight fast. The 1st visit is a medical screening and will involve signing a consent form, completing medical screening, food frequency and activity questionnaires, having height, weight, and hip/waist circumference measurements taken and a sample of blood taken for CBC, urea, electrolytes, LFT, TFT, glucose and insulin analysis. Subjects will then be asked to complete a 3-day diet diary for macronutrient assessment. The 2nd visit will involve having a DEXA body composition scan, an adipose tissue biopsy and a blood sample taken for white blood cell harvest, serum lipids, glucose, insulin, cytokines, appetite hormones and catecholamine analysis. Starting on the following morning, subjects will then consume an orange drink (either OJ or a carbohydrate matched orange flavoured drink) once a day for 12 wks. A 3-day diet diary for macronutrient assessment will be recorded during wks 3,7and 11 of taking the drink, and measurements made at screening will be repeated on visits 3 and 4 which will take place in weeks 4 and 8. The final laboratory (5th) visit will be identical to visit 2.

Official Title
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An Investigation Into the Effects of Orange Juice on Plasma Lipids - an Extension to J/06/2010

Conditions
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Insulin Resistance, Obesity, Dyslipidemia

Intervention / Treatment
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* Dietary Supplement: Orange Juice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 27-35 waist circumference >96cm. Serum Total Cholesterol >5mmol/l Exclusion Criteria: Any clinically significant metabolic or endocrine abnormalities screening blood results (other than lipids) outside of the normal range fasting total cholesterol >7.0mmol/l taking routine medication herbal supplement use food allergies or sensitivities related to the investigational product Regular citrus consumers (whole fruit or juice) daily consumption of sucrose or high fructose corn syrup containing soft-drinks

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Orange Juice<br>Juice high in flavonoids | Dietary Supplement: Orange Juice<br>* 250ml of orange juice or a sugars matched orange drink daily<br>|
| Placebo Comparator: Orange Drink<br>Sugars matched, low flavonoids orange drink | Dietary Supplement: Orange Juice<br>* 250ml of orange juice or a sugars matched orange drink daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Serum Cholesterol concentration | Fasting Serum total cholesterol concentration (mmol/l) | after 3 months' intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High Density Cholesterol (HDL) | Fasting Serum HDL concentration | after 3 months' intervention | 
| Low density cholesterol | Fasting Serum LDL concentration | after 3 months' intervention | 
| Gene expression in adipose tissue | Expression of genes related to lipid metabolism in adipose tissue | after 3 months' intervention | 
| leptin | fasting Serum Leptin concentration | after 3 month intervention | 
| IL-1 | Serum IL-1 concentration | afetr 3 month intervention | 
| Blood Pressure | Resting blood pressure, measured semi-supine | after 3months intervention | 
| Ghrelin | Fasting Plasma Ghrelin concentration | After 3 months intervention | 
| GLP-1 | Fasting Plasma GLP-1 concentration | After 3 months intervention | 
| insulin | Fasting serum Insulin concentration | After 3 months intervention | 
| IL-6 | Serum IL-6 concentration | After 3 months intervention | 
| TNF alpha | Serum TNF-Alpha concentration | After 3 months intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Men, Orange Juice, Cholesterol, Obesity