Obesity, Inflammation and Oxidative Stress

Study Overview
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Brief Summary
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The purpose of this study is to determine whether or not Vitamin C (1000 mg/day) can reduce markers of inflammation, especially C-reactive protein (CRP), in obese persons with baseline CRP greater than 1 mg/dl.

Detailed Description
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The long-term objective of this project is to identify nutritional factors that can reduce the inflammatory component of obesity. Therapies to minimize obesity-related comorbidities are needed, and targeting inflammation may help slow the progression of obesity towards cardiovascular disease and insulin resistance. Adipose tissue is a source of inflammatory cytokines, and obesity is now viewed as a chronic, low-grade inflammatory state. Inflammation itself is a contributor to the chronic diseases associated with obesity. C-reactive protein (CRP) is a key marker of inflammation, and as a downstream marker it provides functional integration of upstream cytokine activation associated with inflammation. We have previously shown that vitamin C, but not vitamin E, reduces CRP in active and passive smokers and in nonsmokers. The reduction is seen primarily in persons with CRP ≥1.0 mg/L, the CDC threshold for elevated cardiovascular disease risk. We also found that 75% of obese nonsmokers had CRP ≥1.0 mg/L. The important observation of reduction in elevated CRP by vitamin C now needs to be confirmed in a rigorous study with adequate sample size, to permit justifiable conclusions about the potential usefulness of this agent in reducing inflammation in the obese. We will conduct a placebo-controlled, randomized trial in 552 healthy obese individuals with moderate CRP elevations (CRP ≥1.0 mg/L). Participants will be randomized to either 1000 mg/day vitamin C or placebo for a period of 2 months. We will also characterize the pathways through which this effect takes place by measuring cytokines and oxidative stress. This project is important because if our previous finding is confirmed in this population, it could offer a low-cost alternative to use of statins to reduce inflammation in persons without other risk factors.

Official Title
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Obesity, Inflammation and Oxidative Stress

Conditions
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Obesity, C-reactive Protein, Inflammation, Oxidative Stress

Intervention / Treatment
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* Dietary Supplement: Vitamin C (ascorbic acid)
* Dietary Supplement: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI ≥ 30 hsCRP ≥ 1 mg/L Age 18+ Member of Kaiser Permanente Health Plan of Northern California Exclusion Criteria: Smoker Unwilling to discontinue vitamin supplements for study duration Unwilling/unable to use acetaminophen in place of OTC anti-inflammatory medications Use of certain medications History of certain medical conditions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Two tablets, daily, for 8 weeks | Dietary Supplement: Placebo tablet<br>* Placebo tablet (two 500-mg tablets), 8 weeks<br>|
| Experimental: Vitamin C<br>Two tablets, daily, for 8 weeks | Dietary Supplement: Vitamin C (ascorbic acid)<br>* 1000 mg/day (two 500-mg tablets), 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| high-sensitivity C-reactive protein |  | After 8 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CRP-related markers of inflammation and oxidative stress, including cytokines and F2-isoprostanes. |  | After 8 weeks of intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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randomized controlled trial, primary prevention, Vitamin C, Antioxidants, C-reactive protein, inflammation, anti-inflammatory agents, obesity