Obesity, Inflammation and Oxidative Stress

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Obesity; Oxidative Stress; C-reactive Protein
• Intervention / Treatment: Dietary supplement: Placebo tablet; Dietary supplement: Vitamin C (ascorbic acid)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94612
      • Kaiser Permanente of Northern California, Division of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Two tablets, daily, for 8 weeks	Dietary supplement: Placebo tablet; Placebo tablet (two 500-mg tablets), 8 weeks
EXPERIMENTAL: Vitamin C; Two tablets, daily, for 8 weeks	Dietary supplement: Vitamin C (ascorbic acid); 1000 mg/day (two 500-mg tablets), 8 weeks

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of California, Berkeley
• Collaborators: Kaiser Permanente
• Investigators: Principal Investigator: Gladys Block, PhD, University of California, Berkeley

Publications and helpful links

General Publications

• Block G, Jensen CD, Dalvi TB, Norkus EP, Hudes M, Crawford PB, Holland N, Fung EB, Schumacher L, Harmatz P. Vitamin C treatment reduces elevated C-reactive protein. Free Radic Biol Med. 2009 Jan 1;46(1):70-7. doi: 10.1016/j.freeradbiomed.2008.09.030. Epub 2008 Oct 10.
• Block G, Jensen C, Dietrich M, Norkus EP, Hudes M, Packer L. Plasma C-reactive protein concentrations in active and passive smokers: influence of antioxidant supplementation. J Am Coll Nutr. 2004 Apr;23(2):141-7. doi: 10.1080/07315724.2004.10719354.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): July 1, 2012

Study Registration Dates

• First Submitted: December 8, 2009
• First Submitted That Met QC Criteria: December 8, 2009
• First Posted (ESTIMATE): December 9, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 2, 2015
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Antioxidants; randomized controlled trial; obesity; inflammation; primary prevention; Vitamin C; C-reactive protein; anti-inflammatory agents
• Additional Relevant MeSH Terms: Pathologic Processes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: DK062378-05