Anti-inflammatory Activities of Vitamin C Supplementation on the Gut Barrier Function in Adults With Obesity

Anti-inflammatory Activities of Vitamin C Supplementation on the Gut Barrier Function in Adults With Obesity

This study is testing whether taking vitamin C every day can help improve gut health and reduce inflammation in adults with obesity. Poor gut health-sometimes called "leaky gut"-can allow harmful substances from bacteria to enter the bloodstream, which may lead to inflammation and increase the risk of heart disease and liver problems.

Participants will complete two study periods, each lasting two weeks, with a two-week break in between. In one period, they will take vitamin C; in the other, a placebo. During each period, researchers will collect blood, urine, and stool samples, ask participants to track their diet and activity, and perform a test to measure gut permeability.

There are minimal risks, such as discomfort from blood draws or temporary stomach upset from a sugar drink. While participants may not directly benefit, their involvement will help researchers learn whether vitamin C is a safe and effective way to improve gut health in people with obesity.

This clinical study aims to evaluate the impact of vitamin C supplementation on gut barrier function and systemic inflammation in adults with obesity. The research builds on preclinical findings that suggest vitamin C plays a critical role in maintaining gut integrity and reducing inflammation. Approximately 40% of Americans have suboptimal vitamin C status, with even higher prevalence among individuals with obesity.

The primary hypothesis is that improving vitamin C status through dietary supplementation will reduce intestinal permeability and metabolic endotoxemia. A secondary hypothesis is that vitamin C will also reduce biomarkers of intestinal inflammation and promote favorable changes in gut microbiota composition, including increased production of short-chain fatty acids (SCFAs), which are essential for intestinal health.

This randomized, double-blind, placebo-controlled crossover trial will enroll 34 obese adults (BMI 30-40 kg/m², aged 18-50 years). Participants will complete two 2-week intervention periods separated by a 2-week washout. In one period, they will receive vitamin C (500 mg capsules taken twice daily); in the other, a placebo. During both periods, participants will follow a low-vitamin C diet to minimize variability in circulating vitamin C levels.

Assessments will occur on Days 0, 7, and 14 of each intervention period and include: Anthropometric measurements; Resting blood pressure; Fasting blood samples; and 3-day food records. On Day 14 of each period, participants will: Provide a stool sample and Complete a gut permeability test using a non-digestible sugar probe solution followed by a 24-hour urine collection. After the first intervention period, participants will undergo a 2-week washout before repeating the procedures with the alternate supplement.

Primary Outcome: Intestinal permeability

Secondary Outcomes: Biomarkers of endotoxemia; Gut microbiota composition; Intestinal and circulating inflammation biomarkers; Plasma vitamin C concentrations; Fecal short-chain fatty acids.

Inclusion Criteria:

• English speaking
• Men and women between 18-50 years of age
• BMI 30-40 kg/m²
• Resting blood pressure <140/90 mm Hg
• No use of multivitamin/vitamin C supplement within past 1-month
• Non-vegetarian/non-vegan
• Willingness to follow a diet low in fruits and vegetables for two, 2-week periods

Exclusion Criteria:

• Current smoker or vaper, including tobacco, cannabis, or nicotine products
• Alcohol consumption >2 drinks/day
• Use of antibiotics within past 1-month
• Use of probiotic supplements within past 1-month
• Use of anti-inflammatory drugs within past 1-month
• Individuals with unmanaged or poorly controlled diabetes, dyslipidemia, hypertension
• Known history of bleeding disorders, hemochromatosis, or kidney stones
• For Women: Pregnancy, lactation, or change in birth control within the past 3-months
• Use of certain medications that may interact with vitamin C, including blood thinners, some antiviral drugs (e.g., indinavir), and certain antipsychotic medications (e.g., fluphenazine).