Anti-inflammatory Activities of Vitamin C Supplementation on the Gut Barrier Function in Adults 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).