Effect of Isoflavone and Vitamin D Supplementation on Serum Vitamin D Levels, Body Composition, Inflammatory Markers, and Quality of Life in Patients With Inflammatory Bowel Disease: An Open-Label Randomized Controlled Trial

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has emerged as a growing global health problem. Although historically more prevalent in Western countries, the incidence and prevalence of IBD have substantially increased throughout Asia over the past decade. The disease is characterized by chronic relapsing inflammation resulting from dysregulated interactions among genetic susceptibility, environmental factors, gut microbiota, and the immune system.

Several lifestyle and dietary factors have been implicated in disease pathogenesis. High-fat and refined-carbohydrate dietary patterns may promote pro-inflammatory responses, impair intestinal barrier function, alter mucus production, and contribute to gut microbial dysbiosis. Many patients experience recurrent disease activity despite clinical remission, highlighting the need for adjunctive strategies that may support long-term disease management.

Malnutrition is a common complication of IBD that encompasses a broad spectrum of nutritional disturbances. Patients may experience lean body mass loss, micronutrient deficiencies, protein depletion, altered hydration status, and reduced physical performance. Conversely, excessive adiposity and changes in fat distribution may also occur and can contribute to ongoing immune activation. Therefore, nutritional status assessment and composition measurements may provide a comprehensive evaluation than body mass index (BMI) alone.

Isoflavones are naturally occurring phytoestrogens found in soy-based foods. Fermentation of soybeans into tempeh increases isoflavone bioavailability by converting glycoside forms into more biologically active aglycones while reducing antinutritional factors. Emerging evidence suggests that isoflavones may modulate inflammatory pathways and influence cytokine production, including tumor necrosis factor-alpha (TNF-α), a key mediator involved in intestinal inflammation.

Vitamin D has important functions beyond skeletal health and participates in immune regulation through its effects on both innate and adaptive immune responses. Vitamin D deficiency is frequently observed in patients with inflammatory bowel disease and has been associated with poorer clinical outcomes. Previous studies have reported improvements in disease activity scores, quality of life, and vitamin D status following supplementation, although data regarding its effects on inflammatory cytokines remain limited.