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

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) is a chronic immune-mediated disorder characterized by recurrent intestinal inflammation, impaired nutritional status, and reduced quality of life. Nutritional deficiencies and alterations in body composition are frequently observed in patients with IBD and may contribute to disease burden and long-term complications.

Isoflavones derived from fermented soy products, such as tempeh, have demonstrated anti-inflammatory properties in both experimental and clinical studies. Vitamin D is an important immunomodulatory nutrient, and its deficiency is common in patients with IBD. However, evidence regarding the combined effects of isoflavone and vitamin D supplementation on inflammatory markers, nutritional status, and quality of life in patients with IBD remains limited.

This study aimed to evaluate the effects of daily tempeh powder supplementation providing approximately 50 mg of isoflavones and 4000 IU of vitamin D3 for 8 weeks in patients with IBD. Outcomes include changes in serum vitamin D concentration, body composition parameters, serum tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and quality of life assessed using the Inflammatory Bowel Disease Questionnaire-9 (IBDQ-9).

Study Overview

• Status: Completed
• Conditions: Crohn Disease (CD); Ulcerative Colitis (UC)
• Intervention / Treatment: Other: Standard medical treatment; Dietary supplement: Tempeh Isoflavone; Dietary supplement: Vitamin D (Cholecalciferol )

Detailed Description

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.

The balance between proinflammatory and anti-inflammatory cytokines is central to the pathogenesis of IBD. TNF-α promotes inflammatory signalling, leukocyte recruitment, epithelial injury, and immune dysregulation. In contrast, interleukin-10 (IL-10) is a major anti-inflammatory cytokine that suppresses excessive immune responses and contributes to intestinal immune homeostasis. The evaluation of both cytokines may provide insight into the immunologic effects of nutritional interventions.

Quality of life is an important patient-centred outcome in IBD because the disease burden extends beyond gastrointestinal symptoms to include fatigue, emotional well-being, and social functioning. The validated Inflammatory Bowel Disease Questionnaire-9 (IBDQ 9) offers a practical assessment of health-related quality of life and has demonstrated good reliability in Indonesian patients.

This study aimed to investigate the effects of an 8-week nutritional intervention consisting of tempeh powder providing approximately 50 mg of isoflavones per day combined with vitamin D3 supplementation at a dose of 4,000 IU per day in patients with IBD. The study will assess changes in serum vitamin D levels, body composition indicators, inflammatory biomarkers (TNF-α and IL-10), and quality-of-life scores using the IBDQ-9. The findings of this study are expected to contribute to the development of evidence-based nutritional strategies that complement standard medical therapy and support the overall management of patients with IBD.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female adults aged ≥18 years, diagnosed with inflammatory bowel disease including ulcerative colitis or Crohn's disease, receiving standard medical therapy for IBD, willing to provide written informed consent

Exclusion Criteria:

• Vegetarian, diagnosed as unclassifed IBD, patient with severe clinical manifestation requiring immediate medical management, with other diagnosed gastrointestinal diseases, pregnancy or lactation, severe hepatic impairment, with implant, with amputation of at least one extremity, with active infectious skin wounds or lesions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tempeh Isoflavone and vitamin D; Participants receive 50 gram/day tempeh powder providing approximately 50 mg isoflavones and oral supplementation of vitamin D3 4000 IU/day for 8 weeks in addition to standard therapy.	Other: Standard medical treatment; Participants do not receive tempeh powder of isoflavone and vitamin D. They receive standard medical therapy of IBD; Dietary supplement: Tempeh Isoflavone; Participants receive 50 gram/day of tempeh powder providing approximately 50 mg of isoflavones, administered orally for 8 weeks in addition to standard medical therapy.; Dietary supplement: Vitamin D (Cholecalciferol ); Participants receive oral supplementation of vitamin D3 4000 IU/day , administered orally for 8 weeks in addition to standard medical therapy.
Active Comparator: Standard Therapy; Participants receive standard medical therapy for inflammatory bowel disease for 8 weeks.	Other: Standard medical treatment; Participants do not receive tempeh powder of isoflavone and vitamin D. They receive standard medical therapy of IBD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum 25-hydroxyvitamin D levels between baseline and week 8	Serum 25-hydroxyvitamin D levels, measured in ng/mL, will be assessed at baseline and week 8. The change both from baseline and week 8 will be compared between the intervention and control groups.	Baseline and week 8
Change in serum tumor necrosis factor-alpha (TNF-α) levels between baseline and week 8	Serum TNF-α levels, measured in pg/mL, will be assessed at baseline and week 8. The change both from baseline and week 8 will be compared between the intervention and control groups.	Baseline and week 8
Change in serum interleukin (IL)-10 levels between baseline and week 8	Serum IL-10 levels, measured in pg/mL, will be assessed at baseline and week 8. The change both from baseline and week 8 will be compared between the intervention and control groups.	Baseline and week 8
Change in Inflammatory Bowel Disease Questionnaire (IBDQ)-9 score between baseline and week 8	Score of IBDQ-9, range: 0-100, will be assessed at baseline and week 8. The change both from baseline and week 8 will be compared between the intervention and control groups.	Baseline and week 8
Change in appendicular skeletal muscle index (ASMI) between baseline and week 8	Body composition will be assessed using bioelectrical impedance analysis (BIA) with electrodes placed on both hands and feet. Appendicular skeletal muscle mass will be expressed as the Appendicular Skeletal Muscle Index (ASMI, kg/m²), calculated as the sum of skeletal muscle mass in the right arm, left arm, right leg, and left leg (kg) divided by height squared (m²).	Baseline and week 8

Collaborators and Investigators

• Sponsor: Indonesia University

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2025
• Primary Completion (Actual): January 19, 2026
• Study Completion (Actual): February 25, 2026

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 14, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: body composition; vitamin D; isoflavones; TNF-alpha; inflammatory bowel disease; tempeh; IL-10
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Colitis; Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Cholecalciferol
• Other Study ID Numbers: 25-05-0719

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared due to confidentiality and privacy considerations

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No