Taiwanese Green Propolis for Lipid Profiles, Fatigue, and Quality of Life in Oral Cavity Cancer Survivors (TGP-OCS)

Effects of Taiwanese Green Propolis (2,000 mg/Day) on Lipid Profiles, Cancer-Related Fatigue, and Quality of Life in Post-Treatment Oral Cavity Squamous Cell Carcinoma Survivors: A Double-Blind, Randomized Controlled Trial

This study examined whether Taiwanese Green Propolis (TGP), a natural bee-derived supplement, can improve blood fat levels, reduce tiredness (fatigue), and improve quality of life in people who have completed treatment for oral cavity (mouth) cancer.

People who had finished treatment for oral cavity squamous cell carcinoma (a type of mouth cancer) and were in the follow-up period were invited to participate. Participants were randomly assigned to take either 4 TGP capsules per day (2,000 mg/day total) or 4 identical-looking placebo capsules for 12 weeks. Neither participants nor the study team knew who received which capsules until after the study ended (double-blind). All participants were followed for a further 12 weeks after stopping the capsules.

At the start and at Weeks 4, 8, 12, and 24, participants had blood tests to measure cholesterol, triglycerides, liver enzymes, and inflammation markers. They also completed questionnaires about fatigue (BFI-T), symptoms (ESAS-r), and quality of life (FACT-H&N), and performed physical tests including grip strength and a 30-second sit-to-stand test.

The study aimed to determine whether TGP can help manage the metabolic and fatigue-related problems common after oral cancer treatment, and to provide data for planning larger future trials. 25 participants were enrolled at a regional teaching hospital in northern Taiwan. Stool and saliva samples were also collected at each timepoint to assess gut and oral microbiota composition (16S rRNA sequencing) and salivary inflammatory markers. Heart rate variability was monitored via smart wristband (minimum 24 hours per timepoint).

Study Overview

• Status: Completed
• Conditions: Dyslipidemias; Head and Neck Squamous Cell Carcinoma; Cancer-related Fatigue
• Intervention / Treatment: Dietary supplement: Taiwanese Green Propolis; Other: Placebo

Detailed Description

Background:

Oral cavity squamous cell carcinoma (OSCC) survivors frequently experience persistent metabolic complications after treatment, including dyslipidemia, chronic low-grade inflammation, cancer-related fatigue (CRF), muscle weakness, and impaired quality of life. The prevalence of metabolic syndrome in this population substantially exceeds that of the general Taiwanese adult population.

Taiwanese green propolis (TGP), derived from Macaranga tanarius (L.) Müll.Arg. (Euphorbiaceae), has a phytochemical profile distinct from Brazilian or Mediterranean propolis, comprising prenylated flavanones-principally propolin C, D, F, G, and H. These compounds have demonstrated hepatoprotective effects (TGF-β/Smad2/3 pathway), anti-inflammatory activity (NLRP3 inflammasome suppression), and lipid-metabolic regulatory properties in preclinical studies. No prior clinical trial has evaluated TGP in OSCC survivors.

Study Design:

Pilot double-blind, placebo-controlled, parallel-group randomized controlled trial (RCT). Intervention period: 12 weeks. Post-intervention follow-up: 12 weeks (total 24 weeks). Assessment timepoints: Week 0 (T0/baseline), Week 4 (T4), Week 8 (T8), Week 12 (T12), Week 24 (T24).

Intervention:

• Experimental: TGP capsules (500 mg/capsule), 4 capsules/day (2 capsules BID), providing 2,000 mg TGP/day containing approximately 200 mg propolin compounds/day; 12 weeks.
• Control: Identical-appearing placebo capsules, 4 capsules/day, 12 weeks. Both capsules were identical in appearance, size, color, and smell.

Randomization and Blinding:

Computer-generated random number sequence with allocation concealment. Participants, care providers, investigators, and outcome assessors were blinded throughout the 24-week study period (quadruple blinding).

Primary Outcomes (T0, T8, T12, T24):

Total cholesterol (TC, mg/dL); Triglycerides (TG, mg/dL); High-density lipoprotein cholesterol (HDL-C, mg/dL); Low-density lipoprotein cholesterol (LDL-C, mg/dL).

Secondary Outcomes:

• Cancer-related fatigue: BFI-T mean score (0-10); T0,T8,T12,T24
• Symptom distress: ESAS-r total score (0-90); T0,T4,T8,T12,T24
• Quality of life: FACT-H&N total score; T0,T8,T12,T24
• Grip strength (kg), dominant hand, mean of 3 trials; T0,T4,T8,T12,T24
• 30-second sit-to-stand test (repetitions); T0,T4,T8,T12,T24
• C-reactive protein (CRP, mg/dL); T0,T8,T12,T24
• Alanine aminotransferase (ALT/GPT, U/L); T0,T8,T12,T24
• Aspartate aminotransferase (AST/GOT, U/L); T0,T8,T12,T24
• Gamma-glutamyl transferase (γ-GT, U/L); T0,T8,T12,T24

Exploratory Outcomes:

Body weight, BMI, waist circumference, hip circumference, body fat %, hemoglobin, albumin, fasting glucose, HbA1c, BUN, creatinine, uric acid, WBC count, TSH, T3, T4. Serum interleukin-6 (IL-6, pg/mL); T0,T8,T12,T24. Gut microbiota alpha diversity (Shannon index) and beta diversity (Bray-Curtis dissimilarity) via stool 16S rRNA amplicon sequencing; T0,T8,T12,T24. Gut microbiota relative abundance of key bacterial taxa; T0,T8,T12,T24. Oral microbiota composition via saliva 16S rRNA amplicon sequencing; T0,T8,T12,T24. Salivary inflammatory markers including IL-6 (pg/mL); T0,T8,T12,T24. Heart rate variability: RMSSD and SDNN via smart wristband (minimum 24 hours per timepoint); T0,T4,T8,T12,T24.

Statistical Analysis:

Generalized Estimating Equations (GEE) with exchangeable working correlation structure; independent variables: group, time, and group × time interaction; adjusted for baseline values. Cohen's d calculated for significant interaction terms. Intent-to-treat (ITT) principle; N=25.

Sample Size:

Target: 62 participants (G*Power v3.1; repeated-measures ANOVA; f²=0.30; α=0.05; power=0.80; 10% dropout). Actual enrollment (pilot phase): 25.

Ethics:

Enrolment commenced in April 2024 under the original approved protocol N202305017 (approved 2023-05-22, Taipei Medical University Joint Institutional Review Board). A protocol amendment (N202407011, approved 2024-08-15) refined the inclusion criteria to focus on post-treatment oral cavity cancer survivors, designated lipid profiles as the primary outcome, and repositioned fatigue and quality of life as secondary outcomes. The amendment applied prospectively to all subsequently enrolled participants. Written informed consent was obtained from all participants prior to enrolment.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Taipei Medical University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 years or older
2. Histologically confirmed diagnosis of oral cavity squamous cell carcinoma (OSCC)
3. Post-primary treatment follow-up phase (surgery with or without adjuvant radiotherapy and/or chemotherapy completed)
4. Alert and oriented; able to complete study assessments independently or with research staff assistance
5. Able to communicate in Mandarin or Taiwanese
6. Not chewing betel quid during the study period
7. Willing to provide written informed consent

Exclusion Criteria:

1. Known allergy to propolis, honey, multiple pollens, or alcohol
2. Psychiatric disorder or cognitive impairment preventing study participation
3. Neuromuscular or joint disorders preventing performance of grip strength or sit-to-stand assessments
4. Pain at testing limb sites preventing physical assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Taiwanese Green Propolis (TGP); Participants receive Taiwanese Green Propolis capsules (500 mg/capsule, 4 capsules/day divided as 2 capsules in the morning and 2 in the evening) for 12 weeks, providing 2,000 mg TGP/day containing approximately 200 mg propolin compounds (propolin C, D, F, G, H)/day.	Dietary supplement: Taiwanese Green Propolis; Taiwanese Green Propolis (TGP) capsules derived from Macaranga tanarius (L.) Müll.Arg. (Euphorbiaceae). Each capsule contains 500 mg TGP with approximately 50 mg propolin compounds. Administered as 4 capsules/day (2 capsules BID, orally) for 12 weeks; total daily dose 2,000 mg TGP containing approximately 200 mg propolin compounds/day.
Placebo Comparator: Placebo; Participants receive identical-appearing placebo capsules (4 capsules/day, divided as 2 capsules in the morning and 2 in the evening) for 12 weeks. Capsules are identical to TGP capsules in appearance, size, color, and smell but contain no active propolis constituents.	Other: Placebo; Placebo capsules identical to TGP capsules in appearance, size, color, and smell, but containing inert excipients with no active propolis constituents. Administered as 4 capsules/day (2 capsules BID, orally) for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Triglycerides (TG)	Fasting serum triglycerides (mg/dL)	Baseline (Week 0), Week 8, Week 12, Week 24
Total Cholesterol (TC)	Fasting serum total cholesterol (mg/dL)	Baseline (Week 0), Week 8, Week 12, Week 24
High-Density Lipoprotein Cholesterol (HDL-C)	Fasting serum HDL-C (mg/dL)	Baseline (Week 0), Week 8, Week 12, Week 24
Low-Density Lipoprotein Cholesterol (LDL-C)	Fasting serum LDL-C (mg/dL)	Baseline (Week 0), Week 8, Week 12, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer-Related Fatigue - BFI-T Mean Score	Brief Fatigue Inventory-Taiwanese version; 9-item; mean score 0-10; higher = greater fatigue	Week 0, 8, 12, 24
Symptom Distress - ESAS-r Total Score	Edmonton Symptom Assessment Scale-Revised; total score 0-90; higher = greater symptom burden	Week 0, 4, 8, 12, 24
Quality of Life - FACT-H&N Total Score	Functional Assessment of Cancer Therapy-Head and Neck; higher score = better quality of life	Week 0, 8, 12, 24
Grip Strength	Dominant hand; mean of 3 trials with handheld dynamometer (kg)	Week 0, 4, 8, 12, 24
30-Second Sit-to-Stand Test	Number of complete sit-to-stand repetitions in 30 seconds	Week 0, 4, 8, 12, 24
C-Reactive Protein (CRP)	Serum CRP (mg/dL); systemic inflammatory marker	Week 0, 8, 12, 24
Alanine Aminotransferase (ALT/GPT)	Serum ALT (U/L); hepatic injury marker	Week 0, 8, 12, 24
Aspartate Aminotransferase (AST/GOT)	Serum AST (U/L)	Week 0, 8, 12, 24
Gamma-Glutamyl Transferase (γ-GT)	Serum γ-GT (U/L); hepatic function marker	Week 0, 8, 12, 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Interleukin-6 (IL-6)	Serum IL-6 concentration (pg/mL) by ELISA	Week 0, 8, 12, 24
Gut Microbiota Alpha Diversity	Stool 16S rRNA amplicon sequencing; Shannon index and observed species richness	Week 0, 8, 12, 24
Gut Microbiota Composition and Beta Diversity	Stool 16S rRNA sequencing; Bray-Curtis dissimilarity and relative abundance of key bacterial taxa	Week 0, 8, 12, 24
Oral Microbiota Composition	Saliva 16S rRNA amplicon sequencing; alpha and beta diversity indices	Week 0, 8, 12, 24
Salivary Inflammatory Markers	Salivary IL-6 and other cytokines (pg/mL) by multiplex immunoassay or ELISA	Week 0, 8, 12, 24
Heart Rate Variability (HRV)	HRV index via smart wristband worn ≥24 hours per timepoint	Week 0, 4, 8, 12, 24

Collaborators and Investigators

• Sponsor: Taipei Medical University

Publications and helpful links

General Publications

• Lin CC, Chang AP, Chen ML, Cleeland CS, Mendoza TR, Wang XS. Validation of the Taiwanese version of the Brief Fatigue Inventory. J Pain Symptom Manage. 2006 Jul;32(1):52-9. doi: 10.1016/j.jpainsymman.2005.12.019.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2024
• Primary Completion (Actual): June 26, 2026
• Study Completion (Actual): June 26, 2026

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: randomized controlled trial; quality of life; dietary supplement; Taiwanese green propolis; propolis; cancer-related fatigue; lipid profiles; oral cavity cancer survivors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Metabolic Diseases; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Lipid Metabolism Disorders; Carcinoma, Squamous Cell; Nutritional and Metabolic Diseases; Squamous Cell Carcinoma of Head and Neck; Dyslipidemias
• Other Study ID Numbers: TMU-N202305017oralcancer; N202305017 (Other Identifier: Taipei Medical University); N202407011 (Other Identifier: Taipei Medical University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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