The Efficacy of Tocotrienol Rich Fraction for Liver Protection in Adult Patients With Alcoholic Fatty Liver Disease (AFLD)

The Effect of Palm Tocotrienol Rich Fraction on Alcoholic Fatty Liver Disease (AFLD): A Phase II Clinical Trial

This clinical study aims to explore the potential liver-protective effects of palm tocotrienol-rich fraction (a form of Vitamin E) in adults with alcoholic fatty liver disease (AFLD). A total of 26 participants aged 18 to 65 years with AFLD will be randomly assigned to receive either tocotrienol (200 mg twice daily) or a placebo for six months. Throughout the study, participants will undergo regular liver health assessments including blood tests, FibroScan, and FibroTest, alongside evaluations of oxidative stress and inflammation markers. The study aims to determine whether tocotrienol can help improve liver function and reduce alcohol-related liver damage. Findings from this trial may provide valuable evidence for future clinical studies and highlight the potential of Malaysian palm-based tocotrienol as a natural, supportive approach to liver health.

Study Overview

• Status: Not yet recruiting
• Conditions: Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Palm Tocotrienol Rich Fraction (TRF); Other: Refined, bleached, and deodorised (RBD) palm olein

Detailed Description

Recent evidence from preclinical studies has shown that tocotrienols, a unique form of Vitamin E derived from palm oil, possess strong antioxidant, anti-inflammatory, and hepatoprotective properties. These effects have been demonstrated in non-alcoholic fatty liver disease (NAFLD) models, suggesting their potential benefit in alcohol-related liver injury as well. However, clinical evidence in human AFLD populations remains limited. Therefore, this study seeks to investigate the efficacy and safety of palm tocotrienol-rich fraction supplementation in patients with AFLD.

This is a randomized, double-blind, placebo-controlled Phase II clinical trial involving 26 adult participants aged 18 to 65 years who have been clinically diagnosed with alcoholic fatty liver disease. Participants will be randomly assigned to either: Treatment group (n = 13): receiving palm tocotrienol-rich fraction soft gels (200 mg twice daily); or Placebo group (n = 13): receiving refined, bleached, and deodorised (RBD) palm olein soft gels (200 mg twice daily). The intervention period will last six months, with follow-up assessments every three months. Participants will complete structured questionnaires on alcohol consumption patterns, lifestyle, and dietary habits at each visit. Blood samples will be collected at baseline and follow-up visits to evaluate liver function tests (ALT, AST, GGT, ALP, bilirubin), oxidative stress markers, haematological parameters, and inflammatory biomarkers such as cytokines. Non-invasive liver assessments, including FibroScan and FibroTest, will be performed twice during the study to monitor changes in liver fat content, and stiffness levels.

This study aims to provide scientific evidence on the efficacy of tocotrienol-rich fraction in improving liver health among individuals with AFLD. If proven effective, tocotrienol may represent a safe therapeutic option for mitigating alcohol-induced liver injury. The findings will also contribute to the development of evidence-based nutraceutical applications of palm tocotrienol and support efforts to diversify and add value to Malaysia's palm oil industry through health-promoting innovations. Moreover, the results will serve as baseline data for larger-scale clinical trials and future research into tocotrienol's broader therapeutic potential.

• Study Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Siti Norain Azahar, Medicine (MD); Phone Number: 60-1126792792; Email: drainazahar@gmail.com
• Study Contact Backup: Name: Professor Dr. Nur Azlina Mohd Fahami, DVM; Phone Number: +60-391459574; Email: nurazlinamf@ukm.edu.my

Study Locations

• Malaysia
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak
      • Contact: Siti Norain Azahar, Medicine (MD); Phone Number: 60-1126792792; Email: drainazahar@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with history of alcoholic use disorder with clinical and biochemical evidence of alcoholic steatohepatitis (AST:ALT >2.0, elevated GGT)
2. Patients with Maddrey's discriminant function ≤ 32, and do not require the treatment of corticosteroid therapy or pentoxifylline.
3. Patients aged 18 to 65
4. Patients who could comply with alcohol abstinence.

Exclusion Criteria:

1. Severe alcoholic hepatitis defined as Maddrey's discriminant function >32

2. Patients with other concomitant liver diseases:

   1. Hepatitis B
   2. Hepatitis C
   3. Non-alcoholic fatty liver disease (NAFLD)
   4. Autoimmune hepatitis (AIH)
   5. Hereditary hemochromatosis
3. Patients who are obese (a BMI of 30 kg/ m2 or more) and with metabolic syndromes
4. Patients with bleeding disorders and who have been on anticoagulant or antiaggregant treatments
5. Patients who have been on corticosteroid therapy or pentoxifylline for alcoholic hepatitis
6. Patients with hepatocellular carcinoma
7. Pregnant patients
8. Patients who are breastfeeding
9. Patients with Childs C liver cirrhosis
10. Patients who have pyridoxine allergy or history
11. Patients who are judged by investigator that participation of the study is difficult due to disease as follow; hepatic cirrhosis, Wilson's disease, malignant tumor, serious metabolic disease, severe renal disease, severe pulmonary disease, severe cardiovascular disease, severe nervous disease/psychiatric disorder, muscle disease and etc.
12. Patients taking vitamin E, herbal supplements, or other investigational products within 90 days prior to the participation in the study.
13. Patients who have been taken any medications that could affect the treatment: hypoglycemic agents, colchicine, penicillamine, corticosteroids, ursodeoxycholic acid, pentoxifylline, long-term use of NSAIDs, statins, neuroleptics, anticonvulsant medications, high-dose acetaminophen(>=2.5g/day)
14. Patients who have received treatment that may affect liver function within 1 month prior to the participation in the study
15. Patients who could not comply with alcohol abstinence.
16. Patient who considered ineligible for participation in the study as Investigator's judgment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment group (mixed tocotrienol); The treatment group will be prescribed with palm tocotrienol soft gel capsules (200 mg twice daily) for six months	Dietary supplement: Palm Tocotrienol Rich Fraction (TRF); The treatment group will be prescribed with palm tocotrienol soft gel (200 mg twice daily). The composition of the tocotrienol mixture is 24.7% α-tocotrienol, 4.5% β-tocotrienol, 36.9% γ-tocotrienol, 12.0% σ-tocotrienol and 21.6% α-tocopherol. It is formulated with a self-emulsifying system (SES) to enhance absorption of tocotrienol. One soft gel will be taken orally, daily after breakfast and dinner to complete the 400 mg daily dose. The treatment period will be 6 months.
Placebo Comparator: Placebo group; The placebo group will receive refined, bleached, and deodorised (RBD) palm olein for six months.	Other: Refined, bleached, and deodorised (RBD) palm olein; The placebo consisted of an equivalent volume of refined, bleached, and deodorised (RBD) palm olein. The placebo was formulated as soft gelatin capsules that were identical to the tocotrienol capsules in colour, size, shape, and surface texture.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Aspartate Aminotransferase (AST) at 3 and 6 months	Reported as absolute and percentage change; Measured in units per liter (U/L); Typical range: 8-48 U/L; Lower values indicate improved liver function.	From enrollment to the end of treatment at 3 and 6 months post intervention
Change from baseline in Alanine Aminotransferase (ALT) at 3 and 6 months	Reported as absolute and percentage change; Measured in units per liter (U/L); Typical ranges: 7-56 U/L; Lower values indicate improved liver function.	From enrollment to the end of treatment at 3 and 6 months post intervention.
Change from baseline in Gamma-Glutamyl Transferase (GGT) at 3 and 6 months	Reported as absolute and percentage change; Measured in units per liter (U/L); Typical ranges: 8 - 61 U/L; Lower values indicate improved liver function.	From enrollment to the end of treatment at 3 and 6 months post intervention.
Between-group difference in AST at 3 and 6 months (Tocotrienol-Rich Fraction [TRF] vs placebo)	Measured in units per liter (U/L); Lower values indicate improvement.	From enrollment to the end of treatment at 3 and 6 months post intervention
Between-group difference in ALT at 3 and 6 months (TRF vs placebo)	Measured in units per liter (U/L); Lower values indicate improvement.	From enrollment to the end of treatment at 3 and 6 months post intervention
Between-group difference in GGT at 3 and 6 months (TRF vs placebo)	Measured in units per liter (U/L); Lower values indicate improvement.	From enrollment to the end of treatment at 3 and 6 months post intervention
Change from baseline in Fatty Liver Index (FLI) at 3 and 6 months	Unitless score (range 0-100); Reported as absolute and percentage change; Higher scores indicate greater hepatic steatosis (worse outcome).	From enrollment to the end of treatment at 3 and 6 months post intervention
Between-group difference in Fatty Liver Index (FLI) at 3 and 6 months (TRF vs placebo).	Range 0-100; Higher scores indicate worse steatosis.	From enrollment to the end of treatment at 3 and 6 months post intervention
Change from baseline in Liver Stiffness Measurement using Transient Elastography (FibroScan® score) at 3 and 6 months	Measured in kilopascals (kPa; typical range 2-75); Reported as absolute and percentage change; Higher values indicate greater fibrosis (worse outcome).	From enrollment to the end of treatment at 3 and 6 months post intervention
Between-group difference in Liver Stiffness Measurement (FibroScan® score) at 3 and 6 months (TRF vs placebo)	Measured in kilopascals (kPa; typical range 2-75); Higher values indicate worse fibrosis.	From enrollment to the end of treatment at 3 and 6 months post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Cytokine Levels (Anti-inflammatory Effect of Tocotrienols) at 3 and 6 months.	Cytokine measured: Interleukin-6 (IL-6) in plasma; Measurement method: Multiplex Enzyme-Linked Immunosorbent Assay (ELISA); Measured in picograms per milliliter (pg/mL); Normal range: < 5-7 pg/mL; Higher values indicate greater inflammation (worse outcome)	From enrollment to the end of treatment at 3 and 6 months post intervention
Change From Baseline in Fasting Blood Glucose [FBG] Concentration at 3 and 6 months	Measured in milligrams per deciliter (mg/dL); Typical ranges: 70-100 mg/dL; Higher values indicate worse metabolic profile.	From enrollment to the end of treatment at 3 and 6 months post intervention
Change From Baseline in Total Cholesterol (TC) Concentration at 3 and 6 months	Measured in milligrams per deciliter (mg/dL); Typical ranges: 125-200 mg/dL; Higher total cholesterol reflect a worse metabolic profile	From enrollment to the end of treatment at 3 and 6 months post intervention
Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) Concentration at 3 and 6 months	Measured in milligrams per deciliter (mg/dL); Typical ranges: 0-130 mg/dL; Higher LDL-C reflect a worse metabolic profile	From enrollment to the end of treatment at 3 and 6 months post intervention
Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) Concentration at 3 and 6 months	Measured in milligrams per deciliter (mg/dL); Typical ranges: 40-60 mg/dL; Higher HDL-C reflects a better metabolic profile.	From enrollment to the end of treatment at 3 and 6 months post intervention
Change From Baseline in Triglyceride (TG) Concentration at 3 and 6 months.	Measured in milligrams per deciliter (mg/dL); Typical ranges: 0-150 mg/dL; Higher triglycerides reflect a worse metabolic profile	From enrollment to the end of treatment at 3 and 6 months post intervention

Collaborators and Investigators

• Sponsor: Universiti Kebangsaan Malaysia Medical Centre
• Collaborators: Malaysia Palm Oil Board; Hovid Berhad
• Investigators: Principal Investigator: Professor Dr. Nur Azlina Mohd Fahami, DVM, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM)

Publications and helpful links

General Publications

• REFERENCES: 1. Liver EAftSot. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. Journal of hepatology 2018;69: 154-181. 2. Institute for Public Health (IPH), National Institutes of Health, Ministry of Health Malaysia. 2020. National Health and Morbidity Survey (NHMS) 2019: Vol. I: NCDs - NonCommunicable Diseases: Risk Factors and other Health Problems. 3. Chacko KR, Reinus J. Spectrum of alcoholic liver disease. Clinics in liver disease 2016;20: 419-427. 4. Deleuran T, Grønbaek H, Vilstrup H, Jepsen P. Cirrhosis and mortality risks of biopsy- verified alcoholic pure steatosis and steatohepatitis: a nationwide registry-based study. Alimentary pharmacology & therapeutics 2012;35: 1336-1342. 5. Setshedi M, Wands JR, de la Monte SM. Acetaldehyde adducts in alcoholic liver disease. Oxidative medicine and cellular longevity 2010;3. 6. Rolla R, Vay D, Mottaran E, et al. Detection of circulating antibodies against malondialdehyde-acetaldehyde adducts in patients with alcohol-induced liver disease. Hepatology 2000;31: 878-884. 7. Nagata K, Suzuki H, Sakaguchi S. Common pathogenic mechanism in development progression of liver injury caused by non-alcoholic or alcoholic steatohepatitis. J Toxicol Sci. 2007;32(5):453-68. 8. Nath B, Levin I, Csak T, Petrasek J, Mueller C, Kodys K, et al. Hepatocyte-specific hypoxia- inducible factor-1α is a determinant of lipid accumulation and liver injury in alcoholinduced steatosis in mice. Hepatology. 2011;53(5):1526-37. 9. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. (2012) 55:2005-23. 10. European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity. EASL-EASD-EA

Study record dates

Study Major Dates

• Study Start (Estimated): May 2, 2026
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): February 15, 2027

Study Registration Dates

• First Submitted: February 12, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Antioxidants; Oxidative stress; Liver diseases; Tocotrienols
• Additional Relevant MeSH Terms: Digestive System Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Fatty Liver; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Liver Diseases; Fatty Liver, Alcoholic
• Other Study ID Numbers: JEP-2021-694; TAP-K010316 (Other Grant/Funding Number: Malaysian Palm Oil Board (MPOB))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication

Drug and device information, study documents

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