Alcoholic Fatty Liver Disease
Conditions
Keywords
Liver diseases, Tocotrienols, Antioxidants, Oxidative stress
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTPalm 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.
OTHERRefined, 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.
Sponsors
Universiti Kebangsaan Malaysia Medical Centre
Malaysia Palm Oil Board
Hovid Berhad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
For the purpose of assigning participants to interventions, each subject was assigned a unique identification number. The researcher who generated the random allocation sequence and assigned participants was masked to the participants' clinical data and was independent of those involved in participant enrolment. Both researchers and participants were masked to the assigned treatment.
Intervention model description
This study is a randomised, double-mask, placebo-controlled (parallel group), phase 2 clinical trial investigating the effect of palm tocotrienol-rich fraction on alcoholic fatty liver disease (AFLD).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in Aspartate Aminotransferase (AST) at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention | 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. |
| Change from baseline in Alanine Aminotransferase (ALT) at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention. | 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. |
| Change from baseline in Gamma-Glutamyl Transferase (GGT) at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention. | 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. |
| Between-group difference in AST at 3 and 6 months (Tocotrienol-Rich Fraction [TRF] vs placebo) | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in units per liter (U/L); Lower values indicate improvement. |
| Between-group difference in ALT at 3 and 6 months (TRF vs placebo) | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in units per liter (U/L); Lower values indicate improvement. |
| Between-group difference in GGT at 3 and 6 months (TRF vs placebo) | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in units per liter (U/L); Lower values indicate improvement. |
| Change from baseline in Fatty Liver Index (FLI) at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention | Unitless score (range 0-100); Reported as absolute and percentage change; Higher scores indicate greater hepatic steatosis (worse outcome). |
| Between-group difference in Fatty Liver Index (FLI) at 3 and 6 months (TRF vs placebo). | From enrollment to the end of treatment at 3 and 6 months post intervention | Range 0-100; Higher scores indicate worse steatosis. |
| Change from baseline in Liver Stiffness Measurement using Transient Elastography (FibroScan® score) at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in kilopascals (kPa; typical range 2-75); Reported as absolute and percentage change; Higher values indicate greater fibrosis (worse outcome). |
| Between-group difference in Liver Stiffness Measurement (FibroScan® score) at 3 and 6 months (TRF vs placebo) | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in kilopascals (kPa; typical range 2-75); Higher values indicate worse fibrosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Cytokine Levels (Anti-inflammatory Effect of Tocotrienols) at 3 and 6 months. | From enrollment to the end of treatment at 3 and 6 months post intervention | 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) |
| Change From Baseline in Fasting Blood Glucose [FBG] Concentration at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in milligrams per deciliter (mg/dL); Typical ranges: 70-100 mg/dL; Higher values indicate worse metabolic profile. |
| Change From Baseline in Total Cholesterol (TC) Concentration at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in milligrams per deciliter (mg/dL); Typical ranges: 125-200 mg/dL; Higher total cholesterol reflect a worse metabolic profile |
| Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) Concentration at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in milligrams per deciliter (mg/dL); Typical ranges: 0-130 mg/dL; Higher LDL-C reflect a worse metabolic profile |
| Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) Concentration at 3 and 6 months | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in milligrams per deciliter (mg/dL); Typical ranges: 40-60 mg/dL; Higher HDL-C reflects a better metabolic profile. |
| Change From Baseline in Triglyceride (TG) Concentration at 3 and 6 months. | From enrollment to the end of treatment at 3 and 6 months post intervention | Measured in milligrams per deciliter (mg/dL); Typical ranges: 0-150 mg/dL; Higher triglycerides reflect a worse metabolic profile |
Countries
Malaysia
Contacts
CONTACTSiti Norain Azahar, Medicine (MD)
CONTACTProfessor Dr. Nur Azlina Mohd Fahami, DVM
PRINCIPAL_INVESTIGATORProfessor Dr. Nur Azlina Mohd Fahami, DVM
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM)
Outcome results
None listed