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. 2023 Mar 2;16(3):385. doi: 10.3390/ph16030385

Table 1.

The effects of tocotrienol on OA.

Researchers Study Design Findings
Pang et al. (2021) [49] Disease model: SW1353 chondrocytes challenged with MIA
Treatment: annatto tocotrienol (10–20 μg/mL) or palm tocotrienol (25–50 μg/mL) for 24 h before or concurrent with MIA
Cell viability:
Pre-treatment
Decreased upon receiving annatto tocotrienol (≥20 μg/mL) & palm tocotrienol (≥12.5 μg/mL) → no subsequent test
Concurrent treatment
Increased upon receiving annatto tocotrienol (10 and 20 μg/mL)/palm tocotrienol (3.125, 25 and 50 μg/mL)
8-Isoprostane F2-α Level:
Decreased upon receiving palm tocotrienol (50 μg/mL) or annatto tocotrienol (10 and 20 μg/mL) in the presence of MIA
Collagen I type α1: Decreased in MIA group, not affected by treatment
Collagen II type α1: Increased upon receiving annatto tocotrienol (10 & 20 μg/mL) in the presence of MIA vs MIA alone or annatto tocotrienol alone
Collagen II type α1/Collagen I type α1: Increased upon receiving MIA + treatment vs treatment alone.
Increased upon receiving annatto tocotrienol alone (10 and 20 μg/mL) vs. MIA alone
Aggrecan and sex-determining region Y box protein 9:
Increased upon receiving MIA + annatto tocotrienol (10 and 20 μg/mL) vs. MIA alone
ADAMTS4: Decreased in MIA group, not affected by treatment
Chin et al. (2019) [48] Animals: Male Sprague-Dawley rats (3 months old)

Disease model: Intra-articular MIA injection at the right knee

Treatment:
annatto tocotrienol at the dose of 50, 100, 150 mg/kg/day, oral for 4 weeks
Normal and OA control were given refined olive oil (vehicle in the study)
Body weight:
Increased in all groups from week 1–week 4
Histological scoring:
Decreased in all aspects for 100 mg/kg/day annatto tocotrienol vs OA control
Decreased in the number of inflammatory cells and synovial hyperplasia for 100 mg/kg/day vs 50 mg/kg/day annatto tocotrienol groups
Reduced synovial hyperplasia and erosions in 150 mg/kg/day annatto tocotrienol group vs OA control
No significant improvement in 50 mg/kg/day annatto tocotrienol group
Serum COMP:
Decreased in 50, 100 & 150 mg/kg/day annatto tocotrienol group vs OA control
Decreased in 100 & 150 mg/kg/day T vs 50 mg/kg/day annatto tocotrienol
Serum hyaluronic acid:
Decreased in 50, 100 & 150 mg/kg/day annatto tocotrienol group vs OA control
Subchondral osteoclast number:
Decreased in 150 mg/kg/day annatto tocotrienol group vs OA control
Serum osteocalcin:
Increased in 50 mg/kg/day annatto tocotrienol group vs OA control.
Decreased in 100 & 150 mg/kg/day annatto tocotrienol group vs 50 mg/kg/day annatto tocotrienol
Decreased in 150 mg/kg/day annatto tocotrienol group vs all other groups except normal group
Serum C-telopeptide of crosslinked collagen type I:
No significant effect
Al-Saadi et al. (2021) [47] Animals: Male Sprague-Dawley rats (3 months old)

Disease model: Intra-articular MIA injection at the right knee

Treatment:
palm tocotrienol treated (100 mg/kg/day; oral)
Glucosamine sulphate treated (250 mg/kg/day; oral)
palm tocotrienol (100 mg/kg/day) + glucosamine sulphate-treated group (250 mg/kg/day) (oral)
Normal and OA control were given refined olive oil (vehicle in the study)
Treatment period; 4 weeks
Grip strength:
No significant change between normal control, OA control & palm tocotrienol between week 0–week 4.
Increased in palm tocotrienol + glucosamine sulphate group vs sham & palm tocotrienol group from week 1–week 3.
Increased in glucosamine sulphate group in week 4 vs week 1.
Increased in palm tocotrienol + glucosamine sulphate group in week 4 vs week 1–3.
Body weight:
Increased in normal control vs OA control, palm tocotrienol & palm tocotrienol + glucosamine sulphate groups at week 1.
Increased in palm tocotrienol, glucosamine sulphate and combination group vs OA control at week 3.
Cartilage histology (Mankin’s score):
No significant change between OA control, palm tocotrienol, glucosamine sulphate and combination group.
Serum COMP:
Increased in OA control vs palm tocotrienol, glucosamine sulphate and combination group.
No significant change between treated group.
Haflah et al. (2009) [46] Subjects: 79 patients with knee OA (Kellgren-Lawrence score of 2 and 3) aged over 40 years
Treatment: Oral palm tocotrienol (400 mg daily) for 6 months
Positive control: Glucosamine sulphate (500 mg thrice daily) for 6 months
Notes: Patients were not allowed to take any other analgesics
Visual analogue scale:
Standing & walking
Decreased in palm tocotrienol & glucosamine sulphate
WOMAC score:
Decreased in palm tocotrienol & glucosamine sulphate
Serum malondialdehyde:
Decreased in palm tocotrienol vs glucosamine sulphate
Serum vitamin E:
Increased in palm tocotrienol vs glucosamine sulphate

Abbreviations: ADAMTS4, a disintegrin and metalloproteinase with thrombospondin motifs 4; COMP, circulating cartilage oligomeric matrix protein; MIA, monosodium iodoacetate; WOMAC, Western Ontario and McMaster Universities’ OA index.