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| STUDY | Type of study/vit E analog | Sample/ population | Methodology | Results
(vitamin E and osteoporosis only) | Comments or outcomes |
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Norazlina et al. 2000 [32] | Animal study
Bone mineral density
α-Tocopherol
Tocotrienol | 3-month-old female Sprague-Dawley rats
(n = 80)
Half of rat were ovariectomised and half were left intact
Rats were assigned into four group (10 rats for each groups)
Duration: 10-month treatment | Three of the four groups were supplemented with palm vitamin E 30 mg/kg (PVE30), palm vitamin E 60 mg/kg (PVE60), or α-tocopherol 30mg/kg (ATF). The other group was supplemented with normal rat chow (RC).
After 8 months of treatment, rats were sacrificed. The left femur and lumbar vertebra were dissected out and cleansed of all soft tissue for bone histomorphometry measurements:
(a) bone mineral density measurements of the left femur and vertebra were obtained using the Dual-Energy A-ray Absorptiometer
(b) bone calcium content
(c) serum biomarkers of bone metabolism
Serum alkaline phosphatase and serum tartrate resistant acid phosphatase were assayed and measured using a spectrophotometer at 405 nm. | (a) Bone mineral density
Bone mineral density did not show any significant difference between all treatment groups. Palm vitamin E 30 mg/kg group of intact rats had higher bone mineral density in the distal part of femur compared to the ovariectomised.
(b) Bone calcium content
Both intact and ovariectomised rats supplemented with palm vitamin E 30 mg/kg weight rat had lower bone calcium content in femoral and vertebral bone. However, PVE60 and ATF groups were able to maintain bone calcium content.
(c) Bone biomarkers
The activity of ALP enzyme did not differ between all treatment groups for both intact and ovariectomised rats. The ALP enzyme of ovariectomised rats for group PVE30 and ATF was higher than intact control. The TRAP enzyme activity, PVE60 supplemented rat, was significantly lower compared to intact ATF group. The enzyme activity is significantly lower in ATF ovariectomised group, if compared to intact group. | Both tocopherol and tocotrienol act on bone, but in different mechanism of action.
Alpha tocopherol reduced the activity of TRAP that maintains bone mineral density. |
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Ima-Nirwanaet and Suhaniza 2004 [54]
| Animal study
Histomor-phometry analysis
α-Tocopherol
γ-Tocotrienol | 4-months-old male Sprague-Dawley rats (n = 42)
Rats were adrenalectomized after two-day receipt
Rats were randomly assigned into six groups. 7 rats for each group
Duration: 8-week treatment | Rats randomly divided into six group as follows:
(a) Group A—dexamethasone 120 μg/kg + vehicle olive oil
(b) Group B—dexamethasone 240 μg/kg + vehicle olive oil
(c) Group C—dexamethasone 120 μg/kg + α- tocopherol 60 mg/kg
(d) Group D—dexamethasone 240 μg/kg +α- tocopherol 60 mg/kg
(e) Group E—dexamethasone 120 μg/kg + γ-tocotrienol 60 mg/kg
(f) Group F—dexamethasone 240 μg/kg + γ-tocotrienol 60 mg/kg
Dexamethasone was dissolved in olive oils and given intramuscularly daily except on Sunday.
Parameters:
(a) body composition measurement were done using a dual-energy X-ray absorptiometer for bone mineral density for:
(i) left femur and fourth lumbar vertebra
(ii) whole body fat mass
(iii) whole body lean soft tissue mass
(b) bone calcium content. | (a) Bone mineral density
Whole body bone mineral density was increased after treatment. However, there was no significant difference between groups at the beginning and at the end of the treatment.
(b) Lean soft tissue
Whole body lean soft tissue mass was increased after the treatment. There was no significance difference between the groups at the beginning and at the end of the treatment.
(c) Whole body fat mass
Whole body fat mass was higher in group A compared to before treatment. There was no significant difference between the groups at the beginning of treatment. However, group A, C, and D had higher body fat mass, if compared with group F at the end of treatment.
(d) Bone calcium content
Fourth lumbar vertebral calcium content was higher in group E and F, if compared with group A and B. No significant difference was seen in left femoral calcium content between groups. | Supplemen-tation with γ-tocotrienol was effective in preventing the increase in body fat mass and has the best effect on body composition, while supplementation of α-tocopherol was not beneficial at all.
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Ahmad et al., 2005 [34] | Animal study
Bone histomorphometry analysis
Tocotrienol and α-tocopherol | 32 male Wistar rats (4 weeks old)
Rats divided randomly into four groups (8 rats each)
Rats were given daily treatment for 8 weeks | First group (control group) was injected intraperitoneally with saline. 2nd group was injected with 2 mg/kg Fe of ferric nitrilotriacetate (FeNTA) which was used to induce diabetes in rats. Group 3 was injected with FeNTA and was given oral doses of 100 mg/kg bodyweight α-tocopherol acetate (AT). Group 4 was injected with FeNTA and was given oral doses of 100 mg/kg bodyweight of palm tocotrienol (TT) mixture (α-TT 30.7%, γ-TT 55.2%, δ-TT 14.1%).
After 8 weeks of treatment, femurs of the rats were removed for bone histomorphometry measurements. Measurements include:
(1) trabecular bone volume (BV/TV)
(2) trabecular thickness (TbTh)
(3) trabecular number (TbN)
(4) mean osteoclast number (OcN)
(5) mean osteoblast number (ObN)
(6) eroded surface/bone surface (ES/BS)
(7) bone formation rate (BFR). | FeNTA injection significantly reduced BV/TV and TbTh of FeNTA and FeNTA + AT groups (P < 0.001). TT was able to prevent FeNTA-induced reduction of BV/TV and TbTh.
FeNTA + TT group had a higher BV/TV and TbTh, if compared to FeNTA + AT group (P < 0.02).
Supplementation with TT was able to prevent the increase of ES/BS and prevent the decrease of ObN and ES/BS due to FeNTA administration.
| FeNTA generates free radicals which damage bone cells and activate osteoclasts which mimic osteoporotic bone structure.
Only palm TT mixture was found to be able to prevent bone damage by FeNTA and is superior to AT in protecting bone against FeNTA toxicity. |
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Smith et al., 2005 [55]
| Animal Study
Serum α-Tocopherol analysis, serum biochemical marker, oxidative status, bone histology, and bone histomorphometry
α-Tocopherol | 96 Sprague-Dawley rats (8.5 months old)
Randomly assigned into 6 groups (16 rats each)
Total 13 weeks study period | 3 dietary treatments of α-tocopherol acetate (AT):
(1) low dose (LD)—15 IU/kg
(2) adequate dose (AD)—75 IU/kg
(3) high dose (HD)—500 IU/kg.
AD is the recommended dose and functions as control group.
Rats were fed one of 3 diets for 13 weeks. After 9 weeks, rats were either hindlimb unloaded (HU) or maintained ambulatory (AMB) for the final 4 weeks.
End of treatment period:
(1) whole body dual energy X-ray absorptiometry (DXA) scan was performed
(2) blood was taken for serum alkaline phosphatise (ALP) and tartrate resistant acid phosphatise (TRAP) level and activity
(3) serum AT level determined using HPLC
(4) oxidative status evaluated using plasma ferric-reducing ability (FRAP) and liver thiobarbituric acid reactive substances (TBARS)
(5) tibias of the rats were harvested for bone histology and the distal third of femur was harvested for bone histomorphometry. Parameters are as previously described. | FRAP improved with HD treatment group compared to LD and AD groups (P < 0.05).
Biochemical markers did not result in significant findings.
HU group had significantly lower bone histomorphometry results compared to AMB group but AT did not have any effect on bone histomorphometry.
Concentrating on HU group, BV/TV increased in AD and HD diets compared to LD diet. (P < 0.05).
AT helped to maintain TbN during unloading. | α-Tocopherol supplementation may provide some protection during hindlimb unloading conditions. However, results were not consistent for all parameters measured.
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Chai et al., 2008 [56] | Animal study
Bone density assessment of aged osteopenicorchidectomized male rats; control versus high-dose α-tocopherol (AT) supplementation
α-Tocopherol | 40 Sprague-Dawley rats (12 months old)
Randomly assigned into 4 groups (10 rats each)
Total 210 days study period | 12-month-old rats were fed AIN-93 M casein-based control diet for 120 days to establish bone loss. Rats were then assigned into 4 groups and given treatment for 90 days:
(1) sham operated (Sham)
(2) orchidectomized + 75 IU AT
(3) orchidectomized + 250 IU AT
(4) orchidectomized + 550 IU AT.
Analysis:
(1) whole body scanning done using DXA at baseline (before surgery), 120 days after surgery and 90 days after dietary treatment. Assessment of bone mineral content (BMC), density (BMD), and area (BMA)
(2) assessment of trabecular and cortical bone structures of distal femoral metaphysic and femoral midshaft using Micro-CT. Parameters assessed; BV/TV, TbN, TbTh, structural model index (SMI), connectivity density (Conn.D), cortical bone area (CoArea), thickness (CoTh), porosity (CoP), and medullary area (MArea)
(3) measurements of bone biochemical markers; serum osteocalcin, urinary deoxypyridinoline (Dpd), and urinary creatinine concentration. | Mean BMD values of Orx animals were significantly different (lower) compared with sham animals at 120 days (P = 0.009) and at 210 days (P = 0.001).
End of dietary treatment:
(1) mean BMD values of AT supplemented groups were not different than Sham group
(2) BMC and BMA were not affected with Orx or AT supplementation
(3) no significant difference of serum osteocalcin and urinary Dpd noted among the four treatment groups
(4) AT supplementation had no effect in preventing Orx-induced unfavourable alterations of trabecular bone parameters
(5) AT treatment had no significant effect on CoP, CoTh and CoArea. | Supplement doses of AT do not increase BMD values in male rat model of osteoporosis – unable to reverse bone loss due to gonadal hormone deficiency.
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Hermizi et al., 2009 [44]
| Animal study
Bone histomorphometry
Tocotrienol-enhanced fraction
α-Tocopherol
γ-Tocotrienol | 3-month-old male Sprague-Dawley rats (n = 49)
Duration: 4-month treatment
Rats were randomly assigned to seven groups with seven rats in each group
| Group 1 was the baseline. (B) was killed at the commencement of the study. Group 2 and 3 were control (c) and nicotine (N) groups. The C group was treated with normal saline for 4 months and the N group was treated with nicotine for 2 months. The other four groups were nicotine cessation (NC), tocotrienol-enhanced fraction (TEF), GTT, and ATF. Treatment for these groups was performed in two phase. In the first 2 months they were given nicotine (7 mg/kg) and in the following 2 months treatment with vitamin E preparation (60 mg/kg).
Rats were sacrificed after 4 months of treatment for bone histomorphometry measurements.
Measurement include:
(a) structural measurements:
(i) trabecular bone volume (BV/TV)
(ii) trabecular thickness (Tb.Th)
(iii) trabecular number (Tb.N)
(b) cellular measurements:
(i) osteoclast surface (Oc.S/BS)
(ii) eroded surface (ES/BS)
(c) dynamic measurements:
(i) single-labelled surface/bone surface (sLS/BS)
(ii) mineral apposition rate (MAR)
(iii) bone formation rate/bone surface (BFR/BS). | All vitamin E treated groups showed significant increase in BV/TV, MAR, and BFS/BS, but there was reduction in sLS/BS and Oc.S/BC compared to the C, N and NC groups.
(a) Structural measurements
TEF and GTT groups had a significantly higher trabecular thickness, but lower eroded surface (ES/BS) than the C group.
(b) Cellular measurements
The TEF group had lower ES/BS than the ATF group.
(c) Dynamic measurements
GTT improved trabecular bone histomorphometric parameter better than TEF and ATF after nicotine administration, by increasing MAR and BFR/BS. | All vitamin E treated group showed significant increase of bone formation and decrease bone resorption.
Palm oil tocotrienol mixture was more potent than α-tocopherol at reversing the deleterious effects of nicotine on BV/TB and Tb.Th.
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Shuid et al., 2010 [57]
| Animal study
γ-Tocotrienol
α-Tocopherol | 3-month-old male Sprague-Dawley rats
(n = 24)
Divided into 3 groups
Duration: 4-month treatment | Rats randomly divided into three groups as follows:
(a) normal control (NC)
Rats were given oral gavage of olive oil (vehicles)
(b) α-tocopherol (ATF)
Rats were given 60 mg/kg ATF body weight orally
(c) γ-tocotrienol (GTT)
Rats were given 60 mg/kg GTT
body weight orally.
At the end of the treatment rats were killed and both femurs of each rat were dissected free of soft tissue for:
(a) bone histomorphometry
(b) bone biomechanical test. | The GTT group had significantly higher trabecular bone volume, trabecular number, and trabecular thickness, but significantly lower trabecular separation than ATF group.
The GTT group have significantly greater load, higher stiffness, higher stress, higher strain, and higher modulus elasticity, if compared to other group. | Vitamin E supplementation produced greater trabecular volume and number, if compared to control rat.
GTT supplementation improves both extrinsic and intrinsic parameters. |
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Mehat et al., 2010 [58] | Animal study
Bone histomorphometry analysis
Tocotrienol Tocopherol | 3-month-old Sprague-Dawley male rats (n = 32)
Duration: 4 months
Rats were randomly assigned into four groups. | The control group was supplemented with oral gavage vehicle olive oil. The treatment group given orally of 60 mg/kg α-tocopherol, δ-tocotrienol, and γ-tocotrienol.
After 4 months of treatment, the rats bone was fluorochrome-labeled with intraperitoneal injection of 20 mg/kg calcein at days 9 and 2 days before the rats were killed. The rats were killed and the left femurs were dissected out and fixed with 70% alcohol. After 1 week the femurs were cut for histology slide samples for:
(a) bone static
(i) osteoclast number (N.Oc)
(ii) osteoblast number (N.Ob)
(iii) eroded surface/bone surface ( ES/BS)
(iv) osteoid surface/bone surface (OS/BS)
(v) osteoid volume/bone volume (OV/BV)
(b) bone dynamic
(i) single-labelled surface/bone surface (sLS/BS)
(ii) mineral apposition rate (MAR)
(iii) bone formation rate/bone surface (BFR/BS)
(iv) double labelled surface/bone surface (dLS/BS)
(v) mineralizing surface/bone surface (MS/BS). | (a) Bone static
All vitamin E treated group had significantly higher in N.Ob, OV/BV, and OS/BS but lower N.Oc and ES/BS.
GTT group had increased availability of osteoclast for new bone formation (significant increase in N.Ob. OV/BV, and OS/BS).
(b) Bone dynamic
The percentages of dLS/BS, BFR/BS, MAR, and MS/BS of rat femora are higher in the vitamin E supplemented groups especially in γ-tocotrienol group compared to normal control group. | Vitamin E may be able to promote bone growth in rats by increasing trabecular bone volume and osteoid volume but reduce in N.Oc and Es/BS (bone resorption).
γ-Tocotrienol group demonstrated the best effect in bone static and bone dynamic measurements. |
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