Human Tissue Distribution of Orally Supplemented Natural Vitamin E Tocotrienol
Study Details
Study Description
Brief Summary
Levels of tocotrienol in human tissues following supplementation is not currently known. The objective of this present study is to determine the levels of this form of vitamin E in the human tissues such as skin, heart, lung, liver, adipose tissue, Brain and cerebrospinal fluid (CSF) following oral supplementation
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
In nature, there are eight members in the vitamin E family: a-, b-, g- and d-TCP, and a-, b-, g- and d-tocotrienol (TCT). Vitamin E research has developed highly asymmetrically. Out of the 25,000+ papers on vitamin E in the PubMed, 99% deal with tocopherols. Recent research has demonstrated the lack of cancer-preventive effects and potential adverse health consequences of tocopherol (6). As a result, more attention has been turned towards non-tocopherol forms of vitamin E (16). Palm oil represents a major source of natural TCT. TCT possess powerful neuroprotective, antioxidant, anti-cancer and cholesterol lowering properties that often differ from the properties of TCP (15).
During the last five years, our and other laboratories have reported several striking beneficial properties of tocotrienols in experimental settings. One major concern that limits enthusiasm for tocotrienol for humans is the report that the vitamin E transporting protein, tocopherol-transport protein (TTP), has a very low affinity to transport tocotrienol. Using TTP-knock out mice, we have recently demonstrated that oral TCT is effectively carried to vital organs and that such transport can take place independent of TTP. With that background, the purpose of this project is to test the hypothesis that orally supplemented tocotrienol reaches the vital organs of humans.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm 1 To surgery patients, Tocotrienol capsules. 200mg (2 100mg capsules) to take by mouth twice daily to total 400mg daily |
Dietary Supplement: To surgery patients, Tocotrienol capsules.
200mg (2 100mg capsules) to take by mouth twice daily to total 400mg daily
|
| Active Comparator: Arm 2 To surgery patients, Tocopherol capsules. 200mg (2 100mg capsules) to take by mouth twice daily to total 400mg daily |
Dietary Supplement: To surgery patients, Tocopherol capsules.
200mg (2 100mg capsules) to take by mouth twice daily to total 400mg daily
|
| Active Comparator: Arm 3 Tocotrienol to healthy subjects - 200 mg to take orally two times a day (400 mg a day). |
Dietary Supplement: Tocotrienol to healthy subjects.
200 mg to take orally two times a day (400 mg a day).
|
Outcome Measures
Primary Outcome Measures
- The Levels of TCT in the Tissues of "Non-healthy" Subjects and in the Tissue of "Healthy" Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) [After at least 1 month of supplementation]
Eligibility Criteria
Criteria
Aim 1 Surgical candidate with a surgery schedule date with a time period of 4-24 weeks (<4 weeks will be excluded; last dose until 24h before surgery) In Aim 1 we expect to have patients, with diverse co-morbidity and medication conditions.
Patient Selection: Because of limitation in obtaining healthy human tissues (as in Aim 2), we plan to obtain these tissues from patients who are scheduled for the following surgeries for subjects in group one:
Heart Heart Transplant Heart Failure- Biopsy taken from diseased heart Lung Lung Transplant, Lung-wedge/resection, Lobectomy Cancer- Tissue sample taken from removed lung or resected portion of lung Liver Liver Transplant, Biopsy, Resection Hepatic Malignancy- Biopsy taken from resected portion of liver Adipose Tissue Panniculectomy Excessive Tissue of the Abdomen Brain & CSF Epilepsy Excised brain tissue and cerebrospinal fluid
To ensure higher enrollment we are not controlling for age of subjects as long as the subjects are 21 years of age or older.
Inclusion Criteria Aim 1:
-
age 21 and older
-
good health
-
non- smoker
-
no current medications
-
non- pregnant or non-breastfeeding
-
no previous use of OTC medications or other form of supplements containing vitamin-E.
Inclusion Criteria Aim 2:
-
age 21 - 40 years
-
good health
-
non- smoker
-
no current medications
-
non- pregnant or non-breastfeeding
-
no previous use of OTC medications or other form of supplements containing vitamin-E.
Exclusion Criteria Aim 1:
-
Long-term use of OTC medications containing vitamin-E or current vitamin-E supplements
-
Scheduled surgery date lesser than 4 weeks or greater than 24 weeks.
Exclusion Criteria Aim 2:
-
Over 40 or under 21 years of age
-
Current smoker
-
Pregnant and breastfeeding
-
Diabetes and HIV diagnosis
-
Immunosuppression therapy
-
Any neurological problems
-
Long-term use of OTC medications containing vitamin-E or current vitamin-E supplements
-
ETOH or drug abuse
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Ohio State University | Columbus | Ohio | United States | 43211 |
Sponsors and Collaborators
- Chandan K Sen
- Carotech Inc.
Investigators
- Principal Investigator: Chandan Sen, PhD, Ohio State University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2005C0034
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm 1- Surgery + Tocotrienol 200 mg | Arm 2- Surgery + Tocopherol 200 mg | Arm 3- Healthy +Tocotrienol 400 mg |
|---|---|---|---|
| Arm/Group Description | Surgery Patients to take Tocotrienol capsules.: 200mg (two 100mg capsules) taken by mouth twice to total 400mg daily | Surgery Patients to take Tocopherol capsules.: 200mg (two 100mg capsules) taken by mouth twice to total 400mg daily | Healthy patients to take Tocotrienol: 400 mg to take orally (two 200 mg capsules) two times a day. |
| Period Title: Overall Study | |||
| STARTED | 40 | 15 | 25 |
| COMPLETED | 24 | 15 | 16 |
| NOT COMPLETED | 16 | 0 | 9 |
Baseline Characteristics
| Arm/Group Title | Arm 1- Surgical + Tocotrienol 200 mg | Arm 2 - Surgical + Tocopherol 200 mg | Arm 3- Healthy + Tocotrienol 200 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Surgical Subjects will recieve either Tocotrienol: 200mg (two 100mg capsules) to take twice daily by mouth to make a total of 400mg per day | Surgical Subjects will recieve Tocopherol: 200mg (two 100mg capsules) to take twice daily by mouth to make a total of 400mg per day | Healthy Subjects will recieve either Tocotrienol: 200mg (two 100mg capsules) to take twice daily by mouth to make a total of 400mg per day | Total of all reporting groups |
| Overall Participants | 40 | 15 | 25 | 80 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
49.37
(12.81)
|
54
(11.56)
|
30.24
(8.59)
|
40.37
(4.61)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
20
50%
|
10
66.7%
|
13
52%
|
43
53.8%
|
| Male |
20
50%
|
5
33.3%
|
12
48%
|
37
46.3%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
40
100%
|
15
100%
|
25
100%
|
80
100%
|
Outcome Measures
| Title | The Levels of TCT in the Tissues of "Non-healthy" Subjects and in the Tissue of "Healthy" Subjects Following Oral Supplementation (200 mg x 2 Per Day for 4-24 Weeks) |
|---|---|
| Description | |
| Time Frame | After at least 1 month of supplementation |
Outcome Measure Data
| Analysis Population Description |
|---|
| Box plots were used to determine outliers defined as values . the 75th percentile plus 1.5 times the IQR or values , the 25th percentile minus 1.5 times the IQR (20). Outliers were identified and it was determined that laboratory procedural errors were the cause and thus removed from the analysis. |
| Arm/Group Title | Arm 1: Surgical, Adipose | Arm 1: Surgical, Brain | Arm 1: Surgical, Heart | Arm 1: Surgical, Liver | Arm 2: Surgical, Adipose | Arm 2: Surgical, Brain | Arm 2: Surgical, Heart | Arm 2: Surgical, Liver | Arm 3: Healthy, Blood, Week 0 | Arm 3: Healthy, Blood, Week 6 | Arm 3: Healthy, Skin, Week 12 | Arm 3: Healthy, Skin, Week 0 | Arm 3: Healthy, Blood, Week 12 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | adipose aTE levels after supplementation (400mg/d) | brain aTE levels after supplementation (400mg/d) | heart aTE levels after supplementation (400mg/d) | liver aTE levels after supplementation (400mg/d) | adipose aTCP levels after supplementation (400mg/d) | brain aTCP levels after supplementation (400mg/d) | heart aTCP levels after supplementation (400mg/d) | liver aTCP levels after supplementation (400mg/d) | Baseline blood levels of aTE prior to supplementation | Blood levels of aTE after 6 weeks of supplementation (400mg/d) | skin levels of aTE after 12 weeks of supplementation (400mg/d) | baseline skin levels of aTE prior to supplementation | Blood levels of aTE after 12 weeks of supplementation (400mg/d) |
| Measure Participants | 5 | 4 | 5 | 4 | 4 | 4 | 3 | 3 | 16 | 16 | 16 | 16 | 16 |
| Mean (Standard Deviation) [nmol/g] |
9.94
(6.9)
|
1.29
(1.06)
|
5.37
(4.28)
|
0.42
(0.43)
|
28.6
(20.7)
|
50.5
(17.2)
|
31.9
(20.0)
|
64.3
(14.9)
|
0.01
(0.02)
|
1.9
(0.7)
|
1.5
(1.8)
|
2.5
(3.0)
|
0.03
(0.1)
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Arm 1 | Arm 2 | Arm 3 | |||
| Arm/Group Description | Surgery patients to take Tocotrienol capsules.: 200mg (two 100mg capsules)taken by mouth twice with foold to make a total of 400mg daily | Surgery patients to take Tocopherol capsules.: 200mg (two 100mg capsules)taken by mouth twice with foold to make a total of 400mg daily | Healthy patients to take either Tocotrienol or Tocopherol: 200mg (two 100mg capsules)taken by mouth twice with foold to make a total of 400mg daily | |||
All Cause Mortality |
||||||
| Arm 1 | Arm 2 | Arm 3 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Arm 1 | Arm 2 | Arm 3 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/15 (0%) | 0/25 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Arm 1 | Arm 2 | Arm 3 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/15 (0%) | 0/25 (0%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Chandan K. Sen, PhD. Professor and Associate Dean |
|---|---|
| Organization | The Ohio State University Wexner Medical Center |
| Phone | 614-247-7658 |
| chandan.sen@osumc.edu |
- 2005C0034