Human Tissue Distribution of Orally Supplemented Natural Vitamin E Tocotrienol

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.

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