Natural vitamin E alpha-tocotrienol: retention in vital organs in response to long-term oral supplementation and withdrawal.
The natural vitamin E tocotrienol (TCT) possesses biological properties not shared by tocopherols (TCP). Nanomolar alpha-TCT, not alpha-TCP, is potently neuroprotective (JBC 275:13049; 278:43508; Stroke 36:2258). The report that the affinity of TTP to bind (alpha-TCT is an order of magnitude lower than that for alpha-TCP questions the bioavailability of orally taken TCT to tissues. Oral supplementation of TCT for 3 years in nine generations of female and male rat was studied. Ten vital organs were examined. To gain insight into the turnover of alpha-TCT in tissues, a subset of supplemented rats was moved to vitamin E deficient diet for 7 weeks. Orally supplemented alpha-TCT was delivered to all vital organs including the brain and spinal cord in significant amounts. In organs such as the skin, adipose and gonads the maximum level of alpha-TCT achieved in response to supplementation was folds higher than baseline values of alpha-TCP in rats maintained on laboratory chow. Females had higher levels of alpha-TCT compared to matched tissues of corresponding males. To gain insight into how quickly alpha-TCT is metabolized in the tissues, washout of alpha-TCT from vital organs was examined. alpha-TCT accumulated in vital organs over more than 2 years was almost completely lost in less than 2 months when the supplementation was stopped. This is in sharp contrast with findings related to alpha-TCP retention. The ability of long-term oral supplementation to maintain and elevate alpha-TCT levels in vital organs together with the rapid elimination of the intact vitamin from all organs studied underscores the need for continuous oral supplementation of TCT.
Patel
Viren
V
Laboratory of Molecular Medicine, Department of Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210, USA.
Khanna
Savita
S
Roy
Sashwati
S
Ezziddin
Omar
O
Sen
Chandan K
CK
D000273:Adipose Tissue / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002490:Central Nervous System / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D006066:Gonads / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D024508:Tocotrienols / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000493:pharmacokinetics
D018696:Neuroprotective Agents; D024508:Tocotrienols; D024502:alpha-Tocopherol