Gamma-tocotrienol is required for normal vitamin D metabolism in female rats

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Date: September-October 2005
From: Indian Journal of Pharmacology(Vol. 37, Issue 5)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Article
Length: 4,055 words

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Byline: M. Norazlina, F. Ng, S. Ima-Nirwana

Objective: To study the effects of vitamin E deficiency and supplementation of vitamin D and bone metabolism in female Sprague-Dawley rats. Materials and Methods: Rats weighing between 200 and 250 g were divided into six groups, that is, rats fed on (a) normal rat chow diet (RC), (b) vitamin E-deficient diet (VED) (c) VED diet supplemented with 60 mg/kg a-tocopherol acetate (ATF), (d) VED diet supplemented with 60 mg/kg ?g-tocotrienol (GTT), (e) VED diet supplemented with 60 mg/kg Tocomin [R] (TOC) and (f) baseline control group which was killed without treatment (BC). Treatment was given for 2 months. Serum 1,25-dihydroxyvitamin D3, serum total calcium, urine calcium, left femur, and fourth lumbar vertebra calcium content and left femur length were measured. Results: In the VED and ATF groups, activation of vitamin D to 1,25-dihydroxyvitamin D3 was inhibited and calcium reabsorption in the kidneys were increased. Both the effects seen in ATF and GTT groups were observed in the TOC group. The GTT group was protected from the effects of the vitamin E-deficient diet. Calcium content of the fourth lumbar vertebra was also decreased by vitamin E- deficiency, which was not reversed by vitamin E supplementation. Conclusion: ?g-tocotrienol and not ?-tocopherol protects vitamin D metabolism and calcium homeostasis from the effects of vitamin E-deficiency.


Vitamin D and its metabolites are among the factors that are important in regulating bone metabolism. Vitamin D<sub>3</sub> is a prohormone, which is hydroxylated in the liver and in the kidney to the active metabolite 1,25-dihydroxyvitamin D<sub>3</sub> and 24,25-dihydroxyvitamin D<sub>3</sub>. In a previous study, supplementation with a 1, 25-dihydroxyvitamin D<sub>3</sub> analogue was able to increase bone mineral density in osteoporotic women.[1] The most potent vitamin D metabolite is 1,25-dihydroxyvitamin D<sub>3</sub> (calcitriol), which stimulates calcium and phosphate transport from the intestine and calcium reabsorption from bone.[2] 1,25-dihydroxyvitamin D<sub>3</sub> has also been reported to act directly on circulating osteoclast precursors to influence osteoclast differentiation.[3]

Vitamin E, a lipid-soluble vitamin with antioxidant properties has an important role in protecting biological systems. There are two types of vitamin E; tocopherol and tocotrienol, and there are 4 isomers for each type: alpha (a), beta (b), gamma (g) and delta (d). Tocopherol has been shown to prevent lipid peroxidation[4] and heart disease in postmenopausal women.[5] Tocotrienol was shown to reduce carcinogenesis,[6] and to inhibit the production of HMG-CoA reductase - the enzyme responsible for cholesterol synthesis.[7]

Palm oil is the major source of vitamin E, mainly the tocotrienol type. Vitamin E-rich extract from palm oil protected the bone against the toxic effects of the oxidizing agent ferric nitrilotriacetate,[8] reduced bone resorption, and increased the survival rate of thyrotoxic rats[9] and prevented the decline in bone mineral density, and bone calcium loss seen in orchidectomized rats.[10]

Palm vitamin E (60 mg/kg) was comparable to a-tocopherol in maintaining bone mineral density and bone calcium content in ovariectomized rats.[11] Tocotrienols and d-tocopherol were able to induce apoptosis in human mammary gland tumor cells.[12] However, a few studies found that...

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Gale Document Number: GALE|A137386378