Clinical Studies - Tocotrienols Protective Benefits
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gamma -Tocotrienol, a vitamin E homologue, is a natriuretic hormone precursor.
Tocotrienol: A Review of Its Therapeutic Potential
Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats.
gamma -Tocotrienol, a vitamin E homologue, is a natriuretic hormone precursor.
Saito H, Kiyose C, Yoshimura H, Ueda T, Kondo K, Igarashi O.
J Lipid Res 2003 May 1
Abstract:
2,7,8-Trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman (gamma-CEHC), a metabolite of gamma-tocopherol and gamma-tocotrienol, was identified as a new endogenous natriuretic factor. However, gamma-tocopherol and gamma-tocotrienol, both precursors of gamma-CEHC, have never directly been observed to have natriuretic potency. Thus, we investigated if gamma-tocotrienol could cause natriuresis and diuresis in rats. The rats were divided to two groups given a control or a high sodium diet for four weeks, then subdivided to a placebo and gamma-tocotrienol subgroup given only corn oil removed vitamin E and the oil supplemented gamma-tocotrienol, respectively. After oral administration of three experimental doses, rat urine was collected and gamma-CEHC, urine volume, sodium and potassium content were determined. Only in rats given a high NaCl diet did gamma-tocotrienol accelerate and increase sodium excretion, showing no effect on potassium excretion. Sodium excretion in the high NaCl group given gamma-tocotrienol showed 5.06 2.70 g/ d, while in the control group given gamma-tocotrienol was 0.11 0.06 g/ d. Furthermore, gamma-tocotrienol affected urine volume in the specific condition of high NaCl body stores and gamma-tocotrienol supplementation. In this study, we found that gamma-tocotrienol, one of the natural vitamin E homologues, stimulates sodium excretion in vivo suggesting that gamma-tocotrienol possesses a hormone-like natriuretic function.
Summary:
gamma-Tocopherol and gamma-tocotrienol are broken down in the body to a compound that helps control the amount of fluid and electrolytes that pass through the kidneys into the urine. A compound that can do this is considered to be a "natriuretic factor." Researchers conducted this experiment to see if supplementation with gamma-tocotrienol directly had this effect. Rats were fed a diet high in salt and supplemented with gamma-tocotrienol. Not only did their urine volume increase but the rate of salt excretion in the urine was significantly higher than in control animals. Potassium excretion was not effected. This study indicates that gamma-tocotrienol, one of the natural vitamin E forms, stimulates sodium excretion in living animals. This may have benefitial implications in controling fluid and electrolyte balance in humans.
Tocotrienol: A Review of Its Therapeutic Potential
Andre Theriault, Jun-Tzu Chao, Qi Wang, Abdul Gapor and Khosrow Adeli
Clinical Biochemistry, Vol. 32, No. 5, 309-319, 1999.
Abstract:
Objectives: To summarize new knowledge surrounding the physiological activity of tocotrienol, a natural analogue of tocopherol. Results: The biological activity of vitamin E has generally been associated with its well-defined antioxidant property, specifically against lipid peroxidation in biological membranes. In the vitamin E group, a-tocopherol is considered to be the most active form. However, recent research has suggested tocotrienol to be a better antioxidant. Moreover, tocotrienol has been shown to possess novel hypocholesterolemic effects together with an ability to reduce the atherogenic apolipoprotein B and lipoprotein(a) plasma levels. In addition, tocotrienol has been suggested to have an anti-thrombotic and anti-tumor effect indicating that tocotrienol may serve as an effective agent in the prevention and/or treatment of cardiovascular disease and cancer. Conclusion: The physiological activities of tocotrienol suggest it to be superior than a-tocopherol in many situations. Hence, the role of tocotrienol in the prevention of cardiovascular disease and cancer may have significant clinical implications. Additional studies on its mechanism of action, as well as, long-term intervention studies, are needed to clarify its function. From the pharmacological point-of view, the current formulation of vitamin E supplements, which is comprised mainly of a-tocopherol, may be questionable.
Summary:
This is an excellent review of the literature on tocotrienols, which have drawn considerable attention in the past few years. This review details the distinct properties of these members of the vitamin e family. Theriault et al discuss the cardiovascular benefits of tocotrienols through their cholesterol and apolipoprotein reducing properties as well as their antithrombotic potential. In addition, this review discusses the antioxidant properties of the tocotrienols and the preliminary work on cancer prevention.
Dose-dependent suppression of serum cholesterol by tocotrienol-rich fraction (TRF25) of rice bran in hypercholesterolemic humans.
Qureshi AA, Sami SA, Salser WA, Khan FA.
Atherosclerosis 2002 Mar;161(1):199-207
Abstract:
Tocotrienols are effective in lowering serum total and LDL-cholesterol levels by inhibiting the hepatic enzymic activity of beta-hydroxy-beta-methylglutaryl coenzymeA (HMG-CoA) reductase through the post-transcriptional mechanism. alpha-Tocopherol, however, has an opposite effect (induces) on this enzyme activity. Since tocotrienols are also converted to tocopherols in vivo, it is necessary not to exceed a certain dose, as this would be counter-productive. The present study demonstrates the effects of various doses of a tocotrienol-rich fraction (TRF25) of stabilized and heated rice bran in hypercholesterolemic human subjects on serum lipid parameters. Ninety (18/group) hypercholesterolemic human subjects participated in this study, which comprised three phases of 35 days each. The subjects were initially placed on the American Heart Association (AHA) Step-1 diet and the effects noted. They were then administered 25, 50, 100 and 200 mg/day of TRF25 while on the restricted (AHA) diet. The results show that a dose of 100 mg/day of TRF25 produce maximum decreases of 20, 25, 14 (P<0.05) and 12%, respectively, in serum total cholesterol, LDL-cholesterol, apolipoprotein B and triglycerides compared with the baseline values, suggesting that a dose of 100 mg/day TRF25 plus AHA Step-1 diet may be the optimal dose for controlling the risk of coronary heart disease in hypercholesterolemic human subjects.
Summary:
Research has shown that the lesser known members of the vitamin E family, tocotrienols, are effective in lowering serum cholesterol. This study was conducted to determine the optimum level of tocotrienol supplementation to lower serum cholesterol. Ninety people with high cholesterol were placed on the American Heart Association (AHA) Step-1 diet for one month. They were then supplemented with 25, 50, 100, or 200 mg/day of a tocotrienol rich supplement. One group received no supplement. The data showed that the tocotrienol rich supplement of 100 mg/day decreased total cholesterol by 20% and LDL-cholesterol by 25%. Triglycerides were reduced by 12%. This study suggests that a nutritional supplement rich in tocotrienols in addition to a low fat diet may be beneficial in lowering cholesterol in persons with high cholesterol. Other studies have shown that reducing cholesterol can reduce an individuals overall risk of heart disease. The implications are that dietary supplements providing vitamin E should also provide the lesser known members of the vitamin E family, tocotrienols.
Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats.
Ngah WZ, Jarien Z, San MM, Marzuki A, Top GM, Shamaan NA, Kadir KA.
Am J Clin Nutr 1991 Apr;53(4 Suppl):1076S-1081S.
Abstract:
The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis.
Summary:
Tocotrienols have anticarcinogenic effects that are currently being investigated in vitro and in vivo. In this study, rats were given a known carcinogen and tocotrienols or placebo. Serum parameters of liver injury measured at 12 and 20 weeks were significantly lower in rats that received tocotrienols as compared to placebo, suggesting decreased cell damage that can lead to hepatocarcinogenesis (liver cancer). These studies are building the evidence necessary to promote further research into the anticarcinogenic properties of these compounds.