Tocotrienols in Health. See presentations by Qing Jiang, PhD, Paul Sylvester, PhD, Sridevi Devaraj, PhD, Chandan Sen, PhD.
Vitamin E Forms: Anti-Inflammatory Activity and Potential Use in Treatment of Asthma
By Qing Jiang, PhD, Assistant Professor, Dept. of Foods and Nutrition, Purdue University. This abstract is from a talk given at an NHRI seminar. Gamma tocopherol inhibits allergic inflammation in rodents.
Vitamin E is a generic term of eight lipophilic antioxidants, which include alpha-, beta-, gamma-, delta-tocopherol and the corresponding tocotrienols. Studies on vitamin E have traditionally focused on alpha-tocopherol, the major form of vitamin E in tissues. Recent studies by us and others strongly suggest that other forms of vitamin E possess properties which are not shared by alpha-tocopherol but important to human disease prevention and therapy. We have found that gamma-tocopherol, the major form of vitamin E in the US diet, has anti-inflammatory properties by inhibition of cyclooxygenase-catalyzed prostaglandin E2 in cell-based studies and in a rat inflammation model. Some vitamin E forms inhibited leukotrienes B4 and leukotriene C4 from stimulated neutrophils and eosinophils, respectively.
We recently showed that gamma-tocopherol inhibits airway allergic inflammation and rhinitis in rodent models. This talk (not available) will review the anti-inflammatory activities and mechanisms of different forms of vitamin E, and discuss the implications including potential use in treatment of asthma.
By Qing Jiang, PhD, Assistant Professor, Dept. of Foods and Nutrition, Purdue University.
Antiproliferative and Apoptotic Effects of Tocotrienols on Normal and Neoplastic Mammary Epithelial Cells
Conference paper presented at the American Oil Chemists’ Society (AOCS) Symposium, May 2008. Theme: Tocotrienols in Health. Tocotrienols (a form of vitamin E) may be used in anticancer therapy either alone or in combination to enhance the therapeutic efficacy and reduce toxicity of other anticancer agents.
Vitamin E is a generic term that refers to a family of compounds that is further divided into two subgroups called tocopherols and tocotrienols. All natural forms of tocopherols and tocotrienols are potent antioxidants that regulate peroxidation reactions and controls free-radical production within the body. However, it is now firmly established that many of the biological actions mediated by individual vitamin E isoforms are not dependent upon their antioxidant activity. One of the most intriguing therapeutic applications for natural vitamin E, particularly tocotrienols, currently being investigated is their use as anticancer agents.
Specific tocotrienol isoforms display potent antiproliferative and apoptotic activity against a wide range of cancer cell types, while having little or no effect on normal cell function or viability.
Experimental studies have also determined that the intracellular mechanism mediating the antiproliferative and apoptotic effects of tocotrienols in normal and neoplastic mammary epithelial cells. Additional studies have also shown that tocotrienol treatment can restore death receptor apoptotic signaling in tumor cells that contain nonfunctional death receptors. These findings strongly suggest that tocotrienols may be used effectively as anticancer therapy either alone or in combination to enhanced the therapeutic efficacy and reduce toxicity of other anticancer agents.
By Paul W. Sylvester, PhD, Pfizer Endowed Professor of Pharmacology and Director of Graduate Studies and Research. College of Pharmacy, University of Louisana, Monroe, LA.
Vitamin E Supplementation, Inflammation, and Cardiovascular Disease
By Sridevi Devaraj, PhD and Ishwarlal Jialal, MD, PhD. Vitamin E at 1200 IU per day caused a significant risk reduction of a marker of inflammation in 90 patients.
There has been much conflict in literature with regards to the benefit of Vitamin E therapy in the reduction of Cardiovascular Disease.However, as we have pointed out previously, many of these trials had many pitfalls including the study population, the dose and form of Vitamin E, the failure to measure biomarkers, etc. In a recently published study, we showed that RRR-alpha-tocopherol supplementation at 1200 IU/day for two years versus placebo in 90 patients with Coronary Artery Disease resulted in a significant increase in alpha-tocopherol levels and a significant reduction in hs-CRP levels (32%) and F2-isoprostanes (37%).
While there was a significant progression in carotid intimal-medial thickness (IMT) in the placebo group, there was no progression in carotid IMT in the Vitamin E group. Furthermore, there was a non-significant 43% relative risk reduction in cardiovascular events in the alpha-tocopherol group versus the placebo. Furthermore, over this two year period the safety of high dose alpha-tocopherol supplementation was established.
Since it has previously been shown that alpha-tocopherol supplementation decreases plasma gamma-tocopherol levels and that gamma-tocopherol has anti-inflammatory effects as it is a potent inhibitor of nitrative stress, we tested the effect of combined supplementation with alpha-tocopherol (800 IU/day) and gamma-tocopherol (800 mg/day) versus either alone in a placebo controlled study in patients with Metabolic Syndrome. In this study, we showed that the combination of alpha-tocopherol (AT) and gamma-tocopherol (GT) was superior to either alone in reducing hs-CRP levels and nitrotyrosine levels. Thus, based on these two studies and the published literature, we suggest that there should be an urgency in conducting well planned multi-centered clinical trials testing this combination on cardiovascular endpoints.
Vitamin E in Neuroprotection: The Tocotrienol Advantage
By Dr. Chandan K. Sen, Professor and Vice Chairmain (Research) of Surgery, Laboratory of Molecular Medicine, Davis Heart & Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio. Email: Chandan.Sen@osumc.edu. Conference paper presented at the American Oil Chemists’ Society (AOCS) Symposium, May 2008. Theme: Tocotrienols in Health
The tocotrienol (T3) form of vitamin E is poorly studied and has, for decades, been overshadowed by the tocopherols. With clinical trials testing alpha-tocopherol providing disappointing results, current interest in vitamin E is being refocused on the non- alpha-tocopherol forms of vitamin E. Long before this current wave of change, seven years ago our laboratory noted that nanomolar alpha-T3, but not alpha-tocopherol, blocked glutamate-induced neuronal death by suppressing early activation of c-Src kinase (J Biol Chem 275:13049,2000; 282(32):23482-90, 2007). A later independent study reporting that Src blockade provides cerebral protection following stroke (Nature Med 7:222,2001) enhanced the significance of our finding that alpha-T3 possesses c-Src regulatory effects. Our efforts to understand the mechanistic basis of neuroprotection by alpha-T3 have led to the observation that glutamate-induced neurodegeneration hinges on two key molecular checkpoints: (i) c-Src activation, and (ii) 12-lipoxygenase (Lox) activation (JBC 278:43508, 2003). Recently we noted that in vivo, alpha-T3 supplementation decreased stroke-induced damage to the brain of spontaneously hypertensive rats (Stroke, 36:2258, 2005). alpha-T3 seems to protect neurons both by antioxidant-independent and –dependent mechanisms (J. Neurochem 98:1474, 2006). Taken together, orally supplemented alpha-T3 is potently neuroprotective and should be considered as a nutritional countermeasure to contain stroke-related injury to the brain.
Supported by NIH grant NS42617. Vitamin E was supplied by Carotech Inc.
