From Nutrition Science News
by Stephanie Gailing, C.N.
For decades vitamin E has maintained a position along with vitamin C and calcium as one of the three most popular single-ingredient dietary supplements. As scientists continue to examine the role of free radicals in disease initiation and promotion, research substantiates this potent antioxidant's ability to treat stroke, cardiovascular disease and cancer. What's more, in the last year alone, vitamin E has shown promise in some unique areas such as treating a complication of pregnancy known as preeclampsia as well as protecting against exercise-induced muscle damage and radiation injury.
The results of a study conducted by researchers at the University of Helsinki, Finland, suggest that vitamin E may be a potent protector against certain types of stroke. The trial investigated the effect of vitamin E on the incidence and mortality of stroke in 28,519 male cigarette smokers, aged 5069, with no previous history of stroke.  The subjects, participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, were randomized and given 50 mg vitamin E (as dl-alpha-tocopheryl acetate), 20 mg beta-carotene, both supplements, or placebo daily. The study period lasted a median of 6.0 years, during which time participants took the supplements and were followed for stroke incidence outcomes.
Results of this study suggest that vitamin E supplementation significantly increased the risk of subarachnoid brain hemorrhage while significantly decreasing the risk for cerebral infarctions in this population of male smokers. The researchers postulated that vitamin E's ability to promote bleeding might be due to its antiplatelet activity.
The same group of researchers conducted an additional analysis of the ATBC study population that further examined the findings to determine if there were any population subgroups such as those at high risk that could fully benefit from vitamin E.  This reanalysis demonstrated that dl-alpha-tocopherol acetate positively affected male cigarette smokers who had a history of both hypertension and diabetes: After vitamin E supplementation, this population exhibited a lower risk of cerebral infarction without experiencing an increased risk of subarachnoid hemorrhage.
Cardiovascular disease is a condition in which vitamin E has shown great promise. However, the Heart Outcomes Prevention Evaluation (HOPE) study, published in the New England Journal of Medicine, showed otherwise. This double-blind, placebo-controlled trial evaluated the effect of daily supplementation of 400 IU d-alpha-tocopherol on 6,996 men and 2,545 women at high risk for cardiovascular events. People at high risk were those having either cardiovascular disease or diabetes mellitus with one other risk factor.  The participants received the supplements for a mean of 4.5 years.
In the study, researchers measured primary outcomes as composites of myocardial infarction and death from cardiovascular causes as well as secondary outcomes including unstable angina, congestive heart failure and death from any cause.
The researchers concluded that vitamin E conveyed no appreciable protective effect on coronary events in this high-risk population, as there were no significant differences in measurements of primary and secondary outcomes among the supplemented and control groups. In an attempt to reconcile these results with previous epidemiological studies that suggest a beneficial relationship between vitamin E and cardiovascular disease, the authors offered a possible explanation. They noted that in the epidemiological studies, vitamin E intake was associated with the consumption of other synergistic antioxidant micronutrients, such as vitamin C and selenium, and suggested that the cardioprotective effects of vitamin E may be derived if it is administered with other cofactor nutrients. Clinical trials currently in progress are investigating this hypothesis.
In contrast, two recent studies have provided evidence that vitamin E supplementation can, indeed, protect against heart problems by reducing plasma levels of C-reactive protein (C-RP). An elevated level of C-RP is a major predictive factor for cardiovascular disease incidents.
One New Zealand study examined the effects of four weeks of daily supplementation with either 800 IU d-alpha-tocopherol, 500 mg vitamin C, 500 mL lycopene-rich tomato juice, or placebo.  The study population consisted of 57 men and women with Type 2 diabetes who were under the age of 75. Only the vitamin E supplementation significantly reduced plasma C-RP levels.
Similar conclusions were also reached in a study conducted by researchers from the Department of Pathology, University of Texas Southwestern Medical Center in Dallas.  This trial compared the effect of a three-month daily supplementation of 1,200 IU RRR-alpha-tocopherol on 23 Type 2 diabetics with macrovascular disease, 24 Type 2 diabetics without macrovascular disease, and 25 matched healthy controls. Although the results showed that C-RP was only significantly elevated at baseline in the Type 2 diabetics with vascular complications, the administration of vitamin E did reduce the levels of C-RP in all three population groups.
Prostate cancer rates are rising, and so is interest in finding natural approaches to treat this condition. Two recent in vitro studies have revealed further insight into the beneficial effect of vitamin E on prostate cancer. While the two differed in focus, both studies demonstrated that vitamin E induced apoptosis (cell death) in human prostate cancer cells.
The first study, conducted at the University of Utah School of Medicine in Salt Lake City, tested the effect of synthetic alpha-tocopherol and two other synthetic antioxidants on three different prostate cancer cell lines that differed in their androgen (hormone) sensitivity.  Vitamin E, in vitro, caused cell death of prostate cancer cells in the cell line that was most responsive to changes in levels of androgens (e.g., testosterone). In other words, vitamin E may help fight hormone-dependent cancers of the prostate.
The second in vitro study, performed by researchers at the University of Texas in Austin, suggested that vitamin E (RRR-alpha-tocopheryl succinate) induced apoptosis in human prostate cancer cells but did not compromise the growth of healthy prostate cells.  In addition, the vitamin E succinate was found to beneficially modulate the signaling of Fas (also known as apo-1), an initiator of the apoptosis cascade. This finding may have additional applications because altered Fas signaling is a hallmark not only in prostate cancer cells but also in breast, colon and central nervous system cancer cells.
Vitamin E appears to be effective at destroying cancer cells in other parts of the body, including the breast. A study by scientists in the Department of Surgery at Southern Illinois University School of Medicine in Springfield included both in vitro and experimental research components that investigated the effect of d-alpha-tocopheryl succinate (VES) on breast cancer cells.  In the in-vitro portion of the study, the team tested the effect of VES on two different breast cancer cell lines and found VES stimulated apoptosis and suppressed vascular-endothelial growth factor (VEGF) gene expression in one of the two cell lines. The study did not explain what caused this difference.
In the experimental component of the study, researchers found supplementing mice with 150 mg/kg body weight/day of VES for 28 days inhibited the growth of established breast cancer tumors. The combined results of the study suggested that VES's effect on tumors might be partially related to its ability to suppress the gene expression of VEGF and therefore inhibit tumor angiogenesis. While the dosage used in this mouse study was extremely high when compared with current therapeutic vitamin E dosage levels (200 IU to 800 IU), the results still represented an important landmark because this study featured the first report of VES's in vivo inhibition of established breast cancer tumor growth.
The benefit of vitamin E in breast cancer management was further highlighted by a study that evaluated its role as an adjunctive therapy for patients undergoing tamoxifen treatment. Because tamoxifen, an antiestrogen drug used to treat breast cancer, has been found to cause severe hypertriglyceridemia, this study tested whether vitamin E along with vitamin C could ameliorate this deleterious side effect. 
The India-based research team studied 54 postmenopausal breast cancer patients, aged 5060, who were taking a 20 mg daily dose of tamoxifen. They compared their lipid profiles before and after 90 days of daily adjunctive vitamin therapy featuring 400 mg vitamin E (all-rac-alpha-tocopheryl acetate) and 500 mg vitamin C. The results indicated that the antioxidant treatment significantly reduced levels of total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglyceride levels and significantly increased high-density lipoprotein (HDL). The coadministration of vitamins E and C during tamoxifen treatment may be effective in reducing the hypertriglyceridemia associated with this drug.
Preeclampsia is a complication of pregnancy that features hypertension and edema. Three research studies published in 2000 lent further evidence that an etiological hallmark of preeclampsia involves oxidative stress and decreased levels of endogenous antioxidants, notably vitamin E.
Two different studies by researchers in India observed significantly lower blood levels of vitamin E (as well as vitamin C) in preeclamptic women as compared to normotensive pregnant and non-pregnant women. One study compared 30 preeclamptic women with 30 normotensive pregnant women, while the other compared 25 preeclamptic women to 25 normotensive women and 25 nonpregnant healthy women. [10, 11] A related study by a Turkish team of researchers also supports these findings while lending further insight by showing that as either systolic or diastolic blood pressure increased in 33 preeclamptic women, there was an observed concomitant decrease in blood vitamin E levels. These results suggest that vitamin E may be effective in treating this condition, but additional studies are needed to confirm the result.
One of the most interesting areas of vitamin E research is in sports medicine. One study explored the potential effects of vitamin E on exercise-induced muscle damage.  The double-blind, placebo-controlled study involved 14 male runners aged 1824. The study period included four weeks of moderate exercise training immediately followed by six days of intense training wherein subjects substantially increased their running distances. The subjects were randomized to receive either 1,200 IU d-alpha-tocopherol or placebo taken daily throughout the entire study period. Levels of serum creatine kinase, lactate dehydrogenase, and LDH isozymesenzymes thought to be indirect markers of muscle damagewere measured before and after the six-day intense training period.
Enzyme levels were increased in both groups following the intense training period, but levels were significantly lower in the vitamin E group compared to the placebo group. These results suggest 1,200 IU of vitamin E daily may be protective against exercise-induced muscle damage.
An experimental Turkish study indicates that vitamin E may be protective against radiation-induced cellular damage.  In the study, rats were supplemented with a nonspecific type of vitamin E, selenium, or both for four weeks prior to intra-abdominal radiation treatment and then compared with both nonsupplemented irradiated and nonirradiated rats. The vitamin E dose was 30 mg/kg every other day, while the selenium was given in the form of a continuous supply of drinking water that contained 8.88 mg sodium selenite per liter (4 ppm). The study's results suggest that both of the antioxidants, as well as their combination, provided moderate preservation of the intestinal mucosa structure because they significantly prevented the radiation-induced decrease in the number and height of ileal villus, which are small intestinal projections that increase the surface area for absorption of water and nutrients. The researchers postulated that vitamin E's radiation protection might have been provided by its ability to inhibit the damage caused by radiation-stimulated free radical production.
This past year's research on vitamin E has added provocative new possibilities to the already extensive body of evidence that exists regarding this nutrient. We look forward to the coming years as researchers further elicit and clarify the important ways that vitamin E can positively effect health promotion and disease prevention.
Different Forms of Vitamin E and Their Biopotencies
Converting Between IU and Mg
2000 Sees New Government Recommendations for Vitamin E
Stephanie Gailing, C.N., is a freelance writer and researcher specializing in natural health. She holds a masters degree in nutrition from Bastyr University in Kenmore, Wash.
1. Leppälä LM, et al. Controlled trial of a-tocopherol and b-carotene on stroke incidence and mortality in male smokers. Arteriosclerosis, Thrombosis and Vascular Biol 2000;20:230-5.
2. Leppälä LM, et al. Vitamin E and beta-carotene supplementation in high-risk for stroke. Arch of Neurol 2000;57:1503-9.
3. Yusuf S, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. New England J of Med 2000;342:154-60.
4. Upritchard JE, et al. Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in Type 2 diabetes. Diabetes Care 2000;23:733-8.
5. Devaraj S, Jialel I. Alpha tocopherol supplementation decreases serum C-reactive protein and monocyte interleukin-6 levels in normal volunteers and Type 2 diabetic patients. Free Radical Biol & Med 2000;29(8):790-2.
6. Gunawardena K, et al. Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis. The Prostate 2000;44:287-95.
7. Israel K, et al. Vitamin E succinate induces apoptosis in human prostate cancer cells: role for Fas in vitamin E succinate-triggered apoptosis. Nut and Cancer 2000;36(1):90-100.
8. Malafa MP, Neitzel LT. Vitamin E succinate promotes breast cancer tumor dormancy. Int J Surg Res 2000;93:163-70.
9. Babu JR, et al. Salubrious effect of vitamin C and vitamin E on tamoxifen-treated women in breast cancer with reference to plasma lipid and lipoprotein levels. Cancer Letters 2000;151(1):1-5.
10. Kharb S. Vitamins E and C in preeclampsia. Euro J Obstet Gynecol Reproductive Biol 2000;93:37-9.
11. Kharb S. Total free radical trapping antioxidant potential in preeclampsia. Int J of Gynecol Obstet 2000;39:23-6.
12. Akyol D, et al. Maternal levels of vitamin E in normal and preeclamptic pregnancy. Arch Gynecol and Obstet 2000;263(4):151-5.
13. Itoh H, et al. Vitamin E supplementation attenuates leakage of enzymes following six successive days of running training. Int J Sports Med 2000;21:369-74.
14. Mutlu-Türkoglu Ü, et al. The effect of selenium and/or vitamin E treatments on radiation-induced intestinal injury in rats. Life Sciences 2000;66(20):1905-13
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