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Vitamin E (alpha-tocopherol)Vitamin E fights damaging natural substances known as free radicals. It works in lipids (fats and oils), which makes it complementary to vitamin C, which fights free radicals dissolved in water. As an antioxidant, vitamin E has been widely advocated for preventing heart disease and cancer. However, the results of large, well-designed trials have generally not been encouraging. Many other proposed benefits of vitamin E have also failed to stand up in studies. There are no medicinal uses for vitamin E with solid scientific support. Vitamin E dosage recommendations are complex, because the vitamin exists in many forms. New vitamin E recommendations are in milligrams (mg) of alpha-tocopherol. Alpha-tocopherol can come from either natural vitamin E (called, somewhat incorrectly, d-alpha-tocopherol) or synthetic vitamin E (called, also somewhat incorrectly, dl-alpha-tocopherol). However, much of the alpha-tocopherol in synthetic vitamin E is inactive. For this reason, you have to take about twice as much of it to get the same effect.1–3 There are other forms of vitamin E as well, such as beta-, delta-, and gamma-tocopherols, all of which occur in food. These other forms may be important; for example, preliminary evidence hints that gamma-tocopherol may be the most important form of vitamin E for preventing prostate cancer.4 On this basis, it has been suggested that the best vitamin E supplement would be a mixture of all these. To make matters even more confusing, vitamin E dosages are commonly listed on labels as international units (IU). Here's how you make the conversion. One IU natural vitamin E equals 0.67 mg alpha-tocopherol; one IU synthetic vitamin E equals 0.45 mg alpha-tocopherol. Therefore, to meet the new dietary recommendations for vitamin E (15 mg per day), you need to get either 22 IU natural vitamin E (22 IU x 0.67 = 15 mg) or 33 IU synthetic vitamin E (33 IU x 0.45 = 15 mg). The official U.S. and Canadian recommendations for daily intake of vitamin E are as follows: Infants 0–6 months, 4 mg The best food sources of vitamin E are polyunsaturated vegetable oils, seeds, nuts, and whole grains. To get a therapeutic dosage, though, you need to take a supplement. The optimal therapeutic dosage of vitamin E has not been established. Most studies have used between 50 and 800 IU daily, and some have used even higher doses. This would correspond to about 50 to 800 mg of synthetic vitamin E (dl-alpha-tocopherol), or 25 to 400 mg of natural vitamin E (d-alpha- or mixed tocopherols). Note: In general, international units rather than milligrams are used in the following discussion, as that was the most commonly used measurement at the time the studies were performed. If you wish to purchase natural vitamin E, look for a label that says "mixed tocopherols." However, some manufacturers use this term to mean the synthetic dl-alpha-tocopherol, so you need to read the contents closely. Natural tocopherols come as d-alpha-, d-gamma-, d-delta-, and d-beta-tocopherol. Observational studies raised hopes that vitamin E supplements could help prevent various forms of cancer as well as heart disease.82–84,86,104–107,144,145 However, observational studies are notoriously unreliable for determining the effectiveness of treatments. Only double-blind trials can do that (for information why, see Why Does This Database Rely on Double-blind Studies?), and such studies have, on balance, found vitamin E ineffective for preventing heart disease or any common form of cancer other than, possibly, prostate cancer. Other potential uses of vitamin E have limited supporting evidence. Intriguing but far from definitive studies suggest that vitamin E might help slow the progression of and cataracts,51–54 improve immune response to vaccinations,42 decrease symptoms of menstrual pain,139, 183 reduce symptoms of PMS,61,62 control symptoms of restless legs syndrome,59 reduce discomfort in rheumatoid arthritis (and possibly help prevent it), and help prevent vascular dementia.60 Evidence regarding whether vitamin E can slow the progression of Alzheimer's disease is inconsistent. Alzheimer's disease43, 184 Studies of vitamin E in combination with vitamin C for prevention of preeclampsia have yielded inconsistent results.41, 185-186 Vitamin E has also shown equivocal promise in diabetes. One double-blind trial found benefits for cardiac autonomic neuropathy,40 a complication of diabetes. Weaker evidence hints at possible benefits for diabetic peripheral neuropathy.46,47 However, the best designed study of all, a long-term trial involving 3,654 people with diabetes, found that use of vitamin E did not protect against diabetes-induced kidney or heart damage.157 Similarly, while a few studies performed by one research group suggested that vitamin E might be helpful for improving glucose control in people with diabetes, subsequent evidence found that the benefits, if they exist at all, are short-term.169, 187 Similarly, studies on whether vitamin E is helpful for allergic rhinitis (hay fever) have produced conflicting results. Vitamin E might help reduce the lung-related side effects caused by the drug amiodarone (used to prevent abnormal heart rhythms).66 Studies have yielded mixed results on whether vitamin E is helpful for controlling seizures in people with epilepsy, tardive dyskinesia aiding recovery during heavy exercise, and treating male infertility. When combined with vitamin C, vitamin E may protect against sunburn to a small extent.34–38 The same combination has also shown promise for acute anterior uveitis.39 A separate study failed to find vitamin E alone (at the high dose of 1600 mg daily) helpful for macular edema (swelling of the center of the retina) associated with uveitis. 188 Vitamin E has been tried for amyotrophic lateral sclerosis (Lou Gehrig's disease), but the results in the first reported double-blind study showed questionable benefits if any.137 Some vitamin E proponents felt that the dose of vitamin E used in this study might have been too low. Accordingly, they conducted another study using ten times the dose, this one lasting 18 months and enrolling 160 people. Once again, vitamin E failed to prove significantly more effective than placebo. Vitamin E is sometimes recommended for osteoarthritis. However, a 2-year, double-blind, placebo-controlled study of 136 people with osteoarthritis of the knee failed to find any benefit in terms of symptom control or slowing disease progression.164 A previous 6-month, double-blind, placebo-controlled trial of 77 individuals with osteoarthritis also failed to find benefit.138 A 4-year, double-blind, placebo-controlled trial of 1,193 people with macular degeneration failed to find vitamin E alone helpful for preventing or treating macular degeneration. Vitamin E has also so far failed to prove helpful for preventing or treating alcoholic hepatitis, asthma, congestive heart failure, fibrocystic breast disease,70 or Parkinson's disease. Although vitamin E is often recommended for menopausal hot flashes, there is no real evidence that it is effective. One 9-week, double-blind, placebo-controlled trial followed 104 women with hot flashes associated with breast cancer treatment, but it found marginal benefits at best.74 Cancer Prevention The results of observational trials have been mixed, but on balance, they suggest that high intake of vitamin E and other antioxidants is associated with reduced risk of lung cancer and many other forms of cancer, including bladder, stomach, mouth, throat, laryngeal, liver, and prostate cancer.83–95,144,145,166 Based on these and other results, researchers developed the hypothesis that antioxidants can help prevent cancer, and set in motion very large, long-term double-blind, placebo-controlled studies to verify it. Unfortunately, these studies generally failed to find vitamin E helpful for the prevention of cancer in people at high risk for it. The one positive note came in a double-blind trial of 29,133 smokers. In this study, 50 mg of synthetic vitamin E (dl-alpha-tocopherol) daily for 5 to 8 years caused a 32% reduction in the incidence of prostate cancer and a 41% drop in prostate cancer deaths. Surprisingly, results were seen soon after the beginning of supplementation. This was unexpected because prostate cancer grows very slowly. A cancer that shows up today actually started to develop many years ago. The fact that vitamin E almost immediately lowered the incidence of prostate cancer suggests that it somehow blocks the step at which a hidden prostate cancer makes the leap to being detectable. Nonetheless, the negative results regarding most other types of cancer have made scientists hesitant to place too much hope in these findings. It has been suggested that alpha-tocopherol alone is less effective than the multiple forms of tocopherol that occur in nature; in particular, it has been suggested that gamma-tocopherol rather than alpha-tocopherol might be the most relevant form of vitamin E for cancer prevention. However, this has not yet been tested. Interestingly, use of alpha-tocopherol supplements may deplete both gamma- and delta-tocopherol levels, potentially producing a negative effect.174 Cardiovascular Disease Most but not all observational studies have found associations between high intake of vitamin E and reduced risk of cardiovascular disease (heart disease and strokes).104–107,150,151 However, as we’ve explained, observational studies by themselves cannot be relied upon to identify useful treatments. Double-blind studies, which provide much more convincing evidence of effectiveness, have generally failed to find vitamin E supplements effective. The Heart Outcomes Prevention Evaluation (HOPE) trial found that natural vitamin E (d-alpha-tocopherol) at a dose of 400 IU daily did not reduce the number of heart attacks, strokes, or deaths from heart disease any more than placebo.96 The trial followed over 9,000 men and women who had existing heart disease or were at high risk for it. Negative results were seen in numerous other large trials, as well.99–102,129,152,153,157,175, 194-195 When the results of these studies began to come in, some antioxidant proponents suggested that the people enrolled in these trials already had disease too advanced for vitamin E to help. However, a subsequent large trial found vitamin E ineffective for slowing the progression of heart disease in healthy people as well.155 As with preventing cancer, critics have suggested that the form of vitamin E used in these studies (alpha-tocopherol) was not the best choice, and that gamma-tocopherol might be more helpful. Gamma-tocopherol is present in the diet much more abundantly than alpha-tocopherol, and it could be that the studies showing benefits with dietary vitamin E actually tracked the influence of gamma-tocopherol. However, an observational study specifically looking to see if gamma-tocopherol levels were associated with risk of heart attack found no relationship between the two.143 Nonetheless, intervention trials of gamma-tocopherol are currently underway. Preeclampsia Prevention Preeclampsia is a dangerous complication of pregnancy that involves high blood pressure, swelling of the whole body, and improper kidney function. A double-blind, placebo-controlled study of 283 women at increased risk for preeclampsia found that supplementation with vitamin E (400 IU daily of natural vitamin E) and vitamin C (1,000 mg daily) significantly reduced the chances of developing this disease.112 While this research is promising, larger studies are necessary to confirm whether vitamins E and C will actually work. The authors of this study point out that studies of similar size found benefits with other treatments, such as aspirin, that later proved to be ineffective when large-scale studies were performed. Furthermore, keep in mind that we don't know whether such high dosages of these vitamins are absolutely safe for pregnant women. Tardive Dyskinesia Between 1987 and 1998, at least five double-blind studies were published that indicated vitamin E was beneficial in treating tardive dyskinesia.113,114 Although most of these studies were small and lasted only 4 to 12 weeks, one 36-week study enrolled 40 individuals.115 Three small double-blind studies reported that vitamin E was not helpful.116,117 Nonetheless, a statistical analysis of the double-blind studies done before 1999 found good evidence that vitamin E was more effective than placebo.118 Most studies found that vitamin E worked best for TD of more recent onset.119 However, in 1999, the picture on vitamin E changed with the publication of one more study—the largest and longest to date.120 This double-blind study included 107 participants from nine different research sites who took 1,600 IU of vitamin E or placebo daily for at least 1 year. In contrast to most of the previous studies, this trial did not find vitamin E effective in decreasing TD symptoms. Why the discrepancy between this study and the earlier ones? The researchers, some of whom had worked on the earlier, positive studies of vitamin E, were at pains to develop an answer. They proposed a number of possible explanations. One was that the earlier studies were too small or too short to be accurate, and that vitamin E really didn't help at all. Another was the most complicated: that vitamin E might help only a subgroup of people who had TD—those with milder TD symptoms of more recent onset—and that fewer of these people had participated in the latest study. They also pointed to changes in schizophrenia treatment since the last study was done, including the growing use of antipsychotic medications that do not cause TD. The bottom line: The effectiveness of vitamin E for a given individual is simply not known. Given the lack of other good treatments for TD, and the general safety of the vitamin, it may be worth discussing with your physician. Immune Support Seniors often do not respond adequately to vaccinations. One double-blind study suggests that vitamin E may be able to strengthen the immune response to vaccines. In this trial, 88 people over the age of 65 were given either placebo or vitamin E at 60 IU, 200 IU, or 800 IU dl-alpha-tocopherol daily.123 The researchers then gave all participants immunizations against hepatitis B, tetanus, diphtheria, and pneumonia, and looked at subjects' immune response to these vaccinations. The researchers also used a skin test that evaluates the overall strength of the immune response. The results were promising. Vitamin E at 200 mg per day and, to a lesser extent, at 800 mg per day significantly increased the strength of the immune response. However, it is not clear whether vitamin E has a general “immune support” effect. One study in seniors found that use of vitamin E did not help prevent colds and other respiratory infections, and, in fact, seemed to slightly increase the severity of infections that did occur.156 In a similar-sized double-blind study of long-term care residents, use of vitamin E at 200 IU daily failed to reduce incidence or number of days of respiratory infection or antibiotic use.176 The researchers managed to find some evidence of benefit by breaking down the respiratory infections by type, but such after-the-fact analysis is questionable from a statistical perspective. Subsequently, the same researchers repeated the study with a larger group, and did find a reduction in frequency of colds. 191 Alzheimer's Disease Evidence is conflicting regarding whether high-dose vitamin E can slow the progression of Alzheimer's disease.124 In a double-blind, placebo-controlled study, 341 people with Alzheimer's disease received either 2,000 IU daily of vitamin E (dl-alpha-tocopherol), the antioxidant drug selegiline, or placebo. Those given vitamin E took nearly 200 days longer to reach a severe state of the disease than the placebo group. (Selegiline was even more effective.) However, negative results were seen in a study of 769 people at high risk of developing Alzheimer's disease based on early symptoms. 192 Participants were given either 2000IU of vitamin E, the drug donepezil, or placebo for three years. Neither treatment reduced the percentage of people who went on to develop Alzheimer's disease. Warning: Such high dosages of vitamin E should not be taken except under a doctor's supervision (see Safety Issues). Dysmenorrhea (Menstrual Pain) In a double-blind, placebo-controlled trial, 100 young women complaining of significant menstrual pain were given either 500 IU of vitamin E or placebo for 5 days.139 Treatment began 2 days before and continued for 3 days after the expected onset of menstruation. While both groups showed significant improvement in pain over the 2 months of the study (presumably due to the power of placebo), pain reduction was greater in the treatment group as compared to the placebo group. Benefits were also seen in a 4 month Iranian double-blind, placebo-controlled study of 278 adolescent girls. 196 The dose used in this study was 200IU twice daily. Low Sperm Count/Infertility In a double-blind, placebo-controlled study of 110 men whose sperm showed subnormal activity, treatment with 100 IU of vitamin E daily resulted in improved sperm activity and higher actual fertility (measured in pregnancies).125 However, a smaller double-blind trial found no benefit.126 Cardiac Autonomic Neuropathy People with diabetes sometimes develop irregularities of their heart-beat called cardiac autonomic neuropathy. A 4-month, double-blind, placebo-controlled trial found that vitamin E at a dose of 600 mg daily might improve these symptoms. The adult safe upper intake level (UL) for vitamin E is set at 1,000 mg daily.128 The equivalent amounts are 1,500 IU of natural vitamin E and 1,100 IU of synthetic vitamin E. (For technical reasons, the conversion factor is a bit different than in the daily intake recommendations above.) For pregnant women under 19 years of age, the upper limit is 800 mg. Vitamin E has a "blood-thinning" effect that could lead to problems in certain situations. In one study of 28,519 men, vitamin E supplementation at the low dose of about 50 IU synthetic vitamin E per day caused an increase in fatal hemorrhagic strokes, the kind of stroke caused by bleeding.129 (However, it reduced the risk of a more common type of stroke,130 and the two effects essentially canceled out.) Based on its blood-thinning effects, there are concerns that vitamin E could cause problems if combined with medications that also thin the blood, such as Coumadin (warfarin), heparin, Plavix (clopidogrel), Ticlid (ticlopidine), Trental (pentoxifylline), and aspirin. Theoretically, the net result could be to thin the blood too much, causing bleeding problems. A study that evaluated vitamin E plus aspirin did in fact find an additive effect. In contrast, the results of a study on vitamin E and Coumadin found no evidence of interaction, but it would still not be advisable to combine these treatments except under a physician's supervision. There is also at least a remote possibility that vitamin E could also interact with supplements that possess a mild blood-thinning effect, such as garlic, policosanol, and ginkgo. Individuals with bleeding disorders such as hemophilia, and those about to undergo surgery or labor and delivery, should also approach vitamin E with caution. In addition, vitamin E might at least temporarily enhance the body's sensitivity to its own insulin in individuals with adult-onset diabetes. This could lead to a risk of blood sugar levels falling too low. In addition, one study found that use of vitamin E can raise blood pressure in people with diabetes. 197The bottom line: If you have diabetes do not take high-dose vitamin E without first consulting your physician. One widely reported meta-analysis (statistical review of studies) that claimed to find a slightly increased death rate among patients taking vitamin E was too statistically weak to get alarmed about; however, it does provide additional evidence that vitamin E is not the cure-all it was once claimed to be. Finally, considerable controversy exists regarding whether it is safe or appropriate to combine vitamin E with standard chemotherapy drugs. The reasoning behind this concern is that some chemotherapy drugs may work in part by creating free radicals that destroy cancer cells. Antioxidants like vitamin E might interfere with this beneficial effect. However, there is no good evidence that antioxidants actually interfere with chemotherapy drugs, growing evidence that they do not, and some evidence of potential benefit under certain circumstances. Nonetheless, in view of the high stakes involved, we strongly recommend that you do not take any supplements while undergoing cancer chemotherapy, except on the advice of a physician. One study appeared to find evidence that use of vitamin E plus beta-carotene may impair the effectiveness of radiation therapy for head and neck cancers.
The Fountain of Youth?What if I told you that it may be possible for you to live to age 100 or even longer, in better health than you are in right now? And, if you are already experiencing the ill effects of aging, what if I told you that it may be possible for you to look and feel 20 years younger and stay that way beyond the age of 100. Aside from the fact that you'd probably call me crazy, I have to tell you that we have never been as close as we are today to actually being able to extend human life!
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