Vitamin E

Overview

Vitamin E (alpha-tocopherol) is a fat-soluble vitamin present in many foods, especially certain fats and oils. It is one of a number of nutrients called antioxidants. Some other well known antioxidants include vitamin C and beta-carotene. Antioxidants are nutrients that block some of the damage caused by toxic by-products released when the body transforms food into energy or fights off infection. The build up of these by-products over time is largely responsible for the aging process and can contribute to the development of various health conditions such as heart disease, cancer, and a host of inflammatory conditions like arthritis. Antioxidants provide some protection against these conditions and also help reduce the damage to the body caused by toxic chemicals and pollutants.

Vitamin E deficiency can be seen in people unable to absorb fat properly. Such conditions include pancreatitis (inflammation of the pancreas), cystic fibrosis, and biliary diseases (illnesses of the gallbladder and biliary ducts). Symptoms of deficiency include muscle weakness, loss of muscle mass, abnormal eye movements, impaired vision, and unsteady gait. Eventually, kidney and liver function may be compromised. In addition, severe vitamin E deficiency can be associated with serial miscarriages and premature delivery in pregnant women.

Uses

Vitamin E helps prevent arteries from clogging by blocking the conversion of cholesterol into the waxy fat deposits called plaque that stick to blood vessel walls. Vitamin E also thins the blood, allowing for blood to flow more easily through arteries even when plaque is present. Studies in the last 10 years have reported beneficial results from use of vitamin E supplements as part of a prevention strategy for heart disease and other types of cardiovascular disease.

A large, important study of postmenopausal women, for example, suggested that vitamin E from foods may reduce the risk of death from stroke in postmenopausal women. The study results do not, however, support any need for supplementation with vitamin E or other antioxidant vitamins as part of a preventive strategy.

There is some evidence for the use of supplemental vitamin E as a treatment for atherosclerosis. For example, a 2-year study of men with a history of stroke compared aspirin with and without vitamin E and found that vitamin E with aspirin significantly reduced the tendency of plaque to stick to vessel walls and decreased the risk of stroke.

Still, when looked at collectively, results of studies have been mixed and a lot more evidence is needed to know if there are benefits to supplementing with vitamin E, whether for prevention or for treatment of cardiovascular disease. Four large, well-designed trials are currently in progress and should help resolve this question.

Cancer

While no firm conclusions can be drawn about vitamin E's ability to protect against cancer, it has been noted that people with cancer often have lower levels of vitamin E. Plus, population based trials (observing groups of people over long periods of time) suggest that diets rich in antioxidants, including vitamin E, may be connected to a reduced risk of certain types of cancer, such as colon cancer. Supplementation with vitamin E, though, does not appear to improve risk of cancer.

Laboratory studies have generally shown that vitamin E inhibits the growth of some cancers in test tubes and animals, particularly hormone responsive cancers such as breast and prostate. There is reason to believe, therefore, that, for these types of cancers at least, supplementation may prove beneficial for both prevention and treatment.

Despite the encouraging results from test tube and animal studies, however, research on people has been much less promising. A large, important study called the Iowa Women's Health Study, for example, involving nearly 35,000 women, looked at the dietary intake of antioxidants and occurrence of breast cancer after menopause. They found little evidence that vitamin E has a protective effect. More research is needed before coming to any firm conclusions about whether added vitamin E has an impact on cancer and, if so, which forms of the vitamin are most effective for treatment and what optimal dosing would be.

Researchers have also pointed to the fact that the body's antioxidant defense system is complex, which suggests that focusing on one vitamin in isolation may not be the best approach. This may be why dietary forms of antioxidants, since they are generally taken together from foods, may be the best way to try to stave off cancer.

Photodermatitis

This condition involves an allergic type reaction to the UV rays of the sun. An 8-day study comparing treatment with vitamins C and E to no treatment found that the vitamin group became significantly less sensitive to the sun. Another study, lasting for 50 days, also showed a protective effect of the combination of vitamins C and E to UV rays.

Osteoarthritis

A few studies suggest that vitamin E may be helpful in both the treatment (pain relief, increased joint mobility) and prevention (at least in men) of osteoarthritis. In a study comparing vitamin E with diclofenac, a non-steroidal anti-inflammatory drug (NSAID) used to treat osteoarthritis, the two were found to be equally effective.

Alzheimer's Disease

There are several reasons why vitamin E might help treat Alzheimer's disease. The fat soluble vitamin readily enters the brain and exerts its antioxidative properties. Oxidative stress is believed to contribute to the development of Alzheimer's disease; therefore, again, it makes at least theoretical sense that antioxidants, like vitamin E, help prevent this condition. In fact, studies have suggested that vitamin E supplementation improves cognitive performance in healthy individuals and in those with dementia from causes other than Alzheimer's (for example, multiple strokes). In addition, vitamin E, together with vitamin C may prevent the development of Alzheimer's disease.

Menopause

According to a review article on alternatives to hormone replacement therapy (HRT) for women with breast cancer, vitamin E is the most effective option for the reduction of hot flashes for this group of women. Presumably, this would be true for other women not taking HRT because they cannot or prefer not to. Vitamin E also helps reduce other long term risks associated with menopause such as Alzheimer's, macular degeneration, and cardiovascular disease.

Eye Health

Because of its antioxidant action, vitamin E may help to protect against cataracts (clouding of the lens of the eye) and age related macular degeneration (ARMD, a progressive deterioration in the retina, the back part, of the eye). Both of these eye disorders tend to occur as people age. These conditions seriously compromise eyesight and ARMD is the number one cause of blindness in the United States. In order to minimize risk of ARMD, research reviews advocate diets high in vitamins C and E and carotenoids, especially spinach, kale, and collard greens. Taking supplements as a preventive measure, as opposed to getting vitamin E from food sources, remains controversial.

Uveitis is another eye disorder for which the antioxidant vitamins C and E may be helpful. A study of 130 patients with uveitis compared treatment with oral vitamins C and E to placebo and found that those who took the vitamins had significantly better visual clarity than those in the placebo group. Uveitis is inflammation of the uvea, the middle layer of the eye between the sclera (white outer coat of the eye) and the retina (the back of the eye). The uvea contains many of the blood vessels that nourish the eye. Inflammation of this area, therefore, can affect the cornea, the retina, the sclera, and other important parts of the eye. Uveitis occurs in acute and chronic forms.

Diabetes

People with diabetes tend to have low levels of antioxidants. This may explain, in part, their increased risk for conditions such as cardiovascular disease. Vitamin E supplements and other antioxidants may help reduce the risk of heart disease and other complications in people with diabetes. In particular, antioxidants have been shown to help control blood sugar levels, to lower cholesterol levels in those with type 2 diabetes, and to protect against the complications of retinopathy (eye damage) and nephropathy (kidney damage) in those with type 1 diabetes.

Vitamin E may also play a role in the prevention of diabetes. In one study, 944 men who did not have diabetes at were followed for 4 years. Low levels of vitamin E was associated with an increased risk of becoming diabetic in that time course.

Pancreatitis

Oxidative stress plays a role in pancreatitis (inflammation of the pancreas). In fact, those with pancreatitis have low levels of vitamin E and other antioxidants. This may be due to lack of absorption of fat soluble vitamins (such as vitamin E) because the enzymes from the pancreas required to absorb fat are not functioning properly. Or, this may be due to poor intake because those with pancreatitis are not eating due to pain and need for bowel rest. Some experts relay that taking vitamin E and other antioxidants may help to reduce the pain and inflammation associated with pancreatitis.

Getting the Facts About Prostate Cancer

Like umpires and plumbing, the prostate gets attention only when things go wrong. Unfortunately, the odds are high that something will go wrong at some point in a man's lifetime. The prostate is a gland that hugs the urethra just below the bladder. It produces fluid that combines with sperm, and then secretes the resulting semen when the time is right.

That's a rather significant contribution to male sexuality, yet this walnut-sized gland remains largely unappreciated. In fact it's something of a mystery to men and women alike and many are unaware of the variety of things that can go wrong with it.

Men under 50 might suffer from prostatitis, an inflammation of the gland that can make urination painful.

More common for men over 50 is prostate enlargement. All prostates grow as time goes by, but problematic growth can result in a condition known as benign prostatic hyperplasia, or BPH. The pressure on the urethra causes bladder control problems, often burdening the sufferer with frequent but incomplete urination.

Both those conditions can be treated and controlled. Far more serious is prostate cancer, the most common tumor in men.

Cancer of the prostate kills more than 4,000 Mexicans each year, or about 11 a day. Worldwide, it's been estimated that men die of prostate cancer at the rate of one every 18 minutes.

They don't necessarily have to. This cancer is curable."Like any other tumor, if you find it early you can treat it," says Armando Castro Gaytán, a urologic surgeon in Mexico City. "If it's still small and local, you can remove it or radiate it."

The problem, Dr. Castro says, is that a prostatic tumor has some characteristics that complicate detection. For one thing, it's usually an unaggressive tumor, meaning it grows very slowly. Slow growth offers the advantage of delayed harm, but it also means that 10 years can pass before it shows up on tests.

Also, prostate cancer develops without symptoms. There are no warning signs you can feel or see until it's too late. That makes the available diagnostic tests an absolute must. "Men should start getting screened for prostate cancer at age 50," Dr. Castro says. "If there's a history of prostate cancer in your family, start at age 40."

There are two types of tests for prostate cancer. One is the digital rectal exam that's usually a part of your yearly check-up (and must be if you're over 50). This is the infamous finger prod, which requires bending over and a test of your ability to relax when you'd rather not.

"What we're looking for as we feel the prostate are irregularities or asymmetries, anything that's different," Dr. Castro says.

The other diagnostic method is a simple blood sample that tests for levels of a chemical from the prostate called prostate specific androgen (PSA in English, and APE in Spanish). A cancerous prostate will usually release more PSAs, so a high PSA count indicates trouble.

Why not just do the blood test and spare yourself the digital discomfort? "Because," says urologist Carlos Vázquez Lastra, a colleague of Castro at ABC Hospital in Mexico City, "rectal exams will miss about 40 percent of cancers, and PSA tests will miss about 23 percent. But combined they'll detect about 75 percent of cancers, including 60 percent of the harder-to-find localized [early] cancers."

If the tests are positive, a biopsy will be taken to confirm the cancer by analyzing actual tissue from the gland. A prostate biopsy is no simple scrape. Instruments with names like transductors need to be inserted through the anus and guided to the prostate, where they're put to work.

The prostate's delicate position close to the anus, urethra, bladder and scrotum comes into play during one of the two major cancer treatments namely prostatectomy, which removes the cancer by removing the cancerous gland. The surgery can be done laproscopically, inserting a tiny camera and four precise instruments through "keyholes." More often, open surgery is performed, working downward from an incision in the abdomen.

Care must be taken, of course, not to damage the urethra, bladder, sphincter or scrotum as the prostate is removed. The success rate of the operation, however, is quite high.

Also important is sparing the nerves that control blood flow through the abundant small capillaries to the penis for erections. This is tricky business, since the nerves adhere to the prostate itself.

The percentage of prostate surgery patients who retain erectile capacity has improved significantly in recent years, but it's still not a sure thing. Age is the main factor. A man in his 40s will almost surely come out of the operation with full potency. But Dr. Castro estimates that only about 35 percent of men over 70 recover erectile function.

Radiation therapy is the second treatment option for early-detected prostate cancers. External radiation zaps the prostate with precisely aimed beams. It works, but it's time-consuming and expensive, requiring daily treatment for weeks. The newer brachytherapy, which inserts radiation-emitting "seeds" into your prostate, is more convenient.

The advanced age of most prostate cancer patients combined with the tumor's slow growth often calls for a third treatment option, which is basically doing nothing. According to Vázquez and Castro, "watchful waiting" makes sense when the patient's life expectancy is less than 10 years. "The vast majority will die from something else before they ever die from prostate cancer," Dr. Castro points out.

Can you take steps to prevent prostate cancer? Nothing's for sure, especially since there's little anyone can do about the two biggest risk factors heredity and age. But researchers think diet adjustments can help.

The saturated fats in animal foods are suspected to raise your risk of prostate cancer. Since these are the same cholesterol-raising fats that contribute to heart disease, it makes sense to cut back. Replace the animal fats with more vegetables, especially tomatoes, which offer a nutrient called lycopene that's been shown to improve prostate health.

Supplementing with vitamin E and selenium are also thought to be preventative.

Diet stands out even more when you look at how prostate cancer shows up in different parts of the world. Though every place has it, the rates are lower in Asia. But when Japanese, for example, relocate to the United States, their risk of prostate cancer goes up. The reason for that, it's presumed, is the migrants' adoption of Western-style diets.

Switzerland, of all places, has the highest incidence of prostate cancer. Mexico occupies a position in the lower part of the middle range. But that doesn't mean prostate cancer isn't a big problem here. It is. And even with better detection and improved treatment, the problem will grow as the population as a whole gets older.

That's because age is such a big influence on prostate cancer risk. Consider: At age 50 you have a 15-30 percent chance of developing prostate cancer. That percentage steadily climbs with the years, reaching 60 to 70 percent at age 80 and an almost-sure-thing of 90 percent for those who make it to 90.

"All men have a time bomb ticking inside of them,"Dr. Castro says. He doesn't mean that fatalistically, but as a call to action. "The main message is for people to be aware of how serious and frequent prostate cancer is," he says. "Then they can detect it early if they develop it and take advantage of the treatments we have for it."


1. Quin J, Engle D, Litwiller A, Peralta E, Grasch A, Boley T, Hazelrigg S. Vitamin E Succinate Decreases Lung Cancer Tumor Growth in Mice. J Surg Res. 2005 Aug;127(2):139-43.

Background: In vitro studies have shown that Vitamin E succinate (VES) arrests lung cancer proliferation; however, in vivo studies have not been performed. This study examined in vivo effects of VES on lung cancer. METHODS: An in vitro dose-response curve of human A549 lung cancer tumors to VES was established. A549 tumors were established in the right submammary fat pads of athymic nude mice (C57/BL/6J-Hfh11nu). Seven days after injection, mice were separated into VES and control groups. VES mice (n = 12) underwent daily intraperitoneal (IP) injection of VES (150 mg/kg in 7% dimethyl sulfoxide, 93% polyethylene glycol); control mice (n = 11) were injected with vehicle only. At 27 days, harvested tumors were measured and weighed. Lungs were stained for metastases using hematoxylin-eosin. Tumor volume and weights were compared using a two-sample t test. Tumor growth curves were compared using a mixed model analysis of variance.

Results: In vitro studies demonstrated dose-dependent manner inhibition of A549 cell proliferation by VES (IC(50) 18 mug/mL). Tumor volumes and weights differed significantly between VES and control mice with volumes of 192.6 +/- 20.4 mm(3)versus 292.9 +/- 31.4 mm(3) (P = 0.01) and weights of 168.6 +/- 20.0 mg versus 255.7 +/- 37.0 mg, respectively (P = 0.05). Tumor growth differed significantly (P < 0.001). Both groups of mice showed pulmonary metastases.

Conclusions: Lung cancer cells appear to respond to VES, albeit incompletely. Because tumor cell response is seen, lung cancer patients may derive some benefit from VES and should be considered in eventual clinical studies using this vitamin E derivative.

2. Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer: The Women's Health Study: A Randomized Controlled Trial. JAMA. 2005 Jul 6;294(1):56-65.

Context: Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. OBJECTIVE: To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women.

Design, Setting, and Participants: In the Women's Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years.

Intervention: Administration of 600 IU of natural-source vitamin E on alternate days.

Main Outcome Measures: Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer.

Results: During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53).

Conclusions: The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.

3. Etminan M, Gill SS, Samii A. Intake of Vitamin E, Vitamin C, and Carotenoids and the Risk of Parkinson's Disease: A Meta-analysis. Lancet Neurol. 2005 Jun;4(6):362-5.

We studied the effect of vitamin C, vitamin E, and beta carotene intake on the risk of Parkinson's disease (PD). We did a systematic review and meta-analysis of observational studies published between 1966 and March 2005 searching MEDLINE, EMBASE, and the Cochrane Library. Eight studies were identified (six case-control, one cohort, and one cross-sectional). We found that dietary intake of vitamin E protects against PD. This protective influence was seen with both moderate intake (relative risk 0.81, 95% CI 0.67-0.98) and high intake (0.78, 0.57-1.06) of vitamin E, although the possible benefit associated with high intake of vitamin E was not significant. The studies did not suggest any protective effects associated with vitamin C or beta carotene. We conclude that dietary vitamin E may have a neuroprotective effect attenuating the risk of PD. These results require confirmation in randomised controlled trials.

4. Hozyasz KK, Chelchowska M, Laskowska-Klita T. Vitamin E Levels in Patients with Celiac Disease. Med Wieku Rozwoj. 2003 Oct-Dec;7(4 Pt 2):593-604.

Celiac disease (CD) is a genetically linked immune-mediated enteropathy triggered by the ingestion of gluten-containing grains food. Deficiencies of trace elements and vitamins may be found in patients with untreated CD. No systematic studies have been carried out on vitamin E status in coeliacs. Tocopherol deficiency is implicated in the biological processes leading to malignant cell transformations, neurological complications, brown bowel syndrome and reproductive disorders. Untreated patients with CD have higher incidences of these disorders than in general population. AIM: The aim of this study was to investigate vitamin E status in patients with celiac disease.

We examined retinol plasma level and tocopherol levels both in plasma and in erythrocytes in 18 patients (age: 2-53 years) with active CD and 12 coeliacs (age: 3-36 years) on gluten-free diet without antiendomysium antibodies for at least 2 years. Vitamins were measured by high-pressure liquid chromatography according to the procedure of Driskell.

In untreated patients levels of plasma tocopherol (13.7 +/-3.8 micromol/L vs. 20 +/-7.1 micromol/L; p<0.02), erythrocytes tocopherol (1.7 +/-0.45 micromol/L vs.2.89 +/-0.52 micromol/L; p<0.001) and ratio of plasma tocopherol to serum total cholesterol (3.36 +/-0.9 micromol/L vs. 4.24 +/-0.85 micromol/L; p<0.02) were significantly lower compared to those on gluten-free diet. In the all patients with active CD, concentrations of tocopherol in erythrocytes were below the norm (N>2.5 micromol/L). In untreated patients vitamin A levels did not achieve a significant difference in comparison with the coeliacs on gluten-free diet (1.75 +/-0.57 micromol/L vs. 1.97 +/-0.72 micromol/L; p>0.05). The lowest levels of tocopherol (in plasma: 5.7 micromol/L, in erythrocytes: 0.74 micromol/L) and retinol (0.8 micromol/L; N>0.7 micromol/L) were detected in the same patient refusing dietetic treatment for more than 10 years.

The conventional treatment of CD is gluten-free diet, but monitoring of tocopherol concentrations, especially in erythrocytes, and correction of its deficiency may offer some benefit for patients who fail to adhere strictly to a gluten free-diet or newly diagnosed coeliacs.

5. Brigelius-Flohe R, Kelly FJ, Salonen JT, Neuzil J, Zingg JM, Azzi A. The European Perspective on Vitamin E: Current Knowledge and Future Research. Am J Clin Nutr. 2002 Oct;76(4):703-16.

Vitamin E is indispensible for reproduction in female rats. In humans, vitamin E deficiency primarily causes neurologic dysfunctions, but the underlying molecular mechanisms are unclear. Because of its antioxidative properties, vitamin E is believed to help prevent diseases associated with oxidative stress, such as cardiovascular disease, cancer, chronic inflammation, and neurologic disorders. However, recent clinical trials undertaken to prove this hypothesis failed to verify a consistent benefit. Given these findings, a group of European scientists met to analyze the most recent knowledge of vitamin E function and metabolism.

An overview of their discussions is presented in this article, which includes considerations of the mechanisms of absorption, distribution, and metabolism of different forms of vitamin E, including the alpha-tocopherol transfer protein and alpha-tocopherol- associated proteins; the mechanism of tocopherol side-chain degradation and its putative interaction with drug metabolism; the usefulness of tocopherol metabolites as biomarkers; and the novel mechanisms of the antiatherosclerotic and anticarcinogenic properties of vitamin E, which involve modulation of cellular signaling, transcriptional regulation, and induction of apoptosis. Clinical trials were analyzed on the basis of the selection of subjects, the stage of disease, and the mode of intake, dosage, and chemical form of vitamin E. In addition, the scarce knowledge on the role of vitamin E in reproduction was summarized. In conclusion, the scientists agreed that the functions of vitamin E were underestimated if one considered only its antioxidative properties. Future research on this essential vitamin should focus on what makes it essential for humans, why the body apparently utilizes alpha-tocopherol preferentially, and what functions other forms of vitamin E have.

6. Collins R, Peto R, Armitage J. The MRC/BHF Heart Protection Study: Preliminary Results. Int J Clin Pract. 2002 Jan-Feb;56(1):53-6.

The Heart Protection Study (HPS), with over 20,500 subjects, is the largest trial of statin therapy ever conducted. It provides important and definitive new information on women, the elderly, diabetics, and people with low baseline cholesterol pre-treatment and those with prior occlusive non-coronary vascular disease. It is a prospective double blind randomised controlled trial with a 2 x 2 factorial design investigating prolonged use (>5 years) of simvastatin 40 mg and a cocktail of antioxidant vitamins (650 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene). The HPS specifically included patients with high risk for coronary heart disease (CHD) but characteristics that excluded them from participation in previous statin trials. Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age, gender or baseline cholesterol value and proved safe and well tolerated.

Results show a 12% reduction in total mortality, a 17% reduction in vascular mortality, a 24% reduction in CHD events, a 27% reduction in all strokes and a 16% reduction in non-coronary revascularisations. Among high-risk patients in this western population (with a minimum total cholesterol [TC] > or = 3.5 mmol/l at entry) there appears to be no threshold cholesterol value below which statin therapy is not associated with benefit; even among those with pre-treatment cholesterol levels below current national recommended targets. Over the 5.5 year study period patients and their doctors were encouraged to add an active non-study statin to the study regimen if they wished to do so. Thus the trial eventually had only two-thirds complying with the original intention-to-treat design. Nevertheless, results were highly significant for the study statin--simvastatin 40 mg once daily. Preliminary results of the HPS are negative for the antioxidant vitamin cocktail but provide reassurance that vitamins do no harm.

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