Drug Summary: Vitamin E is commonly found in the diet, in oils, margarine, and dressings. It is a lipid-soluble vitamin that protects cell membranes and other lipid-containing substances in the body, by interacting directly with free radicals and neutralizing them to prevent oxidative damage. Vitamin E could potentially help treat neurodegenerative diseases such as HD by protecting nerve cell membranes (which are made of lipids) from oxidation by free radicals, which can lead to cell death. (For more information on free radical damage, click here.) Studies in people with Parkinson’s disease or Alzheimer’s disease have shown some correlation between higher vitamin E intake and decreased risk of developing these diseases. (For more information on Alzheimer’s and Parkinson’s, click here.) However, there have been contradictory results in studies that tested whether vitamin E treatment could slow the progression or improve the symptoms of these diseases. Not many studies have been conducted to test the effects of vitamin E in people with HD. Unfortunately, the few results that exist have been inconclusive, with some indicating only slight benefits among some patients with mild symptoms, while others suggesting that vitamin E could potentially even have negative effects on health.
What is vitamin E’s role inside the body?^
Vitamin E is lipid-soluble, meaning that it dissolves in fats. It has to be ingested with minimal amounts of dietary fat to be properly absorbed in the gastrointestinal (GI) tract. Vitamin E exists in eight different chemical forms, but the most common form in the human body is called alpha-tocopherol (α-tocopherol). Alpha-tocopherol’s main role inside the body is to act as an antioxidant. Alpha-tocopherol is lipid-soluble, so it mostly exerts its antioxidant effects on parts of the cell that are also lipid-soluble, such as the cell membrane, an important part of the cell that is made of lipids. Because cell membranes are made of lipid molecules, they are vulnerable to oxidation by free radicals, which can lead to cell death. Alpha-tocopherol plays a very big role in protecting cell membranes by donating its own electrons to free radicals in order to neutralize them.(For more information on free radical damage, click here.) Although alpha-tocopherol loses its antioxidant activity once it donates an electron, other antioxidants like vitamin C can restore alpha-tocopherol’s antioxidant properties. (For more information on vitamin C, click here.)
Besides protecting cell membranes, alpha-tocopherol has also been shown to protect low density lipoproteins (LDL) from oxidation by free radicals. LDL’s are particles made of both lipids and proteins that carry fats and cholesterol through our bloodstream. Research shows that oxidized LDL may increase a person’s risk of developing heart disease. Alpha-tocopherol may therefore exert positive effects in people with HD not only by protecting nerve cell membranes, but also by helping to prevent other complications such as heart disease. (For more information on heart disease and other complications of HD, click here.)
In addition to having these antioxidant effects, alpha-tocopherol affects several other cellular mechanisms and is known to act as a blood-thinner. Blood thinners can help reduce one’s risk of heart attack and stroke by preventing the formation of blood clots in blood vessels. It is important to remember that taking high doses of a blood-thinning compound like vitamin E along with other blood thinners is not advised, and anyone who wishes to take vitamin E as a blood thinner should first consult their doctors.
Could vitamin E supplementation become a potential treatment for HD?^
Several laboratory studies have shown that vitamin E has great potential as an antioxidant. One such study showed that another form of vitamin E, alpha-tocotrienol, protected nerve cells from increased free radical damage and toxicity caused by the neurotransmitter glutamate (Khanna, et al. 2003). Because the nerve cells of people with HD are especially sensitive to glutamate, the prevention of glutamate-induced oxidative damage is very important. (For more information on glutamate toxicity, click here.) In this laboratory study, treatment of nerve cells with alpha-tocotrienol not only decreased cell death but also helped them grow at a normal rate even when treatment with glutamate was continued.
The same researchers found that alpha-tocotrienol not only protects nerve cells by reacting with free radicals directly, but can also prevent free radicals from forming. Alpha-tocotrienol can prevent excessive oxidative damage by inhibiting an enzyme called 12-lipoxygenase (12-LOX), an effect independent of its antioxidant properties. Increased levels of glutamate around the nerve cells cause activation of 12-LOX within the cells, which when activated leads to a cascade of events that lead to production of free radicals and an influx of calcium ions into the nerve cells. These events eventually lead to nerve cell death. Alpha-tocotrienol inhibits 12-LOX from setting off this cascade by binding to it close to its active site. The active site is the spot where an enzyme would normally bind to other molecules, or substrates, in order to set off a reaction in the cell. 12-LOX normally binds to a molecule called arachidonic acid to set off the above-mentioned cascade of events. By binding close to the active site, alpha-tocotrienol prevents 12-LOX from binding arachidonic acid and setting off the reactions that would eventually lead to nerve cell death.
Besides laboratory findings, there is also some clinical evidence that increased intake of vitamin E may help reduce the risk of developing Parkinson’s and Alzheimer’s disease, both of which also involve increased oxidative stress. However, studies that tested whether vitamin E supplementation could help reduce symptoms or slow the progression of these diseases have had varied results. One study of a total of 341 people with Alzheimer’s disease showed that treatment with alpha-tocopherol was associated with a delay in the progression of cognitive symptoms when compared to the placebo group. The group treated with alpha-tocopherol also demonstrated a slower decline in their abilities to perform everyday functions. Research on the protective properties of vitamin E in Parkinson’s disease has been inconclusive in both animals and humans; some studies have shown vitamin E to be protective and others have not.
Peyser, et al. (1995) conducted a 1-year clinical trial with 73 HD patients who were randomly assigned to receive either alpha-tocopherol treatment or a placebo. Since vitamin E interferes with the absorption of vitamin A in the intestines, these researchers decided that subjects in the treatment group should also take a vitamin A supplement in order to prevent the potential development of Vitamin A deficiency. Because vitamin C can restore vitamin E’s antioxidant abilities after it has neutralized a free radical, the treatment group also received daily vitamin C supplements.
These researchers reported that they unfortunately were not able to obtain placebo vitamin A and C pills for the control group, so both the vitamin E treatment group and the control group ended up taking vitamin A and C supplements, which are also antioxidants. Giving both groups these additional vitamins could not produce the same strong evidence as would the use of completely neutral placebo pills. The control group may have also showed some sort of improvement simply because they were given these two vitamins. Furthermore, the vitamin E treatment group may have benefited from the additional vitamins. However, the researchers were still able to establish some specific effects of adding vitamin E to the vitamin A and C combination.
These researchers realized that participants responded differently to the vitamin E supplementation depending on which stage of HD they were in when they started treatment. In order to analyze the results, they split both the treatment and placebo group in two based on the participants’ initial scores on a neurological test. Participants who entered the study with a score of 45 or less were considered to be in the early stages of HD, and participants who had initial scores of more than 45 were considered to be in the late stages. Based on this grouping, the researchers showed that on average, early-stage participants who were treated with vitamin E improved on the neurological examination by the end of the study. Meanwhile, late-stage participants did not show this improvement. This study is important because it shows that vitamin E may have potential to slow HD progression caused by free radical damage, but only if treatment is started before severe nerve cell damage takes place.
A newer study by Kasparova et al. (2006) done on rat models of HD showed that administration of a combination of vitamin E and coenzyme-Q10 (For more information on coenzyme-Q10, click here.) could have potential benefits for HD patients. The rats received coenzyme-Q10 and vitamin E for 10 days before they were injected with 3-NP, a chemical that would create lesions in the striatum, resulting in symptoms similar to HD. Results showed that the increase of creatine kinase, an indicator of brain energy metabolism dysfunction, as well as the decrease of coenzyme-Q10, were prevented in the brain tissue of these rats as compared those in the control group. However, coenzyme-Q10 and vitamin E were not effective in preventing the decline of electron transport chain function (For more information on electron transport chain function and abnormalities in energy metabolism, click here.).
Risks of Vitamin E supplements^
In recent years, researchers at John Hopkins University have reported that patients who take high doses of vitamin E (more than 400IU) had higher risks of death, although it remains unclear why. Vitamin E supplements typically contain 400-800IU (1IU = 2/3 mg), which meets the criterion for high dosage. The data is still inconclusive as to whether lower doses of vitamin E are also associated with this risk. Furthermore, the studies were conducted on older adults, and many of them had heart diseases and other diseases. Nevertheless, HD patients taking high doses of vitamin E should consult with their doctors and might want to consider taking other types of antioxidants.
In conclusion, while vitamin E has beneficial antioxidant effects, it may be toxic at higher doses. Further research needs to be completed to determine whether vitamin E can be a safe and effective therapeutic treatment for Huntington’s disease. As of Spring 2012, not many studies have been conducted investigating the relationship between vitamin E and Huntington’s disease specifically.
For further reading^
- For a good overview of what vitamin E does inside the body, how it is linked to other medical conditions and how it relates to diet and nutrition, visit Oregon State University’s Linus Pauling Institute website.
- Fariss, et al. “Vitamin E therapy in Parkinson’s disease.” Toxicology. 2003 Jul 15;189(1-2):129-46.
This is a fairly complicated article that explains the role of oxidative stress in Parkinson’s disease and then reviews all the research that has been done on vitamin E treatment in Parkinson’s.
- Khanna, et al. “Molecular basis of vitamin E action.” The Journal of Biological Chemistry. 2003 Oct. 31;278(44):43508-15.
This is a very technical article that describes the experiments that showed that alpha-tocotrienol helps prevent nerve cell death by inhibiting 12-LOX.
- Peyser, et al. “Trial of d-alpha-tocopherol in Huntington’s disease.” The American Journal of Psychiatry. 1995 Dec;152(12):1771-5.
This article is of medium difficulty and describes the 1995 clinical trial of alpha-tocopherol in 73 people with HD.
- Sano, et al. “A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease.” The New England Journal of Medicine. 1997 Apr 24;336(17):1216-22.
This is an article of medium difficulty that describes the clinical study of 341 people with Alzheimer’s disease that tested the effects of alpha-tocopherol treatment along with another drug.
– A. Milczarek, 05/03/05, updated A. Zhang, 4/18/12