Antioxidant Vitamins Generally Vitamins A C and E

Relevance to MS. Among all categories of dietary supplements, antioxidant vitamins were among those used most frequently by a large group of people with MS who were surveyed through a study at the Rocky Mountain Multiple Sclerosis Center (the full results of this survey may be seen at www.ms-cam.org). Antioxidant vitamins include:

■ Vitamin A or beta-carotene (a chemical converted to vitamin A)

These vitamins act on free radicals, chemicals that can damage cells in the brain and other organs of the body. For years, it has been proposed that free radicals may play an important role in aging, aging-related diseases, and many other conditions, including MS.

Antioxidants have various actions on the immune system and nervous system—some of these effects could be beneficial for people with MS. Specifically, free radicals may play an important role in MS—using antioxi-dants to decrease the harmful effects of free radicals may be beneficial. In MS, one type of immune cell, the macrophage, injures the myelin coating on nerve cells by releasing free radicals. Also, the axon—the central part of the nerve cell—is injured in MS, and free radicals may be important in causing axonal injury. In addition, immune cells are activated by the chemical products of free-radical injury to the walls (or membranes) of cells. In the animal model of MS, EAE, growing evidence suggests that free radicals are involved, and that some antioxidant compounds decrease the severity of EAE. Biochemical studies indicate that free-radical damage occurs in people with MS. Thus, multiple scientific and clinical studies indicate that antioxidants may be beneficial to the MS disease process.

Theoretical reasons exist why antioxidants could be harmful for MS. Several antioxidants stimulate components of the immune system, including cells known as macrophages and T cells. These cells are already too active in MS—further activation could, in theory, worsen the disease or antagonize the effects of MS medications such as glatiramer acetate (Copaxone), interferons (Avonex, Betaseron, Rebif), mitoxantrone (Novantrone), or natal-izumab (Tysabri).

Although recent basic science and animal-model studies in the area of antioxidants and MS have produced encouraging results, no rigorous clinical trial of antioxidants in MS has yet been undertaken. Limited research results are sometimes used as evidence for the safety of antioxidants in MS. One study found that antioxidant use (vitamin C, vitamin E, and selenium) for 5 weeks in 18 people with MS was not associated with worsening of the disease (1). However, this was only a single, short-term study of a relatively small number of people. Another argument for antioxidant safety in MS is that EAE, an animal model of MS, appears to be improved with some types of antioxidant therapy. The animal model of MS is not a perfect model— thus, encouraging results of experimental therapies in this model must be tested in the actual human disease before these therapies are broadly recommended for people with MS. To improve our understanding in this area, multiple trials of antioxidants in MS are underway or are being planned.

With the limited information available at this time, it is reasonable for people with MS to consume antioxidants with care. For people with MS, one reasonable approach is to not take antioxidant supplements, but rather to obtain antioxidants through food, specifically fruits and vegetables. Individualized information about fruit and vegetable intake may be obtained at www.mypyramid.gov (see the chapter on "Diets and Fatty Acid Supplements"). General daily recommendations are two to four servings of fruits and three to five servings of vegetables. This dietary intake may result in adequate, but not excessive, levels of antioxidants, and may provide other health benefits.

If people with MS choose to use antioxidant vitamin supplements, it is reasonable to take modest doses. Modest daily doses of these vitamins are:

■ Vitamin C—90 to 120 milligrams or less

(For vitamin E, conversions may be made between the different forms and units. For lower, nontoxic doses, 1 milligram of alpha-tocopherol = 1.5 1U of natural vitamin E = 2.2 1U of synthetic vitamin E. For higher and potentially toxic doses, 1 milligram of alpha-tocopherol = 1.1 1U of synthetic vitamin E = 1.5 1U of natural vitamin E.)

High daily doses of certain antioxidants should definitely be avoided because of possible toxic side effects (see Table 43.2):

■ Greater than 10,000 1U of vitamin A may produce multiple toxic effects, including headache, blurred vision, nausea, and liver injury.

■ Greater than 10,000 1U of vitamin A in pregnant women may produce birth defects.

■ Greater than 2,500 milligrams of vitamin C may cause diarrhea, abdominal bloating, and kidney stones.

■ Greater than 1,000 mg (1,500 1U) of vitamin E may produce stomach upset, bleeding problems, and other difficulties

Other important precautions about antioxidant vitamin use should be noted. Vitamin A or beta-carotene supplements should be avoided or used cautiously by smokers because two studies indicate that beta-carotene supplements increase the risk of death and lung cancer in smokers. Vitamin E may inhibit blood clotting and thus should be avoided by people with bleeding disorders, people taking blood-thinning medications (such as warfarin or Coumadin), and people undergoing surgery. Vitamin C may decrease the effectiveness of blood-thinning medications.

As noted, clinical trials of antioxidants in MS are underway or are being planned. The results from such studies will have important practical applications. 1f antioxidant supplements are found to be beneficial, they could be recommended; if they are found to be harmful, their use could be discouraged; if they have no effect, they could be avoided and money could be saved or spent on some other type of treatment.

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