Antioxidant vitamins are among the dietary supplements that are most used by people with MS. Antioxidants act on free radicals, which are chemicals known to damage cells.
Antioxidants can affect both the immune and nervous systems. By decreasing the impact of harmful free radicals, cell damage may be reduced. Free radicals play a key role in the immune system’s attack on the nervous system, helping to damage both nerve cells and the cells that insulate them. By studying EAE, an animal model of MS, researchers have found that free radicals are likely involved in the disease process and that antioxidants may help. However, as many antioxidants have been shown to stimulate the immune system, they pose a theoretical risk for people with MS.
No large-scale, rigorous clinical trials have been conducted to definitively determine the safety or effectiveness of antioxidants in MS. Some small-scale, short-term studies have been cited to prove the safety of antioxidants in MS; however, this work does not definitively prove safety. The beneficial results documented in EAE are also sometimes cited, but EAE is far from a perfect model of MS and results from this work are often not directly applicable to MS. Many research projects are currently underway to further our understanding of antioxidants and MS.
As the research does not provide clear answers at this time, those with MS should approach antioxidants cautiously. It may be reasonable to avoid these supplements altogether and rely on dietary intake of antioxidants. Antioxidants are found in fruits and vegetables. Dietary intake of modest levels of antioxidant-rich foods is likely to result in adequate levels, while avoiding the excess that is possible with supplementation. More information is available at www.mypyramid.gov.
Vitamins A, C, and E
Vitamins A, C, and E are antioxidant vitamins, as is beta-carotene, a compound that is converted to vitamin A. Antioxidants are discussed at length in the above section. If people choose to take antioxidant vitamin supplements, relatively low daily doses may be most appropriate: vitamin A, 5,000 IU or less; vitamin C, 90 to 120mg or less; vitamin E, 100 IU or less.
High doses of these compounds may be associated with toxic effects. Consuming more than 10,000 IU of vitamin A daily may cause nausea, headache, blurred vision, and liver damage. This dose may produce birth defects in pregnant women. Daily doses of 2,500mg or more of vitamin C may produce bloating, diarrhea, and kidney stones. High doses of vitamin E (1,500IU or 1,000 mg daily) may cause bleeding problems, stomach upset and other problems.
There are other reasons to be cautious about antioxidant vitamins. Smokers should be aware that vitamin A and beta-carotene supplements have been associated with an increased risk of lung cancer and death in people who smoke. Since it may inhibit blood clotting, vitamin E should be avoided by people taking blood-thinning medications or undergoing surgery and by those who suffer from bleeding disorders. Those taking blood-thinning medications should also be aware that vitamin C has been shown to decrease the effectiveness of those drugs.
People with MS should approach vitamin C with caution. Claims exist that vitamin C can prevent or treat the common cold and urinary tract infections (UTIs). The common cold is a viral infection that has the potential to trigger MS attacks. UTIs can occur frequently in women with MS. Little evidence exists to support either of these claims about vitamin C. Cranberry juice may be more effective than vitamin C in UTI prevention, and antibiotics should be used for treatment of known UTIs to avoid possible serious complications (See Herbs page for more information on cranberry). Furthermore, vitamin C is known to stimulate the immune system, especially in high doses. This poses a theoretical risk for people with MS. If vitamin C is used, low doses (90-120mg or less daily) may be most reasonable. This is roughly equivalent to amount found in one cup of orange juice.
Vitamin D and Calcium
Vitamin D helps regulate the immune system and maintain bone density. As people with MS have an excessively active immune system and are at increased risk of developing osteoporosis, vitamin D has therapeutic potential.
Vitamin D is both a vitamin and a hormone. Formation of vitamin D is dependent on sun exposure; thus, inadequate sunlight may produce a vitamin D deficiency. Generally, ten to fifteen minutes of casual exposure to the sun is adequate for normal vitamin D production.
Calcium and vitamin D have been shown to work together to produce strong bones. Therefore, vitamin D may help prevent the development of osteoporosis. People with MS are at an increased risk of developing osteoporosis for many reasons: they are usually less active, are more likely to be female than male, usually have less sun exposure, may be taking steroids for treatment, and often have a vitamin D deficiency. People with MS are two to three times more likely to fracture bones than healthy individuals.
Vitamin D may also play an important role in regulating the immune system by suppressing its activity. Vitamin D supplements have been shown to slow the progression of EAE, an animal model of MS.
Large epidemiologic studies have found that sun exposure and vitamin D supplementation are associated with lower risk of developing MS or dying from the disease. Similar trends exist for diabetes and lupus, other immune conditions.
Limited clinical research has been conducted evaluating the effectiveness of vitamin D in MS. One small study, which lacked a placebo group, suggested vitamin D decreases the frequency of MS attacks. Due to the limitations of this study and the fact that it also involved the use of omega-three fatty acids, the results are difficult to interpret (see Diets and Fatty-Acid Supplements page). Another study found that 6 months of 19-nor-vitamin D supplements (a form of vitamin D) treatment did not produce significant clinical benefits nor did it decrease the severity of the disease as measured by MRI. Calcitriol, the active form of vitamin D, was found in one study to be safe and well tolerated by individuals with MS for up to 12 months. Large scale clinical trials are needed to further characterize the safety and effectiveness of vitamin D.
Geographical research has further indicated that vitamin D may play a role in MS. The prevalence of MS is known to increase with distance from the equator. Sunlight exposure decreases with distance from the equator, and as sunlight is necessary for vitamin D production, average levels of vitamin D decrease as well. Therefore the closer to the poles an individual lives, the more likely he or she will develop MS and also have a vitamin D deficiency. In Switzerland, MS was found to be more common at low altitudes. It has been suggested that this is due to the fact that more ultraviolet light is present at higher levels at higher altitude, thus increasing vitamin D levels and possibly preventing MS. Stuides in Norway showed that MS was more common in those who lived in the coastal areas than in those who lived inland. As coastal people eat more fish, which is high in vitamin D, it has been suggested that dietary intake of vitamin D may prevent MS in these people. However, as fish also contain a large amount of omega-three fatty acids, the effects of vitamin D alone are not clear (see Diets and Fatty Acid Supplements page).
Tests may be done to determine blood levels of vitamin D and bone density. If vitamin D supplementation is indicated by these tests, it is often recommended that calcium supplements be taken as well. Dosing should be discussed with a health professional, but the normal adequate intake of vitamin D is 200 to 600IU daily. It is possible that prescription medications may also be necessary, or, in the case of postmenopausal women, hormone replacement therapy. If vitamin D is taken in high doses it may cause abdominal cramps, fatigue, kidney damage, nausea, vomiting, hypertension, and various other adverse reactions. Calcium and iron may affect each other’s absorption and therefore should not be taken together.
MS is a neurological disorder and vitamin B12 is known to be important for maintaining nerve function. Vitamin B12 deficiency can produce symptoms similar to those seen in MS. However, MS and vitamin B12 deficiency are notthe same condition. A lack of vitamin B12 can damage nerves, but no available research suggests that high levels of B12 improve nerve function.
From research concerning vitamin B12 levels in MS, it is clear that most people with the disease have normal levels. However, there may be a small subpopulation of people with MS who have vitamin B12 deficiency. Therefore, people suspected of having MS should be tested for vitamin B12 deficiency. Only if levels are low should vitamin B12 injections or pills be considered. Follow-up is necessary, as lifetime therapy is often needed to treat vitamin B12 deficiency. In general, vitamin B12 supplements are well tolerated. However, rare cases of rashes, itching, and diarrhea have been reported.
People with too little calcium in their diet should consider taking calcium supplements. It may also be appropriate for people with MS to take calcium and vitamin D supplements together if they have osteoporosis or osteoporosis risk factors – see Vitamin D and Calcium on this page. Other uses for calcium supplementation in MS are not strongly supported. Calcium does interfere with iron absorption, and therefore people should not take them together.
Selenium is an antioxidant mineral that is sometimes recommended for people with MS. The rationale behind these recommendations is not entirely clear. It may be because selenium is an antioxidant or it may be due to research suggesting that people with MS have low selenium levels. The safety and effectiveness of selenium supplements are unclear.
Antioxidants, in general, may be beneficial for people with MS, but they are also known to activate the immune system. It is possible for immune system activation to worsen MS. One study of selenium in EAE, an animal model of MS, found that low and normal selenium diets had no effect on the disease course, whereas high levels increased the severity of the disease and increased the death rate. This research suggests possible serious adverse reactions to selenium supplements.
No large-scale studies have been conducted to definitively determine the effects of selenium on MS. Whether selenium supplements are harmful, beneficial, or neither remains unclear, and therefore people with MS may want to avoid these supplements until further data become available.
If selenium supplements are taken, low doses of 20 to 55mg daily may be most reasonable. High doses (400mg or more daily) have been associated with serious adverse reactions such as nausea, dizziness, fatigue, tooth decay, hair loss, and many other problems. High doses may also activate the immune system. Selenium can be found at reasonable levels in whole grains, meat, and seafood.
Zinc supplements have been suggested for treating MS since it was first defined as a disease in the 1880s. However, there is currently no clear evidence supporting zinc supplementation in MS.
There is some evidence that zinc may shorten the duration of the common cold. Although this evidence is not definitive, it is important because viral infections, like the common cold, may trigger MS attacks. Zinc is sometimes recommended due to its role in the polyunsaturated fatty acids pathway (see Diet and Fatty Acid Supplements page), but it is unclear whether supplements are required for this pathway to function normally.
Zinc has the potential to stimulate the immune system, activating T-cells and macrophages. Zinc supplements have also been shown to increase inflammation in EAE (an experimental animal model of MS), suggesting it may be harmful for people with MS. Furthermore, in a mouse model of lupus, another autoimmune disorder, one study found that decreasing zinc intake produced therapeutic results.
One report of a high incidence of MS in a zinc-related industry suggested a possible toxic effect of zinc. Additionally, high zinc intake may cause copper-deficiency myelopathy, a neurological disorder with symptoms similar to those of MS. The research concerning blood levels of zinc in people with MS has produced mixed results, with some suggesting too much zinc and others too little.
The effects of zinc supplements are not well understood. Due to possible harmful effects and the lack of proven therapeutic effect, it may be reasonable for those with MS to avoid zinc supplements. If supplements are taken, it is probably best to take low doses, such as 10 to 15mg or less daily.
5-hydroxytryptophan (5-HTP) is an amino acid that is very similar to tryptophan, another common amino acid. Both compounds have been marketed for treating depression. However, batches of tryptophan contaminated with peak Xand other compounds have caused eosinophilia-myalgia syndrome. 5-HTP preparations may contain similar contaminants, so until further evidence is available, it may be best to avoid this compound.
Acetyl-L-carnitine (ALCAR) has been studied as a possible treatment for memory issues and fatigue. (Note: Acetyl-L-carnitine is not the same as L-carnitine.)
Acetyl-L-carnitine has been studied in MS due to its potential effects on fatigue. One small-scale study found that acetyl-L-carnitine significantly decreased fatigue as indicated by the Fatigue Severity Scale. Amantadine (Symmetrel), a standard MS-associated fatigue medication, did not produce a significant effect. Neither acetyl-L-carnitine nor amantadine affected fatigue as measured by the Fatigue Impact Scale. More work needs to be done to determine exactly how effective acetyl-L-carnitine is for treating fatigue.
Acetyl-L-carnitine is generally well tolerated. Some possible side effects include anxiety, agitation, insomnia, dizziness, nausea, and vomiting. Similar side effects may occur with amantadine. Acetyl-L-carnitine is not known to have any negative drug interaction. Those taking acetyl-L-carnitine should have regular blood tests to monitor blood count and liver and kidney function. When taken, acetyl-L-carnitine is usually administered in two or three doses over the course of a day, adding up to a total of 1,500 to 4,000mg.
Alpha-lipoic acid is present in mitochondria, which produce energy within cells. It is an antioxidant, and as such it acts to reduce damage done by free radicals.
Studies conducted at the Oregon Health Sciences University (OHSU) have found that alpha-lipoic acid may decrease the severity of EAE, an animal model of MS. It is hypothesized that this is because alpha-lipoic acid has the ability to block the flow of immune cells into the central nervous system from the blood. A small study of alpha-lipoic acid treatment in people with MS was conducted at the same university. This study found the compound to be well tolerated and also suggested that it was capable of inhibiting MMP-9 and sICAM-1, two proteins responsible for moving immune cells into the central nervous system. Other research projects aimed at evaluating the effectiveness of alpha-lipoic acid in MS are in progress at OHSU.
Some research suggests alpha-lipoic acid may help with diabetes, another autoimmune disorder, or with diabetes-associated polyneuropathy, a condition of the peripheral nervous system. The available safety data for alpha-lipoic acid is limited, particularly for people with MS and for long-term use.
Caffeine is of interest as it is a commonly available stimulant, which could theoretically help with MS-associated fatigue. See the Herbs page for more information.
Creatine is most often used as a supplement to increase strength and body mass. Some data suggest it may also help protect nerve cells. Creatine is a potentially useful compound in the treatment of MS, as nerve damage and weakness are seen in this disease.
Within the human body, creatine is produced by the pancreas, liver, and kidneys. Muscle cells and other cells use this compound for generating energy. Meat and fish contain creatine, but it is also sold commercially as a supplement.
The clinical data concerning the therapeutic effectiveness of creatine is limited. Healthy people who take creatine supplements may experience improved performance in short, strenuous exercises. In one small study of people with MS, creatine did not appear to have this effect. However, since the study only involved 16 people, the results are not definitive. Limited work in muscular dystrophy has suggests that creatine may decrease muscle fatigue, improve strength, and increase exercise ability in this condition.
In appropriate doses, creatine is usually well tolerated. However, in rare cases, especially those involving preexisting kidney disease, creatine use may result in kidney failure. More common side effects include muscle cramping, diarrhea, stomach pain, weight gain, nausea, and dehydration.
Melatonin is a hormone involved in regulating the normal 24-hour cycles of the body, known as circadian rhythms. Blood levels of this hormone are low during the day and increase during the night.
Melatonin has many potential uses. Some researchers have found that melatonin may help with sleep problems and jet lag.
Some have suggested melatonin may have a role in causing MS. One study reported that people with high levels of melatonin tended to have a later age of onset, as well as shorter disease duration. This relationship is not well understood, and the implications for melatonin supplementation are unclear.
Melatonin may activate the immune system by stimulating T cells. This poses a theoretical risk for people with MS and other autoimmune disorders. The effects of melatonin on the immune system and MS in general need to be further researched to provide any definitive results.
Melatonin has the potential to help with certain sleep issues, but may have adverse effects for people with MS. It may be reasonable for people with MS to avoid melatonin until further research is conducted. If people with MS choose to use melatonin, they should probably avoid high doses and long-term use.
S-adenosylmethionine, also called SAMe or Sammy, is a supplement that is claimed to be an effective treatment for many medical conditions. SAMe occurs naturally within the body and is used in methylation reactions, a common type of biochemical reaction. Methylation reactions also involve folic acid and vitamin B12. Research suggests the SAMe might be beneficial for treating depression, osteoarthritis, fibromyalgia, liver disease, and an AIDS-related spinal cord condition.
SAMe has also been claimed to be an effective treatment for MS. These claims are not based on convincing evidence. There may be a small subpopulation of people with MS who suffer from vitamin B12 deficiency. Some claim that because vitamin B12 and SAMe take part in similar chemical processes, SAMe must be beneficial for MS. SAMe is also sometimes used as a treatment for rare genetic diseases that produce symptoms similar to MS, and many conclude from this is must be beneficial for treating MS as well. No available research suggests that either vitamin B12 or SAMe have a major role in the disease process of MS. SAMe also does not appear to be effective for treating other neurologic conditions, including Alzheimer’s disease, Parkinson’s disease, or epilepsy.
SAMe is generally well tolerated. Minor side effects include diarrhea, nausea, vomiting, dry mouth, constipation, mild insomnia, anxiety, and dizziness. Consult a physician or other healthcare provider before taking SAMe or any other antidepressant compounds. SAMe should not be taken with antidepressant medications. SAMe has been shown to amplify the positive and negative effects of steroids. It has also been reported to reduce the effectiveness of levodopa, a Parkinson’s disease medication.
References and Additional Reading
Bowling AC. Complementary and Alternative Medicine and Multiple Sclerosis. New York: Demos Medical Publishing, 2007, pp. 212-239.
Bowling AC, Stewart TS. Dietary Supplements and Multiple Sclerosis: A Health Professional’s Guide. New York: Demos Medical Publishing, 2004.
Fetrow CW, Avila JR. Professional’s Handbook of Complementary and Alternative Medicines. Philadelphia: Lippincott, Williams, & Wilkins, 2004.
Fragakis AS. The Health Professional’s Guide to Popular Dietary Supplements. The American Dietetic Association, 2003.
Jellin JM, Batz F, Hitchens K, et al. Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Faculty, 2006.
Polman CH, Thompson AJ, Murray TJ, Bowling AC, Noseworthy JH. Multiple Sclerosis: The Guide to Treatment and Management. New York: Demos Medical Publishing, 2006.
Ulbricht CE, Basch EM, eds. Natural Standard Herb and Supplement Reference: Evidence-Based Clinical Reviews. St. Louis: Elsevier-Mosby, 2005.
Anon. Spin the bottle. How to pick a multivitamin. Nutrition Action Healthletter 2003;Jan–Feb:3–9.
Anon. Multivitamins: what to avoid, how to choose. Cons Reports 2006;Feb:19–20. Mai J, Sorensen PS, Hansen JC. High dose antioxidant supplementation to MS patients. Biol Trace Elem Res 1990;24:109–117.
Platten M, Ho PP, Yousseff S, et al. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 2005;310:850–855.
Tomassini V, Pozzilli C, Onesti E, et al. Comparison of the effects of acetyl-L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomized, double-blind, crossover trial. J Neurol Sci2004;218:103–108.
Van Meeteren ME, Teunissen CE, Dijkstra CD, et al. Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr 2005;59:1347–1361.
Wingerchuk DM, Lesaux J, Rice GPA, et al. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psych 2005;76:1294–1296.
Yadav V, Marracci G, Lovera J, et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler 2005;11:159–165.
Zhang GX, Yu S, Gran B, et al. Glucosamine abrogates the acute phase of experimental autoimmune encephalomyelitis by induction of Th2 response. J Neuroimmunol 2005;175:7202–7208.