Allen Bowling, MD, PhD––Rocky Mountain MS Center, Denver, Colorado; Thomas Stewart, JD, MS, PA-C––Rocky Mountain MS Center, Denver, Colorado

Introduction
Although reliable general nutritional information sources, such as the well-known Food Pyramid, are relatively easy to find, it is not as easy to find reliable information regarding MS-specific strategies. Some sources, including some written by mainstream multiple sclerosis (MS) professionals, indicate that there is “no evidence” to suggest that dietary factors are relevant in treating MS. Other sources irresponsibly suggest that MS can effectively be cured by such strategies. Both views are overstated and unhelpful to people with MS.

At the Rocky Mountain MS Center, we have recently conducted a survey related to the use of diet and dietary supplements (“dietary strategies”) in the management of MS. Of the approximately 600 people who responded to our survey, a significant number of people were pursuing dietary strategies because of their MS. More than 10% of those surveyed, for example, were avoiding dairy products, saturated fats, or increasing their intake of vegetable oils. More than 25% had increased their consumption of fatty fish, seeds, and nuts. In addition, a majority of respondents were using at least one dietary supplement. Our survey on this subject continues. If you are interested in participating in the survey, or seeing more details on the subject, please visit www.ms-cam.org, click “Enter,” and then click on “Diet/Dietary Strategies” under the heading “Current Review and Survey.”

Because of the relatively high interest in dietary strategies, we have taken a fresh look at a number of published studies on the subject, some of which are quite old by most standards and some of which provide only relatively weak evidence. Based on this review, we have tried to develop some reasonable and generally safe practical suggestions for those who are interested in
dietary considerations and supplementation.

Current Research
For those who prefer to use only absolutely proven treatments, there’s no diet or supplement to use. For those interested in low-risk, possibly effective dietary strategies—and our recent survey indicates, that this includes the vast majority of people with MS—there may be a few options. It is important, however, to keep in mind that there are Food and Drug Administration (FDA)-approved treatments that have been proven effective. No diet or supplement is being recommended as a replacement for such proven therapies. For those who choose to consider dietary approaches to MS, such approaches should be used in addition to, rather than instead of, FDA-approved medications. Finally, it should be noted that the combination of dietary approaches and FDA-approved medications has received only limited study.

Possible Disease-Modifying Strategies
Disease-modifying strategies refer to strategies that might possibly make MS attacks less frequent or make disability due to MS less likely. Some possibly effective disease-modifying strategies, those that are best-supported by published literature, are described below.

Changing the Proportions of Various Dietary Fats
Probably the most thoroughly-studied dietary strategy relates to dietary fats. Understanding this strategy requires basic knowledge of different types of fat and the building blocks of fats, known as fatty acids. Saturated fats are those that are solid at room temperature, and are generally obtained from dairy and meat sources. Polyunsaturated fats, on the other hand, are liquid at room temperature. Some polyunsaturated fats, such as flaxseed oil and fish oil, are rich in omega-3 fatty acids, and others, such as corn oil or sunflower oil, are rich in omega-6 fatty acids.

Increasing Omega-3 Fatty Acids
The most suggestive studies relate to two kinds of omega-3 fatty acids known as EPA (eicosapentanoic acid) and DHA (docosahexanoic acid). Fish oil is a particularly rich source of EPA and DHA. Additional sources of these fatty acids will be described below.

In one well-designed study, people with MS taking omega-3 fatty acids in the form of fish oil had less disability progression than those taking a placebo (a “sugar pill” or “dummy pill”) (Bates et al.). Unfortunately, this difference was so small that it might have occurred due to chance alone. The benefit from fish oil supplementation was found in a second study as well, but this study is considered to be preliminary and too small to be conclusive (Weinstock-Guttman, Beier, & Feichter, 2003). It is important to note that, in this preliminary study, people were using FDA-approved injectable medications in addition to fish oil supplementation.

There is further suggestive evidence relating to omega-3 fatty acids as well. For example, people with MS who took 3 grams of fish oil experienced immune system changes that would theoretically be useful in people with MS (Gallai et al., 1995). There is also epidemiological evidence, or evidence based on the studies of populations, showing that MS is less common in countries where dietary intake of omega-3 fatty acids is relatively high.

Although no single study of omega-3 fatty acids conclusively demonstrates a favorable effect, the body of evidence, considered as a whole, is quite suggestive. In addition, there are a number of general health benefits possibly related to omega-3 fatty acid intake, such as better heart health and improved mood. Despite these benefits, the average American diet includes relatively small amounts of fatty acid.

“ The American Heart Association recommends that most Americans lower their saturated fat intake to less than 10% of total calories as a way to decrease the risk of heart disease. ”

Increased omega-3 fatty acid intake can increase the risk of bleeding in those with bleeding disorders and can deplete vitamin E. For this reason, those supplementing with fats rich in omega-3 fatty acids should modestly increase their vitamin E intake. It is important to note, that high doses of fish oil, probably greater than 10 grams, may increase blood sugar in susceptible people.

Increasing Omega-6 Fatty Acids
Another kind of fatty acid is the omega-6 fatty acid. This is found in widely-consumed cooking oils such as corn oil. Three older, small studies have examined whether supplementation with omega-6 fatty acids in the form of sunflower oil would be beneficial in MS (Bates, Fawcett, Shaw, & Weightman, 1978; Millar et al., 1973; Paty, 1983). The results of these studies were mixed. In two of the three studies, those supplementing with omega-6 fatty acids in the form of sunflower oil had less severe exacerbations than those taking a placebo. No effect on exacerbation frequency or disability progression, however, was observed in any of the studies.

Another study combined the results of the three studies described above (Dworkin, Bates, Millar, & Paty, 1984). This study, or re-analysis, raised the possibility that supplementation with sunflower oil (rich in omega-6 fatty acids) might help to slow disability progression, at least among those with little MS-related disability. The results of this kind of backward-looking study, however, are generally not as reliable as other clinical studies.

There is other evidence to consider as well. Both epidemiological evidence (studies comparing populations) and animal evidence suggest that diets rich in omega-6 fatty acids may be beneficial. The average American diet generally includes relatively high proportions of omega-6 fatty acids.

Indeed, some nutrition experts argue that the ratio of omega-6 to omega-3 fats is too high in the average American diet. Because fatty acids can deplete vitamin E, those increasing their intake of fats rich in omega-6 fatty acids should increase their intake of vitamin E by modest amounts.

Decreasing Saturated Fats
One long-term, but poorly designed study in people with MS suggests that decreasing saturated fat improves outcomes in MS (Swank & Dugan, 1990). This study, designed and carried out by Dr. Roy Swank, is usually provided as justification for the “Swank Diet,” a diet characterized primarily by low saturated fat intake.

There are also some epidemiological studies suggesting a decreased risk of MS in areas where people consume less saturated fat. No well-designed clinical trial, however, has considered whether decreasing dietary sources of saturated fat improves outcomes in MS. The American Heart Association recommends that most Americans lower their saturated fat intake to less than 10% of total calories as a way to decrease the risk of heart disease.

Increasing Vitamin D and Calcium
Vitamin D and calcium are critically important to prevent osteoporosis, which appears to be an under-diagnosed and undertreated condition among people with MS. The current recommendation for vitamin D levels for adults in the general population (the “AI” or “Adequate Intake”) is 200 IU per day. The upper limit (UL), which is the maximum amount not likely to pose any risk, is 2,000 IU. In amounts greater than 2,000 IU daily, v tamin D may cause nausea, vomiting, cramping, kidney problems, and high blood pressure. For calcium, the current recommendation for adults in the general population is 1,000 mg daily and the UL is 2,500 mg.

A number of facts also suggest a beneficial disease-modifying effect for vitamin D. For example, the incidence of MS seems to increase with latitude, or distance, from the equator. It is possible that this observation can be explained by the fact that sunlight or ultraviolet light exposure, which is important in determining vitamin D levels, also decreases with distance from the equator. In addition, according to one large survey, those who supplemented with vitamin D seemed less likely to develop MS than those who did not (Munger et al., 2004). Other interesting observations that weakly suggest a role for vitamin D in MS include the increased risk of MS among those who live in the Northern hemisphere and were born in May as compared with those born in November, and a report that people with MS tend to have more MS activity, as measured by magnetic resonance imaging (MRI), in the spring. It is possible that both of these observations can be explained in relation to vitamin D, which may be lower in the spring than in the fall for people living in the Northern hemisphere.

Vitamin D has never been studied among people with MS in a direct way. In one small study, cod liver oil, which contains vitamin D as well as omega-3 fatty acids and vitamin A, was given to ten people and a decrease in exacerbation rate was noted; this study however, did not include a control group and is too small to provide reliable results.

“Immune-stimulating” Supplements
MS is a disease that involves the immune system. It is generally thought that MS involves an immune system that is overactive in specific ways. For this reason, supplements that are known to stimulate the immune system may, theoretically, be harmful, especially in high doses or for extended periods of time. A partial list of immunestimulating supplements is provided in Table 1. None of these supplements has ever been carefully studied in MS to identify risks or benefits.

Table 1.

Alfalfa
Asian ginseng
Astragalus
Beta carotene
Cat’s claw
Coenzyme Q10
Echinacea
Garlic
Melatonin
Siberian ginseng
Vitamin A
Vitamin C
Vitamin E
Zinc

Conclusions
Based on the review above, the following strategies may be considered:
1. Increase intake of fats that are rich in omega- 3 fatty acids, which include EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and ALA (alpha-linolenic acid). Sources of omega-3 fatty acids include:
• Fatty fish (especially salmon,
Atlantic herring, Atlantic mackerel, bluefin tuna, sardine, and cod). Fatty fish are the richest sources of EPA and DHA. Some of the studies conducted among people with MS involved amounts of EPA and DHA that would be difficult to obtain from dietary sources alone. The American Heart Association recommends two servings of oily fish per week for healthy adults. The FDA, however, recommends that pregnant women, or women who may become pregnant, consume less than 12 ounces of fish, on average, per week due to concerns about mercury contamination.
• Oils from certain seeds and nuts (primarily flaxseed and walnut). The omega-3 fatty acid found in oils from seeds and nuts (ALA) is probably less potent than the form found in some fish (EPA and DHA). This, however, may be the best option for strict vegetarians.
• Supplements. Omega-3 fatty acids are widely available in supplement form under various labels. Sources of EPA and DHA include: fish oil, salmon oil, and cod liver oil. Sometimes labels simply say “EPA and DHA.” Sources of ALA (probably less potent and generally less studied than EPA and DHA) include flax seed oil and walnut oil. Sometimes labels will indicate “ALA.” (ALA in this case refers to alpha-linolenic acid, but sometimes ALA refers to a different supplement, not relevant here, alpha-lipoic acid.) Studies of EPA and DHA in MS have used between 1 and 3 grams obtained from between 3 and 10 grams of fish oil daily. The FDA has indicated that up to 3 grams of combined EPA and DHA is safe.

2. Maintain or modestly increase your intake of omega-6 fatty acids. Because the average American diet is relatively high in omega-6 fatty acids and low in omega-3 fatty acids, the single most reasonable strategy may be to increase omega-3 intake. Beyond that, and depending on your current diet, it may be reasonable to increase intake of omega-6 fatty acids, which are found abundantly in products like corn oil, sunflower oil, and soybean oil. Evening primrose oil contains a form of omega-6 fatty acid (gamma-linolenic acid, or “GLA”).

3. Decrease dietary sources of saturated fat.
Saturated fat is the fat that is found primarily in meat and dairy products. The American Heart Association recommends that fewer than 10% of total calories come from saturated fat.

4. If you increase the relative amounts of omega-3 and omega-6 fatty acid in your diet, it is important to supplement with modest amounts of vitamin E (100 IU daily). This may b obtained from a vitamin E supplement or a multi-vitamin.

5. Consider increasing vitamin D and calcium.
• Vitamin D: The AI (Adequate Intake is the daily dose that is thought to be sufficient to prevent disease) for vitamin D is 200 IU (or 5 mcg) and the Upper Limit (UL is the maximum dose that is not likely to pose any risks) is 2,000 IU (50 mcg). An ideal dose for people with MS is not known, but it may be reasonable to take 400 to 1,000 IU daily.
• Calcium: The AI for calcium is 1 g daily of elemental calcium. To determine how much elemental calcium is in supplements is sometimes difficult, so it is important to read the label carefully.

6. Exercise caution using high doses of supplements that may stimulate the immune system. Table 1 provides a partial list of relatively popular, potentially immune-stimulating supplements. Although it is possible that some of these supplements may be benign, or even offer some benefits, none have ever been carefully studied among people with MS to assess their safety.

References

Bates, D., Cartlidge, N. E., French, J. M., Jackson, M. J., Nightingale, S., Shaw, D. A., et al. (1989). A double blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, 52(1), 18-22.

Bates, D., Fawcett, P. R., Shaw, D. A., & Weightman, D. (1978). Polyunsaturated fatty acids in treatment of acute remitting multiple sclerosis. British Medical Journal, 2, 6149, 1390-1391.

Dworkin, R. H., Bates, D., Millar, J. H., & Paty, D. W. (1984). Linoleic acid and multiple sclerosis: A reanalysis of three double-blind trials. Neurology, 34(11), 1441- 1445.

Gallai, V., Sarchielli, P., Trequattrini, A., Franceschini, M., Floridi, A., Firenze, C., et al. (1995).
Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. Journal of Neuroimmunology, 56(2), 143-153.

Millar, J. H., Zilkha, K. J., Langman, M. J., Wright, H. P., Smith, A. D., Belin, J., et al. (1973). Double-blind trial of linoleate supplementation of the diet in multiple sclerosis. British Medical Journal, 1, 5856, 765-768.

Munger, K. L., Zhang, S. M., O’Reilly, E., Hernan, M. A., Olek, M. J., Willett, W. C., et al. (2004). Vitamin D intake and incidence of multiple sclerosis. Neurology, 62(1), 60-65.

Paty, D. W. (1983). Double blind trial of linoleic acid in multiple sclerosis. Archives of Neurology, 40(11), 693-694. Swank, R. L., & Dugan, B. B. (1990). Effect of low saturated fat diet in early and late cases of multiple sclerosis. Lancet, 336, 8706, 37-39.

Weinstock-Guttman, B., Baier, M., & Feichter, J. (2003). A randomized study of low-fat diet with omega-3 fatty acid supplementation in patients with relapsing-remitting multiple sclerosis. Neurology, 60S, A151.

MS-relevant complimentary and alternative medicine (CAM) Information:
• www.ms-cam.org––interactive
CAM Web site of Rocky Mountain MS Center.

• Bowling, A.C. (2001).
Alternative Medicine and
Multiple Sclerosis. New York: Demos Medical Publishing, 2001.

• Bowling, A. C., &
Stewart, T. M. (2003).
Current complementary and alternative therapies of multiple sclerosis.
Current Treatment Options in Neurology, 5, 55-68.

• Bowling, A. C., &
Stewart, T. M. (2004).
Dietary Supplements and Multiple Sclerosis: A Health Professional’s Guide,
New York: Demos Medical Publishing, 2004.

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