Essential Fatty Acids

Supplementation with essential fatty acids (EFAs) has proven beneficial in MS. EFAs compete with pro-inflammatory metabolic processes to decrease the synthesis of inflammatory mediators, in addition to suppressing B- and T-lymphocyte proliferation and decreasing antibody production. The two EFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in high concentrations in fatty fish such as cod, salmon, and mackerel. The combination of a low-fat diet and supplementation with omega-3 fatty acids was found to decrease fatigue in patients with MS and to decrease the relapse rate in the disease.31

Alpha-linolenic acid, an omega-3 fatty acid commonly found in Linum usitatissimum (flax), canola, and Glycine max (soy) beans, can be taken as a supplement, although this is considered a secondary choice by many clinicians since alpha-linolenic acid does not appear to be as therapeutically efficient as EPA and DHA supplementation. Studies have also found that treatment of microglial cultures with either omega-3 fatty acids or fish oil inhibits the production of the myelin toxin MMP-9,32 and that supplementation with omega-3 polyunsaturated fatty acids positively affects cytokines in MS patients. The latter study found a decrease in IL-1beta, TNF-alpha, IL-2, and IFN-gamma in association with such supplementation, and a diminished production of the pro-inflammatory eicosanoids prostaglandin E2 and leuko-triene B4.33

B Vitamins

Several vitamins have been shown to be present in suboptimal concentrations in patients with MS. Vitamin B12, which is important for myelin formation as well as for immunomodulatory activity, may be among these vitamins.34 Significantly lower serum levels of vitamin B12 have been found in persons in whom symptoms of MS appear before the age of 18 than in patients with symptoms of later onset.35 In addition to serum B12 deficiency, evidence also indicates decreased levels of red blood cell folate in patients with MS.36

However, at least one study, rather than finding overtly decreased levels of vitamin B12 in MS patients, found that the binding capacity for unsaturated vitamin B12 was significantly decreased in these patients as compared to controls and individuals with other neurologic disorders. When the scientists went on to provide massive supplemental doses of 60 mg daily of methylvitamin B12 for six months to a small group of patients with chronic progressive MS, the scientists found that abnormalities in visual and brainstem auditory evoked potentials improved more often during the therapy than in the period before supplementation.37 Researchers have suggested that vitamin B12 deficiency may make an individual more susceptible to immunologic or viral insults.

Antioxidants

ROS appear to play a role in the pathology of MS. Epigallocatechin-3-gallate (EGCG), a constituent of Camellia sinensis (green tea) known for its antioxidant activity, reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE) in mice when given at or after the onset of EAE in the animals, by limiting brain inflammation and reducing neuronal damage. EAE is the animal model used to study MS as this condition can be induced in laboratory animals. EAE is a demyelinating disease in which the myelin is damaged and exhibits similar clinical progression. EGCG also directly inhibited the formation of neurotoxic ROS in neurons.38 Curcumin, a constituent of Curcuma longa (turmeric) with potent antioxidant activity, is also known for its anti-inflammatory activity. Supplementation with curcumin in animal models of MS decreased the duration and severity of the disease by decreasing secretion of the pro-inflammatory cytokine IL-12 from monocytes and microglial cells resulting in decreased T-cell proliferation and Th1 differentiation.39

Another supplement with antioxidant properties is Ginkgo biloba (ginkgo) extract. When given at a dose of 240 mg per day to persons with MS, this was found to decrease fatigue and improve functionality over that of controls.40 Treatment of animal models of MS with the antioxidant supplement N-acetyl-L-cysteine (NAC) was also found to attenuate clinical

Figure 25-2. Olive oil.

disease, increase the concentrations of anti-inflammatory cytokines such as IL-10, and decrease both nitrite production and the Th1-cell secretion of IFN-gamma.41 Quercetin, a dietary fla-vonoid found in many plants and known for its anti-inflammatory and antioxidant activity, was found to attenuate EAE, and decrease IL-12-induced T-cell proliferation and Th1-cell differentiation.42 A further finding in MS has been that of low levels of the antioxidant nutrients beta-carotene, retinol, alpha-tocopherol, and ascorbic acid in serum or CSF.43

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