The Role of Diet in Multiple Sclerosis - Assignment Example

Introduction Multiple sclerosis (MS) is a disease characterized by chronic inflammation, demyelination, and gliosis. The exact mechanism of the disease is not known. Several hypotheses, including a viral infection, oxidative stress, and autoimmune destruction of myelin have been put forward. MS is also characterized by the presence of low polyunsaturated fatty acid (PUFA) in structural phospholipid and reduced serum linoleate level, which has lead to investigation of the role of dietary factors in MS. But a definite benefit from any particular diet has not yet been proven in MS. The role of minerals, trace elements, antioxidants, vitamins (D and B12) or fish oil is unclear. Role of dietary factors in MS An association between multiple sclerosis and nutrition has been made on the basis of available epidemiological data (Agnello & Palmo, 2004). A higher incidence of MS has been noted in populations with greater intake of foods of animal origin (meat and dairy products) (Agnello & Palmo, 2004). In particular, it has been hypothesised that saturated fatty acids has a role in the etiopathogenesis of myelin damage (Agnello & Palmo, 2004) Polyunsaturated fatty acids (PUFA) Studies in patients with acute and remittent forms of MS have shown a significant effect of treatment with PUFA in slowing down the disease progression (Agnello & Palmo, 2004;Stewart & Bowling, 2005). However, this has been observed only in patients with a slight or no initial degree of disability (Agnello & Palmo, 2004). These studies also point out to the probable association between the severity of the disease and consumption of saturated fats, with improvement in those treated with PUFA (Agnello & Palmo, 2004) In particular, omega-3 and omega-6 fatty acids may play a therapeutic role in MS (Stewart & Bowling, 2005). Supplementation with fish oil could possibly result “in a decrease in the production of the inflammatory cytokines interleukin (IL)-1b, tumour necrosis factor-a, IL-2 and interferon g”(Gallai et al., 1995.) Omega-3 PUFAs Omega-3 fatty acids include alphalinolenic acid (ALA), which is an essential fatty acid, and eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) (Stewart & Bowling, 2005). Fish is a good source of omega-3 fatty acids (Stewart & Bowling, 2005). Fish or fish products rich in omega-3 fatty acids include “salmon, Atlantic herring, Atlantic mackerel, bluefin tuna, sardine and cod liver”(Stewart & Bowling, 2005). Bates et al., 1977, performed a double-blind study with 268 patients of MS with chronic progressive disease. Patients were divided into 4 groups. The patients received either linoleic acid or a mixture of linoleic and linolenic acid. However, the results indicated that there was no alteration in the rate and severity of deterioration of the disease. Weinstock-Guttman et al., 2005, aimed to determine if a low fat diet supplemented with omega-3 could affect the quality of life (QOL) in patients with relapsing-remitting MS (RRMS). This was a double-blind, randomised trial, performed over a period of 1-year. Thirty-one patients were randomised to 2 groups: the "Fish Oil" (FO) group received a low fat diet (15% fat) with omega-3 FOs and the "Olive Oil" (OO) group received the AHA Step I diet (fat 30%) with OO supplements. The primary outcome was measured with the Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36), and other questionnaires. The results of the study indicated clinical benefits in the FO group at 6 months, and reduced fatigue with the OO diet at 6 months. Therefore, this study showed that “a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients on concurrent disease modifying therapies” (Weinstock-Guttman et al., 2005.) Nordvik et al., 2000, investigated if fish oil (0.9 g/day of long-chain marine fatty acids) and vitamin supplementation along with dietary advice could influence the clinical outcome in 16 newly diagnosed multiple sclerosis patients. They were followed-up for 2 years. The results indicated a “significant reduction in the mean annual exacerbation rate and the mean Expanded Disability Status Scale (EDSS) as compared to pre-study values”(Nordvik et al., 2000). In addition, there was an increase in plasma total phospholipid n-3 fatty acids and an increase in the n-6 fatty acids levels (Nordvik et al., 2000). The authors concluded that supplementation with fish oil and vitamins, along with dietary advice could improve the clinical outcome in newly diagnosed MS patients (Nordvik et al., 2000). Omega-6 PUFAs Examples of omega-6 fatty acids include linolenic acid (an essential fatty acid) and its metabolites, gammalinolenic acid (GLA) and arachadonic acid (Stewart & Bowling, 2005). Sources of linolenic acid include sunflower seed oil (70%), soybean oil, corn oil, walnut oil, wheat germ oil, grapeseed oil, safflower seed oil, and flaxseed oil (Stewart & Bowling, 2005). GLA is found in evening primrose oil (EPO), borage seed oil, blackcurrant seed oil and spirulina (Stewart & Bowling, 2005.) Millar et al., 1973, performed a double-blind trial in multiple sclerosis patients who received a vegetable oil mixture containing either linoleate or oleate, for a period of 2 years. It was found that the rates of relapses were less frequent, less severe, and of shorter duration in the group, which received linoleate supplementation than the oleate group. However, there was no clear evidence that this supplementation affected the overall rate of clinical deterioration (Millar et al., 1973) Role of vitamins and antioxidant supplementation Both multiple sclerosis and vitamin B12 deficiency have been found to “share common inflammatory and neurodegenerative pathophysiological characteristics”(Miller et al., 2005). In addition, it has also been found that patients with MS have low or decreased levels of vitamin B12 (Miller et al., 2005). Vitamin B12 has an important role not only as a co-factor in myelin formation, but also has important immunomodulatory and neurotrophic effects (Miller et al., 2005). Therefore, it has been suggested that a deficiency of vitamin B12 might have a role to play in the development of MS (Miller et al., 2005). This also suggests that monitoring vitamin B12 levels and supplementation of vitamin B12 might be explored in MS patients (Miller et al., 2005). There are not many studies, which have investigated vitamin B12 supplementation in MS. One study (Kira, Tobimatsu, Goto, 1994) administered a massive dose of methyl vitamin B12 (60 mg every day for 6 months) in 6 patients with chronic progressive MS. The visual and brainstem auditory evoked potentials improved with this regimen, although there was no improvement in the motor disability. The authors, therefore, concluded that a massive dose of methyl vitamin B12 might be an useful adjunct along with immunosuppressive treatment for chronic progressive MS (Kira, Tobimatsu, Goto, 1994) Vitamin D deficiency has also been implicated in autoimmune diseases including MS, and “might be an environmental factor that normally participates in the control of self-tolerance”(Margherita, Cantorna, Mahon, 2004). One study used vitamin D (cod liver oil: 5000 IU/day) plus calcium and magnesium for a period of 1 year in patients with MS without any control subjects (Margherita, Cantorna, Mahon, 2004). It was found that the rate of MS-related exacerbations decreased (Margherita, Cantorna, Mahon, 2004). Other studies have also reported benefits (Margherita, Cantorna, Mahon, 2004) but clear evidence is lacking (Margherita, Cantorna, Mahon, 2004). Since MS is a chronic inflammatory disease, it is an ideal environment for the generation of reactive oxygen species (Carlson & Rose, 2006). In human and animal models of MS, this generation of reactive oxygen species leads to the production of peroxynitrite and superoxide, which are highly toxic to cells (Carlson & Rose, 2006.) Low-molecular-weight antioxidants improve the cellular antioxidant defences by scavenging free radicals, interfering with gene transcription, protein expression, enzyme activity and by metal chelation (Van Meeteren et al., 2005) However, in spite of promising results in animal models, “there is limited and conflicting evidence of potential therapeutic effects of antioxidants such as vitamins C and E in treating MS”(Carlson & Rose, 2006). Nevertheless, studies with more potent antioxidants have been started in patients with MS (Carlson & Rose, 2006) Discussion An analysis of the various studies on dietary supplementation in multiple sclerosis shows that although a few studies have reported a moderate benefit (Weinstock-Guttman et al., 2005; Nordvik et al., 2000) with PUFA therapy, other studies (Bates et al., 1977;Millar et al., 1973) showed no change or clear evidence that PUFA could help. Vitamin B12, D and antioxidants have also been studied but there is no clear evidence that they have a benefit in MS. A critical analysis shows that most of the studies used very small sample sizes in their studies, except for Bates et al., 1977. A large sample size is needed to provide a representative group size and also enables to compare the efficacy of two or more treatment methods. Small numbers may have an impact on the power of statistical analysis (Polgar & Thomas, 2000). None of the studies made any mention about obtaining consent from the patient for the studies. Any clinical research has a potential of causing harm to the subjects, and ethical guidelines must always be followed (South African Medical Research council, 2001.) Well-designed randomised controlled trials (RCTs), confirming the same hypothesis, have, for many years, been recognized as providing the strongest level of evidence of the treatment effect of therapeutic interventions (Green & Byar, 1984). Most studies have not mentioned about a control group. Without a control group, it is not possible to assess if the effects observed were due to the treatment or due to other factors (Polgar & Thomas, 2000). Conclusion A few clinical trials have demonstrated beneficial effects of PUFA supplementation in MS patients. However, the evidence is not conclusive. Vitamin B12, D and antioxidants have also been investigated but there are only a few studies, and no definite conclusion can be reached on their benefits in MS. It is recommended that more research be conducted especially on the role of PUFA, since it has shown the most promise. More research is also needed on Vitamin B12, D and antioxidants in MS. Future research studies should also try to include a larger sample size, randomize studies, and include a control group in their studies. This will ensure better validation, accuracy and give a clearer outcome. References Agnello, E, Palmo, A (2004). The efficacy of dietetic intervention in multiple sclerosis. Minerva Gastroenterol Dietol. 50(4): 317-23. Bates, D, Fawcett, PR, Shaw, DA, Weightman, D (1977). Trial of polyunsaturated fatty acids in non-relapsing multiple sclerosis. Br Med J. 2(6092): 932–933. Carlson, NG, Rose, JW (2006). Antioxidants in multiple sclerosis: do they have a role in therapy? CNS Drugs. 20(6): 433-41. Gallai, V, Sarchielli, P, Trequattrini, A, Franceschini, M, Floridi, A, Firenze, C (1995). Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol 56: 143–153. Green, SB, Byar, DP (1984). Using observational data from registries to compare treatments: the fallacy of omnimetrics. Statistics in Medicine 3: 361–370. Kira, J, Tobimatsu, S, Goto, I (1994). Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis. Intern Med. 33(2): 82-6. Margherita, T, Cantorna, Mahon, BD (2004). Mounting Evidence for Vitamin D as an Environmental Factor Affecting Autoimmune Disease Prevalence. Experimental Biology and Medicine 229:1136-1142. Millar, JH, Zilkha, KJ, Langman, MJ, Wright, HP, Smith, AD, Belin, J, Thompson, RHS (1973). Double-blind trial of linoleate supplementation of the diet in multiple sclerosis. Br Med J. 1: 765–768. Miller, A, Korem, M, Almog, R, Galboiz, Y (2005). Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. Journal of the Neurological Sciences. 233(1-2): 93-97. Polgar, S, Thomas, SA (2000). Introduction to research in the health sciences.  4th ed. Edinburgh, Churchill Livingstone. Stewart, TM, Bowling, AC (2005). Polyunsaturated Fatty Acid Supplementation in MS. The International MS Journal. 12: 88–93. South African Medical Research council (2001). Ethics and human rights. Retrieved March 24, 2007 from, http://www.mrc.ac.za/ethics/ethicshuman.htm Van Meeteren, ME, Teunissen, CE, Dijkstra, CD, van Tol, EA (2005). Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr. 59(12): 1347-61. Weinstock-Guttman, B, Baier, M, Park, Y, Feichter, J, Lee-wen, P, Gallagher, E, Venkatraman, J, Meksawan, K, Deinehert, S, Pendergast, D, Awad, AB, Ramanathan, M, Munschauer, F, Rudick, R (2005). Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot Essent Fatty Acids. 73(5): 397-404. Read More