Wetenschappelijk onderzoek over de behandeling van Multiple Sclerose

Het protocol voor de behandeling Multiple Sclerose is op basis van wetenschappelijke publicaties ontwikkeld. Hierbij is gebruik gemaakt van hoog gekwalificerd recent onderzoek dat wordt gepubliceerd in de PubMed database. placebo controlled onderzoek, meta analyses en reviews hebben de voorkeur. Dit soort onderzoek valt onder Evidence Based Medicine.

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  1. Baranzini SE, Oksenberg JR, Hauser SL. J Rehabil Res Dev. 2002 Mar-Apr;39(2):201-9 New insights into the genetics of multiple sclerosis
    Tissue injury in multiple sclerosis (MS) results from an abnormal immune response to one or more myelin antigens that develop in genetically susceptible individuals after exposure to a causal agent that is yet undefined.

  • Compston A, Sawcer S. Curr Neurol Neurosci Rep. 2002 May;2(3):259-66. Genetic analysis of multiple sclerosis
    The increased recurrence risk within families indicates a role for genetic factors in the etiology of multiple sclerosis. Genes may influence susceptibility to the development of multiple sclerosis and the subsequent course of the disease. [Abstract]
  • Kidd PM. Altern Med Rev. 2001 Dec;6(6):540-66 Multiple sclerosis, an autoimmune inflammatory disease: prospects for its integrative management
    MS features autoimmune inflammatory attack against the myelin insulation of neurons. Thymus derived (T) cells sensitized against myelin self-antigens secrete tumor necrosis factor, cytokines, prostaglandins, and other inflammatory mediators that strip away the myelin and sometimes destroy the axons.[Article]
  • Dittel BN. Brain Behav Immun. 2008 May;22(4):421-30. CD4 T cells: Balancing the coming and going of autoimmune-mediated inflammation in the CNS

    In a T cell-mediated autoimmune response, such as in multiple sclerosis (MS), the CD4 T cell is thought to orchestrate and drive the immune response resulting in inflammation within the central nervous system (CNS).[Article]
  • oorzaken

  • Bagert BA. Curr Neurol Neurosci Rep. 2009 Sep;9(5):405-10. Epstein-Barr virus in multiple sclerosis

    Recent seroepidemiologic and pathologic evidence suggests that prior infection with Epstein-Barr virus (EBV) may be necessary for the development of multiple sclerosis (MS).[Abstract]
  • Farrell RA, Antony D, Wall GR, Clark DA, Fisniku L, Swanton J, Khaleeli Z, Schmierer K, Miller DH, Giovannoni G. Neurology. 2009 Jul 7;73(1):32-8. Humoral immune response to EBV in multiple sclerosis is associated with disease activity on MRI

    The correlation between elevated Epstein-Barr virus nuclear antigen 1 (EBNA-1) immunoglobulin G (IgG) and gadolinium-enhancing lesions suggests an association between Epstein-Barr virus (EBV) infection and multiple sclerosis (MS) disease activity.[Abstract]

  • Landtblom AM, Flodin U, Söderfeldt B, Wolfson C, Axelson O. Epidemiology. 1996 Jul;7(4):429-33 Organic solvents and multiple sclerosis: a synthesis of the current evidence

    Organic solvents and multiple sclerosis: a synthesis of the current evidence
    Our evaluation is consistent with the hypothesis that organic solvents may be a cause of multiple sclerosis[Abstract]
  • Riise T, Moen BE, Kyvik KR. Epidemiology. 2002 Nov;13(6):718-20. Organic solvents and the risk of multiple sclerosis

    These results are compatible with the hypothesis of organic solvents being a possible risk factor for MS.[Abstract]
  • Aminzadeh KK, Etminan M. J Public Health Dent. 2007 Winter;67(1):64-6. Dental amalgam and multiple sclerosis: a systematic review and meta-analysis

    The pooled OR for the risk of MS among amalgam users was consistent, with a slight, nonstatistically significant increase between amalgam use and risk of MS.[Abstract]
  • Prochazkova J, Sterzl I, Kucerova H, Bartova J, Stejskal VD. Neuro Endocrinol Lett. 2004 Jun;25(3):211-8. The beneficial effect of amalgam replacement on health in patients with autoimmunity

    Mercury-containing amalgam may be an important risk factor for patients with autoimmune diseases.[Abstract]
  • Yamout B, Itani S, Hourany R, Sibaii AM, Yaghi S. J Neurol Sci. 2009 Nov 3The effect of war stress on multiple sclerosis exacerbations and radiological disease activity

    Our study shows that exposure to war-related events is likely to lead to an increase in both clinical relapses and MRI disease activity in patients with MS.[Abstract]
  • Mitsonis CI, Potagas C, Zervas I, Sfagos K. Int J Neurosci. 2009;119(3):315-35 The effects of stressful life events on the course of multiple sclerosis: a review

    There is growing body of evidence that support an association between stressful life events and an increased risk for Multiple Sclerosis (MS) exacerbations.[Abstract]
  • Butcher J. N Z Med J. 1976 Jun 23;83(566):427-30 The distribution of multiple sclerosis in relation to the dairy industry and milk consumption

    This report emphasises the striking correlation between the world distribution of dairy production and consumption and the incidence of multiple sclerosis.[Abstract]
  • Lucchinetti CF, Brück W, Rodriguez M, Lassmann H. Brain Pathol. 1996 Jul;6(3):259-74 Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis

    Our data indicate, that the demyelinated plaques of multiple sclerosis may reflect a common pathological end point of a variety of different immunological mechanisms of myelin destruction in this disease[Abstract]
  • Vitamine D tekort

  • Edlich R, Mason SS, Chase ME, Fisher AL, Gubler K, Long WB 3rd, Newkirk AT. J Environ Pathol Toxicol Oncol. 2009;28(2):143-52 Revolutionary advances in the prevention of demyelinating diseases

    In general, the rate of MS increases with latitude. Clinical studies have pointed out that vitamin D deficiency may exacerbate the development of MS. Because vitamin D3 is an inhibitor of MS, providing supplemental D3 for individuals at risk for MS should be mandatory.[Abstract]
  • Niino M, Fukazawa T, Kikuchi S, Sasaki H. Curr Med Chem. 2008;15(5):499-505. Therapeutic potential of vitamin D for multiple sclerosis

    Multiple sclerosis (MS) is a major inflammatory and demyelinating disease of the central nervous system and has an increasing prevalence in populations residing at higher latitudes. This observation may indicate a protective effect of sunlight exposure, which is reduced at higher latitudes and may contribute to insufficient levels of vitamin D in the MS population[Abstract]
  • Hayes CE, Cantorna MT, DeLuca HF. Proc Soc Exp Biol Med. 1997 Oct;216(1):21-7. Vitamin D and multiple sclerosis

    Recently, it has been clearly demonstrated that exogenous 1,25-dihydroxyvitamin D3, the hormonal form of vitamin D3, can completely prevent experimental autoimmune encephalomyelitis (EAE), a widely accepted mouse model of human multiple sclerosis (MS).
    This theory can explain the striking geographic distribution of MS, which is nearly zero in equatorial regions and increases dramatically with latitude in both hemispheres. It can also explain two peculiar geographic anomalies, one in Switzerland with high MS rates at low altitudes and low MS rates at high altitudes, and one in Norway with a high MS prevalence inland and a lower MS prevalence along the coast. Ultraviolet (UV) light intensity is higher at high altitudes, resulting in a greater vitamin D3 synthetic rate, thereby accounting for low MS rates at higher altitudes. On the Norwegian coast, fish is consumed at high rates and fish oils are rich in vitamin D3.
    Although genetic traits certainly contribute to MS susceptibility, an environmental factor is also clearly involved.[Abstract]
  • Pierrot-Deseilligny C. J Neurol. 2009 Sep;256(9):1468-79 Clinical implications of a possible role of vitamin D in multiple sclerosis

    Hypovitaminosis D is currently one of the most studied environmental risk factors for multiple sclerosis (MS) and is potentially the most promising in terms of new clinical implications. Clinically, most MS patients have low serum levels of vitamin D and are in a state of insufficiency or even deficiency compared to the international norm, which has been established on a metabolic basis.
    In animal studies, vitamin D prevents and improves experimental autoimmune encephalomyelitis.[Article]
  • Smolders J, Peelen E, Thewissen M, Menheere P, Cohen Tervaert JW, Hupperts R, Damoiseaux J. Autoimmun Rev. 2009 Jun;8(7):621-6The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis

    A poor vitamin D status has been associated with several autoimmune diseases, including multiple sclerosis (MS).[Abstract]
  • Mark BL, Carson JA. J Am Diet Assoc. 2006 Mar;106(3):418-24Vitamin D and autoimmune disease–implications for practice from the multiple sclerosis literature

    Recent studies and commentaries link vitamin D with several autoimmune diseases, including multiple sclerosis (MS).
    Adequate vitamin D intake reduces inflammatory cytokines through control of gene expression, thus inadequate vitamin D intake is suggested as a mechanism that could contribute to inflammation and, consequently, development of MS.
    Poor vitamin D status has been associated with increased risk for development of MS, and patients with MS may suffer consequences of vitamin D deficiency, such as bone loss.[Abstract]
  • Hayes CE. Proc Nutr Soc. 2000 Nov;59(4):531-5. Vitamin D: a natural inhibitor of multiple sclerosis

    Inheriting genetic risk factors for multiple sclerosis (MS) is not sufficient to cause this demyelinating disease of the central nervous system; exposure to environmental risk factors is also required. MS may be preventable if these unidentified environmental factors can be avoided
    However, the clearest evidence that vitamin D may be a natural inhibitor of MS comes from experiments with experimental autoimmune encephalomyelitis (EAE), a model of MS. Treatment of mice with 1,25-(OH)2D3 completely inhibited EAE induction and progression.
    The hormone stimulated the synthesis of two anti-encephalitogenic cytokines, interleukin 4 and transforming growth factor beta-1, and influenced inflammatory cell trafficking or apoptosis.[Article]
  • VanAmerongen BM, Dijkstra CD, Lips P, Polman CH. Eur J Clin Nutr. 2004 Aug;58(8):1095-109 Multiple sclerosis and vitamin D: an update

    The prevalence of MS is highest where environmental supplies of vitamin D are lowest.[Article]
  • Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R. Mult Scler. 2008 Nov;14(9):1220- Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis

    Serum levels of 25(OH)D were associated with both relapse rate and disability in MS patients. These results are suggestive for a disease modulating effect of the serum concentrations of 25(OH)D on MS.[Abstract]
  • Gezondheidsraad September 2008 Naar een toereikende inname van vitamine D

    Vitamine D-tekort komt onder alle lagen van de bevolking voor[Article]
  • Smolders J, Damoiseaux J, Menheere P, Hupperts R. J Neuroimmunol. 2008 Feb;194(1-2):7-17 Vitamin D as an immune modulator in multiple sclerosis, a review

    The evidence obtained from these studies strongly supports a model in which vitamin D mediates a shift to a more anti-inflammatory immune response, and in particular to enhanced regulatory T cell functionality.[Abstract]
  • Vieth R. Am J Clin Nutr. 1999 May;69(5):842-56 Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety

    Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit.
    The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required.
    Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 µg (10000 IU)/d to attain [Article]
  • Vieth R. J Nutr. 2006 Apr;136(4):1117-22 Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards

    Exposure of skin to sunshine can safely provide an adult with vitamin D in an amount equivalent to an oral dose of 250 mcg/d.
    The incremental consumption of 1 mcg/d of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D ] by approximately 1 nmol/L (0.4 microg/L).
    Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L (200 microg/L).[Article]
  • Vieth R. J Bone Miner Res. 2007 Dec;22 Suppl 2:V64-8Vitamin D toxicity, policy, and science

    However, because sunshine can provide an adult with vitamin D in an amount equivalent to daily oral consumption of 250 mug (10,000 IU)/d, this is intuitively a safe dose.
    The incremental consumption of 1 mug (40 IU)/day of vitamin D(3) raises serum 25(OH)D by approximately 1 nM (0.4 ng/ml).[Article]
  • Hathcock JN, Shao A, Vieth R, Heaney R. Am J Clin Nutr. 2007 Jan;85(1):6-18. Risk assessment for vitamin D

    The present a risk assessment based on relevant, well-designed human clinical trials of vitamin D. Collectively, the absence of toxicity in trials conducted in healthy adults that used vitamin D dose > or = 250 microg/d (10,000 IU vitamin D3) supports the confident selection of this value as the UL.[Article]
  • 1. http://www.ajcn.org/cgi/content/full/85/1/6
    Kimball SM, Ursell MR, O’Connor P, Vieth R. Am J Clin Nutr. 2007 Sep;86(3):645-51 Safety of vitamin D3 in adults with multiple sclerosis

    In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D3: from 700 to 7000 microg/wk (from 28 000 to 280 000 IU/wk). Patients’ serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.[Article]
  • Mirshafiey A, Mohsenzadegan M. Immunopharmacol Immunotoxicol. 2009;31(1):13-29Antioxidant therapy in multiple sclerosis

    Reactive oxygen species (ROS) play an important role in various events underlying multiple sclerosis pathology. In the initial phase of lesion formation, ROS are known to mediate the transendothelial migration of monocytes and induce a dysfunction in the blood-brain barrier.[Abstract]
  • Schreibelt G, van Horssen J, van Rossum S, Dijkstra CD, Drukarch B, de Vries HE. Brain Res Rev. 2007 Dec;56(2):322-30Therapeutic potential and biological role of endogenous antioxidant enzymes in multiple sclerosis pathology

    We propose that antioxidants may inhibit the development and progression of MS lesions and may therefore represent an attractive therapeutic target for the treatment of MS and other oxidative stress-related neurological diseases[Abstract]
  • Ghafourifar P, Mousavizadeh K, Parihar MS, Nazarewicz RR, Parihar A, Zenebe WJ. Front Biosci. 2008 Jan. Mitochondria in multiple sclerosis

    Mitochondria are one of the main cellular sources of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and play a pivotal role in many neuro-pathological conditions. Mitochondrial dysfunction leading to excessive production of ROS and RNS plays a significant role in the pathogenesis of MS, particularly in loss of myelin/oligodendrocyte complex[Abstract]
  • Schreibelt G, Musters RJ, Reijerkerk A, de Groot LR, van der Pol SM, Hendrikx EM, Döpp ED, Dijkstra CD, Drukarch B, de Vries HE. J Immunol. 2006 Aug 15;177(4):2630-7. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity

    Reactive oxygen species (ROS) play an important role in various events underlying multiple sclerosis (MS) pathology.
    In conclusion, we show that LA has a protective effect on EAE development not only by affecting the migratory capacity of monocytes, but also by stabilization of the BBB, making LA an attractive therapeutic agent for the treatment of MS.[Article]
  • Mirshafiey A, Mohsenzadegan M. Immunopharmacol Immunotoxicol. 2009;31(1):13-29. Antioxidant therapy in multiple sclerosis

    Reactive oxygen species (ROS) play an important role in various events underlying multiple sclerosis pathology. In the initial phase of lesion formation, ROS are known to mediate the transendothelial migration of monocytes and induce a dysfunction in the blood-brain barrier
    Antioxidant therapy may therefore represent an attractive treatment of MS. Several studies have shown that antioxidant therapy is beneficial in vitro and in vivo in animal models for MS.[Abstract]
  • Salinthone S, Yadav V, Bourdette DN, Carr DW. Endocr Metab Immune Disord Drug Targets. 2008 Jun;8(2):132-42 Lipoic acid: a novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS

    LA reduces and recycles cellular antioxidants such as glutathione, and chelates zinc, copper and other transition metal ions in addition to heavy metals. LA can also act as a scavenger of reactive oxygen and nitrogen species.[Abstract]
  • Chaudhary P, Marracci GH, Bourdette DN. J Neuroimmunol. 2006 Jun;175(1-2):87-96. Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis

    Spinal cords from mice receiving LA had significantly reduced inflammation (decreased CD4 and CD11b staining) as compared to EAE mice that received saline. Overall, our data suggest that the anti-inflammatory effects of LA in EAE may be partly due to inhibition of ICAM-1 and VCAM-1 expression by central nervous system (CNS) endothelial cells.[Abstract]
  • Marracci GH, Marquardt WE, Strehlow A, McKeon GP, Gross J, Buck DC, Kozell LB, Bourdette DN. Biochem Biophys Res Commun. 2006 Jun 9;344(3):963-71 Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56(Lck)

    Lipoic acid is an antioxidant that suppresses and treats a model of multiple sclerosis, experimental autoimmune encephalomyelitis. We now demonstrate that treatment of human PBMC and T cell lines with LA downmodulated CD4 expression in a concentration-dependent manner.[Abstract]
  • Morini M, Roccatagliata L, Dell’Eva R, Pedemonte E, Furlan R, Minghelli S, Giunti D, Pfeffer U, Marchese M, Noonan D, Mancardi G, Albini A, Uccelli A. J Neuroimmunol. 2004 Mar;148(1-2):146-53 Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis

    Daily oral administration of alpha-LA, starting at the time of immunization, significantly prevented EAE progression as compared to control mice. This was associated with a reduction of CNS infiltrating T cells and macrophages as well as decreased demyelination.[Abstract]
  • Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D. Mult Scler. 2005 Apr;11(2):159-65 Lipoic acid in multiple sclerosis: a pilot study

    Thirty-seven MS subjects were randomly assigned to one of four groups: placebo, LA 600 mg twice a day, LA 1200 mg once a day and LA 1200 mg twice a day.
    We conclude that oral LA is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. LA may prove useful in treating MS by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.[Abstract]
  • B12

  • Kocer B, Engur S, Ak F, Yilmaz M. J Clin Neurosci. 2009 Mar;16(3):399-403. Serum vitamin B12, folate, and homocysteine levels and their association with clinical and electrophysiological parameters in multiple sclerosis

    Patients with multiple sclerosis (MS) may have low serum vitamin B12 and folate levels and high levels of homocysteine.
    Thus, we found a significant relationship between MS and vitamin B12 deficiency, and also demonstrated a relationship between vitamin B12 deficiency, VEP and posterior tibial SEP in MS.[Abstract]
  • Reynolds EH. J Neuroimmunol. 1992 Oct;40(2-3):225-30. Multiple sclerosis and vitamin B12 metabolism

    Multiple sclerosis (MS) is occasionally associated with vitamin B12 deficiency. Recent studies have shown an increased risk of macrocytosis, low serum and/or CSF vitamin B12 levels, raised plasma homocysteine and raised unsaturated R-binder capacity in MS.[Abstract]
  • Sandyk R, Awerbuch GI. Int J Neurosci. 1993 Jul-Aug;71(1-4):93-9. Vitamin B12 and its relationship to age of onset of multiple sclerosis

    Attention has been focused recently on the association between vitamin B12 metabolism and the pathogenesis of multiple sclerosis (MS). Several recent reports have documented vitamin B12 deficiency in patients with MS.
    In addition, since vitamin B12 is required for the formation of myelin and for immune mechanisms, we propose that its deficiency in MS is of critical pathogenetic significance.[Abstract]
  • Miller A, Korem M, Almog R, Galboiz Y. J Neurol Sci. 2005 Jun 15;233(1-2):93-7. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis

    Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics
    Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects[Abstract]
  • Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E; Heart Outcomes Prevention Evaluation 2 Investigators. Stroke. 2009 Apr;40(4):1365-72 Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial

    We analyzed stroke outcomes among participants of the Heart Outcomes Prevention Evaluation 2 (HOPE 2) trial that randomized 5522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12, or matching placebo, for 5 years.[Article]
  • van Rensburg SJ, Kotze MJ, Hon D, Haug P, Kuyler J, Hendricks M, Botha J, Potocnik FC, Matsha T, Erasmus RT. Metab Brain Dis. 2006 Sep;21(2-3):121-37. Iron and the folate-vitamin B12-methylation pathway in multiple sclerosis

    Some subjects with multiple sclerosis (MS) present with low blood iron parameters. Anecdotal reports and a single patient study suggest that iron supplementation may be beneficial in these subjects. Myelin is regenerated continually, but prerequisites for this process are iron and a functional folate-vitamin B12-methylation pathway.[Abstract]
  • Simopoulos AP. J Am Coll Nutr. 2002 Dec;21(6):495-505 Omega-3 fatty acids in inflammation and autoimmune diseases

    Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—are more biologically potent than -linolenic acid (ALA).
    There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.[Article]
  • Mehta LR, Dworkin RH, Schwid SR. Nat Clin Pract Neurol. 2009 Feb;5(2):82-92 Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis

    Considerable interest has been shown in the potential anti-inflammatory effects of polyunsaturated fatty acids (PUFAs) in multiple sclerosis (MS) and other autoimmune inflammatory disorders. Studies suggest a modest association between consumption of low levels of unsaturated fat and an increased incidence of MS.
    We propose that the potential role of PUFAs as disease-modifying, anti-inflammatory treatments for MS should be revisited in proof-of-concept trials that use accepted MRI outcome measures.[Article]
  • Liuzzi GM, Latronico T, Rossano R, Viggiani S, Fasano A, Riccio P. Neurochem Res. 2007 Dec;32(12):2184-93. Inhibitory effect of polyunsaturated fatty acids on MMP-9 release from microglial cells–implications for complementary multiple sclerosis treatment

    microglial cells–implications for complementary multiple sclerosis treatment
    Our results suggest that a low fat diet supplemented with omega-3 PUFA may become recommended for the well being of MS patients under therapy.[Abstract]
  • Swank RL, Dugan BB. Lancet. 1990 Jul 7;336(8706):37-9 Effect of low saturated fat diet in early and late cases of multiple sclerosis

    144 multiple sclerosis patients took a low-fat diet for 34 years. For each of three categories of neurological disability (minimum, moderate, severe) patients who adhered to the prescribed diet (less than or equal to 20 g fat/day) showed significantly less deterioration and much lower death rates than did those who consumed more fat than prescribed (greater than 20 g fat/day). The greatest benefit was seen in those with minimum disability at the start of the trial; in this group, when those who died from non-MS diseases were excluded from the analysis, 95% survived and remained physically active.[Abstract]
  • Schwarz S, Leweling H. Mult Scler. 2005 Feb;11(1):24-32 Multiple sclerosis and nutrition

    There is some evidence that a high intake of saturated fat increases the incidence of MS.[Abstract]
  • Mollao?lu M, Ustün E. J Clin Nurs. 2009 May;18(9):1231-8. Fatigue in multiple sclerosis patients

    Fatigue is the most common symptom and has the greatest effect on multiple sclerosis patients’ activities of daily living.[Abstract]
  • Shah A. Phys Med Rehabil Clin N Am. 2009 May;20(2):363-72. Fatigue in multiple sclerosis

    In summary, MS-related fatigue can be a severe problem causing interference with home and vocational activities[Abstract]
  • Johnson SL. J Neurosci Nurs. 2008 Apr;40(2):72-7. The concept of fatigue in multiple sclerosis

    Fatigue is one of the most common symptoms of multiple sclerosis (MS), and it can have a major impact on health-related quality of life. Therefore, it is imperative that healthcare practitioners regularly assess fatigue in their patients with MS[Abstract]
  • Kos D, Kerckhofs E, Nagels G, D’hooghe MB, Ilsbroukx S. Neurorehabil Neural Repair. 2008 Jan-Feb;22(1):91-100. Origin of fatigue in multiple sclerosis: review of the literature

    Primary fatigue may be the result of inflammation, demyelination, or axonal loss. A suggested functional cortical reorganization may result in a higher energy demand in certain brain areas, culminating in an increase of fatigue perception. Higher
    Fatigue may be secondary to sleep problems, which are frequently present in MS and in their turn result from urinary problems, spasms, pain, or anxiety.[Abstract]
  • Lebrun C, Alchaar H, Candito M, Bourg V, Chatel M. Mult Scler. 2006 Jun;12(3):321-4. Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue

    Deficiency of carnitine may play a role by reducing energy production through fatty acid oxidation and numerous MS therapies can induce fatigue syndrome.
    Treatment consisted of oral levocarnitine, 3-6 g daily. All patients achieved normal plasma carnitine levels. For 63% of patients treated with immunosuppressive or immunomodulatory therapies, oral levocarnitine adjunction decreased fatigue intensity, especially in patients treated with cyclophosphamide and interferon beta.[Abstract]
  • Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C. J Neurol Sci. 2004 Mar 15;218(1-2):103-8 Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial

    Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale (p = 0.039).
    The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue.[Abstract]
  • Giovannoni G, Heales SJ, Land JM, Thompson EJ. Mult Scler. 1998 Jun;4(3):212-6 The potential role of nitric oxide in multiple sclerosis

    Nitric oxide (.NO) and its reactive derivative peroxynitrite (ONOO-) have been implicated in the pathogenesis of multiple sclerosis (MS). They are cytotoxic to oligodendrocytes and neurones in culture by inhibiting the mitochondrial respiratory chain (complexes II/III and IV) and inhibiting certain key intracellular enzymes.[Abstract]
  • Heales SJ, Bolaños JP, Stewart VC, Brookes PS, Land JM, Clark JB. Biochim Biophys Acta. 1999 Feb 9;1410(2):215-28Nitric oxide, mitochondria and neurological disease

    Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, stroke and amyotrophic lateral sclerosis. There is also a growing body of evidence to implicate excessive or inappropriate generation of nitric oxide (NO) in these disorders. It is now well documented that NO and its toxic metabolite, peroxynitrite (ONOO-), can inhibit components of the mitochondrial respiratory chain leading, if damage is severe enough, to a cellular energy deficiency state.[Abstract]
  • Calabrese V, Scapagnini G, Ravagna A, Bella R, Butterfield DA, Calvani M, Pennisi G, Giuffrida Stella AM. Neurochem Res. 2003 Sep;28(9):1321-8 Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: evidence for a protective role of acetylcarnitine

    Our data sustain the hypothesis that nitrosative stress is a major consequence of NO produced in MS-affected CNS and implicate a possible important role for acetylcarnitine in protecting brain against nitrosative stress, which may underlie the pathogenesis of MS.[Abstract]
  • Referenties nog niet gebruikt in dit artikel

    Het onderstaande onderzoek is nog niet gebruikt in dit artikel.



    1. O’Gorman C1, Broadley SA. J Neurol. 2014 Sep;261(9):1677-83. doi: 10.1007/s00415-014-7397-5. Smoking and multiple sclerosis: evidence for latitudinal and temporal variation
      There is growing evidence for the role of smoking in the aetiology of multiple sclerosis. Smoking appeared to confer a greater risk to females living closer to the equator than to females at higher latitudes. The effect of cigarette smoke exposure on MS risk may not be fixed over time, but could be increasing. [Abstract]
    2. META

    3. Handel AE1, Williamson AJ, Disanto G, Dobson R, Giovannoni G, Ramagopalan SV. PLoS One. 2011 Jan 13;6(1):e16149. doi: 10.1371/journal.pone.0016149. Smoking and multiple sclerosis: an updated meta-analysis
      Our results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. [Article]
    4. META

    5. Hawkes CH1. Mult Scler. 2007 Jun;13(5):610-5. Epub 2007 Feb 16. Smoking is a risk factor for multiple sclerosis: a metanalysis
      Metanalysis of six informative studies show significantly elevated odds or rate ratios, ranging from 1.22 to 1.51, depending on the method of analysis, confirming that the risk of MS is increased for those who smoke prior to disease onset, as measured by commencement of symptoms. [Abstract]
    6. Voeding


    7. Jahromi SR1, Toghae M, Jahromi MJ, Aloosh M. Iran J Neurol. 2012;11(2):47-53. Dietary pattern and risk of multiple sclerosis
      Traditional pattern (high in low-fat dairy products, red meat, vegetable oil, onion, whole grain, soy, refined grains, organ meats, coffee, and legumes) was inversely related to the risk of MS. A similar inverse relationship was noted between MS risk and lacto-vegetarian (high in nuts, fruits, French fries, coffee, sweets and desserts, vegetables, and high-fat dairy products) and vegetarian (high in green leafy vegetables, hydrogenated fats, tomato, yellow vegetables, fruit juices, onion, and other vegetables) patterns. In contrast, the prevalence of MS was higher in those who had high animal fat dietary pattern (high in animal fats, potato, meat products, sugars, and hydrogenated fats and low in whole grains). [Article]
    8. REVIEW

    9. Riccio P1, Rossano R2. ASN Neuro. 2015 Feb 18;7(1). pii: 1759091414568185. doi: 10.1177/1759091414568185. Nutrition facts in multiple sclerosis
      The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. [Article]
    10. REVIEW

    11. von Geldern G1, Mowry EM. Nat Rev Neurol. 2012 Dec;8(12):678-89. doi: 10.1038/nrneurol.2012.194. The influence of nutritional factors on the prognosis of multiple sclerosis
      High vitamin D levels are probably protective against the development of MS, although the efficacy of vitamin D supplementation in slowing progression of MS remains to be established. The influence of polyunsaturated fatty acids (PUFAs) on the development and course of MS has also long been under investigation. Small clinical trials suggest a modest reduction in the severity and duration of relapses in patients with MS receiving PUFA supplements. Other nutritional factors have been evaluated for their effect on MS disease progression, including milk proteins, gluten, probiotics, antioxidants (uric acid, vitamins A, C and E, lipoic acid), polyphenols, Ginkgo biloba extracts and curcumin. [Abstract]
    12. REVIEW

    13. Konikowska K1, Regulska-Ilow B1. Postepy Hig Med Dosw (Online). 2014 Mar 27;68:325-33. doi: 10.5604/17322693.1095838. The role of diet in multiple sclerosis
      Moreover, research demonstrated a correlation between deficiency of omega-3, vitamin D, B12, antioxidant vitamins and folic acid in diet, and the development and exacerbation of symptoms of multiple sclerosis. [Abstract]
    14. REVIEW

    15. Schmitz K1, Barthelmes J1, Stolz L1, Beyer S1, Diehl O1, Tegeder I2 Pharmacol Ther. 2015 Apr;148:85-113. doi: 10.1016/j.pharmthera.2014.11.015. “Disease modifying nutricals” for multiple sclerosis
      The dietary amount and type of fat, probiotics and biologicals, salmon proteoglycans, phytoestrogens and protease inhibitor of soy, sodium chloride and trace elements, and fat soluble vitamins including D, A and E were all considered as disease-modifying nutraceuticals. Studies in experimental autoimmune encephalomyelitis mice suggest that poly-unsaturated fatty acids and their ‘inflammation-resolving’ metabolites and the gut microflora may reduce auto-aggressive immune cells and reduce progression or risk of relapse, and infection with whipworm eggs may positively change the gut-brain communication. [Abstract]
    16. Sears B1, Ricordi C. J Obes. 2011;2011. pii: 431985. doi: 10.1155/2011/431985. Anti-inflammatory nutrition as a pharmacological approach to treat obesity
      The purpose of this paper is to discuss the molecular targets that can be addressed by anti-inflammatory nutrition. These molecular targets range from reduction of proinflammatory eicosanoids to the modulation of features of the innate immune system, such as toll-like receptors and gene transcription factors. From knowledge of the impact of these dietary nutrients on these various molecular targets, it becomes possible to develop a general outline of an anti-inflammatory diet that can offer a unique synergism with more traditional pharmacological approaches in treating obesity and its associated comorbidities. [Article]

    17. . [Abstract]
    18. B12


    19. McCaddon A1. Biochimie. 2013 May;95(5):1066-76. doi: 10.1016/j.biochi.2012.11.017. Vitamin B12 in neurology and ageing; clinical and genetic aspects
      The classic neurological and psychiatric features associated with vitamin B12 deficiency have been well described and are the subject of many excellent review articles. Metabolic evidence of B12 deficiency is also reported in association with other neurodegenerative disorders including vascular dementia, Parkinson’s disease and multiple sclerosis. These conditions are all associated with chronic neuro-inflammation and oxidative stress. [Abstract]
    20. Vitamine D


    21. Duan S1, Lv Z2, Fan X1, Wang L1, Han F1, Wang H1, Bi S3. Neurosci Lett. 2014 Jun 6;570:108-13. doi: 10.1016/j.neulet.2014.04.021. Vitamin D status and the risk of multiple sclerosis: a systematic review and meta-analysi
      To sum up, low vitamin D levels are associated with an increased risk of MS. [Abstract]
    22. META

    23. James E1, Dobson R, Kuhle J, Baker D, Giovannoni G, Ramagopalan SV. Mult Scler. 2013 Oct;19(12):1571-9. doi: 10.1177/1352458513489756. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis
      In conclusion, although no significant association between high-dose vitamin D treatment and risk of MS relapses was found, the studies were limited by several methodological limitations. [Abstract]
    24. META

    25. Dobson R1, Giovannoni G, Ramagopalan S. J Neurol Neurosurg Psychiatry. 2013 Apr;84(4):427-32. doi: 10.1136/jnnp-2012-303934. The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude
      Month of birth has a significant effect on subsequent MS risk. This is likely to be due to ultraviolet light exposure and maternal vitamin D levels, as demonstrated by the relationship between risk and latitude. [Abstract]
    26. META

    27. Simpson S Jr1, Blizzard L, Otahal P, Van der Mei I, Taylor B. J Neurol Neurosurg Psychiatry. 2011 Oct;82(10):1132-41. doi: 10.1136/jnnp.2011.240432. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis
      This, the most comprehensive review of MS prevalence to date, has confirmed a statistically significant positive association between MS prevalence and latitude globally. Exceptions to the gradient in the Italian region and northern Scandinavia are likely a result of genetic and behavioural-cultural variations. [Abstract]
    28. META

    29. McKay KA1, Jahanfar S2, Duggan T1, Tkachuk S1, Tremlett H3. Neurotoxicology. 2016 Apr 1. pii: S0161-813X(16)30042-0. doi: 10.1016/j.neuro.2016.03.020. actors associated with onset, relapses or progression in multiple sclerosis: A systematic review
      Best evidence, which included one or more prospective studies, suggested that lower exposure to sunlight and/or lower serum vitamin D levels were associated with an increased risk of developing MS onset and subsequent relapses, but a similar quality of evidence was lacking for disease progression. [Abstract]
    30. REVIEW

    31. Lommers E1, Lecrompe L, Moonen G, Phan-Ba R, Belachew S Rev Med Liege. 2012 May-Jun;67(5-6):359-65. Vitamin D tweets light to genes in multiple sclerosis
      The relationship between sunlight exposure and the incidence of multiple sclerosis and the understanding of immunomodulatory effects of vitamin D triggered, in recent years, a broad range of investigations. Immunological studies performed in vitro and in vivo have demonstrated how tolerogenic vitamin D can be. Epidemiological studies confirmed an increased incidence of multiple sclerosis in vitamin D deficient subjects and signs of increased disease activity in such MS patients. [Abstract]
    32. REVIEW

    33. Faridar A1, Eskandari G, Sahraian MA, Minagar A, Azimi A. Acta Neurol Belg. 2012 Dec;112(4):327-33. doi: 10.1007/s13760-012-0108-z. Vitamin D and multiple sclerosis: a critical review and recommendations on treatment
      The results from several experimental and clinical studies indicate that vitamin D supplementation may ameliorate the inflammation during the relapse phase and attenuate disease progression. [Abstract]
    34. Gluten


    35. Casella G1, Bordo BM, Schalling R, Villanacci V, Salemme M, DI Bella C, Baldini V, Bassotti G. Minerva Gastroenterol Dietol. 2016 Apr 6. Neurological disorders and celiac disease
      Celiac Disease (CD) determins Neurologic Manifestations in 10% of all CD patients. We describe the most common clinical manifestations as Cerebellar Ataxia, Gluten Encephalopathy, Multiple Sclerosis, Peripheral Neuropathies, SensoriNeural Hearing Loss, Epilepsy, Headache, Depression, Cognitive Deficiencies and other less decribed clinical conditions. [Abstract]
    36. Darmflora


    37. Jangi S1, Gandhi R1, Cox LM1, Li N2, von Glehn F1, Yan R1, Patel B1, Mazzola MA1, Liu S1, Glanz BL1, Cook S1, Tankou S1, Stuart F1, Melo K1, Nejad P1, Smith K1, Topçuolu BD3, Holden J3, Kivisäkk P1, Chitnis T1, De Jager PL1, Quintana FJ1, Gerber GK2, Bry L2, Weiner HL1. Nat Commun. 2016 Jun 28;7:12015. doi: 10.1038/ncomms12015. Alterations of the human gut microbiome in multiple sclerosis
      he gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. [Article]
    38. Chen J1, Chia N2,3, Kalari KR1, Yao JZ2, Novotna M4,5, Soldan MM4, Luckey DH6, Marietta EV7, Jeraldo PR2, Chen X1, Weinshenker BG4, Rodriguez M4,6, Kantarci OH4, Nelson H2, Murray JA6,7, Mangalam AK6,8. Sci Rep. 2016 Jun 27;6:28484. doi: 10.1038/srep28484. Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls
      Multiple sclerosis (MS) is an immune-mediated disease, the etiology of which involves both genetic and environmental factors. The exact nature of the environmental factors responsible for predisposition to MS remains elusive; however, it’s hypothesized that gastrointestinal microbiota might play an important role in pathogenesis of MS. Detailed fecal microbiome analyses revealed that MS patients had distinct microbial community profile compared to healthy controls. We observed an increased abundance of Psuedomonas, Mycoplana, Haemophilus, Blautia, and Dorea genera in MS patients, whereas control group showed increased abundance of Parabacteroides, Adlercreutzia and Prevotella genera. Thus our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and further study is needed to better understand their role in the etiopathogenesis of MS. [Article]
    39. OTHER

    40. Yamamura T1. Brain Nerve. 2016 Jun;68(6):617-22. doi: 10.11477/mf.1416200450. Multiple Sclerosis and Commensal Gut Flora
      Studies using experimental auto immune encephalomyelitis (EAE), a rodent model for studying multiple sclerosis (MS), revealed that onset of MS may be triggered by dysbiosis in the gut. We recently revealed a significant reduction in certain clostridia strains, which probably function to induce regulatory T cells, in the gut microbiota of patients with MS. Results from this study should be consideved when designing strategies for the prevention and treatment of MS. [Abstract]
    41. REVIEW

    42. Choi HH1, Cho YS1. Clin Endosc. 2016 May;49(3):257-65. doi: 10.5946/ce.2015.117. Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives
      The high success rate and safety in the short term reported for recurrent Clostridium difficile infection has elevated FMT as an emerging treatment for a wide range of disorders, including Parkinson’s disease, fibromyalgia, chronic fatigue syndrome, myoclonus dystopia, multiple sclerosis, obesity, insulin resistance, metabolic syndrome, and autism. [Article]
    43. OTHER

    44. Cammarota G1, Pecere S, Ianiro G, Masucci L, Currò D. Dig Dis. 2016;34(3):279-85. doi: 10.1159/000443362. Principles of DNA-Based Gut Microbiota Assessment and Therapeutic Efficacy of Fecal Microbiota Transplantation in Gastrointestinal Diseases
      FMT has diffused to other areas where the alterations of the gut microbiota ecology (or dysbiosis) have been theorized to play a causative role, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), among several other extra-intestinal disorders (i.e. metabolic syndrome and obesity, multiple sclerosis, cardiovascular diseases). [Abstract]
    45. REVIEW

    46. Petra AI1, Panagiotidou S1, Hatziagelaki E2, Stewart JM1, Conti P3, Theoharides TC4. Clin Ther. 2015 May 1;37(5):984-95. doi: 10.1016/j.clinthera.2015.04.002. Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation
      Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. [Article]
    47. REVIEW

    48. Wekerle H1. Swiss Med Wkly. 2015 Oct 2;145:w14189. doi: 10.4414/smw.2015.14189. eCollection 2015. Nature plus nurture: the triggering of multiple sclerosis
      Recent clinical and experimental studies indicate that multiple sclerosis develops as consequence of a failed interplay between genetic (“nature”) and environmental (“nurture”) factors. A large number of risk genes favour an autoimmune response against the body’s own brain matter. New experimental data indicate that the actual trigger of this attack is however provided by an interaction of brain-specific immune cells with components of the regular commensal gut flora, the intestinal microbiota. This concept opens the way for new therapeutic approaches involving modulation of the microbiota by dietary or antibiotic regimens. [Article]
    49. REVIEW

    50. Maranduba CM1, De Castro SB2, de Souza GT1, Rossato C3, da Guia FC1, Valente MA4, Rettore JV1, Maranduba CP1, de Souza CM1, do Carmo AM5, Macedo GC6, Silva Fde S7. J Immunol Res. 2015;2015:931574. doi: 10.1155/2015/931574. Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis
      Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. [Article]
    51. REVIEW

    52. Catanzaro R1, Anzalone M, Calabrese F, Milazzo M, Capuana M, Italia A, Occhipinti S, Marotta F. Panminerva Med. 2015 Sep;57(3):127-43. Epub 2014 Nov 12. The gut microbiota and its correlations with the central nervous system disorders
      A mutual impact of gastrointestinal tract (GIT) and central nervous system (CNS) functions has been recognized since the mid-twentieth century. It is accepted that the so-called gut-brain axis provides a two-way homeostatic communication, through immunological, hormonal and neuronal signals. A dysfunction of this axis has been associated with the pathogenesis of some diseases both within and outside the GIT, that have shown an increase in incidence over the last decades. In this review we discuss recent studies showing that the potential microbiota-gut-brain dialogue is implicated in neurodegenerative diseases. [Abstract]
    53. Probiotica



    54. Fleming JO1, Isaak A, Lee JE, Luzzio CC, Carrithers MD, Cook TD, Field AS, Boland J, Fabry Z. Mult Scler. 2011 Jun;17(6):743-54. doi: 10.1177/1352458511398054. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study
      TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment. [Article]
    55. RCT

    56. Rosche B1, Wernecke KD, Ohlraun S, Dörr JM, Paul F. Trials. 2013 Apr 25;14:112. doi: 10.1186/1745-6215-14-112. Trichuris suis ova in relapsing-remitting multiple sclerosis and clinically isolated syndrome (TRIOMS): study protocol for a randomized controlled trial
      We anticipate that Trichuris suis ova will be well tolerated and more effective than the placebo in preventing new T2 and Gd+ lesions, as quantified by MRI. We also expect the Th1/Th17 proinflammatory response to shift towards the more anti-inflammatory Th2 response. This study has important clinical implications and will involve extensive research on the immunology of helminth therapy. [Article]
    57. Kurkuma


    58. Tegenge MA1, Rajbhandari L1, Shrestha S1, Mithal A1, Hosmane S1, Venkatesan A2. Exp Neurol. 2014 Mar;253:102-10. doi: 10.1016/j.expneurol.2013.12.016. Curcumin protects axons from degeneration in the setting of local neuroinflammation
      Overall, our platform provides mechanistic insights into local axon degeneration, identifies curcumin as a novel axon protectant in the setting of neuroinflammation, and allows for ready screening of axon protective drugs. [Abstract]
    59. REVIEW

    60. Xie L1, Li XK, Takahara S. Int Immunopharmacol. 2011 Mar;11(3):323-30. doi: 10.1016/j.intimp.2010.08.013. Curcumin has bright prospects for the treatment of multiple sclerosis
      Curcumin, a dietary spice from turmeric, has outstanding anti-inflammation and neuroprotective effects. Herein, we review key features of curcumin involved biology, pharmacology, and medicinal chemistry and discuss its potential relevance to pathophysiological progress of MS. [Abstract]
    61. OTHER

    62. Mohajeri M1, Sadeghizadeh M2, Najafi F3, Javan M4. Neuropharmacology. 2015 Dec;99:156-67. doi: 10.1016/j.neuropharm.2015.07.013. Polymerized nano-curcumin attenuates neurological symptoms in EAE model of multiple sclerosis through down regulation of inflammatory and oxidative processes and enhancing neuroprotection and myelin repair
      Our results demonstrated an efficient therapeutic effect of PNC as an anti-inflammatory and anti-oxidative stress agent, with significant effects on the EAE scores and myelin repair mechanisms. [Abstract]
    63. OTHER

    64. Lian YT1, Yang XF, Wang ZH, Yang Y, Yang Y, Shu YW, Cheng LX, Liu K. Phytother Res. 2013 Sep;27(9):1321-7. doi: 10.1002/ptr.4863. Curcumin serves as a human kv1.3 blocker to inhibit effector memory T lymphocyte activities
      Effector memory T cells (T(EM), CCR7⁻ CD45RO⁺ T lymphocyte) have been demonstrated to play a crucial role in the pathogenesis of T cell-mediated autoimmune diseases, such as multiple sclerosis (MS) or rheumatoid arthritis (RA). Our findings demonstrate that curcumin is able to inhibit proliferation and proinflammatory cytokine secretion of T(EM) cells probably through inhibition of hKv1.3 channels, which contributes to the potency of curcumin for the treatment of autoimmune diseases. This is probably one of pharmacological mechanisms of curcumin used to treat autoimmune diseases. [Abstract]
    65. Boswellia


    66. Sedighi B1, Pardakhty A2, Kamali H1, Shafiee K1, Hasani BN1. Iran J Neurol. 2014 Jul 4;13(3):149-53. Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis
      Cognitive impairment is one of the most crucial disorders among multiple sclerosis (MS) patients. Since MS is an inflammatory disease and Boswellia papyrifera has anti-inflammatory effects, the influence of B. papyrifera on cognitive impairment in MS patients has been investigated in the present study. B. papyrifera showed significant improvement in visuospatial memory, but had no effect on verbal memory and information processing speed. [Article]

    67. . [Abstract]

    68. . [Abstract]

    69. . [Abstract]

    70. . [Abstract]

    71. . [Abstract]


    1. Fatigue in progressive multiple sclerosis is associated with low levels of dehydroep

      BACKGROUND AND OBJECTIVE: Fatigue is one of the most limiting symptoms in multiple sclerosis (MS) and the mechanisms underlying its origin are poorly understood. Our aim was to test whether fatigue in MS is associated with endocrine markers. METHODS: We longitudinally studied 73 progressive MS patients. Fatigue was assessed at baseline and at 3, 6, 12 and 24 months using the Fatigue Severity Scale (FSS). Given the longitudinal design of our study, patients were labelled as sustained fatigued when FSS scores were >5.0 at all time points, and as non-fatigued when FSS scores were < or = 5.0 at all time points. Serum levels of dehydroepiandrosterone (DHEA), its sulphated conjugate (DHEAS) and cortisol were measured at each time point. RESULTS: Twenty-nine patients scored >5.0 in the FSS at all time points, and 9 patients (12.3%) scored 5.0 at all time points. Mean baseline levels of DHEAS and DHEA were lower in MS patients with sustained fatigue when compared to patients without fatigue (P = 0.01 and P = 0.03 respectively). Analysis of DHEAS and DHEA over time showed significantly lower hormone levels in patients with fatigue [F(1,31) = 6.14, P=0.019 for DHEAS; F(1,32) = 6.63, P=0.015 for DHEA]. CONCLUSIONS: Fatigue in progressive MS could be related to low serum levels of DHEA and DHEAS. Our results suggest that these hormones should be considered as biological markers of fatigue in MS patients and that hormone replacement may thus be tested as an option to treat fatigue in MS patients.
    2. Dehydroepiandrosterone response to the adrenocorticotropin test and the combined dexamethasone and corticotropin-releasing hormone test in patients with multiple sclerosis

      Basic and clinical research suggest that disturbed neuroendocrine function may be involved in the pathogenesis and course of autoimmune diseases including multiple sclerosis (MS). Dehydroepiandrosterone (DHEA) in this connection is of particular interest as it appears to have effects on the immune system. Moreover, DHEA levels are decreased in chronic inflammatory diseases. To further investigate the role of DHEA in MS, we administered the adrenocorticotropin (ACTH) stimulation test and the combined dexamethasone and corticotropin-releasing hormone (DEX-CRH) test to 24 patients with active MS (13 women, 11 men; age 39 +/- 2 years, mean +/- SEM; Expanded Disability Status Scale, EDSS score 4.4 +/- 0. 4, mean +/- SEM; 12 with acute relapse, 12 with chronic progression) and to 18 healthy controls matched for age and sex (8 women, 10 men; age 37 +/- 3 years). There were no statistically significant differences in the plasma cortisol response to ACTH between any groups. In the DEX-CRH test, plasma cortisol concentrations showed higher values before (DEX-pretreated) and after CRH stimulation in the MS patients than in the controls (AUC(cortisol) 738.3 +/- 154.5 vs. 295.7 +/- 55.8; p < 0.05), this finding was more pronounced in chronic progressive patients. DHEA concentrations were decreased in MS patients (AUC (DHEA) 14.4 +/- 1.6 vs. 23 +/- 2.4; p < 0.05) and cortisol/DHEA ratios were increased in the patients compared to the controls (p < 0.05). There was a positive correlation between the EDSS score and maximum cortisol/DHEA ratio (r = 0.45; p = 0.031). As with the hypothalamic-pituitary-adrenal axis system, our results suggest a dysfunction in the DHEA secretion in patients with MS.


    1. Increased plasma homocysteine levels in patients with multiple sclerosis and depression

      ABSTRACT: BACKGROUND: The aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists. METHODS: Plasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI). RESULTS: Hcy levels were significantly increased in MS patients compared to controls (13.5 +/- 4.7 mmol/l vs 8.5 +/- 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate. CONCLUSIONS: Moderately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding.
    2. Serum homocysteine levels in relation to clinical progression in MS

      BACKGROUND: Elevated homocysteine levels are associated with various neurodegenerative diseases and have even been identified as a risk factor for some of these. Homocysteine levels may be elevated in multiple sclerosis (MS) patients, but large studies are lacking and the relation with disease progression remains to be determined. Our aim was to study homocysteine levels in MS patients and controls, and the relation of homocysteine levels with clinical progression in MS. METHODS: Serum homocysteine levels were compared between MS subtypes (n=219) and controls (n=152). Homocysteine levels were associated with baseline and follow-up clinical severity scores. RESULTS: The results showed that serum homocysteine values were similar in MS patients and controls. Baseline scores on the Expanded Disability Status Scale were higher in patients with secondary progressive (SP) MS in the top compared to the bottom quartile of homocysteine levels (p=0.02). The baseline scores on the Multiple Sclerosis Functional Composite (MSFC) and Paced Auditory Serial Addition Test (PASAT), which measures cognitive functioning, were lower in SPMS patients in the top compared to the bottom quartile of homocysteine levels (MSFC: p=0.02, PASAT: p=0.02). High homocysteine levels were associated with a decline in PASAT scores during follow-up in primary progressive (PP) MS patients (p=0.009). CONCLUSIONS: Serum total homocysteine levels are associated with several measures of disease progression in MS, but are not elevated in MS patients compared to controls. The association of homocysteine levels with cognition in progressive MS patients raises the question whether homocysteine directly impacts MS or reflects a more general neurodegenerative process.
    3. Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis

      Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in various neurological diseases. Cognitive impairment occurs early in multiple sclerosis (MS). Conflicting data have been reported regarding plasma total homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive impairment in MS is not known. This study investigated whether plasma total homocysteine levels are increased in MS and if HHcy is associated with cognitive impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy age-matched controls. We used a neuropsychological test battery that included the Raven’s Coloured Progressive Matrices, the Visual Search Test, the Trail Making Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration, coexisting disease, smoking habit, and physical disability) and laboratory variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were evaluated for their ability to predict cognitive impairment. The mean tHcy was higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L, SD2.53; p < 0.001). Univariate analysis determined the following factors to be associated with cognitive impairment: higher age at observation, chronic progressive course of disease, longer disease duration,moderate or severe physical disability, and frequency of HHcy. With multivariate regression analysis, there remained a significant association only between frequency of HHcy and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are increased in MS and that HHcy is associated with cognitive impairment in this disease
    4. Plasma homocysteine levels in multiple sclerosis

      BACKGROUND: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. METHODS: We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). RESULTS: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) micromol/l) than in controls (10.1 (2.5) micromol/l; p<0.0001). However, there were no significant differences in homocysteine levels between the three clinical subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and folate were not different between patients with MS and controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide production, or plasma diene conjugate levels. CONCLUSIONS: Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B6, vitamin B12, or folate.
    5. Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid

      OBJECTIVE: The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. METHODS: We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (CSF) MMA and tHcy in 72 patients with MS and 23 controls. RESULTS: The mean plasma tHcy level was significantly increased in MS patients (11.6 micromol/L) compared with controls (7.4 micromol/L) (P = 0.002). Seven patients showed low serum vitamin B12 levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B12, serum MMA, mean corpuscular volume (MCV), haemoglobin concentration, CSF tHcy or CSF MMA between patients and healthy subjects. There were no correlations between CSF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum MMA, plasma tHcy, CSF Hcy or CSF MMA were not correlated to disability status, activity of disease, duration of disease or age. CONCLUSIONS: The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. Our findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other factors indicating vitamin B12 deficiency. Analysis of CSF MMA and CSF tHcy, which probably reflects the brain vitamin B12 status better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.


    1. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis

      We determined serum levels of ascorbic acid, betacarotene, retinol and alpha tocopherol and lipid peroxidation (as estimated by thiobarbituric acid reacting substances (TBARS) generation) in 24 multiple sclerosis (MS) patients and 24 healthy sex- and age-matched person as control. The levels of four antioxidant vitamins were significantly lower in MS patients compared to controls (p < 0.05). TBARS levels were significantly higher in the patients of MS compared to the controls (p = 0.001). In MS patients, the levels of beta-carotene, alpha tocopherol and ascorbic acid correlated significantly with each other (r2 = 0.689 - 0.779). It appeared that there was inverse correlation between the serum levels of ascorbic acid or beta-carotene, but not of alpha tocopherol or retinol, and TBARS levels in MS. The present study indicates that antioxidant vitamins (alpha tocopherol, beta-carotene, retinol and ascorbic acid) are decreased in sera of MS patients during an attack, and that this decrease may well be dependent on the increased oxidative burden as reflected by lipid peroxidation products. The role of antioxidant vitamin supplementation in prevention and/or treatment of MS remains to be explored.
    2. High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety, and absorption of selenium

      High-dose antioxidant supplementation has recently been recommended for multiple sclerosis (MS) patients. This study tests the clinical safety, the glutathione peroxidase (GSH-px) activity, and the absorption of selenium during such supplementation. Eighteen MS patients were given 6 tablets especially made for this study, equivalent to 6 mg sodium selenite, 2 g vitamin C, and 480 mg vitamin E a day for five wk. GSH-px, which was lower than in non-MS controls before the start of treatment, increased fivefold during 5 wk of treatment. Side effects were scarce. Ten MS patients were subjected to a 24-h selenium absorption study after ingestion of 2 active tablets, equivalent to 2 mg sodium selenite. Selenium, which was low initially, increased 24% during the first 3 h and then stabilized. It is concluded that the tested antioxidant treatment seems to be safe and that MS patients have low GSH-px, which may be increased by the tested antioxidant treatment.
    3. The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy

      Accumulating data indicate that oxidative stress (OS) plays a major role in the pathogenesis of multiple sclerosis (MS). Reactive oxygen species (ROS), leading to OS, generated in excess primarily by macrophages, have been implicated as mediators of demyelination and axonal damage in both MS and experimental autoimmune encephalomyelitis (EAE), its animal model. ROS cause damage to cardinal cellular components such as lipids, proteins and nucleic acids (e. g., RNA, DNA), resulting in cell death by necrosis or apoptosis. In addition, weakened cellular antioxidant defense systems in the central nervous system (CNS) in MS, and its vulnerability to ROS effects may increase damage. Thus, treatment with antioxidants might theoretically prevent propagation of tissue damage and improve both survival and neurological outcome. Indeed, several experimental studies have been performed to see whether dietary intake of several antioxidants prevents or reduces the progression of EAE. Although a few antioxidants showed some efficacy in these studies, little information is available on the effect of treatments with such compounds in patients with MS. Well-designed clinical studies using antioxidant intake, as well as investigations based on larger cohorts studied over a longer periods of time, are needed in order to assess whether antioxidant intake together with other conventional treatments, might be beneficial in treating MS
    4. Antioxidants and polyunsaturated fatty acids in multiple sclerosis

      Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Oligodendrocyte damage and subsequent axonal demyelination is a hallmark of this disease. Different pathomechanisms, for example, immune-mediated inflammation, oxidative stress and excitotoxicity, are involved in the immunopathology of MS. The risk of developing MS is associated with increased dietary intake of saturated fatty acids. Polyunsaturated fatty acid (PUFA) and antioxidant deficiencies along with decreased cellular antioxidant defence mechanisms have been observed in MS patients. Furthermore, antioxidant and PUFA treatment in experimental allergic encephalomyelitis, an animal model of MS, decreased the clinical signs of disease. Low-molecular-weight antioxidants may support cellular antioxidant defences in various ways, including radical scavenging, interfering with gene transcription, protein expression, enzyme activity and by metal chelation. PUFAs may not only exert immunosuppressive actions through their incorporation in immune cells but also may affect cell function within the CNS. Both dietary antioxidants and PUFAs have the potential to diminish disease symptoms by targeting specific pathomechanisms and supporting recovery in MS.