Multiple Sklerose und funktionelle Ernährungsmedizin

Zusammenfassung

Die Sichtweise auf die Krankheit Multiple Sklerose (MS) hat sich in den letzten Jahren verändert. Immer neue Erkenntnisse legen nahe, dass es sich um ein multikausales Krankheitsbild handelt. Das beeinflusst auch die Therapie: Teilkonzepte mit einseitigen Ansätzen können demzufolge nicht die gewünschten Erfolge bringen, wenn wichtige mögliche Ursachen außer Acht gelassen werden.

Die funktionelle Ernährungsmedizin, die im Beitrag bezüglich der MS vorgestellt wird, kann insbesondere in Kombination mit der Lebensstilmedizin und Schadstoffreduktion in einem Gesamtkonzept eine tragende Rolle spielen.

Abstract

The way of looking at multiple sclerosis (MS) has changed in recent years. New findings suggest a multi-causal clinical picture. This also influences the perspective in therapy: Therefore, partial concepts with one-sided approaches cannot achieve the desired results, if important possible causes are ignored.

Functional nutritional medicine, which is presented in the article on MS, can play a key role in an overall concept, especially in combination with lifestyle medicine and reduction of harmful substances.

Schlüsselwörter

Multiple Sklerose - funktionelle Ernährungsmedizin - Mikronährstoffe

Key words

Multiple sclerosis - functional nutritional medicine - micronutrients

• Weiterführende Literatur

• 1 Böhm U, Epple-Waigel I. Vegetarisch oder Vegan – aber richtig. Hilden: Becker Joest Volk Verlag; 2017
• 2 Böhm U. Zellschutz – Entgiftung – Prävention: Die gesundheitliche Bedeutung von Glutathion. Bremen: Uni-Med; 2013
• 3 Böhm U. Resveratrol in der funktionellen Ernährungsmedizin. Jürgen Hartmann Verlag; 2010
• 4 Böhm U. Alpha-Liponsäure. Freising: SUM-Verlag; 2014
• 5 Böhm U. Die Bedeutung von Vitamin K in der funktionellen Ernährungsmedizin. Freising: SUM-Verlag; 2016
• 6 Böhm U. Die funktionelle Ernährungsmedizin und der Magen-Darm-Trakt.

• Literatur

• 7 www.aerztezeitung.de/medizin/krankheiten/neuro-psychiatrische_krankheiten/multiple_sklerose/article/960411/multiple-sklerose-heute-viele-ms-kranke-gibt.html (Zugriff: 27.5.2019)
• 8 Andersen O. MS from preclinical findings to its lifetime course. https://neurophys.gu.se/english/departments/clinical_neuroscience_and_rehabilitation/neuroscience/ms/ms-from-preclinical-findings (Zugriff: 29.5.2019)
• 9 ClinicSpeak: when does MS actually begin?. https://multiple-sclerosis-research.org/2014/10/clinicspeak-when-does-ms-actually-begin (Zugriff: 29.5.2019)
• 10 Chaudhuri A. Multiple sclerosis is primarily a neurodegenerative disease. J Neural Transm (Vienna) 2013; 120 (10) 1463-1466
• 11 Stadelmann C. Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic Implications. Curr Opin Neurol 2011; 24 (03) 224-229
• 12 Correale J. et al. Mechanisms of neurodegeneration and axonal dysfunction in progressive multiple sclerosis. Biomedicines 2019; 7 (01) pii E14
• 13 Chitnis T, Weiner HL. CNS inflammation and neurodegeneration. J Clin Invest 2017; 127 (10) 3577-3587
• 14 Campbell G, Mahad D. Neurodegeneration in progressive multiple sclerosis. Cold Spring Harb Perspect Med. 2018 8. (10)
• 15 Campbell G, Mahad DJ. Mitochondrial dysfunction and axon degeneration in progressive multiple sclerosis. FEBS Lett 2018; 592 (07) 1113-1121
• 16 Campbell G. et al. Targeting mitochondria to protect axons in progressive MS. Neurosci Lett. 2019 pii: S0304–3940(19)30329–5
• 17 Koudriavtseva T, Mainero C. Neuroinflammation, neurodegeneration and regeneration in multiple sclerosis: intercorrelated manifestations of the immune response. Neural Regen Res 2016; 11 (11) 1727-1730
• 18 Campbell AW. Autoimmunity and the gut. Autoimmune Dis 2014; 2014: 152428
• 19 Mosca L. et al. HLA-DRB1*15 association with multiple sclerosis is confirmed in a multigenerational Italian family. Funct Neurol 2017; 32 (02) 83-88
• 20 Scholz EM. et al. Human leukocyte antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 present complementary peptide repertoires. Front Immunol. 2017 https://doi.org/10.3389/fimmu.2017.00984
• 21 Hollenbach JA, Oksenberg JR. The Immunogenetics of multiple sclerosis: A comprehensive review. J Autoimmun 2015; 64: 13-25
• 22 Sospedra M. et al. Redundancy in antigen-presenting function of the HLA-DR and -DQ molecules in the multiple sclerosis-associated HLA-DR2 haplotype1. J Immunol 2006; 176: 1951
• 23 Souren NY. et al. NA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis. Nature Communications. 2019
• 24 Andlauer TFM. et al. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation. Science Advances 2016; 2: e1501678
• 25 Huynh JL. et al. Epigenetic mechanisms in multiple sclerosis: Implications for pathogenesis and treatment. Lancet Neurol 2013; 12 (02) 195-206
• 26 Aslani S. et al. Epigenetic modifications and therapy in multiple sclerosis. Neuromolecular Med 2017; 19 (01) 11-23
• 27 Küçükali C. et al. Epigenetics of multiple sclerosis: an updated review. Neuromolecular Med 2015; 17 (02) 83-96
• 28 Rito Y. et al. Epigenetics in multiple sclerosis: Molecular mechanisms and dietary intervention. Cent Nerv Syst Agents Med Chem 2018; 18 (01) 8-15
• 29 Bagur MJ. et al. Influence of diet in multiple sclerosis: A systematic review. Adv Nutr 2017; 8 (03) 463-472
• 30 Riccio P, Rossano R. Nutrition facts in multiple sclerosis. ASN Neuro 2015; 7 (01) 1759091414568185
• 31 Armon-Omer A. et al. New insights on the nutrition status and antioxidant capacity in multiple sclerosis patients. Nutrients 2019; 11 (02) pii E427
• 32 Sedaghat F. et al. Mediterranean diet adherence and risk of multiple sclerosis: a case-control study. Asia Pac J Clin Nutr 2016; 25 (02) 377-384
• 33 Matveeva O. et al. Western lifestyle and immunopathology of multiple sclerosis. Ann N Y Acad Sci 2018; 1417 (01) 71-86
• 34 Bagheri M. et al. Several food items and multiple sclerosis: A case-control study in Ahvaz (Iran). Iran J Nurs Midwifery Res 2014; 19 (06) 659-665
• 35 Broomley L. et al. Impact of nutritional intake on function in people with mild-to-moderate multiple sclerosis. Int J MS Care 2019; 21 (01) 1-9
• 36 Hadgkiss EJ. et al. Health related quality of life outcomes at 1 and 5 years after a residential retreat promoting lifestyle modification for people with multiple sclerosis. Neurol Sci 2013; 34: 187-195
• 37 Ghardirian P. et al. Nutritional factors in the aetiology of multiple sclerosis: A case control study in Montreal, Canada. Int J Epidemiol 1998; 27: 845-852
• 38 Nordvik. et al. Effect of dietary advice and n-3-supplementaiton in newly diagnosed MS patients. Acta Neurol Scand 2000; 102: 143-149
• 39 Esmaeil Mousavi S. et al. Multiple sclerosis and air pollution exposure: Mechanisms toward brain autoimmunity. Med Hypotheses 2017; 100: 23-30
• 40 Bergamaschi R. et al. Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. Mult Scler. 2017
• 41 Jeanjean M. et al. Ozone, NO2 and PM10 are associated with the occurrence of multiple sclerosis relapses. Evidence from seasonal multi-pollutant analyses. Environ Res 2018; 163: 43-52
• 42 Esmaeil Mousavi S. et al. Multiple sclerosis and air pollution exposure: Mechanisms toward brain autoimmunity. Med Hypotheses 2017; 100: 23-30
• 43 Bergamaschi R. et al. Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. Mult Scler. 2017
• 44 Hedström AK. et al. Organic solvents and MS susceptibility Interaction with MS risk HLA genes. Neurology. 2018
• 45 Hedström AK. et al. Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk. Int J Epidemiol 2014; 43: 1791-1798
• 46 Pamphlett R, Kum Jew S. Age-related uptake of heavy metals in human spinal interneurons. PLoS One 2016; 11 (09) e0162260
• 47 Thany SH. et al. Neurotoxicity of pesticides: its relationship with neurodegenerative diseases. Med Sci (Paris) 2013; 29 (03) 273-278
• 48 Syburra. et al. Oxidative stress in patients with multiple sclerosis. WMJ 2000; 71: 112-115
• 49 Cross. et al. Peroxynitrite formation within the central nervous system in active multiple sclerosis. J Neuroimmunol 1988; 88: 45-56
• 50 Greco. et al. Cerebrospinal fluid isoprotane shows oxidativ stress in patients with mutliple sclerosis. Neurology 1999; 53: 1876-1879
• 51 Ohl K. et al. Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp Neurol 2016; 277: 58-67
• 52 Adamczyk B, Adamczyk-Sowa M. New insights into the role of oxidative stress mechanisms in the pathophysiology and treatment of multiple sclerosis. Oxid Med Cell Longev 2016; 1973834
• 53 Besler HT. et al. Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutritional Neuroscience 2003; 6: 189-196
• 54 Besler HT. et al. Serum levels of antioxidant vitamins and lipid peroxidation in multiple sclerosis. Nutritional Neuroscience 2002; 5: 215-220
• 55 Calabrese V. et al. Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res 2001; 26: 739-764
• 56 Schulz JB. et al. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem 2000; 267: 4904-4911
• 57 Chu F. et al. Gut microbiota in multiple sclerosis and experimental autoimmune encephalomyelitis: Current applications and future perspectives. Mediators Inflamm 2018; 2018: 8168717
• 58 Cekanaviciute E, Baranzini SE. et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. PNAS 2017; 114 (40) 10713-10718
• 59 Berer K, Wekerle H. et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. PNAS 2017; 114: 10719-10724
• 60 Haghikia A. et al. Role of fatty acids in multipe sclerosis: Therapeutic potential of propionic acid (P1.374). Neurology 2016; 86: 16 (Suppl.)
• 61 Ochoa-Reparaz J. et al. The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis. Ann Transl Med 2017; 5 (06) 145
• 62 Planas R, Sospedra M. et al. GDP-l-fucose synthase is a CD4 + T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis. Science Translational Medicine. 2018; 10: 462 eaat4301
• 63 Stüber C. et al. Iron in multiple sclerosis and its noninvasive imaging with quantitative susceptibility mapping. Int J Mol Sci 2016; 17 (01) 100
• 64 Ropele S. et al. Iron mapping in multiple sclerosis. Neuroimaging Clin N Am 2017; 27 (02) 335-342
• 65 Hametner S. et al. Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol 2013; 74 (06) 848-86159 Rossi S et al. Opposite roles of NMDA receptors in relapsing and primary progressive multiple sclerosis. PLoS One 2013; 8(6): e67357
• 66 Macrez R. et al. Mechanisms of glutamate toxicity in multiple sclerosis: biomarker and therapeutic opportunities. Lancet Neurology 2016; 15: 1089-1102
• 67 Liang P, Le W. Role of autophagy in the pathogenesis of multiple sclerosis. Neurosci Bull 2015; 31 (04) 435-44
• 68 Ykin H. et al. The therapeutic and pathogenic role of autophagy in autoimmune diseases. Front Immunol 2018; 9: 1512
• 69 Deckx N. et al. Neuroendocrine immunoregulation in multiple sclerosis. Clin Dev Immunol 2013; 705232
• 70 Burfeind KG. et al. Hypothalamic dysfunction and multiple sclerosis: Implications for fatigue and weight dysregulation. Curr Neurol Neurosci Rep 2016; 16 (11) 98
• 71 Akcali A. et al. Fatigue in multiple sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis?. Mult Scler Relat Disord 2017; 15: 37-41
• 72 Powell DJH. et al. Circadian cortisol and fatigue severity in relapsing-remitting multiple sclerosis. Psychoneuroendocrinology 2015; 56: 120-131
• 73 Malinova TS. et al. Serotonin: A mediator of the gut-brain axis in multiple sclerosis. Mult Scler 2018; 24 (09) 1144-1150
• 74 Dorszewska J. et al. Serotonin in neurological diseases. intechopen.com 2017
• 75 Bansi J. et al. Persons with secondary progressive and relapsing remitting multiple sclerosis reveal different responses of tryptophan metabolism to acute endurance exercise and training. Neuroimmunology 2018; 314: 101-105
• 76 Lovelace MD. et al. Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology 2017; 112 (Pt B) 373-388
• 77 Lim CK. et al. Kynurenine pathway metabolomics predicts and provides mechanistic insight into multiple sclerosis progression. Scientific Reports 2017; 7: 41473
• 78 www.dgn.org/images/red_leitlinien/LL_2012/pdf/030–050l_S2e_Multiple_Sklerose_Diagnostik_Therapie_2014–08_verlaengert.pdf (Zugriff: 29.5.2019)
• 79 https://onlinelibrary.wiley.com/doi/epdf/10.1111/ene.13536 (Zugriff: 29.5.2019)
• 80 Mirshafiey A, Mohsenzadegan M. Antioxidant therapy in multiple sclerosis. Immunopharmacol Immunotoxicol 2009; 31 (01) 13-29
• 81 Van Horssen J. et al. Radical changes in multiple sclerosis pathogenesis. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease 2011; 1812: 141-150
• 82 Khosravi-Largani M. et al. A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis. eNeurologicalSci 2018; 10: 37-44
• 83 May JM. Vitamin C transport and its role in the central nervous system. Subcell biochem 2012; 56: 85-103
• 84 Kocot J. et al. Does vitamin C influence neurodegenerative diseases and psychiatric disorders?. Nutrients 2017; 9 (07) 659
• 85 Moretti M. et al. Preventive and therapeutic potential of ascorbic acid in neurodegenerative diseases. CNS Neurosci Ther 2017; 23 (12) 921-929
• 86 Guo YE. et al. Vitamin C promotes oligodendrocytes generation and remyelination. Glia 2018; 66 (07) 1302-1316
• 87 Fetisova E. et al. Mitochondria-targeted antioxidants as a prospective therapeutic strategy for multiple sclerosis. Curr Med Chem 2017; 24 (19) 2086-2114
• 88 Miller E. et al. Advances in antioxidative therapy of multiple sclerosis. Curr Med Chem 2013; 20 (37) 4720-4730
• 89 Spain R. et al. Lipoic acid in secondary progressive MS: A randomized controlled pilot trial. Neurol Neuroimmunol Neuroinflamm 2017; 4 (05) e374
• 90 Loy BD. et al. Effects of lipoic acid on walking performance, gait, and balance in secondary progressive multiple sclerosis. Complement Ther Med 2018; 41: 169-174
• 91 Salinthone S. et al. Lipoic acid: A novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS. Endocr Metab Immune Disord Drug Targets 2008; 8 (02) 132-142
• 92 Dietrich M, Kohne Z. et al. Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model. J Neuroinflammation 2018; 15: 71
• 93 Seifar F. et al. α-lipoic acid, functional fatty acid, as a novel therapeutic alternative for central nervous system diseases: A review. Nutr Neurosci 2019; 22: 306-316
• 94 Khalili M. et al. Does lipoic acid consumption affect the cytokine profile in multiple sclerosis pPatients: A double-blind, placebo-controlled, randomized clinical trial. Neuroimmunomodulation 2014; 21 (06) 291-296
• 95 Khalili M. et al. Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: A randomized controlled clinical trial. Nutr Neurosci 2014; 17 (01) 16-20
• 96 Yadav V. et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler 2005; 11 (02) 159-165
• 97 Yadav V. et al. Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters. Mult Scler 2010; 16 (04) 387-397
• 98 Schreibelt G. et al. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J Immunol 2006; 177 (04) 2630-2637
• 99 Chaudhary P. et al. 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. J Neuroimmunol 2006; 175 (01/02) 87-96
• 100 Marracci GH. et al. Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res 2004; 78 (03) 362-370
• 101 Cruz R. et al. Glutathione in cognitive function and neurodegeneration. Rev Neurol 2003; 36 (09) 877-886
• 102 Carvalho AN. et al. Glutathione in multiple sclerosis: more than just an antioxidant?. Mult Scler 2014; 20 (11) 1425-1431
• 103 Ferreira B. et al. Glutathione in multiple sclerosis. Br J Biomed Sci 2013; 70 (02) 75-79
• 104 Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stressmediated neuronal death. Brain Res Brain Res Rev 1997; 25: 335-358
• 105 Mazzetti AP. et al. Glutathione transferases and neurodegenerative diseases. Neurochem Int 2015; 82: 10-18
• 106 Johnson WM. et al. Dysregulation of glutathione homeostasis in neurodegenerative diseases. Nutrients 2012; 4: 1399-1440
• 107 Moccia M. et al. Coenzyme Q10 supplementation reduces peripheral oxidative stress and inflammation in interferon-β1a-treated multiple sclerosis. Ther Adv Neurol Disord 2019; 18 (12) 1756286418819074
• 108 Sanoobar M. et al. Coenzyme Q10 supplementation ameliorates inflammatory markers in patients with multiple sclerosis: a double blind, placebo, controlled randomized clinical trial. Nutr Neurosci 2015; 18 (04) 169-176
• 109 Kahmann L. et al. Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals. Biogerontology 2006; 7 (05/06) 429-435
• 110 Prasad AS. Zinc: Role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care 2009; 12 (06) 646-652
• 111 Maes M. et al. Lower serum zincin chronic fatigue syndrome (CFS): Relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. J Affect Dis 2006; 90: 141-147
• 112 Nowak G. et al. Effect of zinc supplementation on antidepressant therapy in unipolar depression: A preliminary placebo-controlled study. Pol J Pharmacol 2003; 55: 1143-1147
• 113 Makropoulos V. et al. Selenium mediated inhibition of transcription factor NF-kB and HIV-1 LTR promotor activity. Arch Toxicol 1996; 70: 277-283
• 114 Coe S. et al. A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis. J Neurology Neurosurg Psychiatry. 2019
• 115 Theoharides TC. Luteolin as a therapeutic option for multiple sclerosis. J Neuroinflammation 2009; 6: 29
• 116 Hendriks JJA. et al. Flavonoids influence monocytic GTPase activity and are protective in experimental allergic encephalitis. J Exp Med 2004; 200 (12) 1667-1672
• 117 Aktas O. et al. Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J Immunol 2004; 173 (09) 5794-5800
• 118 Herges. et al. Neuroprotective effect of combination therapy of glatiramer acetate and epigallocatechin-3-gallate in neuroinflammation. PLoS One. 2011
• 119 Zhuang H. et al. Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann NY Acad Sci 2003; 993: 276-286
• 120 Araki T. et al. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 2004; 305: 1010-1013
• 121 Savaskan E. et al. Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity. Gerontology 2003; 49: 380-383
• 122 Parker JA. et al. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet 2005; 37: 349-350
• 123 Qureshi M. et al. Therapeutic potential of curcumin for multiple sclerosis. Neurol Sci 2018; 39 (02) 207-214
• 124 Ghanaatian N. et al. Curcumin as a therapeutic candidate for multiple sclerosis: Molecular mechanisms and targets. J Cell Physiol 2019; 234 (08) 12237-12248
• 125 Sedighi B. et al. Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis. Iran J Neurol 2014; 13 (03) 149-153
• 126 Shinto L. et al. Omega 3 fatty acid supplementation decreases matrix metalloproteinas 9 production in relapsing-remetting multiple sclerosis. Prostataglandins Leukot Essent Fatty Acids 2009; 80: 131-136
• 127 Shinto L. et al. The effects of omega-3 fatty acids on matrix metalloproteinase-9 production and cell migration in human immune cells: Implications for multiple sclerosis. Autoimmune Dis 2011; 2011: 134592
• 128 Ramirez-Ramirez V. et al. Efficacy of fish oil on serum of TNFa, IL-1b and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b. Oxid Med Cell Longev 2013; 709: 493
• 129 Harbige LS, Sharief MK. Polyunsaturated fatty acids in the pathogenesis and treatment of multiple sclerosis. Br J Nutr 2007; 98 (Suppl. 01) S46-53
• 130 Bjørnevik K. et al. Polyunsaturated fatty acids and the risk of multiple sclerosis. Mult Scler 2017; 23 (14) 1830-1838
• 131 Mousavi Nasl-Khameneh A. et al. Combination treatment of DHA and all-trans-retinoic acid ATRA inhibit IL-17 and RORyt gene expression in PBMCs of patients with relapsing-remitting multiple sclerosis. Neurol Res 2018; 40: 11-17
• 132 Kong-González M. et al. Polyunsaturated fatty acids for multiple sclerosis treatment: Scientific evidence. Medwave 2015; 15 (01) e6062
• 133 Chen S. et al. n-3 PUFA supplementation benefits microglial responses to myelin pathology. Scientific Reports 2014; 4: 7458
• 134 Siegert E. et al. The effect of omega-3 fatty acids on central nervous system remyelination in fat-1 mice. BMC Neurosci 2017; 18: 19
• 135 Nordvik I. et al. Effect of dietary advice and n-3- supplementation in newly diagnosed MS patients. Acta Neurol Scand 2000; 102: 143-149
• 136 van Meeteren ME. et al. Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr 2005; 59 (12) 1347-1361
• 137 Kouchaki E. et al. High-dose ω-3 fatty acid plus vitamin D3 supplementation affects clinical symptoms and metabolic status of patients with multiple sclerosis: A randomised controlled clinical trial. J Nutr 2018; 148: 1380-1386
• 138 Handunnetthi L. et al. Multiple sclerosis, vitamin D, and HLA-DRB1*15. Neurology 2010; 74 (23) 1905-1910
• 139 Nielsen NM. et al. Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study. Neurology 2017; 88 (01) 44-51
• 140 Kimball SM. et al. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 2007; 86: 645-651
• 141 Sotirchos ES. et al. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology. 2015
• 142 Matias-Gulu J. et al. Vitamin D and remyelination in multiple sclerosis. Neurologia 2018; 33 (03) 177-186
• 143 Linden J. et al. Inflammatory activity and vitamin D levels in an MS population treated with rituximab. Mult Scler J Exp Transl Clin 2019; 5 (01) 2055217319826598
• 144 Simpson Jr S. et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 2010; 68: 193-203
• 145 Simpson Jr S. et al. Sun exposure across the life course significantly modulates early multiple sclerosis clinical course. Front Neurol 2018; 9: 16
• 146 Häusler D, Weber MS. Vitamin D supplementation in central nervous system demyelinating disease – enough is enough. Int J Mol Sci 2019; 20: 218
• 147 Ramagopalan SV. et al. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann Neurol 2011; 70: 881-886
• 148 Muris AH. et al. A low vitamin D status at diagnosis is associated with an early conversion to secondary progressive multiple sclerosis. J Steroid Biochem Mol Biol 2016; 164: 254-257
• 149 Muris AH. et al. Immune regulatory effects of high dose vitamin D3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNbeta; the SOLARIUM study. J Neuroimmunol 2016; 300: 47-56
• 150 Munger KL. et al. 25-hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology 2017; 89 (15) 1578-1583
• 151 Munger KL. et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296 (23) 2832-2838
• 152 Munger KL. et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62 (01) 60-65
• 153 Kassandra L. et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296: 2832-2838
• 154 Burton JM. et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010; 74: 1852-1859
• 155 Pierrot-Deseilligny C, Souberbielle JC. Vitamin D and multiple sclerosis: An update. Mult Scler Relat Disord 2015; 14: 35-45
• 156 Smolders J. et al. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One. 2010
• 157 Soilu-Hänninen M. et al. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon ß-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2012; 83 (05) 565-571
• 158 Salzer J. et al. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012; 79 (21) 2140-2145
• 159 Ascherio A. et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurology 2014; 71 (03) 306-314
• 160 Mowry EM. et al. Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 2012; 72 (02) 234-240
• 161 Runia TF. et al. Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology 2012; 79 (03) 261-266
• 162 Cantorna MT. et al. Vitamin D and 1,25(OH)2 D regulation of T cells. Nutrients 2015; 7 (04) 3011-3021
• 163 Fawaz L. et al. Comparative effect of 25(OH)D3 and 1,25(OH)2D3 on Th17 cell differentiation. Clinical Immunology 2016; 166–167: 59-71
• 164 Mashayekhi F, Salehi Z. Administration of vitamin D3 induces CNPase and myelin oligodendrocyte glycoprotein expression in the cerebral cortex of the murine model of cuprizone-induced demyelination. Folia Neuropathologica 2016; 54 (03) 259-264
• 165 Sandberg L. et al. Vitamin D and axonal injury in multiple sclerosis. Mult Scler 2016; 22 (08) 1027-1031
• 166 Laursen JH. et al. Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab. Mult Scler Relat Disord 2016; 10: 169-173
• 167 Kampman MT. et al. Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: Exploratory outcomes from a double-blind randomised controlled trial. Mult Scler 2012; 18 (08) 1144-1151
• 168 Aivo J. et al. A randomised, double-blind, placebo-controlled trial with vitamin D3 in MS: Subgroup analysis of patients with baseline disease activity despite interferon treatment. Mult Scler Int. 2012
• 169 Nemazannikova N. et al. Is there a link between vitamin B and multiple sclerosis?. Med Chem 2018; 14 (02) 170-180
• 170 Wade DT. et al. A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the “Cari Loder regime”) in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry 2002; 73: 246-249
• 171 Naghashour M. et al. Update on riboflavin and multiple sclerosis: a systematic review. Iran J Basic Med Sci 2017; 20 (09) 958-966
• 172 Uwitonze AM, Razzaque MS. Role of magnesium in vitamin d-activation and function. J Am Osteopath Assoc 2018; 118: 181-189
• 173 Vetter T, Lohse MJ. Magnesium and the parathyroid. Curr Opin Nephrol Hypertens 2002; 11 (04) 403-410
• 174 Rodriguez-Ortiz M. et al. Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration. Nephrol Dial Transplant 2014; 29 (02) 282-289
• 175 Skripuletz T. et al. Pivotal role of choline metabolites in remyelination. Brain 2015; 138 (Pt 2) 398-413
• 176 Skripuletz T. et al. The choline pathway as a strategy to promote central nervous system (CNS) remyelination. Neural Regen Res 2015; 10 (09) 1369-1370
• 177 Morisette GN. „Results of the CaEAP Questionnaire“. Richland Center, Wisconsin: A. Keith Brewer Science Library; 1986
• 178 Lasemi R. et al. Vitamin K2 in multiple sclerosis patients. Wien Klin Wochenschr 2018; 2
• 179 Tankou SK. et al. Investigation of probiotics in multiple sclerosis. Mult Scler 2018; 24 (01) 58-63
• 180 Tankou SK. et al. A probiotic modulates the microbiome and immunity in multiple sclerosis. Ann Neurol 2018; 83 (06) 1147-1161
• 181 Liu Y. et al. Probiotics in autoimmune and inflammatory disorders. Nutrients 2018; 10 (10) 1537
• 182 www.mpkb.org (Zugriff: 29.5.2019)
• 183 Unmüssig E. Behandlung durch das Marshall Protocol. Chronische Borreliose, andere chronische Infektionsleiden und Autoimmunerkrankungen – Gemeinsame Infektionsursache?. Borreliose Wissen 22: 30-31
• 184 Milman N. What is the Marshall Protocol – and should we use it?. Scand J Infect Dis 2011; 43 (04) 319-320
• 185 Milman N. What is Marshall Protocol – and how can we use it?. Ugeskr Laeger 2010; 172 (24) 1852
• 186 www.protocole-coimbra.info/protocole-coimbra/le-protocole/ (Zugriff: 29.5.2019)
• 187 www.coimbraprotokoll.de (Zugriff: 29.5.2019)
• 188 https://lsms.info/index.php?id =185 (Zugriff: 29.5.2019)
• 189 www.vitamind.net/interviews/coimbra-ms-autoimmun/ (Zugriff: 29.5.2019)
• 190 Noack A. et al. Mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils. PNAS 2018; 115 (41) E9590-E9599
• 191 Morris G. et al. Leaky brain in neurological and psychiatric disorders: Drivers and consequences. Aust N Z J Psychiatry 2018; 52 (10) 924-948
• 192 Obrenovich MEM. Leaky gut, leaky brain?. Microorganisms 2018; 6 (04) pii E107
• 193 Ryu JK, McLarnon JG. A leaky blood–brain barrier, fibrinogen infiltration and microglial reactivity in inflamed Alzheimer’s disease brain. J Cell Mol Med 2009; 13 (9a) 2911-2925
• 194 Montagne A. et al. Blood-brain barrier breakdown in the aging human hippocampus. Neuron 2015; 85: 296-302
• 195 Obermeier B. et al. Development, maintenance and disruption of the blood-brain barrier. Nat Med 2013; 19 (12) 1584-1596
• 196 Sintzel MB. et al. Vitamin D and multiple sclerosis: A comprehensive review. Neurol Ther 2018; 7 (01) 59-85
• 197 Simpson SJ. et al. The role of vitamin D in multiple sclerosis: Biology and biochemistry, epidemiology and potential roles in treatment. Med Chem 2018; 14 (02) 129-143
• 198 Fitzgerald KC. et al. Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA Neurol 2015; 72 (12) 1458-1465
• 199 Ascherio A. et al. Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 2014; 71 (03) 306-314