Vitamin B₁₂ - physiologische ­Bedeutung und therapeutische Möglichkeiten

Zusammenfassung

Vitamin B_12, das in relevanten Mengen nur in Nahrungsmitteln tierischer Herkunft vorkommt, hat eine zentrale Bedeutung im Fett-, Protein- und Kohlenhydratstoffwechsel und beeinflusst die Funktion von Nukleinsäuren, Proteinen, Neurotransmittern und Wachstumsfaktoren. Neben einem manifesten Vitamin-B₁₂-Mangel kommt dem funktionellen Mangel im Alter und bei vielen Erkrankungen eine besondere Bedeutung zu. In diesen Fällen ist meistens eine hochdosierte Therapie angezeigt. Zudem kann bei neuropathischen und neurodegenerativen Erkrankungen, chronischen Entzündungen und insbesondere bei chronischen Schmerzen eine hochdosierte Therapie mit Cobalamin-Analoga indiziert sein. Wegen der begrenzten Absorption von Cobalamin nach oraler Exposition sind für eine gute Wirksamkeit oft auch parenterale Applikationen über einen längeren Zeitraum erforderlich.

Abstract

Vitamin B₁₂, which is present in relevant amounts only in food of animal origin, is of central importance in the lipid, protein, and carbohydrate metabolism, and influences the function of nucleic acids, proteins, neurotransmitters, and growth factors. In addition to an apparent vitamin B₁₂ deficiency, a functional deficiency is of great importance in old age and in the case of many diseases. In most of these cases a highly dosed therapy is appropriate. Besides, in the case of neuropathic and neurodegenerative diseases, chronic inflammations, and especially in the case of chronic pain, a highly dosed therapy with cobalamin analogs can be indicated. Due to the limited absorption of cobalamin after oral exposure, often also parenteral applications are necessary for an extended period, to achieve a good effectiveness.

Schlüsselwörter

Vitamin B₁₂ - funktioneller Mangel - Hochdosistherapie - Schmerzen - neurologische Erkrankungen

Keywords

Vitamin B₁₂ - functional deficiency - high-dosage therapy - pain - neurologic diseases

• Literatur

• 1 Almeida OP, McCaul K, Hankey GJ et al. Homocysteine and depression in later life. Archives of General Psychiatry 2008; 65: 1286-1294
• 2 Almeida OP, Ford AH, Flicker L. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. International psychogeriatrics 2015; 27 (5): 727-37
• 3 Ames BN, Elson-Schwab I, Silver EA. High dose vitamin therapy stimulates variant enzymes with decreased coenzyme binding affinity: relevance to genetic disease and polymorphisms. Am J Clin Nutr 2002; 75: 616-58
• 4 Bailey LB. Folate and vitamin B12 recommended intakes and status in the United States. Nutr Rev 2004; 62: 14-20
• 5 Bor MV, von Ca, Kauwell GP et al. Daily intake of 4 to 7 µg dietary vitamin B12 is associated with steady concentrations of vitamin B12-related biomarkers in a healthy young population. Am J Clin Nutr 2010; 91: 571-577
• 6 Bottiglieri T, Godfrey P, Flynn T et al. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 1990; 53 (12): 1096-1098
• 7 Bryan J, Calvaresi E, Hughes D. Short-term folate, vitamin B12 or vitamin B6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr 2002; 132 (6): 1345-1356
• 8 Devathasan G, Mylvaganam A. Methylcobalamin in chronic diabetic neuropathy. A double-blind clinical and electrophysiological study. Clin Trials J 1986; 23: 130-140
• 9 Dharmarajan TS, Adiga GU, Norkus EP et al. Vitamin B12 deficiency. Recognizing subtle symptoms in older adults. Geriatrics 2003; 58 (3): 30-38
• 10 Dierkes J, Domröse U, Ambrosch A et al. Supplementation with vitamin B12 decreases homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease. Metabolism 1999; 48: 631-635
• 11 Dongre YU, Swami OC. Sustained-release Pregabalin with methylcobalamin in neuropathic pain: an Indian real-life experience. International Journal of General Medicine 2013; 6: 413-417
• 12 Eckert M, Schejbal P. Therapie von Neuropathien mit einer Vitamin-B-Kombination. Symptomatische Behandlung von schmerzhaften Erkrankungen des peripheren Nervensystems mit einem Kombinationspräparat aus Thiamin, Pyridoxin und Cyanocobalamin. Fortschritte der Medizin 1992; 110 (29): 544-8
• 13 Hashimoto S, Kohsaka M, Morita N et al. Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans. Neurosci Lett 1996; 220: 129-132
• 14 Honma K, Honma S, Kohsaka M et al. Does Methylcobalamin increase the light sensitivity of human circadian clock?. The Japanese Journal of Psychiatry and Neurology 1991; 4 (1): 171-172
• 15 Hvas AM, Ellegaard J, Nexø E. Increased plasma methylmalonic acid level does not predict clinical manifestation of vitamin B12 deficiency. Arch Intern Med 2001; 161: 1534-1541
• 16 Ide H, Fujiya S, Asanuma Y et al. Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy. Clin Ther 1987; 2: 183-192
• 17 Imai T et al. A Phase II/III study of ultra-high dose Methylcobalamin in amyotrophic lateral sclerosis (ALS) patients. Abstract. Japanese Society of Neurology Meeting 2015; N-03-5
• 18 Ito Y, Yamadera H, Ito R et al. Effects of vitamin B12 in bright light on cognitive and sleep-wake rhythm in Alzheimer-type dementia. Psychiatry Clin Neurosci 2001; 55 (3): 281-282
• 19 Kaji R, Kodama M, Imamura A et al. Effect of ultra-high-dose Methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study. Muscle Nerve 1998; 21: 1775-8
• 20 Kaji R, Kuzuhara S, Iwasaki Y et al. Ultra-high dose Methylcobalamin (E0302) prolongs survival of ALS: Report of 7 years ‘randomised double-blind, Phase III clinical trial.” Abstract. American Academy of Neurology Meeting 2015; P7.060
• 21 Kira J, Tobimatsu S, Goto I et al. Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis. Intern Med: 1994
• 22 Kräutler B. Vitamin B12: chemistry and biochemistry. Biochem Soc Trans 2005; 33: 806-810
• 23 Kuwabara S, Nakazawa R, Azuma N et al. Intravenous Methylcobalamin Treatment for Uremic and Diabetic Neuropathy in Chronic Hemodialysis patients. Internal Medicine 1999; 38 (6): 472-475
• 24 Levine J, Stahl Z, Sela BA et al. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry 2006; 265-269
• 25 Loew D. Pharmakokinetik der Cobalamine: Cyano-, Hydroxo-, Methylcobalamin. In: Rietbrock N, (Hrsg.) Pharmakologie und klinische Anwendung hochdosierter B-Vitamine. Darmstadt: Steinkopff; 1991
• 26 Magana-Villa MC, Rocha-González HI, Fernández del Valle-Laisequilla C et al. B-vitamin mixture improves the analgesic effect of Diclofenac in patients with osteoarthritis: a double blind study. Drug research 2013; 63: 289-92
• 27 Martin DC, Francis J, Protetch J et al. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc 1992; 40: 168-172
• 28 Mastronardi FG, Min W, Wang H et al. Attenuation of experimental autoimmune encephalomyelitis and non-immune demyelination by IFN-beta plus vitamin B12: treatment to modify notch-1/sonic hedgehog balance. Journal of immunology 2004; 172 (10): 6418-26
• 29 Medina-Santillán R, Pérez-Flores E, Mateos-García E et al. A B-vitamin mixture reduces the requirements of Diclofenac after tonsillectomy: a double-blind study. Drug Dev Res 2006; 66: 36-39
• 30 Mibielli MA, Geller M, Cohen JC et al. Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study. Current medical research and opinion 2009; 25 (11): 2589-99
• 31 Pérez-Flores E, Medina-Santillán R, Reyes-García G et al. Combination of diclofenac plus B vitamins in acute pain after tonsillectomy: a pilot study. Proceedings of the Western Pharmacology Society 2003; 46: 88-90
• 32 Ponce-Monter HA, Ortiz MI, Garza-Hernández AF et al. Effect of diclofenac with B vitamins on the treatment of acute pain originated by lower-limb fracture and surgery. Pain research and treatment 2012; p 104782
• 33 Prabhoo R, Panghate A, Dewda RP et al. Efficacy and tolerability of a fixed dose combination of methylcobalamin and Pregabalin in the management of painful neuropathy. N Am J Med Sci 2012; 4 (11): 605-07
• 34 Scalabrino G, Veber D, De Giuseppe R et al. Low level of cobalamin, epidermal growth factor, and normal prions in multiple sclerosis spinal cord. Neuroscience 2015; 298: 293-301
• 35 Skarupski KA, Tangney C, Li H et al. Longitudinal association of vitamin B6, folate, and vitamin B12 with depressive symptoms among older adults over time. Am J Clin Nutr 2010; 92: 330-335
• 36 Solomon LR. Functional cobalamin (vitamin B12) deficiency: role of advanced age and disorders associated with increased oxidative stress. European journal of clinical nutrition 2015; 69 (6): 687-692
• 37 Stabler SP, Allen RH, Savage DG et al. Clinical spectrum and diagnosis of cobalamin deficiency. Blood 1990; 76: 871-88
• 38 Takao I, Yamadera H, Ito R et al. Effects of vitamin B12 on bright light on cognitive and sleep wake rhythm in Alzheimer type dementia. Psychiatr and Clinical Neuroscience 2001; 55: 281-282
• 39 Talaei A, Siavash M, Majidi H et al. Vitamin B12 may be more effective than Nortriptylin in improving painful diabetic neuropathy. International Journal of Food Sciences and Nutrition 2009; 60 (S5): 71-76
• 40 Van As, Pasman JW, van Lier HJ et al. Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons. J Gerontol A Biol Sci Med Sci 2001; 56: 775-779
• 41 Yamane K, Usui T, Yamamoto T et al. Clinical efficacy of intravenous plus oral Mecobalamin in patients with peripheral neuropathy using vibration perception thresholds as an indicator of improvement. Curr Ther Res Clin Exp 1995; 56: 656-670