Vitamin-B₁₂-Mangel im Alter: Ursachen und Konsequenzen

Zusammenfassung

Die Bedeutung des Mangels an Vitamin B₁₂ (Cobalamin) wird vielfach unterschätzt. Vitamin-B₁₂-Mangel lässt sich am zuverlässigsten durch Bestimmung von Methylmalonylsäure (MMA) bzw. Homozystein (HCY) im Plasma oder Serum erfassen. Mit der alleinigen Bestimmung von Vitamin B₁₂ im Serum kann ein klinisch relevanter Vitamin-B₁₂-Mangel nicht sicher diagnostiziert werden. Nach neueren, gründlichen Laboranalysen ist anzunehmen, dass 50 - 60 % der Senioren, die älter als 65 Jahre sind, Zeichen eines Vitamin-B₁₂-Mangels aufweisen. Eine wesentliche Ursache dieser Problematik ist die atrophische Gastritis, die gerade im Alter häufig auftritt. Die klinische Bedeutung dieses Ergebnisses wird betont durch die Tatsache, dass Vitamin-B₁₂-Mangel ein unabhängiger Risikofaktor für kardiovaskuläre Erkrankungen und thromboembolische Ereignisse darstellt und M. Alzheimer bzw. senile Demenz verursachen oder verschlimmern kann. Hämatologische Symptome (makrozytäre Anämie, Panzytopenie) treten nur bei etwa 1/3 der Menschen mit Vitamin-B₁₂-Mangel auf. Die Notwendigkeit einer frühzeitigen Diagnostik wird verdeutlicht durch die Tatsache, dass gerade die neuropsychiatrischen Symptome nach Vitamin-B₁₂-Substitution zunächst häufig reversibel sind. Die Substitution von Cobalamin kann parenteral (bei gastrointestinalen Begleiterkrankungen zu bevorzugen) oder oral erfolgen. Die applizierten Dosen (gerade im Fall oraler Substitution) und die Effektivität der Substitution sollten kontrolliert werden.

Abstract

The clinical relevance of vitamin B₁₂ (cobalamin) deficiency is often underestimated. Vitamin B₁₂ deficiency can be confirmed most reliably by the measurement of methylmalonic acid (MMA) and homocysteine (HCY) in plasma or serum. However, clinically relevant vitamin B₁₂ deficiency cannot be confirmed merely by quantification of vitamin B₁₂ in the serum. According to recent carefully performed laboratory studies 50 - 60 % of the elderly (> 65 years of age) have signs of vitamin B₁₂ deficiency. A major cause of this observation is atrophic gastritis the prevalence of which is high in elderly people. The clinical relevance of such results is emphasized by the fact that vitamin B₁₂ deficiency is an independent risk factor for cardiovascular diseases and thromboembolic events, and it can induce or aggravate neurological diseases such as Alzheimer disease or senile dementia. Haematological disorders (macrocytosis, anaemia, pancytopenia) occur in only ⅓ of persons with vitamin B₁₂ deficiency. The necessity of an early diagnosis becomes clear by the fact that particularly the neurological symptoms arc reversible in many non-advanced cases. Both parenteral (in patients with gastrointestinal diseases preferred) and oral substitution of cobalamin is possible. The doses administered (particularly the oral doses) and the effectiveness of the substitution should be controlled.

Literatur

• 1 Buddecke E. Grundriss der Biochemie. Berlin; Walter de Gruyter 1980: 398
• 2 Pietrzik K, Hages M. Vitamin B₁₂ (Cobalamin). In: Biesalski HK, Schrezenmeir J, Weber P, Weiß H (eds) Vitamine. Stuttgart; Thieme 1997: 96-103
• 3 Matthews D M, Linnell J C. Cobalamin deficiency and related disorders in infancy and childhood.  Eur J Pediatr. 1982;  138 6-16
• 4 Rosenberg I H, Miller J W. Nutritional factors in physical and cognitive functions of elderly people.  Am J Clin Nutr. 1992;  55 (Suppl 6) 1237S-1243S
• 5 van Asselt D Z, de Groot L C, van Staveren W A, Blom H J, Wevers R A, Biemond I, Hoefnagels W H. Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects.  Am J Clin Nutr. 1998;  68 328-334
• 6 Dahele A, Gosh S. Vitamin B₁₂ deficiency in untreated celiac disease.  Am J Gastroenterol. 2001;  96 745-750
• 7 Baik H W, Russell R M. Vitamin B₁₂ deficiency in the elderly.  Annu Rev Nutr. 1999;  19 357-377
• 8 Norman E J, Morrison J A. Screening elderly populations for cobalamin (vitamin B₁₂) deficiency using the urinary methylmalonic acid assay by gas chromatography mass spectrometry.  Am J Med. 1993;  94 589-594
• 9 Crystal H A, Ortof E, Frishman W H, Gruber A, Hershman D, Aronson M. Serum vitamin B₁₂ levels and incidence of dementia in a healthy elderly population: a report from the Bronx Longitudinal Aging Study.  J Am Geriatr Soc. 1994;  42 933-936
• 10 Naurath H J, Joosten E, Riezler R, Stabler S P, Allen R H, Lindenbaum J. Effects of vitamin B₁₂, folate, and vitamin B₆ supplements in elderly people with normal serum vitamin concentrations.  Lancet. 1995;  346 85-89
• 11 Aimone-Gastin I, Pierson H, Jeandel C, Bronowicki J P, Plenat F, Lambert D, Nabet-Belleville F, Gueant J L. Prospective evaluation of protein bound vitamin B₁₂ (cobalamin) malabsorption in the elderly using trout flesh labelled in vivo with 57 Co-cobalamin.  Gut. 1997;  41 475-479
• 12 Björkegren K, Svärdsudd K. Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B₁₂ and folate tissue deficiency markers amongst elderly Swedes - a population-based study.  J Intern Med. 2001;  249 423-432
• 13 Shahar A, Feiglin L, Shahar D R, Levy S, Seligsohn U. High prevalence and impact of subnormal serum vitamin B₁₂ levels in Israeli elders admitted to a geriatric hospital.  J Nutr Health Aging. 2001;  5 124-127
• 14 Herrmann W. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview.  Clin Chem Lab Med. 2001;  39 666-674
• 15 Carmel R. Pernicious anemia. The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking.  Arch Intern Med. 1988;  148 1712-1714
• 16 Lindenbaum J, Healton E B, Savage D G, Brust J C, Garrett T J, Podell E R, Marcell P D, Allen R H. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis.  N Engl J Med. 1988;  318 1720-1728
• 17 Bottiglieri T, Hyland K. S-adenosylmethionine levels in psychiatric and neurological disorders: a review.  Acta Neurol Scand Suppl. 1994;  154 19-26
• 18 Weir D G, Scott J M. Brain function in the elderly: role of vitamin B₁₂ and folate.  Br Med Bull. 1999;  55 669-682
• 19 Gonzalez-Gross M, Marcos A, Pietrzik K. Nutrition and cognitive impairment in the elderly.  Br J Nutr. 2001;  86 313-321
• 20 Joosten E, van den Berg A, Riezler R, Naurath H J, Lindenbaum J, Stabler S P, Allen R H. Metabolic evidence that deficiencies of vitamin B₁₂ (cobalamin), folate, and vitamin B₆ occur commonly in elderly people.  Am J Clin Nutr. 1993;  58 468-476
• 21 Savage D G, Lindenbaum J, Stabler S P, Allen R H. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies.  Am J Med. 1994;  96 239-246
• 22 Stabler S P, Lindenbaum J, Allen R H. Vitamin B₁₂ deficiency in the elderly: current dilemmas.  Am J Clin Nutr. 1997;  66 741-749
• 23 Herrmann W, Schorr H, Bodis M, Knapp J P, Muller A, Stein G, Geisel J. Role of homocysteine, cystathionine and methylmalonic acid measurement for diagnosis of vitamin deficiency in high-aged subjects.  Eur J Clin Invest. 2000;  30 1083-1089
• 24 Klee G G. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B₁₂ and folate.  Clin Chem. 2000;  46 1277-1283
• 25 Herrmann W, Quast S, Ullrich M, Schultze H, Bodis M, Geisel J. Hyperhomocysteinemia in high-aged subjects: relation of B-vitamins, folic acid, renal function and the methylenetetrahydrofolate reductase mutation.  Atherosclerosis. 1999;  144 91-101
• 26 Marcucci R, Prisco D, Brunelli T, Pepe G, Gori A M, Fedi S, Capanni M, Simonetti I, Federici G, Pastore A, Abbate R, Gensini G F. Tissue factor and homocysteine levels in ischemic heart disease are associated with angiographically documented clinical recurrences after coronary angioplasty.  Thromb Haemost. 2000;  83 826-832
• 27 Rasmussen K. Studies on methylmalonic acid in humans. I. Concentrations in serum and urinary excretion in normal subjects after feeding and during fasting, and after loading with protein, fat, sugar, isoleucine, and valine.  Clin Chem. 1989;  35 2271-2276
• 28 Rasmussen K, Moelby L, Jensen M K. Studies on methylmalonic acid in humans. II. Relationship between concentrations in serum and urinary excretion, and the correlation between serum cobalamin and accumulation of methylmalonic acid.  Clin Chem. 1989;  35 2277-2280
• 29 Welch G N, Loscalzo J. Homocysteine and atherothrombosis.  N Engl J Med. 1998;  338 1042-1050
• 30 Hankey G J, Eikelboom J W. Homocysteine and vascular disease.  Lancet. 1999;  354 407-413
• 31 Clarke R, Stansbie D. Assessment of homocysteine as a cardiovascular risk factor in clinical practice.  Ann Clin Biochem. 2001;  38 624-632
• 32 Mauro G L, Martorana U, Cataldo P, Brancato G, Letizia C. Vitamin B₁₂ in low back pain: a randomized, double-blind, placebo-controlled study.  Eur Rev Med Pharmacol Sci. 2000;  4 53-58
• 33 Nilsson K, Gustafson L, Hultberg B. Improvement of cognitive functions after cobalamin/folate supplementation in elderly patients with dementia and elevated plasma homocysteine.  Int J Geriatr Psychiatry. 2001;  16 609-614
• 34 Morrison L D, Smith D D, Kish S J. Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease.  J Neurochem. 1996;  67 1328-1331
• 35 Fekkes D, van der Cammen T J, van Loon C P, Verschoor C, van Harskamp F, de Koning I, Schudel W J, Pepplinkhuizen L. Abnormal amino acid metabolism in patients with early stage Alzheimer dementia.  J Neural Transm. 1998;  105 287-294
• 36 Wang H X, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Vitamin B₁₂ and folate in relation to the development of Alzheimer's disease.  Neurology. 2001;  56 1188-1194
• 37 Fata F T, Herzlich D C, Schiffman G, Ast A L. Impaired antibody responses to pneumococcal polysaccharide in elderly patients with low serum vitamin B₁₂ levels.  Ann Intern Med. 1996;  124 299-304
• 38 Andres E, Kurtz J E, Perrin A E, Maloisel F, Demangeat C, Goichot B, Schlienger J L. Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption.  Am J Med. 2001;  111 126-129
• 39 Dharmarajan T S, Norkus E P. Approaches to vitamin B₁₂ deficiency. Early treatment may prevent devastating complications.  Postgrad Med. 2001;  110 99-105
• 40 Carmel R. Subtle cobalamin deficiency.  Ann Int Med. 1996;  124 338-339