Abstract
Objective: Assessment of functional vitamin B12 status in a subset of the respondents in the British National Diet and Nutrition Survey of people aged 65 y and over.
Setting: National Diet and Nutrition Survey: a British nationwide cross-sectional sample of people aged 65 y and over, living either in the community or in institutions such as nursing homes, during one calendar year spanning 1994–1995.
Methods: Methylmalonic acid (MMA) concentrations were measured in plasma samples from 313 subjects (ca 14% of those originally enrolled in the survey). The results were compared with those for serum vitamin B12, vitamin B12 intakes and other status and intake estimates and with socio-demographic indices.
Results: Of the NDNS participants overall, 20% had serum vitamin B12 concentrations<150 pmol/l. In the subset studied here, 24% of free-living and 46% of institution-living participants had MMA>0.5 µmol/l. Geometric mean MMA increased with age, from 0.25 µmol/l in people aged 65–74 y to 0.38 µmol/l in people aged 85+y. There was little evidence for any gender difference in MMA. It was inversely correlated with serum vitamin B12 and with red blood cell folate; it was positively correlated directly with total homocysteine, but not significantly with serum folate or with vitamin B12 intake. Among respondents with high MMA, a subgroup had normal serum vitamin B12 but higher-than-average plasma urea and creatinine. Socio-demographic co-variates of MMA included receipt of State income benefits, social class of head of household, and educational attainment. These indices were not correlated with serum vitamin B12.
Conclusions: The progressive increase in MMA with age is metabolic evidence for increasing risk of functional vitamin B12 deficiency with increasing age in older people. There is evidence that renal function is linked to high MMA in some older people. Age and renal function are thus both important when establishing upper reference limits for MMA. The socio-demographic observations suggest a link between poverty and poor functional vitamin B12 status in older British people.
Sponsorship: The Department of Health.
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References
Allen, LH & Casterline, J (1994). Vitamin B12 deficiency in elderly individuals: diagnosis and requirements. Am. J. Clin. Nutr., 60, 12–14.
Baik, HW & Russell, RM (1999). Vitamin B12 deficiency in the elderly. A. Rev. Nutr., 19, 357–377.
Bates, CJ, Mansoor, MA, van der Pols, J, Prentice, A, Cole, TJ & Finch, S (1997). Plasma total homocysteine in a representative sample of 972 British men and women aged 65 and over. Eur. J. Clin. Nutr., 51, 1–7.
Bates, CJ, Prentice, A, Cole, TJ, van der Pols, JC, Doyle, W, Finch, S, Smithers, G & Clarke, PC (1999). Micronutrients — highlights and research challenges from the 1994/5 National Diet and Nutrition Survey of People Aged 65 Years and Over. Br. J. Nutr., 82, 7–15.
Bates, CJ, Mansoor, MA, Gregory, J, Pentieva, K & Prentice, A (2002). Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutrition Survey of Young People Aged 4–18 Years, and a comparison with the Survey of People Aged 65 Years and Over. Br. J. Nutr., 87, 71–79.
Bjorkegren, K & Svardsudd, K (1999). Elevated serum levels of methylmalonic acid and homocysteine in elderly people. A population-based intervention study. J. Intern. Med., 246, 317–324.
Bjorkegren, K & Svardsudd, K (2001). Serum cobalamin, folate, methylmalonic acid and total homocysteine as vitamin B12 and folate deficiency markers amongst elderly Swedes — a population-based study. J. Intern. Med., 249, 423–432.
Carmel, R (2000). Current concepts in cobalamin deficiency. A. Rev. Med., 51, 357–375.
Carmel, R, Green, R, Jacobsen, DW, Rasmussen, K, Florea, M & Azen, C (1999). Serum cobalamin, homocysteine, and methylmalonic acid concentrations in a multiethnic elderly population: ethnic and sex differences in cobalamin and metabolite abnormalities. Am. J. Clin. Nutr., 70, 904–910.
Chanarin, I (1979). The Megaloblastic Anaemias, Chap. 14, Oxford: Blackwell Scientific Publications
Chanarin, I, England, JM, Mollin, C & Perry, J (1973). Methylmalonic acid excretion studies. Br. J. Haematol., 25, 45–53.
El-Khairy, L, Ueland, P, Nygard, O, Refsum, H & Vollset, S (1999). Lifestyle and cardiovascular disease risk factors as determinants of total cysteine in plasma: the Hordaland Homocysteine Study. Am. J. Clin. Nutr., 70, 1016–1024.
Finch, S, Doyle, W, Lowe, S, Bates, CJ, Prentice, A, Smithers, G & Clarke, P (1998). National Diet and Nutrition Survey: People Aged 65 Years or Over, Volume1, Report of the Diet and Nutrition Survey London: The Stationery Office
Gompertz, D, Jones, JH & Knowles, JP (1967). Metabolic precursors of methylmalonic acid in vitamin B12 deficiency. Clin. Chim. Acta, 18, 197–204.
Gregory, J, Lowe, S, Bates, C, Prentice, A, Jackson, L & Smithers, G (2000). National Diet and Nutrition Survey: Young People Aged 4 to 18 Years, Volume1, Report of the Diet and Nutrition Survey London: The Stationery Office
Herrmann, W, Schorr, H, Bodis, M, Knapp, JP, Muller, A, Stein, G & Geisel, J (2000). Role of homocysteine, cystathionine and methylmalonic acid measurement for diagnosis of vitamin deficiency in high-aged subjects. Eur. J. Clin. Invest., 30, 1083–1089.
Howard, JM, Azen, C, Jacobsen, DW, Green, R & Carmel, R (1998). Dietary intake of cobalamin in elderly people who have abnormal serum cobalamin, methylmalonic acid and homocysteine levels. Eur. J. Clin. Nutr., 52, 582–587.
Hvas, AM, Juul, S, Gerdes, LU & Nexo, E (2000). The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine. J. Intern. Med., 247, 507–512.
Jacques, PF, Selhub, J, Bostom, AG, Wilson, PWF & Rosenberg, IH (1999). The effect of folic acid fortification on plasma folate and total homocysteine concentrations. New Engl. J. Med., 19, 1449–1454.
Joosten, E, van den Berg, A, Riezler, R, Naurath, HJ, Lindenbaum, J, Stabler, SP & Allen, RH (1993). Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), folate and vitamin B-6 occur commonly in elderly people. Am. J. Clin. Nutr., 58, 468–476.
Koehler, KM, Romero, LJ, Stauber, PM, Pareo-Tubbeh, SL, Liang, HC, Baumgartner, RN, Garry, PJ, Allen, RH & Stabler, SP (1996). Vitamin supplementation and other variables affecting serum homocysteine and methylmalonic acid concentrations in elderly men and women. J. Am. Coll. Nutr., 15, 364–376.
Lindenbaum, J, Healton, EB, Savage, DG, Brust, JC & Garrett, TJ et al (1988). Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. New Engl. J. Med., 318, 1720–1728.
Lindenbaum, J, Rosenberg, IH, Wilson, PWF, Stabler, SP & Allen, RH (1994). Prevalence of cobalamin deficiency in the Framingham elderly population. Am. J. Clin. Nutr., 60, 2–11.
Mansoor, M, Svardal, A & Ueland, P (1992). Determination of the in vivo redox status of cysteine, cysteinylglycine, homocysteine and glutathione in human plasma. Anal. Biochem., 200, 218–229.
Mansoor, MA, Bergmark, C, Svardal, AM, Lonning, PB & Ueland, PM (1995). Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease. Arterioscler. Thromb. Vasc. Biol., 15, 232–240.
Moelby, L, Rasmussen, H, Jensen, MK & Pedersen, KO (1990). The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid. J. Intern. Med., 228, 373–378.
Moelby, L, Rasmussen, K, Ring, T & Nielsen, G (2000). Relationship between methylmalonic acid and cobalamin in uremia. Kidney Int., 57, 265–273.
Moller, J, Rasmussen, K & Christensen, L (1999). External quality assessment of methylmalonic acid and total homocysteine. Clin. Chem., 45, 1536–1542.
Nilsson-Ehle, H (1998). Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy. Drugs Aging, 12, 277–292.
Norman, EJ (1998). Urinary methylmalonic acid/creatinine defines true cobalamin deficiency. Br. J. Haematol., 100, 617–618.
Norman, EJ (1999). Urinary methylmalonic acid/creatinine ratio: a gold standard test for tissue vitamin B12 deficiency. J. Am. Geriatr. Soc., 47, 1158–1159.
Norman, EJ, Martelo, OJ & Denton, MD (1982). Cobalamin (vitamin B12) deficiency detection by urinary methylmalonic acid quantitation. Blood, 59, 1128–1131.
Penninx, BWJH, Guralnik, JM, Ferrucci, L, Fried, LP, Allen, RH & Stabler, SP (2000). Vitamin B12 deficiency and depression in physically disabled older women: epidemiololgic evidence from the women's health and aging study. Am. J. Psych., 157, 715–721.
Pennypacker, LC, Allen, RH, Kelly, JP, Matthews, LM, Grigsby, J, Kaye, K, Lindenbaum, J & Stabler, SP (1992). High prevalence of cobalamin deficiency in elderly outpatients. J. Am. Geriatr. Soc., 40, 1197–1204.
Perry, J, Lumb, M, Laundy, M, Reynolds, EH & Chanarin, I (1976). Role of vitamin B12 in folate coenzyme synthesis. Br. J. Haematol., 32, 243–248.
Rasmussen, K, Moelby, L & Jensen, MK (1989). 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., 35, 2277–2280.
Rasmussen, K, Moller, J, Ostergaard, K, Ostergaard Kristensen, M & Jensen, J (1990a). Methylmalonic acid concentrations in serum of normal subjects: biological variability and effect of oral L-isoleucine loads before and after intramuscular administration of cobalamin. Clin. Chem., 36, 1295–1299.
Rasmussen, K, Vyberg, B, Pedersen, KO & Brochner-Mortensen, J (1990b). Methylmalonic acid in renal insufficiency: evidence of accumulation and implications for diagnosis of cobalamin deficiency. Clin. Chem., 36, 1523–1524.
Rasmussen, K, Moller, J, Lyngbak, M, Pedersen, AM & Dybkjaer, L (1996). Age- and gender-specific reference intervals for total homocysteine and methylmalonic acid in plasma before and after vitamin supplementation. Clin. Chem., 42, 630–636.
Sauberlich, HE (1999). Laboratory Tests for the Assessment of Nutritional Status, 2nd edn. Vitamin B-12 (Cyanocobalamin; Corrinoids), pp135–159, Boca Raton, FL: CRC Press
Savage, DG, Lindenbaum, J, Stabler, SP & Allen, RH (1994). Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am. J. Med., 96, 239–246.
Schneede, J & Ueland, PM (1995). Application of capillary electrophoresis with laser-induced fluorescence detection for routine determination of methylmalonic acid in human serum. Anal. Chem., 34, 812–819.
Stabler, SP, Marcell, PD, Podell, ER, Allen, RH & Lindenbaum, J (1986). Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass-spectrometry. J. Clin. Invest., 77, 1606–1612.
Stabler, SP, Allen, RH, Fried, LP, Pahor, M, Kittner, SJ, Penninx, BWJH & Guralnik, JM (1999). Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women. Am. J. Clin. Nutr., 70, 911–919.
Ueland, P, Refsum, H & Brattstrom, L (1992). Plasma homocysteine and cardiovascular disease. InAtherosclerotic Cardiovascular Disease, Hemostasis and Endothelial Function., ed. Francis RBJ, pp.183–236, New York: Marcel Dekker
van Asselt, DZB, de Groot, LCPGM, van Staveren, WA, Blom, HJ, Wevers, RA, Biemond, I & Hoefnagels, WHL (1998). Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects. Am. J. Clin. Nutr., 68, 328–334.
Whitehead, TP, Robinson, D, Hale, AC & Bailey, AR (1994). Clinical Chemistry and Haematology: Adult Reference Values, London: BUPA Medical Research and Development
Acknowledgements
The survey was commissioned jointly by the Department of Health and the Ministry of Agriculture, Fisheries and Food, whose responsibility has since been transferred to the Food Standards Agency. It was carried out by Social and Community Planning Research (now the National Centre for Social Research), in conjunction with the Micronutrient Status Laboratory of the MRC Dunn Nutrition Unit (now part of MRC Human Nutrition Research). Funding for the measurement of MMA was provided by the Department of Health.
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Bates, C., Schneede, J., Mishra, G. et al. Relationship between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the British National Diet and Nutrition Survey of people aged 65 y and over. Eur J Clin Nutr 57, 349–357 (2003). https://doi.org/10.1038/sj.ejcn.1601540
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DOI: https://doi.org/10.1038/sj.ejcn.1601540
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