Serum cobalamins

Vitamin B12 Low serum cobalamin (< 150 pmol/L) accompanied by increased serum homocysteine (> 13 Nnol/L), and increased serum (> 0.4 -mol/L) and urine (> 3.6 mmol/mol creatinine) methylmalonic acid... 

Nilsson K, Gustafson L, Faldt R, et al. Plasma homocysteine in relation to serum cobalamin and blood folate in a psychogeriatric population. Eur J Clin Invest 1994 24 600-6. 

In spite of Jean Ann Tonich s relatively malnourished state because of chronic alcoholism, her serum cobalamin level was still within the low-to-normal range. If her undernourished state had continued, a cobalamin deficiency would eventually have developed. 

Major vitamin Bi2-dependent metabolic processes include the formation of methionine from homocysteine, and the formation of succinyl coenzyme A from methylmalonyl coenzyme A. Thus, apart from directly determining vitamin B12 concentration in serum, elevated levels of both methylmalonic acid and homocysteine may indicate a vitamin B12 deficiency. Serum cobalamine concentration is often determined by automated immunoassays using an intrinsic factor as binding agent. These assays have mainly replaced the microbiological methods. Literature data about vitamin B12 concentration in serum varies. Values <110-150pmoll are considered to reflect deficiency, whereas values >150-200pmoll represents an adequate status. 

Conversion of Serum Cobalamins into one Molecular Form... 

Besides the two major analytical principles described above, other methods have been applied. Some of these methods also aim at measuring spedlic subgroups of the serum cobalamins. 

HoloTC the Cell-available Fraction of Serum Cobalamins. In... 

Table 26.1 Comparison of four different commercial available methods for analysis of total serum cobalamin. The four methods represent different principles for analysis of cobalamin in human serum.

We chose the method developed by Abbott as an example of automatic protein binding assays for analysis of serum cobalamin. Minor variations occur for other automatic platforms. 

Measurement of total serum cobalamin is used to explore the presence of cobalamin deficiency. 

Serum cobalamin consists of picomolar amounts of several forms of the vitamin bound to transcobalamin or haptocorrin. 

Measurement of serum cobalamin includes release of cobalamin from its binding proteins transcobalamin and haptocorrin, conversion of the various forms of cobalamin into one form of the vitamin, and quantification employing microbiological or protein binding assays. 

Measurement of holoTC, the part of serum cobalamin available for the cells, may be a better marker of cobalamin deficiency than total serum cobalamin. 

Cobalamin deficiency. Cobalamin deficiency is a common condition caused by an insufficient intake of cobalamin or an inability to absorb the vitamin. If left untreated, the condition may result in irreversible neurological damage and eventually death caused by a severe anaemia. Measurement of serum cobalamin is the most commonly employed test in order to confirm or rule out the presence of cobalamin deficiency. 

Valente, E., Scott, J.M., Ueland, P.M., Cunningham, C., Casey, M., and Molloy, A.M., 2011. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B12 status in the elderly. Clinical Chemistry. 57 856-863. 

Smokers, 61 subjects (35M) whose serum cobalamin concentrations are significantly lower than those of non-smokers. Organic nitrites, nitric oxide, cyanates and isocyanates inhaled with cigarette smoke interact with vitamin B12, neutralizing it. 

Vitamin B12 levels are usually within the normal range in patients on unselected AEDs. In patients on monotherapy with AEDs, serum cobalamin is not different from controls, except VPA, which is associated with elevated serum concentrations of cobalamin (Apeland et al. 2003 Belcastro et al. 2010 Krause et al. 1988 Reynolds 1975). Low vitamin B12 levels have been detected among patients on two or more AEDs (Linnebank et al. 2011). 

Possibly, the elevated serum cobalamin in patients on VPA may be due to toxic effects on the liver. A higher level of circulating cobalamin does not necessarily indicate higher vitamin B stores in the liver. The reasons for B12 deficiency in patients on several AEDs may be due to the combined metabolic actions of drugs or an inadequate diet. In a study of 12 patients, PHT, PB and PRD had no effect on the absorption of vitamin B12 from the gut. 

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