Total serum homocysteine levels

In the early stages of reduced vitamin B12 absorption, the amount of vitamin B12 bound to TCII decreases rapidly (10-21 days) without any decrease in the total serum B12 level. The total vitamin B12 concentration begins to decline only when the saturation of TCII falls below 5%. Reduced saturation of TCII is thus one of the earliest indicators of reduced intake of vitamin B12 and is detectable in advance of clinical disease. This makes holo-TCII particularly valuable for use as a screening test in susceptible populations. Elevated serum and urine concentrations of homocysteine and MMA occur somewhat later and represent early evidence of cellular dysfunction that occurs when body (liver) stores have been greatly depleted. 

Ubbink JB, Hayward Vermaak WJ, Bissbort S (1991) Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum. J Chromatogr 565 441-446... 

Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998 55(11) 1449-1455. 

The commonly recognized risk factors for atherosclerosis include increasing age, sex (males > females until menopause, after which the incidence is similar), serum lipid levels (increased total cholesterol and low-density lipoprotein cholesterol, decreased high-density lipoprotein cholesterol, etc.), diabetes melli-tus, hypertension, and obesity. Other less well recognized but very important risk factors include increased plasma homocysteine, fibrinogen, and coagulation factor VII increased blood hematocrit, leukocyte count (increased neutrophils), and C-reactive protein and clinical depression. 

Clarke, R., A.D. Smith, K.A. Jobst, H. Refsum, L. Sutton, and P.M. Ueland. Folate, Vitamin BI2, and Serum Total Homocysteine Levels in Confirmed Alzheimer Disease. Archives of Neurology 55, no. 11 (November 1998) 1449-55-... 

Reference intervals for fasting homocysteine levels have been reported to be 13 to 18flmol/L for serum " and 10 to 15pmol/L for plasma." The reference interval for total homocysteine in pediatric patients has been reported to be 3.7 to 10.3 LlmoiyL. ... 

Vitamin B12 deficiency is generally assessed based on serum vitamin B12 concentration, plasma homocysteine concentration and serum methylmalonic acid (MMA) concentration (Savage et al. 1994). Serum vitamin B12 concentration has been reported by many researchers, including us, to be similar in patients with CKD and healthy individuals (Koyama et al. 2002). However, plasma total homocysteine level is elevated in an inverse relationship with the reduction in renal function (Bostom and Lathrop 1997). 

Figure 22.6 How various factors increase the risk of atherosclerosis, thrombosis and myocardial infarction. The diagram provides suggestions as to how various factors increase the risk of development of the trio of cardiovascular problems. The factors include an excessive intake of total fat, which increases activity of clotting factors, especially factor VIII an excessive intake of saturated or trans fatty acids that change the structure of the plasma membrane of cells, such as endothelial cells, which increases the risk of platelet aggregation or susceptibility of the membrane to injury excessive intake of salt - which increases blood pressure, as does smoking and low physical activity a high intake of fat or cholesterol or a low intake of antioxidants, vitamin 6 2 and folic acid, which can lead either to direct chemical damage (e.g. oxidation) to the structure of LDL or an increase in the serum level of LDL, which also increases the risk of chemical damage to LDL. A low intake of folate and vitamin B12 also decreases metabolism of homocysteine, so that the plasma concentration increases, which can damage the endothelial membrane due to formation of thiolactone.

Serum cystatin C has also been described to be a better predictor than serum creatinine of fasting total homocysteine serum levels, probably because of its closer correlation to GFR (B23, N7). 

Elevated serum MMA and tHcy concentrations can be considered alternative specific metabolic parameters of cobalamin deficiency. Measurement of functional metabolite MMA requires sophisticated equipment and is, therefore, unsuitable for routine use. Total homocysteine is a more sensitive analyte than tfii2 in diagnosing subclinical vitamin B12 deficiency because its plasma levels increase before clinical symptoms appear. However, the lack of specificity of this analyte represents a serious limit to its use. Total homocysteinemia depends on genetic or physiological factors, life style, diseases in progress, and drugs. HHCY is caused by folate or vitamin Bg deficiency and renal failure. 

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