H. Baker et al., COBALAMIN (VITAMIN-B-12) AND HOLOTRANSCOBALAMIN CHANGES IN PLASMA ANDLIVER-TISSUE IN ALCOHOLICS WITH LIVER-DISEASE, Journal of the American College of Nutrition, 17(3), 1998, pp. 235-238
Objective: We wanted to know if alterations in plasma cobalamin (B-12)
concentration and B-12 carriers, e.g., holotranscobalamins (holo TC),
occur in blood and liver tissue from patients with severe alcoholic l
iver disease. Our purpose was to test the hypothesis that liver diseas
e may disrupt B-12 distribution.Method: Total B-12, as well as B-12 bo
und to transcobalamin I, II, III (holo TC), were measured to determine
their concentration in plasma and in liver tissue; Poteriochromonas m
alhamensis-a protozoan reagent served to measure only metabolically ac
tive (true) B-12. Total B-12 as distributed in hero TC in plasma and l
iver tissue of healthy subjects (controls) were compared to patients w
ith severe alcoholic liver disease. Results: Severe liver disease init
iates highly elevated B-12, levels in plasma and a lowered liver tissu
e total B-12 concentration. The percent of B-12 distributed to hole TC
II is significantly depleted during liver disease. In contrast, hole
TC I and III are elevated in plasma during liver disease and contain m
ore B-12 than controls. Total B-12 and B-12 distributed to TC are lowe
r in diseased liver tissue. Conclusion: Severe alcoholic liver disease
involves leakage of total B-12 from liver tissue into the plasma. Hol
e TC I and III concentration increases in plasma; this preserves the h
igh plasma B-12 from being excreted. However, plasma holo TC II B-12 d
istribution is decreased, indicating that there is a depression of exo
genous B-12 entering the plasma and tissues. In severe liver disease,
liver tissue B-12 binding and storage by TC is disrupted and causes B-
12 to leak out of the liver into the circulation. Eventually liver dis
ease could produce enough severe tissue B-12 deficits to cause metabol
ic dysfunction despite elevated plasma total B-12. Elevation of plasma
B-12, accompanied by a lowering of hole TC II distribution, seemed to
be a useful index of liver disease severity suggesting preventative t
reatment.