Severe hyperhomocysteinemia (HHC) is associated with atherosclerosis. In hemodialysis
(HD) patients, one of the main causes of death is cardiovascular disease. In animals,
trace elements such as cobalt, copper, iron, and nickel ameliorated vitamin B-12 deficiency-induced
HHC. However, correlations between plasma total homocysteine (tHcy) and trace elements
in HD patients have not been investigated. Therefore, tHcy, folate, vitamin B-12,
trace elements (cobalt, copper, iron, and nickel), and some laboratory parameters
such as serum total protein, albumin, transferrin, ferritin, C-reactive protein (CRP),
and interleukin-6 concentrations were determined in 122 hemodialysis patients. When
patients were divided into groups according to their tHcy, we found no significant
differences in concentrations of cobalt, copper, and total protein, while nickel was
higher, and folate, vitamin B-12, and iron were lower in patients with lower than
higher tHcy. In univariate regression analysis, tHcy negatively correlated with concentrations
of folate (r=-0.302, p < 0.006), vitamin B-12 (r=-0.347, p < 0.0001), nickel (r=-0.289,
p < 0.006), and CRP (r=-0.230, p < 0.02) and positively with serum albumin (r=0.316,
p < 0.0004) and hemoglobin (r=0.329, p < 0.0001) values. No relationship between tHcy
and serum concentrations of cobalt, copper, iron, or other laboratory parameters was
found in HD patients. The effect of cobalt and nickel on homocysteine production was
assessed in human peripheral mononuclear cells (PBMCs). Nickel but not cobalt at concentrations
found in HD patients significantly inhibited homocysteine, cysteine, and S-adenosylhomocysteine
production in human PBMCs. These results suggest that nickel might also be involved
in the regulation of the methionine-folate cycle in humans, as was demonstrated in
animal experiments.
