Ascorbic acid inhibits the increase in low-density lipoprotein (LDL) susceptibility to oxidation and the proportion of electronegative LDL induced by intense aerobic exercise.

BACKGROUND: We have previously reported the finding of an acute increment in the susceptibility of low-density lipoprotein (LDL) to oxidation and in the proportion of electronegative LDL [LDL(-)] after intense exercise. We have now studied the effect of oral supplementation with 1 g ascorbic acid, immediately before a 4-h athletic race, on the susceptibility of LDL to oxidation, the proportion of LDL(-), and the alpha-tocopherol and lipid peroxides content in LDL, in order to inhibit such deleterious changes, and to confirm the oxidative nature of modifications of LDL induced by exercise. METHODS: We studied seven highly trained runners who received a supplement of 1 g ascorbic acid and a control group of seven who did not receive the supplement. The susceptibility of LDL to oxidation was assessed by measurement of conjugated dienes after CuSO4-induced oxidation, the proportion of LDL(-) was determined by anion exchange chromatography, alpha-tocopherol was quantified by reverse-phase high performance liquid chromatography, and lipid peroxides were measured by the thiobarbituric acid-reactive substances (TBARS) method. RESULTS: After exercise, in the control group there was an increase in both the susceptibility of LDL to oxidation (change in lag phase from 51.4 +/- 4.7 min to 47.0 +/- 4.6 min, P < 0.05) and the proportion of LDL(-) (from 11.1 +/- 1.4% to 13.0 +/- 2.2%, P < 0.05), but these did not occur in the ascorbic acid group (change in lag phase from 49.7 +/- 2.3 min to 50.4 +/- 4.2 min, and in LDL(-) from 9.7 +/- 1.7% to 10.1 +/- 1.7%). No significant changes in the absolute amount of LDL alpha-tocopherol were observed after exercise (ascorbic acid group: 6.65 +/- 0.94 mol/mol apoB before the race, 7.13 +/- 0.88 mol/mol apoB after the race; control group: 7.34 +/-0.69 mol/mol apoB before the race, 7.06 +/- 0.69 mol/mol apoB after the race), but significant differences were found when increments or decrements of alpha-tocopherol were tested (alpha-tocopherol increased 9.9 +/- 11.5% in the ascorbic acid group, and decreased 0.6 +/- 7.3% in the control group; P < 0.018). TBARS did not change after exercise. CONCLUSIONS: We conclude that 1 g ascorbic acid inhibits the increase in LDL susceptibility to oxidation after exercise, preventing this acute pro-atherogenic effect. In addition, the observation that LDL(-) enhancement is prevented by ascorbic acid supports the hypothesis that at least some of the circulating LDL(-) originates from oxidative processes.

Brain pyruvate oxidation in experimental thiamin-deficiency encephalopathy.

Pyrithiamine-induced thiamin deficiency has been used in rat as an experimental form of Wernicke-Korsakoff encephalopathy, a disease associated with chronic alcoholism. Although the main etiological factor is known to be the lack of thiamin, the biochemical mechanisms involved in the pathogenesis remain unclear. Thiamin-dependent enzymes were studied in brain mitochondria: alpha-ketoglutarate dehydrogenase activity exhibited 40% reduction, whereas pyruvate dehydrogenase did not change significantly. Polarographic recordings of mitochondrial respiration revealed a decreased State 3, when using pyruvate/malate, alpha-ketoglutarate or glutamine as a substrate, but the respiration rates remained unchanged with glutamate or succinate. This fall in pyruvate oxidation may be due to the impairment of alpha-ketoglutarate dehydrogenase, which follows pyruvate dehydrogenase in the metabolic pathway. A time course of lactate concentration showed dramatic increases in thalamus, mid brain, hypothalamus and colliculli, consistent with the anatomopathological findings. No increases were found before the onset of neurological symptoms.