Lactic Acidosis as a Result of Iron Deficiency

Abstract

A B S T R A C T Iroin-deficien1t rats halve an1 im11paired work performancice, even when their aniemiiia is correcte(d by exchanige transfusioin. Muscle activity is associate(l with a higher blood lactate concenltrationi thani is observed in iron-replete aniimals. The accumulation of lactate is a result of excessive productioni as lactate clearancie fromn the 1)loo0( was shown to be unaffecte(l. By acljusting the work loa(l to a lower level, it was possible to (livide iron-deficient animilals into two groups, oine capal)le of continued treadlmiill runninig and aniother in which aniimals stoppe(d before 20( min. In the former, blood lactate conicenitrationi reache(d a plateau at moderate levels, whereas it coontiniued to increase in the latter until the anIimial stopped runninig. Levels ofa-glycerophosphate oxidase in skeletal mulscle mitochondria were found( to be mulch lower in the secon(d group (P < 0.001). Lactate infusioin into normiial animals was showin to interfere with work performiiance, anid muainteinance of a normiial pH in iron-deficieint anid iron-replete animiials didinot prevent the impairment in work associated with high bloo(1 lactate concentrations. Additional evidenlce Wcas obtained that energy substrate (blood glucose anid free fatty acids, muscle glycogen) was adequate in irondeficient animiials. Oxygein tension in their vena caval blood was higher than in controls. Fuirthermore, the in situ behavior of electrically stimulated gastrocnemius and soleus muscles appeared similar to that of control animals. Because the stimulation of the single muscle in the iron-deficient animal did not result in appreciable elevation of blood lactate andl did not show impaired contractility further supported the hypothesis that the elevation ofblood lactate caused the decreased work performance. It is concluded that iron deficiency by a depletion in the iron-containing mitochondrial enzyme, a-glycerophosphate oxidase,

Iron Deficiency in the Rat: Effects of Oxidative Metabolism in Distinct Types of Skeletal Muscle

“…measured by rates of phosphorylation with pyruvate-malate, succinate and a-glycerophosphate as substrate. The results are in accord with findings in our previous studies on preparations from unseparated pooled muscle (1, 2, 4,6) and with the more recent reports of other workers (1 1, 13,14,15). These results suggest strongly that iron deficiency results in defective oxidative energy metabolism in red and intermediate skeletal muscle with greatly decreased production of ATP, and decreased activity of the a-glycerophosphate shuttle which is necessary for the conversion of cytoplasmic NADH to NAD and continued operation of glycolysis.…”

“…These results suggest strongly that iron deficiency results in defective oxidative energy metabolism in red and intermediate skeletal muscle with greatly decreased production of ATP, and decreased activity of the a-glycerophosphate shuttle which is necessary for the conversion of cytoplasmic NADH to NAD and continued operation of glycolysis. These metabolic alterations result in excess lactate formation, which at high levels leads to cessation of physical activity (4). It is of interest that the a-glycerophosphate shuttle is not affected in white muscle (which is not of importance in prolonged physical activity) although ATP formation by NADH and succinate is markedly decreased.…”

“…After 6 wk on this diet, hemoglobin concentrations were determined and studies performed only on rats with hemoglobin concentrations of less than 7 g/100 ml blood. Previously, we have shown that the low hemoglobin concentrations found in rats fed the low iron diet were accompanied by greatly lowered levels of plasma iron and increased total iron binding capacity and that the anemia was of a microcytic type (4,5,14). The control groups were fed the low iron diet during the experimental period, but received weekly intraperitoneal injections of 5 mg of iron in the form of iron dextran (Imferon, MerrellNational Labs).…”

“…Previously, we (4,6) have shown that a limited running ability due to iron deficiency in rats may result from decreased levels in skeletal muscle mitochondria of a-glycerophosphate oxidase, and NADH and succinic oxidases which are all iron-containing enzymes and components of the terminal electron transport systems. Studies by other investigators (2,9) suggest that the mitochondrial a-glycerophosphate system in mammals is present mainly in skeletal muscle containing pale muscle fibers (white muscle) and to a much lesser degree in muscle containing mostly red fibers (red and intermediate muscle).…”

Functional consequences of iron deficiency in human populations.

“…After three days of iron treatment, however, the running time of the iron-deficient rats improved. Similar studies by Davies, Finch and co-workers, and Askew and co workers confirm these adverse effects of an iron deficient diet on various intensities of treadmill exercise and indicate that anemia is only one factor in this effect (8)(9)(10). In these studies transfusion that corrected the anemia did not restore running time .…”