The Disparate Roles of Cobalt in Erythropoiesis, and Doping Relevance

Abstract

Some athletes seek to increase their red blood cells, because the aerobic capacity correlates with the mass of hemoglobin. Cobalt as part of dietary supplements is proclaimed to increase erythropoiesis and physical performance. However, the knowledge of the disparate mechanisms of cobalt´s actions in erythropoiesis is generally insufficient. First, there are cobalt-containing corrinoids, termed cobalamin or vitamin B 12. These are naturally present only in animal-derived foods. The active forms in the human body are methylcobalamin and deoxyadenosylcobalamin, which are essential cofactors for the methionine synthase and the L-methylmalonylcoenzyme A mutase. Cobalamin deficiency can result in anemia. However, supplemental cobalamin does not benefit performance unless a nutritional deficit is present. Second, inorganic cobalt ions (Co 2+) stimulate erythropoiesis, even in non-anemic subjects. Co 2+ stabilizes the hypoxia-inducible transcription factors (HIFs) which increase the expression of the erythropoietin gene (EPO). Cobaltous salts are orally active, easy to obtain and inexpensive. Typical side effects associated with chronic Co 2+ exposure include nausea, vomiting, heart failure, hypothyroidism and goiter. The potential misuse of inorganic cobalt deserves attention in anti-doping efforts.

Erythropoietin

“…This action of cobalt is fully separate from that of cobalamin (vitamin B 12 ). Co 2+ stabilizes HIF-α, thereby increasing EPO expression [8] .…”

“…Co 2+ binds to HIF-α, thereby preventing the interaction with the von Hippel-Lindau tumor suppressor protein and the degradation of HIF-α [8] . Intake of cobalt salt is probably the simplest means to stimulate HIF-dependent EPO expression.…”

“…Cobalt doping also has its role in sports involving animals. Of note, one has to differentiate between the potential of Co 2+ to stabilize HIF-α and the role of cobalt as part of cobalamin (vitamin B 12 ) [8] . Cobalamin supplementation has no proven beneficial effect on performance in the absence of a nutritional cobalamin deficit.…”

Niveles de eritropoyetina y reticulocitos en residentes de bajas alturas migrantes a medianas altura

“…La principal función de la EPO está dada en la regulación de la eritropoyesis, mediante el control de la proliferación, diferenciación y supervivencia de los progenitores eritroides. Bajo condiciones hipóxicas, las subunidades de factor inducible de la hipoxia 1α con 1 β se dimerizan en el núcleo y el complejo resultante activa la expresión de EPO, por lo tanto, la producción de esta hormona está directamente relacionada con el grado de hipoxia que se genera en medianas y altas alturas 3 , Para la evaluación de la EPO se tiene en cuenta que el recuento de reticulocitos, lo que permite inferir el comportamiento de la hormona, contando con un estímulo ya presente como el fenómeno hipóxico que genera la altura 4 .…”

Cobalt induces alterations in serum parameters associated with bone metabolism in male adult rat

“…Co 2+ can be used for treating a special kind of anemia (i.e. Co 2+ -containing vitamin B12 is an essential factor for erythropoiesis) (Lison, 2007;Jelkmann, 2012). Due to its advantages, including a high melting point and resistance to oxidation, it is widely used to produce different types of alloys and steel (Lison, 2007).…”