The 7 July 2016, the SECF (Société d'Encouragement du Cheval Français) published international thresholds for cobalt in the blood and urine samples. The thresholds are 0.025 microgram of total cobalt per ml in plasma (25 ng / mg) or 0.1 microgram of total cobalt per ml in urine (100 ng / ml).
Cobalt and doping
Blood doping is an illegal tool to enhance athletic performance by increasing oxygen's carrying capacity of the blood (Lippi et al., 2005). Methods of blood doping currently used involve the stimulation of erythropoiesis by using erythropoietin (EPO) or recombinant form. EPO is an hormone which is in charge of controlling the erythropoiesis i.e. stimulating the production of red blood cells. Thus agents stimulating erythropoiesis can substitute and stimulate erythropoietic activities of EPO to enhance performance (Lippi et al., 2006; Duh et al., 2008). Although these agents may have physiological effects, there are significant risks associated with the illegal use of these substances, which was demonstrated in humans (Franz, 2009).
Cobalt (symbol Co, atomic number 27) is a transition metal in the periodic table. In the biological system, cobalt is an essential micronutriment required for the formation of vitamin B12 complex, directly involved in the oxygen transport of red blood cells and may replace the zinc, cofactor in enzymes. In humans, it has been shown that cobalt administration stimulated erythropoiesis, increasing concentration of EPO, the number of red blood cells and hemoglobin. Cobalt is therefore a substance called « EPO LIKE » which increases sport performance.
Administration of cobalt and physiological effects in horses
• Effects of erythropoiesis on performance
In racehorses, the practice of cobalt supplementation has been recently developed. A recent study tested the effects of cobalt supplementation on the kinetics after administration of cobalt and the potential effects on the performance (Knych et al., 2014). The trial was conducted on 18 Thoroughbred horses who receive a single dose of 109 mg of cobalt chloride (49 mg of cobalt) by intravenous injection. The main results showed that serum levels, after cobalt administration, were relatively high with values up to 429 ng / ml after 30 minutes post administration. These serum levels remained up to six times higher than basal values and for 10 days post administration of a single dose. The authors also showed that half-live of the substance was approximately 6 days, allowing the achievement of anti-doping test. No effect on the erythropoietin or on red blood cells in the blood has been reported.
• Deleterious effects
To our knowledge and as confirmed by Mobasheri et Proudman (2015), no study published "therapeutic" versus "toxic" cobalt chloride doses in horses. Nevertheless, cobalt poisoning has been reported in humans following a large exposure (Goldfrank, 2011). Indeed, high cobalt doses can lead to poisoning and to cardiomyopathy. In addition, cobalt-medication interactions are still unknown. There is also a real concern about the purity of the chemical quality of salts that are currently available and their interactions with other drugs. High doses of impure cobalt chloride may be associated with toxicity.
Although no data is available on the toxicity thresholds and their effects of large exposure in horses, it cleary appears that the quantity administered leads to the toxicity or not of the substance. Moreover, the mode of administration studied, i.e. by intravenous way, results in a real risk of overdose.
Cobalt et Vitamin B12 : what are the links ?
Cobalt is an essential component of the molecule of the vitamin B12 (cobalamin). Vitamin B12 is synthesized by microorganisms in the cecum and colon from cobalt ingested. It is therefore necessary to have cobalt intake, although no feed shortage has been reported in horses fed under conventional conditions. The parenteral support (by injection) is unnecessary from a nutritonnal point of view.
Many studies, both in humans and in animal species (goat, cow,...) have shown that cobalt supplementation increased directly the vitamin B12 levels both in urine and in blood. However, the effects of vitamin B12 supplementation have, to our knowledge, never been tested on cobalt concentrations in horses. A recent study in men (Krug et al., 2014) showed that supplementation with vitamin B12 (500 micrograms / day, containing 22 micrograms of cobalt) did not increased the urinary cobal levels beyond basal values. The average concentration of cobalt in vitamin B12 is generally about 4 %, which is not sufficient to induice an increase in plasma and urine after oral administration.
at cobalt supplementation increased directly the vitamin B12 levels both in urine and in blood. However, the effects of vitamin B12 supplementation have, to our knowledge, never been tested on cobalt concentrations in horses. A recent study in men (Krug et al., 2014) showed that supplementation with vitamin B12 (500 micrograms / day, containing 22 micrograms of cobalt) did not increased the urinary cobal levels beyond basal values. The average concentration of cobalt in vitamin B12 is generally about 4 %, which is not sufficient to induice an increase in plasma and urine after oral administration. " The cobalt supplementation is a relatively new subject from a scientific point of view, explaining the severe lack of data in horses. Recent studies have the merit to complete the literature but many questions remain outstanding. Nevertheless, we can conclude that high concentration of cobalt administration can be dangerous or even lethal in humans, but no toxicity or performance enhancer thresholds exist in horses. As the feed is the only source of cobalt intake, we can assume that the assimilation of cobalt containing in conventional feed may not induced toxic levels in horses. However, any cobalt chloride intravenous injection, excluding by veterinary prescription, requires an ethical debate on the legitimacy of this practice. " concludes Justine Guillaume, Ph.D.
Références bibliographiques
Franz S.E. 2009. Erythropoiesis – stimulating agents: development, detection and dangers. Drug Testing and Analysis, 1:245-249. Duh M.S., Weiner J.R., White L.A., Lefebvre P., Greenberg P.E. 2008. Management of anemia: A critical and systematic review of the cost effectiveness of erythropoiesis-stimulating agents. Pharmacoeconomics, 26:99-120. Lippi G., Franchini M., Guidi G.C. 2006. Blood doping by cobalt. Should we measure cobalt in athletes? Journal of Occupationnal medicine and Toxicology, 1:18. Goldfrank L.R. 2011. Toxicologic emergencies. Ninth Ed. McGraw, New York, NY, USA. Knych H.K., Arthur R.M., Mitchell M.M., Holser I., Poppenga R., Smith L.L., Helm M.N., Sams R.A., Gaskill C.L. 2014. Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses. Drug Test. Analysis, doi:10.1002/dta.1737. Krug O., Kutscher D., Piper T., Geyer H., Schanzer W., Thevis M. 2014. Quantifying cobalt in doping control urine samples – a pilot study. Drug Test Anal., 6:1186-1190. Mobasheri A., Proudman C.J. 2015. Cobalt chloride doping in racehorses: concerns over a potentially lethal practice. The Veterinary Journal, doi: 10.1016/j.tvjl.2015.04.005.
