Iron Overload by Dr Eleanor Kellon VMD
Iron is absolutely essential for life. The high affinity of iron for oxygen is what makes it so useful in trapping oxygen in haemoglobin for delivery to the body tissues.
Iron is also incorporated in some very reactive enzyme systems. However, iron’s high affinity for oxygen and high reactivity also makes it dangerous. Free, ionised iron will react with peroxide or water in the body, ending in the creation of OH*, hydroxy radicals. OH* damages lipids/fats in cell structures and membranes, in the process generating more radicals to produce a chain reaction of destruction.
Iron is absorbed by binding to specific metal transporters in the small intestine, and also passively via the junctions between cells. Work in other species has shown that the volatile fatty acids produced from fibre fermentation enhance iron absorption in the colon. Because the horse is a hind gut fermenter, this likely is a significant source of iron. Iron bound to metal transporters is taken inside the intestinal cells. From there, it may be bound to blood proteins and released, or continue to accumulate and eventually be lost into the manure when the cell dies. By regulating how much iron gets released into the blood, the body has some control. However, the other pathways for absorption cannot be regulated.
If you ask any veterinary pathologist they will tell you that finding black, iron loaded livers at necropsy is common in horses. The colour comes from iron deposits called hemosiderin. This is so common it is considered ‘normal’. There are reports of iron causing liver disease, even death in foals, but chronic conditions related to iron overload were not recognised in horses. Iron overload in humans is usually caused genetic disorders resulting in over absorption, or diseases that require frequent transfusions. However, overload related to diet is also possible. Liver damage or liver failure does occur, but is a late stage. Earlier symptoms include fatigue, joint pain/arthritis and often metabolic syndrome/insulin resistance.
The same syndrome and consequences has been recognised in a variety of animal species, including several birds, black rhinoceros, tapir, lemur, and dolphin. It may also be linked to IR in other old world primates but iron overload has not been studied in them.
Iron overload symptoms in horses include coat changes of bleaching and red ends on dark manes and tails, often hoof issues such as laminitis and abscessing. This study linked iron status to insulin resistance (IR) in horses.
Other areas for exploration to determine if there is a link with iron status include arthritis, raised liver enzymes and other issues, even Cushing’s disease because the changes seen in the brains of horses with Cushing’s are virtually identical to those seen in human brains with iron overload. There is a discussion of this and suggestions for further research in my Equine Congress paper here.
Diagnosis and treatment of iron overload in horses
The only way to accurately diagnose iron overload is with the correct blood work. Serum iron alone is not accurate. It reflects iron in the diet but not how much is stored. Transferrin is the protein that carries iron in the blood. When transferrin and iron are both measured, the percent transferrin saturation can be calculated by dividing serum iron by transferrin and multiplying by 100. That % is useful in interpreting the third test that is needed, ferritin. Ferritin is a measure of the body’s total iron content. High ferritin can mean iron overload but chronic disease involving inflammation or infection may also elevate ferritin.
With true iron overload, transferrin saturation is high normal or elevated. There is currently only one laboratory in the world that can measure equine ferritin, the comparative hematology laboratory at Kansas State Veterinary Diagnostic Laboratory. [Note: The only lab in the world calibrated for horses is in America: Kansas State University. No lab in Australia is calibrated for horses.]
Iron overload in humans is treated by phlebotomy – blood draws. Blood letting sounds positively medieval but is a very effective way to reduce the body’s iron level because of how much iron is in red blood cells. Stored iron is then used to replace the lost red cells. It works in horses too and can have dramatic effects on IR. A case in point was a gelding with PPID (also known as Cushings) and IR that needed to have surgery to break up and remove a very large bladder stone. Despite diet and pergolide control, his insulins were always running around 120 and he was iron overloaded. The surgery took several hours and blood loss was substantial. His insulin dropped to 20 after surgery, despite a postop diet of senior feed.
Dr Kellon VMD
You can read more about iron and the role of copper and zinc supplementation to deal with iron overload in my article on Minerals and Coat Bleaching.
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AZA Prosimian Taxon Advisory Group (PTAG) (2003) Iron storage disease in lemurs. Working paper, PTAG meeting on iron storage disease, 29 March, St. Louis Zoo, St. Louis, Missouri.
Clause M and Paglia DE (2012) Iron storage disorders in captive wild mammals: The comparative evidence J. Zoo Wildl Med. 43(3):S6-18
Kellon E Iron status of hyperinsulinemic/insulin resistant horses
Molenaar F (2005) Assessing iron storage disease in eastern black rhinoceroses (Diceros bicornis michaeli), reference ranges for iron levels and biochemistry
Nielsen B (2012) A potential link between insulin resistance and iron overload disorder in browsing rhinoceroses investigated through the use of an equine model J. Zoo Wildl Med. 43(3):S61-65
Venn-Watson et al (2012) Hemochromatosis and Fatty Liver Disease: Building Evidence for Insulin Resistance in Bottlenose Dolphins (Tursiops Truncatus) J. Zoo Wildl Med. 43(3):S35-47
Kansas State Veterinary Diagnositic Laboratory
Anatomical drawing above of the equine liver, visceral surface sourced from here.