Eleanor M. Kellon, VMD
Since Possible dysmetabolic hyperferritinemia in hyperinsulinemic horses was published, and indeed long before it, the idea that too much iron could be harmful, and that there is a connection between iron and insulin, has generated an enormous push-back.
Most of the objections begin with statements to the effect that iron uptake from the intestinal tract is well regulated and that iron is not toxic to horses. However, dietary iron overload is well documented in humans, lab animals, and many zoo species when taken out of their native habitat . Severe iron toxicity has also been demonstrated in foals and adult horses .
The point here is that it is indeed possible for iron to be over-absorbed and to be toxic, even fatal, to the horse.
The connection between iron and metabolic syndrome is so strong in humans that a paper representing an international consensus statement was recently published in February of this year. If you want to delve deeper, start with the Recommendations section which describes in part:
“In a large prospective cohort of middle-age healthy men conducted in South Korea, elevated serum levels of ferritin were independently associated with development of the metabolic syndrome during the 5-year follow-up period. Furthermore, in a large prospective study on European cases of incident type 2 diabetes mellitus, increased serum levels of ferritin were associated with an increased risk of type 2 diabetes mellitus, even among individuals with no overt inflammation, liver disease, high alcohol consumption or obesity.”
Getting back to the horse paper linked above, rabid criticism centers around the themes that iron does not cause laminitis and does not cause metabolic syndrome. There was even a paper published recently that stated Thoroughbreds fed high levels of iron do not develop metabolic syndrome, so there must be no connection between the two, completely ignoring that there is strong evidence for a root genetic predisposition to metabolic syndrome.
The problem is that nowhere in our paper was it ever stated that iron caused metabolic syndrome or laminitis. What we said was 100% of the hyperinsulinemic horses from the ECIR group tested for iron were overloaded and when results from another study were reexamined we found significantly elevated ferritin (p = 0.05) in horses considered hyperinsulinemic by dynamic insulin testing, compared to horses with a normal response. Our conclusion was simply:
“These results suggest the potential for iron overload in hyperinsulinemic horses, a feature documented in other species and should stimulate further study into the relationship between insulin and iron dysregulation in the horse.”
Both hyperinsulinemia and iron overload are multifactorial conditions. It’s not as simple as Strep causes Strep throat. You can’t expect x units of change in insulin correlates to y levels of iron, or vice versa.
What we do know is there is good evidence of a connection.
About ECIR Group Inc.
Started in 1999, the ECIR Group is the largest field-trial database for PPID and EMS in the world and provides the latest research, diagnosis, and treatment information, in addition to dietary recommendations for horses with these conditions. Even universities do not and cannot compile and follow long term as many in-depth case histories of PPID/EMS horses as the ECIR Group.
In 2013 the Equine Cushing’s and Insulin Resistance Group Inc., an Arizona nonprofit corporation, was approved as a 501(c)3 public charity. Tax deductible contributions and grants support ongoing research, education, and awareness of Equine Cushing’s Disease/PPID and EMS.
THE MISSION of the ECIR Group Inc. is to improve the welfare of equines with metabolic disorders via a unique interface between basic research and real-life clinical experience. Prevention of laminitis is the ultimate goal. The ECIR Group serves the scientific community, practicing clinicians, and owners by focusing on investigations most likely to quickly, immediately, and significantly benefit the welfare of the horse.
REFERENCES
Kellon EM, Gustafson KM. Possible dysmetabolic hyperferritinemia in hyperinsulinemic horses. Open Vet J. 2019 Oct-Dec; 9(4): 287–293. Published online 2019 Oct 21. doi: 10.4314/ovj.v914.2
Lowenstine LJ, Stasiak IM. Update on Iron Overload in Zoologic Species. Veterian Key, Chapter 69 https://veteriankey.com/update-on-iron-overload-in-zoologic-species/
Acland HM, Mann PC, Robertson JL, Divers TJ, Lichtensteiger CA, Whitlock RH. Toxic hepatopathy in neonatal foal.Vet Pathol, 1984 Jan;21(1):3-9. doi: 10.1177/030098588402100102.
Theelen MJP, Beukers M, Grinwis GCM, Sloet van Oldruitenborgh-Oosterbaan MM. Chronic iron overload causing haemochromatosis and hepatopathy in 21 horses and one donkey. Equine Vet J. 2019 May;51(3):304-309. doi: 10.1111/evj.13029. Epub 2018 Nov 5.
Valenti L, Corradini E, Adams LA, Aigner E, Alqahtani S, Arrese M, Bardou-Jacquet E, Bugianesi E, Fernandez-Real JM, Girelli D, Hagström H, Henninger B, Kowdley K, Ligabue G, McClain D, Lainé F, Miyanishi K, Muckenthaler MU, Pagani A, Pedrotti P, Pietrangelo A, Prati D, Ryan JD, Silvestri L, Spearman CW, Stål P, Tsochatzis EA, Vinchi F, Zheng MH, and Zoller H. Consensus Statement on the definition and classification of metabolic hyperferritinaemia. Nature Reviews Endocrinology (2023)Feb 17 : 1–12.
Contact: Nancy Collins
ecirgroup1@gmail.com
Stock photo available