A new theory from a University of Alberta researcher suggests that milk fever may be driven by inflammation, prompting renewed discussion about its underlying causes.
Milk fever is a concern not just in the dairy industry, but in the beef industry as well. It can occur when a cow cannot meet the demand for both milk production and colostrum, affecting her calcium levels. It can cause many different clinical signs, such as loss of appetite, muscle tremors and weakness in the early stages, which may progress into the animal being unable to stand.
WHY IT MATTERS: Understanding what causes milk fever could be a game-changer for both the dairy and the beef industry.
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Because milk fever is such a prevalent illness, understanding what causes it is fundamental. Burim Ametaj, a researcher at the University of Alberta has proposed a hypothesis he calls the Calci-Inflammatory Network. His scientific model is looking more deeply at the causes behind the condition, and, more specifically, how it may be a biological response to inflammation.
Milk fever
Milk fever is also known as hypocalcemia, which is low levels of calcium in the blood. A lot of calcium is necessary when calving to meet high milk production.
Ametaj says milk fever has been a problem for more than 200 years. It was first documented in 1793, but since then, it has been found in almost every dairy herd. Though it is more common in dairy cattle, it can occur in beef females after calving, more frequently in older cows or cows that have a high production of milk. It is also more common in beef herds when the forage quality is low, like after drought or excess rain, according to research by the University of Manitoba.
“That persistence tells us we’re missing something fundamental,” Ametaj said in an emailed interview.
“But milk fever isn’t just one disease. It’s the tip of the iceberg. Cows with hypocalcemia are at dramatically higher risk for mastitis, metritis, ketosis and displaced abomasum. Fixing milk fever could be the key to unlocking healthier transition periods and more profitable herds.”
Burim Ametaj, researcher
University of Alberta
Currently, milk fever is treated through supplemental calcium, either intravenous or oral, or both. Generally, a veterinarian will start with intravenous calcium and then move to the oral supplement once the animal can stand. Usually, the response is pretty immediate. Risks associated with treatment, in the long term and short term, are minimal. One of the main concerns is relapse.
This is why dairy and beef producers have often been told not to supplement with calcium before calving, because it can exacerbate the chance of milk fever and limit the animal’s natural calcium creation.
Ametaj believes this kind of treatment isn’t necessary if more work is done on the front end — and during his research found himself questioning why things are done the way they are.
“If something is truly a deficiency, you should feed it to cure the health effects of that deficiency. Yet here we were telling producers: ‘It’s a calcium deficiency, but don’t feed calcium.’ No one questioned this paradox.”
This is one of the many reasons Ametaj started looking deeper into milk fever and ultimately came up with the Calci-Inflammatory Network.
Calci-Inflammatory Network
The start of his research began many years ago, when Ametaj was working on his post-doctoral studies in 1999 at Iowa State University. At the time, he wanted to investigate the potential association between milk fever and inflammation and proposed the hypothesis that endotoxin was causing hypocalcemia in cattle.
But it wasn’t until he started at the University of Alberta in 2004 as an assistant professor that he had the freedom to pursue his idea. Over the years he has continued his research on this topic, creating an oronasal vaccine and an intravaginal probiotic intended to prevent uterine infections. From the research with those treatments, Ametaj saw a 50 per cent reduction in milk fever incidence.
“This wasn’t about feeding calcium, it was about controlling inflammation,” Ametaj said.
In 2020, he conducted research showing when you prevent the calcium drop and maintain high calcium levels during inflammation, the inflammatory response actually gets worse.
This is what eventually led to him creating the Calci-Inflammatory Network, his scientific model that suggests calcium can be directly correlated with inflammation.
“The Calci-Inflammatory Network was born from synthesizing a quarter-century of research, starting with my original hypothesis in 1999, validated by experiments in 2003, and developed through my own work over two decades,” he said.
And Ametaj thinks it can change the way milk fever is viewed.
“For a century, the prevailing paradigm has been to treat hypocalcemia as a deficiency. But it’s actually a protective, life-saving response — a withdrawal of calcium to ease inflammation, not a deficiency.”
Potential benefits
Ametaj hopes that as he continues his research, the way milk fever is approached and understood will change. The framework of the Calci-Inflammatory Network is just the first step.
For example, he believes treatment can be adjusted so calcium isn’t used to just fix a deficit, but to better align with the cow’s immune state, genetic profile and stage of recovery in each case-by-case scenario.
Ametaj said there are many new approaches that can be derived from this theory, such as better prevention — like the intravaginal probiotic — and limiting transition diseases, such as mastitis, metritis or ketosis by focusing on inflammation.
“Stop thinking of calcium as just a mineral. Think of it as the brake pedal on inflammation. Inflammation appears during dry-off, weeks before hypocalcemia. When calcium drops, your cow is trying to survive. Forcing calcium up, especially pre-partum, might be cutting the brake lines. Not all hypocalcemia needs treatment. What matters is why calcium dropped — protective response or mobilization failure?”
He said this could help the bottom line of an operation as well. Producers may be able to limit their antibiotic use, improve herd health overall and see fewer losses on their operations.
Future plans
Ametaj said the Calci-Inflammatory Network could benefit not just the agriculture industry, but also diseases that might affect humans. Low blood calcium can be found in many serious human illnesses, and he believes his research will correlate.
This is still speculative, but it is something he is hoping to look into more deeply in the future.
“This isn’t just about cows. Human critical care doctors see identical patterns in sepsis patients. … There’s much more coming in the next few months — several new concepts about both cow and human health that will challenge conventional thinking even further.”
Ametaj is planning on continuing this research and finding more tangible ways to use his findings to create treatment.
“From vaccines to probiotics to immunometabolomics — we’re just scratching the surface. There are exciting developments ahead that will provide producers with better tools and strategies.”
