Real Science Exchange-Dairy

Dr. Laura Hernandez and Dr. Tom Overton: The role of the mammary gland in calcium metabolism

Episode Summary

Dr. Hernandez recently presented a Real Science Lecture series webinar on this topic. You can find the link at balchem.com/realscience.

Episode Notes

Dr. Hernandez recently presented a Real Science Lecture series webinar on this topic. You can find the link at balchem.com/realscience.

Dr. Hernandez begins with an overview of how she came to study calcium metabolism in the mammary gland. Over the past number of years, she has worked on research to manipulate what’s happening in the mammary gland in the prepartum period to ensure adequate endocrine, nutritional, reproductive, and immunological status. (5:55)

The panelists discuss how “normal” has changed when it comes to transition cow health. Dr. Overton reminds listeners that 25 years ago, 6-8% of fresh cows in a herd having clinical milk fever was pretty typical. Now, we accept none of that. Subclinical hypocalcemia was not on the radar then, and we thought we had calcium all figured out. Dr. Hernandez’s work shows that this was not the case. She is pleased that a synergism of producers, veterinarians, and academics have been working together to understand the mechanisms of calcium metabolism to find solutions for individual farms based on their situation. (9:22)

Dr. Hernandez then discusses various interventions used in the industry, including low-potassium diets, negative DCAD diets, and zeolite clays. The clays are new to the US, and it seems that they work primarily through a phosphorus reduction mechanism and are best limited to feeding 10-14 days pre-calving. (18:14)

Dr. Overton asks Dr. Hernandez about a point in her webinar that cows are in negative calcium balance through 150-200 days in milk. She confirms that there are approximately 8.5 kilograms of calcium in the bones of a cow, but we don’t know how much of that she loses each lactation. Her dream scenario would be a CT scanner large enough to fit a dairy cow in to evaluate how her bones change throughout lactation. This leads to a discussion of whether or not we should be including higher rates of calcium in dairy cow diets. Dr. Hernandez would like to learn more about what’s happening with calcium absorption in the gut in real-time with endocrine status and stage of lactation, which is a challenging task. (23:17)

Co-host, Dr. Jeff Elliott, asks if the reason multiparous cows are more prone to milk fever is because they’re not as efficient at calcium resorption to the bone. Dr. Hernandez doesn’t have a definitive answer, but it could be due to less effective gut absorption with age, or it may be related to the influence of estrogen on bone density. She also mentions it could be endocrine-controlled or even stem cell-related.  (28:59)

Dr. Hernandez’s hypothesis has always been that you have to have a calcium decrease to trigger the negative feedback loop involved in calcium metabolism. Her advice is to wait until 48 hours to take a blood sample to analyze calcium. This aligns well with epidemiological research on the veterinarian side regarding delayed, persistent, transient, and normal hypocalcemic animals. (33:04)

Dr. Overton asks about a calcium-chelation study that Dr. Hernandez’s group conducted and whether or not chelating calcium had an impact on colostrum production. It did not in that experiment. Dr. Hernandez was surprised at how much chelating agent was needed to overcome the draw of the mammary gland, but that further underlines how much of a priority lactation is in metabolism. (41:45)

Scott asks both panelists their views on what the priority should be for research in this area. Dr. Hernandez’s ideas include more research on how zeolite clays work biologically, finding out what’s happening in the gut, mammary gland, and bone of a dairy cow at different stages of lactation. She emphasizes that research should be conducted at different stages rather than just extrapolating from one stage to another because lactation is incredibly dynamic. Dr. Overton seconded the idea of a better understanding of zeolite clays and their feeding recommendations, as well as research defining what happens to and where all the calcium is pulled from the bone during lactation. (45:32) 

In closing, Jeff, Tom, and Laura share their take-home thoughts. Jeff is excited to learn more about how zeolite clays work and if other products may come to the forefront to help in calcium metabolism management. Tom commends Laura on her work and how it has dovetailed so well with the epidemiological research from the veterinary side. Laura reminds listeners that the mammary gland is running the show and is thrilled that her work as a basic scientist is having an applied impact on the dairy industry. (51:17)

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Episode Transcription

Scott Sorrell (00:09):

Good evening everyone, and welcome to the Real Science Exchange, the pubcast where leading scientists and industry professionals meet over a few drinks to discuss the latest ideas and trends in animal nutrition. Hi, I'm Scott Sorrell. I'm gonna be your host here tonight, the Real Science Exchange. Tonight, we have truly a fascinating topic to dive into the role of the mammary gland in governing calcium metabolism. Joining us is a very special guest, Dr. Laura Hernandez, a renowned researcher and professor from the University of Wisconsin. Dr. Hernandez recently delivered an insightful presentation for the Real Science Lecture series on October 2nd, and you can find that presentation on our website at balchem.com/realscience. And we're thrilled to have Dr. Hernandez with us here today to expand on that discussion. Now, Dr. Hernandez, welcome to the Real Science Exchange. I guess this is your first time to the pub, so welcome.

Dr. Laura Hernandez (01:02):

Thank you.

Scott Sorrell (01:03):

Any, any special drinks that you have tonight? I know maybe may, maybe not, so, but what if, if you, if you were at a pub tonight, what you got bubbler? If you were in a pub tonight, what would you be drinking?

Dr. Laura Hernandez (01:16):

Probably wine. Probably wine.

Scott Sorrell (01:19):

Good. Red or white. Do you have a preference?

Dr. Laura Hernandez (01:21):

Definitely red. Definitely red.

Scott Sorrell (01:23):

Good stuff. I love a good red wine. And see I see you brought a guest with you here tonight. Would you mind introducing your guest and how did you decide to bring him along with you?

Dr. Laura Hernandez (01:33):

Absolutely. Well, I was very honored that Dr. Tom Overton agreed to join us. Tom, I've known since, I think I was in grad school, probably read all the papers and have gotten to know him more since I was a professor. And I think I mentioned offline. I am not a nutritionist. I'm definitely a physiologist. So I always like to have a good nutritionist available to chat with. And I think, you know, he's one of the best and definitely the most practical and works in the space I do. And so I, I think he was the right person to choose to talk about this, so,

Scott Sorrell (02:09):

Yeah, absolutely, they, I'll, I'll second that, Tom, as one of the best. So welcome Tom. It's great to have you back here. This is not your first time at the Pub, so

Dr. Tom Overton (02:19):

No, it's not. Thanks, Laura, for the invite. It was really nice to get that opportunity to join here today.

Dr. Laura Hernandez (02:24):

Yeah, thank you.

Scott Sorrell (02:26):

So, Tom, anything in your glass tonight you'd like to share with us a

Dr. Tom Overton (02:29):

Bottle of Tonic

Scott Sorrell (02:31):

but well, we thank you for joining us, Tom. And not least, I'd like to introduce my trustee, co-host Dr. Jeff Elliot. Jeff, this is not your first time here either. So what's in your glass tonight?

Dr. Jeff Elliott (02:45):

Well, since I work remotely in my home office, no one can tell me not to have a cocktail. While we're doing this this is a take on the tequila sunrise called the Holiday Sunrise. My daughter came up with this over a holiday competition that we're doing this season, started Thanksgiving, going through Christmas, and each of us has to come up with a seasonal cocktail and we judge them, and the pri the winner gets, I think, a prize and I'm probably having to pay, pay for that prize, but I haven't been told what the prize is yet, so, yeah. Yeah. So, but yeah, it's, she did a really good job, so I'm having it again, so,

Scott Sorrell (03:27):

Good deal. Well, thanks for joining us tonight, Jeff. Now I've been in a rut lately, and I think I mentioned that on my last podcast. I've been having woodford's every time, and so I decided I was gonna have something different, so I went and bought a nice bottle of Widow Jane. But that, that plan was foiled. My, our our our pump quit working here at the house. We didn't know what to do. So my wife Mary says, you know what? Our new neighbor, I've never met this guy. He's a retired plumber or electrician or something. I think I'm gonna give him a call and see if he'll come over and look at him. I'm like, okay. You know, I said, gee, can I pay you? And he says, no, you know, I, I, I won't take anything. But, but we had been, while he was there, we had gotten talking about bourbon. So he, he likes bourbon as well. So I tell you what, I got a bottle of widow Jane that I'm willing to part with. So, so Mark, I don't know his last name. Mark's got my bottle of Widow Jane. So that's, that's my story this evening, . Anyway, all good plans, huh? Folks, thank you for joining us tonight. So I look forward to a great conversation. So cheers.

Dr. Jeff Elliott (04:33):

Yeah, cheers. Cheers.

Scott Sorrell (04:43):

The economics of feeding ReaShure Precision Release Choline. ReaShure fed during the transition period. And because it's fed for such a short period of time, it costs just $15 per cow, and yet the benefits will continue to generate income throughout the year. Cows fed ReaShure produce five pounds more colostrum, which pays for your reassure investment on the very first day of lactation cows Fed reassure also produce five pounds more milk per day every day. That means after the first day, every day is payday invest in ReaShure during the transition period and recoup your investment on the very first day of lactation after that. You got it. Payday. So, Laura, I'm gonna jump right into it. In 2024, you hosted a great webinar before the real science lecture, lecture series that led to some interesting conversations and questions. Can you please give us a quick overview of that webinar and help explain the topic of the role of the mammary gland in governing calcium metabolism during the transition period?

Dr. Laura Hernandez (05:55):

Sure, I'd be happy to. So for a while now I've been working in the field of calcium by accident. I really am a mammary gland biologist and was trained to kind of think about things in the production of milk and how that impacts the mom or the cow in this case. And I ran into some things that along the way that suggested that the hormone I'm interested in was regulating calcium. And so I started doing a bunch of experiments over the last 13 years, and lo and behold, I sort of do calcium now. And because I was trained by someone who really thought Dr. Bob Collier that there were things coming from the mammary gland that could manage what the cow was doing. And so I, I've been working on that and looking at that, and over the last several years I've been working on how we can do things in the prepartum period, particularly to manipulate what's happening in the mammary gland to make sure the cow has adequate, not only endocrine status, but nutritional status and cabin better be healthier as a whole from a reproductive standpoint, a nutrition standpoint, like an immunological standpoint.

Dr. Laura Hernandez (07:17):

And what we've seen across a few different types of studies we've done depending manipulating a bunch of different things, was that it's really this drain of the mammary gland of the milk of which it has lots of calcium in it. Highest mineral content was triggering all these mechanisms. And so what I went back in the literature and dug to a really cool paper that I think I mentioned in my talk back when you could do fun things like remove organs, and add stuff back. Yeah. And was a paper Jesse Goff did, where they mastectomized some cows, and it was about two months before partition. And what they showed was that the cows could cal in and maintained normal calcium if they weren't making milk, but if they were making milk, their calcium, you know, rapidly decreased at calving. So we kind of went through that and we've been looking at different ways to improve that.

Dr. Laura Hernandez (08:21):

And in my very, like physiologically manipulative experiments, I crossed paths at one point with Jess McCart looking at a lot of data that Tom has put out from his lab. And really we're seeing similar things from an epidemiological perspective and applied nutrition perspective and what we were seeing that really supports this phenomenon. And it's not the only one that occurs, like you could say the same for like fat and energy and different components that are being secreted into the milk that are having this, what we call negative feedback. And so that's what I've been studying now and I've been looking at a bunch of different ways to manipulate that and try to describe what's actually happening so that nutritionists and producers can make decisions better knowing what's occurring and what's for best, the best strategy for their farm.

Scott Sorrell (09:22):

Yeah, I was watching your lecture again today in preparation for the podcast. And I've got a little bit of an offbeat question for you, but recently Dr. Van Amberg presented some data showing how the percent of protein and fat has exponentially increased over the last few years. And it got me to wondering is has there been any changes in, in mineral content be that calcium or phosphorus, And, and how has that changed anything, if anything?

Dr. Laura Hernandez (09:55):

It's a great question. Calcium and phosphorus are pretty stable in the milk relative to like protein or fat. The, and fat by far is the most variable and protein being the second, but it takes quite a bit to change the amount of calcium or phosphorus going into the milk. The one thing I would say that you, you can consider, and I don't know that it's a fact, is that with higher protein secretion, you get more calcium and phosphorus because there's calcium and phosphorus attached to the protein that's being secreted into milk. So what we would call the bound calcium and phosphorus might be higher but not necessarily the free.

Scott Sorrell (10:40):

Got it.

Dr. Jeff Elliott (10:42):

But going back to his question, it's one of the questions I'd written down that more philosophical, but thinking about what is normal, first of all, and has that changed over the last 50 years, and especially relative to where we are on milk production. Mm-Hmm. So Laura, you're, you know, you're suggesting that calcium and phosphorus, it's hard to, not hard to change it, but it stays fairly the same, but these cows are producing a lot more milk than they were 10 years ago, much less 50, right? So I just wonder is has normal changed?

Dr. Laura Hernandez (11:23):

So that's a great philosophical question because it has, and, and I would say that like one of the things that's difficult with interpreting what we do now versus what even someone did in 1985 is huge because they are producing more, the animals are different sizes, the feed is better. There's a lot to be said for what we do. I do think that normal has changed. I think there's been some adaptation of the animals to maybe be more hearty, should I say. But I think they're more efficient. Like certainly they were more efficient when they were on BST. That's without a doubt. But even without BST, they're fairly efficient, you know? I don't know tons about protein, so don't like, don't shoot the messenger or anything here. It's just like a, a thought exercise. But even if you think about some of the stuff they do with protein, they're always trying to change things.

Dr. Laura Hernandez (12:30):

Every, what I read anyway is like two to two point a half percent. And I can't figure out like how much of a difference they're making in any which direction. It is hard to tell because maybe quality's better. I, I don't know, again, not a nutritionist, but cows are doing really well and we've adapted them to do so. So I feel like normal has changed. And that's where I struggle with like absolute concentrations of things because we live off of that, that's what's published. And sometimes I think we're saying something could be ill or not Well, and she may be fine,

Dr. Tom Overton (13:17):

You know, I think, I think normal has changed, right? So I mean, but I also think it's changed for the better mm-hmm . Fo we're focusing on issues differently, right. So, I mean, and you know, I mean this goes back even kind of my time, right? But I mean, you know, I mean, clinical milk fever rates at five to 10% of cows calving, right? Probably was not unusual. I know for sure that, you know, when I started, you know, in, you know, back 2000 ish, right? I mean herds, you know, six to 8% das percentage of fresh cows on a herd, that was pretty typical, right? And, and you know, we accept none of that anymore. Mm-Hmm. Right. So I do get, occasionally we'll have, you know, Laura and I have some academic colleagues, we'll, we'll say that, you know, well, we haven't made any progress in transition cow health and, and things like that. And I, you know, I quite firmly dispute that. 'cause We know what the farm level indeed we have. Well just look at sematic cell counts.

Dr. Tom Overton (14:15):

Yeah.

Dr. Laura Hernandez (14:16):

Yes.

Dr. Tom Overton (14:17):

I mean, you know, anything, our farmers supported by our, our agribusiness allied industry folks and university folks and things like that, they've made tremendous progress, right? And shows up in, in not just health, but also in milk yield and reproduction and all that stuff. And all this stuff is multifactorial. But you know, I mean, you know, 25 years ago, Laura, probably nobody was, nobody's thinking about subclinical hypocalcemia

Dr. Laura Hernandez (14:41):

No.

Dr. Tom Overton (14:44):

Eighties or nineties, right? It's mm-hmm . And that's now where absolutely the focus. And you know, if you, if you told me 15 years ago that we, that there'd be as much calcium biology research epidemiology as nutrition as we've had since then, I would've been like, oh, we figured calcium out a long time ago. Right? Yes. Mm-Hmm . And it's astonishing what your lab has been able to unravel from a mechanistic standpoint and otherwise that really has supported, you know, some of the, some of our ability to, to kind of get this, get this right out there.

Dr. Laura Hernandez (15:16):

I think so. And I can remember the first grant I submitted, someone said, maybe it was you, Tom, I'm just kidding. Maybe it was, but like someone actually put in their, we don't need to study calcium. Like it's done. I was like, oh, okay. Maybe it is, I'm wrong. But it, it's been fun because I think, like to what Tom points out is it's been a synergism of producers, veterinarians, academics, like really trying to say what is happening and before making any like very definitive claims and how we can adapt stuff better. But I, it's amazing how healthy I think a lot of our animals are.

Scott Sorrell (16:00):

So Tom, you talk about it being multifactorial. Is it genetics? Is it management? Is it our understanding? Yes. yeah, I'll, I say that wouldn't put an emphasis somewhere.

Dr. Tom Overton (16:17):

Well, you know, I think for, probably depends a little bit on what it is, right? I think for, for production traits, components, things like that, genetics is certainly in there as well as the management. I think for the things that we're talking about here today, much of it's the management around it, dietary and otherwise, right? Then helps these cows helps these cows make it through this period better than they used to. So not to say we don't have opportunities still, right? Because we sure do. And there still are, and Laura, you did a nice job. You know, there are a lot, there are still questions out there, right? But, but I think we, we've, our understandings come a long way and our ability to, to manage calcium metabolism has come a long way as well. So,

Dr. Laura Hernandez (17:01):

You know, I, I'd say too, I think that like digging deeper has provided more opportunities for farmers to use practices that work best for their management system rather than only being able to tap into like one thing, here's the one thing you can use and try to shove a square peg into a round hole kind of situation. Whereas like, we have such a large range of size type of farm milking system management practice, you know, people working there. And it really, one thing my colleague Myla Wilbank always says like, double off sync works, but they have to give 'em the shots when they, when they're supposed to, right? Like, and I, I think that could be said for new, for prefresh nutrition too or anything else. Like, so if you have more tools in the toolbox, you can use the one that like the people on at your facility and farm can implement and implement correctly and know how to handle the animals, you know, the response to that more efficiently. Because it's not a one size fits all by any means.

Scott Sorrell (18:14):

Yeah. You know, talking about tools you presented some data during your presentation on, on some of the interventions that that, that are being used. Can you talk a little bit about that data? Maybe, maybe what your recommendations might be?

Dr. Laura Hernandez (18:28):

Sure. I think, you know, kind of the classic things that are out there, like the really like low input kind of strategy would be like a low potassium diet. And there are folks who still do that. And that's good enough for them and they can do it consistently and and manage their herd pretty well from a pretty fresh standpoint. The other two would be like clearly negative DCA diets work. There's a lot of them. It's, if you have some kind of negative DA diet metabolic acidosis and you're urine ping works really well. If the cows are eating it, if the diets mix well. All in all those things work, you can do it for a long period of time without having any issues with the cows. So like, depending on what your Penn strategy is fresh like that might be the easiest.

Dr. Laura Hernandez (19:31):

There's a newer technology to the US anyway was being used more in Europe, but that would be the zeolite clays both of which Tom and I have done a little bit of work with. And that is a, a binder that binds two plus ion, so like magnesium, phosphorus, calcium it was largely thought that it was primarily a calcium binder. My data, and I think more data now suggests that it probably works primarily through a phosphorus reduction mechanism. And that is a more like acute treatment of 10 to 14 days prepartum, which if you can do it appears to work well for calcium purposes but it you can't really feed it for an extended period of time. That's appears to be somewhat contraindicated. And so they're still working out some of the information related to that and application in the US because all the data prior to Tom's study was performed in various situations in Europe.

Dr. Laura Hernandez (20:47):

So I've heard like some of the systems where they are like grazing and they're maybe only milking one time a day, that might be simpler for them to implement. But I, I think I've heard from producers that D ad and works really well if they can do it. The zeolite clay will work really well if that works for them. But again, it gets back to your grouping strategy compliance by the staff on mixing and your in ping if you're doing DCAD. And, you know, those kinds of things become important. But what we've shown is that you have to be looking at things from a couple of different ways because the clay is a phosphorus driven biology. And so management of cows is different I would argue compared to management of cows like in a metabolic acidosis, which is largely a calcium driven biology.

Dr. Laura Hernandez (21:51):

And so I think there's questions from veterinarians surrounding low phosphorus what that might mean long term. And some of the outcomes in post-fresh cows, like if you do have a cow that goes down, she's almost certainly low phosphorus and not low calcium. And I don't think people were thinking about it that way initially. And that's why the work we do is really important because in real life, in real time, the vet or the farm staff has to make a decision of what to do. And if you give a cow who's low phosphorus calcium, you can have rebound milk fever. So those kinds of things are really important. And so I would say from a fresh strategy, those are the two like tools we have in the toolbox beyond managing potassium. But I'd be curious to hear what my colleagues have to say on that.

Dr. Tom Overton (22:53):

Yeah, I mean, Laura, you hit it really nicely, I think. I mean, you know, of course low, you know, low potassium diet is just partway on the way to low dec ad, right? Because it's you one of the cation image. So so Laura, I watched, I did also watch your I'd watch your webinar shortly after. I was invited to join you. And I also watched it at five 30 this morning to for this,

Dr. Laura Hernandez (23:15):

What a way to wake up.

Dr. Tom Overton (23:17):

That and a good cup of coffee was a nice way to start the day. But anyways, I think one of the things when you present this stuff, and I think it's, it's really interesting because you kind of, you refocus this a bit, right? Because a lot of us think about re med metabolic regulation, the transition cow, and it's just like all this stuff happens and all these other body tissues to just like throw stuff the mammary gland. And you kind of think of the mammary gland as, as the receiver in this case, yet you do a great job of kind of reminding us that while the ma isn't actually a very active participant in that regulation and calling the shots, and I think that's, that's fascinating to, you know, kinda takes me back also to, you know, some mutual mentors of ours, like mm-hmm . Bowman, and of course your primary, you know, Bob Coley or people like that. And, and really interesting and, and I think one of the things that also struck me you know, you was listening to your discussion on calcium balance and lactation, and I guess I either didn't realize or didn't pay attention, but I mean, you know, you say these cows are in negative calcium balance through 150, 200 days in milk. That's, that's amazing

Dr. Laura Hernandez (24:24):

Actually. Yeah. It's quite it, it's quite like overwhelming at times. , and every time I've spoken with Jess and I just saw R Nevis a couple weeks ago at Purdue, and I'm like, man, we need to get like a machine that we can put the cow through so we really know what her bones look like. Because she's very resilient and so are all like mammals. When they're lactating, it's quite impressive that they're able to get to this like, neutral and re accrue what they need. And that biology is, is always stuns me that that's kind of one of the conserved phenotypes of like mammals in general. And, you know, you wanna make sure they're getting enough calcium, but there's this compensation, like a lot of different things that's occurring from her directly as we keep pulling milk out until she can hit that peak phase and start to shift gears again. So,

Dr. Tom Overton (25:37):

Because that's not a lot of time between that time and, and when she calves again, right? Seems like she's got a, I mean, I think you said there's like eight and eight and a half kilos of total calcium Yeah. In bone. Is that total in bone?

Dr. Laura Hernandez (25:49):

Yeah.

Dr. Tom Overton (25:50):

So how much, what does she go down to? Do we have any We don't really know.

Dr. Laura Hernandez (25:54):

No. I've like, I saw some really, really old papers but they were largely like in sheep. But I haven't really seen a good one in cow that can in bovine that to, to talk about that. And this is why Ralph told me I can get like a 600 kilo cow into the horse micro ct and I was like, well, I don't know, that might be still too, too small rough. But I, I think I'd really like the opportunity to kind of solve that because maybe she's completely different or maybe it's not as robust, but we don't really know. And the only way like we've thought about is taking like a biopsy from the pin bones to see if we can get it at least turnover within the tissue because it's really hard to decipher an animal that size without ashing her, which is not what I wanna do. So,

Dr. Tom Overton (26:58):

You know, from a nutrition standpoint, I, you know, I occurred you should we be feeding more calcium and lactation

Dr. Laura Hernandez (27:05):

Possibly

Dr. Jeff Elliott (27:05):

Intuitively. That's what it sounds like. Yeah.

Dr. Laura Hernandez (27:07):

Right.

Dr. Tom Overton (27:09):

Or is some of this just hardwired into her regulation Yeah. And metabolism where she's just going to her bone just going to do this regardless of what else we do. And, you know, you think about things like, you know, 25 hydroxy vitamin D and things like, I mean, I, boy, you know, yeah. It's, it's,

Dr. Laura Hernandez (27:27):

It's, well I'd say in humans, like they'll lose up to 10%, sometimes 15 in the, if they're breastfeeding only for the first six months. So it's pretty like hardwired that she'll keep pulling it until they get to parody, right? And then she'll start to like, I don't know if it's that they rapidly increase absorption and that allows for more storage if it shifts the hormonal signals. But that's one thing I'd like to do as well and be able to do it in a live animal accurately. Because that's the other part too is the gut part, right? Trying to understand what's happening in the gut in real time because that's a difficult thing to get at without using like calcium 45 or something, which they are not in favor of you doing these days. So trying to understand that that better is like what's the rate of absorption within the gut and like that in relationship to her endocrine status and her milk production. I'd really like to do that and be able to compare it across stage of lactation. So like the late pregnant cow, the early lactating cow, and then the cow that's like at 150, 200 days in milk and try to see if we could put that puzzle together.

Dr. Jeff Elliott (28:56):

So Laura, You know, I guess I've kind of accepted, you know, as I came into this industry that multiparous cows are more prone to milk fever, you know, that's what we learned first. Calf heifers don't, but, but why, why, you know, we just accepted it and now it's making me think why is that, is there less ability for those cows for bone resorption or is it a in later lactation when the calcium demand's not so great, they're not getting enough calcium back into the bone that they don't have it for the next lactation, right. Or is it just the biology we don't understand?

Dr. Laura Hernandez (29:37):

Right. Those are all great questions. I, I don't have a definitive answer, but I don't know if that as they age, like they're just not as effective in their, in the absorption of the nutrients or if there's also something related to, 'cause we do know females have a harder time with their bone because of estrogen. And so I don't know how how estrogen declines like overall in a cow like, or in her lifetime as it compares to a human. But it's one of the things that they've seen like in humans where that have offspring later in life. They can have issues with bone turnover and they'll see fractures sometimes in those lactating women because their density is lower, because their estrogen levels are lower on the same side. Like, and I wonder this because we've learned too, what you just said, it's what I learned.

Dr. Laura Hernandez (30:40):

But in those growing animals are, is there some kind of missed opportunity there too that we don't know what's happening in them because they're still depositing bone because they see those also occur in like, say, teenage women sometimes as well, that when they have a baby and they feed do breastfeeding, they'll have problems as well because they're still depositing bone until they're like 25. So I don't know if it's an endocrine thing, it's an efficiency of their gut, potentially their absorption or if it's also like you get real technical stem cell sort of thing, kind of like you see in the mammary gland over time as lactation goes on, or you go through subsequent lactations I think it was like Tony Capco that did this work, but like they have less and less stem cell populations in their tissue to have regeneration of the tissue. So I don't know if that's a thing too. But there's these like disparate ends of young and old and then there's the ones in the middle that do mostly Okay.

Dr. Jeff Elliott (31:54):

Yeah. Yeah. Hmm. It's intriguing for sure. I even had a nutritionist call me one day and he asked, and I, I think you and I talked about this at the Cornell conference. He asked me about vitamin K two.

Dr. Laura Hernandez (32:14):

Oh yeah, you did.

Dr. Jeff Elliott (32:15):

And I was like, I don't even know what that is. And he said, well, Alchem makes it. I said, well, we make it on the human side. Scott, I don't know if you're aware of this. Yes, I am. Yeah. But apparently one of its functions I think of vitamin K is blood clotting, but K two vitamin K two, part of his function is getting calcium into the bone. It expedites that. And he was wondering if that, you know, could we feed some of that late lactation to help just basically longevity of the cow as well, Not just about calcium mobilization. Right. Better bones. So it was, yeah, I mean there's, there's, we don't know what we don't know. Sounds like a research project

Dr. Laura Hernandez (33:00):

Exactly. So Exactly.

Dr. Tom Overton (33:04):

You know, Laura, so one of the interesting areas that we, you know, kinda get into right? Is, you know, what farms do at the, or what cruises do at the farm level to give calcium, right? And different way shapes and forms. And I, you know, there's some older data, not that old I guess, where, you know, you know, some folks leave, you know, 500 mils of 23% calcium bora-gluconate IV to, to cows that were just clinical and they got a big spike in calcium and then some rebound hyperemia after that. And I was really interested to, to, when you talk about Megan's study there, right? With your, when you're basically just trying to use calcium gluconate post calving. But what was interesting in yours is that, you know, a farm gives that at 500 mils in a, you know, in a relatively short period of time, whereas you guys spread it out over like 20, I mean, I think it was a hundred miles an hour

Dr. Laura Hernandez (33:55):

For about that, Yeah.

Dr. Tom Overton (33:57):

24 hours and yet they still crashed. Essentially when, when, when you guys quit doing that calcium. So I'm curious what you're, you know, we, we've been, Jess and I have both been pretty, you know, one when farm has milk fever issues. Really trying to get to the bottom of, okay, what is that farm actually doing beyond what might be happen to diet ie. Calcium menstruation. But you know, I mean, I find that really interesting that even in your case where you spread it out, they still crash pretty hard look like.

Dr. Laura Hernandez (34:31):

Yeah. and this gets to the timing and timing is everything. And that's where I showed her that data one time when we were both like on a speaking thing and we were talking, and then she showed me some of hers and Ross data about the, the classification. And that was where this really became interesting because we were trying to keep the cows normal calcemic for the right after calving. I think during that time most people were trying to take a blood sample within the first 24 hours of calving and making decisions, subclinical clinical, this is what our population looks like, this is what we need to do. So our, our goal was to really say like these, and what my hypothesis has always been is that you have to have a decrease to trigger negative feedback. That's how negative feedback works.

Dr. Laura Hernandez (35:34):

So we wanted to keep the cows so normal calcemic during that first 24 hours. And so we were just adjusting our infusion rates based on the cow's response to the, to the calcium. And what we saw was because she never decreased or none of them decreased during that first 24 hours when we stopped giving them calcium, they, they had their negative feedback response and it was like, we need to go down because we need to reset everything to come up to what's appropriate. And we saw that even in the cows that were receiving the negative dec a diet, so we prepped them to Cal in better. And then we did that, and then that kind of erased our negative DCA diet response that we saw when they were just getting control saline. And so to me what that says is that they need that time.

Dr. Laura Hernandez (36:33):

And so when people ask me what to do and I, my, like I try, I am like, try to get to 48 hours before you take a blood sample. Please try. Like if you really are itching to take one earlier, wait till 36, but like ideally wait for 48 hours because calcium, and I think I showed this in the talk, is really a combination of when you decrease your calcium, how far you decrease the calcium, how long it stays decreased and, and when it decreases. And that was exactly what Jess saw in her classifications of like the delay, the persistent, the transient, and the normal hypocalcemic animals. And when they were classifying cows in that way and looking at these clinical outcomes of DA or, you know, take your pick it came back to this like 48 hours timeframe. And because you could take a blood sample at 12 hours and it might be normal, but she hasn't gone down.

Dr. Laura Hernandez (37:51):

And if she goes down later on in those cows that were, that they classify as like your late delayed hypocalcemic cows, you would miss those. And similarly you might get the opposite, treat a cow that you didn't need to treat because she was at her Nader and coming right out of it. Right. And of course, it all depends on what your cut point is, which no one seems to agree on. It depends on what your outcome variable is. And so that has been what I tell folks when they call me you know, and I've told them like, if you can wait unless a cow is ill like letter B. And then if you think she needs a bolus or an iv, like sure if, you know she had milk fever last lactation or maybe had a DA or RP or some other combination thereof, maybe then give her a bolus two. Or if she's like a crazy high producer in her fourth lactation, she could probably use it. But in general, if you could leave them alone for 48 hours they'll probably be all right. Unless you are having bigger issues. And so that's what I try to tell people when they ask me for advice, which is here or there, not, not super often.

Dr. Tom Overton (39:24):

Yeah. And it's interesting. So again, people would do some of this, they do it with good intention because they think totally these cows, I mean their, their heart's in the right place, right? They think, okay, cow needs calcium, therefore I give calcium. And yet, and, and there's at times it's like I don't know, it, it takes a while in the discussion. Sometimes they're reluctant to admit what they're really doing, and so you gotta kind of keep digging and digging and digging and, and then it's like, oh, okay. Yeah. Alright. So Jess and I have had a few of those experiences together. It's also, you know, pull, pull a veterinarian in the nutritionist in, of course you get milk fevers, nutrition gets blamed, right? So regardless of what we going at the herd level, and so, you know, it's why you just gotta try to understand it all, but it's, it's really, really insightful. So

Dr. Laura Hernandez (40:10):

I'd say too, and the other thing we learned and why I think studying this area is important, or any of these like, you know, really metabolic type health issues and under understanding the physiology is you can't give calcium to a lot of those exilic cows because if they go down, I don't know what you, what you guys saw with Allison's study, but they're usually phosphorus, low phosphorus cows, and unless you have a blood phosphorus, you don't know that. And so you give them the calcium and then a lot of times they rebound because what they really needed was phosphorus and their calcium was just fine. At least that's what we saw in our experiment. And we had to like hold the farm staff back. I had to like explicitly in my animal care protocol run the I stat before you give a treatment because you know, you could be giving them the wrong thing. So

Dr. Tom Overton (41:11):

Yeah, we've done that at times in that particular study. We actually didn't have to treat anybody, so we never really,

Dr. Laura Hernandez (41:15):

that's great.

Dr. Tom Overton (41:16):

We really never really bring into that issue of, okay, what do you do with her? 

Dr. Laura Hernandez (41:20):

So yeah, I think we had a couple, so it wasn't like a lot, but we had to take a couple off our study because they just gave the calcium and lo and behold their calcium went super high. And it was a phosphorus issue. And so I, I think that's why our, our, you know, our science is super important for the industry.

Dr. Tom Overton (41:45):

It was also clear, you know, you had that study where you did the prepartum chelation, right? The Prepartum GTA I think it was six hours a day for the last seven days if my Yeah. Notes are accurate from this morning.

Dr. Laura Hernandez (41:57):

Good job.

Dr. Tom Overton (42:00):

You know, I saw they needed more EGTA to as they approached calving to mm-hmm . To really ate that calcium. But I was curious to, you know, I didn't look at the, I dunno if that's fully published or not, but classroom yield, classroom yield in those cows. What, what does something have if you're chelating mm-hmm . You know,

Dr. Laura Hernandez (42:19):

Were they different?

Dr. Tom Overton (42:20):

Yeah. Were they different?

Dr. Laura Hernandez (42:22):

They weren't on this study. It's not huge, right? Because we're doing highly manipulative things, but we didn't have any colostrum differences. It was what I've learned and the purpose of doing that was to make these arguments that like all these things work differently. If you're manipulating calcium, it does one thing. If you do manipulating phosphorus, it's another, if you're dealing with metabolic acidosis, that's something else. And they're all to the same endpoint, but understanding what each is doing would help you manage cows better. And what is one versus the other? But when we were doing this, we were focused on understanding specifically what was calcium doing from the standpoint. And I thought we were gonna have to use not as much EGTA as we did. The early lactation cows that we've done EGTA treatments with they like are very resistant to that calcium.

Dr. Laura Hernandez (43:26):

And I think, you know, it's a, a an effect of lactation. And so I suspect at this period of time, because of the amount of colostrum being pulled together and the higher protein concentration of colostrum that there was probably significantly large draw at that period of time plus like whatever the calf needed as well on top of it. And I believe that's largely why they were more sensitive than even the early lactation cows. But it, it was just another indicator that the mammary gland is like, no , it is for me, and like, cow, you stay okay, you stay good enough. But like they were really fighting with each other on trying to like take it away from her because she wanted it, you know, for partitioning, again, for the calf and for her milk.

Scott Sorrell (44:25):

Yeah. I think that happens with a lot of nutrients, right? Mammogram gets the priority.

Dr. Laura Hernandez (44:31):

Priority. Yeah. Yeah. So I, I don't know, it's kind of funny. I didn't realize I was like saying anything too crazy. But like I went to speak at Cornell the first time, I think when I was in 20, in Syracuse, like in 2014 or something, and Dale was in the audience and he's like, I am so glad you're saying this. And I was like, am I that radical? Like this is, this was the first thing I learned from Bob. But you know, it's definitely a paradigm. Like he, Kevin Haring would be another that I, I think very much thinks from that perspective. But when you read all this stuff and all these maternal species, it, it is quite impressive what these mothers can do. And that's really like the basis of my, my science. So

Scott Sorrell (45:32):

Yeah. Yeah. Kind of a question for both of you, Lori. You started off saying that you know, in the very beginning people said, Hey, we, we, we know everything about calcium and obviously we've talked about a lot of different things today that we don't know where, where should the priority be in at least the near term midterm research that needs to be done in this area

Dr. Laura Hernandez (45:54):

In calcium? Yeah.

Dr. Laura Hernandez (45:57):

I think that there's a lot of opportunity still yet to understand you know, for one, because there has been more uptake of exel it, and it's a newer technology in the US like understanding how that works biologically. Because DCA is really, you know, tried and true, but it wasn't at first either. And it took, it took some time to get there. And so I, I think we should continue to be rigorous in our quest for understanding that. I also think that personally, because I'm interested in, it's this understanding of like the gut what's happening in the mammary gland and in the bone in an actual cow that, you know, in a Holstein or a jersey, but a dairy cow and understanding that biology better. And like I have some thinking of ways to do it without, you know, costing a vet school probably many millions of dollars to buy a, a very nice fancy machine.

Dr. Laura Hernandez (47:03):

But some other thoughts of how we could maybe get at that like by measuring foot health and stuff, because those are high stress points for cows. Like different ways we could maybe answer some questions. But I do think those are really important. And understanding in general, not just calcium, but I think in general as nutritionists and physiologists, that we should look at things at these different components of lactation because a lot of times our studies are focused in the easiest animal to handle because they're more in control. But like data is so different in these animals in a pre fresh cow than it is a mid lactation cow. And you know, we have a tendency to extrapolate because that's our best knowledge, right? And I think more work should be done in those because lactation is very dynamic.

Scott Sorrell (48:00):

Yeah. Tom, from your perspective, what would you say?

Dr. Tom Overton (48:04):

Yeah, you know, a couple things, right? I think from a field practical perspective, you know, in both, both LO's study and, and our study binder, you know, and actually when, when we did ours, it was all about calcium ba, right? There was no discussion of, of almost anything else. Or they're like, well, maybe phosphorus in here somewhere, you know, but we were both at 500 grams per day. And that at the time we did the, it was like, it was like, that's it, period, end of story, you know, doesn't matter what, what else the diet looks like, things like that. It was just that. And now both companies that are marketing these, these binders, they're now relating it to a certain proportion of grams of phosphorus, which brings 'em down into the, you know, 300 plus or minus range, right? So versus the 500.

Dr. Tom Overton (48:50):

And so, you know, nobody's really done that work. Nobody's looked at these things in one group, dry cow system. I, I also share the reluctance to feed them for longer than a standard closeup period, just without just things like chartered waters. I think from a, from a more scientific standpoint accounting for where all the calcium goes, right? It just feels like we don't have a greater understanding either prepartum or postpartum of, you know, 'cause I mean, again, you get a little bit of calcium in the urine, but not a lot. Definitely get some in the, in the feces, obviously you got some going into the bone milk, but I mean, you know, I, I don't know, when we try to do some rough math, it's, it's not always easy to account for where things are going. It's gotta add up to, it's gotta add up to one a hundred percent, you know, gotta add up to, so, so I don't know. So there's, there's still stuff here biologically to, to kind of sort through, I think.

Scott Sorrell (49:47):

Yeah. You know, kind of circling back to something Tom that you had said earlier, and I think Jeff had alluded to as well, is those, you know, they're, they don't start they, they don't reach energy balance until later lactation. And, and do we know if they are depositing enough calcium back? And if not calcium

Dr. Tom Overton (50:07):

Balance, not

Scott Sorrell (50:08):

. Yeah. I'm sorry, calcium balance. Yeah. And then how do we determine that and then how do we improve upon that? You, you kind of mentioned nutrition, or is it, Jeff mentioned the K two. That is kind of intriguing. We, it's cool. We do have that. I have no idea whether or not I think it's expensive. I think that's what I've heard , but I seems to me that might be an area as well. Sounds good. Looks like the girls then just flash the lights. That means it is last call. And so with that, what I'd like to do is ask each of you, let's go around the table and, and what are just a few takeaways that you'd like to leave with the audience tonight. And, and Jeff, if you don't mind, would you lead us off

Commercial (50:52):

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Dr. Jeff Elliott (51:17):

Yeah, certainly. Well, I'd love the reference, 'cause I'd forgotten about it too, that it seems like 20 years ago I'd heard that Oh yeah, we know everything there is about calcium now it's, we're, we're solid there. And, and it goes back to the oak cliche. You know, we don't know what we don't know, and there's still a lot to discover, and we've seen that with kind of the Z light products, new products out there. Are there other ways to, you know, skin the cat? So I think it's gonna be interesting few years in calcium mobilization, but a lot of other things keeping up with milk production and the components that we have. So

Scott Sorrell (51:58):

Yeah. Thanks Jeff. Tom, thanks for joining us here again with Real Science Exchange. What, what thoughts do you have for us?

Dr. Tom Overton (52:08):

Yeah, I just, you know, I've got, I've got a huge amount of respect for, you know, the work that Laura and her group have done, you know, to help us unravel some of these things. Again, Jess McCart on the, on the, you know, again, on the epidemiological applied, you know, calcium treatment side, right. You know, and, and other groups have been in the mix too, on the nutrition side. I mean, Laura, just a quick comment. I mean, you know, my, my group doesn't often complain about sampling schedules, but if they ever do, I'm just gonna point to, to one of your paper briefly because from a, from a rigorous and frequency of sampling standpoint. So, but no, just fantastic work and a privilege just to, just to come on today. So thanks Scott. Thanks Laura. And Jeff.

Scott Sorrell (52:50):

Yeah, thanks Tom. Laura, any final words for us?

Dr. Laura Hernandez (52:56):

I just wanna thank you for the opportunity to talk about it. I know I'm a, like a pretty intense physiologist but I think I was trained to be curious and that lactation is a cycle and that we have to really think about that and how the mammary gland is directing the show. And so I, I like to approach things from that way, but I've been fortunate to learn from a lot of cool people and had a lot of great support and it's been fun as a basic scientist to like cross paths with, you know, epidemiologists and see your work really have impact. And, and that's been a lot of fun in getting to know Jess and Tom and Sabina Mann too. And we've, we've done some cool things together and, you know, I, Tom, I buy them a lot of pizza, and cake and throw a lot of parties, . And I often go out there and sleep at the barn with them if they let me. But I, I've been really lucky with an amazing group of scientists over the years. So they almost always are game, which is a surprise because assembling schedules are brutal.

Dr. Jeff Elliott (54:08):

one, one other thing I would add, I was thinking about is, you know, the last few years we've talked a lot about the longevity of the cow and how many rotations are we getting? And I think what Laura's doing is gonna be key in, in that, aside from just, you know, milk fever, subclinical milk fevers, just yeah. You know, yeah. It's gonna be key in that.

Scott Sorrell (54:31):

Yeah, great point. So, Laura, I'm not an intense physiologist and I admittedly this topic was a bit intimidating to me, but I've gotta say it's, it's been enjoyable and understandable for me and appreciate the two co-hosts here, Tom and, and Jeff for coming along and helping out. This has been a great podcast. I've enjoyed it. And I want to thank you guys for, you know, spending time with us and, and lending your expertise and, and knowledge to the industry and to our loyal listeners as always. We really appreciate the fact that you come here and spend time with us. We hope you learn something. We hope you had some fun, and we hope you see you next time here at Real Science Exchange, where it's always happy hour and you're always among friends.

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