Our Real Science Exchange pubcast always has leading scientists and industry professionals discussing the latest ideas and trends, and tonight we have two very well-known guests. Dr. Lance Baumgard and Dr. Jim Drackley join us to discuss cow management and the dogma that has developed over the years.
Guests: Dr. Lance Baumgard, Iowa State University and Dr. Jim Drackley, University of Illinois at Urbana-Champaign
Our Real Science Exchange pubcast always has leading scientists and industry professionals discussing the latest ideas and trends, and tonight we have two very well-known guests. Dr. Lance Baumgard and Dr. Jim Drackley join us to discuss cow management and the dogma that has developed over the years.
Dr. Baumgard kicks off by explaining the dogma of the transition period - two metabolites reduce the animal’s immune system and predispose them to health disorders. (5:38)
Dr. Drackley continued by saying he was influenced by research that could show in a clinical case of ketosis, there is an underlying subclinical, perhaps inflammatory pressure, causing the problem. (20:39)
Dr. Baumgard mentioned utilizing ketones comes at a metabolic disadvantage: a loss of energy. So what could cows be doing if they’re able to increase their feed intake enough so they don’t have to make ketones? (27:18)
Dr. Drackley said the million-dollar question is if inflammation is the key, what do we do about it? How do we prevent it or treat it? (31:38)
Dr. Baumgard explained his thought process is that if even healthy cows have some level of immune activation going on in the transition period, some of this subclinical hypocalcemia that’s occurring in the transition period could be caused by immune activation. (43:50)
Dr. Drackley said as we select for high-milk production, perhaps part of that is enhanced ability to use ketones. The idea of a tenant of high milk production is you’ve got the time of lower insulin and high growth hormone driving lactation. Those are all tied up with genetic selection. (46:40)
Dr. Baumgard wrapped up by saying from a producer or veterinarian perspective, it’s easy to treat and get out, but what really needs to take place is a full examination; where did this immune activation come from? (54:56)
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Scott (00:08):
Good evening everyone, and welcome to the Real Science Exchange, the pubcast we're 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, one of your hosts here tonight at The Real Science Exchange, and we're here tonight with two well-known university professors to help us walk through the history of the transition cow management, and they'll then help us debunk some of the dogma that it's developed over the years. I'd first like to introduce Dr. Lance Baumer State University, Lance, you're now what we call an expert here at the pub. I guess this is about your third or fourth time. Welcome back.
Lance (00:46):
Thanks for having me, Scott. I appreciate it.
Scott (00:48):
Yep. So, Lance, I've gotta ask what's in your glass tonight?
Lance (00:51):
Well, there's three things I wanted to highlight. I've stumbled upon two new bourbons. One is called Borders Bourbon, and it's made by the 45th Parallel Distillery in Wisconsin. And it is a very tasty adult beverage. And then I've also stumbled recently upon a Rabbit Hole Bourbon. I don't know if you guys have had that one or not, but it's good. It's good. But what I particularly wanna highlight is actually a gin. Now, in all transparency, the distillery is owned by my family, my, some, a cousin of mine, but they make a fantastic gin out of, it's called Ida Graves Distillery. It's a gin that has some unique flavors to it. And so that's what I'm drinking at the moment.
Scott (01:39):
Awesome. That's awesome. I've taken notes there, Lance. I'm gonna have to find those. I've been in a rut lately. Yeah. So, Lance, I see you've brought a guest with you tonight. Would you mind introducing him real quick for us?
Lance (01:54):
Yeah. You may not know him.
Lance (01:56):
That's a joke because he, this is a very well known,
Scott (01:58):
Well known. He's an icon.
Lance (02:01):
An icon, the father of an area. Dr. Jim Drake. Jim, you wanna introduce yourself?
Jim (02:08):
Yeah. I'm Jim Drackley, from the University of Illinois. I realized that I've been here for 34 years, which is amazing. Couldn't find a better job, I guess. So happy to be here with, with everyone and, and it's a great chance to have a good conversation. Looking forward to it.
Lance (02:35):
What are you drinking, Jim?
Jim (02:39):
So, I've been struggling to choose between a Gin and Tonic, which I enjoy from time to time. And a good French White Wine, which is kind of my go-to. So I've got a glass of Sander in front of me, so goes nice and crisp and just goes down real smooth on a nice hot evening like this.
Scott (03:03):
Excellent. And I can't forget my trusted co-host, Dr. Ken Sanderson. Ken, thank you for joining me here once again as my co-host. Do you have anything special in your glass tonight?
Ken (03:13):
Hi, Scott. Thanks for inviting me. I was just saying to the guys before we went live here, that for me, it's a real treat to have both Jim and Lance on the same call. They're, as you said, icons in the transition cow field and people I've watched and followed for years. So, and in my glass, Scott, I don't vary very much. I stick with Molton Canadian of course. And I stay right with that as the beverage of choice.
Scott (03:45):
All right, thank you for that, Ken. As we cuss and discuss the best practices and research on transition cal management, let's first raise our glasses to a quick nod to the dairy industry and to the great conversation to come. Cheers, fellas.
Scott (04:04):
You know what? I actually forgot to tell you what I'm drinking tonight. I'm drinking my forever bourbon. And so what that is I have, I have an old Woodford's bottle, and every time I get about the fourth of a bottle left, I'll pour it into that bottle. So it's a mixture of everything. And the reason I'm drinking that tonight is I'm out of everything else. So, Lance, I'll be ordering some of that Border's Bourbon and Rabbit Hole if I can find it. So, you know, one other thing I wanna point out real quick is that we've done some redecorating here at the real science exchange. We have a new sign, if you see that behind me. So we've got yeah. So unveiled it for the first time here tonight at Real Science Exchange. So Lance, I'm gonna jump right into it. You presented back in January during the Real Science Lecture series, and we came up with a title or actually you did who let the Dogma out of the Transition Cow Management. Let's dive into that a little bit further and explain what we mean about dogma and how did that come about and what does it mean as we get started with this conversation?
Speaker 5 (05:15):
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Lance (05:38):
Yeah, well, so yeah, the actual dogma part of that title, actually, I need to give credit to Steven Leblanc, a friend of mine from, which I'm sure everyone's familiar with on this podcast. But he kinda teased me about that title, and I've kind of stuck to it ever since. So, the dogma, I guess at least the way I understand it, and is that during the transition period, the cow mobilizes adipose tissue, and as a consequence, you have an increase in non of certified fatty acids, and some of those non certified fatty acids are converted into ketones. And we'll just stick on energy at first. And the thought process has been for a long time is that these two metabolites then are causing problems. They essentially the pathological and that they, in essence, reduce an animal's immune system or suppresses an animal's immune system, and then this predisposes them to a variety of health disorders in the transition period. And so we, as an industry in Academia, has spent a lot of time and energy focused on trying to minimize the large swings in NEFA and ketones, the propane glycol, primarily propane glycol, but other strategies, pre-cal strategies. So that's kind of the dogma on the energetic side. The other one is calcium. I guess we can get to that later. But Jim, is that kind of, that I wrap that up properly?
Jim (07:14):
Yeah, I think that's, that's nicely stated in a brief way. Yeah.
Lance (07:20):
Yeah,
Scott (07:21):
Yeah. I was just kinda curious Lance, I mean, maybe Jim can kind of take us back in history and how did we get to the point where these became kind of the prevailing understanding?
Jim (07:34):
Well, I think you know, it goes back a long time. There were some studies, well, back in the thirties and forties even and studies by Bud Schultz at Wisconsin in the sixties. And it was noticed, you know, that we had the ketones being produced, and this was often associated with cows that were clinically questionable, that they were, they had a malaise, they were depressed. Sometimes we had this abnormal nervous behavior, which occurs only in a small number of the cases. So there was a syndrome obviously going on. And, as time went on, there were a number of epidemiological studies conducted, and those showed very strong relationships between ketones and these other problems other health problems. And so there's associations, and I know this is something that landslides to beat on, that there's a lot of associations, but that's not necessarily causation. And so it's all associated with all the nasty things that happen around calving. And the question then becomes, what is the root cause of what we see, and whether it's starting with this negative energy balance and the mobilization of body fat, or as Lance's research has shown, whether it's due to inflammatory pressures and other involvement of the immune system. So I think that's kind of brings us up to where we are today. Is that, is that true, Lance?
Lance (09:22):
Yeah, no, I think that's all very accurate. Right? One of the things that we do and have done for a long time, and I'm just as guilty as anyone else is, and we take cows for the transition period, and you measure, you take blood samples, and you measure this, and you measure that. And then after a certain amount of time, you retrospectively classify them as either healthy or non-healthy, or, you know, poor fertility or not, or good producers, not producers, et cetera. And then this retrospective classification, then you do the, then you do your analysis on that, right? Or alternatively, just simply do a correlation analysis between these NEFA ketones and some type of outcome. And oftentimes there is an association, I would say frequently not very strong of an association, and then oftentimes there's not. That's one of the things that I think is important to the discussion is that the inconsistencies in the literature regarding this relationship with a negative outcome is part of the foundation, I guess, of the way we've been interpreting this association.
Lance (10:34):
One of the very first things that came to my mind was when I went to the University of Arizona, right outta graduate school in 2001, and this was shortly after Jim published his fantastic review, and I think it was 99, the Final Frontier. Yeah. I think he gave it that it was just a, it's the Bible of transition cow biology. If you haven't read it, you need to, so I had, that was fresh in my mind. It was a very exciting area of biology, dairy science. And so when I got to Arizona and started talking to nutritionist and producers, I was convinced that they would have, they would have to have a ketosis problem, right? They're a very high production state. In other words, milk per cow- very high. And they've got five months of pretty severe heat stress.
Lance (11:24):
If anyone should have a ketosis problem, it should be Arizona. And I started talking to nutritionists in the west, and specifically the southwest and dairy farmers, and they just, it's just not existent, right? There are large dairy farms in Arizona that haven't treated ketotic cow in 30 years. And that struck me, right? I'm like, if, how strong should this dogma be if we have, you know, an entire region where they don't have a ketosis problem, they still have high ketones. By the way, these cows still have relatively high ketones and high NEFAs, they mobilize adipose tissue. They're just the dairy producers and nutritionists just aren't focused on it as a problem. So that was one of the first really the germ of the idea. Like, remember in human nutrition, they call it the French Paradox, where eating too much fat and saturated fat in particular is supposed to cause heart disease and cancer. But of course, there's a whole Mediterranean population that don't have that, that association doesn't, that association or relationship doesn't connect. So they call it a French Paradox. Well, maybe we should have an Arizona or a Southwest paradox, right? Where these cows aren't, they're not getting diagnosed with clinical ketosis. And so that was always in the back of my mind for a long time, for like 20 years.
Scott (12:45):
You know, Lance, one of the things you talked about is how you measure what a successful transition is. Andit was quite simple to me. Could you expound on that for the audience? Yeah.
Lance (12:57):
Essentially, the foundation of our thinking has been for a long time that the best indicators of overall health is productivity, milk yield in this particular case, right? So the, a healthy cow will produce a lot of milk, and an unhealthy cow won't. So you know, I don't think you need to have a PhD or a DbM to, to recognize a healthy cow. Our ancestors did this really well. I hear this still often, right? This, I think it's an antiquated view that high productivity is stressful. Well, if we all agree that stress reduces milk yield, like everyone I think on this podcast probably really does if stress reduces milk yield, well then how could high production be stressful? Right? The two just, it's kind of an oxymoron. And the other foundation of our thinking is that mother nature is rarely wrong.
Lance (13:53):
Now, she doesn't make mistakes. So the fact that you have essentially all female animals mobilizing tissue after they give birth to support lactation I don't see you think of her the most important time of her life. She gives birth and she's gotta raise this young, you know, why would Mother Nature create a system where she mobilizes adipose tissue and skeletal muscle to do that, but while simultaneously putting herself at risk and thus her offspring at risk, right? Yeah. And I guess that's kind of the foundation of our way of thinking. We put that in context.
Scott (14:36):
It's interesting Dr. Sanderson's been talking a lot about this as well. In fact, he's written an article that'll be published in Progressive Dairyman coming up in a couple months. Ken, what's the title of that? Wellness is, what is the title?
Ken (14:53):
Yeah. Biomarker for Wellness is Milk Production.
Scott (14:57):
Yep. Yep. Absolutely. Yeah. Ken, do you mind talking to us just a bit about what you know, the thesis of your paper?
Ken (15:06):
Yeah, I think it follows Lance's and Jim's comments. You know, I recall Dr. Bowman's kind of discussion years ago with respect to high milk production and this concept that somehow it's a stressor or workload on the animal. And yet he went on to explain that the biology, the physiology of these high producing cows doesn't really indicate that they retain a normal heart rate, a normal respiratory rate. They're not athletes per say. And that the physiology that goes into high milk production really isn't an athletic or work event. And as such, the obvious consequence of removing stressors from the cow's life, whether it was heat stress or poor stall design, almost inevitably they responded with more milk. And so that was a very good indication that we were helping them be in a state of wellness. So that's kind of the thrust behind the article.
Lance (16:25):
Yep. Yeah. Ken mentioned someone who also has a huge impact on the way, I think, and a Bowman, of course. And he, you know, he was coming at it with regards to somatotropin utilizing somatotropin and encountering this idea that somatotropin is causing stress and odd stuff. And essentially what our group has done is take a play out of his playbook, right. And apply it to the transition period. And yeah, he's had a huge influence on the way people think about milk production and hyperactivity in particular.
Ken (17:05):
I'm curious, Lance, you mentioned Arizona and sort of how you got onto this concept and five months of heat stress, and yet no one was diagnosing, or at least not chasing a litany of ketosis in these herds. Yeah. And yet the heat stress, I'm curious how you dissociate that from the LPS conversation that you, yeah, there seems to be a bit of a disconnect in my…
Lance (17:41):
Disconnect, no, I totally, I can totally see the disconnect as well. So th, you know, in the southwest in particular, Arizona in particular does a very good job of cooling cows. Before Dennis Armstrong got to Arizona, they'd lose 30 pounds of milk during every day during the summertime, and now they're down probably five to six pounds on good dairies. So it's not the, it's not the amount of heat stress that we're typically dealing with on university when we're studying heat stress. You got the severe heat load, you get the leaky gut, you get the LPS, et cetera. And of course, it's more of a, they become acclimated to the heat stress, of course add an adapted the time. So, but if there was an acute heat load and the animal did get the leaky gut, then I think you're gonna, then you're gonna have a clash of these two ideas, or at least clashes of biology, where you have heavily immune activated animals going off feed at the same time, the transition period. And that's when I think you would expect to see then this immune activated phenotype.
Ken (18:56):
I guess, Jim, listening to this sort of trail of changing thought processes, where do you put the Goldilocks diet concept now in your thinking, and what does that, does any of this change your thoughts around that?
Jim (19:20):
Yeah, that's a great question, Ken. And you know, a lot of the rationale for developing that approach or using that approach does center on body fat mobilization and so on. But I, as I've learned more from Lance and, and seen his data and from some others too, the whole idea of the LPS story, I think makes some sense. I think one thing that might tie it in to better success is just what Lance is saying about the Arizona industry. That's a high forage based system, alfalfa based system, and there's not as much starch going into those cows. I think my hypothesis is that we're having some differential effects in the rumen that minimize the inflammatory pressures. And we're actually gonna present a couple of papers this summer at dairy science with some data on that, that we have evidence for, a more inflammatory profile on a higher starch closeup diet than the Goldilocks type of diet.
Jim (20:39):
So I think it comes back, and does tie in. You know, I remember one thing that was very influential for me was the work of Giuseppe Bertoni and Armeno Trei from Italy. They were talking about cytokines and inflammatory issues back in the late 1990s. And I remember having a conversation with somebody, I don't know if it was with Lance or somebody else, but sometime back in the early two thousands, probably the same time Lance was having his visions about whether there really was such a thing as ketosis as a disease, or whether that, you know, when you have a, a clinical case of ketosis, is there an underlying subclinical, perhaps inflammatory pressure that's causing the problem and causing the cows to not eat as well? And then you get into the spiral downward of where things really do get out of balance. And I think that those are, they, they all tie into the same story that's developing, I guess in my opinion. I don't know what Lance thinks about that.
Lance (21:59):
I think you're spot on. And that's a great shout out to Trei and his group because they've just done a job a great job of characterizing this inflammatory response starting prior to calfin, and of course going into early lactation. And, like you said, that started in the late nineties, and he really crystallized this whole area in theearly two thousands, in the 2000 tens and stuff like that. But, to your credit though, Jim, in your foundation, your final frontier paper, you even have a couple comments in there about how the immune activation could be a critical component of the transition cow success at that stage. We didn't know, right? How much, But you, you obviously were on, on top of it enough to know, hey, this is a potential area where there'll be a lot of discoveries.
Lance (22:53):
Yeah. So, yeah, I think that's the key here is that you have an immune activating event going on somewhere, the mammary gland, the uterus, the gut, maybe the lung. And if that immune activation event was going on during mid or late lactation, right? The animal, the mammary gland has TLR4 receptors, so it's a hypothalamus. And so the animal just kind of gives up, right? The mammary gland stops making milk, or at least you have a marked reduction in milk yield. She also stops eating. But because of the reduction in milk yield, you don't have this clash of metabolic adjustment that needs to occur. But if she has this immune activation event during the transition period, now she's got, you know, evolutionary pressure to, to make milk at the same time she's going off feed because of the immune activation.
Lance (23:49):
So now you have an energetic conundrum for her. She's got a, she's gotta feed her offspring, right? So the pedal is to the metal on the mammary gland. She's not eating because the immune activation has caused her to go off feed. And what happens? Well, now she's gotta pull, right? She's gotta pull adipose tissue, large quantities of it and create ketones. So now you have this girl and she has high ketones, high NEFA’s she's gone off feed and she has suboptimal productivity and likely some type of health problem. Then you have her, the alternative, you have the girl who's not, she doesn't have a problem, right? She's healthy, but she's mobilizing adipose tissue, converted ketones because that's the way mother nature metabolically programmed her to make a lot of milk. Now you have these two cows in the fresh pen. One has high NEFA’s, high ketones, and she's milking like a dog or not milking up to her potential, but she's trying, she's trying. And then the other one is milking, like a rockstar, and she also has high NEFA’sand ketones. So I think this is part of the confusion of the transition period, and the confusion for a very long time is that you have metabolically two identical cows, but you know, typically two very different cows.
Jim (25:11):
I was just gonna say that's one thing that maybe I take a bit of issue with Lance, is the idea that I mean, I understand from an adaptive standpoint, the keto production is perfectly normal. It's a way to adapt to an energy shortage or a glucose shortage. Yep. But I would argue that, that that is not normal. That's not the optimal scenario for the cow. That the optimal scenario is like your Arizona situation where you've got cows that are cranking. They have, they have maybe a little higher ketones, but I don't think they're above these associative levels, you know, 1.2 millimolar and so on. And I think that the physiology, the metabolism is optimal when we've got cows that are digesting a lot of fiber, they're getting enough glucose, and they're not making ketones, and that the situation where they are making ketones is not optimal in terms of metabolism.
Jim (26:18):
And so, yeah, you can have cows that are milking great, but I would argue that would they be milking even a little better if they weren't in that scenario? Right. And that's maybe where you get into some of the associative effects. Yeah. I just, you know, anecdotally, I was in Minnesota in April with a nutritionist and we visited four farms that were all averaging over a hundred pounds a day of, you know, milk fat higher than 4.0 protein over three, three s, good reproduction. And they don't have ketosis. You know, they check, they monitor the cows after calving, and if they find one, they consider an abnormal event. So, you know, I'm with you most of the way there, but I would argue that if we do, if we are seeing cows with high ketones, even if they're clinically normal and doing well, that they could be doing a little better if something was tweaked a little bit.
Lance (27:18):
Totally agree with you. A couple points you mentioned. One is Minnesota. It turns out Jim and I are from essentially the same area. The second one is, I totally agree with you, right? Utilizing ketones comes at a metabolic disadvantage, right? You urinate out ketones, you breathe out ketones, and of course, that's a loss of energy. Yeah, no. totally. I totally agree with you. What could they be doing, even if they're making 120 pounds at the 14th day of lactation, what could they be doing if they're able to increase their feed intake enough, quickly enough so they didn't have to make ketones?
Jim (27:54):
Right?
Lance (27:55):
I would totally agree with you that then another thing you said that I totally agree with is ketones levels. What type of ketones levels could you get on just on high pot healthy, high production? And I think you're spot on. It's very unlikely to get ketones over two, two and a half with just high production, right? If I'm just high production, they'd probably run 1.2, 1.5, 1.75 maybe. But if they're two and a half or over, you have an animal that's not eating very, very unlikely to be eating, right? Right. So now we have two differences, we've separated this out. Now we have a healthy cow that’s not eating.
Scott (28:41):
So how do we use this knowledge to manage a herd, Lance? So at what point is optimal? And, and
Lance (28:49):
That's a great question, Scott. And from a management perspective, yeah, I'm not sure. I'm not sure large changes need to be implemented other than, you know, it wasn't very long ago, 10-15 years ago, where a larger dairy in Midwest, they'd lock up Monday and Wednesday and Friday, and every cow would get a urine stick test. And no matter what she was milking or how she was eating or how she was looking, if she got over, if she was over some type of some arbitrary threshold, she was gonna be treated with propylene glycol. And you know that that's a cost, right? And there's potential risk of treating cows with propylene glycol. And probably the biggest economic one is just simply dedicating manpower labor to doing that. You lock up an entire fresh bend three days a week. So there's cost associated with this on the producer, right? And I guess one of my tenets is, you know, let productivity be your guide, right? To just blindly take a blood or blood or urine sample and measure ketones and decide to treat or not treat based solely on that, I think is not necessary.
Jim (30:05):
I think one of the things that's important about those, that strategy of the lockups, you know, the 10 days of daily lockups is that's time away from feed and rest. And I, you know, as we learn more about behavioral physiology and the requirements for rest as well as access to feed, I think that's a real risk to the cows. One of the, one of the beautiful things about this whole inflammatory story too, is that I think it ties it into the, the behavioral stressors because you get immune activation from, from behavioral stressors like overcrowding and you know, first lactation animals mixed with older herd mates and so on. I think it's a great tie into these areas of cow comfort and cow management that really are so important to this transition success.
Lance (31:01):
Yeah. I agree. It turns out, like Jim was saying, there's a variety of stressors where the metabolic and inflammatory footprint is almost identical. And I don't think that that can't be a coincidence or at least it's unlikely to be a coincidence. Most stressors, we now know what caused some hyperpermeability of the intestine. You get the LPS, you get the immune activation. And I think this in large part then also explains why these dairies that have, you know, that are managed properly with stress-free management do so well.
Jim (31:38):
Yeah. But I think the million dollar question is still, if inflammation is the key, what do we do about it? How do we, how do we prevent it? How do we treat it? Do we treat it?
Lance (31:54):
Well, I think that's a great question. And I would go back and say, inflammation's probably not the key. It is immune activation causing the inflammation and then of course, the inflammation is a, is part of the malays. So I think it's preventing the immune activation to begin with. And you know, I think that's one of the reasons why cows can do so well in deserts, like Saudi Arabia and Israel and Arizona, the environmental pathogen load is just so, so low, right? When, when you talk to a nutritionist out west, you know, they almost never have a milk fever problem, but when they do, it's almost always during the rainy season. And we haven't talked about calcium yet, we've been, you know, but I think some of the hypocalcemia is also caused by immune activation. So when they're in, when their environmental pathogen load goes up, because it's raining and the dry lots get sloppy, but then you're gonna have a few cases of milk fever.
Scott (33:06):
Gentlemen, one of the things I, you know, you're talking about inflammation and there can be multiple sources of the inflammation or the immune activation. You know, I heard, Lance, you say mammary, gut, lung. Jim, you said behavioral, how do you, how do you go about detecting the source of your inflammation or the immune stimulation?
Jim (33:27):
We don't have any good diagnostics at this point that are field ready, I would say. But I think it's a, you know, what, we, we all, I think no good management when we see it, it's kind of hard to define it or you know, spell out what that means. But you know it when you see it. And it's, and it's all the little things that lead to cows that are more comfortable and under are subject to fewer stressors. And I think Lance's example there of the desert is a good one. And you just see it on these high producing cows or high producing herds that, you know, the cows are clean and healthy and happy, and they're lying down when they're not eating. And they're, they've figured out how to make group changes and movements that are minimally disruptive to the cows. You have the whole nutritional component, which is important, but probably not any more important than all these other non-nutritional things in the cows environment. So I think those are things that a lot of us have been preaching for years. And I think it ties into this explanatory phenomenon really, really well now.
Ken (34:46):
It's interesting listening to guys talk about Arizona and the Goldilocks diet. And I have this question about anti-inflammatory diets. And maybe, you know, because we did see good success, Jim, with the Goldilocks approach, right? I mean, having that higher fiber, lower energy density diet, did it cost us some milk? Maybe, but it also might have been prescriptive in that it probably was an anti-inflammatory diet. You mentioned that the high forage content of the Western diets and certainly the lack of the higher forage content in some of our more Eastern diets might have precipitated unknowingly much more of a gut challenge to these cows and precipitated some of the LPS absorption that we might associate with what Lance is describing.
Jim (35:58):
Yeah, I think so. I think so. Again, we have some, some limited evidence that those diets may be more anti-inflammatory than a higher grain or higher corn silage diet
Ken (36:14):
With, it would be interesting to make some closer evaluation of LPS. You know, if we could do that based on the style of diet and have a better understanding as one of the management practices, we may have been doing the right thing for the wrong reasons. In the context of the higher fiber fresh.
Lance (36:43):
Yeah. But I do think Ken, that there's space and opportunities for some dietary anti-inflammatory target molecules, you know, and we're all familiar with Barry's work with the aspirin, right? But, so I think there's, that's coming. And the dietary anti-inflammatories are, I assume are going to be working within the gut, probably the distal part of the small intestine, most of the large intestine. And minimizing inflammation or immune activation stem from that segment of the GI tract. So I think there's gonna be opportunities for nutritionists to take advantage of that hopefully soon. Right. It's a, it's an area where I think a lot of companies right now are chasing
Jim (37:35):
No, I was just gonna ask Lance what he thought was the bigger issue, hind gut or rumen?
Lance (37:44):
Well, that's a great question. Three years ago I would've said hind gut for sure. And one of my PhD students, Megan and Beta who's now a practicing nutritionist in Wisconsin, we used rumen fisted cattle to isolate hind gut acidosis. We were infusing abomasal infusing corn starch to cause hind gut acidosis, but not rumen acidosis. And we were really unsuccessful. And we have four papers, I think five papers now that are just recently out in journal dairy science where we were unsuccessful to create the negative phenotype. In other words, we got the, we got the high gut acidosis, but we weren't getting any negative outcomes off feed, reduced milk fever, et cetera, inflammation. So then she developed a, I think a really creative experiment, a little bit bias, but where she caused rumen acidosis in one group of cows and took that fluid, rumen ascitic fluid and abomasal infused it into some healthy recipients. And in doing so, was able to recreate this negative phenotype. So, I don't know, Jim, long story short, I think the hind gut is still a source of problems, potential problems. And, but it might not be PH driven. You know, there's a lot of potentially toxic molecules that are made in the rumen and during rumen acidosis and maybe we need to start giving those toxic molecules more attention rather than just simply pH by itself.
Jim (39:28):
Yeah. I think the work from Canada, the PLE year's group, you know, showing the difference in alfalfa pellets versus corn is really informative there.
Lance (39:42):
I agree.
Jim (39:44):
You get the acid production, but you don't get the inflammatory phenotype.
Lance (39:49):
Yeah, that was, that was an elegant series of experiments that he's, his group did.
Scott (39:57):
Lance, we were discussing gut health and I had a question the other day. The use of butyrate and mono gastrics used is there a role for butyrate in, in dairy cattle?
Lance (40:12):
Yeah, I think so. Especially probably post rumen, right? Small, large intestine. I've seen some pretty convincing data that butyrate can be effective, and improving gut health. I don't know if that's just in the large intestine or if it's also portions of the small intestine, but yeah, I definitely think there's an opportune space there, and the data I've seen is pretty impressive.
Scott (40:44):
Does butyrate in the room or is it destroyed by rumen microbes?
Lance (40:50):
Well, I assume they have to get it past the rumen, because the rumen will do a pretty good job of absorbing it. I, I would think
Jim (40:58):
That's interesting because you, do you know, in high alfalfa rations you tend to have higher BHBA in cows that are presumably healthy. Yeah. So I mean, we know that you tend to have higher butyrate. We seem to have fewer problems in the Arizona, for example, with high alfalfa diets. Maybe it's maybe that butyrate is having an effect on the gut.
Lance (41:28):
Yeah. Yeah. And another point you, you were making too, Jim, is Ithink the GI track doesn't get enough credit as being a source of circulating BHBs and in particular, the large intestine. Yeah. Megan's got some really nice data showing a fairly significant increase in circulating BHBs that had to have stemmed from the large intestine. I used to think alfalfa, there's something magical about alfalfa because it's utilized so much in Arizona and the West, like you, like you said, Jim, and then I did run across some producers that don't use any alfalfa but also haven't treated a ketotic cow for years. So I don't know. So I think you're right though about the high forage, not as much starch.
Scott (42:16):
Lance, you had some discussions during your webinar about milk fever. Just wondered if there was some things there you'd like to share with us on the podcast.
Lance (42:25):
Yeah. Let's switch gears a little bit. Talk about calcium. And I'm certainly not a calcium expert by any means, but we stumbled upon calcium out by accident. A couple students of mine, Sarah Cavedra and Aaron Horst, were doing a LPS challenge with cows. This is probably 2014. And I'm in my office and a cow goes and they give LPS and they cow goes down, physically goes down. So they call me and I run out there and walk into the pen. It's the cow that's 200 days of milk and her, she's recumbent, right? And if you didn't know about her, you'd like, this cow has milk fever. She looks like she has milk fever. And so we gave her some calcium and, you know, she got better. So then we started looking into this idea that immune activation could contribute to hypocalcemia. And it turns out this has been known for a long time, like over 150 years. We've known that, like mastitis, for example, was contributed to milk fever.
Lance (43:35):
And so immune activation, acute immune activation causes hypocalcemia in almost every, in every species that has been looked at from what I, from what I know, including humans. So I guess what our thought process is if every cow is mildly, even overtly healthy cows have some level of immune activation going on in the transition period and we know that immune activation causes hypocalcemia, I think it makes sense then to at least hypothesize that some of this subclinical hypocalcemia that's occurring in the transition period could be caused by immune activation. So that's we, we've gone down this road and tried to calculate how much calcium is actually being pulled out of circulation during immune activation. And you know, certainly not the only reason why cows get subclinical hypocalcemia, right? The work that Ron Horsch and Jesse Goff did is just fantastic.
Lance (44:39):
And all we're thinking is that maybe this immune activation has some role in this subclinical hypocalcemia. And, and of course the same thing goes back to the milk yield, right? We know that cows that have a transient reduction in hyper in calcium, but then bounce back quickly, they go on to make a substantially more amount of milk than the cows that did not become subclinically hypocalcemia. So again, if subclinical hypocalcemia is presumed to be hy pathological doesn't make sense to me that they would go on to make a substantial amount of more milk than the ones that didn't become subclinically Hypocalcemic.
Jim (45:23):
And Jess McCarts work also showed that the cows that had subclinical hypocalcemia and were slow to recover were the ones that got into bad, bad productive and reproductive function later. So that fits with the immune activation as well, that you've got a process going on there that is counter to high productivity and health.
Ken (45:50):
I'm always curious about the influence of genetic merit in production and in this case, how it might tie into the insulin refractory nature of these higher producing cows. I don't know if I'm using the right term, but how do you connect the dots for animals that have higher genetic merit for production and the link to insulin and how that might be influencing their background? So whether or not that's tied to how they might exhibit or use ketones or even NEFA.
Jim (46:40):
Yeah, I think that obviously as we genetically select for high melt production, we're selecting for all these metabolic processes that are going to be able to fuel high melt production. And perhaps part of that is enhanced ability to use ketones or you know, that kind of idea kind of the big 10 of high melt production is that you've got a time of lower insulin and low insulin sensitivity and high growth hormone driving lactation. So I mean, those are all tied up with genetic selection, I'm sure enabled cows to be able to produce large amounts of milk. We know that those adaptations are part of the genetics of a high producing cow.
Ken (47:41):
I'm dragging us back to the ability to predict the likelihood that certain animals will have more problems and potentially have, you know, lower production as a result of it. And trying to understand if we can look at anything from a genetic perspective that might tip us off at this population of animals is more or less likely to be in difficulty and what that would look like. So there was a whole litany of work done some years ago looking at IGF one receptor populations on the surface of the liver, and I think it was Dale and Matt, Lucy looked at this, and I don't recall all that information, but certainly there's a feedback loop too, the anterior pituitary, which was connected to insulin and the, and the refractory nature. But I don't know if, if this is played into some of your work, I'm thinking
Lance (49:01):
Yep, yep. So you're totally spot on. Ron and Steven Butler also did a lot of that IGF stuff insulin receptor. So two things regarding what you just mentioned, Ken. We know higher producing cows have large, have increased circulating concentrations. Somatotropin and high producing cows have much slower insulin concentrations. And so this is a great paper by the heart, heart in the early eighties looking at insulin concentrations throughout the lactation cycle on that high productivity, high producing cows had very low concentrations of insulin and low producing cows had higher concentrations of insulin. And there's a variety of, and then that's been shown now multiple times, right? That insulin concentrations are inversely related and insulin activity are inverse related to milk production. Insulin's not a friend of productivity, at least milk production. And as it turns out, immune activation also increases insulin, by the way, right?
Lance (50:09):
Acutely increases insulin to the point where you can get a hundredfold increase in circulating insulin if you cause a cow to be sick or pig or it doesn't matter what. So part of that genetic selection for increasing milk yield is mediated by both increase in somatropin and a decrease in insulin. And I'm sure IGF one is involved in that as well, but how that ties into this immune activated phenotype in the transition period. That's a great question and I don't have a good answer for you.
Jim (50:50):
I think it's interesting that, you know, some of the new genomic selection indices that are looking at health, I think that might be getting at, or could maybe get at some of that question that the cows that are less susceptible to inflammatory type disorders like metritis or mastitis, you know, that they may have that genotype that is somehow less immune responsive or more immune competent or, I'm not sure what the right terminology would be.
Lance (51:24):
But it would be great to what Ken was talking about, if you could identify a young heifer, you know, this one's gonna be hypersensitive immune responding, and this one over here is gonna be more tolerant to an immune response, that might be play into your decision making on who you get rid of and who you keep, right? So if you could identify those calves early.
Ken (51:48):
You know, what I realize is that the more we learned, the more we have to go back to the basic fundamentals, which is kind of where Lance started us, which is, you know, look at the cow and the, I'll call it the art of what we do is to recognize that all of these blood metabolites are not nearly as effective as your ability to just reconcile into what the cow is telling you, which is if she's eating well and milking well, the metabolites are somewhat secondary to interpreting the picture. I think where we've gone astray is that we have overcommitted ourselves to chasing some of these metabolite profiles, but at the same time, there was, and still is a reason to try and be ahead of, I'll call it a breakdown and have some kind of insight as to what's coming. And I think the more I listen to this, the more I'm not sure we have that yet.
Scott (53:01):
Yeah. Yeah. Well said. Lance, I, if you've noticed, I'm out of bourbon. That means it is now last call. That's last call. Yeah. So I'll ask you guys, you know if a listener today goes away with one thing to do based on the conversation today, what would that be? And Ken, anything to add to what you just said?
Ken (53:28):
I'd love to hear what Jim and Lance are thinking we should be doing next. What's next?
Scott (53:35):
Jim, can we start with you?
Speaker 5 (53:37):
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Jim (54:05):
I think the anti immune activation idea is a key one there that, you know, looking more at what is, what events are causing immune activation and how to prevent that now, how can we, how can we dampen the unnecessary or harmful activation and still allow the cow to have, you know, good disease resistance and so on. I Think those are, are areas and the, the frontier here that need to be fleshed out by Lance
Lance (54:44):
That might take a long time. I think, you know, from a, from whoever's listening to this, a takeaway is if you're a producer or veterinarian, one of the things I think is important is when you get to a farm and you have a sick cow, you know, if it's hypocalcemia or if it's hyperketonemia I think those are symptoms of an issue. So of course, it's easy just to treat and gout, right? Again, you give Propane glycol, you give IV glucose, you give a bolus, you give a IV calcium, whatever, and then now you're on your next to your next farmer. And I think what really needs to take place is a full examination of identifying where this immune activation is coming from. Now if she's down and you can't get a milk sample from her, I know that's tough, but yeah, just showing up at a farm, treating really quickly and getting onto your next client is not doing that particular producer any favors. From a scientist's perspective on where to go next? Yeah, I agree with Jim. We need to be able to one identify where this immune activation is coming from and you know, it's like I said, if I had to rank my likely culprits, it's probably the uterus, then it's probably the mammary gland, and then it's probably the gut, and then it's probably the lung. Obviously these are all epithelium, right? So identifying where that inf that immune activation is coming from, I think is important in order to develop strategies to mitigate some of these things.
Scott (56:34):
Thank you very much for that, Lance. You know, I really enjoyed your webinar that you gave back in January but I enjoyed this podcast even more. I would encourage anybody that's not seen that webinar yet to go listen to that. I think I told Lance today, I think I could get an advanced degree by listening to that thing that, just, just a lot of good information in there. And that was back in January of this year. So we'd highly encourage you to go listen to that. So thank you for that, Lance. And Jim, thank you for joining us. You've been a great guest. I appreciate your knowledge and looking forward to a webinar. We've got schedule with you coming up as well, so the audience be looking forward to that. And Ken, as always appreciate having you. Yeah, you helped me out a lot and I appreciate you. So, and to our loyal listeners, I want to thank you for coming along and spending some time with us once again here this evening. I hope you learned something. I hope you had some fun, and I hope to see you next time here at the Real Science Exchange, where it's always happy hour and you're always among friends.
Speaker 5 (57:41):
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