Gathering together at the 2023 Tri-State Dairy Nutrition Conference for the Balchem Mini-Symposium “New Revelations in Transition Cow Nutrition” are speakers Dr. Mike Van Amburgh, Dr. Jose Santos and Dr. Heather White.
Guests: Dr. Mike Van Amburgh (Cornell University), Dr. Jose Santos (University of Florida), Dr. Heather White (University of Wisconsin-Madison)
Gathering together at the 2023 Tri-State Dairy Nutrition Conference for the Balchem Mini-Symposium “New Revelations in Transition Cow Nutrition” are speakers Dr. Mike Van Amburgh, Dr. Jose Santos and Dr. Heather White.
The mini symposium featured topics such as better understanding essential versus required nutrients, choline research as a nutritional requirement and insights on gaining the next five pounds of milk.
Dr. Van Amburgh of Cornell University led the discussion, summarizing his report on essential and required nutrients such as amino acids and choline. He mentioned when formulating diets for lactating cows, it’s important to understand there are other nutrients that aren’t necessarily essential but are required. 4:53
Shifting the conversation, Dr. Van Amburgh said establishing an optimum value has now replaced nutrient requirements based on energy. Recent evidence indicates that feeding rumen protected choline (RPC) significantly improves milk production. In addition, supplementing choline shows an increase in low-density lipoproteins (VLDL) output from the liver. 7:21
Highlighting her research in supplementing choline, Dr. White shared that studies show a 20 to 25% increase from cells and culture after incorporating the nutrient. She added choline also increased the tricarboxylic acid cycle (TCA) capacity, indicating a shift in nutrient incorporation. 11:45
As milk increases when infusing non-essential amino acids or even by using meta-analysis to supplement choline, how is glucose supply impacted?
Dr. Santos, who focused his research on meta-analysis, said that even with the concurrent increase in dry matter intake, efficiency has still increased. He went on to say that studies from Wisconsin and Michigan highlight the basic understanding of a cow's variable ability to synthesis glucose differently with the ability to produce at least two kilograms more milk consistently. 21:30
Within some of Dr. White’s meta-analysis research, she mentioned mixing choline into the total mixed ration (TMR) allowed for the opportunity to analyze exact intake and also outcome production or energy corrected milk (ECM) fat. 34:08
If cost isn’t an issue, Dr. Santos mentioned that he’s seen experiments feeding choline longer than 21 days postpartum and into 105 days at 12.9 grams. While no major benefit showed at that dosage amount, he added that other studies have shown benefits feeding choline longer and into mid lactation. 39:41
Switching gears, Scott Sorrell, podcast host and director of global marketing for Balchem asked Dr. Santos about epigenetics and the effect choline has on behavioral changes. 44:59
Sharing that epigenetics shifts genomes without changing sequences, Dr. Santos mentioned that through a two-by-two factorial experiment on choline, research indicates calf behaviors shifting and performance increasing. He went on to mention that history shows 30% of calves that were born from control dams and fed colostrum from control dams died from lipopolysaccharide challenges. 51:10
Wrapping up the conversation, Dr. Zimmerman, podcast co-host and technical services manager for Balchem said that research speaks for itself. He stated that higher producing cows continue to prove choline as a required nutrient for transition cows. 55:50
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Scott Sorrell (00:07):
Good evening everyone, and welcome to the Real Science Exchange, the podcast. We're leading scientists and in street professionals, meet over a few drinks to discuss the latest ideas and trends in animal nutrition. Hi, I'm Scott Sorrell, director of Global Marketing for Balchem Corporation. And we're here today at the 2023 tri-State Nutrition Conference where biochem just held a mini symposium. The titled symposia was New Revelations in Transition, Cal Nutrition. We had four speakers, the first of which was Dr. Mike Van Amburgh. His topic was implications for understanding Essential versus Required. The second speaker was Dr. Jose Santos. Topic was Cho, a required Nutrient, followed by Barry Bradford. How do we get the next five pounds of milk? And lastly, Dr. Heather White from University of Wisconsin. New Insights from the University of Wisconsin Transition Cow Research Program. I'm also here with my co-host, Dr. Clay Zimmerman. Welcome back. Clay. Good to see you again. Yeah. And you? Good to be back. Yeah. And you know the drill. What's in your glass tonight?
Dr. Clay Zimmerman (01:12):
My usual day. An angry orchard. This is very, very good.
Scott Sorrell (01:17):
Oh, excellent. Clay, this is the third in a series of seminars that we've put on across the country. Can you tell me what was the background of that? Why did we decide to do that at Biochem?
Dr. Clay Zimmerman (01:30):
Yeah, basically, we've we've been sponsoring as, as usual, sponsoring a lot of research. A lot of it related to, to reassure through the years actually dating back well over 20 years now from a research perspective. But we've had some really seminal studies that have been completed over the last five to six years. So you know, I was counting back. We've had eight different research studies that have either been published since 2018, or they're in the process right now that are, that are really seminal related to this. Starting back with the original Xenobi study that was published in Journal Dairy Science in 2018, there was the Bilotti study published in 2020, the Pot Surman study from 2020. There's another Zen calf study published actually last December in 2022. That was the work from the Turner Schwartz Perry Bradford work that's was published last year in this year out of out of Dr.
Dr. Clay Zimmerman (02:44):
White's lab here, the Henry Waldorf's work that's being published this year. There was the meta-analysis out of Jose's lab, the the Arshad meta-analysis in 2020. And then the the work that Jose shared this afternoon that is in the process of being published right now, that will be published this year. So that's eight different studies. That'll be, that'll be well over 20 peer reviewed papers at that'll will come out of those hate studies. So it's really sort of the next generation work now, showing that that choline is a required nutrient for transition dairy cows.
Scott Sorrell (03:27):
Oh, thank you for that, clay.
Speaker 3 (03:28):
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Scott Sorrell (03:50):
Dr. Van Amber, this is getting to be a habit, sir. Good to see you again. Good to see you. Before we get started, what's in your glass tonight?
Dr. Mike Van Amburgh (03:57):
I think somebody said, this is B
Scott Sorrell (04:00):
Bini excellent choice. Yeah. Yeah, Dr. Palmquist and I have had that on a few occasions. Yeah. Good to see you, doc. So Clay mentioned the word requirement or required nutrient, and that was the, the basis of your talk. Can you kind of give us, kind of sum up what your talk was all about?
Dr. Mike Van Amburgh (04:18):
Sure, Scott. So, so I, you know, when we're formulating diets for lactating dairy cows, generally, we tend to think about nutrients as required. When we talk about amino acids, we think about nutrients or essential amino acids. They're essential amino acids. We tend to think of those only as required because they're essential when in fact, if you look at metabolism and you think about, you know, the metabolic demands of a high producing cow, there are other nutrients that are not essential, but are required. Right? Not essential Amino acids are not essential, but they're required coaling. It's not essential, but it's most likely required, right? So we can go through all of those pathways and say, Hey, you know, we can't manufacture it, right? We can't manufacture it, so that's essential. But if we can manufacture it, that makes it non-essential, but it doesn't remove the need for it, right? So I think that's how I would sum up my talk.
Scott Sorrell (05:29):
Okay. So then the, the next question be required for what? Mike? And then, and, and maybe that's, you ask, maybe I should let you answer that first cuz I got a follow
Dr. Mike Van Amburgh (05:38):
Up question. Oh, I think it's required for any use that she has, right? If you, you know, if you think about amino acids Gerald Loy ran a study or took data from several studies years ago, and, you know, and he was, he was trying to get it the same thing. He, he did, did it in different ways, but he basically followed essential amino acids through their pathways and then looked at their disposal, right? And almost, you know, when we think about balancing a diet for a, a high producing lactating cow, historically, we kind of think in a linear fashion, right? I'm gonna put this amino acid in and it's gonna go to milk protein. Right? And I still have a lot of, you know, old style nutritionist who say, well, that's the only reason I'd ever feed that amino acid is to get more milk protein. And if I don't get more percent milk protein, it failed. Well, what Gerald was able to show is that those essential amino acids, their carbon could end up in milk protein in lactose or in adipose tissue, or in some other, you know, metabolite. So it basically said that carbon can go any, any different direction, many different directions that are obligated, required for that cow to be more energetically efficient. Right. So it's not a linear path.
Scott Sorrell (06:53):
Okay. Makes sense. Now, yet had another question. During the presentation together at the Cornell Nutrition Conference, you asked the question what do you want optimum output, maximum output, or the most efficient output
Dr. Mike Van Amburgh (07:14):
Sure, sure. I talked about that a lot here lately because of that. So here's my example. Let's just, let me just use amino acids and essential amino acids mm-hmm.
Scott Sorrell (08:49):
Yeah. Makes sense. You know, before we get too far along here, I want to go to the audience, see if there's any questions out there.
Speaker 5 (08:55):
This question is for Joce, but really it's for more than Joss say you did a nice job of showing positive responses to supplementing coal. But the other part of the question, which has been with us forever, is how does it do it? And you suggested that part of it. An important part might be to facilitate export of fatty acids from the liver. Now it's pretty well established that the export of fatty acids from the liver by via A V L D L is pretty small. It's probably not more than 5% of the total metabolism of fatty acids. But then the next part of the question, Heather showed some data, I had it in my mind, I was going to say, somebody's gotta do this, and you did it. Now, if I understood your slide correctly, you showed that choline supplementation increased V L D L output from the liver. You did show that That's true, yes. Quantitatively, how, how great was that?
Dr. Heather White (10:14):
Oh, what percent increase? Think it was 20, 25% increase from cells and culture.
Speaker 5 (10:24):
Yes. And that's the best way to do it really because of the difficulties of measuring in vivo. But both Wisconsin Rick drummer and Dave Poland from Michigan State have done nice in vitro work, and Poland did some work from my lab that supported that. It's not great. I would think that it'd be important to follow, follow that up and see what is the specific effect of cho.
Dr. Heather White (10:58):
Yeah. Can I jump in Scott, or do I have to say what I'm drinking before I'm allowed to talk
Dr. Heather White (11:44):
So there was an increased TCA cycle capacity. Very few things increased T cycle capacity, and we were able to absorb that. So more fatty acids are being oxidized to generate energy, more are being packaged and exported. And as it would make sense, if both of those things increased, then we saw less of the third alternate pathway, which is ketogenesis. And so that really suggested to me, and that was several years ago now, that there was differences in nutrient partitioning when we added choline, which means it's having a regulatory effect, not just as a nutrient that's incorporated then. And so that's really interesting. There's also some work, if we look in other species that suggest the fatty acids that are being incorporated are a different profile, and we can find that in cell culture systems as well. So it's selectively using fatty acids for things. That's kind of where we're, where we still need to follow up a little bit more. But the other thing we observe in the cell culture that mimics what we see in vivo is the glycogen. So we see all these same pathways we see in the cow also occur in the cell culture, which tells us that we can trust it. More importantly, lets us dig into it even deeper, like you pointed out, to really figure out how it's happening.
Dr. Heather White (12:54):
You're welcome. Thank you. Yeah,
Speaker 7 (12:55):
Thank you, Heather. Yeah. my question was related to the classroom data quantity and quality. I, I find it interesting research and I'm glad you guys are doing it. I think our industry needs a lot more of it because the classroom quantity issue is a really big concern that is probably under-researched. So certainly there's you know, seasonality effects and day length and nutritional impacts and, and environmental impacts that we're noticing. But in the field, we can't seem to get a handle on classroom qu quantity primarily, perhaps quality as well. And so I'm wondering, based on your data, if there's anything mechanistically you learned from the choline research that gives you broader implications on classroom quality or where research might lead in the future. Anything more there to consider? And I, I guess my question's directed to Heather. Dr. Bradford's not here, but anybody else as well. Thanks.
Dr. Heather White (13:57):
Yeah, I can start and certainly others can jump in. So exactly what you're saying is why we measured it in the first place. We weren't historically measuring colostrum quantity or quality on our research farm, but we heard first from our research farm and everybody else that there was never enough colostrum. In fact, the research farm did not want us to enroll the first few calves from the study because they wanted to be able to pool some colostrum from the right treatment groups and have it in the freezer ahead of time because they were so worried about not having enough. And we hear that from the field all the time, just as you point out. The other thing that we had been hearing anecdotally from farms was that when they fed colon, they got more colostrum. Well, you know, maybe they were measuring it, probably not super precisely right.
Dr. Heather White (14:41):
But if they say there's more, there must have been noticeably more. And so we were really intrigued to follow up on it. As far as how it might happen, we didn't go too far into that. In our paper, I, I didn't touch on it here either because we didn't, we didn't measure anything more than quantity and bricks. So anything I have at this point's hypothesis or speculation. But what I do think is that the same mechanisms that support glucose production and energy production in the liver that would support lacto jenesis is probably also supporting colos Regenesis. And if we're feeding it 21 days before calving, there's plenty of time for that to influence before the colostrum is starting to form. So I would, I would dare say it's probably the same mechanisms. I don't have any data on that yet. So as far as extrapolating that beyond choline, I would say anything that's supporting liver metabolism and would improve milk production, we should probably be measuring colostrum production to see if it's the same effect. I don't know. Josiah, you've done plenty of transition cal studies as well.
Dr. Jose Santos (15:43):
We, we measure colostrum in every experiment. We measure the yield in the very first milking the fat protein, lactose solids, not fat and IgG content in every experiment In the last 12 years, to be a hundred percent honest we did, we pulled, took data together from multiple experiments and we did a large field trial with 21 pins in California, and we pull all of those data together. We had like almost 6,000 cows. A hundred percent of them were genotyped. We can explain maybe 12 or 15% of the variants in colos node with the information that we gather. Things like genotype days in the closeup group diet nested within experiment parity season of Kevin, we explained very little. So if you were to ask me, I think we know very little what affects one cow to give nine kilos of cosst in the very next cow to give only three kilograms of colos.
Dr. Jose Santos (16:48):
And to my surprise, maybe to my ignorance, was that I work with a smart colleague who's a geneticist, and he looks for Mark SNPs that are linked to increased production. Because it always bothered me that we select this cow to be more productive, but we never really select her to give a little bit more colos nest. So it solves the issue of the baby calf when they're born. And there is really no relationship between the marks be associated with milk yielded and the markers that we found to be weekly associated with colos yield. So yeah Mike might have comments here, but I don't think we explained very well. Cornell has done some work. I've seen Sabina has done some work on that. And they, from what I've seen, they are able to explain very little with the epidemiological data of what dictates if a cow will give more or less colo. It's very imprecise at this point.
Dr. Mike Van Amburgh (17:52):
There is a there's still a very, there's a, not a significant, but to Jose's point, there's a effective light, especially if you're a jersey, right? Their pineal gland still responds to less light and they will shut down as the days get shorter, right? So long day lighting, short day lighting would be important for them. Holstein's not so much
Scott Sorrell (18:17):
Very well. Now the question, Steven.
Speaker 9 (18:23):
Hi. My question is for everybody in the group. I'm Steven Emanuel. Dr. Van Amberg, you mentioned that when you infused non-essential amino acids, you had a very large increase in milk yield. And Dr. White, you, you showed a very large increase in milk yield with supplementing choline. And Dr. Santos, you showed a, the meta-analysis. My, my point is none of you talked about the glucose supply reaching the mam gland. To me, it seems you can't get those kind of milk responses without increasing lactose synthesis. Would you comment on the impact of choline on the potential to increase glucose supply to the MAM gland?
Dr. Mike Van Amburgh (19:22):
I'm gonna defer to those two on that particular part.
Dr. Jose Santos (19:25):
Yeah. Had already made a comment that maybe there are changes in how the liver process precursors for gluconeogenesis. Yeah. Like propionate, maybe amino acids, lactate. So all the experiments that we've done with co I'll speak specifically about colon. We haven't seen a concurrent increase in dry matter intake. Okay. So our assumption is that the cow becomes more efficient, but we haven't seen the concurrent increase. Somehow she is not using nutrients for things that would be not linked to production, for example, which you can come up some hypothesis. You know what Barry mentioned, this anti-inflammatory effects of phosphite choline that may take nutrients away from the memory gland. Maybe that part that is part of the story or maybe just the flux of carbon in delivery is different now that more is being diverted into efficient glu eugenic pathways and more becomes available to mam gland.
Dr. Jose Santos (20:29):
So I can't tell you if you do simple meth, you know, the supply supplier nutrients is equal between the control and 3D cows. And the data that I saw today from Wisconsin and from Michigan is the same. The intakes were the same, but the cows gave another, you know, as many as five kilos of milk. Yeah. So obviously the way we do energetic is pretty crude. We assume an average value and we assume that everybody uses that equally. And that is obviously wrong. Yeah. Cows have variable ability to utilize nutrients and probably some nutrients affect how they use other nutrients. Yeah. So it's possible that they may synthesize more glucose and it's possible that more glucose gets direct to the memory gland cuz they will produce at least two kilograms more milk and that is another a hundred grams of glucose. Yeah,
Speaker 9 (21:25):
Well that's what I'm trying, that's what I'm getting at with, with my question is that when you look at lactose, of course it's made up of glucose and galactose and so it takes two molecules of glucose to make lactose. You can't make more lactose, which without having more glucose in the mammary gland. So there has to be a sparing effect. The glucose getting back to what Dr. Bradford indicated, if you reduce inflammation's, a very good chance less glucose is being utilized by the gut tissues and the immune system. And more is, is is reaching the, the mam gland.
Dr. Heather White (22:14):
So it certainly can be yet less utilization by other tissues. It can also be more production. So the thing that's tricky about glucose is we can't just measure blood glucose and assume that meant more or less liver production of glucose because so many tissues are using it really, right? Yeah. So the pool size, the blood concentration's a product of production and of utilization and we've gotta tease that out. So in two instances, we've actually observed that choline supplementation increased regulation of the genes that our rate limiting steps of gluconeogenesis. So in our cell culture model, we observed that, and it was unique to choline from a thine when we were looking at if they were mutually sparing. And then we also observed it in liver samples that were actually from Charlie Staples first transition Cal study where they sent liver up to us at Wisconsin and we looked at those same pathways.
Dr. Heather White (23:03):
And so we see increases in the genes that control gluconeogenesis, which suggests it's not definitive, it's not the gold standard, but we know that these genes are rate limiting. And we know that for those genes, gene expression is correlated with enzyme activity. And so that suggests that there's more glucose production even when blood glucose isn't increased, that may have gotten more blood glucose in the mammary gland, which explains more milk lactose synthesis. Right? The other thing that's related to that is that we consistently see more glycogen. And that's so intriguing because I remember in grad school measuring glycogen and then there was this span in the literature where you don't see anybody measured glycogen, right? We all just stopped doing it. And I was someplace, and Don, I don't remember if it was you or someone else, but there was someone who said, why'd you stop measuring glycogen?
Dr. Heather White (23:52):
And I said, I just don't know, but we should start again. So in the cell culture model, we, we measured it and we observed more glycogen. And at first I thought, well that's because there's no mammary gland draw for that to be glucose, right? There's nothing in the cell culture dish that's telling the liver cell to secrete the glucose. So it stores it as glycogen, but Jos and others have shown it in the cows as well and in vivo studies. So I feel pretty confident across several studies that there's regulation of choline directly on the gluconeogenic pathway. Now just because choline up regulates the genes, the carbon still has to come from somewhere. So I don't know what's being spared there with more oxidation of fatty acids, there's certainly the energy to fuel gluconeogenesis, which is a very energetically expensive pathway. What we don't know yet is where the carbon precursors are. Maybe it's more efficient use of propagate and lactate and the gluconeogenic amino acids like Jose said. But we don't have the data to prove that yet.
Speaker 9 (24:52):
Thank you. Thank you. I just feel we need to re remember that the immune system can suck up a huge amount of glucose and if we can reduce inflammation, that ha may increase the supply at the ma gland.
Dr. Heather White (25:09):
Yeah. Probably happening through both mechanisms. Yes. More production and less wasteful use by the immune system than others.
Speaker 9 (25:17):
Thank you so much. Welcome.
Scott Sorrell (25:19):
Any others from the audience right now? All right, Jose, we haven't officially welcomed you to the exchange tonight. Thank you,
Dr. Jose Santos (25:32):
I'm drinking a merlo from California.
Scott Sorrell (25:35):
Oh, very well. I know you're a wine drinker. Josey, your talk today was about establishing the fact that cho in your opinion is a required nutrient. Can you kind of make that case for us here?
Dr. Jose Santos (25:49):
I guess Mike already alluded to the definitions of required versus essential. Yeah. And the fact that something that is not essential doesn't mean that's not required. And that would be the good example of choline that's used as substrate forin of other molecules. And those molecules can be synthesized denovo in the body. Nevertheless, when you supplement Cho, you see benefits. I think our assumption is that when we formulate diets, the recommendations have to be based. If we look at, for example, de nacin or the NRC on the best data available, sometimes data are just not available to establish. You have to include this in the diet. And that's the limitation that eventually we have. Yeah, the committee has to make decisions and they made, you know, wise decisions with the data that were available at the time. But a lot of times recommendations are based on preventing deficiencies.
Dr. Jose Santos (26:52):
Yeah. Like clinical signs of disease, supplement selenium. So you don't have white muscle disease or vitamin E, but the minimum amounts may not necessarily be the optimal amounts. And I think Cho would fit on those, under those under that umbrella. Obviously the cow has phospholipid synthesizer, otherwise shouldn't be able to produce milk, shouldn't be able to secret milk fat. Yeah, milk fat Glo has phospholipid layers there. But we have seen over and over of, you know, today in other meetings and the published literature that there are benefits to supplementing it. So this is telling me that what the cow is able to make, at least during the transition period is not sufficient for optimum animal performance. Yeah. So I am positive that at some point we're gonna come up to a, an agreement that there will be a, an amount of supplemental calling to be fed to cows, that people will feel comfortable and it's based on reasonable sound scientific data.
Scott Sorrell (28:01):
So my question follow up question would be, which cows right? We've heard forever and partly it's our problem, right? We started out 25 years ago selling choline for fat cows and fatty liver. And you know, you ask people today, they'll say, yes, I use reassure for problem cows. So I'll ask you is
Dr. Jose Santos (28:24):
Cows for, so, you know, if you dig literature, Richard Ardman did experiments with very large dose of choline being infused. And mid lactation cows respond to that, particularly when they had low protein diet. They respond with more milk. A lot of times we interpret data wrong. Yeah. We look at an experiment and we say, you see they don't respond to coal or well, you have to look at the context. What was the dose? What was the circumstance, what cows were talking about? So a lot of times we conclude things that may not necessarily be real. So I think going back to your question, most literature today would support supplementing coal through the transition period to CALSA will start their second or greater lactation. That's where we have most of the data. I think we still lack data on a dose response to know what is the exact optimal amount of coal to be fed. We know very little about CHO and Perus cows. We like to assume that they respond exactly the same. But probably if, if were to ask Mike and Heather and others who do research, oftentimes we find interactions between parity and the intervention that we apply. So assuming that they behave exactly the same is probably not right. And we don't have enough data on Perus and we don't have a lot of data past the transition period. So there, there are still pieces that need to be put together there.
Dr. Heather White (29:58):
Scott, can I add something or, or maybe raise a different area of question that I would ask Mike and Jose. So when we say we don't have dose response studies, I agree and one of the things that I've been thinking a lot about is when we look at the classic studies, we would take a lot of studies and put 'em together and we'd achieve maybe a linear response or you know, quadratic response or maybe a broken stick model. Right? And we hunger hats on those and we said, Hey, this is the point where we don't get an additional response. Right? But that data was comprised of all sorts of different studies. One thing that's really intrigued me is what might be the next generation of data that generates broken stick models or other things which are these feeding gates like what we have and you know, other types of feeding systems where you can mix something in instead of top dress it.
Dr. Heather White (30:53):
So in our study, for sake of time, I didn't go into all this, but we mix the choline into the tmr. So the exact amount that cow ate was not the same for every cow. It wasn't top dressed, right? It was a product of how much feed she ate. And so because we have her exact intake, we know exactly how many grams of choline ion she consumed and we can regress her outcome production, ECM milk fat, any of those. We want to cath growth on the exact amount of cow intake pre partum. And so that gets to be a really interesting model when we think about required nutrient levels. Right. What should the requirement be? Because you can imagine that out of a handful of these studies we could plot out a whole range of intakes of a nutrient choline or or otherwise and plot that out. So I wonder if you have have thought about the different ways that we have the capability to do intake studies now that we didn't before and what that might mean for future rounds of NRC or NASM and requirements in general.
Dr. Mike Van Amburgh (31:55):
Yeah, I've thought about that a lot, which is how we got to tying energy and amino acids together. Yeah. Right. Because you know, to your, to your point about your model, you get one cow come in and she's gonna consume, you know, 15 kilos of dry matter. You need another cow come in, she's gonna consume 19 kilos of dry matter. Well the first thing we know is that energetically they're very different. Right.
Dr. Heather White (32:20):
Unless we have two treatments that had a different concentration of the nutrient in it and we can plot it with an interaction of energy and
Dr. Mike Van Amburgh (32:28):
Nutrient. Oh, sure. But I I was but
Dr. Heather White (32:30):
Otherwise assuming, say agree completely. No. Well, we did have that in ours. Sure. We had a high dose and a regular dose. Sure. Yep. But without that, you're right, everything's confounded by energy, by starch, by amino acids.
Dr. Mike Van Amburgh (32:40):
Right. But that gives us a surface response to say, okay, for every m cal of energy it looks like we get the best response at this level. Yes. Right. Because in the end, what we're trying to discover is she's got an energy output, she's got an energy demand. This can't be some gram mount per cow per day because it's gonna be tied to whatever her metabolic activity is. Oh yeah.
Dr. Heather White (33:03):
Actually, and she doesn't eat a gram of product. Never. She eats a gram of TMR that was mixed with all ingredients in it out on the farm. Right. We don't top dress anything on the farm. Yeah. But we do in our research cuz that's what's allowed us to do those studies. But now we have the ability out a lot of our research farms to mix things into a TMR and look at it proportionally, which may let us answer these nutrient requirement questions across the range of cows, across the range of production and genotypes and components. Right?
Dr. Mike Van Amburgh (33:31):
Yeah. Oh, I'll extend that just a little bit, Heather. The other, you know, within the walls of Morrison Hall, I will push my colleagues to say, if you're gonna, if you, if you're gonna put a diet together and you're gonna test a particular nutrient, make sure nothing else is first limiting. Right. Because you're only gonna get the best response, you're gonna get the next best response of your next first limiting nutrient. And God, that's a hard, hard thing to get through. That's not my hypothesis. No, but it's your, your obs observation's gonna be limited by whatever else was limiting in the diet. Right? Yeah. That's a tough one.
Dr. Jose Santos (34:08):
Just a comment. So one of the limitations that I see is, let's say JOZETTE develops shaz colon product and it's a tough one. Yeah. Because how do I know how much of that is released in the small intestine and actually absorbed? I think that's where things become com difficult to establish with, with a product or a nutrient that has to be protected to be released unless we do things such as intestinal infusion with colon chloride, and then we can measure animal response. So we bypass or escape whatever the microbes are doing to it, then we, and we have some metric or something that tells us this is the value that it's quote unquote optimum. It is hard to come up because with a number, because if you use reassure might be something, but if you use Joss's product, maybe you have to fit maybe twice or three times as much because his protection method is lousy. Yeah. I don't have their technology and that's where we are gonna get in trouble having a body, a scientific body stamping their name and saying, you know, the C N C P S says you have to feed so many grams of colon ion because you may get colon from biochem or from Santos and Santo is pretty bad product
Dr. Mike Van Amburgh (35:38):
Or something like that. That problem exists now suse that doesn't
Dr. Jose Santos (35:41):
Dr. Heather White (35:59):
And just as we don't have one defined metric on undoing a requirement definition, we don't have the one required or one defined metric for a bioavailability assay either. So what's the outcome that we're trying to measure based on the bioavailability? Is it milk fat? Is it ecm? Is it VDL in the blood? We don't have that defined. Right.
Dr. Jose Santos (36:22):
And colon, once you feed it goes everywhere in that first pass through the gut. Probably a lot of it never shows up in the portal vein. Yeah. And that's what Mike, the vet's work shows, even when they infuse colon chloride, they only recover half of it because tissues are using. Yeah. Yeah.
Dr. Heather White (36:39):
It's in every cell membrane there is. So it's very hard to quantify.
Scott Sorrell (36:45):
Carrie, any more questions from the audience?
Speaker 10 (36:47):
Maybe a little different twist because something led to my thought process, what Yoa said about the maintenance of mitochondria. You know, it's one of the things in aging in humans that mitochondria function decreases other things, telomeres and stuff. So should humans be taking choline and maybe live longer?
Dr. Jose Santos (37:14):
Well, I, I guess if you were to ask people who work on choline nutrition humans, they'll make lots of cases why we need to get those 450 to 500 milligrams of choline a day. But if you talk to people who study cardiovascular disease, they'll tell you that maybe you should not take in very large amounts because choline, carnitine are linked to this trimethyl and monoxide production that are at least associated with cardiovascular disease. You know, this whole story of saturated fatty as causing cardiovascular disease. Now, there's a different twist that when you eat animal products, you eat a lot of carnitine, colon and during the process of digestion or microbes will produce this oxide products that they might be the culprit for some of the cardiovascular disease. So you can hear, I think it, it's, it's real biology. Yeah. There is inadequate, there is an O one, there's an excess. And I think that applies to every nutrient and choline is no different. Now, relative to your specific question, I'll diverge to somebody else if they want to comment on colon and mitochondrial survival and activity,
Scott Sorrell (38:33):
Don't look at me
Dr. Jose Santos (38:37):
The, all the data we have on mitochondrial genes are on genes. Usman, who's sitting back there, measure genes linked to mitochondrial activity. But we don't have functional data to say that they really differ
Dr. Heather White (38:50):
If you'll be around tomorrow, I have a little bit of data from our mid lactation feed efficiency work that shows some interesting interactions with oxidation and mitochondrial function and choline and metabolomics work.
Speaker 10 (39:04):
Well that was my kind of follow up to bring it back to dairy is if, if cost wasn't an issue, you know, you show the carrier effect feeding for 21 days postpartum on mil on milk, but what if you fed it longer? Would memory cells maintain their integrity for a longer period of time?
Dr. Jose Santos (39:27):
So we fed colon in one ex as a single experiment that we fed for 21 days or we kept feeding for 105 days at a dose of 12.9 grams of choline ion in a room protected form. We did not see any benefit of extending beyond 21 days at that particular dose. Okay. But like I mentioned, there are other experiments out there in which they fed twice to four times as many grams of choline ion 45 grams per day. And they showed benefits when cows were in mid lactation. So I wouldn't discard that. That can be the case. Yeah. But in our case, we didn't see a benefit of keeping the same dose beyond 21 days postpartum, just to, as I look at this data from multiple experiments, now, you know, from my limited knowledge of memory cell biology, I have to think the CHO is affecting the number of secretory cells. You just don't get discontinued persistence of production without affecting either reducing cell death or maintaining cell actives for a longer period of time. I don't think it's just a nutrient effect early on. May not necessarily be a direct effect as I hypothesize it may be an indirect effect. But I would say that to continuously get another two or three kilos of milk when you stop the intervention, there has to be effects on the memory cells there.
Speaker 7 (41:14):
I was intrigued again by the data, Heather, I think you showed with the meta-analysis, you, you put your data over the top of that and showed higher production cows showing a similar impact, if I remember right. And I, I don't think there was a impact on production in the first three weeks, but it was a tendency later on if I, if I remember that. Right. So is there other than your point of saying Wisconsin cows maybe produce more than oh, okay. All right. No, thanks for making
Dr. Heather White (42:14):
Yeah. So before I take a stab at answering that, I wanna disclose, all joking aside, the meta-analysis covers like a couple decades of research, right? So the fact that the cows in our study made 35% more ECM than the average of the meta-analysis is also influenced by production level over three decades, different days fed different products, right? There's a lot of things. So of course, when I'm giving a talk in Wisconsin, I love to say, Hey, we're doing a good job, Wisconsin cows are making more milk. But that joke aside it is intriguing to see that we still see response that high of production level as the default or the starting point, right? So I'm trying to remember, Jose, if you and Usman did this in your meta-analysis, but Rick Drummer did a really interesting approach when he did one of the first meta lyses where he went through and he said, what's the likelihood that if you feed it, you won't see a response, which is the question on everybody's mind, right?
Dr. Heather White (43:13):
And he found a very slim error, basically, right? If we talk about type one, type two error, a very slim error that you would feed it and not see a response. And it wasn't different by starting point production level. And as you saw plenty of data today, it doesn't seem to be affected by body condition score or any of those factors, right? So it does seem to be a response across the board, which makes sense if we think about the mechanism of action being through liver metabolism, nutrient use, efficiency, maybe mammary gland action, which I agree probably some of that's going on. I don't wanna be the one that test it, but probably some of it's going on. And so I haven't seen any reason to suspect that it wouldn't happen with some random subset of the cows that we haven't magically thought to question yet. I think we've all run the data a lot of different ways, and there's a lot of farms that put cows on it, compare it to cows that aren't on it. So I think it's a pretty consistent response, which again, makes sense based on the biology and the mechanism.
Speaker 7 (44:16):
Yeah, I, and I, anecdotally in the field, I would tend to agree, I think, you know, you do see the responses at high production levels. I was just surprised by how, how far above, you know, I mean, those production responses are really different, right? Or those cows are really different as you get the higher production responses. So I was just surprised by how big a gap there was in that data in the analysis. So thanks.
Dr. Clay Zimmerman (44:39):
If you look at Barry's study, I mean, on a, those, his graph was on a just pure milk ke but if you looked at energy corrected milk, those cows were producing quite high as well mm-hmm.
Scott Sorrell (44:59):
Very well. All right. Why don't we switch gears a little bit and talk a little bit about in utero programming. And Josiah, I'm gonna throw this to you first because I think the first research that we'd seen was started probably by Charlie Staples. So why don't you talk us through a little bit about what is epigenetics and what role does choline play in epigenetics?
Dr. Jose Santos (45:23):
Dr. Jose Santos (46:58):
And that create this whole field of epigenetics, which to me, I think we tend to try to explain too many things with epigenetic. I guess when we don't have an explanation, we say that's probably changes in the epigenome of the individual, but I'm not making jokes. It, it's actually a pretty serious area, and it's a very complicated area that is above and beyond me. But calling through bating plays some an important role in that. And probably the best example would be anybody who, any woman who's pregnant or anybody who's married to a woman who was pregnant, probably had to get 400 micrograms of folic acid every day. And that's to avoid narrow tube defect, which comes when you have folic acid deficiency. And that creates, this changes in methylation that creates abnormalities in the phenotype. And that's a pretty bad abnormality to have a neuro tube defect on a baby.
Dr. Jose Santos (48:01):
So colon, through the process of producing bein can effect the epigenome in the case of the experiments that have been discussed here, the epigenome of the placenta, for example, perhaps the epigenome of the memory cells, the epigenome of the baby calf, and that can alter the phenotype of the individual for either good or bad. Yeah. So you can go either direction, depend upon what gets methylated, what genes are affected, and then what genes are primarily silenced. But they can be overexpressed. But it's sort of a how should, it's, it's not a targeted approach, eh, we have no control over that. If I feed more methyl donors, more methin, I have no idea what's gonna happen relative to methylation. The expectation is that there will be something good coming out of that, which in general, that's what people observe through this methyl donor groups influence in animal responses.
Dr. Jose Santos (49:05):
So people are interested in that area because it can affect how the calf behaves. Perhaps that can affect how the calf grows relative to resistance to disease perhaps. But we are just crawling at this time in the bovine researcher. So there's not a lot of data there, there. And, and the biggest challenge we have is that for those experiments, we need large number of animals, and these are all interventions that are done through diet. We have to feed animals individually to have the animals experimental unit, and that creates a major limitation, what we can accomplish. It's a, it's a slow process. Eventually we'll learn more, I think.
Scott Sorrell (49:49):
So just kind of briefly I know you've guys done some research. What are some of the outcomes you've seen in calves?
Dr. Jose Santos (49:55):
So in the study that an experiment that Juan bti and Marco Z Obi did when they were in grad school at Florida they looked at colos yield from the cows. And in both experiments, colossal increase. So that's somewhat of a consistent response. You saw that here today. Barry showed some data. I think Heather maybe also showed some data. So this cows produced more colostomy, but then the calves that were born from cows that received coal, we randomized them, our coal, our control diet, we randomized them to receive either colossal from coal fed cows or control cows and, and vice versa. So we, in the, in the calf part, we arranged that as a two by two factorial in the experiment. But calves that were born from coal fed cows, they performed better. It's a small experiment, had a hundred calves they performed better.
Dr. Jose Santos (51:00):
And in the mayo calves, the bull calves, when they were also fed colostrum from the dams, and they were challenged with LPs, none of them died. When the calves were born from control dams and fed colostrum from control dams, I think 30% of them died from the LPs challenge. So there's, there's, there's some indications showing that they can withstand a challenge better, perhaps they have less of a pro-inflammatory response to an LPs challenge, which is sort of a, a bomb that we give to the calf. It doesn't necessarily mimic a disease event, but it gives you insights on that process. So there were benefits to doing that.
Scott Sorrell (51:50):
Heather, I wanna circle back real quick on the epigenetic aspects and for the benefit of our listening audience who did not hear the presentation today. Can you talk a little bit about the results you saw in the calves in your research study?
Dr. Heather White (52:04):
Yeah. So overall in our study we observed improvement in average daily gain in the zero to two week range in the Holstein heifer calves. And not later, but in the beef cross calves, the Holstein by Angus calves, we observed an increase from four to eight weeks, and then improvements in the body weight from two to nine months, and then feet efficiency in the finishing period. So we put 'em on a, basically a, a six week feed efficiency study as they were growing. We saw some differences in metabolites, circulating metabolites, and really interestingly, improvements in marbling score in the beef cross calves. To get back to what Josiah was saying, it's, it's not a targeted focus with epigenetics. And we were asking the same question, did supplementing the cow with choline influence DNA n methylation? And so we took a really big picture approach and we measured global DNA n methylation.
Dr. Heather White (53:00):
So you take a blood sample and you just measure snapshot, big picture DNA n methylation. So we didn't look gene by gene or anything like that, and we did see an improvement in the beef cross male calves in, in global methylation. But what's really interesting is we saw improvement in growth in all of the female calves too, and we didn't see an increase in methylation. And that brings up some really interesting things. First of all, the approach is global. So it's big picture. We don't know if there wasn't methylation that's targeted to genes in all of the animals, because we didn't dig into that. But the other thing is that we do know across species methylation patterns are offspring, sex dependent, and jossy, that was something that you didn't address. I'd be interested to know if you guys have looked at those interactions, interactions by sex at all in any of the studies.
Dr. Heather White (53:51):
I think you had the one study with bull cals and heifer calves, right? But across species, we know that male offspring have differences in methylation, and they're more likely to show increases in methylation patterns than female. So that's, that's just something to throw out there that exist. Despite that, we saw improvements in growth in male and female in Holstein heifers and in the beef cross. And so I think that really highlights what Jo Z said is, yeah, methylation of DNA n epigenetics is probably one part of it. But I don't think it's the whole s the whole explanation.
Scott Sorrell (54:27):
Guys, this has been a lot of fun, but it is last call, and I've been out of bourbon for about 20 minutes now. So we're gonna have to call this thing to a close. What I'd like to do is have each of you guys kind of share a key takeaway from our conversation today. And Mike, I'm gonna start with you. What's one key takeaway from our conversation?
Speaker 3 (54:46):
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Dr. Mike Van Amburgh (55:13):
Well, nothing that I talked about, it's what I heard from everybody else here that I'm thrilled as a guy who's spent quite a bit of time working on calves that you guys can show metabolic responses to calves from either in utero effects or colostrum, is fantastic. So keep it up
Scott Sorrell (55:29):
Very well.
Dr. Jose Santos (55:32):
It's complicated.
Scott Sorrell (55:46):
All right. Very well, clay.
Dr. Clay Zimmerman (55:50):
I, I think the research speaks for itself. As far as cho being a required nutrient for transition cows, we consistently see these responses. And the responses are, I think we're actually getting better over time in these higher producing cows.
Dr. Heather White (56:10):
Well, I, I will overlap a little bit on the consistency, but from a different angle. For me, it's that when everything points to something, it makes us feel really good about something. Cuz we can do studies a bunch of different ways. We, we can analyze data a bunch of different ways, but when you get the same overall pattern, either in the metabolic pathways, in production responses, in the, the pathways that are coming up important, that tells me that we're looking in the right places, we're looking at the right direction for mechanism for, for nutrition, for nutrient use efficiency. And that means keep it up, keep going, right? More studies keep us busy until we retire, which is quite a while for me.
Scott Sorrell (56:52):
Yep. All right. Well, thank you very much for joining us. Thank you for the distinguished speakers today. Great presentations. Really appreciate it. Thank you for the live audience for joining us here. And thank you to our loyal listeners here at the Real Science Exchange. Thank you for joining us here. Once again, we hope you learned something. We hope you had some fun, and we 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 3 (57:16):
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