Guests: Dr. Bill Weiss, The Ohio State University; Dr. Helene Lapierre, Agriculture and Agri-Food Canada, Sherbrooke Research and Development Centre, Quebec; Dr. Susanna Räisänen, ETH Zurich Dr. Räisänen completed this research during her Ph.D. at Penn State. The meta-analysis included 17 different studies published between 1999 and 2022 investigating supplemental histidine for lactating dairy cows. They divided the type of supplemental histidine between infused histidine and rumen-protected histidine and the basal diets between corn silage-based and grass silage-based. (4:34)
Dr. Räisänen completed this research during her Ph.D. at Penn State. The meta-analysis included 17 different studies published between 1999 and 2022 investigating supplemental histidine for lactating dairy cows. They divided the type of supplemental histidine between infused histidine and rumen-protected histidine and the basal diets between corn silage-based and grass silage-based. (4:34)
Primary response variables measured in the meta-analysis included dry matter intake, milk production, milk composition, and milk component yields. The researchers also calculated the efficiency of utilization of histidine and other amino acids supplied to the cow by the diets. Lastly, they calculated marginal recovery of histidine and evaluated the interaction between histidine supply and energy supply and how that impacts the efficiency of utilization. (7:38)
Dr. Lapierre gives a little history of histidine research. When recommendations were coming out about lysine and methionine requirements, the different studies recommended relatively similar amounts of lysine and methionine based on the proportion relative to MP supply. On the other hand, recommendations for histidine varied widely depending on the study, ranging from less than 2% to almost 4%. As emphasis has been placed on reducing the footprint of dairy production, interest has risen in feeding lower-protein diets. In this scenario, we would expect an increase in the microbial protein; however, microbes are relatively low in histidine content. If we look at the proportion of histidine relative to MP, as the crude protein concentration of a diet decreases, this proportion of histidine decreases. (8:34)
The meta-analysis revealed a clear response to histidine in milk production, dry matter intake, and milk true protein yield. Susanna and Helene are not sure if the dry matter intake response was due to a pulling effect because of increased milk and milk protein yield or if histidine has an independent impact on the brain, as has been observed in some monogastric studies (16:15)
Clay asks the guests what they think the histidine requirement is, and both agree that providing one number is not practical given the other interactions from basal diet to the efficiency of utilization to the concentration of other amino acids in the diet. (32:01)
Practical implications from the meta-analysis include an understanding that lower protein diets may very well need supplemental histidine for optimum performance, and cows pay a penalty when inadequate histidine is supplied. (35:09)
Helene’s take-home message is that histidine should be taken seriously. If you don't supply enough of it, then you'll have a penalty in your cows’ production. Further, the efficiency of histidine utilization will be affected by the energy supply, and we have tools with NASEM to assess if a herd is receiving sufficient histidine. Susanna echoes Helene’s message and adds that a rumen-protected histidine product on the market would be very helpful. (45:35)
The paper can be found here: https://www.journalofdairyscience.org/article/S0022-0302(23)00416-2/fulltext
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Scott (00:07):
Good evening everyone, and welcome to the Real Science Exchange, the pubcast where leading scientists and literacy professionals meet over a few drinks to discuss the latest ideas and trends in animal nutrition. And we're back here for another episode of the Journal Club with Dr. Bill Weiss, emeritus Professor from the Ohio State University. Bill, welcome once again for another exciting rendition of the Journal Club. Why don't you start off Bill by introducing the guest that you brought with you tonight, and maybe just a little bit about the pre or the, the, the paper that she's brought for us.
Bill (00:44):
Okay, Scott, it's good to be back. The guest I invited was Dr. Helen LaPierre, who I got to know very, very well during several years of working on Nasscom. And she brought a guest who I'll let her introduce 'cause she knows her better, but the paper is gonna be on lactation performance effects of supplemental histamine and dairy cows, a meta analysis. So, Helen, if you could just introduce the person you brought, then we'll get, get into the paper and what, welcome to the, the podcast.
Helen (01:17):
Well, thanks, bill. And actually I thought that Susanna had to be on board because she's the one who wrote that paper. Right. So, Dr. Susanna Hyen, she's from Finland, and she did her PhD with Alex Christophe at Penn State University. And then she went back for a beginning of postdoc in Finland and then moved to Zurich. And now she's currently working in Zurich, still interested in a mine acid and protein nutrition dairy. Right, Susanna?
Susanna (01:48):
Yes, very much so. Thank you for the introduction, and thank you for inviting me on the podcast as well. I'm very excited to talk about this topic of histidine. This was also a large part of my PhD that I did with Dr. Al at Penn State. So I'm excited to share the results of our meta-analysis with you. Good,
Bill (02:10):
Good. Good to have you. I forgot to mention, this is published in the journal Dairy Science this year. I don't have the month, but very quite recently. I guess if you could just start, I don't know which one you wanna address, but with meta-analysis, we always wanna know how many studies went into the analysis and just a little bit of the background of the data you used for the meta-analysis.
Scott (02:35):
Bill, before we get started if you don't mind, I kind of just wanted to introduce my co-host. Once again, it's gonna be Dr. Clay Zimmerman, and you might notice for those of you that's watching at home on YouTube, that Klan R is side by side, not just on the screen, but literally here, physically, side by side. And we are here in a conference room at our corporate headquarters in Montvale, New Jersey. So I just wanted to kind of point that out. Also, want to thank Helena and Suzanne from, for, for joining us. Suzanne, this is, this is not your first time to the pub, so welcome back. Appreciate thank you for having you here. So go ahead, Bill, why don't just start then with your introductions. No,
Bill (03:12):
No problem. I guess again, if you could just give us a little brief background of the data used for the meta-analysis. Without going into too much statistical detail,
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Susanna (04:34):
Sure. Maybe I can take this, Ellen. So this meta-analysis, we included a total of 17 different studies published between 99 and 2022. So from some time ago until very recent publications investigating supplemental histamine for dairy cows lactate in dairy cows. And then in some of the studies they were, there were different combinations of treatments. So we then were able to divide them some publications into sub studies. So in total we had 22, 22 different kinds of studies totally included. And then one important point was for us to, to divide also the type of supplemental histamine used in different studies. So there were studies that had different forms of infused histamine but then a lot of the studies also included the studies we did at Penn State used women protected histamine.
Susanna (05:36):
And we actually, as we get into the results, we saw some significant differences between that type of supplemental histamine. And then another point to, to make about the, the studies included is also the basal diet. So we had both corn silage based diets, and those also included the Reuben protected history in most cases. And then most of the infusion studies were actually done with grass silage based diet. So there were a few confounding factors. I, I think, is something that hopefully in the future we can continue this animal studies to investigate also different basal diets with room protective histidine. But that was kind of the dataset we had available.
Bill (06:19):
And there, there was a wide range of inclusion rates or supplementation rates of histamine with the different studies. Quite a wide range of
Susanna (06:27):
Them. Yeah, for sure. Yes. And then also this one important point is also that the level of histamine in the basal diet itself was also quite different, so that also expanded the range of different doses as well. Yeah,
Bill (06:42):
I thought one other important thing is, at least most of 'em, it may have been all of 'em, but you made a comment in the paper that supplemental RP methionine and lysine was fed maybe to all of 'em, I can't remember. So that likely we're not limiting in these studies.
Susanna (06:58):
Exactly, yes. And, we made the point to, to include only comparing like studies where we, everything else was the same between within the study, so only the additional histamine was different between the treatment. So that was an important factor as well. And then, yeah, most of the studies included either lyin and meth or a lot of the infusion studies then included other amino acids as well. Yeah.
Bill (07:26):
Okay. And then briefly on what, what all, we'll get into the details, but what all was measured or what were the res the primary response variables.
Susanna (07:38):
So we looked at all the important lactational performance parameters. So first trim TER intake, and then milk production, energy, protein, milk, and milk composition and also milk milk component yields. And then we also calculated efficiency of utilization of histamine, including, and then also for all the other amino acids that were supplied to the cow from the diets. We also then calculated the efficiency of, of I mean marginal recovery of, histamine. We can talk about it a little bit later as well. And then another important factor that we looked into was histamine supply in relation to energy supply as well, and the interaction there and how that affects the efficiency of utilization. So those were the major factors we included.
Helen (08:34):
Maybe just to step back once just why we were interested in study, you know, why we all begin that story working ity. It's like years, years ago when we began to have a little bit more information or more recommendations for lision and methionine, all the different approaches, they were suggesting fairly similar supply of lysine and methionine that were at that time recommended based on the proportion relative to MP supply. But for histamine, depending of the different studies that were conducted, the proportion did vary for the recommendations between like less than two to almost 4%. So we decided at that time that we should really begin to have a closer look at histidine, because previously most of the work has been focused on lysine and methionine. So that's where we began to work on histidine. And then I'm, we made like a very focused study.
Helen (09:31):
And after that Susanna just took over the little review that was made at the end of this study, just to have a broader perspective with the new studies that she added as well when she was doing her PhD. So there was really like this question mark about edine that we couldn't solve in terms of what would be the recommendations. Because recommendations were just so different between the different proposals that were coming from France or, you know, from, well, different areas. And also, as Susanna mentioned, yeah, there might be something that was related to the type of study or the type of diet that the animals were being fed that was sold later on in, in the lab of Hal. So that's why we focused our intention on our attention on histamine.
Bill (10:20):
What, what are some major, are there any good basal ingredients that provide histamine, you know, large amounts of histamine?
Susanna (10:31):
I think that what, well, what I've seen is histamine . We used actually in one of the animal studies that I did at Penn State we used a blood mill, which has overall quite a good profile of different amino acids and histidine especially is quite high. I think from, from, you know, common feeds, fed, fed on farms, histidine is not usually limiting if the metabolizable protein is, is adequate and or higher levels. And it's very difficult to increase histamine per se from just feed stuff. That's what I've understood. So that I, I would say I don't know if Len has any input on that.
Helen (11:16):
Well, maybe just to mention that while also his became such a hot topic, if I could say so, is that because all the consumers demand and all the emphasis that was put on reducing the footprint of dairy production, we want to work more and more with diets that are lower in terms of protein supply. And what we always learn at, it's cool that microbes add a really good profile of amino acid, but if we have a closer look, actually the microbes, they have a low acid concentration compared to a lot of the feed
ingredients. So when we try to reduce the protein content of the diet, usually we increase the proportion of microbial protein because it, you know, it, we know that this is like a cheap good source of protein to have like high microbial protein, but when we do, so, then we decrease the supply of INE at a higher rate, then we decrease the supply of other amino acids.
Helen (12:16):
So basically, initially it was thought that it was with grass silage diets, for example, that INE was being limiting. But then we realized that no, it's because when the grass silage diets were being fed, they were low protein diet. But if we feed low corn diets, low protein corn diets, we're facing the same situation. Really, if we look at the proportion of s cine relative to mp, as the true protein concentration of diet decreases, this proportion of a CD decreases. So if we want to work with a low protein diet, then we'll have to put more attention online, which we didn't have to do when we were feeding cows with like 18 protein, 18% C protein diets. But if we want to go with lower supply, then we have to pay attention to histidine. And as Susanna was saying, a blood meal is quite good but it's not allowed in all the countries. And sometimes when we look at the cannula meal, for example, it's not like a super ingredient compared to a blood meal, but it might bring a little bit more heine than other types of protein supplementation as well.
Susanna (13:29):
So yeah, and this is something we have also, I was involved in, in some studies we've done at Penn State comparing canola meal and, and soybean meals. And there we see the profile of histamine is slightly better in canola milk compared to soybean milk. Yeah. And I, I would add also to, to the point Len was making about the low protein diets, and I think this is a lot of the work. Before I joined Dr. ISO's group at Penn State, they already did quite a few studies with these low protein diets and supplying both meine lysine and then later his still, and this histamine work really came about because of the low protein, low metabolizable protein diets, and they were obor observing very low levels of plasma histamine. And that's kind of where this histamine came into play there, and I was very excited to join that line of research and kind of completed this meta-analysis, what came off full circle. I, I, I, I feel
Scott (14:29):
So Susanna, how, how do you define a low protein diet? What does that mean?
Susanna (14:35):
Yes, this is a good question as well. I, I think we, we work really with think looking at metabolizable protein deficiency based on then NRC 2001 which now maybe LM can then explain more what's, what's new in the, the current improved models. But we were really looking into metaly blue protein and then deficiency in terms of req recommendations in the MRC. And we were basing it between 10 10, around 10% five to 15 I would say we were working with. And then there, the crude protein content, I think we had around 15% crude protein in those studies that we, I did at, at Penn State.
Bill (15:25):
Yeah, so they're, they're not rock bottom low. They're only like five or 10% deficient based on the old system. So they're not really, really low. They're quite, quite I'd say reasonable diets in today's environment. So and so with all this emphasis on, you know, blood mills limited in countries, and it may eventually become limited in the US with low protein diets, it's the, the need for supplemental histamine is likely gonna increase in the future, not decrease or the
Susanna (15:57):
Right.
Bill (15:59):
So I think this is very relevant to what's going on now. So if, again, at big picture, let's just start with production. What, what basically did you find with the effects of supplemental histamine on, on production measures?
Susanna (16:15):
So we really saw, so how we did, did the, the analysis was first we, we looked at just the overall effect of histamine quite as a more simplified approach to look at the effect size. And there we saw a clear response in, in production, so milk production, trim intake, and milk through protein yield. And that milk through protein yield really was one of the parameters that responded quite really well to, to supplemental histamine, quite a clear effect there. And then we also did a regression analysis, so then looking at the increasing dose and, and and how, how then the different variables responded to, to increasing histamine supply. And there also we saw positive effects on trim intake, milk yield, and then milk through protein yield. So those were the major parameters that we had a positive response in. Milk fat is interesting. We've seen also in the animal studies that there is a slight decrease actually in milk fat concentration especially but, but but milk fat yield, then usually there is no, no much effect there. Yeah.
Bill (17:33):
So, on the, you know, the milk protein yield, demes, you know, you're providing more amino acids, what on the intake, which wasn't big, but it was pretty consistent. Yes. What, what do you, is it because of the demand for more food for the higher milk production? Or does histamine have a physiological effect on intake control?
Susanna (17:55):
Yeah, this is very interesting because it's been quite consistent as especially with the, with the studies we've done at Penn State and, and with low protein diets. And it's very interesting because we don't really, that's kind of what we only can speculate for now, and we maybe something to, to look into a bit more if it's a pool effect, you know, of the increased milk yield or, or if, because there are some amino acids, including histamine mostly in more like mono gastric models that have been shown some possible signaling effect that his history would have on, on the brain. But this is still quite speculative and we don't have really clear evidence on that in Derek house, but it's a very interesting effect that hasn't, hasn't been really shown with other AM acids. As far as I know,
Bill (18:51):
Like I said, it was very consistent across all these studies. So yeah.
Helen (18:55):
Well, actually, it's too bad because when we were doing the studies with hil and the initial studies were we fed room infected histidine, we put a grand proposal to have a look at the mechanism of actions, but that never got accepted. But that I was, as you said, it's very consistent and it's, it's yeah, it's, it's, it really seems to be there. So is it a pull from the increased milk protein yield, or is it something which has, I know, is it, is this in acting on the appetite control? So that would've been nice to get the measurement. And just to add to what Susanna said, and then I'll come back to the sem, is really one of the reason why actually we, I think we saw an effect when we fed increased, increased or when we infused this in, when
we had higher supply of iodine, that in the initial treatment or in the control treatment, actually, when we look at the efficiency of utilization of iodine, that we can calculate with the NSM now, but that basically it is like the total outputs of protein times their minus acid concentration.
Helen (20:03):
So it's gonna be milk metabolic, fecal protein mainly, and growth. If, if there is any growth and we divide by the supply when this efficiency actually is, is too high, the calculated deficiency, it means that we're asking the cow to use the supply that we're giving at like an 85 or 100%. And actually, when we look at the tables that Susanna made we see that in the infusion type of studies or in the deletion type of studies, the actual efficiency of visine was above 100%, which means that, in theory, we were asking the cow to be using the supply of Visine above 100% of efficiency, which is not biologically possible E either the cow is using, its for the reserve, it has some labile pool ofid as well. So obviously when we gave extra histidine, then the cow was making more milk because then she was able to, well, she had sufficient of sufficient supply of this amino acid to increase its protein output.
Helen (21:10):
And at the same time, what it did is that it increased efficiency of utilization of the other amino acids. But the other around, sometimes when we look at what happens, if we are feeding a cow, it supply an ex an extra supply of iodine, but the cow is already using because of the diet that she's being fed meth at an efficiency of more than 100%. The cow will not respond to his toine because she has to use, you know, she's already chopped in terms of reproduction by the supply of the other amino acid. So we really have to look at all the amino acid one relative to each other. And I think that, you know, this concept of efficiency needs to be refined in terms of, you know, what's the exportation and how, how, how they are affected by d intake, for example, by protein supply.
Helen (22:00):
But with the knowledge that we have now, you know, we know that we cannot ask an animal to be efficient at more than 100% if she does. So, it's because she's taking on, on her body reserves. So, so I think that it's, it's quite clear in, in the grafts and in the stats that Susanna did that when the cows were under fed, you know, with an efficiency of ization above 100%, which was basically the infusion study and the deletion study, the milk protein response was much greater. Then when the cows were receiving a diet that was supplemented. Because then with just a diet, we cannot decrease the relative supply of obesity as much as we can when we do a deletion study or an infusion study. So we'll have to look at this ratio, I think, which is quite important.
Scott (22:54):
Are, are the responses the re responses to supplemental histamine, are they pretty immediate or is there a lag effect before you see a response in the cows?
Susanna (23:07):
So I think for us with the regression analysis, we did see, I mean, it was like a logistic log, logistic model that we use because of this kind of a coline response. Where at lower levels there is a bit of a lag before we see that the response and then it, it's kind of plateaus after the maximum is reached. But this is also what el kind of plays into what Ellan was saying also, especially for the milk true protein yield, where we really had a very low supply of histamine from the basal diet already with the, the infusion studies and especially the deletion studies. And there, there, I think that's kind of where we, we start, it's a more, a gradual response, but then once, once we hit the, I mean the, those starts to increase, then, then the response also it's, is much, much greater when we are especially infusing, infusing the histamine.
Susanna (24:10):
And then at one point to make, also with therum protected histamine, the studies already, the basal diet was supplying quite more histamine that compared to the infusion studies. So there, the response is also a bit not as great as we, we approach higher, higher doses of histamine. And there maybe this is a time to bring up the bio availability also, which can muddy a little bit that the or or why we also saw the, the differential responses in between the, the different type types the supplementation methods for the true protein yield and also plasma histamine. When we, when we looked at that, and there may be the there is some overestimation of, of some of the products that were used in, in different studies. And then, you know, the actual dose maybe was lower. And the, the response was a bit underestimated in, in relation to the dose
Bill (25:13):
For the RP products.
Susanna (25:15):
Yes, yes. Yeah.
Bill (25:18):
And one thing that I, on all these graphs, and there's some, I know there's effects of, of method of supplementation, but almost everything plateaued around 60 grams of meth except plasma. That kept going. It was linear, everything else plateaued. That didn't make sense to me. 'cause I was expecting if, you know, if it's plateauing, why it just, that relationship or that different relationship didn't make sense. Could you, could you make it make sense to me please?
Susanna (25:51):
I think maybe this is also, we can bring in again, the efficiency of utilization. And this was also for the efficiency of utilization. We kind of hit the optimal efficiency at, at the 60 grams per day, more or less. And I think that has to do with, with how we, what we also saw in the production parameters. And here we separated, there was also a differential response depending on the metabolizable protein supply. So actually with lower protein diets, the optimal supply in, in relation to the efficiency of utilization was actually higher. So at lower protein supply, then the cow needs more, more histamine supplied because what we talked about the, the microbial protein there, the, the ratio or amount of histamine supply then is, is lower. And, and that's why for the low lower protein diets, we would need more, more histamine. So can, but I, yeah,
Bill (26:54):
Because again, you know, the plasma concentrations didn't mimic their production responses or the profile. So can we use pla, does plasma amino acids have value in like developing diets and supplementation strategies, or
Susanna (27:11):
This is, maybe Ellen wants to talk about liver extraction at this point, or.
Helen (27:16):
Yeah, but I think that the first one maybe be able would be that actually it's when we look at the graphs, when we put all the studies together there's not that many studies where we had dose response, right? Mm-Hmm,
studies, we could really see that at high supply we reach a plateau of, of concentrations, which was going in the same way as the plateau in production. And again, just as Susanna opened the door, which is quite interesting for us, is that when we look at the efficiency of utilization, and if we look at the contrast, which would be the inefficiency of utilization of iodine, for example, when we had been measurements of liver removal of iodine, they matched quite nicely, which meant that the inefficiency actually was quantitatively pretty much the same as the quantity that the liver was being removing.
Helen (28:21):
So the more we give, the more the liver will be removed. And when we get to really high supply, then this is why actually the concentrations will plateau. Because, you know, once the cow doesn't have anything to do with the histidine, well, just to avoid any toxic effect of hyper amino acid concentrations, then the will will just pump out all of the histidine as it will do for methionine. For example, there's a group of amino acid which are really remove by the liver and this inefficiency, which was quite nice, you know, for our calculation, the, the calculated efficiency or the calculated inefficiency that can be inputted by nutritionist using SEM for example, really matched quite nicely, deliver removals, which means that it is not just like a theoretical concept to amused scientist, but it's really a concept that can be used on, on the, on the farms.
Helen (29:18):
And that would be one way, for example, to examine the diet to see if it can be responsive or if ICIC is limiting or not in this type of diet, would be to look at the efficient, I'm, I'm always coming back to that because for me, it's really the main message, and I think this is something that can be real applied on the farms, is that if you look at the efficiency, and if you are, you know, we had a target efficiency of about 75%, I think in, in sm if we're running at inefficiency of 85 or 90%, it really means that the cows are missing some eine. But if we're below 70% saying Eine is not the mindless to target, there's other things to add. But within a single study, to come back to your question, if I come back within a single study, if we have like a lot of dose that we infuse at high doses, we're seeing a plateau in the concentrations which are matched by increased liver removal.
Bill (30:15):
And I wanna ask, ask this question, and that is on the relationship between energy and histidine. You, you did, energy intake is not, not mega cows per kilogram, but mega cows per day. And a lot of that variation is actually, you know, dry matter intake is a major source of variation in that energy supply. So do, do you think if you, if you just, if you fix dry matter intake, so intake of all the nutrients are the same except energy, do you think you'd still see what you, you were seeing or is 'cause again, is net energy intake increases intake of everything is increasing not just energy or usually because they're just, there's not a lot of variation in the concentration of energy. There's a lot of variation in the intake of energy though. And I'm just wondering is is it energy or is it just nutrients or dry matter?
Susanna (31:14):
Yeah, this we only did for, so we calculated the histamine supply per net energy for lactation supply. And this was then we looked at the effect of that on the efficiency of utilization. So there then we got a very nice response showing the relationship of, of or the optimization of, of both, both histamine and, and energy supply. And I think el also, this is included in the neo nasem also, we have this effect of energy on, on the utilization efficiency. So,
Scott (32:01):
So I've got a few questions. So the first one is, what do we think the requirement is for histamine histidine in a lactating diet?
Helen (32:11):
Well, I am biased because I've been working on that, but I think we should target an efficiency of 75% with a correct energy supply. Because as Susanna mentioned, and it has been shown by many studies, actually deficiency of utilization of the mine acid will be affected by the energy supply. But we, if we have a correct energy supply, I think we need to look at how much milk we want our workout to produce, how much protein, then do the calculations then fit the 75% efficiency, just divide. And that will give us a supply. So it's not like a man. I don't think we can just go with the magic number. It's easier. I would, it's much easier to go with like X percent, but I think that as the milk production will vary and the dry magine intake will vary, then the outputs in terms of metabolic fecal output, which is quite important in milk, the proportion of one relative to each other does vary as well. That will affect the absolute amount of, we need. So I really, it's not as easy because we need to go through calculations, but I think that targeting like 75% efficiency for now, maybe after we'll have done a bit more studies or more application on the field, on the farms, we will, we will be able to fine tune this number. But I think that for now it seems reasonable.
Susanna (33:44):
And I would also add also what we also saw in the meta-analysis, that this depends also on the overall protein, for example, protein supply, if we talk about metaly per protein or, or energy. So it's hard to give one number. And I also agree that this efficiency of utilization is a nice target because then, then you can adjust the absolute supply as crunch per day, for example, based on, on the other variables in the diet as well.
Helen (34:14):
But obviously if you reach that target for edine, but if you're above target or if you're just not supplying another mine in sufficient quantity, then you do not allow the cow to express fertilization of this. Mine wise. It, so everything really needs to be looked at in relation in, in, in a global scheme. You cannot just pinpoint one of mine and say, okay, I'm gonna feed that one and I'm clear, you really need to look at all of the minor acids. 'cause They're all important, right?
Susanna (34:44):
Yes,
Helen (34:45):
It is just, it depends on how much we find in the feeding ingredients that is changing our perspective. But actually for the cow, they are, they're all, they are all important.
Scott (34:57):
So what are, what are some practical implications of, of the hi, you know, the histamine work and the meta-analysis are, are there some things that you know, can be applied in the field today?
Susanna (35:09):
Well, I think as we, we just mentioned about the, the, the way the diets are formulated, I think especially in, in terms of, of looking at the, the total protein content of the diet. If this is something a farmer wants to decrease for, for different reasons which I think will be increasingly sold then I think his in and this efficiency of utilization should be taken into account and see how, how those diets can be formulated. And currently unfortunately, we don't have the room protected histidine available. But hopefully this is something as we also saw in the meta-analysis that histamine is important and increasingly so. I think that's another point. I would say,
Helen (36:02):
Yeah. And, I would say that the meta-analysis also clearly shows that if we are not supplying enough meth edine, there is really a pen in terms of milk kill in terms of dramatic intake, in terms of meal protein yield. So really this is something that we need to take into account. And also one point, which is not in the paper per se, but in the experimental material is the marginal recovery that Susanna has been talking about, which is like from the extra SD new supply, how much actually you will find back in, into mill. And on average, I think it was around 20%, which is much higher than what is usually seen for the room protected methionine, which is more about around 7%. So the, the, there's really options actually to make sure that we do have enough cine, and if we do not have enough cine, there is a penalty that our cows will be paying. So, there's a way to actually check if the cows are receiving sufficient SCD.
Scott (37:03):
So Susanna, you had, you mentioned early on and the, in our discussion today that in the infusion treatments there were different sources of histamine utilized. Did I hear that correctly?
Susanna (37:18):
So the infusion studies were different types of infusions. So we had infusions.
Scott (37:24):
Okay.
Susanna (37:25):
Yes. Not, not, so the histamine that was supplied was, was all studies used l histamine. Yeah.
Scott (37:34):
You know, kind of related to that, I think you also said that the, the infused histamine studies were done mostly with cattle on grass and the run of protected histamine was done with cows on silage. Was that because of where those studies were done, or, yeah, just looking for some background on that.
Susanna (37:55):
Yeah, so the early work with histamine was mostly done in Europe. In Finland, actually, my previous professor I worked under Ila van at the University of Helsinki. And, and her colleagues, they did some infusion studies in, on based diets. And then in the UK they also conducted some studies with different infusions of histidine. And then EL did also these deletion studies, but she used a corn silage based diet. So those, those are the exceptions o of the infusion category, I, I would say
Scott (38:35):
Very well. I guess another question I have is, you know, we typically talk about lysine, methionine, histamine being the, the most limiting amino acids. So what would be next after those three?
Susanna (38:48):
Well, actually in the meta-analysis, we were also looking at the efficiency of utilization of other amino acids in and how that would affect the efficiency of, of history utilization. And one, one that in addition to lyin and methane, we saw lien was also there having an impact. But otherwise I know in the MUAs there are also other amino acids included that maybe require some future work as well to, to see the, the full profile of, of his not histamine, but amino acids and how, how those play and what are the optimal supplies and how we can reach the optimal efficiency for, for the group of, of amino acids. I don't know if l has any
Helen (39:39):
Well, yeah, well, actually, I, I would just answer it really depends what you feed the cows, right? So great. If you feed a cow with a lot of corn, for example, you won't be short in le but if you don't feed any corn, then lucine you might become short of. So it really depends. I think that this is sometimes what we hear is that the cow is like this diet is limiting for the cow, actually. This is really depending on what's being put into the diet. There is not any, not this diet, but this am i acid is limiting for the cow. There's not anoma I acid, which is limiting for the cow. It depends on the diet which is being fed. And I think this is really something that we need to keep in mind. It depends so much of what's being fed.
Helen (40:22):
So as I was saying before, you know, for example, feather meal we know is really, really, really low in histidine. So then if you feed that, that's for sure that isin will be underground. And yeah. And, and I think probably it's a major difference sometimes between Europe and United States, where in Europe it will feed less corn. And I think that in some cases they've shown that lucine might be, it will be worth it to have a look at lucine, for example. Whereas if you have plenty of corn, well, you will have a look at it, but the chances that it is limiting that it's gonna be in short supply, I, I think I prefer to see in short supply rather than seeing limiting will decrease. So it depends so much. What, what are the feeding ingredients?
Scott (41:10):
Any other questions for you? No, I got one last question. I'm kind of curious about you know, what's the next steps for histidine as Bill had mentioned, you know, he anticipates that it's gonna be more and more important as we begin to feed cows a little differently. So what's some of the next steps relative to research?
Susanna (41:31):
Yeah, so for me, I really, really do want to continue the work I've been doing on histamines. And I think we didn't touch too much on it today, but the libel histamine sources, the endogenous histamine sources that we have in hemoglobin, for example, and, and different muscle deep peptides that can be mobilized during deficiency. And this is something we have seen in some studies but require long-term investigations. This is something I would like to look into. And in general, I think long-term studies would be interesting to see. And then different lactation stages of the cows as well. Transition cows are quite challenging to study, but I would say histamine would be interesting amino acids to look into there as well. I know there has been a lot of work on methionine, but I would think histamine is also important in that stage of lactation. And then I think also this energy, energy histamine interactions is something also interesting to continue working on as we saw a very strong relationship there as well in the meta-analysis.
Scott (42:40):
So, Susanna, you, it is the reason why blood meal such is good source of histamine is because it's high in hemoglobin?
Susanna (42:51):
Probably yes. I actually haven't thought about it too much, but now that you say it, it makes total sense. Yes.
Helen (43:00):
Yeah, yeah, yeah, yeah. As Susanna was saying, this is something that we see if the cows are being short in histidine, for example, their hemoglobin level will slightly decrease. So that we'll offer the cow like an endogen source of, of histidine. There's some dip peptides as well, like Carine mm-Hmm. That will be replaced by another type of peptides that will have the same buffer function in the muscle, but so that it can mask the hasin deficiency. And actually in human nutrition, it has been quite a challenge to define what would be the hissin requirements because of that. Mm-Hmm. 'cause If you take a human being and if you put it on a diet which is short or with no, because we can do artificial diet, it's tough to, we won't see very quickly his in deficiency because of the use of all these internal sources. So the same thing will happen with the cow, but the cow is pumping so much milk out, then you know, the deficiency occurs much quicker.
Speaker 5 (43:57):
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Scott (44:20):
Bill, if you will, can you give us kind of a few takeaway thoughts regarding what we heard today? Okay.
Bill (44:27):
Well, one is, you know, meta-analyses are powerful statistical tools. They do have limitations, but they are powerful tools. And with this analysis, they show all the raw, the, the, the, the, the, the, the results by treatments or by experiments. So you can see the consistency. And they also did some other things to look how important it is, if one study is biasing the results. And so I think this is a good, good analysis. It clearly shows histamine's importance, and again, with the discussion they have in the table, in the, in the text, it's gonna become more important with the way we are, we're gonna change formulations, it's gonna become more important. So I think it's a very well done meta analysis, and I think it has a lot of practical importance.
Scott (45:14):
Helene, one last question for you. Our audiences consist of a lot of consulting, nutritionists out there building diets every day for, for their dairy farmers. What's a couple key takeaways from the meta-analysis that you think that the consulting nutritionists out there ought to take away from this discussion?
Helen (45:35):
I think the major point actually is, as I mentioned before, is that this needs to be taken seriously. If you don't supply enough of it, then you'll have a pen LT in your Cal production. So I think this is really, for me, the, the, the main message, which is coming out of that, and again, deficiency utilization will be affected by the energy supply as well. And they have tools, we have tools actually with, with an SM to look at this efficiency, and we can assess actually if the herd is being re or the cows are receiving sufficiently of ine. But also the other mine was, but again, what the metaanalysis clearly showed is that if there is not enough ine in the diet, if the cow does not receive enough edine, there's penalty on milk, milky milk, keel milk, protein yield, and also it might have an effect on dry matter intake, which is also like a vicious circle. So I think the message is really clear on those three main points for nutritionists.
Scott (46:36):
All right. Very well, thank you for that. And Susanna, any final words you'd like to leave with the audience?
Susanna (46:42):
Yes I think I, I a hundred percent agree with Ellen. I would like people to remember that histidine is important and if there is anyone out there wanting to, to produce room protective histamine, this is also a you know, important message for me as I want to continue this line of research into the future.
Scott (47:05):
All right. Perfect. Thank you for that. You know, I think it's pretty unanimous. All of our guests says that histamine's important. So I'm going to surmise that we're gonna have additional conversations be they podcast or webinars on this subject. So I would ask our audience to stay tuned. With that, I want to thank you guys for joining us today. This has been a great discussion. I've enjoyed it. Looking forward to the next one. To our loyal audience, thanks for joining us 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 5 (47:42):
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