Description

Trace minerals are vital components of the antioxidant enzymes required to combat oxidative stress and essential for the body’s immune system. This webinar reviews the importance of trace minerals for cattle health and performance, requirement levels and how they can vary, current sources of trace minerals and the implications of these for bioavailability. The webinar concludes by introducing a new veterinary approach to boost trace mineral availability and how this can help improve the performance of cattle.

Transcription

Good evening, everybody, and welcome to tonight's webinar. My name is Bruce Stevenson, and I have the privilege of chairing tonight's webinar. We've got a couple of exciting things for you tonight.
We've got two different speakers on. So when our first speaker is finished, don't go away anywhere. We've got Doctor Patrick O'Neill coming on at the end.
And he is a vet from Ireland who is going to be talking to us about Min. Really worthwhile listening to that. So don't go anywhere.
Before I introduce our main speaker, James, just a little bit of housekeeping for you. We have a surprise at the end, so stay tuned after Patrick, we will be making an announcement of, a really nice prize draw at the end. So, listen out for that.
For those of you that are new to webinars, if you have any questions for us, simply hover your cursor over the screen. Your control bar will pop up. There's a little Q&A box.
Click on that, type in your question, and it'll come through to me and we will hold those over for both James and Patrick at the end, and we will discuss all the questions that you have. So, don't forget, just pop them in there and we will get to those. Very, very important but of housekeeping tonight is a huge big thank you to Verba.
We have Linda on with us tonight from Verbank. So Linda, very welcome to the webinar vet and a huge big thank you to you and to Verbe for sponsoring tonight's webinar. Guys, remember, we need to support those that support us.
So, you know, companies like Verbank that are putting their money where their mouth is and sponsoring these webinars, let's show our appreciation by supporting their products. So tonight's main speaker is James and he graduated from Cambridge University in 1993. He spent approximately 10 years in veterinary practise specialising in cattle.
He became a Royal College of Veterinary Surgeons recognised specialist in cattle health and production in 2013, and a diplomat of the European College of Bovine Health Management in 2006. In 2005 with Richard Vachery, he founded EBVC, now known as the Evidence Group. And James is a special lecturer at the University of Nottingham since 2006 and provides nutritional advice for some of the best dairy herds in the UK and throughout the whole of the EU.
So who better to present tonight? James Husband, welcome to the webinar vet and it's over to you. Thank you very much, Bruce, and good evening to everyone.
The title of my talk is on the screen at the moment, so it's the role of trace animal, Trace Minerals in cattle Health and Performance, a new veterinary Approach to boost trace mineral availability. I will deal at the beginning of the talk with, the background to this, and then I'll hand on, as Bruce has said, to, Patrick O'Neill, to show the details of the product later on. Talk about in my part of the talk is disease incidents in the periparurian period, the metabolic changes we see during the metabolic period during the periparurian period, sorry, going from, pre-carving to calving, and also how the metabolic changes and immunity, can be linked.
I'll introduce you to the concept of the metabolic stress triad. And then we'll talk about the oxidative stress and role of enzymes in countering its effects, before going on to trace element supplementation, how we do it at the moment, and difficulties with it. .
A lot of the papers that I've drawn on for tonight's talk have been taken from Lorraine Sordillo. And one of the papers that's particularly good if you did want to do any more reading on this topic, is a nice review paper in the Journal of Dairy Science from 2016, and the details there are on the screen. And that's really worth a, a read to sort of join all these concepts together.
OK, so without further ado, let's carry on. It's very evident from our experience in practise and also from, tonnes of literature that, cattle are susceptible to an increased incidence and severity of, of both metabolic and infectious disease in the periacterian period. You can see there that LeBlanc published that 75% of disease incident occurs in the first month, and there's plenty of other papers as well that corroborate that, as well as our experience, of course, in practise.
The idea of dysfunctional immunity, has been around for, several years, and that probably occurs for several weeks, post calving. If you go back to the first work that was done on it, going back 30 years or more, the emphasis very much and the focus was on, what was happening with white blood cells around the time of calving, and the fact that they, seem to be more sluggish and less reactive. As research has progressed, the emphasis has changed slightly.
It's still important, the role of cells. But a lot of what I'll talk about tonight is on the later research which concentrates very largely on the role of excessive fat mobilisation and and the effect, the effect that has on immunity and also on oxidative stress. One of the things that runs throughout the literature is that it's really impossible to separate metabolic and infectious disease in the periparurian period.
As we'll see, there is a common aetiology between a lot of the diseases that we see, whether they are metabolic er or infectious, and strong theories now about the predisposing interactions and causes of these diseases. And we'll take that on in a little bit more detail later. We'll also see in the literature, there are several studies, a lot of them recent, but if you do go back into the 80s and 90s, that link the increases in metabolic activity and the changes you also see around the, around that time with oxidative stress and linking those two things with this increased susceptibility.
Of disease and this increased incidence of disease that we see. So the role of oxidative stress, will become apparent through the talk. That's a very important part, a very important underlying predisposing factor for both the metabolic and the infectious diseases that we see around the time of calving.
So, using a dairy cow, example. As we said, we see a lot of metabolic and infectious disease around the time of calving. And if we're looking at what we're trying to do on farms, so if, if we were going, to a farm and we were setting up a, a nutritional programme that would involve also the, the management aspects of nutrition, which we'll touch on a little bit later.
I would be focusing very much on prevention of metabolic disease, and we're quite familiar these days with the idea that fatty liver, ketosis, they have a strong predisposing factor towards, displaced abemazins, which we would consider aberrant, energy metabolism. We would also try and prevent the preventable, and I would consider milk fever as a, a very preventable disease. Certainly, we shouldn't see much more than 2 or 3% of clinical milk fever.
Resulting from poor, nutritional management pre-carving. We'd also be looking at the second point, not to compromise other or uterine health. And that could be around housing, grouping, and also looking at the immunity, the effects of immunity on other and uterine health.
And they will focus on, as we'll see later, a lot of it is to do with energy balance and trying to avoid excessive fat mobilisation around the time of calving. Hypocalcemma again, that has a big effect on immune function, and also on, nutritionally managing the vitamins and trace minerals, so that we've got optimum levels around the time of calving. And if we want to look at, positive fertility effects, well, normally I think that if we're not getting problems with metabolic disease, and we're not getting problems with, especially uterine health, then we're probably not going to be compromising the reproductive performance of the cows either.
So we're gonna be seeing, hopefully positive fertility effects at the same time. So these are the areas that we are focusing on. And again, very important to make the point that, you know, we're not taking metabolic disease and we're taking infectious disease separately.
They're very much all part of the same prevention strategies, and in preventing one set of diseases, either the metabolic types, we're also going to, prevent the infectious and vice versa. So there's a very, very strong, link between the two. OK, so this should be a fairly familiar territory.
So if we look at the, I use my mouse here, if we look at the graphic here, and we look down the left hand axis, we can see the energy required per day. And here's carving and days relative to carving running along the x axis. And what we see is The lead up to calving, the ME required, so that's the red line, is actually very comfortable.
Cows, dairy cows are very, very good at coping with the energy demands prior to calving. It really isn't a problem for them at all. But unfortunately, just at the point we get to the huge metabolic demands of lactation, so obviously starting here, you can see the red line, rising almost vertically when the cows start to lactate.
Suddenly there is a challenge. The, the gestational demands are relatively small, the lactational demands are huge, and just at the time when we want. Our dry matter intake to increase, to help us to to cope with this increased energy demand.
It does exactly the wrong thing, and the dotted line here shows that dry matter intake actually drops rather than goes up. So, inevitably, in the early part of lactation, so this time here for the first probably don't get into positive energy balance for about 6 weeks, post calving. That 1st, 3 weeks or so certainly, but as I say, extending to, to 6 weeks, we're going to see a mobilisation of fat, and that mobilisation of fat, is likely to have a very negative effect on the immune function post calving.
Especially if it's excessive, a certain amount of fat mobilisation is completely normal. It's when it becomes excessive that we have problems. So what we're talking about.
At the same time is we have this huge increase for energy. We also have a huge increase, demands of protein, so, cows often lose quite a lot of tissue, protein in the first, few weeks post calving. There's also an increase in mineral and vitamin requirements, and those are things that we'll touch on, in a bit more detail towards the end of the talk.
And the important point to make out as well, of course, is, is if we get these things wrong, the costs of disease are, are very, very high. So really we're looking at a reduction in the productive capacity of the cows, an increase in mortality rates, a knock-on effect on fertility, and the cost, of course, of increased microbial use and other treatments, plus, of course, the farmer's time in, in treating the animals. OK, so here's a a table taken from .
So Sordillo paper, and in this, she links up the, interaction between immune suppression at the top of the, of the graphic there with other diseases underneath. And what's quite important here, the point to make is that metabolic diseases, they tend to occur in complexes, and they tend to occur in complexes that also include, infectious diseases. So, you can see the complicated interactions that occur between the different diseases, and there's loads of epidemiological studies that show links between, for instance, retained placenta and instance of mastitis.
So again, linking a disease that we think perhaps is not as an infectious related disease, a retained placenta, for instance, and an induced, and the incidence of mass status, which of course is an infectious disease. So the same is true as well in epidemiological studies between the link with, ketosis and mastitis, and there are loads of other links as well. So, very important, this concept that we don't just get one disease on its own, we tend to get one disease that's linked with several others, and that's probably because there is something, there's some underlying, aetiology that is, increasing the rival of them.
And when you get one, then you tend to increase the, the chances of another one occurring as well. So A Little bit more about negative energy balance and immunity as we've mentioned. That time post calving, there's a huge increase in energy demand.
The cow's dry matter intake has unfortunately dropped at the time we wanted to increase, so we're going to get mobilisation of fat from the fat reserves, and this is normal, a degree of fat reserves a fat mobilisation from the reserves is something that we expect. And that leads to an increase in, Niha concentrations which go into the bloodstream and then go off to the liver to get processed. I'm not gonna go into what happens in, in the liver in any detail, but we should all be fairly familiar with the fact that around calving we get increases in non-sterified fatty acids in the bloodstream.
And we also then, through oxidated burning, get in the levels of ketones, stroke, put oxybutyrate. And again, this is something that we normally expect. It will happen and it is useful, because Neiers can be used as alternative energy sources when the cow is struggling to produce enough glucose, and the glucose tends to get pushed into.
Milk production, so we need alternative energy sources to be able to, power things like skeletal muscle. So it's important to have, a certain amount of fat mobilisation to fill that energy gap, and that is, is fairly normal. So normal levels are too high, we expect it.
If you get excessive need for concentrations, there's. A whole plethora of published papers linking that to problems with poor neutrophil function, for instance, also increases in retained placenta, metritis, and mastitis. So there is a strong link between excessive fat mobilisation and the increased incidence of, those diseases.
And poor energy balance characterised by reduced white blood cell function. And there's the thought that is it energy balance alone, or is the, the effect of carving something that is significant per se? And there were some very elegant studies carried out by Kimura in 1999 and 2002, where there were groups of cows, mastectomized cows, and, and normal cows.
And what they found was that in the mastectomized cows, there was an effect. They were looking at the, metabolic indicators and also immune indicators post calving, where obviously there was milk production in the, in the normal cows and no milk production in the mastectomized cows. And in the mastectomized cows, there was an effect per se of calving, that they did see, some, increase in leaffas and some, reduction in immune function.
But That effect was really quite mild, and the big negative effect was when you had a degree of negative energy balance caused by the milk production. So in the, the normal cows, there was, obviously a much greater energy demand, and that big energy demand. Really, drove the reduction in the immune function of those cows.
So calving per se has some effect, but calving plus, negative energy balance has a much bigger effect on a reduction in immune response around the time of calving. And one of the things that comes out in the literature, quite regularly, and it's probably something that you're quite familiar with, are this idea of pro-inflammatory cytokines increasing in cows that are, are fatter and mobilising more fat around the time of calving. So, increases in nethers can cause an increase in these inflammatory c cytokines such as the tumour necrosis factor.
And what we find is that that you get a dysfunctional inflammation. So again, a degree of inflammation is what we want. We need a degree of inflammation.
It's an important part of the innate immune system. But when you get excessive fat mobilisation, and when you get an increase in these inflammatory cytokines, then that inflammatory response is not properly shut off, and that has severely negative effects on immunity and also on the metabolic health. So we can see here that if we get excessive, nonaerified fatty acids, we get an increase in the reactive oxygen species, which I will talk about later.
And so beta oxidation, so that is the producing production of the ketones, as well as that excessive fat mobilisation, does drive these pro-inflammatory cytokines and the production of reactive oxygen species. OK, so I'll introduce you to the idea of the metabolic stress triad. So, OK, we talked a fair bit already about excess lipid mobilisation from these cows that, what we're saying it's, it's normal to have some fat mobilisation, but excessive fat mobilisation is a problem.
So if we follow through from the bottom left here with the excessive lipid mobilisation through, we get Nethers and BHPs, so we've got Nethers and ketone bodies, and they are in themselves immunosuppressive. When they're at, higher than normal ranges. So that can lead to an increase in inflammatory and immune dysregulation, and we can get a feedback the other way from pro-inflammatory tumour necrosis factor promoting lipolysis directly and also by a reduced dry matter intake.
Studies looking at the level of tumour necrosis factor in cows post calving have shown that cows with higher levels of TNF, will have reduced dry matter intake. So we've got their arrows that point, in both directions, and you have a destructive loop, that's feeding back from the inflammatory and immune dysregulation back to the excessive lipid mobilisation, which makes things worse. If we follow that one round from the inflammatory and immune dysregulation.
We get a, again, tumour necrosis factor induces reactive oxygen species in non-phagocytes. Reactive oxygen species, as we'll see, they're actually, useful again, at the correct level. They're useful in phagocytes for actually, killing bacteria.
But if they're at very, very high levels, they can have negative effects. So again, it's this effect that some is normal, but increased levels can have negative effects. And again, if we get then an increase in oxidative stress and if the term oxidative stress seems.
Something that you're not very familiar with, we will come on to explain that a little bit later. But increased oxidative stress, then increases the activity, and production of the react, reactive oxygen species again, and that feeds back to more inflammation. So you can see that there are several feedback loops here, that all feedback negatively and are destructive, potentially.
And one of the things that we're going to talk in a little bit more detail now is this idea of oxidative stress and how oxidative stress is probably one of the main predisposing factors, maybe the common etiological point between the increased incidence and severity of metabolic and also infectious diseases around the time of calving. And just to finish the loop off, elevated non-nasterified fatty fatty acids increase the oxidative stress, and the other negative loop oxidative stress increases lipolysis. So you can see that you've got a pretty destructive feedback loop from all these three points in the metabolic stress triad, and it's probably the oxidative stress that is causing a lot of the problems and the and predisposing to the animals to disease around the time of calving.
So Again, a Sordillo study er from the early 90s, and in this study, what she was looking at was, cows that had been, treated in different ways, prior to the challenge. So some cows were, fatter than others. And if they were challenged then with coliform, mastitis, so, E.
Coli challenge that zero hours here. The ones that were fatter had an excessive cytokine response, and those were the ones that were more likely to die. The ones that had a degree of inflammation, and remember, tumour necrosis factor is part of the innate inflammatory response.
Those, it did its trick, it did its work, and those animals survived. So again, it's this idea that you can get an excessive amount of inflammation. And an excessive production of cytokines, and you may have heard this term talked about of a cytokine storm around the time of calving.
So we have dysfunctional inflammatory response and that is the probably the common link between the metabolic and infectious diseases around the time of calving and this idea of of oxidative stress. So oxidative stress, yeah, key part of the metabolic stress triad and impacts immunity directly involved in enhancing both metabolic and effects susceptibility in cattle and also reducing, of course, through that the of those animals. So let's have a look at that in a little bit more detail.
So when there is, aerobic metabolism, molecular oxygen, is required, and you get a sequential reduction, which is the addition of electrons, leading to the formation of these reactive oxygen species. And they have extremely high chemical activity, and they can damage cells. So what you find, if you can remember from A level chemistry, this idea of oil rig, oxidation is loss, reduction is gain of electrons.
Well what these reactive reactive oxygen species do. They steal electrons er from cells, so they create oxidation, it's lost, they create an oxidative state in cells, and that is potentially a damaging state. A level of of reactive oxygen species is useful.
It's involved in the regulation of normal cellular processes, also involved in, in regulating vascular tone, and needed to increase blood flow to, areas of infection. And also, as we've already mentioned, the destruction of invading pathogens, after bacterial phagocytosis. So, reactive reactive oxygen species are, are present in neutrophils and macrophages to kill, pathogens.
At the bottom of the screen there you can see the re reactive oxygen species. So we've got the superoxide anion, peroxide, hydroxyl radical and hydroxyl iron as well. And What we'll find then next is, with oxidative stress, there's various definitions of oxidative stress that all really amount to very much the same thing that you see the top one there.
It's talking about deleterious processes resulting from an imbalance between excessive formation of these reactive oxygen species, and an imbalance between those and, antioxidant defences. Second one amounts to the same thing, it's the disturbance in the pro-oxidant, antioxidant balance, resulting in tissues, being damaged, and cells as well. So again, it, it, it's a balancing act, and on the left hand side, at times of increased, metabolism, especially when we've got, excessive inflammation.
We get a an increase in the amount of oxidants. And what we need on the other side is an increase in the antioxidant defences. And those have anti-peroxidation actions, so they're trying to stop the negative effect of those, of those prooxidants.
And the things that you might be familiar with, alpha tocopherol, alpha tocopherol is, the precursor for vitamin A, beta-carotene, precursor for vitamin E. So those two are, of course, vitamins. And also, The areas that we're we're coming on to more now, the trace elements.
So selenium, copper, manganese, zinc, and the reason I put iron in brackets there is, we always have iron in diets at a higher level than it's actually being required, but we, that isn't the case for selenium, copper, manganese, and zinc. So, the antioxidant enzymes, so this is where the trace elements come in. The idea of the antioxidant enzymes is to try and decrease the damaging capacity of the reactive oxygen species.
So starting with superoxide dismutase, what that does is it, changes oxygen and the hydrogen into hydrogen peroxide, and copper, zinc, and manganese are all, key trace mineral components of those enzymes. Cataase, as we mentioned, this is something that's dependent on iron, and there's usually a large excessive diet, so we don't need to worry about adding iron, but iron is involved in catalase. Which is an enzyme responsible for the decomposition of hydrogen peroxide to water and oxygen.
And the other one that, you may be familiar with as well, because of its use, when we're trying to determine the status of animals, with respect to selenium, because it is a selenium, enzyme, the psyllium containing enzyme is glutathione peroxidase. And glutathione peroxidase, converts hydrogen peroxide into, into water. So, trace elements here, they're key components of the anti antioxidant enzymes, and these antioxidant enzymes are there to combat oxidative stress.
OK, so we've talked a lot about metabolic function. And carries around the time of calving. There's also a lot of evidence relating oxidative stress to, reproductive performance.
We know from experience in the field and also a huge amount of published literature, that postpartum uterine diseases have a negative effect on reproductive function. So if we've got an animal with endometritis, whites, we know we're much less likely to get that animal pregnant. In a timely fashion.
Oxidative stress probably plays a role in retained placenta. When we talk about increased retained placenta incidence on farms, people often jump to the conclusion that it's selenium, related. It can be, because selenium is one of the, enzymes, is one of the components of the enzymes, that can be used in countering the oxidative stress.
So it certainly can be, and that's been linked in the literature. There's probably a lot of other things as well that can cause retained placenta, such as, for instance, excessive fat mobilisation again, that tends to increase the incidence of retained placenta. A couple of published papers showed a role, for reactive oxygen species in reproductive function.
So again, this idea that some is required for normal, reproductive function, but associated with ovarian disease and reduced reproductive, performance when the, level was too high and there wasn't a balance against the antioxidants. And supplement supplementation studies, vitamin D and selenium, there's been a huge amount of work done on vitamin E and selenium over the years, and they've generally, not always, but generally showed positive results on immune status. And the example below will show perhaps why sometimes you get a response and sometimes you don't.
So Aashiga showed that vitamin E and selenium supplementation 21 days prior to calving, showed an improvement in pregnancy rate, but supplementation 14 days after showed no effect at all. So, there's going to be different, status, antioxidant status of cows pre and post calving. And depending on the status, you're gonna have potentially a beneficial effect or not an effect at all.
So it does depend quite a lot on the timing and the and the and the oxidative stress that that animal is under at the time to see whether you get a response or not. Very interesting paper published this year by Wellow with the er the hypothesis that oxidative stress. Is important in the calf dealing with extrauterine life, and it may contribute to high neonatal mortality.
And a few other studies have shown that, maternal, oxidative stress status may induce changes again in TNF and haptoglobin in the calf. So what's happening in the mother may have a, a, a potential negative effect on the calf. There was some trial work done back in 2006 or published back in 2006 from France, linking the maternal status of animals.
These were mainly beef animals, and they were looking at the maternal status of these animals two months prior to calving, roughly, and the status of the calf, and showing that the maternal selenium status had a very strong effect on neonatal mortality rates. So there is quite a lot of work linking oxidative stress in the neonatal period and to disease rates in calves, and looking at the effect of supplementation of the mother and getting the status of the mother correct to pass on that potentially protective effect to the calf. So there's some promising data.
Looking at maternal supplementation in the last month, prior to calving, with some rate limiting amino acids, methionine is one that is most often given, and also trace minerals, on the, the health of the calf. So again, protective effect, given to the mother that is passed on to the calf. So, if we want to touch on just the nutritional strategies for improving immunity, the most important thing, by a long way is getting cows in the correct.
Body conditions score at drying off in the car, so we're looking at getting animals in at around about 2.75 at drying off and keeping them there at calving and not overfeeding them, during the dry period where energy demands are relatively easily covered, . And an excess, especially if it's an excess in the form of a, of a lot of starch, can cause you problems with excessive fat mobilisation and that increase then in TNF.
Prevent hypocalcemia effectively, that goes without saying, and suitable environment to decrease stresses. So, you know, if we're going to increase stresses such as not having animals in the transition group for at least 21 days, moving them at critical moments, putting them into a, potentially a subordinate situation, so putting heifers in with dominant cows very close to calving. We're potentially then gonna have negative effects on these animals, reducing their dry matter intake, increasing their stress, and going through the whole idea of excessive fat mobilisation.
So, heat stress is an important one, too. Virtually every supplementation study, if you're looking for a, a, a suitable candidate to do, a suitable herd of cows to do a supplementation study for, proving that an antioxidant will work, you do it at a time of heat stress, because they always, almost always have an effect, when there is an effect of heat stress. And of course, ensuring adequate fat-soluble vitamins and trace minerals to improve the antioxidant status.
So supplementation in that time around calving, the lead up to carving. OK, so. We very rarely get the situation where we see clinical deficiency problems.
So this isn't something in practise you tend to see very much of, certainly not in dairy practise, we would see it very often at all. You might see it more so in beef practises where they're, much less supplemented potentially. But it isn't something that we see very, very commonly in in dairy practise.
And what you see from the plateau up here where we've got optimum trace mineral status down to here where we've got clinical deficiency signs, is a . A spread where at first when you start losing the trace mineral status, you're probably not going to see any tangible effect unless you look at the data quite closely and you look at compromised growth and you look potentially at compromised fertility as you then move further down, . Towards clinical trace minimal deficiencies, but still not seeing anything clinical, then you're more likely to see the poor growth and fertility problems.
And really, we don't know how much of the time we're going to be here or whether we're going to be down here, and it's largely going to change depending on what part of the production cycle you're in. There's an idea that trace minerals, there's a demand versus supply, of course, and demand for trace minerals is not static. And around the time of carving and the lead up to carving, there are higher demands for trace minerals and also for vitamins as well.
So carving, breeding. Increased risk of oxidative stress and resulting increased demand for trace minerals to combat this risk. So we'll just have a look now at how animals are normally supplied and so.
Normally there'll be a background level, of course, of trace minerals as well as macro minerals, and what we're trying to do is to see how much of those are there in the diet, so we know how much needs to be supplemented to get us to these optimum levels. So here's the Macro minerals, which we're not talking about this evening, but they'll be fed at at much higher levels than the trace elements. So we're talking milligrammes per kilogramme of dry matter intake for the trace elements, and we're talking percentages of dry matter up here.
So an awful lot less of the trace elements are required. There are 26 trace minerals that are required, but 20 of them are in the diet at levels that we don't need to worry about supplementing. And the ones that we will supplement, so if we're putting together a trace mineral package, we'll always, consider copper, cobalt, selenium iodine, zinc, and manganese.
So on, on every mineral sack that you'll see on a farm, you will see how much of those 6 trace elements are being added. And the amount of supplementation is, is very dependent on the forage base. How are they supplied?
Well, normally, it will be, if it's a total mixed ration herd, it will be a supplement that's in the total mixed ration. It can be included in the concentrate feed, in the parlour. Occasionally trace elements, can be supplemented to the water, which can be a reasonably effective way, and, injectable, and Patrick's gonna talk about the injectable side.
Historically in the UK at least we've Concentrated usually on vitamin E and selenium if we're going to do that, hasn't been the broader trace elements that Patrick is going to mention. But that would be typical levels, a typical modes rather of supplementation on most dairy farms. So either one, some, or potentially all of the following routes.
So looking at the different forages, we've got grass silage on the left, and we've got maize silage on the right. And really, we're really only interested in the trace element part, so the, the bits on the left hand side of the graph here, so, calcium 3 to, sulphur, those would be macro minerals, but the trace element side of these ones here. As we see with iron, the reason we say we don't need to, supplement with iron is, iron is normally way in excess of what we require.
So we don't put iron into mineral packages. Manganese, if you're repeating a lot of, of grass or grass silage, manganese, on paper at least, we'll talk about the absorption a bit later on. But on paper, you're sort of hitting NRC requirements for 35 litres.
. If you look there at copper, zinc, cobalt, iodine, and selenium, whether it is in grass silage or if it's in maize silage, there's still, a long way to go to be able to fulfil the dairy crowd requirements for 35 litres. So. The forages have an effect, but really, whether it, it doesn't matter whether it's grass silage or maize silage, the trace elements are all going to require supplementation.
The 6 trace elements that we talked about are going to require, supplementation. And with oral supplementation. Intake can vary dramatically.
So again, that issue of if you have a dominant cow, and you have heifers coming in there, the dominant cows potentially, can push the subordinate animals out of the way. And also there's quite a lot of work now showing that before animals are actually, showing signs of being ill, post calving, their dry matter intakes are often reduced for some weeks prior to calving, so potentially there's the. The idea of, of, the lack of supplementation just through a lack of dry matter intake for whatever reason, prior prior to carving.
And important point to make in ruminants in monastery, it's relatively easy that if you give trace elements to them, they will be absorbed. And the trouble with ruminants is the rumen, and there are complex mineral interactions which occur in the rumen, and there's a real web of antagonisms that go on. It's very difficult to calculate these antagonisms accurately, so.
People like Neville Stuttle have looked at, at trying to characterise this. So if you have, for instance, a, you know, a very high level of, let's say, sulphur, what does that do to availability, but they're quite difficult to, to model very accurately. The ones that are perhaps the main ones are, the relationship between zinc and calcium.
So there's a tie up that if you feed too much calcium, you get a tie up on the zinc availability, copper and manganese with sulphur and iron, that's a very well known one. Manganese, antagonises with, with copper and with phosphorus, and selenium is an antagonism with sulphur. So there's, there's several more antagonisms, but it just shows you there that the, the problems that you can have with predicting, even if you've gone to NRC requirements, and whether you're going to actually get uptake from the gastrointestinal tract actually into the bloodstream where you need it.
So achieving NRC recommendations is what you do. You must get NRC recommendations and you don't want to be over supplementing, you don't want to be under supplementing, you want to be, supplemented to the NRC recommendations. But it doesn't necessarily mean adequacy, and it doesn't necessarily mean adequacy certainly at times when the requirement is increased at the time of, of greater metabolic stress.
So if you look at absorb you'll see in quite in some mineral packs there will be a You'll see collated, which is organic. Minerals, so that would be a trace element that is, that has a a amino acid attached to it, and that can increase absorption, so it can increase absorption by 30 to 50%, but it still doesn't get around the problem of of tie up in the tissues, tie up issues, sorry, completely. So it may have some effect, but if you've got too much of another, trace element at a very high level, then potentially it is just not going to get around that, that problem with antagonism.
And recently, there's been more argument for using additional supplementation above NRC recommendations. The NRC recommendations are 18 years old now, and they're due to be updated soon, and they, there's a lot of leakage of information from the committee that is updating them. But there are researchers that are talking about increasing recommendations during times of greater oxidative stress, e.g.
The the times of the production cycle that we've already been talking about. Evolving. And one of the ideas would be that you provide background levels of minerals in the diet to NRC recommendations, which, as I say, we would always go to NRCD recommendations.
And then the the idea which Patrick's going to take you on to with injecting with trace elements that are there in the, in the enzymes to counter the reactive oxygen species, to try and bypass the rumen antagonism problems. So to summary, to summarise before I hand over to Patrick, accelerated cellular metabolism, so times like calving, neonatal life, breeding, vaccination, they will all increase the levels of reactive oxygen species and the stress, that those animals are under. Some reactive oxygen species are useful, but it's an imbalance of oxidative stress and antioxidants that can cause damage to cells and increase the incidence of, metabolic and infectious disease.
So this idea of oxidative stress, being at the centre of, of an increase in the, in the, so at the centre of the aetiology to cause that increase in severity. Of metabolic and infectious diseases. Excessive fat mobilisation, I hope you've got that, got through to you, is, is a bad thing.
It's going to increase cytokine excretion, and we're going to get huge inflammatory responses, and management strategies should be focused on decreasing, excessive fat mobilisation, as I briefly mentioned. Vitamins and trace mes can play an important role in antioxidant enzymes. They're crucial components of them.
Oral supplementation to NRC is certainly what what we'd recommend. It's the best approximation, but it may be inadequate at certain times, or increased an antioxidant requirements, especially when you've got reduced feed intakes from, for instance, bullying or a disease process, and certainly with remal antagonism. So Patrick, I take you on to the next point now with the injectable trace minerals at targeted times, which may be useful to improve the antioxidant stress of, antioxidant status, sorry, of animals.
So Patrick, I'm just gonna pass over to you and myself. Brilliant. Thanks a lot James.
It was a really, really interesting presentation and from the data there, you can see that while NRC recommendations of feeding are, are very important, the key issue is that all oral minerals, they're quite poorly absorbed, and they're all subject to that harsh ruminant antagonism. And at critical times in the breeding and production life cycle, there can be a fall in the dry matter intake. So, You can have a really well put together diet, but the problem is you have these increases in demand at periods when that intake will fall.
So cattle can often develop that subclinical deficiency, as James Graf highlighted, and leave them kind of vulnerable to the adverse effects of oxidative stress if they're in subclinical mineral deficiency, meaning they don't have the building blocks of those antioxidant enzymes, so. I work for Bourbon Technology with the parent company of the Multiman Group. So we've looked at how strategic supplementation with injectable trace minerals can overcome this idea of subclinical deficiency in cattle, subclinical mineral deficiency and oxygen.
A state of stress. And we've developed multimin, and multimin is a unique combination trace mineral injection. So, like James highlighted, when you strategically supplement cattle at at certain periods in the breeding production life cycle, you're raising the mineral levels, and you're raising the antioxidant levels and mitigating the effects of oxidative stress.
So Multimemin is a POMV in the UK, a prescription only POM in the Republic of Ireland and in France as well. . It's a new concept and a new product to Europe, but it is not a new product globally.
We've 24 peer reviewed published studies on this field of strategic supplementation, oxidative stress. The key to our studies have been that we've always had cattle that are fed to the NRC recommendations, and we've supplemented around those high demand periods. So cattle on well managed oral diets and using strategic supplements on these.
So, If we begin, multi-min is used in simple subcutaneous injection is really well tolerated by cattle. Very fast acting, so within 8 to 10 hours, we see raised plasma levels of the 4 trace minerals. Within 24 hours, we see raised liver concentrations of these trace minerals.
And within 15 days, we see statistically significant increases in those crucial antioxidant enzymes, superoxidate, bimutase, and glutathion peroxidase. So, again, we supplement ahead of these high demand periods like pre-calving, pre-breeding, weaning, we raise the antioxidant levels and we mitigate the cattle's per percentage chance of getting oxidative stress. So, as I mentioned, we've 24 peer-reviewed published studies.
This is one from 2013, from Cornell University. So we had 3 farms with around 1400 head of cattle, dairy cattle, and they're all managed on diets to the NRC recommendations and above. So all very, very well fed.
And what we did here was we supplemented by one group of cattle at drying off, again, pre-calving, and 35 days in milk. So 60 days pre-calving, 3530 days pre-calving, and 35 days post calving. So, coming up to drying off and in the during that dry period, it's very important for cattle to have adequate mineral levels for, for cellular metabolism and for, repair of the other.
And also you've got, growing foetus and at this period as well, you'll have a big fall in dry matter intake, around 35 to 40% drop in dry matter intake. So, Often cattle here, even on well-managed diets can fall into that subclinical deficiency. So in this study, even though the cattle are on that top or programme, when we supplemented strategically, we found a 22% decrease in mastitis, clinical mastitis in your multiparous cows.
We found a 23% decrease in subclinical mastitis in all the cattle. When you're supplementing your cows in calf, you're also, you're supplementing the cow, but you're also supplementing that calf in euro. So we found the knock-on effect of this, of course, was a 29.5%, nearly a 30% reduction in your stillbirths.
Endometritis, again, you, as James highlighted, your trace minerals are essential for good uterine health here, when we supplemented accordingly, we found a reduction in endometritis. So in this study also, Despite the cattle being on well-maintained diets, the control group here had somatic cells of around 289,000 cells, whereas our supplemented group, the cells were much lower at 218, so. Again, this is a US based system, so a lot of UK farms would have on average probably lower sales, but you can see here how strategic supplementing benefited these cows and importantly, mitigated the use of antibiotics in these cattle by lowering the clinical disease.
So, just something to note. In 2012, we supplemented a group of cattle pre-calving and pre-breeding in beef animals. And what we found was, compared to cattle on well-managed diets, when we supplemented on top of these diets, we found that we improved our pregnancy rate.
The control cattle in this group, in this study had an 89% pregnancy rate. And the supplemental group had a 93% pregnancy rate. But crucially, when we supplemented the cattle, we found the supplemental group had an improved calving distribution.
So had a statistically significant increase in cows going back in calf in that 1 to 20 day period. So again, when we supplemented the cow pre-calving, We're overcoming that dry matter intake fall, and we're overcoming the fact that she is mobilising a lot of her mineral reserves and putting minerals into the calf to improve its survivability. So a lot of times the cows can leave themselves subclinically mineral deficient.
And again, because it's subclinical deficiency, the farmer, the producer, the vet. Won't see any signs of this deficiency, but they may just see the knock-on effect in terms of cows not going back in calf or needing repeat services, whereas when we found in this study, when we supplemented, we were improving that chance of going back in calf in that crucial window that really determines profitability of our beef farms. And I know it's very late and we want to have time for questions at the end, so we'll just wrap this up very quickly.
But what we found also was when we supplemented vaccination, we found improvements in antibody tigers. In this study from 2012, we supplemented at the same time as we gave a IBR vaccine, or BVHP1. And what we found was cattle that were supplemented and vaccinated.
Had higher antibody titers. So we're talking about oxidative stress and the need for trace minerals here for antioxidant enzymes, but at vaccination, it's just the trace minerals themselves that are so important. So you're Antigen presenting cell requires selenium.
Your B cells and antibodies during replication will require a lot of selenium. Zinc is essential for transcription factors and protein metabolism in these rapidly dividing cells. And your copper, again, very important in the mitochondria of these rapidly dividing cells.
So the trace minerals are really, really important for your adaptive immunity. So when we supplement at the time of vaccination, we're seeing in this study, higher antibody titers, and in the 2016 study in the University of Georgia, what we found was supplemented and vaccinated cattle had An improvement in overall population serial conversion in that 53% of vaccinated cattle reached 4 times antibody titers, whereas when we vaccinated and supplemented, we had an 80% level of serial conversion. So 80% of the cattle effectively reached 4 times antibody titers.
So, What we've done in our study data is we've highlighted the key times for supplementation. So again from that study from 2013, a drying off in a pre-calving window, again pre-calving in 35 days in milk. And if we look at our heifer groups, so all of the, the issues James highlighted in during his presentation in terms of increased demand for minerals and the possibility of the submical issue developing and how, our intake can fall and our energy demands increase.
This is all true for your heifers as well as your cows, but crucially, your heifer group in a dairy herd ideally will be calving down at 2. 4 to 28 months. So they're all still going to be growing.
So there's a lot of research showing that there's a serious decrease in your superoxide dismutase levels, your your antiox enzymes in first lactation heifers after calving. So they're very vulnerable to the effects of oxidative stress. So when we supplement this group, pre-calving and again pre-breeding, we really see the benefit, .
In terms of calves, we've seen positive results in terms of supplementing calves at birth. There's a study from 2014 in Cornell University, where we supplemented dairy calves at birth, and we found a reduction in diarrhoea, pneumonia. And ultitis in these cabs.
What we also found was statistically significant increase in our glutathione peroxidase enzymes. So when we supplement ahead of these high demand periods, we're mitigating the effects of oxidative stress by raising those antioxidant enzymes. In our beef studies, as we mentioned, you're supplementing pre-calving and pre-breeding, and as we highlighted earlier, supplementing vaccination can yield very, very positive results.
So. Again, you, you identify those high demand periods, those critical points when your demand will increase and your dry matter intake may fall, and there's a risk of that oxidative stress when we supplement strategically, we're mitigating those, the, the free radical imbalance, the free radical damage that can be caused, and we're improving performance in the cattle as a whole, so. As I said earlier, multi-min is combination trace mineral injection, so it's copper, zinc, selenium, and manganese.
It's delivered by subcutaneous injection in that tissue in the neck. The max injection is 1, excuse me, 7 mils to one injection site, but those can be divided up for heavier cattle. You can see we have 3 distinct dose rates as younger animals will have increased demand.
Per body weight for trace minerals. So young cattle, it's 1 mL per 50 kg for cattle 1 to 2 years old, it's 1 mL per 75 kgs. And for adult cattle over 2 years old, it's 1 mL per 100 kg.
Crucially, there is zero milk withdrawal on this product, so It is licenced for newborn animals, for lactating animals, for pregnant animals, for in for beef or dairy, so it's an essential supplement for any part of bovine production. So zero milk withdrawal and only in 8 days meet an a withdrawal. So, to summarise, multi-million is designed for strategic supplementation in advance of these critical high demand periods in the breeding and production life cycle.
So ahead of breeding time, ahead of calving, weaning, vaccination. So by injecting the trace minerals, or bypassing that harsh ruin antagonism and those poor oral absorption rates, and acting very, very fast to raise the cattle, excuse me, raise the cattle's trace mineral levels, and by doing this, raising those crucial antioxidant enzymes. As an injectable, it's very fast acting, very convenient, and as well, it lends itself to very accurate dosing because it's so easily injectable as an aqueous solution.
So, Thank you all for listening and for James as well and we just like to open up for Q and A. Patrick, thank you very much. I'm glad to see that the storm didn't interfere with your voice much, but, it seemed to have caught James a little bit at the end.
So, folks, we apologise for that, little bit of interruption in the sound, but, it, the, the storms in the atmosphere are beyond our control, I'm afraid. Now, at the beginning, I did promise you guys some interesting news and some exciting news. And basically, what it boils down to is that Verbek, the sponsors of tonight, once again, thank you, Verbach, and thank you also because they have had or told me that they are going to have A prize draw for a two-day seminar pass to Total Dairy 2020, which is being held in Stratford upon Avon.
So not only is it a beautiful setting, you are also getting an amazing prize draw for the two-day seminar pass. So really, Verbach, thank you for your sponsorship and thank you for your kind generosity of that two-day pass. We do have a couple of questions coming in.
Patrick, the first one comes, for you. Rebecca wants to know, are you going to be bringing out a copper-free version of this, multimin for farms that have exceptionally high copper levels that have actually been tested as dangerously high levels? Unfortunately, we just have the current formulation available at the moment which does contain copper.
So, it might be something that would be interesting, interested in down the line, but for the moment we're just trying to launch the one product. That's, that's an important point to note that of course, you know, trace minerals, there is difficulty in supplementing in some areas, but in other areas where trace minerals can actually be quite high in the soil. So it's, it's just an area where vets.
Can get more engaged, with the idea of strategic supplementation and whether or not it is needed on the farm and they can prescribe judiciously. So as I said, as you can see from the slide, it is a POM product and a POMV in the UK so vets can prescribe it judiciously. Excellent, excellent.
Those are very important points. Chris has asked, he says, we have had a large increase in uterine prolapses this season in 2019 compared to 2018. We saw 20 prolapses between January and April of this year compared compared to only 5 over the same period last year.
Is there a chance that trace element deficiencies could be playing a role with this other than just calcium? And could body condition score be affecting this as well? I suppose James is in a better position to answer that.
Is he there? James, are you back with us? James, you need to unmute yourself.
You are still muted. There we go. Yeah, we can hear you now.
I was there. Bruce, would you mind just repeating that question, please? Yeah, so they've had an increase in uterine prolapses this season compared to last, and he wants to know if there's a possibility that trace element deficiencies other than calcium could be playing a role in this.
That's a difficult one to answer. I, I, my, my initial thought on that would be almost always, I will say the first thing to do when you're getting uterine prolapses is to make sure that you haven't got hypocalcemia problems. Because I think the lack of, of, of muscle tone is probably the most likely thing that will cause it.
I'm, to be honest, I'm not particularly aware of a trace element link that could do that. I'm not saying, it's impossible, but my focus would be, on, certainly on hypocalcemia. I'm not sure if there's anything Patrick, you've come across in.
In any research work on that, but my thought was, I, I certainly wouldn't promise anything on that. I would be going for the hypocalcemia first. Yeah, I, I would concur with that.
All right. Another question, that's come up related to the copper toxicity is, is there any benefit to doing blood tests before you start supplementing for minerals trace elements? Well, James might, correct me if I say anything incorrect here, but, bloods for copper, they can be some inaccuracies here.
They can be affected by infection or sorry, they can be affected by infection or by the, the status of the animals. So, liver biopsy has been a more accurate way of determining, . The baseline kind of mineral levels of the cattle.
Would you agree, James? Yes, I think, I think it's notoriously difficult to know a copper status from a copper blood sample and for the reasons that, that Patrick says, and also the trouble with copper is, you can get relatively normal levels of serum copper, even when you're at very high levels of oral supplementation. So, I, I'm always wary of, of.
Of giving too much copper, and I think one of the things that that we've done is we've dialled back the amount of oral copper that's going in the trace element packs that very often there was this link made between hypo remia causing problems with fertility. And on, so on many farms, it's absolutely nothing to do with that at all, so we've been dialling those right back. My approach, I think now would be more that we take the copper right the way back, make sure that there isn't gonna be a, a toxicity issue, so stick to the NRC recommendations, which is sort of, you know, not to go more than about 12 to 17 milligrammes per kilo of dry matter.
And then when you've got it to that sort of level, then when you do need to strategically, supplement, then, you know. They, that would be when you'd want to be giving potentially, multi men as, as Patrick was saying, but, you know, I would, I would want to dial the cop of that first and stick to NRC recommendations. But my understanding from what I've read of the multi men is that it isn't the same, you don't have the same toxicity risk as you have with long standing oral supplementation, which just gradually goes into the liver, and then causes a hemolytic crisis.
The. Patrick will know this better than me, but the, the copper that is given, via injection, is not actually in the bloodstream for that long and doesn't seem to cause too many issues. I'm not sure if there's any issues actually.
So, you've got two crucial points here. So as James said, the the plasma, the blood levels can be unreliable as well. If you look at the study from Swenson from 1998.
They took blood samples, serial blood samples and and a series of liver biopsies as well, they found it was in the steer card coming up the calving, while the plasma levels were maintained, the actual liver levels of the animals dropped very, very low because of the mobilisation of stored . Stored minerals into the calf, and then when the cow calve down, she lost all this mineral, obviously. So again, you can get a false negative and, or sorry, a false high and a false low, from the excuse me, your plasma level from For for copper can mask a false high and a false low.
Liver biopsy is more accurate there, and the key thing from a safety factor is again that that 2. 13 study here, these cattle were all fed to NRC level of recommendations. So if you are on a herd or you're managing a herd where the intake is appropriate and recommended levels, and multi-in is perfectly safe to do on our 24 peer reviewed published studies, we've had no adverse events with at all when cattle are fed to the recommended levels.
So like James said, if you stick to that NRC recommendation and you supplement strategically, it's perfectly safe. OK, that's excellent. We do have, more comments along this.
The, the one that's coming in from Robert has said, most minerals given orally or under feeding regulations and not over supplementation, is the responsibility of the farmer and the nutritionist. This product is under vet medicine regulation. How do you suggest that vets ensure that they do not go over maximum permitted levels for total diet or cause liver accumulation of multiple supplementations?
Well, this is the, the whole idea. It's a prescription only medicine, so it's under the vet's remit, and it is, it is for the use in, in terms of the bigger conversation on a whole herd treatment. So the vet, the farmer or herd manager, and the nutritionist all working together for the best outcome for the, for those cattle.
OK. I would also, sorry, I would also add the point actually that, you know, we, we think that mineral supplementation on farm is correct if there's a nutritionist doing it, but often it isn't correct. And if you look at the supplementation that's given, on farm, quite often it's a, it's sort of historic mineral speck that they're using.
That hasn't been changed when other feeds have been changing, and you know, if you look at the minerals that are fed on farm, which I think you should do if you're gonna, if you're gonna use multimillion, I think you need to be looking at the supplementation that's going on farm, in my view. And I think if you're gonna, if you're gonna do that, you'll find that very often they're not actually that accurate, and even when you've got a nutritionist to feed company there, they can often be out and they're certainly worth looking at. OK, excellent.
Andy has asked, or made the comment, that he's been told not to use multi men in beef cows that have been bolused with all trace. Any comments? That's correct.
So, if you read the label for most bolus, products, they will say not to be used with other mineral supplements, and likewise multimin on our SPC, the contraindication is not to be used with, additional mineral products, so. Obviously, you, you don't want different products interacting and oversupplying. So as I said, all of our studies have been done with cattle who are fed to NRC level of feeding, and then multi men given as the supplement outside of that.
So, yes, that would be correct, not for use with bonuses. Excellent, . Guys, I'm, I'm, I must apologise to everybody attending.
We have had some problems in the last 5 or 10 minutes, with all of our sound qualities, I believe. There's not a lot we can do about it at this stage, folks, I do apologise if your sound is, either echoing or if there seems to be a bit of a breakup. Patrick did tell us that beforehand he had quite a bad storm heading his way.
So I think we've done quite well to get past that. But I do apologise if your sound has been breaking up a little bit. Matthew wants to know, he says, related to James's presentation, farmers are keen on switching towards chelated trace mineral supplementations in feed, i.e.
The organic forms. How much improvement shall we expect from such trace mineral forms? If the basic absorption rate is about 5% for mineral forms, how much does it reach if it's in a chelation form?
Thank you. That's a, that's a very good question, and you will get very differing opinions on how much having a collated mineral will increase the the uptake. And I, I mean, our, our view is that we are, we, well, if you look at a lot of the literature, they'll show that if you use collated minerals, it usually does increase the the uptake.
But it's also significantly more expensive than using non-collated minerals. We've not been, as a company, an Evans group, we've not been particularly, wowed by any of the collated mineral claims, and we've tended not to use it at all, actually. So for us, we tend to stick with normal NRC recommendations.
And we haven't really had any incorporation of, collated minerals at all, because it doesn't really get around the problem of, antagonism. You've still potentially got antagonism. They're in the rumen, in the rumen, sorry.
So for us, we're not terribly convinced by it. I mean, there's, there's plenty of research literature that people throw at you showing it does increase the availability by 20, 30% perhaps, but for us we've not been particularly convinced by it, to be honest. Well, I suppose the thing that comes to my mind is that, is that 20% of the 5%, cause that's always an interesting variation on, on marketing.
Yes, yes, that's right. I mean, the thing to say is the. I in the presentation, there were the the, the percentage uptakes potentially in the ranges.
Of course that is taken into account with NRC so they're not, it's not NRC has taken into account that the uptake is, is, is relatively low for things like manganese. But within that range, there's obviously . There there's quite a lot of difference, so potentially then if you thought, well, the NRC is saying manganese uptake is, say, 3% and it's not 3%, it's 1%, then, you know, you've potentially got quite big background changes there in the uptake and.
Whether the extra absorption you get from chelated is significant enough to go for, at the moment I'd say that the jury's certainly out with us, we haven't adopted it. Excellent. Last question is aimed for Patrick, and Patrick, an anonymous person has said, how persistent is the supply of your product?
I am, that's a kind of a question we get asked a lot. Most people are kind of they get hung up on this whole concept of how long it lasts and the persistency, but this is very variable compared to the depending on the status of the animals. So, obviously a cow will have increased demand for trace minerals if she's pregnant compared to if she's not pregnant.
So, that's why we've always said, Supplement at these high demand periods and measure the performance of the cattle. Look at your, your KPIs in terms of supplemented cattle having, improved fertility or improved, cell counts during the transition period. So, it's, it's very, very difficult to quantify.
So we've always measured multi-m in terms of how well it has improved things, how well it has worked, rather than how long it has lasted. So, because it's, it's very variable, and multi-in isn't a depot injection, so it's not injected under the skin and slowly releasing. It's metabolised into the bodies, into the, into the.
Plasma into the liver, into the body tissues for structural components into your antioxidant enzymes. So it's very, very complex. So to, to boil it down to how long it lasts, it's, it's a very, very complex idea.
So in terms of residues, that's not a problem. In terms of withdrawal, zero meat and or excuse me, 8 days meat and zero milk, in terms of persistency, but, how long it lasts is, it's, we're not about that. We're about how well it works.
Performance Performance, strategy, not longevity. So target demand periods, supplement accordingly and measure the performance of the cattle through these periods, and you won't be disappointed. Excellent.
That brings us to the end of the questions tonight. We have run over a little bit, but very interesting topic and some very interesting questions coming at the end. So I'm sure nobody has minded running over.
. Again, apologies if your sound has been affected. There isn't much we can do about the storms, I'm afraid, folks. But, we, I think we've got, the, the message through.
And, another big thank you to Verbek, our sponsors. Linda, thank you for coming on tonight and thank you for your sponsorship. It really is great to have, the support of companies like Verbek bringing us such wonderful webinars and such important information.
So from my side, Patrick and James, thank you for your, your presentations tonight and your time to be with us. We really do appreciate it. Thanks everyone for coming online and listening to us.
Thank you very much, James, for a great presentation as well. Thank you, Patrick, and good night to everybody. Thanks for listening.
And to Dawn, my controller in the background, thank you for everything from myself, Bruce Stevenson. It's good night till the next time.

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