Uncontrolled Inflammation: How Nutritional Management Can Help

They are mathematical systems that predict nutrient supply and requirements to help nutritionists formulate rations. CNCPS and NASEM are two widely used examples.

CNCPS takes a mechanistic approach, simulating processes such as rumen fermentation. NASEM relies more on empirical relationships drawn from research data. Because their assumptions differ, their predictions can differ too.

Neither model is perfect. The best results come from understanding each model’s assumptions and checking outputs against what you see on the farm.

Sensor data on rumination and rumen health may improve intake predictions and flag health events earlier. AI and stochastic modeling could help account for variable animal responses.

Not always. The right intake target depends on forage quality, available resources and environmental conditions on each operation.

Welcome and Panel Overview (00:00)

Scott Sorrell: Good evening, everyone, and welcome to the Real Science Exchange, the podcast where leading scientists and industry professionals meet over a few drinks to discuss the latest ideas and trends in animal nutrition. We’ve got a special one here, folks. I’ve got a great cast, and I’m looking forward to this conversation. We’re going to be talking about uncontrolled inflammation and how nutritional management can help.

Joining me today is Dr. Eduardo Rico from the University of Pennsylvania. We don’t get many professors from the University of Pennsylvania. In fact, we’ve only had one, and this is your second time to the pub. So, welcome back.

Dr. Eduardo Rico: I’m here representing Pennsylvania.

Scott Sorrell: Eduardo, why don’t you start us off by introducing yourself?

Dr. Eduardo Rico’s Background (00:52)

Dr. Eduardo Rico: I’m a nutritionist, originally from Colombia. I came to the U.S. about 15 years ago for my master’s and PhD. I went to Michigan State, West Virginia, and Cornell for my postdoc. Then I became a professor in Maryland for about three years before moving to the vet school at UPenn, where I am now. So I’m a nutritionist on a little island in a medical-oriented field.

Scott Sorrell: A nutritionist in a sea of vets.

Dr. Eduardo Rico: Yes, exactly. That’s an interesting thing for me.

Dr. Mark Fox’s Background (01:23)

Scott Sorrell: To your left is Dr. Mark Fox from Thumb Veterinary Services. With Thumb Veterinary Services, we know where you’re from.

Dr. Mark Fox: Well, in Michigan, we always use our hands.

Scott Sorrell: Exactly. Mark, tell us about yourself.

Dr. Mark Fox: I’m a dairy practitioner. I graduated from Michigan State in 1984 and have been in dairy practice in the Thumb of Michigan, and now the greater part of Michigan, for 42 years. I’ve always had an interest in nutrition and did a lot of nutritional programming over the years. For the last five or six years, I don’t do day-to-day balancing anymore, but I consult and team with a lot of advisers on the nutrition side. My mantra is prevention, not treatment. I’ve been a veterinarian surrounded by nutritionists for most of my career, and I’ve enjoyed that ride.

Scott Sorrell: Excellent, Mark. Looking forward to the conversation today.

Dr. Kelly Mitchell’s Background (02:21)

Scott Sorrell: Dr. Kelly Mitchell was a moderator for a session today here at the Tri-State Dairy Nutrition Conference. Kelly, tell us a little bit about yourself.

Dr. Kelly Mitchell: Thanks for having me back.

Scott Sorrell: I’m glad to have you. You did a great job last time.

Dr. Kelly Mitchell: We’ll see if I can keep it going. I’m originally from Tulare, California. I did my undergrad at Davis and my master’s with Dr. Heidi Rossow at Davis. Then I moved to The Ohio State University for my PhD with Dr. Jeff Firkins, and I lived in Ohio for about seven years. When I finished my PhD in 2022, I started with Elanco while still in Ohio. As I was telling the guys before the podcast started, California is a black hole. There are a lot of cows, and it dragged me back. I’ve recently relocated to the Visalia area.

Scott Sorrell: We were talking off stage a moment ago. Where are the better cows, California or Michigan?

Dr. Kelly Mitchell: I was going to throw it down and make it a WWE show.

Dr. Eduardo Rico: Pennsylvania.

Dr. Kelly Mitchell: Great cows in both places. We’ll just leave it at that.

Scott Sorrell: Dr. Rico, the title of your talk was “Uncontrolled Inflammation? How Nutritional Management Can Help.” Is there such a thing as controlled inflammation?

Defining Controlled vs. Uncontrolled Inflammation (04:50)

Dr. Eduardo Rico: By definition, yes. The opposite of uncontrolled would be controlled, meaning the immune system can do what it has to do. The immune system is responsible for inflammation, but it’s a natural, protective response that should occur. That’s the first thing to define. It’s something we need to happen, but we need to make sure it’s contained in terms of extent and duration. That’s why we draw a parallel with fires. It should be a controlled fire, not a wildfire out of control. As long as you can do that, the response will lead toward good health.

Biological Mechanisms and Resolution of Inflammation (05:24)

Scott Sorrell: Would it be worthwhile defining inflammation for this talk, and why it can be good as well as bad?

Dr. Eduardo Rico: Inflammation is a response of the immune system. It’s protection from an insult, which could be an injury or a pathogen, whether viral or microbial. It’s a defense mechanism. When you get the inflammatory response, you get things like cytokines, which are proteins produced by the immune cells that are reacting.

One way to see it is as an army responding to a situation. They respond first, start the inflammatory response, recruit allies and mount that response. Then, just as important as starting it is finishing it. Another group of immune cells does the job of saying, “OK, that was enough. We did what we needed to do. Let’s go back home.” That’s the resolution of inflammation, which we discussed today. Both aspects are important, and when they aren’t controlled sufficiently, either to start or to stop, we run into issues. That’s the premise.

Briefly, inflammation is also a natural response in processes that are critically important for cows. At calving, for example, you need inflammation to occur. A little spike in inflammatory markers is usually associated with the cow being able to deliver the calf. You don’t want a huge, uncontrolled, overextended response, but you need it for calving, uterine involution, mammary involution and many other important things. It cannot be turned off.

Scott Sorrell: Thank you for that, because we typically think of inflammation as just a bad thing. In fact, it’s part of the defense mechanism, and we need it, but it needs to be controlled, as you’re saying.

Role of Nutrition in Immune Support (07:27)

Scott Sorrell: The other part of your talk was how nutritional management can help. Can you give us some ideas of what you talked about?

Dr. Eduardo Rico: I started with a question, and I’m glad you’re here, Dr. Fox, because I asked: is inflammation a concern only for veterinarians, or does nutrition have something to say about this? On the veterinary side, we usually think, “There’s inflammation, so we’re going to tone it down with anti-inflammatory substances,” such as non-steroidal anti-inflammatory drugs, or NSAIDs. That seems to work to some extent, and in the transition cow it could be a reasonable alternative, though there may be drawbacks.

My question is more fundamental. What can the animal do to defend itself when there’s a situation to respond to, and are we arming that animal sufficiently to respond? That means giving the immune system the nutrients it needs to mount the best response it can. We argue that in some cases there’s evidence we’re not providing everything they need, especially in the modern dairy cow, which is challenged to produce at ever-increasing levels. There could even be opportunities to increase milk production, because you’re doing something in the background that improves the cow’s ability to manage those nutrients more efficiently, stay healthy and produce even more.

Scott Sorrell: So it sounds like that’s prevention.

Dr. Eduardo Rico: Yes, exactly.

Scott Sorrell: Dr. Fox, you said you really focus on prevention, which makes a whole lot of sense.

Clinical Pathology and Long-Term Consequences (09:07)

Dr. Mark Fox: Dr. Rico did a great job talking about inflammation in his presentation. Dr. Bradford and Dr. Contreras at Michigan State, and a whole circle of great scientists, are working in this area now. The emphasis initially has been the transition cow: what happens pre-fresh, right up to calving and post-fresh, and how that influences periparturient disease.

When I was a young vet walking onto farms with respiratory outbreaks, there was often inflammation, both the good and the bad. When animals are presented with pathogens, whether viral, bacterial or protozoan, they mount an immune response. But sometimes, even after treatment, you get chronic issues, and some of those last the lifetime of the animal.

Take chronic respiratory disease. The animal resolved the inflammation on its own, maybe with help from antimicrobials. It fought the good fight, but it was left with what I’d call the cleanup parts of inflammation. With respiratory disease, that could be adhesions and microabscesses in the chest. We also think of the liver abscesses that are common in the cattle industry. The infection has been cured, at least in that spot, but there are long-lasting effects on our cattle. I see animals that had disease in their first week or two of life show up in the transition calf barn three or four months later with recurring pneumonia.

Then there’s the mammary gland. We do bulk tank testing for somatic cell count, which is mostly neutrophils, and chronic mastitis is a problem for the dairy industry. We talk about 200,000 as the cut point for the chances of being infected or not. Whether it’s mammary gland inflammation, respiratory inflammation or lameness, the list is fairly long, and the economic consequences of chronic inflammation are dire in our industry.

Scott Sorrell: With some of these chronic inflammations, can we ever really cure them? The lung adhesions you were talking about, for example?

Dr. Mark Fox: No. One of the gratifying parts of being a field veterinarian is that I get to open up a lot of animals with the caregivers circled around me. Those are great teachable moments, myself included. We’ll open up the chest of a three- or four-month-old calf, or do a post-mortem on a cow. You can see they diagnosed the disease and gave appropriate treatment, but the inflammation had gone too far. There was no way a calf that had lost two-thirds or three-quarters of its respiratory system could ever survive.

The Wisconsin researchers talk about this even with digital dermatitis, or hairy warts, in dairy cattle. We can control that inflammation and infection when the onset is early and the treatment is early. But given a head start, disease tends to become chronic, and for chronic diseases, the treatment options are very limited.

Scott Sorrell: Hence prevention.

Dr. Mark Fox: Hence prevention.

Key Nutrients: Fatty Acids, Niacin and Vitamin D3 (13:05)

Scott Sorrell: Kelly, anything?

Dr. Kelly Mitchell: Eduardo, on that pathway, there’s a moment that’s like a decision point for the immune system: am I going to be in this chronic state, or am I going to resolve? What are some of the metabolites or markers that define where the immune system goes?

Dr. Eduardo Rico: The way I approach this is to ask which nutrients the immune system can use to come back from the immune response it just mounted. One example is the omega fatty acids. To activate the immune response and to resolve it, you need omega-6 fats and omega-3 fats. They’re not just one random nutrient for the immune response. They’re directly responsible for initiating and terminating it. That’s called lipid class switching. You go from the omega-6 pathway and the compounds produced downstream of it to activate the immune response and start the little fire. Then, on the back end, you need the omega-3s to come in and put out the fire. Unresolved inflammation goes in the direction where the immune cells don’t have enough of the tools they need to reduce and finalize that response, and then you run into issues.

I also mentioned niacin, or nicotinic acid. It’s important in many places in metabolism, but it’s central to the defense against reactive oxygen species, the famous ROS, which are constantly wreaking some havoc. Molecules like NAD need to be present in sufficient amounts for the cells’ antioxidant systems to respond. If you don’t have enough niacin, in theory, you’re limiting that system, because NAD, which comes from niacin, is present everywhere you look in the antioxidant system. That matters because if you have too much oxidative stress, you’ll have more inflammation. They feed off each other.

Then there are the classical nutrients. We talk about minerals, which is very intuitive with antioxidant systems: zinc, copper, selenium and manganese. We know the antioxidant system requires those to work properly. What we’re trying to do is expand that list beyond trace minerals to include vitamins. That brings us to vitamin B3, the niacin and NAD system I just discussed, the omega-3s, and vitamin D3.

Vitamin D3 isn’t directly my research, but I’m related to it because my twin brother works on it. During COVID, one of the best predictors of how severe the consequences of infection would be was vitamin D3 status. People with high enough levels of vitamin D3 responded better and didn’t develop such a severe reaction to the virus. In the dairy cow world, Dr. Sordillo from Michigan State, whom I cited during the talk, showed that you could use prepartum vitamin D3 status to predict the incidence of many periparturient disorders postpartum. It’s not that we don’t discuss vitamin D3, but maybe not in this context, as a critically important way to potentially prevent disease. It goes back to furnishing every nutrient the cow could need to mount a better response, whether to initiate it or to terminate it.

Scott Sorrell: So those are three examples: vitamin D3, vitamin B3 and omega-3s. Everything with three, the triad of threes.

Dr. Eduardo Rico: That’s what we’re thinking about, but there could be more, and I don’t want to neglect other nutrients. For nutrients we give cows every day, there could be an opportunity to understand how much we need to give beyond what we consider requirements for production. That’s usually how nutritionists think about requirements: how much is needed in normal, good conditions to get maximum productivity. That doesn’t mean we’re doing something for prevention, which is feeding the army, the immune cells, well enough to mount a very competent response. That brings us to the concept of immunocompetence, because a huge immune response doesn’t necessarily mean something good. It could actually be very inefficient.

High Production and Supplementation Levels (18:10)

Dr. Kelly Mitchell: You brought up production, and we talked about this a little yesterday. Are higher-producing animals going to be more inflamed, or more chronically inflamed?

Dr. Eduardo Rico: I like to use the analogy many people use of the high-performance athlete, the Usain Bolt type of character. They perform at a very high level, granted that you provide everything the body needs to perform at that elite level. The cow is the elite performer in this analogy. It doesn’t mean the animal has to get sick, or have oxidative stress that runs amok, or inflammation derived from it, as long as you provide every building block needed for the protective part of the response. As long as Usain Bolt is eating well, exercising properly and not overdoing it, he shouldn’t get sick from being a super performer.

The same goes for cows. Some of the things we’re beginning to understand may be more important than we usually give them credit for. If cows are getting them, maybe we don’t need to worry as much about the cow being unable to defend herself, because she’s better armed. There may be more nutrients than the ones I’m mentioning, but it’s a good starting point to ask ourselves: are we giving enough, beyond productivity, for protection? Are we giving enough vitamin D3, omega-3s and niacin?

Scott Sorrell: Just to check my listening: even though we’ve been supplementing these for years and they’re part of the NASEM recommendations, your hypothesis is that we’re probably under-supplementing today?

Dr. Eduardo Rico: Potentially.

Scott Sorrell: Do you have evidence for that? What makes you think so?

Dr. Eduardo Rico: Some studies presented today show what happens when you go above the NASEM recommendations. I’ll concede that some nutritionists already give more. With vitamin D3, for example, you probably give a bit more than one times the requirement. But when it’s been tested at three or four times the recommendation, the immune response seems to improve. Rectal temperatures during an immune challenge are less dramatic, with less fever, but a response still happens. Inflammatory markers are also toned down. They still increase, as you’d expect during heat stress or an inflammatory challenge, but they don’t run out of control. That supports the idea that if you give these nutrients, the immune response will probably be more efficient.

So it follows that maybe we’re underfeeding in some situations. The situations I’m describing are situations of stress, not the normal, healthy situation where everything is good. Say summer comes and the cow is suffering from environmental stress. In that situation, does it make sense to boost some of these nutrients? That’s the question we’re trying to pose.

Timing and Accumulation of Nutrients (21:03)

Dr. Eduardo Rico: It doesn’t mean we’re not good at knowing requirements for normal production. It’s just that in situations of challenge, we may have room to improve a little.

Scott Sorrell: In the interest of prevention, when do we start, say, before heat stress? I assume you don’t mean using it as a treatment once cows are in heat stress. How far ahead of time would you start?

Dr. Eduardo Rico: That’s a difficult question, because the research doesn’t tell us the exact timing. But you can assume that before heat stress arrives, you need a buildup of these nutrients in circulation. B-complex vitamins are quickly metabolized. They have very short lives and don’t really accumulate, so starting supplementation some weeks before the weather turns may be a good approach. Fat-soluble vitamins like vitamin D3 accumulate over a long time, so the timeline could be different, because you need to build up sufficient stores. Depending on the nutrient, the timing may differ. Omega-3s are another example. For omega-3s, we don’t even have a requirement. We call them essential fatty acids, but when you look in the books for how much, we don’t know.

Scott Sorrell: And how much compared to omega-6? You said one starts the fire and the other puts it out. I assume there needs to be a balance somewhere.

Dr. Eduardo Rico: In the monogastric world, people talk about ratios of omega-6 to omega-3, like five to one or ten to one. When I did a lot of work on dog and horse nutrition, those ratios were much easier to control. You’d see improved sperm quality with omega-3s, tamed inflammatory responses and fewer arthritis-related problems in high-performance horses. But in cows, you have the rumen, which begs the question of what’s happening in there. How much of these fats gets destroyed? How much is the cow actually getting? It’s difficult to tell, so you can’t set a requirement when you don’t know how much is being received.

Rumen Metabolism and Omega-3 Inefficiencies (23:22)

Scott Sorrell: And they’re not all the same. I assume linolenic acid is not as potent as DHA or EPA.

Dr. Eduardo Rico: There are many inefficiencies built into the process. Say a cow gets a lot of linolenic acid, an 18-carbon omega-3, from the diet. You can even get it from grasses. That’s great. But it goes into the rumen, where biohydrogenation happens, and 80 to 100% of it gets destroyed, depending on how you count. The estimate is that with diets rich in omega-3s, you might get 12 grams of alpha-linolenic acid to the cow’s intestine. Is that enough? We don’t know.

Then there’s a second bottleneck. Even if she absorbs those 12 grams per day, the efficiency of converting that parent omega-3 into DHA and EPA, the big bioactive ones we care about for immunity, is extremely low across mammals. It doesn’t matter if you’re a human or a cow. With that second bottleneck, it takes longer to accumulate. So the shortcut is to provide it through dietary supplementation, which of course raises the question of how much, and how to evaluate the cost-benefit. That’s another hurdle, because it’s difficult to answer.

Dr. Kelly Mitchell: Outside of nutrition, since we’re still learning about requirements and timing, what should we be looking at on the management side? Take vaccinations. We want an immune response, and we’re vaccinating for the animal’s health, but what else can we do to make sure we’re not adding to that chronic potential breaking point in the pathway? I’d like to hear from you on some of those things.

Vaccination Protocols During Stress (25:14)

Dr. Mark Fox: That’s a great question, and there’s a lot of good thinking about it on dairies. Let’s start with the neonate. In the wet calf phase, calf ranches and calf growers often want to incorporate, or are advised to incorporate, a number of vaccination programs. And as we’ve been saying, the immune response takes energy.

I’m from the upper Midwest, and over the decades in Michigan we’ve had some cold, nasty winters for baby calves, like this past winter. Their energy requirements go up just for maintenance, before growth. If a calf isn’t growing, whether she’s a month old or three months old, a needle might pose an adverse inflammatory response. She certainly won’t respond positively to that immunization, and there’s a good chance it could actually be negative. A wet calf might have 2 megacalories of energy, and if she’s in cold weather and we get out the needles and vaccines when she’s not gaining, it could take 50% more energy just to run a proper inflammatory response to that immunization.

A lot of folks in the past, and we’ve all been guilty of it, immunize animals during periods of stress. We’ve known that’s a big no-no in bovine respiratory disease for decades. Yet we immunize in the face of outbreaks and adverse conditions, including nutritional shortages. As the industry progresses, we need to set those animals up, whether it’s a 4-month-old calf or a dry cow getting ready for dry-off, with proper nutrition and an immunization program while she’s still in a healthy phase and can mount a good immune response.

The new technology has taught us a lot. Now that we have cowside sensors, I’ve had to back off some of the immunization schedules I proposed or followed until just a few years ago. When you follow those sensors on cows after even a simple one- or two-antigen immunization at dry-off, or worse yet, when they move from far-off to pre-fresh, you see it. We immunize that cow going into pre-fresh three weeks before calving, and this whole conference over the last two days has centered on transition disease. So what are we doing? We call that iatrogenic, meaning I did it. We provided a needle and a stimulus for an adverse inflammatory reaction. If that cow feels dumpy and mopey and feverish, like our kids did after immunizations, that’s a proper immune response to immunization. But if it comes at a bad time in her life, negative outcomes will happen.

Then you overlap that with intake changes, pen moves and all the other stressors in our dairy animals from the day they’re born until the day they leave the farm. I wish we had a way to measure these stress events as they relate to innate and acquired immune response, and we will get there. We know from clinical observation that it’s big.

Cowside Technology and Monitoring (29:01)

Scott Sorrell: When you say cowside sensors, would that be something like rumination collars, as one of the indicators you could follow?

Dr. Mark Fox: Yes. smaXtec is a bolus now, one of several on the market, and it measures body temperature and rumination activity. It gives us comments right from the cow, like the ones you or I would make after our COVID shot. My wife’s first one didn’t bother her a bit, and it hit me hard. On the booster, we reversed. We could vocalize that to each other. Now we have a mechanism through cowside sensors to let cows talk to us. I’ve always said as a veterinarian that I wish my animals could talk to me, and as the decades have gone forward, now they can.

We have to be astute at watching not only the sensors but also stocking density, bunk space and having the feed there. It’s nice to fortify the diet with what we feel will support a proper immune response, but cows still have to get it, and in a meaningful way.

Dr. Eduardo Rico: The basics need to be secured, right? Social stress, feeding management, all the things that should be in place before we even think about the top tier of supplementing with extra fancy stuff.

Dr. Mark Fox: Yes.

Transition Cow Management and Minimizing Interference (30:31)

Dr. Kelly Mitchell: Dr. Fox, in your experience, where are those time points? I did transition research for my master’s, and one thing I walked away with is that there are times when it’s really good to just leave cows alone if they’re doing well.

Dr. Mark Fox: Absolutely.

Dr. Kelly Mitchell: So where are those moments where there’s inflammation, and unless there’s a reason, you leave them alone to get them through it?

Dr. Mark Fox: For the adult lactating and dry cow, it’s from pre-fresh, in the bigger herds that have a pre-fresh pen, to post-fresh. It’s kind of the classic three and three: three weeks prior, three weeks post. To be honest, I don’t want to mess with my cows much then. I want to provide them with the right immunity support through nutrition, but I’m focused on cows lying down, chewing their cud, getting up to the feed bunk, driving big intakes, and on staying out of their lives.

Twenty years ago in the veterinary field, the notion was to run fresh cows through a very labor-intensive screening process, collecting urine or blood, taking temperatures and so on, to get a head start. That’s all going the other way, and I’m glad it has. When the cow is rolling along, her biggest, most profound medicine in her toolbox is a rumen full of feed. She could have a 1.2 on BHBA. She could have a little smelly discharge from metritis. But if she’s got a belly full of feed, for me, that’s the trump card.

Dr. Eduardo Rico: We discussed this a little in the talk. If cows are ruminating well prepartum, you can be more assured they’re less likely to have issues postpartum. But if you detect changes prepartum in their ability to ruminate, chew their cud, as you said, and just lie down and chill, something is already going on that could be a risk factor postpartum.

Scott Sorrell: We talked about that in an earlier podcast today, about making sure there’s plenty of space for the cow to lie down and plenty of bunk space. It seems easy.

History of Overfeeding and Fat Cow Syndrome (32:48)

Scott Sorrell: But it doesn’t always happen.

Dr. Mark Fox: In my opinion, having been in the industry my whole life, we still struggle with it. I was taught by Dr. Dave Morrow, who published Bovine Theriogenology. I had him as an instructor, and he described what was called fat cow syndrome in the ’70s, a term we used through the ’70s, ’80s and ’90s. In the upper Midwest at that time, we had much smaller herds, and we didn’t do dry cow nutrition right at all. The classic Michigan dry cow diet might have been almost ad libitum corn silage plus all the rough grass hay they could eat from a round bale feeder. You’d come back to the same farm a week later, the round bale had hardly been touched, and the corn silage was always cleaned up. We were obviously way overfeeding cows during the dry period.

Fast forward through the 14 years we had BST in the States, from January 1994 until 2008. That helped some producers in a few ways. In layman’s terms, bovine somatotropin made the fresh cow think she was fresher longer, that her calf was younger longer. Because of that, there was a milk response, but it also prevented excess weight gain in the second half of lactation.

When we got away from that, we went back to fat cows. Even on big dairies, and I know California does a better job of this, in the upper Midwest we still feed a lot of one-group TMRs: highly fermentable diets made for a nice bunch of milk. They’re great diets and they make a lot of milk. But there’s a subset of cows, typically mature cows more than first-lactation cows, that don’t need to be overfed when they hit mid-lactation. What if we overfeed energy by 25%? That would make almost anybody’s hair stand up at this nutrition conference, but that’s what we do. These cows gain excessive weight, and I have a lot of cows at dry-off scoring 3.75 and 4. Mammalian physiologists over the last decade have converged on the fact that obesity is not a friend of mammals. Whether it’s a mouse, a man or a cow, obesity leads to chronic inflammatory change.

Dr. Eduardo Rico: Yes, the human literature is ripe with that.

Dr. Mark Fox: If you look at the ailments in our world today, our population takes a lot of anti-inflammatory medicine every day to try to break the cycle of chronic inflammatory disease. Part of that comes back to the basic metabolism of heavy animals.

Obesity and Chronic Low-Grade Inflammation (36:08)

Dr. Eduardo Rico: We have a name for that: low-grade inflammation, sustained over a long period because of the fat mass that’s causing it. That’s an issue for everyone, from humans to dogs to cows. The fat cows are the high-risk group for inflammation going wrong, for uncontrolled inflammation.

Dr. Mark Fox: And the intakes you showed on your graph, along with others since Dr. Huzzey’s work 20 years ago, show that heavier cows eat less all through the dry period, and in the last three weeks they eat much less. We strategize on farms with pen averages, and I think we get a bit cocky about that. We don’t know individual cow intakes. We could have a pen of pre-fresh mature cows with a dry matter intake of 32 or 33 pounds, and we feel pretty good about that. But within that, there’s a bell-shaped curve, and in my experience the heavier cows are way down on that curve.

Dr. Eduardo Rico: And that early reduction in appetite comes with inflammation already happening in those cows, which you’d expect in an overweight animal.

Dr. Mark Fox: Exactly. And all of a sudden they’re getting 30% less of all the goodies we put in the diet. It’s a double whammy.

Dr. Eduardo Rico: And they don’t recover afterward, because their intakes start going down before calving. At calving, intake drops for all cows, since they don’t eat that day. But for those cows, appetite recovery afterward is much slower. It’s a double impact, before and after.

Dr. Mark Fox: It’s that high-fertility cycle that was mentioned, which Michigan State says came out of their work and Dr. Fricke says came out of Wisconsin. Paul, if you’re listening, I apologize, but Richard Pursley says they did it on our side of the pond. On the reproduction side, it’s all about getting cows bred, and we’ve known that for a long time. But I challenge the high-fertility cycle to back up the wheel a little. It has to start in late lactation. You can’t even wait until parturition.

Practical Challenges in Pen Grouping (38:21)

Scott Sorrell: So how do you do that with a one-group TMR?

Dr. Mark Fox: It’s pretty tough. And I don’t think that’s just a trend in Michigan. I think it’s a trend across the country.

What’s driving it? I ask my excellent producers. They’ve taught me a lot, whether they have 100 cows, 5,000 or 15,000. Over a decade ago, Dr. Mike Allen proposed a maintenance diet at this conference, not for all cows but for a subset that reaches mid-lactation. Sensors and AI technology may really help us there, because body condition scoring is so subjective. I have a lot of nutritionist friends and veterinary friends, and if I tell the nutritionist I’m teaming with on a farm, “The cows are getting kind of heavy,” it’s like telling my wife she’s a little heavy, or her telling me the same thing. It’s subjective.

But Mike’s point, and the point of others doing this well, is to take first-lactation animals, whose lactation is much more persistent, and keep them by themselves anyway. I think their negative inflammatory response is going to be lower if they’re in a heifer group. They’re more submissive at the bunk and don’t need all that competition, so they might be able to stay on the high diet the whole lactation. If so, so be it. But the mature animals, second through sixth lactation, need to be throttled back a bit if they show positive weight gain in mid- or late lactation. Take out a little of that starch and come in with more fermentable fiber. Mike Allen has a whole approach for that subset.

The point is that once cows go dry, you can’t change much. We go on a dry cow diet and wheel them back to 16 or 18 megacalories of energy, but by that point, the body fat and all that internal fat is there to be mobilized. We have to be more preventive.

To come back to your question, my good operators tell me the reason they don’t do it is chains and gates. It’s a management thing, and it’s hard. You might have a 10-pen dairy and decide to try two pens of a maintenance diet for mature cows. They tell me, and I can’t argue because they’re there every day, “Mark, I could have that pen populated perfectly, and you come back two weeks from now and it won’t be populated perfectly.” Stuff happens. Gates get mixed up, half a line of the parlor gets dumped, and it’s a huge frustration. In a perfect world with AI technology and cowside sensors, a lot of this would be easier, but we have the humans to deal with on farms. Sometimes we’re helpful, sometimes we aren’t, and sometimes we’re the opposite.

Dr. Eduardo Rico: That makes me think the nutrients I discussed today are fine-tuning at a level we can’t always expect to achieve if the basics aren’t perfect yet, and they’re not easy to manage, as your examples show. If those aren’t corrected and optimized first, I don’t know how much stock you can put in fine-tuning other aspects of the diet. The bulk of the issues could be managed with simpler approaches. Maybe not so simple, like the gates you described.

Execution of Consistent On-Farm Management (42:19)

Dr. Mark Fox: In the end, it’s all people. We’ve all worked with great producers and caregivers, and they all have to be trained and motivated, and most of them want to be. It means taking our responsibility one step beyond our laptops: going out, having a look and having a heart-to-heart talk about how we, as a farm team, can do things differently to advance health and productivity.

Transition disease has been such a big part of my veterinary career. I’m an old guy, and we’ve learned a crazy amount about the biology of transition disease in the last 20 years. But if you look at NAHMS data and health data on a lot of dairies, we haven’t done so well.

Dr. Eduardo Rico: It hasn’t changed.

Dr. Mark Fox: Not after all that awesome research on transition cow biology, because so often it comes back to the things that are really hard to do: excellent husbandry and management, every day. The panel Corey Geiger led yesterday had three producers, and I really appreciated their comments. Fat and protein are a big part of their milk check. But every one of those dairy people said it wasn’t the last two grams of palm fat or going from 5½ to 6 pounds of high beans. They said things like, “We’ve got to have the best forage in the world. We have to be able to feed higher-forage diets. Maybe we can lean off starch a tick if it helps our inflammatory challenges.” They all talked about forage quality and doing the basics really, really well.

Dr. Kelly Mitchell: And consistently.

Dr. Mark Fox: And consistently, starting in the dry period. All three hammered that home, and I thought it was awesome.

Scott Sorrell: We had them on a panel as well, and they were very insightful. This has been a great discussion. I almost hate to shut it down, but we’ve got a few more minutes.

Botanicals and Polyphenols in Dairy Nutrition (44:38)

Scott Sorrell: Eduardo, anything we haven’t covered yet?

Dr. Eduardo Rico: I wanted to raise this because Kelly is here and Elanco is working on this type of product. One thing I mentioned today that we could use to control inflammation and oxidative stress was botanicals: things from plants that we don’t consider nutrients.

Dr. Kelly Mitchell: Nutraceuticals.

Dr. Eduardo Rico: Yes, nutraceuticals: secondary compounds plants make to protect themselves from the environment. That brings us to polyphenols, which include flavonoids and non-flavonoids. They appear to be beneficial, there’s mechanistic evidence for that, and there are a couple of studies using a Chinese root extract that suggest potential for improving milk production even in cows that appear healthy. I found that interesting. The producers talked about this yesterday: the invisible production that’s there even when you don’t see anything wrong, but that you’re missing out on. Botanicals may be a good way to drill into the idea that there’s invisible productivity we’re missing. So my question is, how do you see the use of these types of products?

Dr. Kelly Mitchell: There’s a lot of interest from producers. The product Eduardo is referring to is called Dairy Relieve. Dr. Bradford has done research on it, and a lot of that research is publicly available. It looks at helping animals through this time period. What producers have really locked into is that it’s not black and white. Is inflammation actually the problem in their transition period? That’s what they’re looking into.

I have some great colleagues in this area, Dr. Sarah Cavidra and Dr. Erin Horst, and I’m learning about inflammation by osmosis, because it’s not my background. Dr. Horst has done a lot of good on-farm work on markers producers could use to determine how the transition period is going from an inflammation perspective. She’s used A:G ratio work to show producers what it means for production if their cows fall in different quartiles. It’s been quite dramatic, even on commercial farms. Those ratios predict an animal’s ability to produce in the coming lactation, so producers are very interested.

We’ve gotten so detailed in how we manage animals that we’re getting to individual-cow work, like Dr. Fox talked about, and I find that incredibly interesting. Some animals handle this process well, and some struggle. Supporting that struggling group, which brings your average down, makes a huge difference to overall production on the farm.

I’m a big fan, and I think a lot of us here are, of asking what management we can do first. Do we need fresh cow vaccines? What are we really doing on farm, and are we taking action for true reasons? Then, if it becomes a useful tool in your toolbox, can we use nutrition strategies, polyphenols and other things to influence these pathways in a positive way? It’s a really fun area of research. It’s not black and white, and I enjoy living in the gray and working through it with producers. Dr. Fox, I don’t know if you have those conversations often, but producers really care about transition health, and this inflammation research from Elanco and researchers like Dr. Rico really resonates with them.

Dr. Mark Fox: Oh, big time. Good dairy people don’t like sickness. I learned that a long time ago. Whether it’s the calf caregiver at the calf ranch who’s needling and IV-ing, or the broken transition cows, or the dead cows hauled out in the first couple of weeks, farmers don’t like it. It’s emotional, and it hurts them to their core. So whatever we can do to enhance a proper immune response matters.

The Pre-Adjuvant Concept and Animal Welfare (48:58)

Dr. Mark Fox: I was thinking about immunization strategies again. Take a yearling on the dairy, between 8 or 9 months of age and breeding age, or maybe a bred heifer. She’s in a perfect spot to tailor her immunization strategy, because she’s past neonatal disease and hasn’t gotten close to the start of a new lactation. In the vaccine world, we give adjuvants that aim to produce a positive immune response, and there’s good data on them. But could we do a pre-adjuvant in the form of a nutraceutical? If we know we’re going to vaccinate a group of calves a week from now, what can we do nutritionally beforehand?

Dr. Eduardo Rico: Vitamin D3, for example, is exciting there, because there’s some evidence in humans that it could help the immune system respond better to real viruses or tamed viruses, like vaccines. Maybe something like that, and there could be more.

Dr. Mark Fox: I think everything that leads up to the shot is really important. Make it as stress-free as we can, knowing there will always be issues, and really baby that transition cow. When she leaves the fresh pen, we want to see her in the first run up to the parlor. Cows have their habits, and to this day I watch cows all the time and think about those first loads in the parlor. Those cows have it figured out. What separates them from the last ones in the parlor? The last ones are often the cows with a bit of a soft tire, a sore foot. They get the worst of everything: the longest time away from feed and the bunk. When they do get up to the bunk, they slug-feed, eating a few big meals instead of six or eight a day, because they’re crippled. That’s why lameness is such a precursor to a lot of bad things. And as you all know, a lame dry cow is a cow that won’t survive transition. She just won’t.

Our dairy cow is an amazing mammal, and we’ve surrounded her with good caretakers and farmers who want to do their best. If we can start to delve into the emerging science on dietary things we can do to enhance their performance, it’s awesome.

Scott Sorrell: I like the concept of a pre-adjuvant. That makes a whole lot of sense.

Dr. Eduardo Rico: It sounds good, actually.

Scott Sorrell: It does, doesn’t it? Dr. Fox, that’s a nice way to transition us to wrapping up. Great comments. Eduardo, before we close, did we miss anything?

Dr. Eduardo Rico: No, I think we covered the basics. The idea that nutrition can help cows mount better immune responses is probably the important concept we’d like to get out. It needs more research, because we haven’t fine-tuned the requirements. The classical view has focused on production, not on preparation for stress. Stressful situations are something these animals have to live with, because they’re doing so much. So how do we prepare them? That’s the question.

Scott Sorrell: Good. As we close, I’d like each of you to share your key takeaways from today’s conversation. Kelly, would you mind if I start with you?

Panel Final Takeaways (54:26)

Dr. Kelly Mitchell: Absolutely. It’s something I feel very passionate about, and I’ve talked to Dr. Fox about it: management is still number one on a farm, and it matters every single day. I also really like Eduardo’s point that life isn’t perfect. Real life is going to happen. What do we do to prepare for those not-so-great days on the farm? I think that’s a great strategy to start thinking through as you manage your animals.

Scott Sorrell: Great comments. Dr. Fox?

Dr. Mark Fox: It’s been another great conference. Thank you for the invite. This has been helpful to me.

Scott Sorrell: This has been awesome. Appreciate your participation.

Dr. Mark Fox: The advancing science on immune function, the goods and the bads, and how we can address it with nutrition is awesome. Cowside technology is gaining so much momentum around the globe that now I think we can ask our cows questions, and still look them in the eye and try to make the right decisions. It’s a great industry. It’s always interesting and exciting to see all the new science and the new scientists here. Thanks again.

Scott Sorrell: You’re very welcome. Dr. Rico, final words?

Dr. Eduardo Rico: Something I didn’t mention before is that we’re improving our ability to detect inflammation early, and I’m excited about that. Some work out of Cornell is helping us measure something that isn’t like ketones, where we measure postpartum and cows are diagnosed or not. We’re starting to make inroads into measuring, cowside and in advance, the inflammation that could precede all of these issues. That will help us understand when we’re doing something good with nutrition early and tweak it a little better. So, nutrition has something to say about inflammation. That’s my take-home.

Scott Sorrell: Excellent.

Closing Remarks and Real Science Lecture Series (56:23)

Scott Sorrell: We’ve had a lot of podcasts this week, but I have to say this is one of the best, maybe my favorite so far. Thank you all for joining us. To the audience, thanks for coming along with us. I hope you learned something and had as much fun as I did, and I hope to see you next time here at the Real Science Exchange, where it’s always happy hour and you’re always among friends.

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Balchem’s Real Science Lecture Series webinars take place on the first Tuesday of every month, covering the top research and nutrition topics that will impact your business. We also include small ruminant, monogastric and companion animal topics throughout the year. Visit balchem.com/realscience to see upcoming topics and register for future webinars. You can also access past webinars and search for the topics most important to you.