Tick Bites, “Red Meat Allergy” and Alpha-gal Syndrome: What's the Connection?

Interview with Dr. Scott Commins, Professor of Medicine, University of North Carolina

Dr. Scott Commins is an expert in something called alpha-gal syndrome or AGS, which is often referred to as "red meat allergy" or "mammalian meat allergy." Strangely enough, alpha-gal syndrome seems to be triggered by a tick bite. People who have eaten meat all their lives - without any trouble - suddenly become allergic after being bitten by a tick! The reactions can be very different for different people, and some reactions are severe, even including anaphylactic shock. What's going on here? Check out the interview to find out!


Additional Information

Alpha-gal Syndrome | Centers for Disease Control and Prevention (CDC)

Alpha-gal Information Website (non-profit organization)

Alpha-gal and Red Meat Allergy (American Academy of Allergy, Asthma and Immunology)

What is a red meat allergy? (Excellent short presentation video by Dr. Scott Commins)

Cracking the meat-allergy mystery with the tick-bite link (Nature)

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Transcript of the Interview

Mark at Insect Shield

We're talking today with Dr. Scott Cummins, who is a professor at the University of North Carolina School of Medicine. And he specializes in allergies and the immune system. He sees patients at the allergy clinic there. And he also runs a laboratory, which is devoted to research into something called the alpha-gal “meat allergy”. And so we're going to talk about that today. And there's a special kind of characteristic of this allergy where a tick bite is involved. So, we want to try to understand that and help our viewers know a little bit more about this disease. Scott, welcome.

Dr. Commins

Thank you. Glad to be here.

Mark at Insect Shield

So I think there's growing awareness of alpha gal, and it's kind of interesting, because a lot of times it's called red meat allergy. And that's a little deceiving, I guess in terms of what it really is, and what really all the causes can be for the allergy. But maybe you can just give us a brief overview of what the allergy is like, and what [the] symptoms [are], who it affects and so forth?

Dr. Commins

Yeah, sure. So, I tend to call it alpha gal syndrome, or AGS for short, because, as you mentioned, Mark, the allergic reactions involve or can involve more than just eating hamburgers, hot dogs, beef, pork, lamb, etc. So at its basis, alpha gal syndrome is an allergic response to a sugar. Alpha gal is technically a sugar. So it's unusual in that sense, most of what we think and know about allergies occurs to proteins. So alpha gal, AGS, is somewhat different in that regard. But that's just the tip of the iceberg in terms of its differences from traditional allergic responses and allergic syndromes. 

The second, probably biggest difference is that for people who develop AGS, the reactions typically take hours to develop after eating beef, pork, lamb, etc., or coming in contact with foods or medications that might [contain] a mammalian product. So underlying the sort of biology of alpha gal is this very unique distribution, where humans don't make this alpha gal sugar, but all lower mammals so to speak, do, so any mammal that's not human or certain primates will have alpha gal sugar as just a part of its DNA, per se. 

So it's present in anything from cows, pigs, sheep, goats, rabbits, down to cats and dogs. And when folks develop AGS, their symptoms can be as severe as what we in the allergy world call anaphylaxis. So a severe allergic reaction where you would have hives and shortness of breath, and even low blood pressure. Or they can have other more subtle presentations where you may just have itching and hives. 

Interestingly, we've come to be aware of folks who strictly have gastrointestinal symptoms as well. So really, no hives, no swelling, no redness, nothing that would really have led you to an allergist, but instead they have nausea, vomiting, diarrhea, severe abdominal cramping and pain. And, and we're learning more about these different presentations of AGS as we go along.

Mark at Insect Shield

Yeah, that's amazing. And so there are a lot of, I guess, characteristics that make it very hard to diagnose. And especially this delayed response, because it sounds like a lot of people who have gotten exposure to Alpha gal may have a meal but they don't associate the meal at all with the onset of all these symptoms, right? Because they can happen six hours later, or something like that.

Dr. Commins

Yeah, exactly. If you can imagine having a hamburger for dinner at seven or eight o'clock at night, and then literally nothing happens for four or five or six hours. So all of a sudden, at midnight, 1 am, you start to get some itching or hives, or GI distress. And it's just not natural to think about, Well, what did I have for dinner as the cause of that? So you're 100% correct, that the diagnosis can be exceedingly difficult to make. And often, there needs to be a little bit of a, as we say in medicine an “index of suspicion”; you have to be aware of the syndrome, and almost begin to sort of suspect it and ask questions around it to help patients make the diagnosis.

Mark at Insect Shield

Yeah, and this is really interesting. There's certain similarities, I guess, just between diagnosis and Lyme disease, because that's been not very well understood for a long time. And doctors just wouldn't even consider it, I guess, initially. So this kind of falls into that basket.

Dr. Commins

Yeah. And the other part of that, too, is there's these regional differences. And I think this is where the tick populations come into play. So probably in the northeast (northeast of the US) there's a very real awareness of Lyme disease. And that may not be true in other parts of the US. And I think that's kind of true of alpha gal syndrome as well.

Mark at Insect Shield

Right. So who gets this [allergy] – there’s kind of an interesting backstory about how it was discovered, I guess, looking at correspondence between, I don't know, one of the things that I read was just like, look for any correspondence whatsoever in populations of humans, and who's getting this and who's not? So how did that come about? I mean, the tick, the involvement of the tick was kind of mysterious. Right?

Dr. Commins

Right. We understood. That's probably an overstatement. We were aware of AGS before we were aware of the association with tick bites. So we'd had some patients coming just a few, really, to the allergy clinic, who were sort of telling us a unique and different story that they thought they were allergic to beef or pork, or lamb or all three. And that it was not happening right away. So they can eat at the restaurant or at home. And then it took hours of delay. And as we began to put more and more of these folks together, obviously, our natural question was, why is this happening? At the time these were all adults. Why are these adults who have safely tolerated beef pork lamb for 40 or 50 years, suddenly losing tolerance, suddenly becoming allergic to that? 

And it just happened to turn out that there were a few people in our laboratory group who actually developed the allergy themselves. And that turned out to be really important in making the association with tick bites, but we were not aware of that at first.

Mark at Insect Shield

The researchers you mean, who were in the lab group? 

Dr. Commins

Correct. There's this also, there's a really interesting facet to this where, even though what you and I are talking about, it's predominantly centered around the US population that initially, this is happening globally. And so it turns out there was a researcher and clinician in Australia, Dr. Cheryl van Noonan, who actually described a very similar phenomenon occurring in Australia. And she was seeing it among her patients, and she suspected ticks. She didn't really have a sense that the Alpha gal sugar was involved. But it began to give some credence to what we were seeing as well, just this idea that someone across the globe was also seeing a very similar phenomenon raised the prospect that this could have really been true.

Mark at Insect Shield

Hmm. And, yeah, I mean, if this is sugar, And it's in the lower mammals. It's just really interesting, like what happened first you see this emergence of allergy? And then think, okay, there are these similar stories, I guess. But you have to sort of identify the sugar. But then how did the tick, I mean, they could have gotten the sugar from anywhere, right, to give them this reaction.

Dr. Commins

Yeah. We were initially thinking that it made a nice story that the tick bites a deer or a dog, or in the Australian case, maybe a bandicoot, but a small mammal that would carry Alpha gal as a part of its DNA. It's just a blood group substance. So the tick feeds on an animal that has Alpha gal, and then goes to the next life stage and bites a human. And in so doing then, sort of inoculates the human with alpha gal from the lower mammal, and probably in the setting of tick saliva, causes this allergic immune response to be triggered in humans, makes a great story. 

And I still think it’s possible that that's true. But what our further research has shown us is that the ticks themselves seem to carry an enzyme that may actually create either Alpha gal, or a very similar sugar. And it may not even require a blood meal before they bite a human. Yeah, so that's still evolving a little bit. For us it is a tough study to do, because we generally are in the business of asking people not to get tick bites. So you've got to get the naturally occurring ones. And we don't really want people to keep the ticks on them to sort of study how long does it take after a bite to develop the allergic response, too.

Mark at Insect Shield

Interesting. So I mean, that's part of the science of this study is that you can't really create the environment or conditions like you don't necessarily want to try to create those conditions, I guess.

Dr. Commins

Yeah. Yeah, that's true. That's right. Yeah, we use a mouse model. There are mice that are engineered to not have alpha gal. And there's a backstory there. There are pigs that also lack the ability to make alpha gal and potentially could be useful as a model as well.

Mark at Insect Shield

Right. There's been in the news lately, the heart transplant from a pig that was engineered not to have alpha gal, I think, was that right? And that worked for about two months. And in that case, the tick is not a part of the picture at all. 

Dr. Commins

Yeah, the tick is not part of that picture. It's a really interesting story. It's not a side note at all. But the biology of this is complicated. Because all humans make an immune response to this alpha gal sugar. The people that develop AGS happen to make an allergic immune response to the sugar. But because all humans make an immune response to Alpha gal, it is the barrier for what we call hyper acute rejection. 

So essentially, the reason you couldn't transplant a pig liver into a human is because we would all reject it right away. And so that's why they initially, were looking at alpha gal, and could we engineer an animal model to not express it, and perhaps it would be a source of organ transplantation. So that existed before we described AGS. And obviously, now, we're very interested in those animals, not only for pork but equally and probably more important for the medical aspects. You can imagine. You wouldn't want to put a porcine heart valve in someone who's allergic to Alpha gal, you would rather have that Valve come from an alpha gal safe or alpha gal free pig.

Mark at Insect Shield

Yeah, yeah. So you've described, I mean, the symptoms or the reaction can be very much different in different people. And so that makes it more difficult to diagnose sometimes. So in terms of getting in to see an allergist, for example how does somebody kind of go into that allergist? What am I trying to say, if somebody is bitten by a tick, and they think, well, alpha gal is a possibility here. What should they do? I mean, there is a test. Should they get that test? Should they go get that test right away? Or is it you know, what's their course of action?

Dr. Commins

And typically, you're correct, there is a test, there's a blood test available. But we think it takes a few weeks for the allergic response to develop following tick bites, if it's a brand new response. So getting the test done right away is probably not the best idea, I think there is a period of time where people could test negative equally, in the same respect that we don't run tick borne infection testing every tick bite, we also don't actually do that for the Alpha gal syndrome aspect, either, we tend to take a history and essentially wait for some sense of symptoms to develop. 

And part of the reason for that is allergy testing by blood work in particular can have a fairly high false positive rate. So when we look at groups of people in the southeast in particular, as much as 20 to 30% of tick-bitten folks can test positive but have no symptoms whatsoever. So we really like for there to be some initial symptoms that we feel could be indicative of this allergy. And then we have the testing done to confirm it.

Mark at Insect Shield

Right. So I don't know if we mentioned it, but it's the lone star tick that has kind of been identified as the tick that's spreading this.

Dr. Commins

Yeah, that's correct. In the US, and globally, it seems like there are local species in each of these places where it's been described. But correct in the US, we think the lone star tick is really the bad, bad offender.

Mark at Insect Shield

And that was part of how this sort of discovery of the association was made. Because there's areas where the lone star tick is prevalent. In the southeast, I think. Is that right? 

Dr. Commins

Correct. That's correct to where we first sort of made this association between the allergic response and tick bites, it was, you're right, in places where lone star tick numbers were high. And, people were pretty heavily bitten.

Mark at Insect Shield

Yeah, there is something to be aware of, I guess, in terms of the allergic response is that additional bites can really have an impact in the sense of heightening the allergic reaction. Is that right? So if you're bitten, and you know you have alpha gal, do you really want to avoid additional bites? I mean, you kind of want to be hyper vigilant on that.

Dr. Commins

Right. There's two reasons I think you definitely are correct, and the data are pretty conclusive that additional bites seem to not only push your blood test number higher, but often can make people more sensitive. So in large part, we ask people to avoid all forms of mammalian meat. So beef, pork, lamb, goat, venison, etc. And then, some patients lose dairy as part of this as well. 

But what we've seen is that if you're, maybe you might consider yourself one of the lucky ones who initially is able to continue to eat cheese and have cow's milk. Additional tick bites will sometimes cause that tolerance to wane, and you'll actually then have to remove dairy from your diet. Okay, so the other reason to avoid tick bites is we think this syndrome will, over time, go away. But the caveat is additional tick bites seem to sort of stoke the fire and make that allergic response appear again. So whatever we can do for, for tick avoidance really is critical in alpha gal syndrome.

Mark at Insect Shield

Right? I mean, I guess it almost would be possible, like having that reaction, additional tick bites might make it lessen. I mean, that that wouldn't be out of the question, depending on the kind of allergy, I guess, but that's not the case. Right?

Dr. Commins

Right. You could, it could have been flipped, where additional bites somehow desensitized you. Right. But in large part, that does not seem to be true.

Mark at Insect Shield

Yeah, so we'll put a little plug in here for Insect Shield, which is if you want to avoid those bites, it's a really easy way to do that; just put the clothes on, get the socks and pants and so forth. 

There are other kinds of mammalian derived products that you have to watch out for that aren't just like a steak, right, or a hamburger. So what are some of those other things?

Dr. Commins

So, I think, in passing, I mentioned this idea of the heart valves. Right. So we always like to have conversations with patients. If they develop AGS and need a heart valve, we want to be in touch with their providers. 

But beyond that, some of the most common kinds of medical exposures are Heparin, which is a pretty common blood thinner, which is actually derived from pigs and cows. There are some pancreatic enzymes that people use to supplement if they happen to have had their pancreas function diminish or have it removed. And those are often derived from mammals. 

There's some natural thyroid hormone replacements that are mammal derived. There's surgical mesh that can be derived from animals as well. So that's just a partial list. But those are kind of a high point. So yeah, that's, I think, really where it lends itself to this idea of a syndrome more than just a food allergy.

Mark at Insect Shield

Right. I read different people saying that red meat allergy is kind of a misnomer. I mean, it. And if you look on the internet, of course, there's a ton of results for red meat allergy, which I guess is good. You know, but it's not exactly what it should be called. Yeah, gelatin capsules are another one. Right. And the one that I was very sad to hear about was marshmallows.

Dr. Commins

In there, gummy candy. Yeah, that fits in there. There's certain vaccinations that have gelatin in them as well. So yeah. And nowadays, right? Well, there's a lot of focus in the pharmaceutical industry in these very targeted therapies. In some of the cell lines that are made to produce these fairly fancy antibodies can be mammalian derived cell lines. So mouse cells or rat cells. Not all of them are bad or a risk, but we just need to be careful and cautious about it. So raising awareness is really important.

Mark at Insect Shield

Yeah. Right. It's just getting more information to kind of arm yourself. There are stories and I don't know how much these are still around, but people are going to their PCP and saying I seem to be having this allergic reaction. But there's not a lot of awareness on the part of general practitioners about the connection that might be happening there. So do you feel like doctors are, are getting better about this? Are they getting more information to be able to help diagnose or not?

Dr. Commins

Yeah, I feel like we're getting there. But there's still a lot of work to do. And my sense is that a lot of this at least matters where you live. Because I do think there are pockets, particularly in the southeast, but Long Island, for example. There are pockets where the population is fairly affected. And I think in those geographic areas, the providers are really beginning to notice this and diagnose people quite quickly. 

But there are other places where we hear stories that folks have been just sort of not validated for many years. And there's a publication from a group here at UNC, that indicated that the median time to diagnosis was seven years. I hope we're getting better than that. But you're correct that there's still a fair amount of work to be done.

Mark at Insect Shield

Below the interview here, we'll put links to resources, and we'll connect with you about the best ones. What, what are the best resources that people can arm themselves with when they go in to talk to a doctor a lot of times? You know, it's like, Dr. Google kind of thing. And doctors are encountering this all the time. But are there places that a patient could point the doctor to get more info?

Dr. Commins

Yeah, the CDC website, and now has information about AGS and links. There are. There's various websites, alphagalinformation.org is one. And it's, I guess, sort of widely available in some of the search engines there's been, gosh, there's been publications in the New York Times Magazine, the Washington Post, Wall Street Journal, CNN, a lot of the major outlets have carried this. So I think those are all helpful. 

Sometimes the biggest thing though, is the blood test. And most of the samples that are tested for alpha gal allergy in the US flow through one of the Core Labs called Eurofins. Veracore, and their website has a PDF that you can print off and take to your provider and say, This is how you order it. This is the test number. And I think that actually tends to be fairly helpful as well.

Mark at Insect Shield

Sure. Wow, that's great. Well, I think we've covered a lot of ground here in a short amount of time, and I really appreciate your coming to talk to us today. Making the trip to Seattle, as they say. So we'll get more research resources from you. We'll put some links below the video here. And we'll be keeping in touch with you and your lab and so forth.

Dr. Commins

Yeah, we are more than happy to talk again.

Mark at Insect Shield

Great. Thanks so much. That's Dr. Scott Commins from the University of North Carolina School of Medicine.