The kind of loopy name – alpha-gal syndrome – belies its significance. The alpha-gal syndrome is no joke and may even be mimicking diseases like post-treatment Lyme Disease, irritable bowel syndrome, mast cell activation syndrome (MCAS), orthostatic intolerance, or even fibromyalgia or chronic fatigue syndrome (ME/CFS). One paper stated:
“This case series illustrates the need to consider a diagnosis of AGS in patients with prolonged, nonspecific symptoms such as GI distress, fatigue, arthralgias, and mild cognitive dysfunction following a tick exposure.”
Alpha-gal syndrome
Alpha-gal syndrome begins when the immune system attacks a sugar found in red meat.
Alpha-gal syndrome is an allergic reaction to a sugar found in red meat (beef, lamb, pork, rabbit) that’s produced by a tick bite. It’s apparently been around for a long time but wasn’t discovered until 2002. Oddly enough, it first showed its face when a cancer drug trial of cetuximab – which contains the alpha-gal sugar – caused up to 22% of people in Tennessee to develop anaphylaxis within minutes of taking the drug. The fact that only about 1% of people in New York developed anaphylaxis suggested that something in the Tennessee patients’ environment was causing the reaction.
It’s the result of a strange process: a tick inserts a sugar called galactose-alpha-1,3-galactose into the skin. That same protein is also found in red meats, but apparently, the presence of the protein in a place it shouldn’t be – the skin – triggers an IgE antibody response to it called “anti-gal”.
When those affected by alpha-gal eat red meat again (or in some cases gelatin or dairy or other products), their immune system attacks the protein causing the symptoms. Note that the vast majority of people bitten by these ticks will not come down with alpha-gal – but a small percentage will.
A recent review of the syndrome called it a “fascinating new entity (that) has completely changed the paradigms of allergy because it’s directed against a carbohydrate or sugar (oligosaccharide) and the reactions can be both immediate and delayed. Because the alpha-gal sugar is found in many pathogens (Borrelia, Leishmania, Trypanosoma, Mycobacterium), our immune systems are primed to respond to it. Never before, though, has it triggered a chronic allergic reaction in humans.
Symptoms
Most websites state the reaction includes rash, hives, nausea or vomiting, joint pain, difficulty breathing, drop in blood pressure, dizziness or faintness, and possibly severe stomach pain and anaphylaxis. A published case series, though, suggests that fatigue and brain fog commonly result as well, and a survey added anxiety, depression, sleep disturbances, and irritability to the list. (It also suggested that the sensitivities might be able to spread to things that don’t contain red meat such as household chemicals, etc.)
Jennifer Platt, DrPH, cofounder and director of Tick-Borne Conditions United and adjunct professor at the University of North Carolina Gillings School of Global Public Health, reported in Healio that “AGS impacts every body system” and that “Many patients are still told, ‘it’s all in your head,’ prescribed anxiety/depression medication, and sent on their way.”
Prevalence
Amblyomma americum (Lone star tick) appears to be the most common carrier in the U.S. (from Wikimedia Commons)
Most websites report that the alpha-gal sugar is carried by the most common tick in the southern and central regions of the US – the (Ixodes holocyclus) in Australia.
A recent review, however, which tracked alpha-gal allergy in people taking the cancer drug cetuximab, reported that of 76 patients studied in the southwest US, 33% developed hypersensitivity, and 21% of healthy controls from the same region had detectable cetuximab sIgE (i.e. had an IgE immune response to the drug). The number dropped to 6% in California and just 0.6% of healthy controls in Massachusetts. The authors concluded that cases clustered in areas with a high prevalence of Rocky Mountain Spotted Fever transmitted by Amblyomma americanum and Dermacentor variabilis.
Indeed, other websites noted that alpha-gal is suspected to occur in other ticks and cases have been reported in portions of the Western and Northern United States where the lone star tick is not present. The syndrome appears to be most prevalent in southern, central, and mid-Atlantic regions of the U.S. and has been reported on every continent except Antarctica.
Alpha-gal prevalence from the 2023 CDC study. Note that the CDC believes the prevalence is greatly underestimated.
THE GIST
- Alpha-gal syndrome is an allergic reaction to a sugar found in red meat (beef, lamb, pork, rabbit) that’s produced by a tick bite.
- A tick inserts a sugar called galactose-alpha-1,3-galactose into the skin. That same protein is also found in red meats, but apparently, the presence of the protein in a place it shouldn’t be – the skin – triggers an IgE antibody response to it called “anti-gal”.
- The reaction includes rash, hives, nausea or vomiting, joint pain, difficulty breathing, drop in blood pressure, dizziness or faintness, possibly severe stomach pain and anaphylaxis, fatigue, brain fog, anxiety, depression, sleep disturbances, and sensitivities to other factors.
- The alpha-gal sugar is carried by the most common tick (the lone star tick (Amblyomma americanum)) in the southern, central, and mid-Atlantic regions of the US – but is clearly present in other ticks as the condition is found in other areas of the U.S. It appears to be the most common in the southern, central, and mid-Atlantic regions of the US and has been found on all continents except Antarctica.
- It may mimic other conditions such as post-treatment Lyme disease, irritable bowel syndrome, ME/CFS, fibromyalgia and orthostatic intolerance.
- Alpha-gal syndrome made the headlines last week because of two CDC studies that reported: a) alpha-gal syndrome is much more prevalent than previously thought; and b) many doctors don’t know how to diagnose or treat it. With physician ignorance high, the data suggested that almost a half million people in the U.S. may have alpha-gal syndrome, most of whom don’t know it.
- The reaction is often missed because it usually occurs 2-6 hours after eating red meat (beef, pork, lamb). Note that if you have alpha-gal syndrome you may also react to a wide variety of products that contain meat by-products.
- Several antibody tests are commercially available (see blog). Note, though that most people who have antibodies to the sugar do not come down with alpha-gal syndrome. Still, a test could indicate if you are a candidate for it.
- Treatment usually involves staying away from red meats (beef, lamb, pork) and possibly foods or substances with red meat by-products in them, but one case series reports that twice-daily oral antihistamines can often help. After abstaining from red meat for a time some people apparently can resume eating it without symptoms.
Alpha-gal syndrome made the headlines last week because of two CDC studies that reported: a) alpha-gal syndrome is much more prevalent than previously thought; and b) many doctors don’t know how to diagnose or treat it. With physician ignorance high, the data suggested that almost a half million people in the U.S. may have alpha-gal syndrome, most of whom don’t know it.
Little Known, Hard to Recognize Syndrome
The syndrome is harder to recognize than other allergic reactions because it usually occurs 3-6 hours after eating something that contains the sugar. Even in people with alpha-gal syndrome, it doesn’t always occur. Leading one doctor called the reaction “consistently inconsistent“, plus one survey reported that the reaction can sometimes occur within ten minutes in some people. Plus, the reaction often takes months after a tick bite to manifest itself.
Because red meat products can make their way into many foods, the Allergic Insider reports that some people with alpha-gal may also react to soup-stock cubes, gravy packages, flavor ingredients in prepackaged products, meat extracts used in flavoring, dairy products (e.g., milk, cheese, yogurt, butter), canned tuna (which can be contaminated by dolphin or whale), chicken or fish cooked on a grill contaminated with red meat, pork-gut casings for sausages, pork fat (used for cooking and often found in pastries and venison burgers), and suet.
Gelatin-containing foods (readymade meals, marshmallows, dips, glazes, icing, some processed meats; yogurts and ice cream as a fat substitute; wine and juices as a clarifying agent) present another possible issue. An Australian study found that most people with allergies to red meat were also allergic to gelatin products.
There’s more – some shampoos, various vaccines, antivenom, and medical tablets (e.g., acetaminophen, oxycodone, lisinopril, and oxycontin), some ingredients made from red algae, such as carrageenan (sometimes found in beer, condiments, infant formulas, salad dressing – and “much more”.
Testing
Antibody tests can determine if you might have alpha-gal syndrome. Most people with alpha-gal antibodies, however, do not appear to have the condition.
Skin-prick allergy testing for an allergy to meat to meat is ineffective. If you suspect you might have alpha-gal syndrome, the Allergy Insider recommends that you ask your doctor for an alpha-Gal allergy blood test. You can also get “an allergen component test for alpha-Gal allergy which may help to pinpoint the specific sugar molecule that is causing symptoms” and helps to assess how severe your reactions are. Another test that assesses skin and basophil activation is reportedly the most sensitive but is costly.
Lymedisease.org reports that Viracor is the main laboratory for AGS testing and that “the Viracor specific IgE galactose-alpha-1,3-galactose” test can be taken at most commercial laboratories like Labcorp and Quest and shipped to Viracor. It also provides a warning:
“Warning: The test for alpha-gal is often mistaken for ‘alpha-galactosidase’ or ‘a-galactosidase A deficiency’—note these are the wrong tests! Because the test is so new, it is recommended to take the proper testing codes with you to the doctor and the laboratory. Click here to download and print a PDF on the proper testing codes for alpha-gal syndrome.”
Note, though, that because people can have the antibodies without having the syndrome it might be better to carefully monitor your reaction to red meat over time.
Disease Mimic?
Could some people with ME/CFS, FM, Post-Lyme Disease, MCAS or POTS have alpha-gal syndrome?
Given its transmission through a tick bite, it’s not surprising that a Lyme misdiagnosis is common. One survey found that 12% of respondents had been misdiagnosed with Lyme and treated accordingly. Sixteen percent of 518 Swedish patients who had been diagnosed with Lyme disease had detectable α-gal antibodies. The gut symptoms the syndrome produces – some alpha-gal patients only have gut symptoms – has led some to be misdiagnosed with irritable bowel syndrome. Given the syndrome’s ability to rapidly drop blood pressure, orthostatic intolerance is another possible outcome. Given the many symptoms the syndrome can produce, ME/CFS and fibromyalgia are two other possibilities.
Treatment
Treatment usually involves staying away from red meats (beef, lamb, pork) and possibly foods or substances with red meat by-products in them, and possibly dairy products, but one case series reports that twice-daily oral antihistamines can often help. After abstaining from red meat for a time, some people apparently can resume eating it without symptoms.
Conclusions
Alpha-gal syndrome – an allergic reaction to red meat and red meat by-products caused by a tick bite – is a little-known disorder that appear to be much more prevalent than previously thought. While the exact number of people with alpha-gal syndrome in the U.S. is unknown, one estimate suggests it may be as high as 500,000.
It appears to be much more prevalent in the southern, central, and mid-Atlantic regions of the United States but has been found across the country. Several tests are available, but note that most people who carry the antibodies are not affected. The test would seem to be a way to indicate, though, if you are a candidate.
Charting one’s reactions to red meat (beef, lamb, pork) and possibly red meat products (which occur in a wide variety of foods and substances) – which typically occur 2-6 hours after ingestion or exposure – is one way to assess if alpha-gal syndrome is present. The reactions should be observed over a period of time as they may not consistently occur.
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At least there is a test! Now to get the DRs educated. And the news that many people seem to recover is great news! Not so good that other ticks have been found that carry it and symptoms are similar to other TBDs. Thanks for the update!
This brings back memories. As far as I am aware, this was first discovered on the northern beaches area of Sydney. People were turning up to emergency wards suffering anaphylaxis and the emergency doctors were trying to unravel what illicit drug consumption was responsible. The patients were saying “I just had a steak and a BBQ and the next thing I couldn’t breathe”. I also seem to recall that the immunologist responsible for its discovery was using a fork and a steak from the supermarket to do skin reaction tests in the early days.
The other thing that sticks in my mind is that alpha-gal was (at the time) the only known carbohydrate based anaphylaxis inducing immune response (or something like that). At the time, I saw my GP, explained to them that maybe this should be considered an avenue to explore. They’d never even heard of it (I’d seen it on a local popular science show a couple of days before) but there was a standard test for it even back then (about eight years ago I think). It was a negative result, and I felt like a mad scientist asking for it, but it is interesting now that it is showing up more broadly.
Yes, the articles referred to a tick in Australia that carries it but not to other ticks elsewhere. It was apparently one of the first places it was uncovered.
Yeah it seems like a true moment of independent scientific discovery in multiple places. That doesn’t happen that often.
Great to see it getting some awareness on this blog. It is such a left field condition (and left field aetiology even) but you’d want to know about it if you had it. A wise retired doctor once told me that just because you’ve got one chronic illness, that doesn’t make you any less likely to develop any other medical condition (than the general population). Given the food intolerances that come with ME/CFS, you wouldn’t want to assume you were just having a reaction to amines in red meat rather than this.
Hi folks, are there any antihistamines that don’t cause drowsiness?
I was vegetarian for years after I suddenly found that eating roast beef or roast pork had me waking in the night sweating with absolutely agonising gut pain. 1st time was a family Christmas dinner of roast beef. Before having M.E., I would have visited A&E with such pain: but I just rode it out as I had had to do with many of my symptoms, because my ill health was repeatedly disbelieved since contracting M.E.
The worst one lasted three days: worse than childbirth pains! I was all dressed and ready to go to A&E after the second terrible night of pain and realised I was more terrified of the cruel treatment meted out at hospital than dealing with it myself.
I believe the unique delay of several hours between eating and onset of symptoms is diagnostic, reflecting the time it takes for the breakdown of fats where the culprit is concentrated.
During this period I also found that if my medication was in gelatin capsules it made me unwell (but not gut pain); another reason for my consultant to lose patience with me!
Absolute abstention from meat and gelatin over several years eventually resolved the symptoms. I only read about alpha-gal later and realised what it was I had been dealing with.
This occurred separately from very nasty full-blown Lyme disease et al. that I later contracted on a camping Buddhist retreat infested with ticks when we set up camp in a glade normally occupied by wild deer.
All of these ‘joys’ I encountered during 30 plus years of myalgic encephalomyelitis triggered by a severe viral infection in the winter of 1990: I have since been re-diagnosed as PoTS, EDS & MCAS. (picking up several viruses along the way – EBV, CMV, Cocsackie etc. & typhoid [despite vaccination], toxoplasmosis & CPN).
I would say it is likely the viral infection in 1990 changed my immune system in ways that it has never recovered from, leaving me vulnerable to all these adventitious pathogens that a healthy body may have fought off. It looks like Long-Covid may prove to be exactly the same.
I don’t recall tick bites before the alpha-gal onset, but often that is the way with ticks. I was already several years into this chronic ill health, that was triggered by a winter virus. I think in my case alpha-gal was a result of an impaired immune system, rather than it being the genesis of my 30 plus years of poorly understood sickness.
I think many people will feel unwell eating fatty meat and encountering gelatin in its many forms, but not realise the alpha-gal connection. I am a research scientist by profession, so I was used to making observations and recognising patterns and associations: but it was subtle and easy to miss. or dismiss. I never had the blood test, which I am not certain is available in UK and the symptoms had subsided by the time I was aware of alpha-gal. I am glad to see it is being discussed again. Alpha-gal was another straw on the camel’s back, that could be teased out and dealt with, reducing the burden of inexplicable symptoms.
This is incredibly interesting Cort. It makes me wonder how many odd ball things are out there..not yet discovered . I live in a high tick concentration area ( northeast).. They make outside summer activities scary. Nightly full body checks are necessary . Just watching my grandchildren roll around in the grass gives me anxiety ! I ‘ll add this to the ever growing list of reasons why I HATE ticks. I was in my 30’s before I saw my first tick ….. Now it’s commonplace.
I have visited a location in usa that was previously thick with ticks. When I visited, numbers were lower due to hungry growing chickens and guinea fowl.
Maybe we need to support bringing back prairie chickens, spruce grouse, etc.
My dad has alpha gal, contracted it in 1989. He likes to hunt, so has had contact with ticks through the years. He made the connection that he couldn’t eat red meat anymore; not sure when he realized it was caused by a tick. Anyway, his symptoms do not include anything other than a reaction to beef, so I guess he is lucky.
Makes me wonder if there is some genetic connection between alpha gal and me-CFS ….
Appreciate this important reporting, Cort.
(quick side note) I saw in Mass ME’s e-mail today, “Congratulations to ME/CFS Advocates in Minnesota!
A group of dedicated advocates helped to craft legislation that establishes a comprehensive, statewide monitoring and support program for individuals suffering from Long COVID, ME/CFS, Dysautonomia, and POTS. The legislation is included in the state’s 2023 Omnibus Health Care bill, signed by the Governor and implemented as SF2995, Section 50: Long COVID and Related Conditions Assessment Monitoring. (Pg 213). The legislation is supported by funding for the Minnesota Department of Health in the order of $3.14M per year for each of the next 4 years.’
This feels like a pretty big advocacy win for the community (if this has happened before please let me know) – will there be future reporting on this? Just was curious.
Thank you for raising awareness about AGS. I have it. Your article needs editing. It suggests that it is “red meat” allergy, which it is not. My suggestion is to refer to it as mammalian food allergy/syndrome. The vast majority of AGS patients react to dairy and other sources of AG, and there is even more who don’t even know they react. Relatedly, one of the biggest recent findings in AGS research is that AG sensitized individuals have a much higher chance of hidden reactions; think heart problems, atheroscleroris. So it is important to explain the risk and dietary restrictions. The problem is that here in the US many still view and treat AGS as “red meat” allergy. As a result, they are contributing to cascading health issues. This can simply be avoided by telling patients and the general public to stop ingesting the AG allergen, which is in dairy, mammal meat and byproducts.
Actually if you read the article a bit more closely it does mention dairy and many mammalian by-products.
Here’s a couple of articles from the New York Times’s “Diagnosis” column on this:
https://www.nytimes.com/2018/01/04/magazine/a-strange-itch-trouble-breathing-then-anaphylactic-shock.html
https://www.nytimes.com/2022/05/09/magazine/meat-allergy-diagnosis.html
I have had Alpha Gal for 8 years now. I am highly reactive to everything and now suffer from Mast Cell Activation as well as lymphatic involvement. Oh and esophageal spasms from fumes and exposure. It has rocked my world. I try to spread awareness and am very thankful for this article. I live in Maryland, USA and this syndrome is spreading very quickly here.