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Alpha-gal syndrome is reaching new regions, but delayed reactions and GI-only symptoms can leave patients undiagnosed for months or years.
As the lone star tick pushes into new parts of the country, a familiar pattern is following it into clinics.
A patient with recurrent nausea and abdominal cramping sees a gastroenterologist. The workup comes back clean. Symptoms keep returning, often hours after dinner or in the middle of the night. After months or even years of searching, the patient has their gallbladder removed, hoping it will finally help.
It doesn’t. The episodes continue because the gallbladder was never the problem. The patient has alpha-gal syndrome (AGS), a tick-borne allergy to a sugar found in red meat and other mammalian products.
“It’s because of [this misdiagnosis that] these people will continue to be exposed to whatever allergen it may be,” said Shaun Cross, PhD, assistant professor in the department of environmental, agricultural, and occupational health at the University of Nebraska Medical Center, in an interview with HCPLive.
As the lone star tick expands its range, AGS is reaching patients and clinicians who never have encountered it. An estimated 450,000 people in the US may be affected, and a growing number of states now require it to be reported.1,2 Clinician awareness has not kept pace.
Beyond gallbladder removal, there have been several reports of patients undergoing exploratory surgery or appendectomy before receiving an AGS diagnosis.3 Although these cases have been described, no study has yet quantified how many patients with AGS undergo such procedures before diagnosis.
In a cross-sectional survey of 201 farmers and ranchers with a self-reported AGS diagnosis, Cross and colleagues found that respondents averaged nearly 3 provider visits before diagnosis.4 The respondents came from 26 states, with most from Missouri and Oklahoma.
Investigators identified 4 distinct symptom clusters.4 The most reported symptoms included abdominal cramping, diarrhea, itchy skin, and nausea. Women reported more gastrointestinal discomfort, and men were more likely to fall into the mild symptom group. More than half (53.2%) were not familiar with AGS before their diagnosis, though most knew ticks could cause a food allergy (68.2%).
In a 2022 nationwide CDC survey of 1,500 health care providers, 42% had never heard of AGS. Another 35% were not confident in their ability to diagnose or manage the condition.5
The gap extends to gastroenterologists, who are often the first specialists these patients see. When HCPLive approached 2 gastroenterologists at the American College of Gastroenterology (ACG) 2026 meeting in Nashville, both declined to discuss AGS, saying they did not know enough about it.
“It's a lot more recognizable [now],” said Chirag Patel, MD, an allergist and immunologist from Hackensack Meridian Health. “If I mentioned it 5 years ago, [my peers would be] like, ‘What are you talking about?’ But now, everyone that I talk to in the clinical world…definitely knows something about alpha-gal. They may not know exactly what it is, but they know something about it.”
Arkansas, Delaware, Iowa, Kentucky, Nebraska, New Jersey, North Dakota, South Carolina, Tennessee, Virginia, West Virginia, Massachusetts, Oklahoma, and Missouri.
Patel believes the tick’s spread into the Northeast plays a role in why more people know about AGS in recent years. Large news organizations have reported the uptick, including The New York Times.6
The lone star tick was once found mainly in the South, but as temperatures have warmed, its range has pushed north. It is now common in coastal areas, including New Jersey and Long Island.7
Many states are now requiring reporting of AGS, including Arkansas, Delaware, Iowa, Kentucky, Nebraska, New Jersey, North Dakota, South Carolina, Tennessee, Virginia, West Virginia, Massachusetts, Oklahoma (as of November 1, 2026), and Missouri.2 New York City, but not New York state, also has mandatory AGS reporting. States with voluntary AGS reporting include Kansas, Louisiana, Minnesota, Pennsylvania, Rhode Island, and Wisconsin.
Missouri’s law, signed this summer, requires laboratories to report positive alpha-gal test results to the state’s Department of Health and Senior Services, which will follow up to identify true cases.8 Better data will show which communities are most affected and where clinicians need training, he added.
“I think many of us believe that [estimate] is probably a significant undercount,” said Benjamin W. Casterline, MD, PhD, an assistant professor of dermatology at the University of Missouri School of Medicine, in an interview with HCPLive “There are many more people affected than that.”
He noted that case counts can also shape federal policy. When data show a condition affects a significant number of Americans, initiatives such as allergen labeling tend to be more successful, he said.
On February 10, 2025, Rep. Jeff Van Drew (R-NJ) reintroduced the Alpha-gal Allergen Inclusion Act (H.R. 1178), which would add galactose-alpha-1,3-galactose (alpha-gal) to the federal list of major food allergens.9 The bill was first introduced in August 2024 but died at the end of that congressional session. If it passes, foods containing alpha-gal would have to disclose it on their labels, as is already required for allergens like peanuts and milk. As of October 2026, the bill remains in the House Energy and Commerce Committee, where it was referred shortly after its reintroduction.
The alpha-gal sugar molecule is found in most non-primate mammals, including cows, pigs, sheep, deer, and bison.5 A bite from a lone star tick can sensitize a person to this molecule, after which they may react to red meat, dairy products, or products containing gelatin.Safe foods for individuals with AGS include poultry, seafood, eggs, fruits, and vegetables.
AGS symptoms include hives, swelling, wheezing, cramping, abdominal pain, diarrhea, and nausea. Patients may have skin symptoms, GI symptoms, or both.
Outdoor workers face particular risk. Because their jobs put them in tick habitat, they are more likely to be bitten repeatedly, Cross said.
Evidence also suggests black-legged ticks can cause AGS.10 Cross stressed the importance of being aware of AGS, especially if the clinician treats farmers or ranchers.
“Historically, farmers and ranchers are pretty good about pushing through [symptoms],” Cross said. “What would be really important here for physicians is thinking about the fact that there can be a wide range of things, and that alpha-gal syndrome is something that’s here.”
He said clinicians treating farmers and ranchers need to look beyond what these patients eat. For rural workers, alpha-gal exposure can come from the job itself, including handling animals, deworming cattle, contact with amniotic fluid during birthing, and fumes. When taking a history, clinicians should ask when the symptoms appear, he said. Itching around animals or anaphylaxis during calving could point to AGS.
Cross noted that because specialists are scarce in rural areas, general practitioners and nurses often make the diagnosis, so they need AGS education rather than defaulting to a specialist referral.
Alpha-Gal Syndrome: Closing an Underrecognized Allergy Diagnostic Gap by Scott Commins, MD, PhD
When it comes to AGS, Patel believes clinicians should think “outside the box.” Patients with AGS often have scattered symptoms, such as intermittent abdominal pain or random hives, that are easy to mistake for viral or chronic spontaneous urticaria, Patel said. The key is asking when reactions occur. Alpha-gal reactions are typically delayed and often strike in the evening or overnight, while chronic spontaneous urticaria can flare at any time.
“Symptoms are quite variable, and they don't happen every time,” Casterline said. “So, someone who gets sick from a hamburger one night might not make them sick the next night for reasons that we don't understand.”
For patients without symptoms, Patel said test results need careful interpretation, since food allergy testing has roughly a 50% false-positive rate and serves as a risk assessment tool, not a diagnosis. A higher alpha-gal IgE level means a higher probability of true allergy, not a more severe one, he said. Even though lab reports may label results as “moderately” or “highly” allergic, a patient either is allergic or isn’t.
“It's not a test of alpha-gal syndrome. It's a test of the alpha-gal sensitization,” Casterline said.
AGS can only be diagnosed clinically based on symptoms after exposure. Severity is just as hard to predict, Casterline added. Patients with barely detectable antibody levels can have dangerous reactions, and some with very high levels have mild symptoms or none at all.
Patel uses an “alpha-gal ladder” to counsel patients. Mammalian meats and fatty mammalian products sit at the top because alpha-gal concentrates in fat. That concentration also helps explain the delayed reaction, since fat takes longer to digest. Dairy comes next, followed by gelatin and medications. Patients who tolerate dairy can generally take vaccines, tablets, and gelatin capsules without serious concern, unless a medication contains large amounts of alpha-gal, he said. As patients’ IgE levels decline, he gradually reintroduces mammalian products into their diets.
Unlike protein allergies such as peanut, which rarely resolve after early childhood, AGS can fade over time because the immune system doesn’t form lasting memory against carbohydrates, Patel said. As long as patients avoid new tick bites, their alpha-gal IgE levels typically decline. Once they drop low enough, patients may be candidates for an oral challenge or gradual reintroduction of mammalian meat.
“Because people are now more aware of the tick bites, they’re making sure they're wearing long-sleeve clothes when they're going gardening or out in the woods,” Patel said.
Patel said alpha-gal labeling would help patients but would be hard to implement. Alpha-gal content varies with the cut and fat content of meat, which is why reactions don’t happen every time a patient eats it, and even allergists struggle to quantify how much a given product contains.
“But I think if they can figure out how much alpha-gal is in a certain product and … what the threshold for tolerance is, that would certainly help the patients know that, ‘Okay, I can tolerate this, but not that much,”’ Patel said.
For Casterline, the case for labeling comes down to the toll of uncertainty. Patients spend a lot of time scrutinizing ingredients, unsure whether something like “natural flavor” comes from a mammalian source, and that worry affects their mental health, quality of life, and ability to work or attend school.
“Having clear labeling [of] what could have a mammalian alpha-gal versus what doesn't…would relieve a lot of stress off people and improve patient safety as well,” Casterline said.
Until better data, labeling, and treatments arrive, Patel said awareness remains clinicians’ most important tool. He cautioned that not every symptom a patient attributes to AGS is caused by it. Unexplained reactions should still raise suspicion.
“If you have random reactions that have features of an IgE-mediated reaction, then you should probably consider alpha-gal as part of your differential,” Patel said.
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