Alpha Gal Allergy

The Centers for Disease Control and Prevention has warned that alpha-gal syndrome is an emerging public health concern. CDC estimates that alpha gal syndrome affects up to 450,000 Americans. The number of new cases has been increasing by approximately 15,000 each year. 

Alpha-gal is is a sugar (galactose-α-1,3-galactose) that occurs naturally in some ticks’ saliva. It is not naturally present in fish, reptiles, birds, or humans. When alpha-gal is transferred to humans through a tick bite, it can induce the production of alpha-gal–specific IgE antibodies. 

Most patients appear to be sensitized through the bites of Lone Star tick, Amblyomma Americanum, whose host is deer. The Lone Star tick is prevalent in Arkansas, Kentucky, Missouri, Virginia and Tennessee. More recently, alpha gal syndrome has been linked to bites from black-legged ticks (Ixodes capularis) in Maine and from western black-legged ticks (Ixodes pacificus) in Washington state.

Alpha-gal syndrome is triggered when a person who has been sensitized to alpha-gal by a tick bite is again exposed to alpha-gal by ingesting beef, pork, dairy products, or mammalian-derived products such as gelatin. Alpha-gal is absorbed by the GI tract bound to glycolipid, and incorporated into chylomicrons, which enter the circulation in approximately 2 hours.

When alpha-gal binds to IgE antibodies present on mast cells in the GI tract, the mast cells degranulate and release histamine and other immune mediators. They bind to sensory nerve endings causing abdominal pain, intestinal smooth muscles contractions, and mucous gland secretion. Symptoms typically appear 2 to 6 hours after exposure and include hives, wheezing, abdominal pain, diarrhea, nausea, and vomiting.

While the most common presentation is a delayed allergy to meat, anaphylaxis to alpha-gal has been reported after routine childhood vaccinations, possibly due to gelatin and/or calf serum in the vaccines. Other products, including colloid solutions, gelatins, bovine or porcine heart valves, and some hemostatic agents, have also been implicated.

Diagnosis of the alpha-gal syndrome can be confirmed by testing for IgE antibodies to alpha-gal. ImmunoCAP o215 measures alpha-gal-specific IgE antibodies using the Phadia 250 instrument. 

Alpha-gal IgE testing appears to have low specificity for alpha-gal syndrome. A seroprevalence study of 3,000 blood donors was performed in 10 states that have established populations of lone star ticks during 2024 and 2025. The highest estimated prevalence of alpha-gal IgE antibodies was found in Arkansas, where 31% of adults were estimated to be seropositive. Missouri followed, at 26%, with Virginia, Kentucky, and Tennessee all above 21%. Together, these five states had an estimated seroprevalence of 24%. Many of these donors had not experienced clinical signs and symptoms of alpha-gal syndrome. This rate far exceeded the 450,000 US adults estimated to have alpha-gal syndrome (0.14% of the population). Reliance on positive alpha-gal IgE test results without considering whether patients also have clinical signs and symptoms of AGS might result in over-diagnosis and unnecessary dietary restrictions. 

Patients who are diagnosed with alpha-gal syndrome should be instructed to adopt an alpha-gal avoidance diet that eliminates beef, pork, venison and related products such as lard, dairy, and ice cream. If patients are able to avoid tick bites, it may be reasonable to repeat alpha-gal IgE levels 6 to 12 months after diagnosis. As the IgE level decreases or becomes negative, patients may be able to resume eating dairy, and then mammalian meat products.

References

Stone CA, et al. Anaphylaxis after vaccination in a pediatric patient: further implicating alpha-gal allergy. J Allergy Clin Immunol Pract 2019; 7:322.

McGill SK, et al. AGA Clinical Practice Update on Alpha-Gal Syndrome for the GI Clinician: Commentary, Clin Gastroenterol Hepatol, 2023, 21:891-896.

Thompson JM, et al. Suspected Alpha-gal Syndrome Cases-United States, January 2017-December 2022. MMWR Morb Mortal Wkly Rep 2023;72:815-20. 

Van Beusekom M. Research ties bites from 2 more types of ticks to red meat allergy. CIDRAP, March 20, 2025.

Saunders EF, et al. Alpha-gal Immunoglobulin E Seroprevalence Among Blood Donors — 10 States, 2024–2025. MMWR Morb Mortal Wkly Rep 2026;75:315–321.