What Is Alpha-gal Syndrome?
An unusual allergy
A tick-borne disease
Tenth most common
food allergy
A major drug allergy
A leading cause of anaphylaxis
Beyond allergy
Learn more
An unusual allergy
Alpha-gal syndrome (AGS) is a serious and sometimes life-threatening allergy to alpha-gal (galactose-α-1,3-galactose), a sugar found in most mammals. People with AGS experience IgE-mediated allergic reactions to products made from mammals and made with ingredients derived from mammals, including certain foods, medications, medical devices, personal care items, and household products. Reactions may also occur from topical exposure to mammalian fluids, such as blood or amniotic fluid.
While reactions to alpha-gal in parenterally administered medical products are immediate, reactions to alpha-gal in food are typically delayed, often occurring several hours after exposure.
Alpha-gal is found in:
- Non-primate mammals, their tissues, cells, and fluids
- Mammalian meats and organs (beef, pork, lamb, etc.)
- Milk and dairy products
- Gelatin/collagen
- Hundreds of mammalian byproducts
- Carrageenan
- Thousands of drugs and medical devices
- Many personal care and household products
- Lipid bioaerosols from cooking meat
A tick-borne disease
Alpha-gal syndrome is caused by tick bites. In the United States, the lone star tick causes most cases, although other tick species in the U.S. and around the world can also cause AGS.
In high-prevalence areas, AGS accounts for the bulk of the vector-borne disease burden, with annual cases greatly exceeding the total number of all other vector-borne diseases combined.
10th most common food allergy
More than half a million Americans are estimated to be affected by AGS, making it the 10th most common food allergy in the U.S.
A major drug allergy and a top cause of perioperative anaphylaxis
Unlike other food allergens, alpha-gal is also a significant drug excipient allergen and a leading cause of perioperative and drug-related anaphylaxis. For this reason, allergy to alpha-gal isn’t a simple food allergy and is classified as a syndrome.
The clinical risk is broad and poorly understood. Hundreds of thousands of drugs, biologics, and medical devices are mammal-derived or contain mammal-derived ingredients, and no comprehensive list exists. A recent search of the FDA’s DailyMed database found that over 64% of listed drugs—more than 230,000 products—contain mammal-derived or potentially mammal-derived ingredients, spanning common medications, vaccines, monoclonal antibodies, and numerous products used in perioperative settings.
Critically, some alpha-gal-containing medical products pose a greater risk to patients with alpha-gal syndrome than mammalian meat itself, making AGS a significant and underrecognized patient safety concern in surgical settings.
A leading cause of anaphylaxis
60 to 75% of people with AGS have life-threatening, anaphylactic reactions—a higher percentage than seen with any other food allergy, even peanut allergy. In high-prevalence areas, alpha-gal reactions can be a top cause of anaphylaxis, causing more anaphylaxis in some groups than all other food allergies combined. A number of fatalities have occurred.
In one study of people aged 9 and older in a high-prevalence area, AGS accounted for a third of all cases of anaphylaxis, more than all other food allergies combined.
Figure 1. Etiologies of anaphylaxis based on proposed “definitive cause.”
Alpha-gal, galactose-α-gal-galactose.
Source: Pattanaik D, Lieberman P, Lieberman J, Pongdee T, Keene AT. The changing face of anaphylaxis in adults and adolescents. Ann Allergy Asthma Immunol. 2018;121(5):594-597.
Beyond allergy
The impacts of alpha-gal syndrome extend well beyond allergic reactions. Associations have also been observed between AGS and the onset of mast cell disorders and chronic urticaria.
Emerging evidence suggests AGS may be an independent risk factor for atherosclerosis and cardiovascular disease.
Preliminary data suggest that in high-prevalence areas, AGS may be a significant and underrecognized driver of chronic disease—including irritable bowel syndrome and arthritis–and may contribute to a range of other adverse health conditions and outcomes.
Despite these serious and far-reaching impacts, AGS remains underrecognized and inadequately addressed in clinical care and public health policy.
Alpha-gal syndrome is associated with:
- Mast cell activation syndrome
- Chronic hives
- Rheumatological disorders
- IBS
- Atherosclerosis and cardiovascular disease
- Transfusion reactions
- Premature degeneration of bioprosthetic heart valves
Preliminary data also suggests that alpha-gal syndrome may play a role in some kidney issues.
The broader alpha-gal immune response has also been implicated in autoimmune disease.