Alpha-gal Syndrome (AGS)
Alpha-gal syndrome (AGS) is an allergic condition in which people are allergic to alpha-gal, a sugar found in the tissues of all mammals except humans and other primates. It is also known as mammalian meat allergy, alpha-gal allergy, red meat allergy, and tick bite meat allergy.
When people who are allergic to alpha-gal eat beef, pork, lamb, or meat from other mammals, they have an allergic reaction that causes a range of symptoms, including a rash, nausea, vomiting, and diarrhea. Symptoms usually occur three to six hours after eating. In some cases, people may have an immediate life-threatening anaphylactic reaction that requires medical attention.
Alpha-gal is also found in many other foods, medications, and medical products made using materials from mammals. Dairy products, for instance, contain alpha-gal. Many other foods and medications contain gelatin, which is often made from mammal-derived collagen or other materials that come from animals. Alpha-gal is also found in other medical products, including snake anti-venoms and prosthetic heart valves taken from cows or pigs. People with AGS have varying degrees of allergic reactions to these foods, medications, and medical products. Some people may not experience any reaction when exposed to these foods and products, while others may have allergic reactions ranging from mild to severe.
People of any age can have AGS, and the condition has been reported in Africa, Asia, Australia, Europe, and North America. In the United States, AGS is primarily caused by the lone star tick, a tick species that inhabits the eastern, southeastern, and south-central states. The lone star tick can transmit alpha-gal to people through its saliva, which can trigger the immune system to produce antibodies against alpha-gal, causing AGS. (In other parts of the world, other tick species have been associated with AGS.) While the number of cases in the U.S. is not known, a 2023 study identified just over 110,000 suspected cases between 2010 and 2022. That study estimates that there may have been up to 450,000 cases of AGS between 2010 and 2022, with many cases undiagnosed.
While there is no treatment for AGS, people with an allergy can prevent allergic reactions from occurring by avoiding meats and other products that contain alpha-gal. Over time, however, the levels of antibodies that cause the allergic reaction decline, meaning some people may eventually be able to consume alpha-gal-containing meats and products without an allergic reaction.
What is alpha-gal syndrome?
AGS is an allergy characterized by an allergic reaction to a carbohydrate called galactose-α-1,3-galactose, also known as alpha-gal. Alpha-gal is found in all non-primate mammals. In people with AGS, the consumption of beef, pork, lamb, venison, and other mammalian meat—all of which contain alpha-gal—causes an allergic reaction that can be severe and life-threatening. Some people with AGS may also have an allergic reaction after eating other foods and products that contain alpha-gal, including dairy products and some medications.
In the U.S., the lone star tick is the main cause of AGS. Unlike other diseases associated with ticks, such as Lyme disease and Powassan disease, AGS is not caused by a bacterial or viral infection. Lone star ticks can have alpha-gal in their guts and saliva.
When a lone star tick bites someone, it can pass alpha-gal to the person in its saliva. This can trigger the individual’s immune system to respond by producing antibodies (known as immunoglobulin E, or IgE) against alpha-gal. This is known as sensitization because the immune system is now sensitive to alpha-gal. When a person sensitized to alpha-gal consumes or is exposed to alpha-gal again—for instance, by eating mammalian meat, IgE binds to the alpha-gal, which, in turn, prompts the immune system to release chemicals that cause an allergic reaction. (While mammalian meat and other products contain alpha-gal, consuming them does not cause AGS.)
People with AGS need to avoid eating meat from mammals to prevent allergic reactions from occurring. They can, however, continue to eat chicken, turkey, fish, and other non-mammalian meats because those meats do not contain alpha-gal.
Over time, the level of IgE antibodies against alpha-gal decreases, and, as a result, some people with AGS may again be able to eat beef, pork, and other mammalian meats and other products that contain alpha-gal without having an allergic reaction. Additional lone star tick bites (or bites from other species of ticks associated with AGS in other parts of the world) can cause IgE antibody levels to rise or prevent them from decreasing.
What are the symptoms of alpha-gal syndrome?
AGS symptoms typically begin three to six hours after eating meat, dairy, or other products made from mammals. However, if medications that contain alpha-gal are given intravenously (via an IV), symptoms may begin immediately. Symptoms of alpha-gal syndrome include:
- Hives or itchy rash
- Nausea or vomiting
- Heartburn or indigestion
- Shortness of breath
- Difficulty breathing
- Drop in blood pressure
- Swelling of the lips, tongue, or eyelids
- Dizziness or faintness
- Severe stomach pain
Symptoms can range from mild to severe and include anaphylaxis (also called an anaphylactic reaction), an immediate life-threatening allergic reaction that requires urgent medical attention.
How is alpha-gal syndrome diagnosed?
To diagnose AGS, your doctor will review your medical history, conduct a physical exam, and order one or more diagnostic tests.
Your doctor will ask you about your symptoms, including when they began and whether you have a history of tick bites, any reactions you might have had to a tick bite, or if you’ve been outdoors in areas where ticks are known to live. During a physical exam, your doctor will examine your skin, check your blood pressure, and listen to your lungs using a stethoscope to check for symptoms that may be caused by a reaction to alpha-gal.
To confirm a diagnosis, your doctor may order blood tests to check for the presence of antibodies against alpha-gal and/or against specific types of meat, such as beef or pork.
How is alpha-gal syndrome treated?
While there is no treatment or cure for AGS, treatments are available for the allergic reactions, including anaphylaxis, that people with the condition can experience. People with AGS can also prevent allergic reactions by avoiding exposure to foods and products that contain alpha-gal. Some strategies that may be recommended include:
- Treatments for allergic reactions caused by alpha-gal exposure. These treatments include epinephrine (also known as adrenaline), antihistamines, and oral corticosteroids. People with a known allergy to alpha-gal should keep self-injectable epinephrine and antihistamines accessible in case of an allergic reaction.
- Avoidance of additional tick bites. People in the U.S. who are allergic to alpha-gal should avoid new bites from the lone star tick because they increase the level of IgE antibodies against alpha-gal, thereby increasing sensitivity to alpha-gal. The level of these antibodies typically declines in individuals who avoid further tick bites, meaning that over time, some people can once again consume meat or other alpha-gal-containing products without having an allergic reaction.
- Avoidance of meat, dairy products, and other products that contain alpha-gal. Individuals diagnosed with AGS should completely avoid the consumption of mammalian meat, including beef, pork, lamb, venison, goat, and rabbit.
Many medications are made from materials derived from mammals and, therefore, contain alpha-gal. People with AGS should avoid these medications and medical products, including:
- Cetuximab (a chemotherapy drug)
- Gelatin-based colloid plasma substitute (used to treat hypovolemia, a condition in which there is a decrease in the volume of blood circulating in the body)
- Thyroid hormone supplements derived from cows or pigs
- Anti-snake venom therapy derived from horses or sheep
- Avoid dairy products. Because around 5% to 20% of people with AGS have allergic reactions to dairy products (which contain alpha-gal, though at lower levels than meat), health care providers may also recommend that some individuals with AGS avoid consuming dairy products, in particular those whose symptoms are not adequately controlled through meat avoidance alone.
- Avoid food or medicines derived from mammals. A small percentage of people with AGS also have allergic reactions after consuming food or medications made from materials derived from mammals, or from using medical products that contain alpha-gal. People in this group may be advised to avoid:
- Heparin (a blood thinner)
- Pancreatic enzymes (derived from pigs)
- Gel capsules
- Vaccines that contain gelatin (such as the measles, mumps, and rubella [MMR] and yellow fever vaccines)
- Prosthetic heart valves from cows or pigs
- Foods that contain gelatin, such as marshmallows, jellybeans, and Jell-O (and other gelatin desserts)
Many other products and medications may also contain alpha-gal. People with AGS should consult with their health care provider about which foods or other products they should avoid.
What is the outlook for people with alpha-gal syndrome?
While there is no cure for AGS, the levels of antibodies against alpha-gal decrease over time, and some people are again able to eat meat and other alpha-gal-containing products without an allergic reaction. Your doctor will discuss your history of reactions and monitor blood tests to help determine whether alpha-gal-containing foods can be eaten again. Your doctor can also help safely determine whether the alpha-gal syndrome has been outgrown through a monitored reintroduction in the clinic.
What makes Yale unique in its approach to treating alpha-gal syndrome?
“Yale Allergy & Immunology is a regional leader in the diagnosis and management of alpha-gal syndrome,” says Yale Medicine allergist and immunologist Elise Liu, MD, PhD. “Our physicians and nurses are highly knowledgeable and on the cutting edge of advancements in alpha-gal syndrome. In addition, Yale Allergy & Immunology offers individualized care for every patient. We aim to address each area that alpha-gal syndrome intersects with health and well-being to help our patients manage this condition optimally.”