Alpha-gal syndrome

Did You Know?

• Anaphylactic reactions occur in approximately 60% of afflicted individuals.
• AGS disproportionately affects people in their 40s and 50s, and 30–40% of patients have cardiac symptoms during reactions.

Prevalence

Alpha-gal allergy has been reported in 30 countries across all six continents where tick bites occur, with particularly high numbers in the United States and Australia. Prevalence correlates with the distribution of tick species known to carry the molecule, such as the Lone Star tick in the US and the paralysis tick in Australia. Alpha-gal has also been found in the saliva of Ixodes scapularis but not in Amblyomma maculatum. In the United States, data on AGS prevalence is limited because positive test results and clinical diagnoses are not required to be reported in federal public health statistics; only some states mandate reporting. Arkansas became the first US state to make AGS a reportable condition in September 2023, and by June 2026 thirteen states tracked positive tests. Australia had the highest rate of alpha-gal syndrome and tick paralysis worldwide as of November 2019. From 2010 through 2022, over 100,000 cases were diagnosed by a laboratory in the US, while the CDC’s national estimate totaled 450,000 cases, likely an underestimate due to underreporting and lack of provider awareness. A 2010–2018 study identified more than 34,000 suspected cases, and annual positive test results rose from 13,371 in 2017 to 18,885 in 2021. Virginia reported 14,000 positive cases from September 2025 to June 2026, ten times its rate of Lyme disease. AGS is more prevalent in the central and southern US, corresponding to the Lone Star tick’s range; in the Southern US allergy rates are 32% higher than elsewhere. Unexpectedly high rates in western and north-central areas suggest another tick species may spread the allergy, and cases have occurred in Hawaii where no associated ticks are found.

Deaths

More than ten deaths have been linked to alpha-gal reactions triggered by medications, though no reliable count of total fatalities exists. Because many doctors are unfamiliar with the condition, alpha-gal syndrome often goes unrecognized, and deaths are not captured in official health records. A study in North Carolina reviewed over one hundred medical visits by AGS patients, including 28 emergency room trips and two urgent care visits; less than 10% of those encounters led to a correct diagnosis or a proper referral. The first known U.S. death occurred in 2006 after a patient received the cancer drug cetuximab. Between 2010 and 2012, researchers estimated that roughly eight deaths in Italy and France were caused by anaphylaxis to cetuximab, with one additional unreported fatality. They noted that tick bites likely explain the uneven geographic distribution of these reactions. In 2021, a forensic investigation in South Korea confirmed that a fatal cetuximab reaction was due to alpha-gal syndrome. An Australian review identified two deaths from cetuximab before July 2022. In 2023, experts reported three cetuximab-related AGS deaths in Australia and eight elsewhere, for a total of eleven. A Washington, D.C., case report described three alpha-gal reactions in 2022 and 2023 from transfusing type B blood into a type O patient, including one death from Transfusion Related Alpha-Gal-Syndrome. A Kansas woman may have died from AGS in 2025 following heart surgery.

Sources of alpha-gal epitope

Galactose-alpha-1,3-galactose, known as alpha-gal, is a carbohydrate present in many natural and manufactured items. It occurs naturally in mammal-derived foods like beef, pork, lamb, venison, rabbit, gelatin, and milk. People with an alpha-gal allergy can safely eat reptile meat, insects, poultry, and seafood, which do not contain this molecule. Alpha-gal also appears in some seaweeds; carrageenan, a substance extracted from red algae, contains the alpha-gal epitope. Carrageenan is used as a gelling, thickening, and stabilizing agent, and to clarify beer, juice, and wine. It is sprayed on fruits and vegetables, applied to fish to retain moisture, and found in medications, medical products, personal care items, and household goods. Some reactions blamed on dairy may actually be due to carrageenan. Many medications include alpha-gal in inactive ingredients from mammals, such as gelatin, lactose, glycerin, magnesium stearate, and polysorbates. A 2023 report noted that over half of alpha-gal syndrome patients who reacted to medications had systemic or anaphylactic reactions. The condition can cause life-threatening intolerance to medicines, vaccines, antivenoms, infant formula, sutures, contact lenses, tattoo inks, and glycerin-based soaps and surfactants. Biologic therapies like cetuximab and ustekinumab have been linked to allergic responses in these patients.

Cause and mechanism

Alpha-gal syndrome is a unique allergy because it can cause anaphylaxis hours after exposure, unlike most food allergies. It is also the first food allergy linked to a carbohydrate rather than a protein. During a reaction, the body produces an overload of immunoglobulin E (IgE) antibodies. A natural human antibody called anti-gal specifically targets the carbohydrate structure known as the alpha-galactosyl epitope. This alpha-gal molecule occurs naturally in all mammals except catarrhines—apes, Old World monkeys, and humans. It is also present in the saliva of certain insects, including some tick species. People with type B or AB blood may have some natural protection because the type B antigen resembles alpha-gal.

The allergy typically develops after a tick bite. In the United States, the lone star tick (Amblyomma americanum) and the black-legged tick (Ixodes scapularis) are responsible. Other ticks linked to the syndrome include the European castor bean tick, the paralysis tick and Ixodes australiensis in Australia, Haemaphysalis longicornis in Japan, and an unidentified tick in South Africa, possibly Amblyomma hebraeum. Research using alpha-gal knockout mice has confirmed that lone star tick bites cause the condition. Larvae, nymphs, and adult ticks can all trigger it. Tick larvae are very small and often mistaken for chiggers when many bite at once. Cases have also been reported from true chiggers, mites, fleas, and hookworms.

When a tick bites, it injects alpha-gal into the skin. Recent studies show that lone star tick saliva contains alpha-gal and enters the bloodstream. Scientists have not yet identified the exact component in tick saliva that sparks the immune response. The immune system then releases a flood of IgE antibodies to fight this foreign sugar. After this sensitization, eating mammal meat containing alpha-gal can cause an allergic reaction. Only a small percentage of people—children or adults—develop a red meat allergy after a lone star tick bite.