Cases of red meat allergy, considered rare only a decade ago, are on the rise worldwide. Formally known as alpha-gal syndrome, the potentially life-threatening allergy is provoked by tick bites, becoming more severe the more times a person is bitten.

Although ticks have been around for ages, in the United States, alpha-gal syndrome was only first described in the medical literature in 2009, raising the question of whether the syndrome always existed under the radar or if the number of cases is actually growing.

Johanna Salzer, an epidemiologist working in the Centers for Disease Control and Prevention’s Division of Vector-Borne Diseases, thinks both are probably true. “This increase may be due to both more testing because of increased awareness by healthcare providers and patients, and a true rise in the number of people affected by alpha-gal syndrome,” she said.

According to Salzer, the growing geographical range of the lone star tick — the main tick species responsible for spreading alpha-gal to humans in the United States — could also contribute to the rise in cases. Warming temperatures are at least partly to blame for their pervasiveness.

“Changes in populations of animals that ticks feed on, like white-tailed deer on the east coast, have also contributed to changes in tick populations in some areas,” she noted.   

Michael Levin, professor and head of pediatric allergy training at the University of Cape Town, South Africa, has also seen his share of cases in South Africa. “The rural Eastern Cape, where people live in traditional homesteads with domestic animals, has such a high concentration of alpha-gal syndrome,” Levin told us.

“There is also evidence that animals carrying the tick are increasing their range, bringing ticks into contact with humans living in that wider geographical area,” he added.

Mysterious evolutionary loss of alpha-gal

Why some people develop alpha-gal allergy is linked to our evolutionary history. Most mammals harbor the sugar molecule galactose-α-1,3-galactose — alpha gal, for short — on their surfaces, but humans and great apes evolved without it at some point in time. Exactly when and why this happened is a mystery, but Salzer shared one theory.

“We do not really know why alpha-gal was lost in the human population, but a possibility is that a germ emerged that had alpha-gal, and humans that did not have it were able to better respond to this germ as something foreign to them,” she stated.

As a result, some people develop a sensitivity to alpha-gal upon repeated exposure, meaning their immune systems produce specific antibodies in response. When the antibody level becomes excessive — which is proportional to how often a person is exposed to alpha-gal — an allergic reaction can be triggered.

Scientists know that tick saliva containing alpha-gal causes the allergy, but there is a common misconception about where the alpha-gal comes from.

Alpha-gal produced in tick saliva

The circulating belief is that only ticks that have bitten a mammal first can provoke alpha-gal syndrome in humans, but Salzer says this is a misconception. “In fact, ticks produce the alpha-gal sugar molecule in their saliva, so larval tick bites can also cause alpha-gal syndrome,” she explained.

“One hypothesis about why ticks also have alpha-gal sugar in their saliva is that it may have evolved to help them resemble the animals they feed on, as a sort of chemical disguise to not get noticed,” she added.

She says that tick bites are the only known cause of alpha-gal syndrome in the United States, but other parasites have been associated with alpha-gal syndrome in different parts of the world. 

For example, Levin’s research has found that roundworm infection in the gut can stimulate alpha-gal sensitization. “But it is also possible that alpha-gal syndrome requires both sensitization to alpha-gal, as well as a second pro-inflammatory signal, perhaps due to components in tick saliva,” Levin added.

Both Levin and Salzer pointed out that many people are sensitive to the sugar without having alpha-gal syndrome because they have developed a tolerance, particularly those who live in regions with lone star ticks or areas with a high burden of parasitic infections.

For those who do develop an alpha-gal allergy, diagnosis can be difficult due todelayed onset of symptoms — which range from mild gastrointestinal discomfort to life-threatening anaphylaxis –– normally two to six hours after ingesting red meat or other product containing alpha-gal.

As a result, the allergic reaction might not be immediately associated with what that person ate hours before. Adding to the uncertainty, that person may not have even noticed or forgotten that they had been bitten by ticks, as not all bites are painful or itchy. 

Salzer says that preventing tick bites is the best defense, as alpha-gal syndrome can be provoked within a few hours of tick bite attachment. This is in contrast with Lyme disease, also spread by ticks, which takes over 24 hours to transmit to a host.

If a person suspects they have alpha-gal allergy, they should consult an allergist or other medical professional for testing and, if diagnosed, come up with a management strategy with their doctor.

But alpha-gal antibody testing should only be conducted if a patient has symptoms of allergy, Salzer stresses. “We do not want healthcare providers to misattribute symptoms to alpha-gal syndrome, and we do not want people to eliminate protein sources from their diets if they do not have allergy,” she stated.   

Preventative measures are key

Although there is currently no treatment for the allergy, avoiding alpha-gal in the diet is key to preventing a bad reaction. This includes all red meats, such as beef, lamb, and pork, and possibly dairy, gelatin, and meat broth, as some patients also react to these animal-derived products.

“It is also important to know that medical products can contain animal ingredients, like gelatin capsules of certain pills,” Salzer cautioned. She also advises patients to consult with their doctor to see if an epinephrine auto-injector (EpiPen) is needed in case of accidental exposure.

Despite the lack of treatment options, the good news is that a patient with alpha-gal syndrome may develop a tolerance to alpha-gal if they can avoid subsequent tick bites. This is because alpha-gal specific antibody levels decrease over time.

“For some patients, this decrease in the allergic antibody has allowed them to reintroduce red meat and to tolerate it symptom-free,” said Salzer. 

If spending time outdoors in wooded areas where ticks thrive, wearing clothes that minimize skin exposure and treating those clothes with approved insect repellents are simple precautionary measures. Thoroughly checking the body for ticks after going indoors is also important. The CDC’s checklist for preventing tick bites can be found here.

Reference: Mengyuan Zhan, Jia Yin, Tengda Xu, and Liping Wen, Alpha-Gal Syndrome: An Underrated Serious Disease and a Potential Future Challenge, Global Challenges (2024). DOI: 10.1002/gch2.202300331

Feature image: Marino Linic on Unsplash