Understanding Alpha-gal Syndrome and Its Growing Geographic Overlap With Lyme Disease
Learn about alpha-gal syndrome, a tickborne allergy to red meat, its causes, symptoms, testing, and relation to Lyme disease- as well as prevention tips and current research insights.
The Basics
Alpha-gal syndrome is a more recently identified (c. 2009) tickborne disease. It differs from Lyme disease, babesiosis, anaplasmosis and ehrlichiosis in that it is not a tickborne infection – it is a tickborne allergy. Alpha-gal syndrome is an allergy to red meat and other products containing alpha-gal, including dairy and gelatin for those with more sensitive allergy.
Alpha-gal syndrome’s best recognized cause is tick bites, and it has been described on 6 continents, with the culprit tick species varying across the globe. Lone star tick (Amblyomma americanum) bites are the primary cause of alpha-gal syndrome in the United States. Recently, rare cases linked to blacklegged and western blacklegged ticks (Ixodes scapularis and I. pacificus) have been reported in Maine, Washington state, and the upper Midwest, well outside of the lone star tick range (Thompson et al. 2023). Despite this early evidence that blacklegged ticks and western blacklegged ticks can cause alpha-gal syndrome, they are thought to be an uncommon cause given how few cases have been recognized in high-incidence Lyme regions, particularly of the northeastern United States.
The Timeline: tick bite to food allergy
It is not intuitive to connect how a tick bite can cause food allergy.
To begin with, a typical timeline of the development of allergy is as follows: a tick of a culprit species bites a human. (It is not yet known why some bites do and others do not cause alpha-gal syndrome.) Sometimes the tick bite that preceded new allergy is described as leaving an erythematous, inflamed, and itchy “bite site” lasting weeks. Many tick bites go unnoticed.
Weeks to months after the tick bite, a person who previously ate meat without incident has a meal containing red meat, such as a steak. However, they do not react right away. The allergic symptoms – which can include a combination of hives, facial and throat swelling, wheezing and difficulty breathing, vomiting and other gastrointestinal distress, and anaphylaxis – occur 2-6 hours after eating red meat.
The “classic” story of an initial reaction is someone who eats red meat for dinner, and then wakes up itching in the middle of the night, looks in the mirror, and is surprised to see hives and sometimes facial swelling. There are also less classic clinical presentations, such as people with isolated gastrointestinal distress who eat red meat frequently and may have a hard time connecting the two. Vegetarians and vegans who consume or are exposed to mammalian products may also manifest symptoms of alpha-gal syndrome. Tragically, the first case report of a death from alpha-gal syndrome has been recorded (Platts-Mills 2025).
The alpha-gal molecule and delayed reaction
Alpha-gal syndrome is an allergy to alpha-gal, which is a carbohydrate molecule. (Most food allergies are to proteins.) Human ancestors lost the ability synthesize alpha-gal tens of millions of years ago, but most mammals other than humans – including those that humans eat – do produce alpha-gal. Therefore, “red meat” – or meat from cows, pigs, sheep, deer, and other game – contains alpha-gal. (Fish and birds do not produce alpha-gal.) The alpha-gal carbohydrate in meat is attached to both fats and proteins. The fatty form, glycolipids, take time to be metabolized and enter the bloodstream. That’s why allergic symptoms often appear 2–6 hours after eating, rather than immediately.
In addition to mammals, ticks also have alpha-gal in their saliva, without ever biting a mammal. Why? One compelling explanation is molecular mimicry. Ticks have many ways of trying to disguise their bite to avoid being detected, so expressing alpha-gal may be one additional way to look like their hosts (deer, mice, and other mammals whose cells express alpha-gal). Of tick species in the United States, lone star ticks, blacklegged ticks, brown dog ticks (Rhipicephalus sanguineus) and the invasive Asian longhorned tick (Haemaphysalis longicornis) have been shown to have alpha-gal in their saliva.
Testing for alpha-gal syndrome
Only if you have allergic symptoms, or unexplained gastrointestinal symptoms, should you be tested for alpha-gal syndrome. The test for alpha-gal syndrome is a serum test for alpha-gal IgE. IgE is a type of antibody that the immune system produces in response to allergens. A positive does not necessarily mean you have the allergy. Instead, it shows that your body has made IgE antibodies against alpha-gal, a state called being “sensitized” to an allergen, in allergy terminology.
A high percentage of adult populations screened for alpha-gal IgE in areas with lone star ticks are sensitized to alpha-gal, in the realm of 20-30% and even higher in heavily tick-exposed populations such as forestry and outdoor workers. However, most sensitized individuals in groups that have been screened are “sensitized only” and do not report allergy symptoms.
Alpha-gal syndrome and Lyme disease
There is no established connection between alpha-gal syndrome and Lyme disease in the United States. That’s partly because lone star ticks are the primary cause of alpha-gal syndrome whereas blacklegged ticks transmit the Lyme bacteria. It is important to note that western Europe is different: there, a single tick species—Ixodes ricinus—can both trigger alpha-gal syndrome and transmit Lyme bacteria. Even there, however, being bitten by one of these ticks doesn’t mean a person will develop both conditions. A Swedish study (Tjernberg et al. 2017) found no link between Lyme disease history and having alpha-gal antibodies.
[Ixodes ricinus is commonly known as the castor bean tick or the sheep tick]
Considerations for Lyme-endemic regions of the United States
It is important to recognize that the lone star tick range is expanding, particularly northward and eastward, and prominently along the northeastern coastline. Lone star ticks are now well-established in eastern Long Island, where there are also blacklegged ticks and Lyme disease. Lone star ticks are also increasingly found on Martha’s Vineyard. They are considered an aggressive human-biting tick. Deer are an important host for lone star ticks, whereas white-footed mice (Peromyscus leucopus) are not. EPA-registered insect repellents such as DEET and picaridin for skin and clothing and permethrin for clothing and gear remain important for lone star tick bite prevention, as for blacklegged and other tick bites. An important distinction from Lyme disease is that alpha-gal syndrome can likely be caused by a tick attached for as little as a few hours. The metric of removing a tick within 24 hours, while good advice for Lyme disease, should therefore not be considered protective for alpha-gal syndrome.
Tick bite avoidance
Not only is avoiding tick bites important to avoid developing alpha-gal syndrome, but it remains important for those who have the allergy. Over time (years), some patients with alpha-gal syndrome who avoid tick bites have declining alpha-gal IgE levels that correspond to a remission of their allergy and the ability to reintroduce red meat into their diets. Reintroducing red meat is a very individualized decision to be made with a knowledgeable healthcare provider and incorporating safety considerations. If a patient returns to eating red meat, new tick bites could cause allergic symptoms to return.
Current unknowns and research questions
Much of what is currently understood about alpha-gal syndrome, outlined above, comes from excellent, collaborative research. Yet important questions remain:
- What percentage of people bitten by lone star ticks develop alpha-gal syndrome?
- What percentage of people sensitized to alpha-gal go on to develop alpha-gal syndrome?
- What genetic and immunologic factors determine whether someone sensitized to alpha-gal develops alpha-gal syndrome?
- Why are some ticks (i.e., lone star ticks) more effective in sensitizing to alpha-gal and causing alpha-gal syndrome than others (i.e., blacklegged ticks)?
- What compounds in tick saliva along with alpha-gal provoke the human immune system to produce allergic antibodies (IgE)?
- What aside from ticks (and possibly chiggers, and Ascaris roundworms) can sensitize a person to alpha-gal? (Stoltz et al. 2019, Murangi et al. 2022)
There has been differing evidence about whether the molecule alpha-gal is produced by the tick itself or is synthesized by bacteria that are part of the tick microbiome. In either case, scientists have asked whether bacteria living in ticks could affect the amount of alpha-gal produced in tick saliva (Kumar et al. 2022, Cabezas-Cruz et al. 2018).
New treatments and future directions
For patients suffering from alpha-gal syndrome, the mainstay of management is avoiding red meat and—for some—dairy and other ingredients containing alpha-gal. For those patients sensitive even to minor exposures to alpha-gal, there also now exists a medication called omalizumab that has been effective in decreasing symptoms. It is an anti-IgE monoclonal antibody, and so works not only for alpha-gal syndrome but for IgE-mediated food allergy more broadly. Omalizumab may also be appropriate for those with unavoidable occupational exposures, such as those working in kitchens with skin and fume exposures to meat, and those who birth animals or dress deer and may be exposed to large amounts of body fluids containing alpha-gal (Nuñez-Orjales et al. 2017).
For patients who crave red meat but are allergic, GalSafe® pork is made from a genetically modified pig that doesn’t express alpha-gal, and so can be consumed by patients with alpha-gal syndrome. The technology of gene-editing mammals could also lead to medical products like gelatin and heparin (a blood thinner) being made without alpha-gal. Although reactions to these products are rare, concerns about alpha-gal have complicated medical care for some patients.
Tick control strategies
New strategies to control lone star tick populations are needed, both environmental controls and interventions under study such as a universal tick vaccine. Alpha-gal syndrome has reanimated some of these goals, both through the threat of people no longer being able to eat meat and dairy; through a growing understanding of how ticks interface with the human immune system; and through geography, which unites a growing swath of the United States population in a campaign against ticks and tickborne disease.
Short and sweet
A simple way to explain alpha-gal syndrome to others is double delay, double avoidance. There is a delay of weeks to months from tick bite to the first allergic reaction, and there is a delay of hours from eating red meat to when allergic symptoms appear. The treatment for alpha-gal syndrome is to avoid red meat and avoid further tick bites.
References:
Madison Area Lyme Support Group 