What is Alpha-gal Syndrome?

The Mammalian Meat Allergy

What Is Alpha-gal Syndrome (AGS)?

The term α-Gal syndrome describes a novel IgE-mediated immediate-type allergy to the disaccharide galactose-α-1,3-galactose (α-Gal). Its classification as a syndrome is proposed on the basis of its clinical relevance in three different elds of allergy: food, drugs, and tick bites.

Fischer, et al (24)

Alpha-gal syndrome (AGS)

also known as mammalian meat allergy, is an allergy involving an IgE antibody response to galactose-α-1,3-galactose (1). This sugar, commonly known as alpha-gal, is found in all mammals except for Old World monkeys, apes, and humans (99), as well as some other organisms. The onset of AGS is associated with tick bites (3).

Alpha-gal syndrome was first described in 2009 (1). It is poorly understood within the medical community because of its recent discovery and its varied and atypical presentation. Reactions to alpha-gal are often severe and sometimes fatal. They can be immediate, as with hypersensitivity reactions to injected drugs, or delayed by 2 to 10 hours or more, as is typical after consumption of mammalian meat (118). Delayed-onset reactions often occur in the middle of the night (1).

Alpha-gal allergic reactions can occur after exposure to:

  • Mammalian meats, organs, and blood (57)
  • Dairy products, gelatin, and other foods derived from mammals (57)
  • Foods that contain mammalian byproducts (57)
  • Drugs, medical products, personal care, household and other products with mammalian ingredients (57)
  • Products containing carrageenan, which isn’t from a mammal, but which contains the alpha-gal epitope (54,57)
  • Flounder eggs (26)

Symptoms→

Diagnosis→

Management→

Alpha-gal

Galactose-α-1,3-galactose (alpha-gal or α-gal) is a disaccharide sugar.

  • Alpha-gal is a common component of mammalian glycolipids and glycoproteins and is found in the cells, tissues, and fluids of all mammals except for Old World monkeys, apes, and humans (58,70,93,94,95,96,97).
  • Some bacteria, protozoa (58), invertebrates (73), fungi (such as aspergillus) (73), and red algae (71) (including those used in the manufacture of carrageenan) (54), also express alpha-gal.
  • Many viruses incorporate alpha-gal into the glycoproteins of their envelopes (58).
  • Numerous human pathogens express alpha-gal (58).
  • Most non-mammalian vertebrates do not normally express alpha-gal, although it is found in cobra venom (58, 72) and the eggs of some teleost fish (including flounder) and amphibians (26,58,74). There are other exceptions as well (58,75).
  • Unlike proteins, alpha-gal is not denatured at normal cooking temperatures (70).

A Paradigm-Shifting Allergy

AGS differs from typical allergies in significant ways:

  • AGS is associated with tick bites (3).
  • It is one of only two carbohydrate allergies that cause life-threatening reactions (4).
  • Lipids, in addition to proteins, are an important source of the allergen (100).
  • Its presentation is atypical and includes delayed-onset reactions that can occur 2-10 hours or more after exposure, often in the middle of the night (1,5,6).
  • Reactions do not occur after every exposure or follow an obvious pattern. This lack of consistency has been described as “almost a diagnostic hallmark” by experts (57).
  • Co-factors such as alcohol consumption and exercise can dramatically impact the severity of reactions or whether they occur at all (22,23,57).
  • In 3-20% of cases, patients report gastrointestinal symptoms alone, without other symptoms. Prior to diagnosis, many patients are misdiagnosed with IBS or other GI conditions (57).
  • AGS is associated more with adults than children, and onset in adults and older children who previously tolerated red meat is common (57).
  • Hunters, foresters, and other populations with high exposure to ticks are more at risk of developing AGS (57,59,69,98). In some regions, twenty times as many people living in rural areas may be sensitized than people living in nearby urban areas (98).
  • The allergy component of AGS is only one dimension of a complex immune response that may have other health implications (7). Conditions tentatively linked to the alpha-gal immune response include some autoimmune diseases (7), arthritis (60), and atherosclerosis (79,80).

“Activity, alcohol consumption, and exercise can have profound influence on reactivity. Some patients appear to have reactions that require co-factors such that they can tolerate exposures in isolation; consistent with a diagnosis of co-factor dependent-AGS.” (57)

Dr. Scott P. Commins, MD PhD

University of North Carolina

“Unlike more traditional food allergies where consumption of an allergen produces symptoms within minutes, AGS reactions typically occur 3-8 hours after eating. Thus many patients fail to consider food as a possible trigger and many healthcare providers do not routinely recognize the characteristic delay–both issues can prolong tie to reach a diagnosis.” (57)

Dr. Scott P. Commins, MD PhD

University of North Carolina

“While GI complaints are not uncommon as part of an allergic reaction, 3-20% of patients with AGS report abdominal pain, nausea, emesis, diarrhea, or heartburn in isolation of cutaneous, cardiovascular or other signs/symptoms.” (57)

Dr. Scott P. Commins, MD PhD

University of North Carolina

“…there are also patients who have episodes of abdominal pain without any skin involvement. Those cases are a problem because the possibility of food allergy is not obvious, and they can be severe… Other diagnoses that arise less commonly are arthritis and chronic pruritis. Distinguishing [AGS] from chronic hives can be challenging.” (6)

Thomas Platts-Mills, MD

University of Virginia

An Emerging Epidemic

A Growing Threat

As tick populations swell and their ranges expand (3,9,10,15) the number of people being diagnosed with alpha-gal syndrome is rising (8).  Models suggest that this will continue (10,15).

  • AGS is already a common allergy in some regions of the world, including the U.S. (11), where the number of diagnosed cases has risen from 12 in 2009 to over 34,000 in 2019 (63).
  • The primary U.S. lab testing for alpha-gal IgE, ViraCor Eurofins, reported over 14,500 positive test results in a recent twelve-month period (81).
  • In populations with high exposure to ticks, 15-35% of individuals can be sensitized to alpha-gal (57). Even for people without the clinical symptoms of AGS, alpha-gal sensitization could be a risk factor for coronary artery disease (79,80).
  • In some areas, including much of the southeastern U.S., up to 3% of the population is estimated to have clinical AGS with anaphylactic reactions (57,61). The vast majority are undiagnosed or misdiagnosed with other illnesses.
  • People in rural areas and others in frequent contact with ticks, including foresters, hunters (57,59), loggers, and people with outdoor hobbies (15) are especially at risk.
  • AGS is the leading cause of adult-onset food allergy and anaphylaxis throughout the South and much of the eastern U.S. (12).

Source: Olafson, P. Ticks and the mammalian meat allergy. USDA Beef Research, (2015)

Source: Bianchi J, Walters A, Fitch ZW, Turek JW. Alpha-gal syndrome: Implications for cardiovascular disease. Global Cardiology Science and Practice. 2020 Feb 9;2019(3).

At a threshold for positivity of 0.35IU/ml, up to 9% of people sensitized to alpha-gal have clinical alpha-gal syndrome with anaphylactic reactions after eating mammalian meat or organs (59). At the lower threshold for positivity of 0.1IU/ml, as few as 1% of people sensitized to alpha-gal have clinical alpha-gal syndrome (57). In populations with high rates of infection with endoparasites, sensitization to alpha-gal may be more common but less associated with clinical symptoms (18).

“The reported prevalence of individuals in the United States with elevated allergen-specific titers of anti-gal IgE (i.e. allergen positive) has been reported to be in the range of 8% to 46%, with highest prevalence within the geographic distribution of the Lone Star tick. Similar prevalence rates have been reported in other regions around the world.”

“Children within the geographic distributions of certain ticks are projected to have allergen positive prevalence comparable to the adult population. As one might expect, hunters and forest service workers have been reported to have a prevalence that is more than twice that of the general population. It appears that the prevalence of AGS equates to 10% of the allergen-positive population. Thus, in the southeastern United States, approximately 3% of the general population exhibits anaphylaxis after consumption of mammalian meat.” (61)

John Bianchi

Revivicor

A Leading Cause of Anaphylaxis

  • Roughly 60% of people with AGS have anaphylactic reactions (24,78,87,88,89, 119) and 30-40% have cardiac and respiratory symptoms (90).
  • In one recent study of anaphylaxis, AGS was found to be the number one trigger, accounting for 33% of cases with a definitive cause. The number two cause was all other food allergies combined at 28% (44).
  • In the same study, recognition of AGS led to a reduction in the percentage of anaphylaxis cases without a definitive cause from 59% to 35% of total cases. (44)
  • In a second study, nine percent of all patients referred with unexplained anaphylaxis were found to have AGS (62).

Figure 1. Etiologies of anaphylaxis based on proposed definitive cause.Alpha-gal, galactose-a-1,3-galactose.

Source: Pattanaik D, Lieberman P, Lieberman J, Pongdee T, Keene AT. The changing face of anaphylaxis in adults and adolescents. Annals of Allergy, Asthma & Immunology. 2018 Nov 1;121(5):594-7.

A Lack of Physician Awareness

  • Due to its recent discovery, its unusual presentation, and lack of physician awareness, AGS is underdiagnosed and often misdiagnosed (13,14,57).
  • Diagnosis tends to be patient-driven, even in areas where AGS is prevalent (14).
  • Reports of occurrence are strongly influenced by the efforts of individual research groups and clinicians (15).
  • Many people with AGS who only have GI symptoms have had a colonoscopy, endoscopy, and/or cholecystectomy performed before being diagnosed (7).
  • In populations with high exposure to known vectors, AGS should be ruled out in cases of unexplained urticaria, angioedema, recurrent anaphylaxis, GI symptoms (7,82,83,84) and even arthritis (60).

Source: Flaherty MG, Kaplan SJ, Jerath MR. Diagnosis of life-threatening alpha-gal food allergy appears to be patient driven. Journal of primary care & community health. 2017 Oct;8(4):345-8.

Source: Flaherty MG, Threats M, Kaplan SJ. Patients’ Health Information Practices and Perceptions of Provider Knowledge in the Case of the Newly Discovered Alpha-gal Food Allergy. Journal of Patient Experience. 2020 Feb;7(1):132-9.

How Do You Get Alpha-gal Syndrome?

  • Alpha-gal syndrome is associated with the bite of certain species of ticks. In different parts of the world, different tick species are implicated (15).
  • In the United States, the Lone Star Tick (Amblyomma americanum) is thought to be the primary cause of AGS (16), based geographical range and tick salivary factors (57).
  • The Asian Longhorned Tick (Haemaphysalis longicornis), recently introduced in the U.S., is known to trigger AGS in Asia (19). As of yet, it has not been tied to any cases in the U.S.
  • Alpha-gal has been found in the saliva of Black-Legged Ticks (Ixodes scapularis) (8). It is possible that Black-legged Tick bites may trigger AGS, as do other species in this genus, but this has yet to be demonstrated.
  • The Cayenne Tick (Amblyomma cajennense), which is found in southern Texas and Florida (64), has been linked to cases of alpha-gal syndrome in Central America (65).
  • Preliminary data suggests that exposure to Ascaris lumbricoides roundworms may play a role in both sensitization to alpha-gal and development of alpha-gal syndrome (106).
  • Limited data suggests that bee and wasp stings can cause a rise in alpha-gal IgE, but it has not been shown that they can drive the initial alpha-gal IgE response (57).
  • It is likely that additional tick species (8), possibly other ectoparasites (like chiggers (17) and mites (66)) and endoparasites (3,15,18) may be able to sensitize people to alpha-gal. Some may cause levels of sensitization too low to cause clinical reactions (5) and others likely induce full-blown AGS with anaphylactic reactions.
  • Only a small percentage of people who are bitten by ticks associated with AGS actually develop clinical symptoms (6).
  • Even if you have been bitten by ticks before and did not develop AGS, a future bite could trigger it (3).
  • Repeated tick bites are associated with a rise in alpha-gal IgE (20).
  • Multiple tick bites are associated with the onset of AGS (3). Many patients report that they were bitten by ticks for many years, and then after being bitten by multiple ticks at once, they developed alpha-gal syndrome.

Ticks and Alpha-gal Syndrome→

Avoiding
Tick Bites→

What to Do If You Are Bitten by a Tick→

What Is Alpha-gal Found In?

Alpha-gal in Foods, Drugs, Medical and Other Products

Primary Sources of Alpha-gal in Food, Drugs, and Other Products

Mammals

Mammals are the primary source of exposure to alpha-gal.

  • Alpha-gal is found in the meat, organs, tissues, cells, and fluids of all mammals except for humans, great apes, and Old World monkeys (1).
  • Alpha-gal is also found in products made from mammals or that contain ingredients made from them (6,57).

Flounder eggs

The eggs (roe) of some flounder have been found to contain alpha-gal, and can cause severe reactions in people with AGS (26, 104). See more information below. 

Red Algae

Many red algae make carrageenan, which contains the alpha-gal epitope (54).

What Is a Mammal?→

“Alpha-gal or similar epitopes are ubiquitously expressed on many bacteria, fungi and parasites, as well as in all mammals 97 except for old-world primates and humans ” (122)

Hils, et al.

Other Organisms That Express Alpha-gal

A variety of organisms express alpha-gal, sometimes only in specific tissues.  For most of these, there is a lack of evidence as to whether they are associated with reactions in people with alpha-gal syndrome.

  • Some fish eggs, in addition to flounder eggs (see above) (58,74,104)
  • Green Sea Turtles express high levels of alpha-gal epitopes (108)
  • The ocular tissue of some non-mammalian vertebrates (105)
  • Cobra venom (58, 110)
  • Many invertebrates, including some ticks (8), mosquitoes (111), and helminths (worms) (106)
  • Some human pathogens, such as those that cause malaria, leishmaniasis, and Chagas disease (58).
  • Some fungi, including
    • Aspergillus mold (107). Whether people with AGS are more likely to have mold allergies is unknown.
    • Schizosaccharomyces pombe (112) –yeast used to make millet beer (pombe) in East Africa
    • There is no evidence of alpha-gal in mushrooms that we commonly eat, and people with AGS usually tolerate mushrooms.
  • Many protozoa (58)
  • Many bacteria, including those that live in our gut (58)
  • Many viruses, depending on the host they are incubated in (58)

Alpha-gal in Foods

Mammal-Derived Foods and Food Ingredients

Mammal-derived food and food ingredients include, but are not limited to, the below. 

Mammalian meat, organs, and other parts of mammals

These include some of the riskiest sources of alpha-gal. Examples include:

  • Mammalian meats (1), such as beef, pork, lamb, bison, venison, goat, horse, rabbit, squirrel, kangaroo, antelope, buffalo, camel, guinea pig, bats, whales, etc.
    • If you are not sure which animals are mammals, there is a guide here.
  • The internal organs of mammals, like liver (21), lung, heart, intestines (tripe), sweetbreads, and kidneys (6,57)
    • Internal organs can contain even more alpha-gal than meat  (22,23,24,25,26,27,94).
    • Some people who do not react to meat react after eating organs, like pork kidneys (24,59).
  • Mammalian gut sausage casings
    • Even turkey and chicken sausages often have these (6,57).
    • Removing the casing from chicken or turkey sausages and then eating the sausage without the casing is not advised, as this can lead to severe reactions. 
  • Mammalian fat, like lard, tallow, and suet
    • Mammalian fat is often in cooked foods, such as sauces, pastries, pie crusts, tortillas, tortilla chips, refried beans, baked beans, vegetable dishes, mashed potatoes, and desserts.
    • Some baking mixes (like Jiffy Corn Muffin Mix) contain lard.
    • Beef fat is often added to fry oil to enhance flavor (6,57).
  • Bones and bone marrow
  • Testicles (Rocky Mountain or prairie oysters)
  • Mammalian collagen (e.g. beef collagen sausage casings) (6,57)
  • Meat broth, bouillon, and stock (6,57)
  • Gravy (6,57)
  • Mammalian blood, found in soups, black pudding, blood sausage, blodplättar, and other foods
  • Meat extracts, like Bonox and Bovril
  • All other mammalian body parts, organs, tissues, cells, and fluids, such as tendons, brain, heart, nerves, skin, mammalian bile (Papait seasoning), and the products that contain them.

Most of the foods on this list should be avoided by everyone with alpha-gal syndrome. Many of us need to avoid all of them.

Rennet

Rennet is a complex set of enzymes that is used in the manufacture of some foods, such as cheese. Most rennet is extracted from the stomachs of ruminant mammals, although sometimes vegetable and microbial rennets are used. Some people with AGS can eat dairy products, as long as they don’t contain rennet from mammals.

Milk, other dairy products, and foods that contain them as ingredients (1,6,57,115)

Ten to thirty-three percent of people with AGS react to dairy products, especially those high in fat, like ice cream (6,57,85). A list of dairy products can be found here.

Gelatin and foods that contain gelatin (6,27,28,57)

Fewer than 10% of people with AGS react to gelatin in foods, although many more may have severe reactions after other types of exposure to gelatin, such as the intravenous administration of gelatin-based plasma volume expanders or gelatin-containing vaccines administered via intramuscular injections (6,57).

Natural flavors or flavorings

These are often beef or pork (57) and need to be avoided by many people with AGS. To find out whether the “natural flavors” in a product are derived from a mammal, contact the manufacturer. However, in the U.S., manufacturers are under no legal obligation to disclose the identity of ingredients that they call “natural flavors or flavorings.” Often, when asked, they will not disclose whether are derived from mammals or not.

Mammalian byproducts

An untold number of foods, especially processed foods, contain mammalian byproducts. There are hundreds of these byproducts often with obscure names, like oleic acid and monoglycerides. As of now, there is no comprehensive list of mammalian byproducts added to food in the U.S., much less information about their alpha-gal content. Most people with AGS do not react to mammalian byproducts in food, but some do (6,57), and severe reactions have documented (29). Some mammalian byproducts may not contain alpha-gal at all. Further research is needed to determine alpha-gal content and safety of mammalian byproducts for people with alpha-gal syndrome (6,57). See our guide to mammalian byproducts here.

Cross-contamination

Some people with AGS react if their food is cross-contaminated by foods that contain alpha-gal, for example, if their poultry or seafood is cooked on a grill used for red meats (57).

Flounder Eggs

The eggs (roe) of some flounder have been found to contain alpha-gal, and can cause severe reactions in people with AGS (26, 104).

  • The meat of flounder does not seem to contain alpha-gal or cause reactions in people with AGS (104)
  • There is no evidence that other commonly consumed fish eggs (salmon, herring, flying fish, caviar) contain alpha-gal, although its possible that some less commonly consumed fish eggs might, as alpha-gal has been found in the eggs of other teleost (bony) fish (58,74).

Carrageenan in Food

  • The food additive carrageenan is made from red algae, not mammals, but contains the alpha-gal epitope (54).
  • At least 1-2% of people with AGS report that they react to carrageenan (57).
  • Some people with AGS report severe carrageenan reactions with rapid onset.
  • Read people with AGS describe their reactions to carrageenan here.

Carrageenan

a guide for people with alpha-gal syndrome→

Foods that can contain carrageenan include, but are not limited to, the below. 

Foods that can contain carrageenan

  • Dulse (Irish Moss, Sea Moss)
  • Many dairy products including ice cream; milk shakes, like Dairy Queen blizzards; yogurt; flavored, evaporated, and condensed milk; whipped topping; cheese; and sour cream (76)
  • Many dairy-free substitutes (57)
  • Desserts, including custard, flan, pudding, mousse, sorbet, gelato, and gel desserts (76,77)
  • Drink mixes, such as powdered lemonade (77)
  • Juice (76,77)
  • Ready to spread icing (76,77)
  • Jams and jellies (76,77)
  • Candy (76,77)
  • Salad dressing, mayonnaise, and relishes (77)
  • Poultry and poultry products (77)
  • Drinks, such as beer and juice clarified by carrageenan  (77)
  • Seafood, such as fish treated with carrageenan to improve moisture retention  (77)
  • Infant formula  (77)
  • Tofu (77)

Carrageenan as a processing agent

When carrageenan is used as a processing aid, for example when it is used to clarify beer and juice, as a spray on fresh cut fruit, or on fish to aid in retention of moisture, manufacturers are not required to list it on the label.

Other edible red seaweeds

As many red seaweeds contain carrageenan (71), it’s possible that some other forms of edible red algae may also contain the alpha-gal epitope.

Other Foods That May or May Not Be a Source of Alpha-gal

Limited data and/or anecdotal evidence suggest that some foods that do not obviously contain mammal or red algae derived ingredients can cause reactions in some people with AGS for reasons that aren’t clear. These include:

  • Possibly some other types of edible fish roe (in addition to flounder eggs) (58,74), although as far as we know, there is no evidence that salmon roe, flying fish roe, herring roe, or caviar are a problem.
  • Canned tuna (6)
  • Koji is made from aspergillus (108), which expresses alpha-gal (107).
    • There is a lack of data as to whether koji can cause reactions in people with AGS, but most of us seem to tolerate products like miso and soy sauce that are made from it.

More Information

Food: First Steps

a guide for people with alpha-gal syndrome→

Cross-contamination

a guide for people with alpha-gal syndrome→

Gelatin

a guide for people with alpha-gal syndrome→

Carrageenan

a guide for people with alpha-gal syndrome→

Mammalian Byproducts

a guide for people with alpha-gal syndrome→

Alpha-gal in Drugs and Medical Products

“Due to the parenteral route of administration, allergists consider alpha-gal-containing drugs even more dangerous for allergic patients than mammalian meat.” (91)

Jörg Fischer, et al.

Mammal-Derived Drugs, Medical Products, and Ingredients 

Note:
• The
risks associated with the use of different medical products that contain mammal-derived ingredients are highly variable and poorly studied.
• There is no data on the risk of reaction associated with many products on this list. They included based on being derived from mammals or containing ingredients derived from mammals. See papers cited for more information.
• Work with your healthcare providers to weigh the relative risks and benefits of using or not using individual medical products that may contain alpha-gal. 

Drugs, medical products, and ingredients used in them that may contain mammal-derived materials or ingredients include, but are not limited to, the below. 

  • Cetuximab (a drug that played a role in the discovery of AGS) (6,30,31,57)
    • Cetuximab has caused fatal reactions in people with AGS (86).
  • Other monoclonal antibodies (mAbs) produced in non-primate mammalian cell lines (6,57)
    • Both abatacept (Orencia) (57) and infliximab (Remicade) have been associated with reactions (6,67)
    • Evidence for alpha-gal expression on most other mAbs is minimal (6,57), but expert opinion is to proceed with caution on first-dose of any mAb produced in a mammalian cell line (57).
  • Pancreatic enzyme replacements, such as pancrealipase and other enzyme replacements (e.g. Viokase, Pertzye, Zenpep (Allergan), Creon)(6,36,57,103) and Pancreatin (Now Foods, Bloomingdale, Ill)– an over-the-counter dietary aid (103).
  • Thyroid hormone replacements, including Armour Thyroid (Allergan) (57,103)
  • EnteraGam (Entera Health, Cary, NC), a bovine immunoglobulin and immunoprotein isolate intended for the management of irritable bowel syndrome and inflammatory bowel disease (103)
  • Estrogen therapy drugs that contain estrogen derived from horse urine, e.g. Premarin, Prempro
  • Heparin, including low molecular weight heparin such as enoxaparin (Lovenox)(57).
    • Dr. Scott Commins reports: “Importantly, we have not had issues with routine heparin prophylaxis for deep venous thrombosis (DVT) and our experience suggests this can be safely administered for the over- whelming majority of patients with AGS. There are, undoubtedly, exceptions that will require alternate forms of DVT prophylaxis. Heparin-based reactions that are much more common include those clinical scenarios where heparin is given at high doses for more complete anti-coagulation, such as during heart catheterization, valve procedures, and extracorporeal membrane oxygenation (ECMO).” (57).
    • There are a number of papers on the use of heparin in patients with AGS, e.g. Safety of Intravenous Heparin for Cardiac Surgery in Patients with Alpha-Gal Syndrome by Hawkins, et al. Search the AGI Publications Database using keyword “heparin” for more information. 
    • Perioperative implications of patients with alpha-gal allergies by Nourian, et al includes a risk stratification algorithm for AGS patients requiring perioperative parenteral anticoagulation.
    • NOTE: Fondaparinux, which is NOT animal-derived can sometimes used in place of heparin for some purposes (121).
  • Heparin treated products, such as heparin-coated vascular grafts e.g. GORE® PROPATEN® Vascular Graft
  • Gelatin-based plasma volume expanders, such as Gelafundin, Gelofusine, Gelaspan, Haemaccel (not commonly used in the U.S. if at all) (6,28,52,57,101).
    • Even some people who are not reactive to mammalian meat react to these products (28). Platts-Mills, et al, recommend avoidance for everyone with active AGS (6).
  • Many vaccines, including those that contain gelatin or other mammalian byproducts. Gelatin appears to be the most problematic vaccine ingredient for people with AGS.
    • In the U.S., vaccines that contain gelatin include: Zostavax, MMR, yellow fever, rabies, oral typhoid, FluMist, some tetanus vaccines (including Boostrix), and others (6,28,39,42,43,57,92)
  • Antivenom, such as crotalidae polyvalent immune Fab (CroFab) (6,50,51,57)
  • Bioprosthetic (bovine and porcine) heart valves (6,45,46,47,48,49,57,103) including:
    • Epic Supra porcine bioprosthetic aortic valve (Abbott, Abbott Park, Ill) (103)
    • Perimount Magna Ease (bovine bioprosthetic aortic valve (Edwards Lifesciences, Irvine, Calif) (103)
    • CryoValve SG pulmonary valve decellularized human pulmonary valve conduit (Cryolife) (103)
  • Other products made from mammalian tissue or organs, such as:
    • Heart/pericardial/epicardial patches, e.g. CorMatrix Cor™ PATCH (103) and XenoSure Biologic Patch
    • Photofix (decellularized bovine pericardium (Cryolife, Kennesaw, Ga)– used in heart and vascular repair (103)
    • Collagen scaffolding, e.g. Cardiocel acellular collagen scaffold (LeMaitre Vascular, Burlington, Mass)– used in heart and vascular repair (103)
    • Extracellular matrix (ECM) scaffolds
    • Hernia mesh (121) e.g. OviTex
    • Orthopedic implants (121)
    • Mammal-derived and collagen impregnated vascular grafts e.g. ProCol bovine mesenteric vein (LeMaitre Vascular) (103),  Artegraft Collagen Vascular Graft, Hemashield
    • And more
  • Hemostatic agents, such as:
    • Surgiflo (53)
    • Floseal hemostatic matrix and
    • Surgifoam powder (Ethicon, Raritan, NJ, USA)(6, 121)
    • Absorbable gelatin sponge (6,121), like Gelfoam
    • Thrombin sprays which are porcine- and hamster-derived, like Recothrom (Baxter, Deerfield, IL, USA)(121)
  • Other products that contain gelatin/collagen, such as:
    • Gabapentin oral solution (6)
    • Lidocaine patch (6)
    • Gummy supplements (57)
    • Vaginal capsules (37)
    • Suppositories (28,87)
    • Collagen-containing agents, including implants, such as ENDURAGen (28,87, 120)
    • Medications with gelatin capsules (6,57)
  • Many other perioperative, prescription, and OTC drugs  (32,33,34,35,57). Some of these pose a known risk to people with AGS; others contain mammalian-byproducts for which there is little data on alpha-gal content or their ability to contribute to clinical reactions, such as:
  • Many other medical products and devices, may contain mammal-derived products, including (but not limited to):
    • Collagen/catgut and sutures, e.g. chromic sutures, plain gut sutures, mild chromic gut sutures
      • We are not aware of any literature on reactions to collagen sutures, but a number of anecdotes, including reports of adverse outcomes, such as infection and disfigurement, have been shared in AGS support groups.
    • Lubricants (e.g. gelatin-based)
    • Topicals (e.g. contain gelatin and lanolin)
    • Adhesives (including bandage adhesives)
    • Collagen/thrombin glues (121)
    • Propofol (e.g. if glycerin used to rehydrate it is mammal-derived) (121)
    • Intralipid (e.g. if glycerin mammal-derived) (121)
    • See  6,32333435, 102, 121 for more information.
  • Some products used in dentistry.

See also below information about carrageenan 

Carrageenan in Drugs and Medical Products

Medications other medical products that can contain carrageenan

Carrageenan is made from red algae, not mammals, but contains the alpha-gal epitope (54).

  • At least 1-2% of people with AGS react to carrageenan (57) in foods.
  • There is no published information about the relevance of carrageenan in medical products for people with AGS and very little even in the way of anecdotal information.
  • Carrageenan in drugs and medical products may or may not be medically relevant for people with alpha-gal syndrome; more research is needed.

Based on limited information about carrageenan in medications and medical products, it appears to be used in the below products. There may be many other medical products that contain carrageenan; we have not been able to find much information about this. 

Other Alpha-gal Exposures

Airborne Alpha-gal

Airborne exposures

Some people with AGS report reactions to airborne forms of alpha-gal (57), including:

  • Suspended fat droplets in smoke or fumes from cooking meat, especially from grills
  • Other forms of airborne alpha-gal

Support for people with reactions to airborne alpha-gal

There is a Facebook support groups for people who react to airborne alpha-gal.

Airborne Alpha-gal Reaction Support Group

Reactions to Airborne Alpha-gal

a guide for people with alpha-gal syndrome→

Mammal-derived Ingredients in Personal Care and Household Products

Personal care and household products that can have mammal-derived ingredients

Products containing “hydrolyzed protein” (gelatin), lanolin, glycerin, collagen, and tallow tend to be the most problematic. Hundreds of additional mammalian ingredients whose alpha-gal content is unknown are also added to personal care and household products, including:

  • Skin care products, including lotion
  • Hair products, such as shampoo and conditioner
  • Make-up
  • Deodorants and antiperspirants
  • Liquid soaps and other cleansers
  • Toothpaste
  • Hand sanitizers
  • Latex condoms
  • Personal lubricants
  • Perfumes
  • Toilet paper, which is sometimes impregnated with gelatin
  • Many cleaning products
  • Dryer sheets made with lanolin– these are problematic for many of us, triggering both airborne reactions and rashes.
  • Detergents and fabric softeners, such as Downy fabric softener
  • Crayons

Personal Care Products

a guide for people with alpha-gal syndrome→

Carrageenan in Personal Care and Household Products

Carrageenan

Carrageenan is made from red algae, not mammals, but contains the alpha-gal epitope (54).

  • At least 1-2% of people with AGS react to carrageenan (57).
  • Some people with AGS react to carrageenan in personal care and household products, as well as in food.

Personal care and household products that can contain carrageenan

  • Many toothpastes
  • Liquid soaps and other cleansers
  • Skin care products
  • Hair products
  • Make-up
  • Air fresheners
  • See the Environmental Working Group’s Skin Deep database for more information about personal care products that contain carrageenan.

What Foods CAN We Eat? 

As far as we know, alpha-gal is not typically found in:

  • Birds, like chicken, turkey, quail, and emu don’t normally express alpha-gal (58), although alpha-gal has been found in the ocular tissue (eyes) of some birds (105)
  • Most reptiles, like snakes, crocodiles, and lizards (58), although Green Sea Turtles have high levels of alpha-gal epitopes (108) and cobra venom also contains it (58)
    • Alligator meat does not seem to be a problem for most people with AGS
  • Amphibians, like frogs, with the exception of some amphibian eggs (58)
  • Fish or seafood (58) except for flounder eggs (26104) and the eggs of some other teleost (bony) fish (58,74,104)
  • Crustaceans, like shrimp, prawns, crawfish, crabs, and lobster
  • Molluscs, like oysters, mussels, and clams
  • Plants, including fruits, vegetables, and grains
    • Note that algae are not plants, and red algae (seaweed) do contain alpha-gal.
  • Edible fungi, like mushrooms
    • Possible exception: koji, which is made from aspergillus fungi

Poultry sausages may have casings made from the intestines of mammals.

Some of these foods–especially chicken, turkey, and seafood–may be injected, treated or sprayed with mammalian substances or carrageenan or otherwise contaminated by them. These may be listed among the ingredients, but if they are considered a processing aid, as with gelatin used to clarify juice and wine or carrageenan sprayed on cut fruit or fish, they will not be.

Some people with AGS report reacting to canned tuna (6) for reasons that are not clear but which may be related to the use of processing agents or fillers.

There are unverified, anecdotal reports of people who are highly sensitive to alpha-gal reacting to chicken eggs when the chicken are not fed a vegetarian diet. Duck eggs or eggs from chickens fed a vegetarian diet may be better tolerated in these rare cases.

In general, the less processed your food, the less likely it is to contain alpha-gal. Read labels and buy from trusted sources. Be careful when eating out. Cooking your own food will help you avoid alpha-gal.

More Information

Checklist for the Newly Diagnosed→

Determining Your Tolerance: First Steps

a guide for people with alpha-gal syndrome→

Help Find a Cure→

Physician Experts→

Publications Database→

References

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2. Commins S, Lucas S, Hosen J, Satinover SM, Borish L, Platts-Mills TA. Anaphylaxis and IgE antibodies to galactose-alpha-1, 3-galactose (alphaGal): insight from the identification of novel IgE ab to carbohydrates on mammalian proteins. Journal of Allergy and Clinical Immunology. 2008 Feb 1;121(2):S25.

3. Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, Perzanowski MS, Kocan KM, Fahy JV, Nganga LW, Ronmark E, Cooper PJ. The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1, 3-galactose. Journal of Allergy and Clinical Immunology. 2011 May 1;127(5):1286-93.

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43. Stone CA, Hemler JA, Commins SP, Schuyler AJ, Phillips EJ, Peebles RS, Fahrenholz JM. Anaphylaxis after zoster vaccine: Implicating alpha-gal allergy as a possible mechanism. Journal of Allergy and Clinical Immunology. 2017 May 1;139(5):1710-3.

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79. Wilson JM, Nguyen AT, Schuyler AJ, Commins SP, Taylor AM, Platts-Mills TA, McNamara CA. IgE to the mammalian oligosaccharide galactose-α-1, 3-galactose is associated with increased atheroma volume and plaques with unstable characteristics—brief report. Arteriosclerosis, thrombosis, and vascular biology. 2018 Jul;38(7):1665-9.

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87. van Nunen S. Tick-induced allergies: mammalian meat allergy, tick anaphylaxis and their significance. Asia Pacific Allergy. 2015 Jan 1;5(1):3-16.

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92. Platts-Mills TA, Commins SP, Biedermann T, van Hage M, Levin M, Beck LA, Diuk-Wasser M, Jappe U, Apostolovic D, Minnicozzi M, Plaut M. On the cause and consequences of IgE to galactose-α-1, 3-galactose: a Report from the National Institute of Allergy and Infectious Disease Workshop on Understanding IgE-Mediated Mammalian Meat Allergy. Journal of Allergy and Clinical Immunology. 2020 Feb 10.

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95. Iweala OI, Choudhary SK, Addison CT, Batty CJ, Kapita CM, Amelio C, Schuyler AJ, Deng S, Bachelder EM, Ainslie KM, Savage PB. Glycolipid-mediated basophil activation in alpha-gal allergy. Journal of Allergy and Clinical Immunology. 2020 Feb 20.

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