Alpha-gal syndrome (AGS), the delayed, potentially fatal red meat allergy acquired through tick bites, has increased dramatically in the United States, and cases have also been reported in Sweden, Germany and Australia.1 As of 2013, more than 5,000 people in the Southwest U.S. have been diagnosed with the condition.2
In 2007, Scott Commins, MD, an allergist and associate professor of medicine at the University of North Carolina, Chapel Hill, was among the first physicians to identify the meat allergy in patients with tick bites by overlapping the geographic distribution of the allergy with the Lone Star tick.3 4
Alpha-gal is short for Galactose-alpha-1,3-galactose, a carbohydrate molecule found in mammalian meats such as cows, pigs and lamb. Humans do not make this sugar, but they make an immune response to it. Ticks are believed to get it from feeding off wild animals, such as mice or squirrels, that also carry alpha-gal, which are injected into humans when they bite. “Whatever the tick is doing, it seems it’s a very potent awakener for our immune system to produce antibodies,” Commins says.
After Eating Meat, Severe Alpha-gal Allergy Symptoms Follow
Symptoms generally start three to six hours after consuming mammalian meat and include hives or severe itching; swelling of lips, tongue, face and throat; wheezing or shortness of breath; abdominal pain, nausea, diarrhea or vomiting; sneezing; rapid decrease in blood pressure; and anaphylaxis, a life-threatening medical emergency.5 6 The presence of symptoms before a severe reaction is common, but not a requirement, and the symptoms do not occur with every exposure to red meat.
One set of researchers note that every person with the alpha-gal allergy had consumed red meat without complications for many years prior to the onset of the syndrome.7 Diagnosis is made by a combination of personal history and a blood test confirming the presence of IgE antibodies to alpha-gal, and an individual with confirmed alpha-gal allergy must carry an epinephrine injector at all times in case of an anaphylactic emergency.8
A 2018 study7 found that 28 of 85 cases of anaphylaxis studied were the result of AGS, and the U. S. Health and Human Services (HHS) Tick Borne Disease Working Group reports that in central Virginia, alpha-gal allergy is the most common cause of anaphylaxis in adults.9
The delay and potency of the reaction is particularly strong with fatty meat, which takes longer to digest, and suggests to researchers that the alpha-gal may be carried in the fat of these animals rather than muscle.10 The reaction may be easier to elicit in the presence of a more recent (one to four weeks) tick bite.4
High Risk Factors: Mast Cell Disease, Certain Drugs
Risk factors for mammalian meat syndrome includes spending a lot of time outdoors, receiving multiple Lone Star tick bites, and having a mast cell abnormality such as indolent systemic mastocytosis.5
Mast Cell Activation Syndrome (MCAS), which appears to be increasing in prevalence in the U.S. and other countries, is associated not only with chronic anaphylactic reactions but also with various brain and immune system disorders ranging from asthma, inflammatory bowel disease and chronic fatigue syndrome to ADHD, depression, autism and cancer.11
Alpha-gal syndrome is more than a red meat allergy, however. Cosby Stone, MD, a fellow in Vanderbilt University’s Asthma, Sinus and Allergy Program (ASAP), said recent patients in their clinic have led researchers to take a deeper look into alpha-gal as not only as a food allergy, but a medication allergy. Medications they are investigating include antibodies derived from animals, like rattlesnake anti-venom, certain cancer treatments like Cetuximab, and products that contain gelatin (certain vaccines contain gelatin) or gel-based products.
Heart valves that are harvested from pigs and used to replace a failed valve have also been reported to cause reactions or a more rapid breakdown of the valve in alpha-gal allergic patients.12 Desiccated porcine thyroid found in natural thyroid replacement medications such as Armour, Westhroid and Naturethroid, is also derived from animals and could cause a reaction.13 14 Dr. Stone said:
What is difficult is predicting which alpha-gal patients will react to which drugs, foods or treatments, because the reaction varies by the patient. Some patients report reacting to alpha-gal in the context of beef, but not pork, dairy or gelatin, for example. At the same time, others will react to pork and not beef. Some alpha-gal allergic patients react to medicines or vaccines, and others do not. We don’t currently know how to predict which patients will react to which foods and drugs, and that is a major focus of our ongoing research.
Some product ingredients mask the fact that they are derived from a mammal, such as magnesium stearate, stearic acid, sucralose, and “natural flavors”. Sugar is another ingredient to avoid as it is processed over bone char, with the exception of certified organic sugar, which is safe.15
Cosmetics, Home Products, Many Foods Contain Alpha-gal
Though much of the concern about the Alpha-gal allergy has focused on meat and medications, patients can be exposed to the allergen in many other ways. About half of all people with AGS react to milk or dairy products, and a third react to airborne particles in fumes from cooking meat or dairy. Pet saliva and dander, exposure to farm animals and their waste, and even the semen of a sexual partner if he has consumed mammalian meat 48 hours prior to sexual activity may trigger a reaction. Bagged compost for use in gardens may contain manure or bone meal, and even the lanolin in lip balm or lotions may provoke a reaction.16
Gelatin is an ingredient in many food products and household items used in daily life, such as contact lenses, sutures, collagen implants, shampoo, tinned hams, salami, sausage coatings, fat substitutes, glazes and icing, dips, food thickeners and candy such as marshmallows. Mammalian products are also used to clarify fruit juice or wine, and as a binding agent in some tablets, capsules and suppositories.17
Some patients with AGS have sensitivity to some types of glycerin that are derived from animal fats. Glycerin is a food additive found in canned goods, candy, fondant, processed fruits, jams and energy bars. It is also used in medications, syrups, toothpaste, mouthwash, and tobacco, among many other products.4 17
Manufacturers Not Required to Label Alpha-gal Content
Manufacturers do not currently report alpha-gal content in their package inserts or test for alpha-gal content in products. Inactive ingredient information can change at any time, and the U.S. Food and Drug Administration (FDA) does not require manufacturers to disseminate this information.18 Arkansas Representatives Julie Mayberry and Dwight Tosh submitted a citizen petition to request the U.S. Food and Drug Administration support Congressional action requiring the labeling of all products intended for human ingestion or injection if they contain mammal meat or mammalian meat products.6
Are vaccines safe for individuals with alpha-gal allergy? Animal-derived products used in vaccine manufacture can include amino acids, glycerol, detergents, gelatin, enzymes and blood. Cow milk is a source of amino acids and sugars such as galactose. Cow tallow derivatives used in vaccine manufacture include glycerol. Gelatin and some amino acids come from cow bones. Cow skeletal muscle is used to prepare broths used in certain complex media. Many difficult to grow microorganisms and the cells that are used to propagate viruses require the addition of serum from blood to the growth media.19
CDC Chart Lists Vaccine Ingredients Sourced from Mammals
The CDC’s “Vaccine Excipient and Media Summary Excipients Included in U.S. Vaccines, by Vaccine“ lists the following mammal-derived ingredients: bovine, pig, canine, calf, mouse brains, Cocker Spaniel, Africana Green Monkey, Guinea Pig cell cultures, lactose, magnesium stearate, sugar(s), glycerin, hydrolyzed porcine gelatin, Mueller’s growth medium, Mueller-Miller casamino acid medium (without beef heart infusion ) (casamino acid medium is made with many ingredients including casein, which is mammal derived), and Medium 199 (may contain mammal sub-ingredient “Minimum Essential Medium” made using a number of ingredients, including fetal bovine serum).20 21
Mammalian-derived ingredients are included in vaccines such as influenza, rabies, rotavirus, varicella (chickenpox), zoster (shingles), IPV (polio), Japanese encephalitis, typhoid, yellow fever, MMR/MMRV, and DTaP (multiple manufacturers),22 and vaccines have been specifically identified as causing anaphylactic reactions in those with alpha-gal allergy.23 24 25 26 27
Traditionally, influenza viruses are grown on hen’s eggs, but the Flucelvax Quadrivalent influenza vaccine for the 2019-2010 flu “season” is an egg-free, “cell based” vaccine manufactured with cultured mammal cells.28 Manufacturing influenza vaccines using mammalian cell-based technology has been identified as a priority for national security reasons due to increased flexibility for rapid production,29 and is expected to be used to a greater degree in future vaccines.
Tick-Borne Diseases Threaten Health in U.S.
The CDC reports that tick-borne diseases increasingly threaten the health of people in the U.S. As the geographic range of the lone star tick continues to expand from its original territory in the southeastern United States into the northern and mid-western states, states like Maine report they are “bracing for the worst” in the face of the “aggressive” lone star tick. A warming climate provides conditions that favor a population explosion of deer and other mammal hosts, while urbanization and the fragmentation of forests has brought many of these animals and the ticks they host directly into human habited areas.29 30 31
Avoiding tick bites is the only known prevention for alpha-gal allergy, and avoiding mammal-derived products is the only known treatment, which leaves those individuals living with the allergy extremely vulnerable.
1 Aubrey A. Red Meat Allergies Caused By Tick Bites Are On The Rise. NPR June 25, 2018.
2 Platts-Millsa TAE, Comminsa SP. Emerging Antigens Involved in Allergic Responses. Curr Opin Immunol December 2013; 25(6): 769–774.
3 Alpha-Gal Allergy – with Dr. Scott Commins. University of North Carolina School of Medicine.
4 Commins SP, Platts-Mills TAE. Delayed Anaphylaxis to Red Meat in Patients with IgE Specific for Galactose alpha-1,3-Galactose (alpha-gal). Curr Allergy Asthma Rep February 2013; 13(1): 72–77.
5 Alpha-gal syndrome. Mayo Clinic.
6 Carrison B. Vaccines–Are they Alpha-gal Safe? Tick-Borne Conditions United May 22, 2018.
7 Pattanaik D, et. al. The changing face of anaphylaxis in adults and adolescents. Annals of Allergy, Asthma & Immunology November 2018; 121(5): 594-597.
8 Steinke JW, et. al. The alpha gal story: Lessons learned from connecting the dots. J Allergy Clin Immunol March 2015; 135(3): 589–597.
9 Priority #3: Alpha-gal Meat Allergy. U.S. Department of Health and Human Services May 9, 2018.
10 Migala J. What Is Alpha-Gal Allergy? How a Tick Bite Can Make You Allergic to Red Meat. Prevention June 29, 2019.
11 Fisher BL, Hendler C. Mast Cell Disease and Vaccination: Is There Increased Risk? The Vaccine Reaction July 24, 2018.
12 News Wire. Alpha-Gal Found to be Both a Medication and Red Meat Allergy SnackSafely.com Apr. 17, 2018.
13 Slayden TA, et. al. A Bull In A Pill Shop: Alpha-Gal Allergy Complicating Treatment Options For Postprocedural Hypothyroidism. AACE Journals 2019.
14 Graedon J, Graedon T. Meat allergy could cause trouble with medications. St. Louis Post-Dispatch June 11, 2017.
15 Food. VeganWithASideOfChicken.com
16 Alpha-gal Tolerance Levels. AlphagalInformation.org.
17 Alpha-gal: Personal Impact. Arkansas Department of Health.
18 Kar I, et. al. Alpha-Gal (Mammalian Meat) Allergy: Implications for Pharmacists. Pharmacy Times May 27, 2015.
19 U.S. Food and Drug Administration. Bovine Derived Materials Used in Vaccine Manufacturing Questions and Answers. FDA.gov Mar. 23, 2018.
20 U.S. Centers for Disease Control and Prevention. Vaccine Excipient Summary. CDC.gov January 2019.
21 Potential Allergens in Vaccines per 0.5 mL dose. Institute for Vaccine Safety Dec. 4, 2018.
22 Stone CA, et. al. Anaphylaxis after vaccination in a pediatric patient: further implicating alpha-gal allergy. The Journal of Allergy and Clinical Immunology January 2019; 7(1): 322–324.e2.
23 Bircher AJ. Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a review. European Journal of Dermatology 2017; 27: 3-9.
24 Arumugham V. Evidence that Food Proteins in Vaccines Cause the Development of Food Allergies and Its Implications for Vaccine Policy. J Develop Drugs 2015; 4(4).
25 Caubet JC, et. al. Managing a child with possible allergy to vaccine. Pediatric Allergy and Immunology Oct. 16, 2013.
26 Bradfisch F, et. al. Case series of anaphylactic reactions after rabies vaccinations with gelatin sensitization. Allergo Journal International 2019; 28: 103-106.
27 CDC. Cell-Based Flu Vaccines. CDC.gov Oct. 11, 2019.
28 Executive Order. Executive Order on Modernizing Influenza Vaccines in the United States to Promote National Security and Public Health. White House Sept. 19, 2019.
29 CDC. Lyme and Other Tickborne Diseases Increasing. CDC.gov Apr. 22, 2019.
30 Charns D. ‘Bracing for the worst’: Aggressive lone star tick expanding into Maine, New England. WMTV8 Dec. 6, 2019.
31 The tick population is booming. Is climate change to blame? And will ticke-borne diseases increase? The Washington Post May 22, 2019.