The Explosion in Alpha-Gal

“Every time I take my morning medications, I crash for 6 hours.”  As pharmacists, assessing therapeutic effectiveness often begins with a simple comment or question when patients pick up their monthly medications. This was the complaint of a long-time patient who subsequently scheduled an appointment to discuss his medication regimen and these challenging side effects. He had a long history of nagging chronic health challenges and had recently retired due to their impact, the primary complaint being debilitating fatigue. His quest for health had recently led to being diagnosed with an increasingly common condition known as Alpha-Gal Syndrome.

Alpha-Gal Syndrome (AGS) (also called alpha-gal allergy, red meat allergy, or tick bite meat allergy) is a serious, patient-specific, potentially life-threatening allergic reaction. In the United States, the condition usually begins with the bite of the Lone Star tick. The bite transfers to the host a sugar molecule called alpha-gal (galactose-α-1,3-galactose). In some, this sugar molecule triggers an immune system response. (Interestingly, this is the sugar molecule contributing to the severe immune response present with animal-to-human organ transplantation.[i]) This causes mild to severe allergic reactions to red meat (all mammalian proteins, except those found in catarrhines[ii]), such as beef, pork or lamb.[iii]     

Reactions to the alpha-gal molecule are frustratingly variable, unpredictable, and patient specific. AGS reactions can range from a mild runny nose, itching, and nausea, to life-threatening anaphylaxis, severe abdominal pain, drops in blood pressure, and swelling of lips, throat, tongue, or eye lids. In 70% of cases, the reaction is accompanied by respiratory distress and as such is particularly harmful to those with asthma.[iv] Symptoms commonly appear 2-12 hours after exposure to meat, dairy products, or products containing alpha-gal. People may not have allergic reactions after each exposure to alpha-gal, making the condition frustratingly difficult to diagnose, predict or manage. Foundational AGS management begins with the aggressive removal of all red meat and alpha-gal containing products from patient consumption. This is where the clinical community pharmacist is uniquely critical to supporting patients in managing this life-threatening condition.

Most modern pharmaceutical, nutraceutical, and vaccine therapies utilize alpha-gal containing excipients in their production.[v] Gelatin capsules, bovine extract, glycerin, and magnesium stearate are a few common components of these therapies. Even the most common excipient, lactose, has been implicated in potentially contributing to the alpha-gal reaction.[vi] Alpha gal is present in the anti cancer drug cetuximab. Blood thinners and thyroid replacements as well as replacement heart valves derived from porcine tissues may also contain alpha-gal.[1] While not all AGS patients receiving these products will result in a severe response, for some, these alpha-gal containing products can contribute to life-threatening allergic reactions as well as disease severity and progression.

For our patient, a comprehensive therapeutic review, pharmaceutical, nutraceutical, and cosmeceutical, confirmed the presence of many alpha-gal containing excipients.  The patient reported that they had experimented with not taking any of their medications, resulting in immediate resolution of fatigue. This often too common patient response of abruptly discontinuing critical therapies, creates potentially life-threatening sequelae. This presents a challenging clinical conundrum that can be helped with the intervention and care of the clinical community pharmacist. Potential therapeutic strategies include:

• Evaluation and comparison of inactive ingredients of ingested therapies
• Immediate sourcing of therapies that are produced as vegetarian.
• Compounding of alpha-gal-free formulations
• Seek or compound therapies that may have multiple actives in one dosage form.
• In those formulations not available for compounding, (i.e., no active ingredient available, name brand availability only, etc.) discuss with physician possible therapeutic interchange or impact, in an effort to minimize amounts of alpha-gal triggers.
• Re-enforce and support disease understanding and often difficult lifestyle changes (i.e. referral to certified nutritionist, education resources, recipes, emotional support, etc.)

Foundational to improving clinical outcomes and ultimately, patients lives, is a dedicated clinical appointment and a therapeutic relationship with a trusted pharmacist. In the paid consultation with their clinical community pharmacist, we were able to create improved therapeutic outcomes by assisting the patient and physician in minimizing the adverse effects from alpha-gal hiding in their regimen. There will be an increase recognition and diagnosis of those reacting to alpha-gal over the next decade.[2] This will accelerate the need for the therapeutic over-site and contribution of the clinical community pharmacist in personalizing therapies and creating optimal health outcomes.

Kathy M. Campbell, PharmD, DrKathy Health, LLC

Dr. Campbell is a clinical community pharmacist and community pharmacy owner having served her community of Owasso, Oklahoma for 31 years. She can be contacted at [email protected]

1 Sandrin MS, McKenzie IF. Gal alpha (1,3)Gal, the major xenoantigen(s) recognised in pigs by human natural antibodies. Immunol Rev. 1994 Oct;141:169-90. doi: 10.1111/j.1600-065x.1994.tb00877.x. PMID: 7532618.

2 Galili U (1993). "Evolution and pathophysiology of the human natural anti-alpha-galactosyl IgG (anti-Gal) antibody". Springer Seminars in Immunopathology. 15 (2–3): 155–71. doi:10.1007/bf00201098. PMID 7504839. S2CID 33149564.

3 https://www.cdc.gov/ticks/alpha-gal/index.html

4 Wolver SE, Sun DR, Commins SP, Schwartz LB. A peculiar cause of anaphylaxis: no more steak? The journey to discovery of a newly recognized allergy to galactose-alpha-1,3-galactose found in mammalian meat. J Gen Intern Med. 2013 Feb;28(2):322-5. doi: 10.1007/s11606-012-2144-z. Epub 2012 Jul 20. PMID: 22815061; PMCID: PMC3614139.

5 https://www.cdc.gov/ticks/alpha-gal/products.html

6 Slayden TA, Shakir MKM, Hoang TD. A BULL IN A PILL SHOP: ALPHA-GAL ALLERGY COMPLICATING TREATMENT OPTIONS FOR POSTPROCEDURAL HYPOTHYROIDISM. AACE Clin Case Rep. 2020 May 11;6(3):e101-e104. doi: 10.4158/ACCR-2019-0495. PMID: 32524021; PMCID: PMC7282276.

7 Zaraska M (December 3, 2013). "Want hives with that burger?". The Washington Post. pp. HEALTH, E01

8 Sharma SR, Karim S. Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack. Front Cell Infect Microbiol. 2021 Jul 20;11:680264. doi: 10.3389/fcimb.2021.680264. PMID: 34354960; PMCID: PMC8331069.