What Is The Mechanism Of Action Of AGS?

Most people throughout history have eaten meat without any problems. Think of hunter-gatherers. Humans typically eat meat and metabolize the Alpha Gal carbohydrate molecule without issue. 

The mechanism of how a tick bite causes the immune system to develop antibodies is unclear (Sharma SR, 2021). How the tick itself acquires Alpha Gal and then causes a person to develop an immune response to Alpha Gal is also not known. There are some theories. The Alpha Gal antigens from the tick may be residual or recycled mammalian glycoproteins or glycolipids from previous blood feeding or they may come from the tick’s viruses, parasites, or bacteria (Sharma SR, 2021). Or Alpha Gal may possibly just originate in the tick itself (Sharma SR, 2021).

We do know that Alpha Gal comes from the saliva of the lone star tick (Sharma SR, 2021). The saliva contains the galactose-alpha-1,3-galactose or Alpha Gal molecule (Sharma SR, 2021). 

How Does Tick Saliva Induce AGS?

The saliva of ticks is a mixture of substances that have immunomodulatory properties. When the tick bites, it injures the host’s skin. This prompts the mechanisms of wound healing in the host to begin. 

These mechanisms include coagulation, vasoconstriction and platelet aggregation in the blood followed by responses of the innate and adaptive immune system. For the tick to feed off of the host’s blood, it has to stop or counteract the defense mechanisms of the host. So, substances in the tick saliva are able to suppress the host’s immune responses that would otherwise prevent efficient feeding and damage the tick (Román-Carrasco P, 2021). 

Tick saliva can decrease proinflammatory mediators (like IL-12, IL-1β or TNF-α) and increase anti-inflammatory cytokines (like TGF-β or IL-10) (Román-Carrasco P, 2021). Prostaglandin E2, or PGE2, can do this. It induces vasodilation and impairs wound healing while reducing inflammation. Large amounts of PGE2 is present in tick saliva. 

High levels of anti-inflammatory cytokines like TGF-β, IL-10 and IL-4 are found in mice infested by ticks (Román-Carrasco P, 2021). These amounts increase after every exposure to ticks. Repeated exposure to tick saliva can push the immune response toward a Th2 profile, inducing allergies and suppressing the pro-inflammatory Th1 response (Román-Carrasco P, 2021).

Human immune systems see Alpha Gal as a foreign body, so the immune system produces IgE antibodies to Alpha Gal (Commins SP, 2009). Anyone bitten by the lone star tick, who develops IgE antibodies to Alpha Gal, will have an allergic reaction when re-exposed to Alpha Gal. Re-exposure can come from mammalian meat, further lone star tick bites or from unexpected things with Alpha Gal like certain medications, candy, and even cosmetic products. 

In most Alpha Gal cases, patients were able to eat red meat before first getting symptoms. A tick bite then triggers the production of IgE antibodies against Alpha Gal (Román-Carrasco P, 2021). 

We know that the gut dysbiosis that is more common today is linked to the increase in food allergies. Dysbiosis or imbalanced gut bacteria can lead to food allergies. Or it may be an issue with mucosal barrier regulation that leads to an allergy. Current research shows that AGS is more prevalent in countries with higher numbers of allergy cases (Sharma SR, 2021). 

AGS does not seem to be related to hygiene or a disposition toward allergies (Sharma SR, 2021). AGS has been reported in people with no history of a tendency towards allergies (Sharma SR, 2021). It happens to people living in both rural and urban locations around the world. 

Allergic reactions caused by other types of insects are different. They usually cause an immediate skin reaction at the bite site. 

Why Is The Reaction Time Delayed?

Most food allergens are usually proteins. But Alpha Gal is a carbohydrate. It can bind to either a protein or a lipid. It mainly seems to bind to lipid molecules rather than proteins (Román-Carrasco P, 2021). In fact, people with AGS seem to have more severe reactions after eating fattier meats vs muscle tissue. The fact that some may tolerate leaner cuts suggests that glycolipids carrying Alpha Gal might be involved in the onset of allergic reactions (Román-Carrasco P, 2021). 

Digestion and absorption of lipids takes longer than digestion of proteins (Román-Carrasco P, 2021). By binding to glycolipids instead of glycoproteins, there is a delayed reaction time. It typically takes 3-6 hours after meat consumption for symptoms to present (Román-Carrasco P, 2021).

Blood levels of Alpha Gal-carrying glycolipids increase with alcohol consumption and exercise  (Román-Carrasco P, 2021). This can explain why patients experience more severe allergic episodes when red meat is accompanied with alcohol or followed by exercise (Román-Carrasco P, 2021). 

How Can AGS Be Avoided?

Currently, there is no cure or treatment for Alpha Gal Syndrome (AGI, 2020). So, it is best to prevent AGS in the first place. The best prevention is to avoid tick bites. 

To avoid tick bites, wear light colored protective clothing. Clothing can be treated with natural insect repellents based on essential oils. Essential oils have been found in studies to be effective for repelling ticks. Many essential oils can give some degree of protection. Studies have found that the most effective are oregano oil, thyme, citronella, and clove bud oils (Štefanidesová K, 2017). One study found that clove bud, creeping thyme and red thyme essential oils were most efficient in repelling ticks and that a mixture of creeping thyme and citronella was even more effective than individual essential oils (Štefanidesová K, 2017). 

Another option for reducing the risk of tick bites is permethrin spray (spray pants and shoes in a well-ventilated area when not wearing them and allow them to dry). Once sprayed, clothes will maintain tick repelling properties for up to a couple of wash cycles.

If  bitten by a tick, remove it as soon as possible using specialized tick removal tweezers to minimize the amount of saliva the tick secretes. 

Once bitten by a tick with Alpha Gal, you will most likely develop the IgE antibodies to Alpha Gal and suffer from AGS. There is limited research, but AGS may be reversible (Vaz-Rodrigues R, 2022). It seems that in some cases, people who can successfully avoid tick bites for 1-2 years after contracting AGS have a reasonable chance of recovering tolerance to meat products and reintroducing red meat into their diet (Vaz-Rodrigues R, 2022). 

Is There A Treatment For AGS? 

Currently there is no cure. The main treatment doctors recommend is to avoid Alpha Gal (Platts-Mills T, 2020). This means avoiding mammalian meat and dairy, in some cases. Very sensitive cases will have to be careful with other products containing mammal tissue, such as medications, candies, cosmetic products, etc., as mentioned earlier in this blog. 

Patients who need to avoid red meat should check iron and vitamin B12 levels. Supplements can be taken if needed, to avoid an iron or B12 deficiency that may arise. 

In addition to avoiding mammalian food products, it is best to avoid additional tick bites (Patel C, 2020). It is possible for symptoms of AGS to decrease or even disappear over time if there are no further tick bites from ticks with Alpha Gal (Vaz-Rodrigues R, 2022).

If an allergic reaction happens, it can be treated with an OTC antihistamine. Stronger reactions might need to be addressed with epinephrine. Doctors may recommend an epinephrine auto injector or epi pen to help with allergic reaction (AGI, 2020). Emergency treatment may be needed for a more severe anaphylactic reaction. 

One medication that may be effective to improve and treat symptoms is Omalizumab, or Xolair by Genentech. It is an anti-IgE antibody drug approved by the FDA. It is currently used for moderate to severe asthma and chronic hives or rashes. In research, it is well-tolerated by patients with AGS (Michael, 2020). After 12 weeks of taking Omalizumab, people with AGS had less itching and hives (Michael, 2020). 86% of patients on Omalizumab had an improvement in symptoms after exposure to butter or other dairy products, while some patients had no symptoms after exposure (Michael, 2020). Several people in the study had no symptoms even after eating beef or pork while on Omalizumab (Michael, 2020). In early research, Omalizumab looks like an effective treatment for AGS (Michael, 2020). 

Are There Any Alternative Treatments for AGS?

Acupuncture

The majority of AGS research says avoiding meat is the only treatment. But one study looked at a special type of acupuncture, called Soliman Auricular Allergy Treatment (SAAT), and how it can help with AGS (Bernal M, 2021). SAAT is a specialized acupuncture technique where one needle is placed in the ear. It is often successfully used to treat allergies. SAAT reprograms the immune system to stop over-reacting to allergens. Conventional and functional medicine agree that allergic responses develop due to an overreaction or dysfunction of the immune system. According to SAAT, if the body has the ability to develop the over-reactive immune response, it has the ability to reverse it as well. 

SAAT can be done as a single procedure that often significantly reduces allergic responses and provides the longest relief from allergy symptoms compared to other common treatments (Bernal M, 2021).

One study found that SAAT acupuncture was effective for most patients with AGS. In the study, 60% had mainly gastrointestinal symptoms and 45% had dermatologic symptoms from eating meat and in some cases dairy (Bernal M, 2021). 96% of these participants said their symptoms were in remission after SAAT treatment (Bernal M, 2021). No adverse reactions occurred as a result of SAAT auricular acupuncture (Bernal M, 2021). 

Other Alternative Treatments May Include:

• Natural antihistamine nutrients such as vitamin C, quercetin, copper, nettles, DAO enzyme
• Broad spectrum enzymes with each meal that can help with carbohydrate breakdown
• Work with a functional medicine practitioner to identify any underlying root causes for TH2 immune system dominance, which may exacerbate allergic reactions
• Gut diagnostics that identify overgrowths, infections, yeast, and dysbiosis may help restore immune balance when treated effectively

Can AGS Sufferers Eat Genetically Modified Meat? 

People with AGS can actually safely eat some genetically modified meat (Michelson, 2022). In a very recent development, pigs are being genetically modified for organ transplants. The human body will reject an organ from a pig, partly due to the Alpha Gal molecule, as the human immune system sees the pig organ as a foreign object. Scientists are working on genetically modifying the pig to create an organ that the human body will accept. This modification involves removing Alpha Gal. Also, the Food and Drug Administration approved genetically modifying pigs for human food and cosmetics in December 2020 (Michelson, 2022).

A biotech company called Revivicor is producing these pigs without Alpha Gal. They were involved in the first pig-to-human heart transplant. They are now sending Alpha Gal-free pork products, such as bacon, ham and chops, to AGS sufferers. This is effectively the test phase. If the experiment works, they will likely commercially produce Alpha Gal-free meat products from these genetically modified pigs. 

Although there may be AGS-safe meat available, there are unknowns about whether there may be any problems associated with the genetic modification altering anything other than Alpha-Gal and thus there may be yet-to-be seen health consequences. While AGS-safe meat may possibly be a viable option, proceed with caution.

Summary

Alpha Gal Syndrome is relatively unknown, difficult to diagnose, and sometimes a serious allergy. Although treatments are limited, there are steps you can take to prevent, diagnose, and manage this disorder. Prevention is always best and avoiding tick bites is a vital way to prevent this and many other tick-borne diseases. 

If it is determined that you have Alpha Gal Syndrome, testing and treatment options may include:

Testing Options:

• IgE for Alpha-Gal blood test or skin prick test
• Other blood testing for histamine and mast cell related markers (tryptase, plasma histamine, prostaglandin-2, total IgE)
• Avoidance of meat (except chicken, turkey and fish) for 4 weeks to see if symptoms reduce

Treatment Options:

• Avoiding the consumption and application of products with Alpha Gal such as red meat, pork, and dairy (for those who are particularly sensitive).  
• Using over the counter (OTC) antihistamines such as Zyrtec and Claritin
• Epinephrine in severe cases
• A specific form of acupuncture known as Soliman Auricular Allergy Treatment
• Natural antihistamine nutrients such as vitamin C, quercetin, copper, nettles, and DAO enzyme
• Add broad spectrum enzymes with each meal that can help with carbohydrate breakdown
• Work with a functional medicine practitioner to identify any underlying root causes for TH2 immune system dominance, which may exacerbate allergic reactions
• Gut diagnostics looking for overgrowths, infections, yeast, and dysbiosis when treated may help restore immune balance when treated effectively

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