How AGEs Affect Allergies
by Jason E. Barker, ND
Our understanding of the molecular mechanisms of action behind the physiological effects of food and environmental sensitivities is well elucidated; however, our knowledge of the “why” behind their symptoms continues to remain a mystery. Clearly, immunologic processes exist to protect us, but sensitivities can develop at any point in a person’s life regardless of their health history.
So what does leave certain people more vulnerable to sensitivities than others? While there are likely a variety of factors that play a role, researchers are beginning to explore the very real possibility that a relationship exists between the development of food or environmental sensitivities and Advanced Glycation End Products (AGEs), which explains why in my clinical practice and those of other health care practitioners we have noticed a worsening of symptoms that seem to occur in patients who consume diets high in processed (sugary) foods and who experience blood sugar imbalances.
This article will discuss the possible link between AGEs and environmental and food sensitivities.
AGEs Recap
AGEs are created during the normal course of metabolism; however, they form at an accelerated rate in instances of hyperglycemia. AGEs are created as a byproduct of carbohydrate metabolism when sugars react with the free amino acid portions of nucleic acids, proteins and lipids. They are also formed as a result of food preparation and processing (heating and cooking). AGEs form irreversible bonds with tissue proteins and accumulate in the body over time, promoting imbalances and impacting health throughout.
AGEs form crosslinks with other proteins, altering the protein’s structure and function. AGEs accumulate in a variety of tissues throughout the body, creating inflammatory imbalances and pro-oxidative reactions that are increasingly associated with common health concerns.1-2
The Allergic Process
The basic etiology of food and environmental reactions consists of an antigen -antibody (immunoglobulin IgE) complex stimulating already-primed mast cells or basophils leading to the degranulation of histamine, a major mediator of type 1 (immediate hypersensitivity) reactions. Additional inflammatory chemicals are released from these cells during degranulation including cytokines, leukotrienes, prostaglandins and interleukins. These chemicals cause the symptoms associated with food and environmental sensitivities including smooth muscle contraction, mucous production and vasodilation; the results are pruritis (itching), rhinorrhea, temporary dyspnea and other familiar symptoms.3 Type 1 immediate hypersensitivities of this type are primarily driven by histamine and occur with rapid onset. That being said, individuals with sensitivities of this type can experience their symptoms somewhat regularly.
AGE-Induced Sensitivities
Newer research is beginning to uncover the relationship between AGEs and food and environmental sensitivities. More specifically, the link between AGEs and mast cells is being explored because of this set of cells’ major involvement in inflammatory responses. Mast-cell involvement in inflammatory responses also contributes to the progression of several adverse health conditions. Because AGEs have been shown to interact with mast cells, theoretically, they may also play a role in histamine-driven sensitivity-related responses.
A novel study measured the effect of AGEs on mast cell histamine secretion; it showed that AGEs will induce mast cell exocytosis (the release of histamine) in a dose-dependent fashion.4 AGEs led to maximal degranulation within 20 seconds of contacting the mast cells, and this activity lasted for 3 hours, returning to normal by 6 hours post-exposure. Degranulation is the process by which mast cells release histamine. Along with mast cell degranulation, AGEs also induced production of reactive oxygen species (ROS), otherwise known as free radicals. Another similar study showed that mast cells do indeed express the binding receptor for AGEs (RAGE) and will degranulate when exposed to AGEs.5
Researchers in the above study also determined that AGE stimulation of mast cells led to the generation of ROS, activation of the AGE receptor (termed RAGE) and a generalized imbalance in the inflammatory response that may not be conducive to optimal health. However, our interest for the purposes of this article lies in the fact that AGE-stimulation leads to histamine release from the mast cells.
The fact that these molecules, produced, for example, by consuming a high-sugar diet, can induce the release of histamine in mast cells deserves a lot of attention on behalf of individuals with sensitivities. If AGEs (which are both consumed in a high-sugar, processed-food-rich diet and created in the body as a result of this diet) stimulate histamine production from mast cells, this only serves to increase sensitivities.6 Taking this theory further, it may also explain those patients who experience symptoms year round despite living in climates (dry, snowy) where environmental sensitivities are near non-existent during the winter months. It is also interesting to note that in at least one study, investigators observed the co-occurrence of sensitivities and type 1 diabetes7 that may theoretically be in part due to the elevated blood sugar levels that occur in uncontrolled diabetes as well as the increased AGE production that occurs in diabetics.
The Food Sensitivity Link
There is an interesting link between AGEs and food sensitivities as well. Preliminary studies show that AGEs derived from the model food allergen ovalbumin (AGE-ova) were internalized at a significantly higher rate by dendritic (antigen-presenting) cells compared to non-AGE derived ovalbumin. CD4(+)T cells cultured with the AGE-ova loaded dendritic cells produced higher levels of interleukin-6 and induced a stronger Th2 cytokine response, indicating that AGE-ova has more sensitivity-inducing potential than non-AGE ovalbumin.8-9
These studies give additional reason for avoiding high sugar and processed foods that contain or produce AGEs in the body, as these molecules may serve as immunological foci in food sensitivities. And, based on the empirical theory that total allergenicity is a sum of its parts, food sensitivities may help to precipitate other accompanying effects.
AGE Blockers
Based on this newer research, one may be able to attenuate the effects of their sensitivities over time by decreasing the amount of AGEs consumed as well as the foods that favor production of AGEs. This includes consuming little to no high-sugar or processed foods, avoiding high temperature cooking of foods, and increasing vegetable consumption.10-11
Other strategies include blocking the formation of AGEs in the body through specific nutritional factors found in Advanced Glycation Defense®. N-acetyl cysteine (NAC) is an important precursor to glutathione, the body’s most potent antioxidant. It has been shown to confer protection from AGEs to the retina, platelets, cells of the nervous system, and even LDL cholesterol.12-14 Carnosine, another nutrient found in Advanced Glycation Defense, can impede the transformation of LDL into AGEs15 and will also impair the formation of intermediate molecules (Schiff bases) prior to the creation of AGEs.16
Another important antioxidant, alpha lipoic acid, along with vitamin B1 in the form of benfotiamine will both block the production of AGEs following the consumption of AGE-containing and promoting foods.17-18
The fruit guava (Psidium guajava) blocks the formation of AGEs by inhibiting glycation of LDL19 and Yerba Maté (Ilex paraguariensis) has a similar AGE-preventing efficacy compared to aminoguanidine, the agent used in much AGE-reducing research.20
Histamine Defense
The natural histamine-balancers quercetin, bromelain and vitamin C (all found in QuerCelain®) can be paired with the AGE-blocking substances mentioned above without drowsy, dry mouth side effects. Quercetin is a flavonoid compound that has well known inflammatory balancing, antioxidant and sensitivity-reducing effects.21 Quercetin can directly inhibit the release of histamine from mast cells and basophils, making it the perfect supplement to help with spring and summer challenges.22-24 It is best absorbed on an empty stomach.
Bromelain is a proteolytic enzyme derived from the pineapple. It exerts several inflammation-balancing effects such as blocking pro-inflammatory prostaglandins, stimulating inflammation-modulating prostaglandins and slowing migration of neutrophils to sites of inflammation.25-27
Vitamin C may possibly serve as a histamine detoxifier. Daily supplementation can decrease blood histamine levels by 38 percent after one week of supplementation.28
Conclusion
AGEs are implicated in a growing number of health issues associated with inflammatory imbalances. And while newer research has just begun to explore the link between AGEs and food/environmental sensitivities, the evidence shows that these molecules (and the dietary patterns that promote their uptake and synthesis in the body) will stimulate mast cells to release histamine, the primary allergic mediator in the body. Therefore, high consumption and production of AGEs can theoretically lower the threshold for sensitivity-related symptoms and may explain the occurrence of year-round effects in some patients. Controlling bodily production of AGEs through diet, lifestyle and specific supplements may serve to address (and decrease) the overall effects of food and environmental challenges.
References
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