Salicylate Sensitivity
*This article is not medical advice. Before starting on any health related regimen, seek the advice of your Primary Care Physician or an M.D.
What Are Salicylates and What Causes Salicylate Sensitivity ?
Salicylates are salts or esters of salicylic acid, an acid found in some plants that is thought to serve as a defense mechanism due to its irritant quality. Salicylic acid is present in willow bark, in wintergreen leaves, and in many commonly eaten foods. Some medicines also contain salicylates, the most well-known of which is aspirin, or acetylsalicylic acid.
A small number of people report significant sensitivity to foods and herbs high in salicylates. Many of these same people report sensitivity to oxalates, but not all. In this article, I will discuss what causes salicylate sensitivity and what can be done about it.
Why Read This Article?
You may be interested in this article if you:
Want to learn what foods contain salicylates.
Want to learn about how salicylates are metabolized in the body.
Want to understand what genes may be involved in salicylate metabolism and processing.
Want to understand what genes are negatively impacted by salicylates
What Foods Contain Salicylates?
Knowing which foods have the highest levels of salicylates can be helpful in identifying potential sensitivities and reducing consumption. Some salicylate-containing foods include:
Fruit (especially berries and dried fruits)
Herbs and spices (eg. curry powder, paprika, rosemary, thyme)
Coffee and tea (tea is substantially higher)
Wintergreen flavored products
Meat, dairy, cereals, and fish contain negligible amounts of salicylates. Vegetables contain varying amounts.
What Genes Process Salicylate Acid?
The following genes are involved in the metabolism of salicylate acid:
Phase 1 CYP 2C9 (major); 1A2 and 2E1 (minor)
Phase 2 Detoxification
Genes involved in Sulfation (SULT1A1, SULT1A3)
Genes involved in Glucuronidation (UGT1A6 - major, 1A1 - minor, 2B7 - minor)
Genes involved in Glycine Conjugation (ACSM2A/B, GLYAT)
In addition to the SULT and UGT genes mentioned above, (which are heavily loaded/consumed by the processing of salicylate acid) the following genes are inhibited by salicylate acid:
FECH (in the heme pathway)
Antioxidant Genes
SOD2 - Mitochondrial Superoxide Dismutase
GPX1 - Glutathione Peroxidase
CAT (Catalase) - reduces hydrogen peroxide
PRDX3, PRDX5 - defense against hydrogen peroxide
GCLC, GCLM - rate-limiting genes in the synthesis of glutathione
Mitochondrial Genes
Complex I: NDUSF1, NDUFV1
Complex II: SDHA, SDHB
ATP Synthesis : ATP5F1A, ATP5F1B
Mitochondrial Fusion: MFN2, OPA1
Mitochondrial Biogenesis: PGC1A
Nutrient Transporters
2A5 - carnitine transport
SLC25A20 - carnitine transolcase
SLC5A6 - multi sodium dependent transporter for : B5, B7, Lipoic Acid
SLC19A2, SLC19A3 - thiamine transporters
Inflammatory Pathways / Genes
NFKB
PTGS1/COX1, PTGS2/COX2, TXA2 - Prostaglandins and Thromboxanes
NMDA Receptors
Salicylate exposure increases expression of NR2B (GRIN2B) NMDA receptor, sensitizing it and contributing to auditory issues like tinnitus.
TRP Channels
TRPV1 - sensitizies to pain and thermal sensitivity.
TRPA1 - sensitizes to oxidative stress and lipid peroxidation, enhancing nociceptive responses. Relevant in airway irritation, gut sensitivity, or pain.
TRPM2 - activation by salicylate acid can lead to calcium influx, which promotes neuroinflammation.
Voltage Gated Sodium Channels - reducing neuronal excitabiilty but contributes to confusion, dizziness, or CNS depression
Voltage Gated Potassium Channels - may inhibit Kv channels, altering repolarization, effcting cardiac and neuronal excitability at toxic levels
L-Type Ca2+ Channels - may effect mitochondrial uncoupling and ROS
What Common Issues and Genetics Do I See With Salicylate Sensitivity?
The salicylate sensitivity cases I have come across often have significant compromise on the SULT, UGT, TRP, and/or FECH genes. Interestingly, oxalates are also metabolized via the SULT pathway, as well.
What Has Helped Lower Sensitivity to Salicylates and Levels of Salicylate Acid on Organic Acid Tests?
Lowering the burden on UGT, SULT, TRP, and FECH genes.
Lowering detoxification burden on UGT, SULT genes by removing mycotoxins
Supporting UGT with herbs like dandelion, pterostilbene, astaxanthin; and later, rosemary
Activation of Nr1H4 and AhR that stimulate SULT and UGT systems broadly
Lowering inhibition of UGT by removing supplements like Milk Thistle
Supporting SULT by using epsom salt baths and dill; lowering 4-cresol
Removing toxins like DDT that inhibit FECH gene, and ensuring sufficient B6, Zn, Cu, and Iron levels
Using a digestive enzyme called No Fenol to help process and remove phenols and salicylates
Using herbs to lower TRP receptor activity (Cayenne - desensitizes, Saffron, Magnolia, Chrysin, Evodia, Decursinol-50, and exogenous ketones), depending on which specific genes are mutated
Facilitate glycine conjugation