Salicylate Risks & Benefits, Fibromyalgia & POTS
Salicylate Risks & Benefits, Fibromyalgia & POTS
Salicylates are pain relieving chemicals found in many plants besides the willow or myrtle tree bark in which it was initially discovered. Willow bark extracts became commonly used as aspirin. Excessive doses of aspirin are harmful and may have been an underlying causal factor in the historical Spanish Flu that caused many deaths in the US. Was it the Flu? or the high dose aspirin that caused deaths? (and was the ‘Flu’ really an adverse vaccine reaction?)
Excessive doses of aspirin or salicylates is still a risk that kills a few tens of thousands of people each year. Misdiagnosis and lack of recognition of salicylate as the cause of a patient’s negative symptoms is part of the reason for salicylate related deaths.
Addition 12/31/2023, useful food list that combines low oxalate and low salicylate food lists and has printable condensed sheet to be able to take along for grocery shopping: (eatbeautiful.net).
This is also a useful salicylate list with entries for foods high in amines or natural glutamates (MSG-like): (alessandraedwards.com/).
Salicylate Toxicity
People can overdose on aspirin type of sources, topical anti-pain creams may add to the total and also the use of more herbs and spices and mint tea or ginger, etc - the food lists, in the person’s diet.
“Lack of awareness that such substances* contain salicylate [*mint tea and ginger] explains why patients may not know that they have ingested salicylates. Preexisting kidney disease or a salicylate-induced decrease in kidney function can contribute to increased plasma levels.” (Palmer and Clegg, 2020)
To remove salicylates from the body we need the urine to be less acidic and more alkaline or the chemistry is shifted back towards reabsorption of the salicylates instead of excretion into the urine collecting side of the kidney tubules.
To modify salicylates into a less active and potentially harmful form, we need the amino acid glycine in the dimethylglycine form (DMG) instead of the trimethylglycine form (also called betaine or TMG).
Salicylate Sensitivity
Some people can get negative side effects due to salicylate toxicity at lower levels because they may not have enough glycine to make it dysfunctional, and their urine might be too acidic or other for other unknown reasons. For these people smaller amounts of dietary spices containing salicylates may lead to the negative symptoms. It is considered a “pseudoallergy” or “pseudoimmunopathy” as mast cells are triggered among other immune cells, but due to COX inhibition rather than a true allergic reaction. Normal production of prostaglandins derived from endocannabinoid release and breakdown into arachidonic acid is inhibited withe the inhibition of Cyclooxygenase (COX1 or COX2) enzymes, more so with COX1. (Baenkler, 2008)
I have a genetic difference in my BHMT gene that makes me unable to convert betaine/TMG into DMG. I take DMG powder as a supplement, but inconsistent habits led to inconsistent health. I likely need to take a little more of it too and more often during the day possibly in order to be less sensitive to dietary sources, let alone taking an Excedrin or aspirin. I have not ever been a regular user of either, ibuprofen worked better for me during my worse pain years, but recently I have used Excedrin for the caffeine boost occasionally.
As I looked at food lists of salicylate sources it was clear that I had been using a lot of them. Mint and essential oil of mint/s are very high and I also had been using a chapstick with mint in it. I also regularly used rosemary, thyme, oregano, Bay leaves, cumin, and Black Cumin Seed Oil. My symptoms got worse when I briefly added ginger and hot pepper back to my diet, and then cut them out again as I suspected the TRP channel activation was causing histamine symptoms - that may have been happening too but they are also both high in salicylates.
A website & post, low-sal-life.com, focuses on why Food Lists vary so much - plant content varies with growing conditions and peel/outer leaves versus inner fruit/food content; and testing accuracy has varied. Older lists that aren’t updated likely have old information. the author adds celery, garlic, green peas, cucumbers, to the moderate rather than low lists. I still have been having symptoms even after stopping use of a bunch of herbs, spices, and foods. I had still been using garlic and celery generously and Romaine or green-leaf lettuce which are not the same as ‘Iceberg lettuce’.
Symptoms of Salicylate excess, whether due to an unknown ‘sensitivity’ or due to total excess intake.
It is easier to overdose than realized when breath mints, aspirin-containing, and other more concentrated topical or medicinal mint containing products are being used.
Warning signs that I am now aware of as salicylate excess - fairly immediate gassy bloating effect in the gut and/or discomfort after eating or drinking the item. The bloating can extend to the ankles, and calves, and everywhere else, as the problem becomes more severe with a bigger salicylate load. The headache comes the next morning or later at night. As the symptoms worsened, congestion and asthmatic symptoms were starting for me. And after reading symptom lists and thinking about it - “ADHD” symptoms can worsen. I was more scattered, having difficulty making decisions or keeping appointments, and losing things. When mental symptoms are part of a health problem it can become even more difficult to try to figure out what changed, what happened?
It was also wild strawberry and black raspberry season, and those delicious, all over my backyard, and good salicylate sources.
Salicylate sensitivity symptom list
“Symptoms vary between individuals as can the severity of the reactions. A salicylate sensitivity may show itself at any time throughout a person’s life.”
*Someone like me with a lifelong lack of glycine might have salicylate symptoms chronically until the problem is learned. Someone with a temporary excess of acidity in the urine might have short term or fluctuating sensitivity to salicylates whenever the acidity level is too great for the kidney tubules.
“Common symptomatic reactions include:
Rashes, hives, tingling /rash on lips,
Anxiety, panic attacks, Irritability, restlessness
Symptoms of ADHD / ADD,
Rapid heartbeat,
Headaches and migraines, Tinnitus,
Sleep disturbances,
Asthma, Sinusitis, Rhinitis, Constant clearing of throat,
Nausea, Stomach aches, Flatulence, Bloating,
Eczema,
Joint pain”
“If you are suffering from some of the above symptoms and feel you may have a salicylate sensitivity, the best way to assess the situation is a trial for two weeks avoiding foods containing very high and high levels of salicylates from the list provided. Symptoms will disappear or greatly reduce if salicylates are a causative factor. Low salicylate foods include all fresh meat, poultry, eggs, dairy, shellfish and cereals.”
- Salicylate sensitivity (naturopathlife.com.au) *The quoted list is rearranged to be shorter here.
Reading that list was eye-opening for me. I have had the entire list at some time in my life, even “Constant clearing of throat.” That was recently with the increased congestion and asthmatic feeling, it felt like a stuck hairball for a cat - can’t cough out the sticky congestion.
I can add increased edema especially in the lower legs and sodium sensitivity. I was told that people of normal health would not have kidney function that is that sensitive to COX2 inhibition (*COX2 inhibition by pomegranate peel, other antioxidants, or salicylates). Maybe I have early-stage kidney damage, I don’t know.
Knowledge is power to change for the better.
An elimination diet followed by a food trial is the typical way to assess whether salicylate sensitivity is present. There are not really lab screening tests for it. The amounts of salicylates that a sensitive person reacts to is smaller than toxicity amounts would be for average people. In children with ADHD comparing the skill used in coloring pages or written tasks during the elimination phase with work done in the trial day is a tip. (foodmatters.com/Assessing Salicylate Tolerance in children with ADHD) (health.selfdecode.com/salicylate-sensitivity)
Salicylate Content in Foods
Food lists are helpful to identify what might be adding to health problems or which might be more tolerable and worth trying if they are not part of someone’s usual diet. More variety of whole foods used routinely is helpful for microbiome diversity too and may increase total variety of nutrients and trace minerals in a diet, in addition to other phytonutrients like salicylates. For people who are not sensitive to it, or overusing breath mints, Pepto-Bismol, and aspirin, salicylates in plant foods are beneficial and likely protective against cancer.
Food content lists are based on chemical analysis of plant samples, averaging several samples for each type.
“To estimate the intake of salicylates we used several database of salicylates contents in food [30,32,33,34,35,36,37] including our own studies [9,38,39].” (Gajewska, et al., 2020) *most of those links have a paywall.
Vegans were found to consume more salicylates, almost double that of omnivores, and herbs and spices added significantly to estimated salicylate intake. (Gajewska, et al., 2020) The team has a non-paywall article describing their lab process and the explain the controversy in salicylate content as a difference in free forms versus other forms, along with sensitivity of expensive equipment and complicated steps to do the sample preparation and chemical analysis. Their results were consistent with most of the other published results. (Szkop, et al., 2017)
In a study by Janssen, et al., based on urinary excretion of salicylates, the average diet of the study participants was low in salicylates. The research team suggested dietary salicylates may not be very bioavailable, however they found a positive correlation between fiber intake and salicylate excretion suggesting vegetables were more significant sources in that study. (Janssen, et al., 1996) I would guess that the average US diet is not very rich in high salicylate herbs, spices, fruits and veggies. Breath mints might add up quicker.
Food lists for salicylate content can be used to either avoid the sources if sensitive or using other medications that might lead to an excess total intake; or they can be used to add more beneficial phytonutrient rich ingredients to your diet. Where there are salicylates, there are also other helpful polyphenols and the anti-cancer benefits of the foods may be due to the range of phytonutrients rather than the salicylates alone. (Duthie, Wood, 2011)
As food sensitivities accumulate, finding foods that are low in all the problem phytonutrients or chemicals can become trickier. I had increased use of rooibus tea because it is low in oxalate content but it is high in salicylates - more so with a higher heat water. (Santos, et al., 2016) Using it to make a weak Sun Tea, a structured water method, was more tolerable for me, which I tried before learning that it is a salicylate source and problem ingredient for me.
Salicylate content seems to vary and food lists may list foods in different categories. Above 1 mg/kg is considered Very High and between 05-1 mg/kg High. This webpage has printable tables of foods rated by their salicylate content into Negligible, Low, Moderate, High, and Very High. (Salicylate Foods - Food List | ATP Science)
Drier, hotter, more severe growing conditions can increase phytonutrient concentration in a plant - the chemicals are being made to protect the plant from inflammatory conditions or to repel insects or other parasites from eating the plant. Peels and outer leaves may have more salicylate content than the interior of a fruit or younger leaves.
Other things in my routine that add salicylate - Gingko biloba. “Previous studies have shown that ginkgo increases prothrombin time and serum salicylate levels.67” (Wong, et al., 2012)
Fibromyalgia, guaifenesin, and salicylate sensitivity - Dr. St. Amand’s protocol.
Dr. St. Amand felt that he had cured his own case of fibromyalgia with the anti-congestant medication guaifenesin/Mucinex, in combination with reducing salicylates in the diet. His theory as to why it helped seems wrong based on an analysis by Mark London, but the protocol may still be helping people with fibromyalgia as long as they are not also allergic to guaifenisin. Dr. St. Amand used his protocol clinically and eventually told patients that the medication might cause negative symptoms first before it helps them but Mark London says that has never been reported anywhere else while allergy to guaifenesin has been observed. He recommends stopping use if symptoms worsen when the medication is tried. (London, 2007)
This post has more excerpts, discussion and a segue into Retinoid Toxicity as a possible causal factor for some people. Alzheimer’s patients may also be helped by guaifenesin use.
See: Guaifenesin, fibromyalgia, and salicylates.; Opens with a brief look at the need for individualized treatment, that starts 20 years ago ideally ;-) if we want to prevent conditions like Alzheimer's dementia. (Substack) That post also has a partial copy of a food list grouped by salicylate content.
Mark London’s analysis includes a variety of reasons why someone might be ‘salicylate sensitive’ in addition to low DMG or over-acidic urine.
Singulair for a leukotriene sensitivity might help in addition to avoiding salicylates. (London, 2007)
Aspirin’s ability to inhibit cyclooxygenase may be involved. (London, 2007)
COX 1 and 2 inhibition as a factor is discussed in this post: Salicylate strikes again (me); leg edema and COX inhibitors & pomegranate against cancer; There is a learning curve and trial and error to find what works for you with food sensitivities. And "Dose makes the medicine or the poison." (Substack).
Salicylate sensitivity is associated with low glutathione levels and reduced glutathione-peroxidase activity. (Malmgren, et al., 1986; cited by London, 2007)
Nrf2 promoting herbs and spices that are not also rich in salicylates would be helpful then. What do we have left? Leeks, onions, garlic, chives, scallions, shallots, Nasturtium leaves, flowers, seeds, mushrooms; omega 3 fatty acids; delphinidin in black chickpeas or blackbeans, purple carrots, purple cabbage; pomegranate fruit (the peel needs cautious use); chamomile tea if you don’t have seasonal allergies to flower pollen,
Sweet Wormwood, resveratrol as an extract; Moong dal; parsley, apples, pears, figs; Vitamin D and sunshine; probably some other fruits and veggies too.My first Substack post- Nrf2 and NFkB - 2 proteins to know. (Substack)
Fibromyalgia patients may have sleep apnea and being less congested would help that. (London, 2007)
Salicylates can block vitamin K and easy bruising is a common symptom in fibromyalgia. (London, 2007)
*Including me. Taking extra vitamin K2 may be helpful. See the next section for herbs and nutrients that can increase bleeding risk. (Wong, et al., 2012)
Salicylates may increase risk of hypoglycemia (low blood sugar and a tendency for late night eating, to help stay asleep) and low blood sugar could make a fibromyalgia patient feel worse. (London, 2007)
Mark London suggests that avoiding salicylates would also end up reducing phenol and flavonoid intakes. Quercetin and peppermint oil were on Dr. Arman’s avoid list but they are not known sources of salicylates but are rich in flavonoids which may reduce thyroid function. (London, 2007) *Here Mark London may be wrong about peppermint oil - he says salicylate content research has had errors in the past, but mint seems conclusively to be a rich source among fairly recent research papers that I found - did they repeat the chemical analysis? I don’t know. Mint was also highlighted in the toxicity review paper as a frequently unrecognized source of excess salicylates. (Palmer and Clegg, 2020)
Hypothyroidism is common among people with fibromyalgia who tend to improve when the thyroid condition is improved. (London, 2007) *I also had low thyroid symptoms when fibromyalgia was worse for me.
Salicylic acid may cause problems by increasing loss of sulfate in the urine. Sulfur may be low in fibromyalgia patient and lack of it may affect connective tissue in a way that feels like lumps under the skin. (London, 2007)
*Muscle knots/tiny cramp points that never seem to relax. I swear by magnesium sulfate, Epsom salt baths, foot or hand soaks.
The dose of guaifenesin recommended for the Armand/fibromyalgia protocol is quite high compared to use just for occasional congestion. I have a 400 mg immediate release dose and a 1200 mg extended release which is stated to last 12 hours. Up to 5000 mg per day may be the weight-based dose of the drug if used to cause temporary paralysis in animals. Fibromyalgia patients tend to use 600 mg to 3600 mg/day which may have muscle relaxant and pain-relieving effects in addition to the congestion relief. A dose of 1500 mg/day is used for the muscle relaxant version called guaifenesin carbamate. Mark London suggests that the muscle relaxant effect is what is leading to a clearing of mucus as guaifenesin does not have direct effects on mucus (*like citrus peel does via bitter taste receptors in lung cells). Guaifenesin also has an anti-anxiety effect - a relaxant for worrying perhaps. (London, 2007)
Cautions with use of guaifenesin: Perhaps not coincidentally, guaifenesin has anticoagulant effects.
Guaifenesin has an anticoagulant effect (Buchanan, et al., 1977) and two other drugs used by Dr. St. Amand for fibromyalgia do also (anturane and probenecid). People with Chronic Fatigue Syndrome/Fibromyalgia Syndrome (CFS/FMS) have been found to have hypercoagulant activity and initial trials with heparin found some success. (Lassesen, 2016) (Cited by London, 2007)
Guaifenesin is not a strong anticoagulant and it breaks down quickly but may have additive impact along with other drugs or supplements with anticoagulant effects. (London, 2007) Ginger, vitamin E, lots of nuts (vit E source), omega 3 fatty acids, are a few food sources with anti-coagulant effects. (Wong, et al., 2012)
Other cautions with long term use of guaifenesin - stop use if hiatal hernia occurs or if joint pain worsens instead of improving. The negative symptoms stopped with cessation of the guaifenesin. (London, 2007)
Bleeding risk from medicinal plants or other nutrients
A review article by Wong, et al., 2012 includes a handy list of herbs and nutrients that may increase bleeding risk post-surgery, so stopping them a few weeks prior to elective surgery is recommended. If bruising is occurring too easily and extra vitamin C isn’t helping, then it may be a combination of too many foods, nutrients and herbals with anti-coagulant or anti-platelet properties. Vitamin E plus ginger, garlic, and salicylates sources can add up to easy bruising - mystery bruises where you don’t remember bumping into anything. Elbow pressure from leaning on top of the knees shouldn’t really cause bruises. The article also lists scullcap, licorice, and bromelain (and many others). (Wong, et al., 2012)
Anyone may be at risk from Salicylate Toxicity from chronic combined use of salicylate containing medications, mint products, and other food sources. Salicylate sensitive people would just reach toxic levels faster.
What we don’t know can hurt us. It can also hurt our mitochondria and gut microbiome. Excess salicylates can inhibit methylation cycles which can lead to mitochondrial dysfunction and chronically could increase risk of genetic changes that lead to cancer or Parkinson’s disease. Salicylates can inhibit acetylation of histones (Shirakawa, et al., 2016) which is an epigenetic control that activates genes. (Lee, et al., 2020) This may be how salicylates are helpful in tamping down overactive genes in cancer conditions if excess acetylation of gene histones is a problem. (Xu, Wan, 2023)
“Results: Salicylate inhibits CBP/p300 acetyltransferase activity by directly competing with acetyl-CoA in vitro” (Shirakawa, et al., 2016)
Salicylate excess may disrupt autophagy and reduced autophagy can be a factor in cancer, aging and neurodegenerative conditions. (Xu, Wan, 2023)
“Importantly, dysfunction of p300-regulated autophagy has been implicated in a number of human disorders, such as cancer, aging and neurodegeneration…” (Xu, Wan, 2023)
Epigenetic control by acetylation of histones upregulates gene expression, while methylation of gene histones can cause either up or down regulation of a gene. (Lee, et al., 2020)
“Histone acetylation occurs at lysine residues and it increases gene expression in general. (B) Histone methylation: Methylation is catalyzed by histone methyltransferase. Histone demethylase reverses methylation. Methylation activates or represses gene expression depending on which residue is methylated.” (Lee, et al., 2020)
“It is well known that DNA methylation and histone deacetylation both repress gene transcription. When histones are acetylated, their electrostatic interactions with DNA become weaker, resulting in relaxed chromatin, which upregulates transcription; the opposite happens when histones are deacetylated by HDAC.36,37” (Lee, et al., 2020)
Epigenetics, a definition.
“The definition of epigenetics is the study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence (i.e., a change in phenotype without a change in genotype). Epigenetic mechanisms include DNA methylation and histone modifications, which consist of acetylation, methylation, phosphorylation, deimination, ubiquitylation, sumoylation, and ADP ribosylation, and these modifications affect the chromatin structure and create affinities for chromatin-associated proteins, thereby modulating gene expression. MicroRNAs (miRNAs) are short, non-coding RNA molecules that mediate RNA silencing and regulate gene expression. Therefore, miRNAs have also been identified as components of the epigenetic machinery.” (Lee, et al., 2020)
Tangent - POTS is a comorbid condition with Fibromyalgia, and it involves epigenetic lack of acetylation of histones (causal link probably, rather than coincidental) - meaning it can be reversible - Good News!
Lack of acetylation may be a causal factor in Postural Orthostatic Tachycardia Syndrome (POTS), leading to reduced expression of a transport protein needed for reuptake of norepinephrine. (Khan, et al., 2017) I have had POTS like symptoms twice and got myself better twice. Fibromyalgia and POTS are known to be comorbidities. Migraine was the most frequent comorbid condition with POTS, followed by fibromyalgia, Chronic Fatigue Syndrome, and Irritable Bowel Syndrome. (Chemali, McNeeley, 2014)
What helped me get better twice from POTS symptoms was consistent use of methyl B vitamins and to reduce both smoking and secondhand smoke (medical marijuana). Methyl folate is needed to breakdown formaldehyde and stress and bad air can increase that. Formaldehyde interferes with acetylation of histones - the endogenous, self-formed type possibly more than external sources. (Chen, et al., 2017) Stress and smoking would be additive and there can be dietary sources of formaldehyde.
Common medications that contain salicylates & incidence rate of salicylate poisoning.
“Salicylates are found in a myriad of prescription and over-the-counter medicinal preparations, including acetylsalicylic acid tablets and analgesic mixtures. Methyl salicylate (oil of wintergreen), found in topical liniments and solutions used in hot vapors, is the most concentrated form of salicylate: 1 ml of a 98% solution contains 1400 mg of salicylate.4 A large amount of salicylate (8.7 mg per milliliter) is also found in bismuth subsalicylate, which is sold as a generic medication under the brand name Pepto-Bismol. The widespread availability, ease of access, and frequent coingestion of multiple salicylate-containing agents, combined with the nonlinear pharmacokinetic properties of salicylate, make salicylism a common and sometimes fatal occurrence (Figure 1). On the basis of data from 2014 through 2018, approximately 25,000 exposures to acetylsalicylic acid are reported annually to poison control centers in the United States.8,9 In 2018, acetylsalicylic acid alone was involved in 17,380 cases* of salicylate poisoning, with unintentional exposure more common than intentional exposure.9 [26 of the patients died in 2018.] (Palmer and Clegg, 2020)
Obituary to avoid: Died slowly, from chronic over-use of baby aspirin, Pepto-Bismol and breath mints.
Other posts about salicylate sensitivity:
Salicylate Toxicity vs Sensitivity and our Microbiome; Good news, increasing dimethylglycine intake might help, as the liver uses it to deactivate salicylates. Preventing acidity within the body & urine also would help, small amounts of baking soda. (Substack)
Salicylate Sensitivity & more food lists, protein in beans, Indian cuisine, Type 2 DM, alcoholism and boundaries; Another walk around the block post. With fruit! *So I added a tl;dr. (Substack)
Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of Fair Use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a *functional health professional for individual health care purposes.
Reference List
Assessing salicylate tolerance in children with ADHD, foodmatters.com, https://www.foodsmatter.com/allergy_intolerance/salicylate/research/salicylate_tolerance.html
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Salicylate Foods - Food List | ATP Science)
Salicylate Sensitivity, health.selfdecode.com, https://health.selfdecode.com/blog/salicylate-sensitivity/
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