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.

Picky eating ~ less than 15 whole foods eaten on average.

Healthy gut biodiversity promoting goal ~ 40 or more whole foods eaten on average is a goal for better gut and microbiome health according to Sarah Greenfield, RDN, CSSD. A wider range of foods, even the different varieties within a food type, can include a different range of phytonutrients, vitamins and trace minerals, such as a red apple compared to a Granny Smith green apple. Purple/black varieties of produce or beans have delphinidin.

Food lists can be helpful to remind you of things you don’t eat regularly, or that might be better tolerated. Food lists can help get you closer to 40 foods in your average diet instead of 15.

• Gut Brain Superhighway webinar slides; Host: Susan Allen-Evenson, RDN, CCN, FMN, Presenter Sarah Greenfield, RDN, CSSD, (pdf in my Dropbox)

Why talk about salicylate sensitivity - because it is a risk that can also be a toxic risk in greater excess and even lead to death. It also interferes with methylation when in excess and our cells and our mitochondria need to be able to methylate with the Citric Acid Cycle for better health and a less acidic body. The gut problems associated with salicylate sensitivity would be disrupting microbiome health too.

What is Methylation and Why Should I Care? (nbwellness.com) *The article includes the graphic but has only a brief overview about methylation cycles rather than trying to explain it. The take home point from the plate of spaghetti graphic is - our body’s function is really complex and it needs our help instead of us taking health for granted. It isn’t just ‘our’ health at stake- it is also our microbiome and mitochondria’s health that our diet and other choices affect. We are symbionts, not a ‘single’ organism. Let’s try not to be a selfish host for our collective community of tiny supporters.

This post, Salicylate Sensitivity vs Toxicity, is third in a series on salicylate sensitivity: post 1: Guaifenesin, fibromyalgia, and salicylates. (Substack) post 2: Salicylate Sensitivity & more food lists, protein in beans, Indian cuisine, Type 2 DM, alcoholism and boundaries. (Substack)

*Addition - 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 includes more foods than the link in my last post about salicylates. (Salicylate Foods - Food List | ATP Science)

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)

What we don’t know can hurt us. It can also hurt our mitochondria and gut microbiome.

“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 Pepto-Bismol and breath mints.

It seems that ‘salicylate sensitivity’ is a misnomer. Having a ‘Food sensitivity’ suggests digestive intolerance to me more than a potentially life-threatening accumulation of a bioactive chemical which the liver isn’t breaking down properly, and or the kidneys aren’t able to excrete because the urine is too acidic. I am sensitive to TRP channel activators but they cause digestive upset for me more than a toxin overload. Oxalates can cause bladder pain and may create kidney stones but are not a ‘toxin’ that can cause brain damage typically. Dietary sources alone are unlikely to reach the clearly toxic amounts available in aspirin or essential oil of mint/wintergreen/peppermint.

What is a toxin? Anything that becomes toxic in an individual. The other food sensitivities can also lead to, or follow, microbiome dysbiosis, which can be caused by stress or even a brief social discomfort, (animal-based study). (Galley, et al., 2014) Our large intestine/colon microbiome is particularly beneficial for protecting the colon from cancer due to the anti-inflammatory effects of the short chain fatty acid (SCFA) butyrate, which activates the niacin GP109 receptor. SCFAs are also a food supply for our colon cells, so they go hungry if our microbiome is unhealthy and not making butyrate and other types of short chain fatty acids. (Ríos-Covián, et al., 2016)

Chiron, the wounded healer of mythology, is an archetype that I fit. I learn how to heal myself and share the info in hope of helping others learn and heal themselves - and maybe to encourage myself to stick with self-care routines. Blogging is also my way of taking notes that I later organize into topic web pages, initially on effectivecare.info and more recently on jenniferdepew.com. I strongly believe that the public deserve free public health education that will work and isn’t too hard to understand - that part is a little difficult.

Why am I “salicylate sensitive”? - maybe low glycine and excess acidity.

Give myself a prize, or a Cheerful Juice - I am salicylate sensitive probably, because of my genetically low dimethylglycine. Glycine is used in the liver in the processing of salicylic acid.

“Figure 1. […] SA is mainly metabolized by the liver into its glycine conjugate, salicyluric acid, and its glucuronic acid conjugates, salicyl phenolic glucuronide and salicyl acyl glucuronide.” (Palmer and Clegg, 2020)

And having more alkaline urine helps the body to excrete it, while more acidic urine helps the kidney tubules reabsorb it. So, the baking soda water after high dose niacin is important for me. I have tended to be too acidic with the high dose niacin intake. In between meals and a cautious amount, is the goal with baking soda in water because you need stomach acid to digest food properly and cautious because our acid/alkaline balance is delicate. As we have seen, small amounts of chemicals can cause a big impact, even in the form of strawberries and raspberries.

“Figure 3 - “Acidic urine favors protonation of salicylate, increasing its solubility and enhancing absorption by the tubules. In contrast, as the urinary pH rises from 5 to 8, the amount of free ionized salicylate excreted increases logarithmically from 3% of the total salicylate dose to more than 80% through ion trapping in the urine.” (Palmer and Clegg, 2020)

Acute and Chronic Salicylate Toxicity is often misdiagnosed, or delayed diagnosis due to multiple tests and screening for the other wrong diagnoses.

“The diagnosis of acute intoxication is generally straightforward, but chronic salicylate poisoning can be difficult to diagnose, in part because there is no clear history of excess ingestion. Although clinical findings overlap, classic symptoms and signs tend to be milder or absent in cases of chronic toxicity and may in fact be attributed to other disease processes or the ailment that was being treated (Table 1). Age-related decreases in hearing acuity may attenuate the perception of tinnitus or its cause. Tachypnea and rales on pulmonary examination may be attributed to preexisting lung and cardiac disease as opposed to salicylate-induced noncardiogenic pulmonary edema. Hyperpyrexia and altered mental status can be mistaken for sepsis, and metabolic acidosis accompanied by circulating ketone bodies may be ascribed to diabetic or alcoholic ketoacidosis. (Palmer and Clegg, 2020)

Bad news - excess salicylates can affect the brain, mood, and lead to even worse mental symptoms before descending into seizure and then a coma. Clearly, too much accumulation of salicylates in the medicine cabinet, topical, and diet is a toxic risk.

Neurologic abnormalities, such as agitation, confusion, hallucinations, slurred speech, seizures, and coma, occur more frequently in patients with chronic salicylate poisoning than in those with acute intoxication. “Salicylate jag” refers to restlessness and mental aberrations that are reminiscent of alcohol intoxication. In one series, 60% of patients underwent intensive neurologic investigation, which delayed the diagnosis of salicylism for up to 3 days after admission.¹⁰ Delays in diagnosis and therapy account for the higher morbidity and mortality associated with chronic intoxication than with acute intoxication. A high level of suspicion for chronic salicylate intoxication is needed in evaluating at-risk patients who have tachypnea, acid–base disturbances (particularly an unexplained respiratory alkalosis), and nonfocal neurologic abnormalities and in elderly patients who have a deterioration in activities of daily living with no known cause. Even in the absence of a documented history of ingestion, plasma levels should be measured if salicylate intoxication is suspected.” (Palmer and Clegg, 2020)

What is going wrong in the body with too much salicylate present?

Salicylate excess inhibits normal methylation cycles, shifting it away from the Citric Acid Cycle to glycolysis. Glycolysis is the partial breakdown of glucose without the use of oxygen. It is more inefficient, producing more acidic waste and less usable energy in the form of ATP.

Pathophysiology “Toxic levels of salicylate exert a direct stimulatory effect on the respiratory center of the medulla, causing an increase in the rate and depth of respiration and the development of respiratory alkalosis. Salicylates also uncouple oxidative phosphorylation and inhibit citric acid cycle dehydrogenases, causing a shift in metabolism to glycolysis for energy production²⁹ (Figure 2, Mechanisms of Acid–Base Disturbances in Salicylate (SA) Toxicity.).” (Palmer and Clegg, 2020)

With less available energy from burning glucose, the body starts to breakdown the body more to make up the difference. This may increase membrane and muscle problems along with upset biochemistry. Details below:

“A compensatory increase in body catabolism and substrate breakdown is required to supply the energy needed for the increasingly inefficient production of ATP from ADP through glycolysis. This response is manifested by increased oxygen consumption, increased heat production (leading to hyperpyrexia, diaphoresis, and dehydration), depletion of liver glycogen, and increased metabolic production of carbon dioxide. Although it is not common, neuromuscular irritability manifested as paratonia and extreme muscle rigidity can develop, further contributing to hyperthermia and increasing the risk of rhabdomyolysis.^39-41 The accumulation of ketoacids and other organic acids accounts for the majority of the increase in the anion gap. The contribution of salicylate is minor (<5 mmol per liter). Increased renal bicarbonate excretion in response to respiratory alkalosis decreases buffer capacity, potentially worsening the degree of acidosis as organic acids accumulate (Figure 2). (Palmer and Clegg, 2020)

Medical dictionary STAT. “…neuromuscular irritability manifested as paratonia and extreme muscle rigidity can develop…” (Palmer and Clegg, 2020)

Paratonia - inability to relax muscles even when trying to move the limb passively - see training video (Youtube). It may be taken as a patient not understanding directions instead of having an abnormal stiffness in their muscles.

I have muscles in my left shoulder that stay too rigid all the time and it has been worse lately. A many decades long problem for me, suggesting salicylate sensitivity has been a many decades long problem or lifelong issue for me too.

The article by Palmer and Clegg, 2020 includes treatment information for acute and chronic cases and it is potentially tricky because of the acid/alkaline upset. Sodium bicarbonate is not given orally to promote more alkaline urine if it is an acute ingestion of tablets that may not be fully dissolved. Sodium bicarbonate is given by IV. Hemodialysis is used in more severe cases or for patients with mental symptoms. The concern is that if the blood becomes more acidic the salicylate can easily enter cells and the brain and brain cells and cause more severe damage.

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

(Galley, et al., 2014) Galley JD, Nelson MC, Yu Z, Dowd SE, Walter J, Kumar PS, Lyte M, Bailey MT. Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota. BMC Microbiol. 2014 Jul 15;14:189. doi: 10.1186/1471-2180-14-189. PMID: 25028050; PMCID: PMC4105248. https://pubmed.ncbi.nlm.nih.gov/25028050/

(Palmer and Clegg, 2020) Palmer, B.F, Clegg, D.J., Salicylate Toxicity, N Engl J Med 2020; 382:2544-2555 DOI: 10.1056/NEJMra2010852  https://www.nejm.org/doi/full/10.1056/NEJMra2010852 *You can register for two free articles a month - so I made an incomplete copy, it is missing a Table that needs to be scrolled regarding hospital type treatments. (pdf in my Dropbox)

(Ríos-Covián, et al., 2016) Ríos-Covián D, Ruas-Madiedo P, Margolles A, Gueimonde M, de Los Reyes-Gavilán CG, Salazar N. Intestinal Short Chain Fatty Acids and their Link with Diet and Human Health. Front Microbiol. 2016 Feb 17;7:185. doi: 10.3389/fmicb.2016.00185. PMID: 26925050; PMCID: PMC4756104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756104/