S is for Salicylate

Salis-a-What!!

I know what you are thinking, not another chemistry lesson! Please keep reading because THIS one is important, at least it has been VERY important to OUR family.

When I was in 2nd or 3rd grade I remember being told never to take Aspirin, and that I was allergic to it. My parents don’t really remember why. I remember having really bad nosebleeds in school, maybe that was my reaction to those memorable little orange flavored St.John’s “Baby Aspirin”, who knows. I haven’t thought about it much over the years (other than writing it on a few medical forms here and there under the medication allergies category)….until recently.

As you may know from reading this blog, my daughter is currently being evaluated for mitochondrial disorder/metabolic disorder. We still do not have a definitive diagnosis and may not for some time. And while we do not know, yet, what to call the “thing” that is happening in her little body, we do know one “thing”: She is EXTREMELY sensitive to certain foods and chemicals. For the last year I have been on a quest (an thus the inspiration for this blog) to feed her the healthiest diet I could: organic fruits, vegetables, and meat. As we slowly introduced foods over the last year, we had a short list of things her body could tolerate and a LONGER list of things her body could no tolerate (as in it came FLYING through her with lots of screaming and crying to boot, sorry for the TMI). Being the chemist I once was (and still am in my heart!), it concerned me every time the DO NOT EAT list grew, especially when the foods I was adding to it were WHOLE ORGANIC FRUITS and VEGETABLES. How could this be, I wondered, the healthier I seemed to feed her, the worse things seemed to be getting (or if they weren’t getting worse, they surely weren’t getting any better). I sat down with a spreadsheet (geeky, I know!) and filled in all the foods she could not eat…and asked myself what they all had in common. After many a google search later, I realized that the foods on her DO NOT EAT list all contained: PHENOLIC compounds (a benzene ring with an alcohol group hanging off of it!)

As I read further I found links to the AUTISM community and children there who are highly sensitive to phenols  (editor’s note- the FOOD LIST on this website is not the one we follow, see below) and then I had my A-HA moment she was reacting to: SALICYLATES (an aspirin like compound that occurs naturally in fruits and vegetables as the plants natural defense mechanism against insects…aka a natural pesticide built right into the food by God!)

So for those of you who are following along (thank you for reading this far!), here are some links that helped me realize how all these foods my daughter was reacting to were linked and how I realized there are other people out there who are struggling with Salicylate Sensitivity (kids), and adults, even Wikipedia has a listing about it!

So off I went, searching and searching for more answers…and what I found along the way was really eye-opening to me. I truly believe God has led me on this path of discovery to help my daughter, but also to help someone else (hopefully lots of someone elses!)

There are 4 major “clues”  that have links to Salicylates that I have discovered:

Here is my Hypothesis:  Salicylate Sensitivity is a symptom of an underlying metabolic malfunction involving intermediates of the Krebs Cycle (Citric Acid Cycle) and oxidative phosphorylation in Mitochondrial energy production (ATP), and for those who have this underlying metabolic issue (either genetic and Inborn or toxicity induced), salicylates can add insult to injury (further disrupting this perhaps already damage metabolic cycle). I believe this hypersensitivity can extend to natural salicylates found in fruits and vegetables (causing similar physiologic symptoms that aspirin can cause in sensitive individuals), since it is possible to ingest nearly equivalent amounts to a baby aspirin (81mg) of salicylates in a few servings of HIGH salicylate containing foods.

A database of adverse side effects of ASPIRIN- here

Here are the References I have found for each of the 4 Areas:

Mitochondrial:

One of the initial clues that salicylates may be a problem was after listening to this Webinar about mitochondrial Toxicity on http://www.mitoaction.org:  http://www.mitoaction.org/blog/medication-exposures-mitochondrial-toxicity

And seeing Aspirin (as well as MANY other well known medications (both prescription and OTC) on this MITOCHONDRIAL TOXICITY chart: http://www.mitoaction.org/files/Mito%20Toxins%20Chart.pdf

1962 Paper Salicylates Uncouple Oxidative phosphorylation in Rat Liver:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1243602/pdf/biochemj00802-0191.pdf

Aspirin Textbook referencing Mitochondrial toxicity

Oxidative Stress Is Responsible for Mitochondrial Permeability Transition Induction by Salicylate in Liver Mitochondria:  http://www.jbc.org/content/280/40/33864.full.pdf

Salicylate Toxicity/Aspirin Overdose which explains how Salicylates influence metabolism: “Meanwhile organic acids (pyruvate & lactate) accumulate in the periphery because ATP is no longer being generated through the Krebs cycle, as several of the Krebs cycle enzymes are blocked by excess salicylate. The body becomes increasingly dependent on the less efficient anaerobic energy pathways by way of which more energy is dissipated as heat. This produces fever & increased utilization of glucose. This inhibition of glucose oxidative metabolism is particularly hazardous to the brain because of the inability of neuronal tissue to employ fatty acids as an alternative fuel. The resulting lipolysis increases production of ketones & organic acids culminating in metabolic acidosis when the body’s buffering capacity becomes sufficiently depleted. These metabolic changes eventually lead to renal depletion of fluid & electrolytes, hypoglycemia, hypokalemia & a mixed picture of respiratory & metabolic alkalosis coupled with metabolic acidosis which may provoke cardiac dysrhythmias, acute pulmonary edema, renal failure or neurological injury.” excerpt from here

Effect of organic synthetic food colours on mitochondrial respiration.

Abstract

Eleven organic synthetic dyes, currently or formerly used as food colours in Brazil, were tested to determine their effect on mitochondrial respiration in mitochondria isolated from rat liver and kidney. The compounds tested were: Erythrosine, Ponceau 4R, Allura Red, Sunset yellow, Tartrazine, Amaranth, Brilliant Blue, Blue, Fast Red E, Orange GGN and Scarlet GN. All food colours tested inhibited mitochondrial respiration (State III respiration, uncoupled) supported either by alpha-ketoglutarate or succinate. This inhibition varied largely, e.g. from 100% to 16% for Erythrosine and Tartrazine respectively, at a concentration of 0.1 mg food colour per mitochondrial protein. Both rat liver and kidney mitochondria showed similar patterns of inhibition among the food colours tested. This effect was dose related and the concentration to give 50% inhibition was determined for some of the dyes. The xanthene dye Erythrosine, which showed the strongest effect, was selected for further investigation on mitochondria in vivo. reference here.

Gastrointestinal:

The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine: http://www.ncbi.nlm.nih.gov/pubmed/21373261

Mitochondrial disorders in NSAIDs-induced small bowel injury: http://www.ncbi.nlm.nih.gov/pubmed/21373263

2005 paper  SIGNIFICANCE OF SALICYLATE INTOLERANCE IN DISEASES OF THE LOWER GASTROINTESTINAL TRACT: http://www.jpp.krakow.pl/journal/archive/09_05_s5/pdf/89_09_05_s5_article.pdf

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat:  http://www.ncbi.nlm.nih.gov/pubmed/10792129

A scientific journal article written in 2006, Germany, all about Salicylate Intolerance:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696737/

Neurologic:

Many more studies listed here (particularly for artificial salicylates (food additives and coloring): http://feingold.org/research.php  

(We found the Feingold resources to be useful, however our daughter reacted to MANY of the foods allowed in STAGE 1 of their program.)

Salicylate sensitivity in children reported to respond to salicylate exclusion:  http://www.ncbi.nlm.nih.gov/pubmed/364260?dopt=Abstract

Hypersensitivity Of Salicylates from 1964 paper: http://www.feingold.org/Research/shelley.html

Reye’s Syndrome:

www.reyessyndrome.org

Biochemical relationships between Reye’s and Reye’s-like metabolic and toxicological syndromes:   http://www.ncbi.nlm.nih.gov/pubmed/2671597

Effect of Salicylic Acid on Mitochondrial Peroxisomal Fatty Acid Catabolism: www.reyessyndrome.org/pdfs/Effect_of_Salicylic_Acid_on_Mitochondrial-Peroxisomal_Fatty_Acid_Catabolism.pdf

Reye syndrome and Reye-like syndrome

http://www.ncbi.nlm.nih.gov/pubmed/18725066

http://www.ncbi.nlm.nih.gov/pubmed/18711704

http://www.ncbi.nlm.nih.gov/pubmed/21400838

“Reye syndrome (RS) is an acute metabolic encephalopathy and hepatopathy affecting children and adolescents. Outbreaks of RS were common in United States until the early 1980s. However, after the abolition of salicylate (aspirin) therapy for infectious diseases such as influenza or varicella in patients under 18 years of age the incidence decreased. Now classical RS is rare and RS is considered a secondary mitochondrial disease. Reye-like syndrome (RLS), resulting from congenital errors of mitochondrial fatty oxidation, especially medium-chain acyl-CoA dehydrogenase deficiency, has increased due to progress in diagnostic techniques and methods after 1990. Diagnostic differentiation between RS and RLS is difficult because the end results of mitochondrial dysfunction inRS and RLS may be similar.”

I do not have full access to this journal article but recently salicylate intoxication has been noted in infants through teething gel exposure:  http://www.ncbi.nlm.nih.gov/pubmed/21299491

Medical Subject Heading for Reye’s:

http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Reye+Syndrome

Reye’s Statistics/History:

 http://www.web-pub.com/library/brochure/reye-syd.html

Resources for Implementing a LOW SALICYLATE DIET:

A video on Salicylate Sensitivity and Diet:  http://fedup.com.au/images/stories/VSalicylates.mp4

and link to a fact sheet on salicylates:                    http://fedup.com.au/factsheets/additive-and-natural-chemical-factsheets/salicylates

The most comprehensive testing and list of measured amounts of Salicylates in Foods (starting on pg. 32): Anne Swain’s Thesis:  http://www.sswahs.nsw.gov.au/rpa/allergy/research/students/1988/AnneSwainPhDThesis.pdf

Top 10 foods with HIGH Salicylates (if you or your child has problems with these, they may have a salicylate issue…): http://www.ifood.tv/blog/top-10-food-contianing-salicylates

I like this easy to read chart (handy to print and take to the grocery store):  Salicylate level Chart

Here is a LONG list of Salicylate Sensitivity Symptoms (say that 5 times fast!)

2 COOK BOOKS for Salicyalte Sensitivity Cooking:

http://www.salicylatesensitivity.com/downloads/the_salicylate_sensitivity_cookbook.pdf  (online and FREE)

http://www.salicylate.org/www.salicylate.org.html (Costs around $20 but WELL WORTH IT FOR IDEAS!)

A great blog about Salicylate Sensitivity:  http://salicylate.org/www.salicylate.org.html

Eating Fruits and vegetables can Equal nearly a “baby” aspirin’s worth of Salicylate “Vegetable and fruit intake at a level consumed by vegetarians provides a level of dietary salicylates that appears to be equivalent to 75 mg of aspirin”                     Urinary excretion of salicyluric and salicylic acids by non-vegetarians, vegetarians, and patients taking low dose aspirin:  http://www.ncbi.nlm.nih.gov/pubmed/12944546

Cranberry Juice (high in salicylates) excretion in urine: http://pubs.acs.org/doi/abs/10.1021/jf040393b

Salicylic Acid Content of Spices (high in salicylates) and Its Implications:  http://pubs.acs.org/doi/abs/10.1021/jf058158w

So what does this all mean… well for us it means a VERY limited diet for my daughter which consists of about 25 foods that we attempt to rotate on a daily basis, trying each day to make them look and taste “new” to her and attempting to broaden her diet slowly and carefully. But discovering  our little gals sensitivity to this chemical (by the grace of God!) has meant the difference for her (and us) BETWEEN: pain, misery, tears AND joy, laughter, and smiles. For you or your family it may mean nothing…because you do not have a genetic predisposition or toxic exposure that makes you sensitive to this compound (salicylates)… for your family “it” may be something different… casein, gluten, sulfates, nitrates, histamine, oxalates, etc. I challenge you to investigate and look for the “it” that troubles your health and your families!

It NOW makes PERFECT sense to me how Brilliant this quote by Lucretius is:

What is food to one man is bitter poison to others.   

Others I have met on this journey who are also dealing with Salicylate Sensitivity-

The Paleo Mom

Are your veggies attacking you? You might have salicylate sensitivity!