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.

This post is the first of a series about salicylate sensitivity and toxicity, and guaifenesin for fibromyalgia too.

• 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)

• Post 3: Salicylate Sensitivity vs Toxicity, (Substack)

A couple good passages, out of order here, from a longer post about the need for live-in treatment, healing food and education, for people with chronic fatigue and brain fog type conditions. Alzheimer’s is something to prevent 20 years ago. So, start early. (Substack) It wanders a bit - these are key points:

“Similar Steps” as I mentioned earlier - does not mean treating everyone with the same “Protocol” or “Stack of supplements”. It means screening everyone similarly to find out what they individually may need from the list of 20 or more nutrient factors that may be involved in mitochondrial dysfunction. Or what may be in excess and needs to be reduced.

Major point not to forget - the mental illness progression seems to be, mild anxiety/depression, get prescribed antidepressants/anti-anxiety pills → those cause mitochondrial support nutrient depletion —> leading to bipolar or schizophrenia diagnosis and more prescriptions —> which deplete more of the important nutrients —> leading to Alzheimer’s or other dementia.

Chronic fatigue patients may have mental symptoms that get them put on the above slippery slope or they may receive other meds that cause nutrient imbalance.

What neither group tends to get is an analysis of 20 nutrients to see which of the 20 or more are deficient or in excess.

What I discovered in a series last summer was that the list is even longer really of factors that might be causal of ‘schizophrenia’. When a condition is given a ‘name’ then it is treated as if it is a ‘single thing’, rather than as a systemic dysfunction that can have multiple causal factors all adding to the condition - and all needing to be addressed potentially before the ‘condition’ will be ‘cured’.

When you have 20 things wrong with you and your insurance company and doctor only want to look for one thing to treat, then that leaves you with 19 unresolved issues or 20 unresolved issues and possibly an unnecessary treatment that may cause other incidental harm.

Methylation and Smoking or nicotine, are bad, um kay!

Reviewing the methylation information in a recent post highlighted for me that both nicotine and smoking are bad, um kay. I no longer seem to need nicotine to control spike symptoms, I just like nicotine. But it doesn’t like me. It causes digestive upset too easily and it turns out is directly interfering with my ability to methylate properly, which I don’t do well due to gene alleles anyway. I am going to try again to switch to non-smoked cannabinoid sources and stop the nicotine lozenges.

All the hard work on buckthorn removal did leave me a little wiped out for a day or too but no new shingles at least. I took some of my Sweet Wormwood/Black walnut extract this morning as I was feeling worse, and extra bromelain, quercetin and an extra nattokinase. I am congested. My hesperidin product meant for weight control also helps congestion. Hesperidin is a citrus peel nutrient that doesn’t cause histamine problems.

Guaifenesin for fibromyalgia - a protocol by Dr. St. Amand that may help for reasons other than his theory for why it helps. Also avoiding salicylates may help.

I am also restarting guaifenesin which was mentioned in a comment regarding fibromyalgia treatment. I had used it in the past for a while and it helped but it wasn’t for fibromyalgia specifically. While my fatigue and all over pain has been better for the most part, a long-term muscle cramp in my left shoulder has been worse and that was also part of my fibromyalgia symptoms.

“Amand claims that guaifenesin relieves fibromyalgia symptoms by ridding muscles, tendons, joints, and other tissues of harmful calcium phosphate ...” - Dr. Andrew Weil 2014 (drweil.com) *He does not recommend it, not enough positive research or any peer reviewed at the time.

Dr. Weil hasn’t had to cure himself of the problem, so his opinion is not one of lived experience. Dr. St. Amand felt that he had cured his own fibromyalgia with the guaifenesin plus avoiding what he considered sources of salicylates - they are also sources of phenols and flavonoids (discussed later).

Avoiding salicylates in food sources or from aspirin is recommended as part of the guafenesin protocol developed by Dr. St. Amand and a review of salicylate sensitivity symptoms looks like I am looking in a mirror….hmmm. News or me to use! See: Salicylate sensitivity (naturopathlife.com.au)

“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. 

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.

Foods that are very high or high sources of salicylates do include several of my favorite spices and this information helps explain why I had such a gassy reaction after increasing use of ginger and hot pepper - both are very high sources of salicylates. More on food sources to follow.

Dr. St. Amand’s theory as to why guaifenesin helped and why avoiding salicylates was needed to make it work - are not accurate according to this thorough analysis:

• The Truths and Myths of the use of Guaifenesin for Fibromyalgia -or- Guaifenesin:  One Medicine, Several Effects, by Mark London, Last modified: 11/24/2021 (web.mit.edu)

Mark London suggests the ‘phosphorus’ theory by Dr. Armand is really a problem of low magnesium levels, which I agree with 100%. He thinks guaifenesin at higher doses, around the clock, could be helping fibromyalgia due to its muscle relaxing and pain-relieving benefits. He does not think salicylate intake would make guaifenesin less effective though unless it was a very large dose - medicinal dose - of salicylates (aspirin). He thinks fibromyalgia patients may have salicylate sensitivity, and when you add enough extra pain signaling, then the anti-inflammatory or pain-relieving medications you are using may not seem to be working as well.

“In large enough doses, salicylates significantly inhibit oxidative phosphorylation, the process that creates ATP.  ATP is source of energy for the body, and ATP  levels has been shown to be low in people with fibromyalgia.  Whether people are exposed to high enough levels for this effect to be noticed is unknown.” - Mark London, (web.mit.edu)

*In other words, high dose salicylates might be inhibiting use of the Citric Acid Cycle which would reduce methylation and energy level.

Mark London lists several biochemical reasons that some people may be salicylate sensitive and how guaifenesin use might help people with fibromyalgia.

Summary tips -

• Singulair for a leukotriene sensitivity might help in addition to avoiding salicylates.

• Aspirin’s ability to inhibit cyclooxygenase may be involved.

• Salicylate sensitivity is associated with low glutathione levels and reduced glutathione-peroxidase activity. (Malmgren, et al., 1986)

• Fibromyalgia patients may have sleep apnea and being less congested would help them.

• Salicylates can block vitamin K and easy bruising is a common symptom in fibromyalgia. *including me.

• Salicylates may increase risk of hypoglycemia which could make a fibromyalgia patient feel worse.

• Mark London suggests that avoiding salicylates would 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. Hypthyroidism is common among people with fibromyalgia who tend to improve when the thyroid condition is improved. (web.mit.edu) *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. (web.mit.edu) *Muscle knots/tiny cramp points that never seem to relax.

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 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). It also has an anti-anxiety effect - a relaxant for worrying perhaps. (web.mit.edu)

So, far I have just used a 400 mg dose once yesterday and twice so far today. The anti-congestion benefit does seem to wear off in a few hours. Having a 400 mg dose, every 6 hours, would add up to 1600 mg, or every 4 hours, would be 6 pills for 2400 mg. Two of the extended release would also be 2400 mg and simpler to remember. Robaxin might help similarly, see excerpt below. Some people have allergy reactions to this group of medications and the recommendation is to not use them, so Dr. St. Amand’s suggestion that guaifenesin treatment might make things worse before it gets better may have been people having allergy reactions.

Cautions to keep in mind if using high dose guaifenesin for a while - it is converted into a lactic acid type of chemical and excreted in the urine, so increased acidity may be an issue. The increased acidity may also increase calcium excretion or lead to a guaifenesin calcium type of kidney stone. (web.mit.edu) My self-care tip: Taking a little dash of baking soda in water a few times of day may help offset the increased acidity load. Excess would be bad. I use a very small amount and drink to taste. A cause of muscle cramps can be excess acidity in the body and the baking soda water can help relieve that gradually, not instantly.

“The following paper documents a study comparing the effects of mephenesin, guaifenesin, mephenesin carbamate, and guaifenesin carbamate:

Journal of Pharm. Expt. Ther. 1958, 122;239 (Truitt and Little)

This study shows that all these drugs exhibit a comparable muscle relaxant activity at similar doses.  However, guaifenesin carbamate was effective over a much longer time, so it  could be used effectively in humans as a muscle relaxant. It is now known as methocarbamol or Robaxin, the latter being the brand name.

It has been found that all of these propanediol derivatives act as central-acting skeletal muscle relaxants by selectively depressing transmission of nerve impulses at the internuncial neurons of the spinal cord, brainstem, and subcortical regions of the brain.  At low doses they act to relax hypertonic muscles and to lower response to sensory stimuli, i.e. pain.  Thus, they might be very useful for people with fibromyalgia.  At high enough of a dose, they can cause temporary muscle paralysis. To achieve muscle paralysis, the recommended dose for large animals is 50mg per pound.  Assuming a similar dose rate for humans, for a person weighing 100 pounds, the recommended dose would be 5000mg.  Of course, this amount is meant for extreme relaxation to allow for surgery.  A muscle relaxant effect would still be seen at much lower doses.  Patients on guaifenesin for fibromyalgia take anywhere from 600 to 3600mg per day.  Dr. St. Amand's own wife takes as much as 4800mg per day.  So this effect would likely be significant in these people.

Additionally, in the previously mentioned study that compared Robaxin and guaifenesin, it was found that the two drugs had comparable muscle relaxant effects at similar dose levels.  Since the maintenance dose for Robaxin is 1500mg, we can infer that the same level dose of guaifenesin would also have significant relaxant effects.  And in fact, many people with who take guaifenesin, take a dose that is close to that amount.” - Mark London, (web.mit.edu)

This information may help protect against Alzheimer’s dementia too.

The mephenesin has been found to increase brain glycine levels which would reduce irritability or anger. (Stern, Catović, 1975) Gycine is a calming signaling amino acid within the brain. The group of medications and other -diol medications may also inhibit NMDA receptors, (Peoples, Ren, 2002), which would be helping anyone with overactivity from excitotoxins or excess histamine and could be protective against risk of later schizophrenia or Alzheimer’s dementia. NMDA receptor inhibitors may be helpful for treatment of fibromyalgia too. (Henriksson, Sörensen, 2002) Which they would be, if my own theory about Retinoid Toxicity and histamine excess being involved in fibromyalgia is correct, or correct for some patients, as histamine adds to NMDA activity. (Cited by Mark London, web.mit.edu)

“The released histamine directly stimulates the polyamine-binding site of the NMDA receptors as histamine acts on the polyamine-binding site of the NMDA receptors. Therefore, histamine indirectly activates the tachykinin NK₁ and NMDA receptors via the spinal release of substance P and glutamate, respectively.” (Hayasha, et al., 2020)

What we do know about fibromyalgia is that it is not a muscle disorder.

Multiple studies have shown that strength training for people with fibromyalgia leads to similar increases in muscle strength as for the healthy control group. (Hannonen, Fibromyalgia) Other findings also have led to the conclusion that the muscle cells of fibromyalgia patients are not the primary cause of the condition, (Simms, 1996), or even is a muscle disorder. (Simms,1998) (Cited by Mark London, web.mit.edu)

Activity of the Retinoid X Receptor is increased in fibromyalgia

“Studies of proteomics and fibromyalgia have found 5 dominant enriched routes: acute phase response signalling, LXR/RXR activation, FXR/RXR activation, coagulation system and complementary system. There are also 6 complementary proteins (C1S, CFAH, CO7, CO2, C1QC, CO9) with increased expression in fibromyalgia. Haptoglobin and fibrinogen have been shown to be associated with fibromyalgia, and this may be considered to be a plasma protein signature.⁵⁵ Other authors have used proteomics to show over-expression of 3 proteins associated with oxidative stress: α1-antitrypsin, transthyrretin and retinol binding protein 4 in fibromyalgia.^56” (Rodríguez, Mendoza, 2020)

Transthyrretin, (TTR), is a transport protein made in the liver which is used to carry thyroid hormone or vitamin A, retinol, in the blood. Retinol binding protein 4 also is a transport protein that carries retinol. (gene/5940) Alpha1-antitrypsin (AAT) is made in the liver and is an inhibitor of activated protein C (APC) which is an anti-coagulant. (Burghaus, et al., 2006)

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 Mark London, web.mit.edu)

AND a few cautions:

• Guaifenesin is not a strong anticoagulant and it breaksdown quickly, but may have additive impact along with other drugs or supplements with anticoagulant effects. (web.mit.edu) (Ginger, vitamin E, lots of nuts (vit E source), omega 3 fatty acids, are a few food sources with anti-coagulant effects.

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. (web.mit.edu)

Summary points about Mark London’s lengthy fact checking of Dr. St. Amand’s guaifenesin protocol for fibromyalgia.

Extracts of the guaiac tree have been used to make an extract used for rheumatism pain since the 1500’s. GuaiLife is a form of guaifenesin, developed by Gregory Penniston, a chiropractor, who recommends it for a variety of pain conditions including pelvic pain, Ehlers-Danlos Syndrome and restless leg syndrome. (web.mit.edu)

Guaifenesin may help fibromyalgia pain because it reduces pain and muscle cramps. Good to know. The anti-anxiety, anti-congestion, anticoagulation benefits and NMDA receptor inhibition are bonuses.

The phosphate theory seems quite wrong and Dr. St. Amand’s protocol has been ignored by the medical community but is still talked about online. My take - guaifenesin may help but cutting out salicylate foods seems to be a need for me and Retinoid Toxicity DOES seem to be an underlying factor in fibromyalgia based on the proteomics studies mentioned in the excellent review of research about fibromyalgia by Rodríguez and Mendoza, 2020. Making it important to restrict vitamin A and carotenoids potentially, and for life possibly, if the liver is over-activating it and causing the inflammatory pain condition.

Salicylate rich foods, for people who aren’t sensitive to them, are generally beneficial and have anti-cancer properties.

Salicylates in Fruits

Thankfully pomegranate is on the Low list along with pawpaw, golden apples, pears, peeled, and bananas. Moderate adds the pear peel back, red apples, figs, lemon and mango. I avoid bananas though for latex sensitivity, lemon as a histamine trigger and mango as a rich carotenoid source. Equals = it is not easy to have food sensitivities, but knowing is better than the pain.

Fruits - high sources: Apple –granny smith, Avocado, Grapefruit, Kiwi Fruit, Mandarin, Nectarine, Passionfruit, Peach, Watermelon.

Fruits - very high sources: Apricot, Blackberry, Blueberry, Cherry, Cranberry, Dates, Grapes, Pineapple, Plum, Prune, Orange, Raspberry, Rockmelon, Sultana, Strawberry.

Well - avocado, strawberries, raspberries, dates, grapes and plums or prunes are foods I have been eating fairly often or daily with strawberries all over my backyard.

Salicylate in Herbs and Spices

Negligible - Clover, Fennel, Fenugreek, Parsley, Sea salt.

Low - Chives, Garlic, Malt Vinegar, Saffron, Soy sauce, Tandoori, Vanilla

Moderate - None listed. *In general herbs and spices are good sources of salicylates which can beneficial for health when not sensitive.

High - All spice, Caraway, Cardamom, Cinnamon, Cloves, Coriander, Cumin, Ginger, Mixed Herbs, Mustard, Nutmeg, Oregano, Pepper – black and white, Rosemary, Tarragon, Turmeric, Vinegars.

Very High - Aniseed, Cayenne, Curry, Dill, Fish Paste, Gravy, Sauces, Tomato Paste.

Salicylate in Vegetables

Negligible - Bamboo shoots, Beans - dried, Cabbage — green, Celery, Lentils, Lettuce - iceberg, Potato - no peel.

Low - Beans - green, Brussel Sprouts, Cabbage - red, Chives, Leek, Mung beans, Peas - green, Turnip.

Moderate - Asparagus, Beetroot, Broccoli, Carrot, Cauliflower, Corn, Lettuce, Mushroom, Onion, Parsnip, Potato - sweet, Potato - red, Pumpkin, Spinach, Snow peas.

High - Alfalfa sprouts, Chili, Cucumber, Eggplant, Watercress, Zucchini.

Very High - Capsicum, Chicory, Gherkin, Olives, Radish, Tomato.

This site also has a Drinks and Sweets category to see if interested: Salicylate sensitivity (naturopathlife.com.au). The main things that I would need to change or use moderately are licorice and honey, listed as Very High in salicylates.

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This is kind of mind-blowing information - whether the guafenesin helps or not - seeing the list of symptoms and sources makes it clear that I am congested and worse in part because it is strawberry and raspberry season and I use quite a few of the herbs and spices and a few of the vegetables that are High or Very High sources.

That list is just a starting point. I have an older post about salicylates as an anticancer phytonutrient, so I knew herbs and spices are rich sources. I don’t know if nasturtium leaves and flowers are though.

What you don’t know, can hurt you.

Nasturtium flower and leaves in a salad with strawberries. The peppery taste is nice with the sweet fruit.

Nasturtium is mentioned as an oxalate source, but I don’t see anything suggesting it is a significant source of salicylates, even though peppery in flavor. It is a rich source of some healing terpenes though and potent in flavor. Eating three nasturtium leaves a day was a health recommendation by someone online.

“The main compounds of the oil of leaves were myristicin (57.6%), α-terpinolene (8.9%) and limonene (6.7%). Caryophyllene oxide (37.2%), p-cymene-8-ol (17.6%), α-terpinolene (15.2%) and limonene (11.8%) were the main components in stems, whereas limonene (43.6%), α-terpinolene (19.7%), p-cymene-8-ol (7.6%) and caryophyllene oxide (6.7%) were the major constituents in the oil of flowers.” (Amiri, 2011)

Methanol extract of the leaves had higher anti-inflammatory activity than the oil extract, (Amiri, 2011), This suggests that the polyphenol and anthocyanin and vitamin C content are doing a lot for us.

“The flowers and other parts of the garden nasturtium are a good source of micro elements such as potassium, phosphorus, calcium and magnesium, and macro elements, especially of zinc, copper and iron. The essential oil, the extract from the flowers and leaves, and the compounds isolated from these elements have antimicrobial, antifungal, hypotensive, expectorant and anticancer effects. Antioxidant activity of extracts from garden nasturtium is an effect of its high content of compounds such as anthocyanins, polyphenols and vitamin C. Due to its rich phytochemical content and unique elemental composition, the garden nasturtium may be used in the treatment of many diseases for example the illnesses of the respiratory and digestive systems. High content of erucic acid in nasturtium seeds makes it possible to use its oil as treatment in adrenoleukodystrophy. It is also applied in dermatology because it improves the condition of skin and hair.” (Jakubczyk, et al., 2018)

Nasturtium leaves and the pretty flowers make a tasty addition to a salad and are fairly easy to grow if you have enough sunshine. Less sunshine will still get you some green leaves, just unlikely to flower. The seeds, raw, are a oxalate source and should not be eaten raw. They are pickled or cooked into a caper-like food.

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This post wandered around the block and picked some flowers, but then we have flowers at least. Happy weekend to you!

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

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(Hayasha, et al., 2020) Hayashi T, Watanabe C, Katsuyama S, Agatsuma Y, Scuteri D, Bagetta G, Sakurada T, Sakurada S. Contribution of Histamine to Nociceptive Behaviors Induced by Intrathecally Administered Cholecystokinin-8. Front Pharmacol. 2020 Oct 29;11:590918. doi: 10.3389/fphar.2020.590918. PMID: 33250769; PMCID: PMC7673449. https://www.frontiersin.org/articles/10.3389/fphar.2020.590918/full

(Henriksson, Sörensen, 2002) Henriksson KG, Sörensen J. The promise of N-methyl-D-aspartate receptor antagonists in fibromyalgia. Rheum Dis Clin North Am. 2002 May;28(2):343-51. doi: 10.1016/s0889-857x(01)00013-8. PMID: 12122922. https://pubmed.ncbi.nlm.nih.gov/12122922/

(Jakubczyk, et al., 2018) Jakubczyk K, Janda K, Watychowicz K, Łukasiak J, Wolska J. Garden nasturtium (Tropaeolum majus L.) - a source of mineral elements and bioactive compounds. Rocz Panstw Zakl Hig. 2018;69(2):119-126. PMID: 29766690. https://pubmed.ncbi.nlm.nih.gov/29766690/

(Lassesen, 2016) Lassesen, Heparins and CFS, CFS Remission, 2016, https://cfsremission.com/2016/03/08/heparins-and-cfs/

London, Mark, The Role of Guafenesin in Fibromyalgia, 2007, web.mit.edu, http://web.mit.edu/london/www/guai.html

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(Rodríguez, Mendoza, 2020) García Rodríguez DF, Abud Mendoza C. Physiopathology of fibromyalgia. Reumatol Clin (Engl Ed). 2020 May-Jun;16(3):191-194. English, Spanish. doi: 10.1016/j.reuma.2020.02.003. Epub 2020 Apr 9. PMID: 32279983.

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(Simms, 1996) Simms RW. Is there muscle pathology in fibromyalgia syndrome? Rheum Dis Clin North Am. 1996 May;22(2):245-66. doi: 10.1016/s0889-857x(05)70271-4. PMID: 8860798.

(Stern, Catović, 1975) Stern P, Catović S. Brain glycine and aggressive behavior. Pharmacol Biochem Behav. 1975 Jul-Aug;3(4):723-6. doi: 10.1016/0091-3057(75)90202-6. PMID: 1237900. https://pubmed.ncbi.nlm.nih.gov/1237900/