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."

Salicylate sources transitions into herbs and nutrients that may cause bleeding, returns with a white paper about wild blueberries, and transitions to leg edema and drugs that cause that besides excess salicylates - and the list includes similar ones to pomegranate peel’s mechanism of action that makes it so superior as an anti-cancer agent. We end with a brief look at Persephone/Proserpine, the mythological person who got caught eating pomegranate seeds in a bad location. Don’t touch the royal fruit if you don’t want to become Queen of the Underworld.

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Rooibus tea is a salicylate source and that is part of its medicinal benefits. Higher heat brewing would draw more of the phenols out, including salicylate, so my cooler sun tea preparation probably was more tolerable for me because of the lower heat of sun warmth. (Santos, et al., 2016)

I had another bad morning after eating food at 9:30 pm that would have contained salicylates - thyme seasoned tofu. I had even used less thyme but ended up rinsing it off the next day to eat the tofu. Tofu also has salicylates but I need to eat protein food more than I need to eat thyme.

I have been drinking quite a bit of rooibus tea as it is low oxalate, but high salicylate, oh.

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, everything, as the problem becomes more severe/bigger salicylate load. The headache comes the next morning or later at night.

What spices do I have left? Not many, sadface. Cilantro and coriander, parsley, garlic, the onion family, saffron (if I can afford it). Celery. *and nasturtium leaves and flowers - peppery goodness that is growing well in my mini-garden. I think I will start drying leaves to try as a crumbled dry herb.

I have to be more cautious about my use of Black Seed Oil as that is also cumin seeds and cumin is a good source of salicylates. Addition - it was shared in the comments that Nigella sativa ‘Black seed oil’ is not the same plant as standard cumin seeds so I will need to look at it closer. Cumin and Black Cumin seeds are both are good sources. See Table 1, Examples of total salicylate content of food items, (Duthie, Wood, 2011) excerpt below:

• Black cumin - 25.05 mg/Kg

• Cumin - 29.76 mg/Kg

• Thyme - 28.60

• Mint - 54.20

• Fennel (seeds) - 14.00

• Celery, vegetable - 0.04 (to give myself some food hope)

• Green beans - 0.07, (Duthie, Wood, 2011)

Reminder - helpful anti-inflammatory and anti-pain phytonutrient for people who can break it down properly. The food sources would not be giving as much as an aspirin except for concentrated mint things potentially. But if someone, like me, was using cumin, ginger, hot pepper, mint, rooibus, thyme, rosemary, basil, oregano, etc, and some aspirin then it might add up a little faster.

Maybe my focus should be on increasing use of the Dimethylglycine which is what the liver needs to properly break down the salicylates. A recommended guideline is not available but ~ 2.5 to 10 grams per day is something I saw somewhere as a suggested target. A teaspoon of powder is roughly 5 grams.

Tangential point - I have gotten two different genetic screenings from professionals who also provide guidance to purchasers about what to take or do for certain gene alleles - AND - neither of them suggest or even mention that a BHMT gene allele may lead to a need for methionine and DMG supplements. I figured that out for myself by reading about what the BHMT gene does. It does a lot more than methylation cycles too. Point - do your own research even with alternative health practitioners. It is hard to know about everything and their guidance is based on we don’t know exactly what.

I will have to keep looking for research studies that mention salicylate content as food lists are based on something, ideally - chemical analysis of samples of the foods.

Plants make more phytonutrients when they are in harsher growing conditions and in the outer peel or leaves where insects are to be repelled. A salicylate page suggested avoiding peels and outer leaves to reduce salicylate content. So variable data would be likely from plant samples - growing condition and which parts of the plant being tested could affect the salicylate and other phytonutrient content.

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)

Tangent: Bleeding risk from medicinal plants or other nutrients

*That article is 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)

Wild Blueberries - a superfood that is also a salicylate source (Wintergreen berries have lots more though - and is a COX 1 and COX 2 inhibitor).

Wild Blueberries white paper about a product (in my Dropbox) - What to look for in a wild blueberry product? Or go pick some if you live in the correct areas for that luxury. They are low bush unlike commercial blueberry shrubs and tend to be in northern areas where pine forests are natural. If you are not salicylate sensitive blueberries are a cognitive enhancer possibly due to the antioxidant and cardiovascular benefits.

Wintergreen is also a low growing plant in the same type of locations and has an edible red berry with a minty flavor. They are in the cranberry family and have an odd white styrofoamy texture inside of the red exterior. If you want to eat a few for the minty flavor, have them fresh. The flavor disappears with cooking. I was experimenting with them a few years ago and did get very puffy legs at that time and stopped eating wintergreen berries after reading more about COX 1 and 2 inhibition. I didn’t learn of ‘salicylate sensitivity’ as a chronic issue at that time though.

Pomegranate peel is a COX-2 inhibitor and too much can cause leg edema all by itself, no extra Excedrins needed.

NSAID pain relievers inhibit both COX-1 and -2 enzymes, while newer pain relievers have been attempted that are only COX-2 inhibitors (like antioxidants and pomegranate peel do). The COX-1 inhibition tends to cause bad GI side effects which COX-2 inhibitors don’t. Both types can lead to the edema problems.

“All COX-2 inhibitors have the potential to lead to salt and water retention, edema, exacerbation of CHF and increased blood pressure. Traditional NSAIDs do cause an increase in baseline blood pressure especially when the patient is taking beta-blockers, calcium channel blockers and ACE inhibitors.” (Rampetsreiter, 2002)

Peripheral edema, puffy extremities, is not uncommon as a medication side effect and it is often misdiagnosed and mistreated per a review article, if it is recognized at all. Until recently, with increased use of diuretic herbs, I had never had thin ankles, ever, even when I was thin. Capri pants and ballet flats? - not for me. I thought I just had fat ankles - instead I had genetic differences leaving me slightly edematous all of my prior life.

“Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often noninflammatory and bilateral, some drugs are associated with peripheral oedema that is readily erythematous (eg, pemetrexed) or unilateral (eg, sirolimus). Thus, drug-induced peripheral oedema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory oedema), sodium/water retention (renal oedema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability oedema). The underlying mechanism has significant impact on treatment efficacy.” (Largeau, et al., 2021)

And pomegranate extract is also a potent anti-cancer agent by inhibiting the PI3K/AKT/mTor signalling pathway.

Pomegranate peel would fit in the protein kinase inhibitor category of “Table 2. Main drugs and their potential mechanisms involved in peripheral oedema” by Largeau, et al., 2021. It might be like these drugs, PI3K/AKT inhibitors:

“PI3K/AKT: idelalisib,⁵⁰ alpelisib⁵¹ Lymphedema⁵² through PI3K/AKT inhibition that prevents VEGFR-3/VEGFC-dependant lymphangiogenesis⁵³.” (Largeau, et al., 2021)

Pomegranate peel inhibits the PI3K/AKT/mTor signalling pathway; see: Fig. (2) Molecular mechanisms of action of pomegranate derived products. (Syed, et al., 2013) That helps explain why pomegranate peel is so helpful against breast cancer and other cancer types.

Table 2 also mentions estrogens and Tamoxifen as possible factors in lower leg edema. (Largeau, et al., 2021)

Pomegranate peel is a COX 2 inhibitor and among the changes in my routine that I made yesterday, was to have pomegranate peel only once in the day instead of two or three times. Dose makes the medicine, dose makes the toxin. If I am not as puffy then I don’t need as much diuretic, which is nicer because you lose potassium, magnesium and sodium and that can leave you feeling disoriented or muscle crampy or both.

Mechanism of action of pomegranate fruit extract used topically to prevent skin cancer in an animal study where the animals were treated topically with a cancer-causing agent (the poor animals).

“Topical application of pomegranate fruit extract (2 mg/animal) prior to TPA, afforded significant protection against TPA-mediated increase in skin edema and hyperplasia and epidermal ODC activity in the SKH-1 mice. This correlated to a decrease in the protein expressions of ODC and COX-2 in the murine skin. Pomegranate treatment resulted in inhibition of TPA-induced phosphorylation of ERK1/2, p38, and JNK1/2 MAPKs, as well as activation of NF-κB. Notably, only 30% of pomegranate treated mice developed tumors as compared to the control where 100% of the mice developed tumors at 16 weeks [31].” (Syed, et al., 2013)

Proserpine, 1882. Artist: Dante Gabriel Rossetti, Birmingham Museums Trust, Photo by Birmingham Museums Trust on Unsplash

Proserpine doesn’t need to be unhappy, she has pomegranate! Supposedly it was her downfall. Proserpine is the Latin name for Persephone, the mythological person who lives 6 months in the underworld and 6 months above ground each year. She had been abducted and a complete rescue was deemed not possible upon discovering the pomegranate seeds in her mouth. They are a treasure. (columbia.edu)

Addition - this myth was an explanation of seasonal change. Proserpine’s mother is Demeter, goddess of crops and harvest, and she was so sad at the abduction of her daughter by Hades that nothing was growing. Proserpine was rescued to please Demeter, but then when it was found she hadn’t heeded a warning not to eat anything while in the underworld, she had to go back for half the year every year = the winter season.

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List

(Duthie, Wood, 2011) Duthie, G., Wood, A., (2011). Natural salicylates: Foods, functions and disease prevention. Food & function. 2. 515-20. 10.1039/c1fo10128e. https://www.researchgate.net/publication/51606872_Natural_salicylates_Foods_functions_and_disease_prevention

(Largeau, et al., 2021) Largeau, B, Cracowski, J-L, Lengellé, C, Sautenet, B, Jonville-Béra, A-P. Drug-induced peripheral oedema: An aetiology-based review. Br J Clin Pharmacol. 2021; 87: 3043– 3055. https://doi.org/10.1111/bcp.14752 https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14752

Matt Rampetsreiter, DPM, What You Should Know About COX-2 Inhibitors, Oct. 2002, hmpgloballearningnetwork.com, (https://www.hmpgloballearningnetwork.com/site/podiatry/article/893)

(Santos, et al., 2016) Santos, J.S., Deolindo, C.T.P., Esmerino, L.A., Genovese, M.I., Alice Fujita, Marques, M.B., Rosso, N.D., Daguer, H., Valese, A.C., Granato, D., Effects of time and extraction temperature on phenolic composition and functional properties of red rooibos (Aspalathus linearis), Food Research International, Vol 89, Part 1, 2016, pp 476-487, ISSN 0963-9969, https://doi.org/10.1016/j.foodres.2016.08.041. https://www.sciencedirect.com/science/article/pii/S0963996916303702 *via a Reddit conversation: “3a6o4i •1 yr. ago “Rooibos is actually very high in salicylates. It's roughly 1.8 mg salicylic acid per gram dried mass. You can do the maths based on this paper.”

(Syed, et al., 2013) Syed DN, Chamcheu JC, Adhami VM, Mukhtar H. Pomegranate extracts and cancer prevention: molecular and cellular activities. Anticancer Agents Med Chem. 2013 Oct;13(8):1149-61. doi: 10.2174/1871520611313080003. PMID: 23094914; PMCID: PMC4052369. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052369/

(Wong, et al., 2012) Wong, W.W., Gabriel, A., Maxwell, G.P., Gupta, S.C., Bleeding Risks of Herbal, Homeopathic, and Dietary Supplements: A Hidden Nightmare for Plastic Surgeons?, Aesthetic Surgery Journal, Vol 32, Issue 3, March 2012, pp 332–346, https://doi.org/10.1177/1090820X12438913 https://academic.oup.com/asj/article/32/3/332/217185