Pomegranate extract update – has similar mechanism to NSAIDs

Update, 8/18/2018, for anyone interested in phytonutrient biochemistry or herbal medicinal foods: Wintergreen and wintergreen berries are also a natural source of a painkiller in the NSAID group – aspirin. The plant can also be a source of phytonutrients that activate TRPA1 channels which can affect fluid balance and other symptoms. Winterberries are in the cranberry family and have a minty flavor. They are in season currently and eating more of them seems to increase my symptoms of inflammation and swelling more than the pomegranate extract or pomegranate seeds. Having too many variables in an experiment makes it unclear which factor might be a cause or if both may be involved. Experimental method tries to narrow variables to one factor at a time. Stopping both pomegranate products and wintergreen berries helped but other symptoms got worse, adding pomegranate back to my diet didn’t make the inflammation/swelling symptoms much different but more recently adding the wintergreen berries back into my diet did make the symptoms of lower leg inflammation/swelling and pain worse.

An excerpt from one of my other websites, G3.6.1.5: People with overactive TRPA1 channels may be sensitive to:

  • “(Winter-green),” (G3.67); Wintergreen is a natural flavoring herb in the mint family. It is typically used as an essential oil as a flavoring in many foods and other types of products. It has medicinal benefits related to it containing the chemical that acts as the pain killing ingredient of aspirin.(G3.73) (effectivecare.info, G3)

My ongoing self study of pomegranate extract for my mental and physical health symptoms has led me to use a fairly small dose, daily though is still best. Missing even a few days seems to increase mood and anxiety problems but using a very large serving has some side effects. Lower leg and foot swelling is associated with some physical health problems but it can also be a side effect of NSAIDs pain killers such as ibuprofen. (7) Pomegranate extract has been shown to reduce pain and inflammation by the same mechanism as NSAIDS – inhibition of cyclooxygenase enzymes (COX1 and COX2,  with more inhibition of COX2 than COX1). It also may have an anti-inflammatory effect by reducing inflammatory cytokines that signal increase in production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2). (1) Prostaglandin E2 is made from arachidonic acid and is involved in the inflammation associated with rheumatoid arthritis and osteoarthritis. (2) Nitric oxide can be beneficial but it can also transform into reactive oxidative species and add to the antioxidant burden of metabolism. (5) (9) Other studies including an animal study on obesity found pomegranate extract reduced inflammatory biomarkers and increased nitric oxide, which might make it helpful for Metabolic Syndrome. (6)

Pomegranate extract was found helpful in a dose related level against mammary tumerogenesis in an animal study, (0.2-5 gram/Kg body weight was used). Reducing COX2, heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) pathways, and increasing Nrf2 pathways were found to be part of the mechanism for benefit. (4) That amount could be quite a lot. Equivalent amounts for a 75 kilogram/165 pound human would be 15-375 grams per day or roughly one tablespoon (15 grams approximately)-13.4 ounces/27 tablespoons per day. (Mammary tumerogenesis means the initial onset of breast cancer tumors.)

It helps to prop my feet when sitting or even lay down with my feet above my heart. I’m getting better at typing while laying down. Better mood and having feeling in my fingertips is worth it. There may some other health or diet issues affecting the leg swelling. Heart or kidney or vein problems can be a cause. (7) I do have vein problems and may have heart issues, which can be an increased risk with hyperthyroidism. Cutting back on salt, daily exercise, and elevating the lower legs above the level of the heart several times per day for a half an hour is recommended, wearing compression socks is also a recommendation and that makes me feel old. (7) Maybe 52 is old.

Lymphedema – lower leg swelling due to reduced drainage from vein problems may be the best fit for my personal history, and lack of stretching exercises lately may be part of the reason the problem has become worse lately. Physical therapists explain the problem and provide exercise, massage and compression wrapping suggestions in a free video available online. (8) The exercise routine is similar to what I generally do when I do stretching exercises – so that seems like a good habit to return to my daily schedule.

Lower leg swelling has been a symptom for me at various stages of previous ill health and with some other medications I’ve used in the past, but currently it does seem worse when I use larger amounts of the pomegranate extract. One teaspoon a day helps with the stable mood and I haven’t had numbness in my fingertips in months with the ongoing daily use of pomegranate extract in larger amounts, 2-3 tablespoons was typical. I stopped use of it altogether when the leg swelling became a problem to see if the swelling would get better but the mood symptoms got worse again after having seemed fine for quite a while – quite a while while using pomegranate extract daily and the leg swelling didn’t get a lot better. Being not well is unpleasant and some side effects can be better than being unwell.

Breast cancer treatments currently may cause hair loss, severe vomiting and may leave the patient with cognitive decline afterwards, and pomegranate extract doesn’t cause any of those symptoms in the amounts that I’ve tried. It is a diuretic and causes increased urination which I cope with by drinking extra fluids and using the pomegranate extract early in the day rather than at night. I may be preventing breast cancer tumor development (4) while drinking extra fluid and urinating in increased amounts – getting old isn’t great but the alternative isn’t better. I may go buy my first pair of compression socks and feel young at heart if not in body.

Industry math – one pomegranate peel makes about six cups of extract by my method which would provide 288 teaspoons/96 tablespoons. It may have improved somewhat but the worsening in mood was more obvious.  From an industry perspective getting 288 servings of a mood and nerve treatment from one pomegranate peel seems like it could be profitable. Dehydrating one teaspoon into a capsule serving also seems possible. Side effects with psychiatric medications are unfortunately common and can include swelling/edema of the lower legs or more severe edema including facial edema.

/Disclaimer: This 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 health professional for individual health care purposes./  

  1. Shukla, Meenakshi & Gupta, Kalpana & Rasheed, Zafar & A Khan, Khursheed & Haqqi, Tariq. (2008). Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX-II activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes in vitro. Journal of inflammation (London, England). 5. 9. 10.1186/1476-9255-5-9.
  2. Jean Y. Park, Michael H. Pillinger, Steven B. Abramson, Prostaglandin E2 synthesis and secretion: The role of PGE2 synthases, Clinical Immunology, Vol 119, Iss 3, 2006, pp 229-240, ISSN 1521-6616, https://doi.org/10.1016/j.clim.2006.01.016.
    https://www.sciencedirect.com/science/article/pii/S1521661606000453 (2)
  3. Arachidonic Acid – an overview, ScienceDirect, https://www.sciencedirect.com/topics/neuroscience/arachidonic-acid (3)
  4. Mandal A, Bhatia D, Bishayee A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling PathwaysNutrients. 2017;9(5):436. doi:10.3390/nu9050436. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452166/ (4) From Abstract: “Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2–5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-κB, inhibitory κBα (IκBα) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IκBα, hindered the translocation of NF-κB from cytosol to nucleus and increased the expression and nuclear translocation of Nrf2 during DMBA-induced mammary tumorigenesis.” From Introduction:”During the last decade, pomegranate fruit has been gaining a widespread reputation as a dietary supplement as well as a functional food due to emerging scientific evidence on potential health benefits, including prevention and/or treatment of cardiovascular ailments, neurological disorders, oncologic diseases, dental problems, inflammation, ulcer, arthritis, microbial infection, obesity, diabetes, acquired immune deficiency syndrome and erectile dysfunction [,,,,,]. Pomegranate fruit contains phytochemicals, including flavonoids (e.g., anthocyanins and catechins), flavonols (e.g., kaempferol and quercetin), flavones (e.g., apigenin and luteolin), conjugated fatty acids, hydrolyzable tannins and related compounds which are thought to be responsible for various biological and pharmacological activities [,,,,,]. Based on preclinical and clinical studies conducted by various laboratories worldwide, pomegranate-derived substances, such as juice, extracts and phytoconstituents exhibited cancer preventive and therapeutic effects against colon, liver, lung, prostate and skin cancer [,,,,]. Various extracts, fractions and phytochemicals from pomegranate fruit, peel, seed and flower demonstrated cytotoxic, antiproliferative, proapoptotic, antiangiogenic, anti-invasive, and antimetastatic properties against estrogen receptor-positive and ‑negative breast cancer cells [,,,,,,,,,,,,,]” (4)
  5. Matsubara K, Higaki T, Matsubara Y, Nawa A. Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia. Miller FJ, ed. International Journal of Molecular Sciences. 2015;16(3):4600-4614. doi:10.3390/ijms16034600. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394437/ (5)
  6. Filomena de Nigris, Maria Luisa Balestrieri, Sharon Williams-Ignarro, Francesco P. D’Armiento, Carmela Fiorito, Louis J. Ignarro, Claudio Napoli,
    The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats, Nitric Oxide, Volume 17, Issue 1, 2007, pp 50-54, ISSN 1089-8603, https://doi.org/10.1016/j.niox.2007.04.005.
    (http://www.sciencedirect.com/science/article/pii/S1089860307000432) (6)
  7. Swollen Legs: Causes and Treatments, WebMD, https://www.webmd.com/dvt/why-legs-puffy#1 (7)
  8. Bob Schrupp, Brad Heineck, 10 Exercises for Leg Lymphedema (Swelling or Edema of the Lower Extremities). physicaltherapyvideo, https://www.youtube.com/watch?v=3t8Kp99e50k&feature=youtu.be (8)

  9. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative Stress in Preeclampsia and Placental Diseases. International Journal of Molecular Sciences. 2018;19(5):1496. doi:10.3390/ijms19051496.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983711/ (9)

Links on heart disease, calcium and iodine

Whether nutrient deficiencies or other metabolic imbalance is the cause is not clear or it may be a response to oxidative stress, however levels of the trace nutrients magnesium, selenium, zinc, and vitamin D3 were found to be low and the level of calcium elevated in myocardium, a type of muscle tissue in the heart. (1)

The short story – adequate nutrition is needed to support pregnancy and lactation (breast feeding) – longer duration breast feeding (6-12 months or more) is associated with less heart disease (2) and breast cancer (3risk. Increased amounts of iodine is needed for pregnancy and lactation (4) and low iodine and low selenium may be involved in breast cancer risk. (5)

A high protein diet, especially one high in dairy products is associated with more heart disease risk. (6) Background information – a high protein diet creates more work for the kidneys in order to excrete the extra nitrogen from protein that was converted into energy (ketones) (7(29) instead of being used to build muscle or other proteins.

Magnesium may help protect against calcification in heart disease in two important ways. It is needed for the kidneys to be able to excrete excess calcium. It also acts as a calcium channel blocker by providing electrical power from inside of cells or organ tissue in order to help keep excess calcium from entering the soft tissue and blood vessels through the membrane calcium channels. Medications used for hypertension include several calcium channel blockers.

Potassium is also important to protect against calcification of blood vessels by preventing increased calcium entry into the cell. The mineral is also important for preventing high blood pressure/hypertension – in addition to excess sodium/salt, too little potassium can be a problem. See excerpt with the link. (29)

Five to nine servings of vegetables or fruits per day is the recommendation for a healthy balanced diet (five) or potentially cancer preventing diet (nine). They are a good source of potassium and magnesium in addition to other trace nutrients.

Cholesterol plaque formation (atherosclerotic plaques) along vessel membrane walls may be simply acting as a coating to prevent the electrically active calcium ions from entering cells or doing other damage by plastering it in place, like plaster or spackle on dry wall. Calcium and magnesium levels in normal health are very carefully controlled by the kidneys. Lack of potassium and excess sodium may also affect the kidneys ability to excrete excess calcium.

The current understanding of atherosclerosis does not describe the role of magnesium in this way – current description: (8) and (9).

The role of potassium, magnesium and calcium in hypertension is available here: (10) and (29).

Magnesium has been found to help reduce vascular calcification (atherosclerotic plaques in blood vessels) in animal based research, (11) {and I believe in a few human research studies too but I have to find the links again. See Table 7 for a list of symptoms common to magnesium deficiency, hypertension and myocardial infarction are included: (14)} Magnesium may also help reduce prostate cancer risk or progression, (15), and low magnesium levels may be an underlying factor in the formation of cancer tumors, (18); and depression (16) can be a symptom of magnesium deficiency (14) and frequently co-occurs with other diagnoses. (17)

The short story – excess calcium may increase heart disease risk while adequate iodine, selenium, magnesium, potassium and vitamin D are all important for a healthy pregnancy, ability to lactate for a longer duration and reduce the risk of heart disease and breast cancer.

Addition, miscarriage history and history of having more than four pregnancies/four children has been associated with increased risk of heart disease for the mothers. (12) Increased losses of iodine and magnesium stores from the bones may be an underlying factor.  Premature infants born to multiparous women (women who had previous pregnancies) are more likely to have low Thyroid Stimulating Factor – which is associated with hypothyroidism which can simply be due to low iodine levels during the pregnancy. (13)

The long story is in the links below;

except for references about magnesium, potassium and vitamin D for pregnancy and breast feeding but they are also important for pregnancy and lactation. The baby may not thrive or may be fussier if the breast milk is low in essential nutrients or it may be difficult to maintain an adequate supply if the woman is malnourished.

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 health professional for individual health care purposes. Thanks.

  1. Karl T. Weber, William B. Weglicki, Robert U. Simpson, Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium, Cardiovasc Res. 2009 Feb 15; 81(3): 500–508. https://www.ncbi.nlm.nih.gov/pubmed/18835843 (1)
  2. Katherine Lindemann, Mothers who breastfeed may be less likely to suffer from heart disease and stroke later in life, an interview with Sanne A. E. Peters, University of Oxford, Research Fellow in Epidemiology, June 21, 2017, researchgate.net blog post,   https://www.researchgate.net/blog/post/breastfeeding-may-have-long-term-health-benefits-for-mothers-too  Benefits were seen/measured with six months increments in breastfeeding duration, with a large group of Chinese mothers, “Mothers who had breastfed their babies had a nine percent lower risk of heart disease and an eight percent lower risk of stroke.” (2)
  3. Loren Lipworth, L. Reness Bailey, Dimitrios Trichopoulos,

    History of Breast-Feeding in Relation to Breast Cancer Risk: a Review of the Epidemiologic Literature, JNCI: Journal of the National Cancer Institute, Volume 92, Issue 4, 16 February 2000, Pages 302–312, https://academic.oup.com/jnci/article/92/4/302/2624708 “Overall, the evidence with respect to “ever” breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer. […] It appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women. It has been hypothesized that an apparently protective effect of breast-feeding may be due to elevated breast cancer risk among women who discontinue breast-feeding or who take medication to suppress lactation; however, the evidence is limited and should be interpreted with caution” (3)

  4. Angela M. Leung, MD, MSc, Elizabeth N. Pearce, MD, MSc,* and Lewis E. Braverman, MD, Iodine Nutrition in Pregnancy an Lactation, Endocrinol Metab Clin North Am. 2011 Dec; 40(4): 765–777. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266621/  Iodine needs are increased during pregnancy and lactation and in iodine replete geographic areas breast milk levels seemed adequate for the infant’s needs. 250-290 micrograms is estimated to be needed compared to the RDA of 150 micrograms. That level did not seem adequate in geographically low area of New Zealand: ” In a recent study, the iodine needs for breastfed infants in iodine-deficient New Zealand remained inadequate even when their mothers were supplemented with 150 μg/d of iodine during the first 6 postpartum months.” (4)
  5. Peter PA Smyth, The Thyroid, Iodine and Breast CancerBreast Cancer Res. 2003; 5(5): 235–238.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC314438/ Autoimmune thyroid disease and goiter is more common in patients with breast cancer. Iodine and selenium may be protective against both conditions, a review of literature rather than a study. (5)
  6. Heart Risk of High Protein Diets, June 4, 2018, The Hippocrtic Post,  https://www.hippocraticpost.com/ageing/heart-risk-of-high-protein-diets/?utm_source=website&utm_medium=webpush&utm_campaign=notifications The group of men with the highest intake of protein in percentage of total calories had increased risk of heart disease, except for protein from fish or eggs. “When they compared men who ate the most protein to those who ate the least, they found their risk of heart failure was:33 percent higher for all sources of protein;
    43 percent higher for animal protein;
    49 percent higher for dairy protein;
    17 percent higher for plant protein.” (6)
  7. Sherwin RS, Hendler RG, Felig P.,  Effect of Ketone Infusions on Amino Acid and Nitrogen Metabolism in ManJ Clin Invest. 1975 Jun;55(6):1382-90.
       https://www.ncbi.nlm.nih.gov/pubmed/1133179 (7)
  8. Isabella AlbaneseKashif KhanBianca BarrattHamood Al‐KindiAdel Schwertani, Atherosclerotic Calcification: Wnt is the Hint, Basic Science for Clinicians, February 8, 2018 Journal of the American Heart Association,  http://jaha.ahajournals.org/content/7/4/e007356 (8)
  9. The Cardiovascular System in Disease, Diseases of the Vessels, Chapter 6, Ch006-M3430.indd 4/19/2007, http://booksite.elsevier.com/samplechapters/9780723434306/9780723434306.pdf (9)
  10. Mark C. Houston MD, MS, Karen J. Harper MS, PharmD,  Potassium, Magnesium, and Calcium: Their Role in Both the Cause and Treatment of Hypertension, JCH, Vol 10, Issue 7, pp 3-11, July 2008,  https://onlinelibrary.wiley.com/doi/full/10.1111/j.1751-7176.2008.08575.x (10)
  11. Fatih Kircelli, Mirjam E. Peter, Ebru Sevinc Ok, Fatma Gul Celenk, Mumtaz Yilmaz, Sonja Steppan, Gulay Asci, Ercan Ok, Jutta Passlick-Deetjen, Magnesium reduces calcification in bovine vascular smooth muscle cells
    in a dose-dependent manner, Nephrol Dial Transplant (2012) 27: 514–521, https://watermark.silverchair.com/gfr321.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAZ0wggGZBgkqhkiG9w0BBwagggGKMIIBhgIBADCCAX8GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMbSRHWigPf17i-jCnAgEQgIIBUIkKsm3S-WvD5qd-tNiIBBwsoiqBg-FrbTXdm2oS2q2AdX0wuviR-rsM-hi6IMVKWwMEinUYTbh7DopBg7SWLxBIi4bHXaQft3IHdQqhDKr_RiB69uxkVRwW_2aHFGYjR0FzhUSfhDrmVLweVHZRTIYDVbrSkgaVgLnFq4YHvxohG08oMbAeF4C26XL026jpA7J1xbOodHz_o5MUvoQgVcxwhrIFuu7ysxD_B7bjJehfrw6SLjkrm3Q43jrsS3vS37v_hIig_lTQyFCPe5L6UhFwlQvH1mwPIKPNituSvoob5OxY5odMFjtcXNg0Wz2tqLajbKP_Cg4Rt1X0c67CLvTGMkos_d7QLKbxwiFibtfpcrPJlIfbPPEIjd4jKRI2MWFePBaQTQLnUOoC934JHOp4abLCC5jRaOAgHykzJhZPOpvgmvrgj-jJmZBtfdgW9g (11)
  12. Kashmira Gander, Having More Kids Linked to Heart Disease Risk in Mothers, According to New Study, June 4, 2018, newsweek.com, http://www.newsweek.com/kids-linked-heart-disease-risk-mothers-according-new-study-956066 (12)
  13. Kelli K Ryckman, M.S., PhD, Cassandra N Spracklen, M.S., John M Dagle, M.D., PhD., Jeffrey C Murray, M.D.Maternal Factors and Complications of Preterm Birth Associated with Neonatal Thyroid Stimulating Hormone, J Pediatr Endocrinol Metab. 2014 Sep; 27(0): 929–938. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260397/ “Maternal and neonatal thyroid levels are tightly correlated and hypothyroidism …. Multiparous women had infants with lower TSH levels (P=8×10−4) compared to …” (13)

  14. R. Swaminathan, Magnesium Metabolism and Its Disorders, Clin Biochem Rev. 2003 May; 24(2): 47–66.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855626/ (14)
  15. Oseni, Saheed & Quiroz, Elsa & Kumi-Diaka, Jim. (2016). Chemopreventive Effects of Magnesium Chloride Supplementation on Hormone Independent Prostate Cancer Cells. Functional Foods in Health and Disease. 6. 1-15.  https://www.researchgate.net/publication/291164181_Chemopreventive_Effects_of_Magnesium_Chloride_Supplementation_on_Hormone_Independent_Prostate_Cancer_Cells (15)

  16. Eby GA, Eby KL, Rapid recovery from major depression using magnesium treatment.Med Hypotheses. 2006;67(2):362-70. Epub 2006 Mar 20. https://www.ncbi.nlm.nih.gov/pubmed/16542786 (16

  17. Hee-Ju Kang, Seon-Young Kim, Kyung-Yeol Bae, Sung-Wan Kim, Il-Seon Shin, Jin-Sang Yoon, and Jae-Min Kim, Comorbidity of Depression with Physical Disorders: Research ad Clinical ImplicationsChonnam Med J. 2015 Apr; 51(1): 8–18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406996/ (17)
  18. : Castiglioni S, Maier JAM. Magnesium and cancer: a dangerous liason. Magnes Res 2011; 24(3): S92-S100 doi:10.1684/mrh.2011.0285   http://www.mgwater.com/Magnesium%20and%20Cancer.pdf (18)
  19.  Pharmacology of Cardiac Potassium Channels, Cardiovascular Research, Volume 62, Issue 1, 1 April 2004, Pages 9–33, Oxford Academic – see Table 4, https://academic.oup.com/cardiovascres/article/62/1/9/373105 (19)
  20. Lakshman Goonetilleke, John Quayle, TREK-1 K+ Channels in the Cardiovascular System: Their Significance and Potential as a Therapeutic Target, Cardiovascular Therapeutics 30 (2012) e23–e29  https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1755-5922.2010.00227.x (20)
  21. University of Pittsburgh: Cardiovascular system during the postpartum state in women with a history of preeclampsia, Chapter 2: Cardiovascular System,  pp 190-191, Advances in Physiology Research and Application: 2012 Edition, Scholarly EditionsDec 26, 2012, ebook, https://books.google.com/books?id=3SyvNMZLBU0C&pg=PA190&lpg=PA190&dq=TREK+1+preeclampsia&source=bl&ots=2SzKQHcFJ0&sig=fGwDeK6cMIkUXhtwPDNKqio1zIQ&hl=en&sa=X&ved=0ahUKEwirhN_h6-XbAhUSbq0KHWDZCS0Q6AEIUjAF#v=onepage&q=TREK%201%20preeclampsia&f=false (21)
  22. Ma R, Seifi M, Papanikolaou M, Brown JF, Swinny JD, Lewis A.TREK-1 Channel Expression in Smooth Muscle as a Target for Regulating Murine Intestinal Contractility: Therapeutic Implications for Motility Disorders.  Front Physiol. 2018 Mar 6;9:157, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845753/ (22)
  23. Antidepressant Drugs Suppress Activity of Potassium Channels, Lawrence Berkeley National Laboratory, Feb. 8, 2011, psypost.org,  https://www.psypost.org/2011/02/antidepressant-ssri-potassium-channel-4068 (23)
  24. Nicholas J. Talley, SSRIs in IBS: Sensing a dash of disappointment. Clinical Gastroenterology and Hepatology, May 2003, Volume 1, Issue 3, Pages 155–159.  https://www.cghjournal.org/article/S1542-3565(03)70030-5/fulltext (24)
  25. Tülay Özkan Seyhan, Olgaç Bezen, Mukadder Orhan Sungur, İbrahim Kalelioğlu, Meltem Karadeniz, and Kemalettin Koltka,

    Magnesium Therapy in Pre-eclampsia Prolongs Analgesia Following Spinal Anaesthesia with Fentanyl and Bupivacaine: An Observational Study., Balkan Med J. 2014 Jun; 31(2): 143–148.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115934/ Exerimental group needed less fluid replacement and waited longer before requesting additional pain killing medication than the women with normal (no preeclampsia) deliveries. (25)

  26. Ramanathan J, Vaddadi AK, Arheart KL. Combined spinal and epidural anesthesia with low doses of intrathecal bupivacaine in women with severe preeclampsia: a preliminary report. Reg Anesth Pain Med. 2001 Jan-Feb;26(1):46-51. https://www.ncbi.nlm.nih.gov/pubmed/11172511 (26)
  27. KCNK2 potassium two pore domain channel subfamily K member 2 [ Homo sapiens (human) ], Gene ID: 3776, updated on 23-May-2018,   https://www.ncbi.nlm.nih.gov/gene/3776 (27)

     

  28. Tayyba Y Ali, Fiona Broughton Pipkin, and Raheela N Khan, The Effect of pH and Ion Channel Modulators on Human Placental Arteries. PLoS One. 2014; 9(12): e114405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260857/  “In vessels isolated from placentae of women with pre-eclampsia (n = 6), pH responses were attenuated.” (28) *attenuated means a weakened response, less responsive to the stimulus.
  29. Qi Qian, Dietary Influence on Body Fluid Acid-Base and Volume Balance: The Deleterious “Norm” Furthers and Cloaks Subclinical Pathophysiology, Nutrients 2018, 10(6), 778; Open Access, http://www.mdpi.com/2072-6643/10/6/778/htm “Recently, Sun et al. [53] demonstrated a causal role for dietary K+ in the regulation of osteogenic differentiation and calcification of vascular smooth muscle cells, both in vitro and in atherosclerotic animal models. Specifically, lower levels of extracellular fluid K+ induce vascular smooth muscle cell osteogenic transformation by elevating intracellular calcium. The latter activates CREB (cyclic AMP response element-binding protein) leading to an enhanced expression of osteogenic markers, e.g., RUNX-2, and simultaneously reduced smooth muscle cell markers, e.g., α-actin. Remarkably, even a slight serum K+ reduction (mean K+ level, 3.70 ± 0.21 mEq/L) in mice can trigger significant vessel calcification associated with elevated pulse-wave velocity, a reliable indicator of aortic stiffness. On the contrary, when K+ levels are raised to ~4.73 mEq/L by dietary modification, signs of osteogenic differentiation were abrogated, and vascular calcification prevented. Consistent with the notion of K+ being protective to vasculature, a high ratio of urine Na+/K+ excretion (indicative of high Na and low K+ intake) has recently been linked to the genesis of HTN [54].?” (29)
  30.  Robert Vink, Mihai Nechifor, editors, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf  See page 20 re TRPM7 channels and different effects of oxidative stress on calcium versus magnesium being allowed through the ion channel. Magnesium helps survival while calcium can increase risk to the cell.  other notes about the book:   https://twitter.com/deNutrients/status/1012685811001806849?s=19

Carrots, spices and baby aspirin help prevent cancer and inflammation

 Aspirin has two active parts that help reduce pain and swelling. The salicylate was first isolated from myrtle and willow tree bark but it has since been identified in many plants and is particularly rich in herbs and spices including turmeric and mint. A compound similar to curcumin found in the spice turmeric has been found to have similar bioactivity and structure to salicylic acid. Benefits may include reduced breast, colon and prostate cancer risks:

“Dibenzoylmethane (DBM) has been reported to exhibit chemopreventive activities in several animal models, including mammary, colon and prostate tumorigenesis during the past few years.2,12–16” [2]

Production of the isolated phytochemicals are being studied but in the meantime spicing up the diet with plenty of fruits, vegetables, herbs and spices seems like a good bet and it looks like a baby Aspirin might help protect against breast and prostate cancer as well as cardiovascular disease. Eating more fiber rich produce and spices would help protect against ulcer risks associated with regular use of Aspirin or ibuprofen (I think if I looked that ibuprofen would have similar protective effects because it also reduces the breakdown of endogenous cannabinoids which would reduce free arachidonic acid availability for breast or prostate cancer cells).

From the research article: Table 1: Examples of total salicylate content of food items. [1]
Fruits
Vegetables
Food Item
Salicylate/ mg/kg
Food Item
Salicylate / mg/kg
Blackberries
0.81
Asparagus
1.29
Blueberries
0.57
Carrots
0.16
Gala melon
0.62
Celery
0.04
Grapefruit
0.44
Green beans
0.07
Green apple
0.55
Mange tout
0.20
Kiwi fruit
0.31
Mushroom (button)
0.13
Nectarine
3.29
Onion (white)
0.80
Strawberry
0.61
Tomato
0.13
Drinks
Spices and Herbs
Apple juice
0.83
Black cumin
25.05
Cranberry juice
0.99
Cumin
29.76
Grapefruit juice
0.10
Chat masala
  5.74
Orange juice
0.68
Garam masala
12.85
Pineapple juice
4.06
Paprika
28.25
Tomato juice
1.32
Turmeric
20.88
White wine
0.44
Thyme
28.60
Red wine
0.50
Mint
54.20
Tea
1.06
Fennel
14.00

1. [pubs.rsc.org] Garry G. Duthie and Adrian D. Wood, Natural salicylates: foods, functions and disease prevention, Food Funct, 2011, 2, 515-520, DOI: 10.1039/C1F010128E (full text free with login registration)

“Rodent models using ‘‘nutritional’’ rather than ‘‘pharmaceutical’’ dietary intakes indicate that salicylic acid modulates a range of proteins involved in protein folding, transport, energy metabolism and cytoskeletal regulation.40,41 The biological significance of these changes is unclear. However, several of the identified proteins are known to be involved in two major redox pathways (thioredoxin and glutathione). This strongly suggests that salicylic acid modulates interactive components of the cellular redox system, such as glutathione S-transferase yb-2, p53 and AP-1.42 Oxidative stress is implicated in the pathogenesis of many diseases, including heart disease, diabetes and several cancers.43 Consequently, cellular exposure to low concentrations of salicylic acid may benefit health by regulating the activity or expression of transcription factors involved in modulating oxidative stress, such as the antioxidant response element.44 This potential effect is not, however, unique to salicylic acid as other dietary-derived phenolic compounds, such as flavonoids, also activate this enhancer sequence, thus mediating the transcriptional activation of genes in cells exposed to oxidative stress.45”

“The bioactivity of Aspirin is unique in that it is characterised by two compounds within the same molecule. In addition to salicylic acid, the acetyl moiety is released within minutes of Aspirin consumption by enzymatic hydrolytic cleavage by esterases in the intestine, blood and liver.68 The binding of the acetyl group to serine530 in platelets inactivates the active site of cycloxygenase-1, thus preventing the access of arachidonic acid and irreversibly inhibiting prostaglandin synthesis. (*** also preventing access by prostate and breast cancer cells to the arachidonic acid breakdown metabolite 5-HETE) The resultant prevention of platelet aggregation is a major reason for the widespread use of Aspirin in the prevention and treatment of cardiovascular disease.69 However, the other primary metabolite of Aspirin , salicylic acid, has a much longer half-life of several hours.70 It is likely that its broad spectrum of cellular targets, already discussed, contributes to disease prevention through, for example, its anti-inflammatory, antiproliferative and antioxidant activity. This view is supported by meta-analyses,71–73 which strongly corroborate the hypothesis that the regular consumption of Aspirin -derived salicylic acid can inhibit the incidence and progression of several diseases where platelet function is not a major consideration. However, the doses employed in such trials (30–1300 mg day 1) exceed that which can be obtained from diet alone. Current clinical data are most supportive of a 75 mg daily dose of Aspirin 74 (equivalent to 66 mg salicylic acid), which is readily available from pharmacies and retail outlets in the UK. Larger doses may be required to obtain significant anticancer effects, although a recent population study75 showed for the first time that doses of around 100 mg day 1 may confer some protection. This does not preclude the possibility that the sustained lower intakes achievable by the regular consumption of salicylate-rich diets may also have a disease-preventative activity. However, to date, no double-blind randomised controlled trials using doses of 5–10mg salicylic acid have been conducted in support of the hypothesis that dietary salicylates have long term health benefits. It should also be pointed out that even with therapeutic doses of acetylated salicylic acid of 75mg day 1, there is a peptic ulcer incidence of 5–10% over 3–6 months of usage, a bleeding complication rate of 0.5–2.0 per 100 patient years and a mortality rate of ulcer complications of about 5% of those who have been admitted to hospital due to ulcer bleeding.76 It is likely that the risk of GI toxicity from salicylate levels in food is low, but as a note of caution, Aspirin intakes as low as 10mg day 1 are reported to produce demonstrable gastric damage in humans.77”

Future perspectives

“Interest in the potential beneficial effects of dietary salicylates has arisen, in part, because of the extensive literature on the disease preventative effects of Aspirin . However, it should not be forgotten that plant products found to contain salicylic acid are generally rich sources of other phenolic acids. For example, rich sources of hydroxycinnamic acids such as ferulic, synapic and caffeic acids include legumes, cocoa, fruit, herbs, nuts and cereals. In addition to salicylic acid, other hydroxybenzoic acids such as protocatechuic, vanillic and syringic acids are present in wine, berries, herbs, fruit juices and tea.78 Daily intakes of many may markedly exceed that of salicylic acid. Estimated intakes of caffeic and ferulic acid in a Finnish population are 417 and 129 mg, respectively.79 Many of these compounds also have a marked anti-inflammatory and redox-related bioactivity in mammalian cells.80 Their potential protective effects should not be overlooked. In this context, the importance of dietary salicylic acid should not perhaps be over emphasised. “

***This research team is encouraging the use of whole foods and the intake of a variety of active phytochemicals in the same dose. Earlier within the article the anti-cancer benefits of the dose available from food intake are compared with the dose from a baby aspirin or regular dose aspirin. Within the discussion section, excerpted above, the authors point out that many other active phytochemicals contained within a food would boost the active dose from eating more produce, herbs and tea (and moderate amounts of wine).

2. [pubs.rsc.org] Chuan-Chuan Lin, Yue Liu, Chi-Tang Ho and Mou-Tuan Huang, Inhibitory effects of 1,3-bis-(2-substituted-phenyl)-propane-1,3-dione, β-diketone structural analogues of curcumin, on chemical-induced tumor promotion and inflammation in mouse skin, Food Funct., 2011, 2, 78-83 DOI: 10.1039/C0FO00098A
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 health professional for individual health care purposes.