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)

Pomegranate health benefits, serving size and extract recipe summary

For ease of use, a summary of the links and information available about health benefits of pomegranate seeds, juice and peel; serving size information that is based on animal based research studies and my own use of different pomegranate ingredients; and a concise recipe for the pomegranate peel extract recipe that I’ve developed.

Health benefits of pomegranate:

Pomegranate extract has been studied in animal based research to examine in more detail how it helps hypertensive blood pressure problems and reduce oxidative stress. The mechanism was found to involve increasing Nrf2. The formation of mitochondria increased, and their function improved. Before treatment the hypertensive animals had fewer of the specialized proteins that are involved in production of mitochondria. Mitochondria are the cellular organelles primarily responsible for turning blood sugar/glucose into usable energy. (5)

This study uses a pomegranate extract that incorporates the peel, seeds and juice as all contain the bioactive phytonutrient, punicalagin, thought to be most helpful for anti-inflammatory, anti-tumor and anti-diabetic effects. The animals who received the extract were found to have better blood pressure, reduced heart hypertrophy ( a sign of worse heart health) and a lower heart rate. Neuronal/nerve cell activity and oxidative stress markers were decreased in the experimental treatment group compared to the control group which received a saline solution and no pomegranate extract. Angiotensin converting enzyme which is involved in blood pressure control was lower in the experimental group  that received pomegranate extract and may be the mechanism for the lower blood pressure. Pro-inflammatory cytokines were reduced in the experimental group after treatment, an indication that hypertensive inflammation was reduced. The pomegranate extract treatment led to increased levels of phosphorylated AMPK which then leads to an increase in Nrf2 and its resulting increases in antioxidant proteins which protect against injury and inflammation from oxidative stress chemicals. (5)

Serving size that might be needed for general health or for special health needs:

Animal based research used a range  of 1 – 10 grams/kilogram for 8 weeks was found to be beneficial for treatment of hepatocellular carcinoma (6); which for a human sized person might be equivalent to a  a quarter to a half cup to a couple cups per day. (See this post for more details) The larger dose would likely be most beneficial used in smaller amounts throughout the day or in a couple portions. For example: Half a cup per day might be used for someone who is less ill and someone with more severe illness or genetic needs such as myself (I can’t make phospholipids and the pomegranate seeds and peel are a source) might use up to a half a cup every three to four hours throughout the hours spent awake – or whatever helped the symptoms. If every cell of the body needs the substances, every hour of the twenty-four, then one dose one time per day might leave the body under-treated for most of the 24 hours and only relieve symptoms for a few hours. The peel extract has a diuretic effect so using it earlier in the day and having a few extra glasses of water is mentioned in more detail later in this section.

I have found 1/3 to 1/2 cup of fresh seeds or pomegranate juice per day to help relieve my symptoms of anxiety and finger numbness (similar to Raynaud’s Disease but no diagnosis). Other patient forum feedback suggests one capsule of commercially available pomegranate juice concentrate was also helpful for Raynaud’s disease finger numbness or pain. (Avoiding letting the hands get too cold also can help prevent the condition from feeling as painful rather than just being a constant numbness in the fingertips.)

If I have pomegranate extract on hand I use a few tablespoons to about  1/3 cup per day and find it even more beneficial for relieving symptoms of anxiety or nerve numbness. However it has a diuretic effect so it is better to use it earlier in the day rather than at dinnertime and to have plenty of water or other water based beverages early in the day so sleep isn’t interrupted with a need to relieve the bladder. It is important to drink a little extra water or the urge to urinate can be painful and produce little flow. The body removes acidity by making a more concentrated urine – so add water yourself or a dilute juice or herbal tea and the kidneys will also be removing other toxins too which may increase health benefits.

Dried powdered pomegranate seeds are available at some India food grocery stores or websites look for a small box labeled Anardana. It seems to be a dried powder of the whole seeds and it is gritty and tart with a fruit flavor. I added a couple tablespoons to a batch of soup and that seemed to soften the gritty effect. It was good added after cooking, giving a nice tartness but there was a slight gritty texture occasionally, not too noticeable though. Anardana Powder, dried pomegranate seed powder – an example of the product available online:

  • Yogijis.co.nz      Phone:  (03) 390 3434      Email: orders@yogijis.nz
  • Anardana Powder, Powder of Dried Pomegranate Seeds: net Wt. 100 g//3.5 oz for $3.99

An organic pomegranate juice concentrate is also available in the same quantity for a larger price. That seems like a lot of money for a 3.5 oz package which is slightly less than a half cup amount, unless you were comparing it to prepared capsules of a pomegranate product which might cost 20 to 30 dollars for one bottle of capsules:

  • Matakanasuperfoods.com, PO Box 18, Matakana 0948 New Zealand / Physical address: 108 Omaha Flats Rd. Auckland, New Zealand, Phone: 09 422 9618    Outside New Zealand:  +64 9 422 9618
  • Organic Pomegranate Juice Powder, 100g, $NZ 29,95

Sumac and Za’atar

A spice commonly used in Middle Eastern cooking and readily available at Middle Eastern grocery market may provide some similar health benefits to pomegranate. It is a dried powdered form of Sumac that has a lemony flavor. it is typically sprinkled on food individually at the table alone or in a mix with salt or with a few other spices and sesame seeds in a mixture called za’atar (link). I have found that using more than a half teaspoon  can cause the diuretic effect similar to the pomegranate extract’s effects. Studies on health benefits of Sumac have found benefit for a number of inflammatory conditions so using some in small amounts daily may have preventative health benefits against oxidative stress.

Pomegranate Extract Recipe  and Spicy variation:

Pomegranate Extract, basic recipe:

  • Peel and inner membrane of two pomegranates
  • Two to three cups of water
  • Two Tablespoons of Coconut oil
  1. Rinse the pomegranates before separating the seeds from the peel. Cutting the rind about a quarter inch deep in six sections can make it easier to open and remove the seeds. Save the juicy seeds for use fresh or place in a freezer container and store in the freezer for later use. Trim the peel to remove any spoiled or discolored spots on the outer peel or inner membranes. Discard. Rinse the remaining peel and chop into quarter to half inch sections.
  2. In a soup or stock pot place the chopped peel, water and coconut oil and bring to a gentle simmer and turn down the heat to continue at a gentle simmer. Try not to reach a vigorous boiling point. Simmer the mixture for 20-30 minutes while stirring occasionally to prevent the fibrous slightly sweet membrane particles from sticking to the pan.
  3. Remove from heat and strain the liquid into another large pan or bowl. The peel and membrane fiber is pulpy and can be rinsed with additional water to increase yield of the pulpy extract. Add one cup warm water and stir and strain the pulp and then add another one cup warm water, stir and strain, and maybe one or two more cups until the liquid seems more water like instead of a slightly thickened pale pinkish or creamy yellow color.
  4. Store the pomegranate extract in the refrigerator if it will be used in other recipes within a few days or freeze the excess in small containers for gradual use.
  5. It is very acidic and using a couple spoonfuls per day added to a soup or salad in place of lemon juice or vinegar can be a tasty way to use it. Diluting a few spoonfuls to 1/3 cup with an additional 2/3 cup of water or regular juice of some sort and adding a pinch of baking soda  can make it tolerable as a beverage. One third cup per day should provide adequate health benefits for someone using it for that purpose.

Pomegranate Extract made with dehydrated pomegranate peel

Repeat the above steps using pomegranate peel and membrane that had been prepared and diced into 1/4-1/2 inch sections and dehydrated for long term storage – planning ahead for when pomegranates were no longer in season. One pomegranate peel/membrane produced approximately 30 grams of dried peel and which measured at slightly less than a 1/2 cup of dried pieces loosely packed. Per one pomegranate amount of peel simmer with one tablespoon of coconut oil and 2 cups of water, about 20-30 minutes on low heat. After straining the heated peel I rinsed the peel with two cups of water poured over it gradually while stirring. The yield was three cups of pomegranate extract.

Spicy Pomegranate Extract, Slightly less acidic and slightly thickened and emulsified Spicy:

  • 6 cups of pomegranate extract  (previous post) (in a more recent version I include 2 tablespoons of Rosemary and 2 tablespoons of Thyme during the simmering process, and strain out the herbs along with the simmered pomegranate peel. Both herbs have anti-inflammatory and other beneficial effects. They add a savory flavor to the mixture that is less noticeable once the Cardamom is added. I use a spoonful in my cup of coffee in the morning or in a bowl of soup. One or a few spoonfuls per day seems to help balance my mood (7, 8) and symptoms of numbness in my fingertips.)
  • 2 Tablespoons Cardamom powdered spice
  • 1 teaspoon Gumbo File powdered spice (Sassafras Leaves, powdered and used in Gumbo soups or stews in Creole style cooking)
  • 1 teaspoon Baking Powder
  1. Add the Cardamom and Gumbo File to the Pomegranate Extract and stir well to break apart any dry lumps of the powdered spices. The Gumbo File acts as an emulsifier and is a digestive aid and the Cardamom adds flavor, phytonutrients and would help alkalize the mixture in addition to the alkalizing power of the Baking Soda.
  2. Bring the mixture to a boil.
  3. Add the Baking Soda and stir. Remove the mixture from the heat and keep stirring. It will froth up and stirring helps keep it from frothing over the top of the pan. The color changes from pinkish to brown from the Cardamom spice.
  4. To drink as a beverage dilute with equal parts water to Pomegranate Extract.

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.

References: