Aging biomarker found to be increased in LongCovid, epigenetic changes possible

Evidence of aging, five years on average, was found in survivors of Covid who experienced ongoing illness after an apparent recovery or even only ever having had mild symptoms initially. (1) Other research has found evidence of autoimmune antibodies against certain types of G-protein coupled receptors – need a different post for that.

  • Evidence for Biological Age Acceleration and Telomere 2 Shortening in Covid-19 Survivors. Alessia Mongelli, Carlo Gaetano, Michela Gottardi Zamperla, et al., medRxiv, April 27, 2021, preprint, (1)
  • The results show a consistent biological age increase in the post-covid population (mean 58,44 DS 14,66 ChronoAge Vs. mean 67,18 DS 10,86 BioAge, P<0,0001), determining a DeltaAge acceleration of 10,45 DS 7,29 years (+5.25 years above range of normality) compared to 3,68 DS 8,17 years for the COVID19-free population (P<0,0001). A significant telomere shortening parallels this finding in the post-COVID19 cohort compared to COVID19-free subjects (post-COVID19 TL: 3,03 DS 2,39 Kb vs. COVID19-free: 10,67 DS 11,69 Kb; P<0,0001).” (1)
  • Additionally, ACE2 expression was decreased in post-COVID19 patients compare to COVID19-free, while DPP-4 did not change. ” (1)

ACE2 receptor expression was expected to be decreased in patients with increased viral load due to the virus destroying the cells with the receptors. Eventually less ACE2 function would be left and patients would exhibit symptoms similar to genetic ACE2 knockout mice – bred to not have ACE 2 receptors in order to see the effect on health. It can provide information about what function something has to see what goes wrong when the animal doesn’t have it.

Also of interest – stopping the virus from entering the ACE2 receptor means that it can’t replicate and go on to infect other cells or people – pomegranate peel may block access: Pomegranate peel – anti-COVID19, may block ACE2 receptor access to the SARS-CoV-2 virus. I ate some pomegranate peel today. *Recipe at the end of this post, more information about pomegranate prep & benefits G13. Pomegranate.

Pomegranate extract reduces inflammation and modulates health and gene transcription.

Pomegranate extract, of the whole fruit or peel is a very potent anti-inflammatory and modulator of health, (6), even epigenetics to some extent – epigenetics effects which genes will be transcribed into proteins by the cell. Pomegranate extract was found to modulate/effect microRNAs which control which mRNA will get transcribed. (2)

Pomegranate extract intake reversed the surgery-mediated upregulation of various miRNAs and mildly reduced expression of selected miRNAs in tumour tissue compared with normal tissue.” (2)

What is microRNA? — “Noncoding (nc) RNAs also possess a regulatory effect on gene expression. MicroRNAs (miRNAs) are small ncRNAs of 20–22 nt that inhibit gene expression at the posttranscriptional level either by imperfect base-pairing to the mRNA 3′-untranslated regions to repress protein synthesis, or by affecting mRNA stability (reviewed in [23]).” (2)

What is mRNA? — “Messenger RNA (mRNA) molecules carry the coding sequences for protein synthesis and are called transcripts;” (3) Messenger RNA is copied from the double helix strands of DNA that make a gene. The messenger RNA is a single helix – one ladder leg instead of both sides of the spiraling ladder with nucleotide steps, or one side of a zipper.

What is epigenetics? — “The term ‘epigenetics’ refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Major epigenetic mechanisms include DNA hyper- and hypomethylation [11], remodelling of the chromatin, modification of histones by histone acetylation and methylation (among others), and noncoding RNAs [12].” (2)

What are methyl donors? — Folate in the bioactive methylated form and methylated B12 are both helpful for providing the methyl groups needed for DNA methylation. The small chemical group added onto genes is like turning the light switch off, that gene is no longer in the ready to be transcribed mode. Choline is another methyl donor in the B vitamin group. See: Methyl Donors & BPA.

EGCG found in Green tea & Pomegranate Peel may protect length of Telomeres.

Pomegranate peel is also a source of EGCG (more commonly associated with green tea) which has been found protective of telomere length, by inhibiting a telomerase enzyme.

Epigallocatechin-3-gallate, a major component of green tea polyphenols, downregulated expression of human telomerase reverse transcriptase (hTERT), a major enzyme determining telomere stability, through causing promoter hypomethylation and histone deacetylations, thereby inhibiting proliferation of breast cancer cells [12].” (7)

Polyphenols, alkaloids, triterpenes, and xanthones may be plant nutrients that help inhibit the overactivity of the telomerase enzyme seen in some types of cancer cells. (8) EGCG is a polyphenol. Alkaloids include “morphine, strychnine, atropine, colchicine, ephedrine, quinine, and nicotine.” (11) Triterpenes include sterols (such as vit. D group, 12) and carotenoids (vit A). (9) xanthones are found in the Garcinia, mangosteen fruit. (10) Telomeres are a section of non protein encoding DNA at the end of genes. Telomeres get shorter as we age and longer ones indicate younger metabolic age. Excessive lengthening of telomeres can occur in cancer and that isn’t good either.

The really good news about epigenetic changes – they can be changed back.

In contrast to irreversible genetic alterations (mutations, deletions, etc.), genes silenced by epigenetic modifications are still intact and can be reactivated [13,14].” (2)

Many genes are turned on or off with the change from night to day/day to night. We do more active energy using work during the day, which produces waste chemicals, and more growth and repair, clean up, at night while we sleep. It is very unhealthy to chronically miss sleep.

Sunlight in the day & blackout curtains at night help immune function with melatonin & sunshine vitamins.

Sunlight in the morning or at some point in the awake hours of the day also helps health.

People have a feeling of wellbeing when exposed to sunlight. This may be due to the fact that keratinocytes produce β-endorphin when exposed to UV radiation.67 ” (12)

A full spectrum lamp with UVB capability for a half hour of artificial “sun” during winter months or for night shift workers may be more beneficial for health, and mood, than a vitamin D2/D3 supplement. Our bodies make other forms of the vitamin D group of sterols, some water soluble, and other forms of vitamin A are also made. (12, 13)

Bright light treatment requires a minimum of 2,500 lux to be effective, & the brightness recommended by researchers & clinicians for most people is 10,000 lux – an amount significantly higher than standard indoor lighting.” (14) This reference is recommending no UV in the light treatment, however for the vitamin D and A chemistry UVB is needed and UVA may also have some role in health in moderation.

Seasonal Affective Disorder (SAD) lamps may not provide the UVB, and the UVB intense ones are only meant for 30 minute use or less per day, as sunburn possible, so that type of light wouldn’t treat the SAD problem in the same way as the no UVB lights. (13, 15) The 10,000 lux lamps may be helping patients with Seasonal Affective Disorder (14) by increased beta-endorphins. Serotonin increase is involved in the benefit of Bright Light Therapy (BLT) which was found to be better than placebo in a metareview. (16) Bright Light Therapy was found to reduce cerebral monoamine oxidase A (MAO-A) levels which have a seasonal decrease in healthy controls compared to participants with SAD. Serotonin receptors and transport proteins may also be affected by the light treatment. (17)

Black out curtains at night and covering all little alarm clock lights and other device lights helps our body switch into night-time biology of clean-up and repair. Melatonin is also made at night and lights can reduce the amount that is made. It helps immune function and seems helpful against COVID-19. Melatonin produced in the lungs prevents infection by novel coronavirus. (18)

Lack of niacin, which is needed in increased amounts during infection or inflammation, would lead to overuse of tryptophan instead. Lack of tryptophan would lead to a lack of serotonin and melatonin, both of which are made from tryptophan. (19)

We may need a healthy gut microbiome, to have overall health.

The microbes in our intestines may have a larger role in health than we realized because they also impact our epigenetics – we want our good guys to be helping us then.

Recent research has indicated that the gut microbiota and gut microbial metabolites might be important mediators of the diet–epigenome interaction (previously reviewed in [2931]).” (2)

Obesity has been found to be related frequently to less beneficial microbiome species. (4) Anxiety can also be linked to microbiome species. (5) “Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota–gut–brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic–pituitary–adrenal (HPA) axis early in life, and stress reactivity over the life span.” (5)

More information about POTS & epigenetic changes:

I go into more detail about epigenetic changes, methyl donors and Postural Orthostatic Tachycardia Syndrome (POTS) – a problem that has been occurring for some Covid survivors and a problem I’ve had symptoms of twice and got better from twice – See: Epigenetic changes may also be involved in Covid19 or LongCovid. I prefer being healthy to being unhealthy and I’m willing to work to get better when I can.

Seasoned Peas and Pistachios, with Pomegranate peel.

Peas with pistachios, with cumin and coriander and a little pomegranate peel (inner pith)..

*Pound of frozen Peas, boil for a few minutes with a cup of Pistachios in water to cover the food – then pour off the water. It may contain oxalates from the pistachios. Add a 1/4 cup of fresh water to the drained food along with a half teaspoon of Cumin, Coriander and Gumbo file; one tablespoon powdered or minced dehydrated Pomegranate Peel (inner pith); and simmer with the peas & pistachios for a minute or two to set the Gumbo file thickener and mix the flavors. Serve the peas hot or cold with a little Apple Cider Vinegar and Salt to taste. Makes about four 3/4 cup servings.

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.

Reference List

  1. Alessia Mongelli, Carlo Gaetano, Michela Gottardi Zamperla, et al., Evidence for Biological Age Acceleration and Telomere 2 Shortening in Covid-19 Survivors. medRxiv, April 27, 2021, preprint, https://www.medrxiv.org/content/10.1101/2021.04.23.21255973v1
  2. Clarissa Gerhauser, Impact of dietary gut microbial metabolites on the epigenome. Royal Society, 23 April 2018, https://doi.org/10.1098/rstb.2017.0359 https://royalsocietypublishing.org/doi/10.1098/rstb.2017.0359
  3. Ribosomes, Transcription, and Translation, nature.com/scitable https://www.nature.com/scitable/topicpage/ribosomes-transcription-and-translation-14120660/
  4. Davis CD. The Gut Microbiome and Its Role in Obesity. Nutr Today. 2016;51(4):167-174. doi:10.1097/NT.0000000000000167 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082693/
  5. Stefanie Malan-Muller, Mireia Valles-Colomer, Jeroen Raes, et al., The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders. OMICS J of Integ Biology, Vol 22, 2, 2018, Mary Ann Liebert, Inc. DOI: 10.1089/omi.2017.007 https://www.liebertpub.com/doi/pdfplus/10.1089/omi.2017.0077
  6. Ceci C, Lacal PM, Tentori L, De Martino MG, Miano R, Graziani G. Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid. Nutrients. 2018;10(11):1756. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266224/Published 2018 Nov 14. doi:10.3390/nu10111756
  7. Yan Bian, Juntong Wei, Changsheng Zhao and Guorong Li, Natural Polyphenols Targeting Senescence: A Novel Prevention and Therapy Strategy for Cancer. Int J Mol Sci. 2020, 21, 684; https://www.dropbox.com/s/wckq66cgye3yjr4/ijms-21-00684-v3.pdf?dl=0doi:10.3390/ijms21020684
  8. Kumar Ganesan ID and Baojun Xu, Telomerase Inhibitors from Natural Products and Their Anticancer Potential. Int. J. Mol. Sci. 2018, 19, 13; doi:10.3390/ijms19010013 https://www.dropbox.com/s/xjhguj3dnbop6h2/ijms-19-00013.pdf?dl=0
  9. Triterpenes, sciencedirect.com, https://www.sciencedirect.com/topics/chemistry/triterpene
  10. Xanthones, sciencedirect.com, https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/xanthone
  11. Alkaloids, sciencedirect.com, https://www.sciencedirect.com/topics/food-science/alkaloid
  12. Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013;5(1):51-108. doi:10.4161/derm.24494 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897598/
  13. CK Eternity, The Truth about Vitamin D Metabolism, Mar 12, 2021, Patreon.com, https://www.patreon.com/posts/truth-about-d-48683534
  14. Bright Light Treatment Research. sunbox.com, https://www.sunbox.com/research/bright-light-treatment-research/
  15. Ezvid Wiki, The 6 Best Vitamin D Lights – 2019, Nov 28, 2018, youtube.com, https://www.youtube.com/watch?v=iqk9hzYC5Mc&feature=youtu.be
  16. Pjrek E, Friedrich M, -E, Cambioli L, Dold M, Jäger F, Komorowski A, Lanzenberger R, Kasper S, Winkler D: The Efficacy of Light Therapy in the Treatment of Seasonal Affective Disorder: A Meta-Analysis of Randomized Controlled Trials. Psychother Psychosom 2020;89:17-24. doi: 10.1159/000502891 https://www.karger.com/Article/Abstract/502891
  17. Spies, M., James, G.M., Vraka, C. et al. Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy. Transl Psychiatry8, 198 (2018). https://doi.org/10.1038/s41398-018-0227-2 https://www.nature.com/articles/s41398-018-0227-2
  18. Elton Alisson, Melatonin produced in the lungs prevents infection by novel coronavirus. Agência FAPESP, Jan 27, 2021 https://www.eurekalert.org/pub_releases/2021-01/fda-mpi012721.php
  19. Dmitry Kats, Tweets & images regarding tryptophan, melatonin, and niacin. “Yes, and melatonin is depleting as a result of tryptophan depleting due to inflammation, and only exclusively sufficient niacin supply can flush this inflammation out to then accordingly restore auxiliary biochem and health” “Funny how melatonin is being pushed through publications in relation to #COVID19, whilst they purposefully censor or “ignore” the inflammatory biochemical mechanism that causes this melatonin deficiency & how sufficient niacin supply nips the inflammation in the bud to restore ithttps://twitter.com/NiacinIsHealth/status/1354624867300241408?s=20

Pomegranate Peel/extract may help increase NAD+

Niacin supplementation may help when NAD+ is low during inflammatory conditions, which might include a viral infection or recovery. This topic was introduced in the recent post Kale & Carrots – super good right? maybe not for everyone. NAD+ levels also tend to be reduced with aging and may be a factor in chronic illness associated with aging. Promoting better NAD+ levels may help protect against aging and chronic illness associated with aging. “NAD+ levels decline during ageing, and alterations in NAD+ homeostasis can be found in virtually all age-related diseases, including neurodegeneration, diabetes and cancer. ” (3)

Providing niacin (6) and niacinamide would be helpful to promote more NAD+ as niacin can be made into the chemical. Preventing breakdown is another way to promote more NAD+. (3) EGCG was mentioned within the reference list of the Kale & Carrots post in some excerpts. EGCG may be able to promote more NAD+ within cells, and a few other flavonoid phytonutrients that may help reduce breakdown of NAD+ by inhibiting the enzymes involved in its metabolism. (7)

  • EGCG: “NMNATs are also attractive targets for raising NAD+ in cells because they have dual substrate specificity for NMN and nicotinic acid mononucleotide (NaMN), and they contribute to both de novo and salvage pathways (Zhou et al., 2002). The green tea compound epigallocatechin gallate [EGCG] has been reported to activate NMNAT2 by more than 100% and NMNAT3 by 42% at 50 mM, although this needs to be confirmed, as no data were presented in the paper (Berger et al., 2005).” (7)

Pomegranate peel/extract is also a source of EGCG. Pomegranate preparation tips and more information about health benefits is able on page effectivecare.info/G13. Pomegranate. It may have anti-inflammatory activity through down regulation of Fox03a (4) which is a protein that can increase oxidative stress damage in mitochondria (5) where the NAD+ chemical reactions are taking place.

  • Other phytonutrients may also be helpful to promote NAD+ by decreasing breakdown of it: “An alternative approach to raising NAD+ is to inhibit its degradation either by inhibiting PARPs or NADases, also known as glycohydrolases. The major NADase in mammals, CD38, is inhibited in vitro at low micromolar concentrations by flavonoids including luteolinidin, kuromanin, luteolin, quercetin, and apigenin (IC50 < 10 mM) .” (7)

Luteolinidin is an plant extract (a deoxyanthocyanidin) that is still in research phases for use as a CD38 inhibitor. (1) Kuromanin is also a plant extract, an anthocyanin, available for sale (expensive), under investigation as a CD38 inhibitor (preventing breakdown of NAD+) and neuro protectant. (2)

  • Luteolin is a flavonoid “found in celery, thyme, green peppers, and chamomile tea,” (18) and “chrysanthemum flowers, sweet bell [green/red/orange] peppers, carrots, onion leaves, broccoli, and parsley [78]. (21)
  • Quercetin – is in onions, garlic, green leafy veg, citrus peel, figs, and is a focus of several recent posts: Citrus Fig jam: (14), Hesperidin & quercetin content in citrus peel: (15), Decongestant properties of hesperidin/citrus peel: (16).
  • Apigenin is a flavonoid found in “grapefruit, plant-derived beverages and vegetables such as parsley, onions, oranges, tea, chamomile, wheat sprouts and in some seasonings.” (19) (Intake of more dietary flavonoids on average was associated with a reduced cancer risk. (19))
  • For references (14, 15,16, 18, 19, 21) see post: Phytonutrients that may help against SARS-CoV-2.

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.

Reference List

  1. Luteolinidin chloride, medchemexpress.com, https://www.medchemexpress.com/luteolinidin-chloride.html
  2. Kuromanin chloride, goldbio.com, https://www.goldbio.com/product/4730/kuromani-chloride
  3. Katsyuba, E., Romani, M., Hofer, D. et al. NAD+ homeostasis in health and disease. Nat Metab 2, 9–31 (2020). https://doi.org/10.1038/s42255-019-0161-5 https://www.nature.com/articles/s42255-019-0161-5?proof=t
  4. Liu S, Zhang X, Sun M, Xu T and Wang A: FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med 40: 175-181, 2017 https://www.spandidos-publications.com/10.3892/ijmm.2017.3003
  5. Tseng AH, Shieh SS, Wang DL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med. 2013 Oct;63:222-34. doi: 10.1016/j.freeradbiomed.2013.05.002. Epub 2013 May 7. PMID: 23665396. https://pubmed.ncbi.nlm.nih.gov/23665396/
  6. Pirinen E, Auranen M, Khan NA, Brilhante V, Urho N, Pessia A, Hakkarainen A, Kuula J, Heinonen U, Schmidt MS, Haimilahti K, Piirilä P, Lundbom N, Taskinen MR, Brenner C, Velagapudi V, Pietiläinen KH, Suomalainen A. Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy. Cell Metab. 2020 Jun 2;31(6):1078-1090.e5. doi: 10.1016/j.cmet.2020.04.008. Epub 2020 May 7. Erratum in: Cell Metab. 2020 Jul 7;32(1):144. PMID: 32386566. https://pubmed.ncbi.nlm.nih.gov/32386566/

Pomegranate Peel Extract – compilation of research

Around the world there are many teams working on uses of pomegranate peel for industrial, agricultural, food application, and human and veterinarian health care purposes. Much of it is organized in an initial draft along with links to some of my previous work on developing home recipes for personal use of pomegranate peel extract.

  • See: https://docs.google.com/document/d/1biWxjYHOHd-i73Wui69QIO6zVuqNwGHZdYU56H9pLTw/edit?usp=sharing
  • I will continue to work towards combining the previous information I’ve found and recipes and the new list of research references into one cohesive document, however in the interest of open research and advancing health and sustainability I’m sharing the initial draft now.
  • The health benefits have seemed like a miracle to me, sharing the good news in hope that it reaches more people is my goal.

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.

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)
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