Author: Jenny

I am a public health nutrition counselor with fifteen years experience in the field of prenatal and early child health and lactation education (breast feeding support). Autoimmune disease, Autism Spectrum Disorders, and genetic defects that can cause nutrient deficiencies are also research interests.
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Anemia of Inflammation, IL-6, Hepcidin, Iron and Vitamin C.

During bacterial infections iron is shifted out of hemoglobin production and into ferritin and intracellular storage. (Iron and Anemia of Chronic Inflammation, post) If amounts of the free iron overloads the cell capacity and antioxidant capacity then cell death may result and other damage. The shift of iron involves an increase in the inflammatory cytokine IL-6 (Interleucon-6) which causes an increase in hepcidin, which causes the removal of iron from hemoglobin. (5)

Having extra antioxidants in the diet can help the body cope with the sudden increase in free iron – think of rust – iron oxidizes and the body doesn’t want rust anymore than you want it on your car. Antioxidants like vitamin A and C and bioflavonoids can all help stabilize the chemically active iron. The anti-malarial herbal extract called artemisinin may help by binding some of the excess free iron stores. (4) *addition – quercetin, EGCG, resveratrol, turmeric are also iron chelators and lactoferrin is a milk based iron chelator that has not been found an allergy risk for people with a milk-based allergy.

ACE2 receptors are likely more prevalent in the lung cells of smokers (1) and COPD patients, (3), and people living in air pollution because it has a protective effect against lung injury. It helps decrease levels of the inflammatory cytokine IL-6. (2) Which suggests that extra vitamin C and bioflavonoids, and other nutrients may also help reduce the risk of anemia of chronic inflammation and other lung and heart risks from chronic hypoxia (low oxygen levels in the blood).

The COVID-19 illness may have a risk of sudden death due to cardiovascular problems upon relapse/reinfection (6) because of the shift in iron and resulting risk of cell death due to excess free iron. The use of iron chelators or artemisinin and continuing the use of extra antioxidants such as vitamin C and bioflavonoids might help prevent excess coagulation and reverse the shift of iron atoms from hemoglobin molecules to ferritin and free iron within cells. Infectious microbes need iron too so it is a self defense strategy that may become excessive in the case of severe COVID-19 illness.

There is more about bioflavonoids, vitamin C, and coagulation risks of SARS-CoV-2 infection in this post: Bitter Taste Receptors in the Lungs – Hesperidin’s Decongestant Properties.

Reference List

  1. SJ Brake, K Barnsley, Wenying Lu, et al., Smoking Upregulates Angiotensin-Converting Enzyme-2 Receptor: A Potential Adhesion Site for Novel Coronavirus SARS-CoV-2 (Covid-19). J. Clin. Med.2020, 9(3), 841; https://doi.org/10.3390/jcm9030841 https://www.mdpi.com/2077-0383/9/3/841/htm
  2. Lin CI, Tsai CH, Sun YL, Hsieh WY, Lin YC, Chen CY, Lin CS. Instillation of particulate matter 2.5 induced acute lung injury and attenuated the injury recovery in ACE2 knockout mice. Int J Biol Sci 2018; 14(3):253-265. doi:10.7150/ijbs.23489. Available from http://www.ijbs.com/v14p0253.htm air pollution studies – ACE2 would be protective against ACE->IL-6 “Increased ACE levels cause the activation of AT1R by Ang II, consequently inducing the expression of the inflammatory cytokines IL-6, TNF-α and TGF-β1 [17]. ACE2 counter-regulates the effects produced by Ang II by converting Ang II to Ang-(1-7), activates Mas to repress the signaling pathways of STAT3 and extracellular signal-regulated kinases (ERK) [18], and acts as an anti-inflammatory factor [19]. “
  3. ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19. https://erj.ersjournals.com/content/early/2020/03/26/13993003.00688-2020
  4. Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium falciparum https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590262/ “Artemisinin found in the Chinese medicinal plant (Artemisia annua) binds iron to form ferric-dihydroartemisinin complex, resulting in reactive oxygen species (ROS)-mediated potent anti-malarial activity against ring and late stage of CQ-resistant P. falciparum malaria parasites [5]. “
  5. Covid-19 – Liver – iron overload – lung cascade – coagulation a forum topic on peakprosperity.com with links to research, excerpts and discussion re COVID-19 – Liver – iron overload – lung cascade – coagulation. https://www.peakprosperity.com/forum-topic/covid-19-liver-iron-overload-lung-cascade-coagulation/
  6. Jules Quartly, Exclusive: Chinese doctors say Wuhan coronavirus reinfection even deadlier. Feb 14, 2020, TaiwanNews.com, https://www.taiwannews.com.tw/en/news/3876197
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Phytonutrients that may help against SARS-CoV-2.

  • Anthemis hyalina, a medicinal daisy like herb, carvocrol and alpha-pinene were main components. It was most potent at preventing coronavirus replication in a cell based study compared with Nigella sativa oil and citrus peel extract, however citrus peel is easier to find at the grocery store. (1, 2)
  • Citrus peel (peel of Citrus sinensis – standard oranges) contains potent phytonutrients with antiviral & decongestant properties. (1, post)
  • Nigella sativa/Black Seed Oil/Black Cumin Seed, (1), contains “thymoquinone (TQ) (30- 48%), flavonoids, anthocyanins, alkaloids and essential fatty acids, particularly linoleic and oleic acid.” Thymoquinone/Nigella sativa oil has been found to promote the beneficial Nrf2 pathway and inhibits the inflammatory NfKb pathway in addition to acting as an antioxidant. It also has been found to help protect liver and kidney health in the presence of a variety of chemical and pathogenic toxins. (3)

Citrus peel, Black Seed oil, and a medicinal daisy are fairly specific foods or herbal supplements however there are ten other phytonutrients found in many different foods, that are also suspected of having antiviral benefits against the SARS-CoV-2 virus. Computer modeling of the chemical shapes of the nutrients and the virus was used to estimate potential bond strength of the Spike portion of the virus and the phytonutrients and the medication hydroxychloroquine. The phytonutrients were estimated to be more effective at bonding with and inhibiting the virus at the Spike protein compared to the medication hydroxychloroquine, (a lower number – more negative in this case- indicates a stronger bond energy):

“Among these phytochemicals, flavonoids and non-flavonoids have been found to be the active source of different anti-microbial agents. Recently, studies have shown that these phytochemicals have essential anti-viral activities.”

“Kamferol, curcumin, pterostilbene, and HCQ [hydroxychloroquine] interact with the C-terminal of S1 domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively.”

“Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol and apigenin on the other hand, interact with the S2 domain of spike protein with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2, -7.9, -7.7 Kcal/mol, respectively.”

*The lower the number, the stronger the molecular bonding is estimated to be – energy required to break the molecular bond between phytonutrient or medication and the viral protein – the C-terminal of the S1 domain of the Spike protein on the SARS-CoV-2 virus or the S2 domain. Note that the binding energy of hydroxychloroquine is the weakest (closest to zero).

(Rane et al., 2020)(4)

The phytonutrients are found in wide range of foods, some in many foods, and others may be found in a few specific foods – the variety may be adding up to health. These nutrients and others in whole foods can help reduce the risk of Metabolic Syndrome or improve it. Having Metabolic Syndrome, obesity, and/or Type 2 diabetes has been associated with greater risk of more severe symptoms if sick with COVID19. (20)

“Given the speed at which health markers for metabolic disease improve from dietary interventions, an equally strong if not more significant population health message should now be to “eat real food, protect the NHS and save lives.””

Covid 19 and the Elephant in the Room, (20).

Phytonutrients that may inhibit the Spike protein of the SARS-CoV-2 virus and block entry into cells.

“Quercetin, a plant pigment is a potent antioxidant flavonoid and more specifically a flavonol, found mostly in onions, grapes, berries, cherries, broccoli, and citrus fruits.” (26)

  • 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). Quercetin represents a large group of similar chemicals and is fairly common in small amounts in many fruits, vegetables and leafy herbs. It is found primarily in the leaves or edible peels. It has anti-viral ability as a zinc ionophore – carrying zinc into iron rich cells where it disrupts protein replication. In normal health zinc and iron is kept out of cells in quantity. Iron rich cells tend to be infected or cancerous. See my COVID19 page for more information.
  • Kamferol – is a flavonoid found in similar green veggies as quercetin, including kale, leeks, onions, broccoli, and also is in blueberries, strawberries, kiwi, and other fruits and berries, (myintakepro), and cinnamon. (23) (The camphor in cough drops that helps as a decongestant is different, it is a terpene, and is extracted from a couple tree species. It is also found in the herb rosemary. (wikipedia.org/Camphor)
  • Curcumin is an extract of turmeric root which is used in curry spice mixes. It is a vitamin D analog, and active hormone D is essential for a healthy immune response, some is essential but too much D can also be harmful.
    • Curcumin and catechins have been found to be active at the coronavirus Spike protein and human ACE2 receptor where the virus enters cells. (7)
  • EGCG and other Catechins are also flavonoids, and are found in green & black tea, apples, blackberries, dark chocolate, red wine, cherries, guava, pears, sweet potatoes & purple potatoes. (8, 7) Pomegranate fruit, juice and peel (G13.Pomegranate), is also a good source of EGCG and other catechins and ellagitannins. (24) EGCG may be protective as a preventive or treatment for Covid19. EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection (25)
  • Pterostilbene is found in almonds & Vaccinium berries – blueberries, cranberries, also in grape leaves/grapes but doesn’t last through the wine making process. It is chemically similar to resveratrol which can be found in grapes & wine. (9)
  • Resveratrol is found in grapes/grape skins/wine, and in “peanuts, pistachios, grapes…wine, blueberries, cranberries…dark chocolate.” (10)
    It is an estrogen receptor modulator/analog & estrogen can have anti-inflammatory effects for health. (11)
  • Genistein is found in soybeans, soy products like tofu, tempeh & miso, also is in chickpeas/other legumes, in smaller amounts. It is an estrogen receptor analog/modulator (like resveratrol) and estrogen can have anti-inflammatory effects. (12)
    • While men tend to have more ACE2 receptors and that is thought a possible reason for a higher rate of mortality for men than women from COVID19, may be estrogen is having a protective effect also.
  • Fisetin– is a “flavonoid found in…(strawberries, apples, mangoes, persimmons, kiwis, & grapes), vegetables (tomatoes, onions, and cucumbers), nuts, & wine that has shown strong anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic” properties. (13)
  • Isorhamnetin is a flavonol, and a derivative of quercetin. It is found in “parsley, green bell peppers, and dills and in a lower concentration in garden cress, black chokeberries, and honey,” (17), and in cinnamon. (23)
  • 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 [7 8]. (21)
  • 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)

“During the past two decades, plant-derived bioactive compounds have been reported as novel health-giving agents for prevention and/or mitigation of different human diseases such as cancer, inflammation, cardiovascular, and neurodegenerative diseases [5]. Among these compounds, more than 5000 flavonoids have been identified and are distributed in a wide range of plants. On the basis of their chemical structures, these flavonoids have been grouped into 10 categories, 6 of which including:  flavones, flavanones, anthocyanidins, flavonols, 

isoflavones, and catechins, are commonly present in the human diet.” *

(Imran, et al., 2019) (21) *links are to ScienceDirect topic pages.

Many of these phytonutrients and others found in plant foods help our bodies to have enough of an immune response without having an overactive autoimmune or allergy type of response, acting as immunomodulators. They also help the body switch from inflammatory chemical pathways, that are more typical of daytime hours of our circadian cycle, to anti-inflammatory pathways more typical of sleep hours.

Pitch blackness at night and some full spectrum daylight during wake hours of an individual’s circadian 24 hour day can also help the body to stop the day time stress response inflammatory chemistry and start the nighttime anti-inflammatory healing activity. More on this topic is available in a book that is in very early stages of being written/rewritten from work I’ve completed elsewhere: Tipping the Circadian Clock Towards Health.

Some other tips for lifestyle changes that can help protect health and may even help promote growth of new brain cells in the hippocampus, (the area of the brain that is damaged in Alzheimer’s dementia). 22

Anti-inflammatory Phytonutrients/nutrients from a previous post; promote p53 or inhibit NLRP3:

Addition 12/23/2021: “Here we performed bioinformatic analysis to investigate the interaction of S2 subunit protein of SARS-nCoV-2 of novel coronavirus with tumor suppressor proteins p53 and BRCA-1/2.” (27)

The anti-aging/anti-inflammatory p53 protein seems to be inhibited by the S2 subunit of the spike protein. The p53 protein helps inhibit the cell killing NLRP3 inflammasomes – their mission is to destroy allergens. Cells with spike lodged in a surface receptor would likely be taken as an infected or allergen producing cell that needs to be killed.

There are a variety of phytonutrients that help reduce NLRP3 inflammasome production or promote the p53 protein:

Other phytonutrients including quercetin which is found in citrus peel, also can help inhibit production or activity of the inflammatory NLRP3 inflammasome which has been found to be elevated during more severe COVID19 illness. Sulfarophane (broccoli, etc), resveratrol (grape skins, etc), EGCG (green tea, pomegranate peel), curcumin (turmeric/curry powder), gensenoside (ginseng), emodin (aloe vera gel), mangiferin (mango) and genipin (from a fruit used as a Traditional Chinese Medicinal) are also phytonutrients that may reduce activity or production of NLRP3 inflammasomes. (17*) **

Increasing activity of a protein called p53 seems to help inhibit the production or activity of the NLRP3 inflammasome. Phytonutrients and nutrients that may promote p53 activity also include zinc, artemisinin (wormwood herb), goldenseal (berberine, also found in a few other herbs), Black seed oil (Nigella sativa), ginger (6-gingerol), feverfew, chamomile, and cordyceps mushrooms. (18*)** Replication of human coronaviruses and the SARS-CoV-1,(2003 strain) virus has been found to be inhibited by p53 and have also been found to cause the production of an additional protein that leads to breakdown of the p53 protein which may help explain the dysfunction of immune function in more severe infections. (21*, 22*)**

Inactivating the NLRP3 inflammasome seems to have anti-inflammatory benefits (17) that may help prevent age related changes. It is an area of research being pursued for pharmaceutical development. (11*)** Sleep masks/pitch blackness during sleep, with the alarm clock and light leaking in the window covered, could help your body inactivate the NLRP3 inflammasome on a nightly basis with no ongoing copay. **(See the post Bitter Taste Receptors… for references 11*, 17*, 18*, 21*, 22*)

Options exist and are worth trying in an order of least toxicity risk to greater toxicity risk – foods and herbs and spices or herbal supplements are generally low toxicity and would taste too strong as an indicator of an excess being used. First-aid/self care type of treatments can include the bowl of hot and sour spicy soup or orange with the pith layer left on, or a cup of hot steamy green tea or herbal tea with slippery elm powder, (a mucilaginous/water soluble fiber source, see the post ACE2, Diarrhea… for more food mucilaginous foods and food sources of hydrolyzable tannins, both groups can be beneficial for inflammatory bowel/diarrhea types of conditions or symptoms).

Mix it up – and it may add up to health, have some healthy ingredients along with whatever favorite foods you may also love. Experiment with adding more herbs and spices to favorite foods, gradually, and taste preferences can adapt and new discoveries may become old favorites eventually.

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

  1. Ulasli M, Gurses SA, Bayraktar R, et al. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family. Mol Biol Rep. 2014;41(3):1703–1711. doi:10.1007/s11033-014-3019-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/
  2. Abdolhossein Rustaiyan, Shiva Masoudi, Laleh Ezatpour, Elmira Danaii, Mahboubeh Taherkhani & Zahra Aghajani (2011) Composition of the Essential Oils of Anthemis Hyalina DC., Achillea Nobilis L. and Cichorium intybus L. Three Asteraceae Herbs Growing Wild in Iran, Journal of Essential Oil Bearing Plants, 14:4, 472-480, DOI: 10.1080/0972060X.2011.10643603 https://www.tandfonline.com/doi/abs/10.1080/0972060X.2011.10643603
  3. Desai S D, Shaik Hussain Saheb, Kusal K Das, Haseena S, Phytochemical Analysis of Nigella sativa and Its Antidiabetic Effect. J. Pharm. Sci. & Res. Vol. 7(8), 2015, 527-532 https://www.jpsr.pharmainfo.in/Documents/Volumes/vol7Issue08/jpsr07081506.pdf
  4. Rane, Jitendra Subhash; Chatterjee, Aroni; Kumar, Abhijeet; Ray, Shashikant (2020): Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12094203.v1 https://chemrxiv.org/articles/Targeting_SARS-CoV-2_Spike_Protein_of_COVID-19_with_Naturally_Occurring_Phytochemicals_An_in_Silco_Study_for_Drug_Development/12094203
  5. Kaempferol Rich Foods, myintakepro.com, https://myintakepro.com/blog/kaempferol-rich-foods/
  6. Camphor, wikipedia.com, https://en.wikipedia.org/wiki/Camphor
  7. Atala B. Jena, Namrata Kanungo, Vinayak Nayak et al. Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and implication for intervention, 08 April 2020, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-22057/v1 https://researchsquare.com/article/rs-22057/v1
  8. 10 Ways to Get Your Catechin Fill, cleaneatingmag.com, https://www.cleaneatingmag.com/clean-diet/10-ways-to-get-your-catechin-fill
  9. What is Pterostilbene?, elysiumhealth.com, https://www.elysiumhealth.com/en-us/science-101/what-is-pterostilbene
  10. Resveratrol Offers Health Boost, health.harvard.edu, https://www.health.harvard.edu/blog/diet-rich-resveratrol-offers-health-boost-201405157153
  11. Resveratrol, ScienceDirect.com, https://sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/resveratrol
  12. Sutrisno Sutrisno, Hardianti Aprin, Happy Marthalena Simanungkalit, et al., Genistein modulates the estrogen receptor and suppresses angiogenesis and inflammation in the murine model of peritoneal endometriosis. J Trad & Comp Med, 8;2, April 2018, pp 278-281, https://doi.org/10.1016/j.jtcme.2017.03.002 sciencedirect.com, https://www.sciencedirect.com/science/article/pii/S2225411017300366
  13. Pal HC, Pearlman RL, Afaq F, et al., Fisetin and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:213-244. https://ncbi.nlm.nih.gov/pubmed/27671819
  14. Citrus Fig Marmalade Jam, transcendingsquare.com, https://transcendingsquare.com/2020/04/12/citrus-fig-marmalade-jam/
  15. Hesperidin & quercetin content in citrus peel, transcendingsquare.com, https://transcendingsquare.com/2020/04/14/hesperidin-and-quercetin-content-in-citrus-peel/
  16. Bitter Taste Receptors in the Lungs – Hesperidin’s Decongestant properties, transcendingsquare.com, https://transcendingsquare.com/2020/04/07/bitter-taste-receptors-in-the-lungs-hesperidins-decongestant-properties/
  17. Showing Compound Isorhamnetin (FDB000604) foodb.ca https://foodb.ca/compounds/FDB000604
  18. USDA/Agricultural Research Service, Luteolin stars in study of healthful plant compounds. July 16, 2010, ScienceDaily.com, https://www.sciencedaily.com/releases/2010/07/100708141622.htm
  19. Shukla S, Gupta S. Apigenin: a promising molecule for cancer prevention. Pharm Res. 2010;27(6):962–978. doi:10.1007/s11095-010-0089-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874462/ )
  20. Aseem Malhotra, Covid-19 and the Elephant in the Room, April 16, 2020, europeanscientist.com, https://www.europeanscientist.com/en/article-of-the-week/covid-19-and-the-elephant-in-the-room/
  21. Imran M, Rauf A, Abu-Izneid T, et al., Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacother. 2019 Apr;112:108612. doi: 10.1016/j.biopha.2019.108612 https://www.sciencedirect.com/science/article/pii/S0753332218367180?via%3Dihub “During the past two decades, plant-derived bioactive compounds have been reported as novel health-giving agents for prevention and/or mitigation of different human diseases such as cancer, inflammation, cardiovascular, and neurodegenerative diseases [5]. Among these compounds, more than 5000 flavonoids have been identified and are distributed in a wide range of plants. On the basis of their chemical structures, these flavonoids have been grouped into 10 categories, 6 of which including  flavones, flavanones, anthocyanidins, flavonols, isoflavones, and catechins are commonly present in the human diet.“
  22. Andrea Donsky, You Can Make New Brain Cells and Improve Your Memory, naturallysavvy.com, https://naturallysavvy.com/restore/you-can-make-new-brain-cells-and-improve-your-memory/
  23. Rao PV, Gan SH. Cinnamon: a multifaceted medicinal plant. Evid Based Complement Alternat Med. 2014;2014:642942. doi:10.1155/2014/642942 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003790/
  24. Huertas M. Díaz-Mula, Francisco A. Tomás-Barberán, and Rocío García-Villalba, Pomegranate Fruit and Juice (cv. Mollar), Rich in Ellagitannins and Anthocyanins, Also Provide a Significant Content of a Wide Range of Proanthocyanidins. J Agr and Food Chem 2019 67 (33), 9160-9167 DOI: 10.1021/acs.jafc.8b07155 https://pubs.acs.org/doi/10.1021/acs.jafc.8b07155
  25. Mukesh Chourasia, Purushotham Reddy Koppula, Aruna Battu, et al., EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection. Molecules 2021, 26(5), 1200; https://doi.org/10.3390/molecules26051200 https://www.mdpi.com/1420-3049/26/5/1200/htm
  26. Anand David AV, Arulmoli R, Parasuraman S. Overviews of Biological Importance of Quercetin: A Bioactive Flavonoid. Pharmacogn Rev. 2016;10(20):84-89. doi:10.4103/0973-7847.194044 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214562/
  27. Nishant Singh, Anuradha Bharara Singh, S2 subunit of SARS-nCoV-2 interacts with tumor suppressor protein p53 and BRCA: an in silico study. Translational Oncology, Vol 13, Issue 10, 020, 100814, ISSN 1936-5233, https://doi.org/10.1016/j.tranon.2020.100814. https://www.sciencedirect.com/science/article/pii/S1936523320303065
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Hesperidin and Quercetin content in Citrus peel.

Based on yield ranges in a review article (1), the whole citrus peel, colorful zest and white pith layers, contained across a variety of types of citrus, greater than 2000 micrograms/gram Fresh Weight (ug/gr FW) Quercetin Equivalents (group of similar chemicals), and 83-234 milligram/gram Fresh Weight (mg/gr FW) Hesperidin (for an average of 158.5 mg/gr FW). (1)

  • An average size navel orange weighed 212.18 grams, ~ 7.5 ounces
  • and yielded 32.48 gram orange zest peel, ~ 1 ounce
  • 32.30 white pith peel, ~ 1 ounce
  • 144.49 orange wedges, ~ 5.2 ounces
  • small amount of unusable trimmings.

The citrus peel may contain 64 milligrams of quercetin and 5120 milligrams of hesperidin in the whole peel – the original measurements were of whole citrus peel (1) so it is unknown how much the white pith contains in comparison to the orange zest layer which likely contains more of the bitter tasting phytonutrients. Hesperidin was reported as being most prevalent of flavonoids being measured and equivalent across thin and thick skinned citrus species suggesting that more is in the thin zest layer (the flavedo) than the thick white pith layer (the albedo). (1, 4)

The white pith layer would likely contain a majority of the beneficial fiber and pectin, which makes up 64% of the whole peel of oranges, (1), or at least 21 grams of the yield of white pith or the orange zest in this example would be fiber/pectin. The jam in the last post had thickened even without the added pectin which led to it being too firm of a gel.

Citrus peel, the white pith, albedo layer, and the orange zest, flavedo layer, with the orange.

Health benefits may be provided from both types but in varying concentration. When I am feeling congested the pith of the whole orange is enough to clear the congestion and to help me breath more clearly again. See this post: Bitter taste receptors in the lungs & Hesperidin’s decongestant properties. Some of the zest is remaining on the white pith layer in small amounts too, but it is potent in flavor. The citrus peel jam in the last post is stronger in flavor than the white pith and a generous spoonful is plenty for a serving, and I usually mix it with other foods rather than eating it all at once.

The orange zest when minced made about a quarter cup/25 grams so the amount of 2 1/2 cups citrus zest in the jam recipe may have 250 grams potentially containing the majority of the 5120 mg of hesperidin per ounce – roughly 5000 x 10 1/4 cups = 50,000 mg for the 6 cup yield, 8,330 mg/cup or 1040 mg per two tablespoon serving of the Citrus Fig Marmalade/Jam, last post.

How much might be too much hesperidin? roughly about 28 oranges if 5120 milligrams were available with each pith layer of the peel that is eaten – however just one or two oranges per day, spaced out across the day, were good for my symptoms of congestion while I was ill, or when I am congested with spring allergies. The potentially Lethal Dose for 50% of lab animals for hesperidin, the LD50 dose, is 2000 mg/Kg. (2)

*addition – there is likely more hesperidin in the white pith than in the orange zest:  “The French chemist Lebreton (1828) was first to isolate hesperidin from the white inner layers of citrus peels.” (7)

Hesperidin, rutin, citrus bioflavonoids are mildly estrogenic (so is resveratrol) and may be helpful against endometrial cancer. (2) Hesperidin may help against endometrial cancer cells by down-regulating estrogen receptors/progesterone & increasing apoptosis of the tumorous cells. (5) Bioflavonoids also seem to help reduce risk of Metabolic Syndrome, and related problems of obesity, high blood pressure, and insulin resistance, and reduce risk of cardiovascular problems. (3, 4, 6) Hesperidin can help reduce capillary fragility (6) – potentially preventing microvascular hemorrhages. More about the potential anti-viral and other health benefits of hesperidin and citrus bioflavonoids is in the post: Bitter taste receptors in the lungs & Hesperidin’s decongestant properties.

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

  1. Shafiya Rafiqa, Rajkumari Kaula, S.A.Sofi, et al., Citrus Peel as a Source of Functional Ingredient: A Review, J Saudi Society of Ag Sci, 17;4, Oct 2018, pp 351-358, https://www.sciencedirect.com/science/article/pii/S1658077X16300960
  2. Chapter 76 – Cardiovascular Effects of Hesperidin: A Flavanone Glycoside. Polyphenols in Human Health and Disease. Vol 2, 2014, pp 989-992. https://www.sciencedirect.com/science/article/pii/B9780123984562000761
  3. Assini JM, Mulvihill EE, Huff MW. Citrus flavonoids and lipid metabolism. Curr Opin Lipidol. 2013 Feb;24(1):34-40. doi: 10.1097/MOL.0b013e32835c07fd. https://www.ncbi.nlm.nih.gov/pubmed/23254473
  4. Bobbie Randall, RD. Citrus Albedo is Better Than You Thought, Jan 22, 2020, delgazette.com, https://www.delgazette.com/opinion/81450/citrus-albedo-is-better-than-you-thought
  5. Cincin ZB, Kiran B, Baran Y, B.Cakmakoglu. Hesperidin promotes programmed cell death by downregulation of nongenomic estrogen receptor signalling pathway in endometrial cancer cells. Biomedicine & Pharmacotherapy, Vol 103, July 2018, pp 336-345 https://www.sciencedirect.com/science/article/abs/pii/S0753332217332407
  6. Hesperidin/ScienceDirect, https://www.sciencedirect.com/topics/neuroscience/hesperidin CITRUS FRUITS | Processed and Derived Products of Oranges C.M. Lanza, in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003 // A Review of the Effects of Citrus paradisi (Grapefruit) and Its Flavonoids, Naringin, and Naringenin in Metabolic Syndrome Bibi Marjan Razavi, Hossein Hosseinzadeh, in Bioactive Food as Dietary Interventions for Diabetes (Second Edition), 2019
  7. “The French chemist Lebreton (1828) was first to isolate hesperidin from the white inner layers of citrus peels.” Ganesh Chandra Jagetia, T Lalrinpuii Hesperidin, A Citrus Bioflavonoid Attnuates Iron Induced Biochemical Oxidative Stress in Mouse Liver.  Biomed J Sci & Tech Res August 17, 2018  https://biomedres.us/pdfs/BJSTR.MS.ID.001602.pdf 
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Citrus & Fig Marmalade Jam

Figs are also rich in quercetin (1) and pomegranate peel also contains significant amounts of the phytonutrient, (2). Quercetin can act as a zinc ionophore when zinc is present and carry the zinc into infected or cancerous cells where the zinc disrupts replication, see the last post, and Treatments vs ‘a cure’.

Orange Marmalade is a sweet jam made from citrus juice and peel. I made a modified low sugar version using the orange zest part of the orange peel that I had been removing when eating an orange with the white pith left on (see last post – it acts as a decongestant fairly quickly when eaten in that large of an amount (the whole orange with the white pith layer left on).

*This was an initial attempt and turned out too thick – just skip the jam part of the recipe if you want to simply make a fruit sauce preserve. Freeze the amount that you won’t be able to use fresh within a week or two as low sugar fruit sauces or jam are more likely to spoil – the large amount of sugar makes jams and jellies less likely to spoil. See: How does sugar act as a preservative? (sciencefocus.com) However if the goal is a way to preserve citrus peel for antiviral benefits than low sugar is going to be more supportive of immune function than a full sugar product.

— the point is not a recipe – the point is demonstrating a way to save time and preserve a large batch of outer citrus peel at once so small amounts can be used throughout the day and keep congestion cleared. Fruit preserves can be a mix as the jam package suggests and the basic ratios and which fruits might be more similar in acidity are grouped together on the instruction sheet pectin package.

*simpler way to get bioflavonoids in the diet of many people at once -add powdered citrus bioflavonoids citrus bioflavonoid powder to applesauce or yogurt or a smoothie type beverage or a breakfast porridge or soup. It is available in varied concentration. The preserved citrus jam could be used in a similar way but might be stronger in flavor than a concentrated powder.

I also had some fresh pomegranate peel on hand which I had peeled the outer more tannin rich layer from, (4), and an eight ounce package of dried figs and one pear for sweetness and to reduce the acidity somewhat.

Stevia is an herbal alternative sweetener which also has health benefits, including activation of the p53 protein, (3, also discussed in the last post), and I used a low sugar pectin mix that uses calcium to aid in gelling, Pomona’s Universal Pectin. It includes basic recipes that you can modify depending on your available fruit and sugar preferences. So without going into the specific jam details, here is a list of ingredients that I used, roughly estimating it as a double batch, however it thickened readily and I could have used pectin and calcium for one batch. (pomonapectin.com)

The cardamom powder and pomegranate peel cause the darker color, Citrus peel and fig would likely look more like a traditional orange marmalade.

Citrus Fig Savory Marmalade: Ingredient list (trial 1)

  • 2 1/2 cups minced orange peel
  • 1 1/2 cups minced inner pomegranate peel
  • 1 cup pear, peeled and minced
  • 1 1/2 cups figs, stem removed and minced, (8 ounce package dried)
  • 4 cups water
  • 1 tablespoon cardamom, powdered spice
  • 1 cup brown sugar – added to the stewing fruit, simmer gently to preserve phytonutrients, approximately 20 minutes to soften the citrus peel.
  • 6 tablespoons lime or lemon juice, bottled – for a double batch following the Pomona’s directions
  • 2 tablespoons of the calcium water solution – for a double batch
  • 1 cup Stevia sugar substitute with 1/2 cup = 1 cup sugar – measure into a separate bowl and mix in the pectin powder – to add to the fruit at the end, stir in thoroughly and let simmer for 1-2 additional minutes
  • 3 tablespoons of the Pomona’s pectin, (pomonapectin.com)

The jam cooled to a firm consistency, I could have used a single batch of lime juice, calcium water, and pectin. It made six cups which I froze most of and will keep the rest in the refrigerator as low sugar jams are more likely to mold/spoil than full sugar jam – the large amount of sugar acts as a preservative as it is too concentrated for bacteria to grow in, though mold may still occur. See: How does sugar act as a preservative? (sciencefocus.com)

The jam is mildly sweet and slightly spicy with the cardamom which also may have some antiviral and anticancer benefits by helping activate the p53 protein, which is involved in apoptosis – the killing and safe removal of infected or cancerous cells by our white blood cells. (6)

In addition to using a spoonful on toast, it is good added to a breakfast hot cereal or yogurt and would be easy to add to a cookie recipe if fresh orange peel isn’t available, see previous post: Dark Chocolate Orange Peel Cookies – Recipe.

Health can taste delicious. The taste buds will become more sensitive to the natural sweetness in foods after eating a lower sugar diet for a while.

The following is a series of jam/jelly recipes using citrus and pomegranate peel (fresh and/or dried/powdered). Both citrus and pomegranate peel have anti-inflammatory and other health benefits including antiviral properties.

The simplest way to prepare citrus peel for later use would be to mince the washed peel (collected over a few days in the refrigerator), and simmer it with water and a little brown sugar and possibly a spoonful of coconut oil or butter to help draw out fat soluble phytonutrients.

In a sauce pan bring the orange peel, 1 cup of water, 2 tablespoons of coconut oil & 1 tablespoon of stevia to a boil and remove from heat. (From Dark Chocolate Citrus peel Cookies recipe)

Citrus Plum: Ingredient list (trials 3 & 3.2)

  • 1 1/2-2 cups minced orange peel
  • 1 1/2 cups minced inner pomegranate peel and/or 6 tablespoons powdered dehydrated pomegranate, inner peel
  • 2 cups plums, minced
  • 1 cup prunes, minced,
  • 3 cups water – if more or less fresh fruit is available then adjust the water up/down to make up the difference, leaving a cup to simmer the citrus peel for a few minutes initially with the brown sugar, before adding the fresh plums and other ingredients.
  • 1-2 teaspoon cardamom, powdered spice
  • 1 cup brown sugar – added to the stewing fruit, simmer gently to preserve phytonutrients, approximately 20 minutes to soften the citrus peel.
  • 6 tablespoons lime/lemon juice, bottled, or 2 Tbs apple cider vinegar
  • 2 tablespoons of the calcium water solution – for a double batch
  • 1 cup Stevia sugar substitute with 1/2 cup = 1 cup sugar – measure into a separate bowl and mix in the pectin powder – to add to the fruit at the end, stir in thoroughly and let simmer for 1-2 additional minutes
  • 2 teaspoons of the Pomona’s pectin, (pomonapectin.com), if the 6 tablespoons of powdered dried pomegranate inner peel is used. The fresh pomegranate peel and citrus peel have pectin type fiber and less additional pectin may be needed to thicken the jam or jelly made with it, however the powdered dried peel is more thickening. Some additional pectin still seems to be needed for a full gel reaction

Additional trial, larger batch, notes – 2 cups citrus peel, 6 Tbs pomegranate peel powder, 2 cups brown sugar, 1 cup Stevia powder, 1-1 ratio equiv to sugar, 4 cups water, 4 cups fresh plums, 1 cup prunes, 1 Tbs cardamom, 1/2 cup lime or lemon juice, 2 Tbs calcium water, 2 teaspoon Pomono’s pectin (mixed with one of the cups of brown sugar).

The fruit jam can be made into a chocolate sauce or thicker ganache that can be used as a cookie or cake filling or frosting, or be made into chocolate truffle candies.

Citrus Chocolate Ganache/Fudge sauce

Simmer one-two cups of the citrus plum jam in a double boiler, – metal bowl that fits in a sauce pan that has a couple inches of simmering hot water – and add one teaspoon of vanilla, (optional), and one tablespoon coconut oil per cup of jam, stir until it is mixed in evenly, and then add 1/4 cup cocoa powder per cup of jam, stir until the powder is all incorporated into the chocolate fudge mixture. It will be lumpy because of the fruit pieces but the chocolate sauce should mix into a chocolate-y smoothness where there isn’t fruit pieces.

Whether the mixture will be a thin or thick sauce or a frosting like ganache texture depends on the ratio of cocoa powder to liquid that you use. Pomegranate juice could be used to thin the ganache if a sauce were needed. Thicker ganache can be rolled into truffle like dessert candies, coated with cocoa powder to prevent stickiness. Store and serve chilled from the refrigerator or freezer.

Chocolate citrus peel truffles (without a solid chocolate coating added).

Pomegranate Jelly, made with powdered pomegranate peel (and violets) – ingredient list

  • 6 tablespoons powdered dehydrated pomegranate, inner peel
  • 4 cups pomegranate juice
  • 1 cup violets, (optional) rinsed and drained gently
  • 1 cup brown sugar – added to the stewing fruit,
  • 2 Tbs apple cider vinegar or lime/lemon/juice (I was making a citrus free batch for people with allergy).
  • 2 tablespoons of the calcium water solution (if using Pomona’s Pectin)-
  • 1 cup Stevia sugar substitute with 1/2 cup = 1 cup sugar – measure into a separate bowl and mix in the pectin powder – to add to the fruit at the end, stir in thoroughly and let simmer for 1-2 additional minutes
  • 2 teaspoons of the Pomona’s pectin, (pomonapectin.com), if the 6 tablespoons of powdered dried pomegranate inner peel is used. The fresh pomegranate peel and citrus peel have pectin type fiber and less additional pectin may be needed to thicken the jam or jelly made with it, however the powdered dried peel is more thickening. Some additional pectin still seems to be needed for a full gel reaction
Pomegranate Jelly, made with powdered pomegranate inner peel, and violets (peppery). It was good served hot over a vegetable salad. Jam and jelly can be used as a tangy extra along with an entree (mint jelly and lamb, cranberry gelatin with turkey, chutney with Indian meals).
Purple violets and white with purple centers. If using edible flowers for cooking or fresh avoid chemically treated lawns or flowerbeds and private property or public lands.
More violets than lawn.

*Why violets? – they contain a fragrance phytonutrients that may help protect against retinal deterioration common with aging, and increase melanin production in the skin, helping protect against skin cancer potentially. How many violets is a serving? They are peppery, I enjoy eating a a few at a time.

Reference List

  1. Brian, 93 Quercetin Rich Foods, 2 October 2018, MyIntakePro.com https://myintakepro.com/blog/quercetin-rich-foods/ via @HiperacusiaCAT
  2. X. Zhao, Z. Yuan, Y. Fang, Y. Yin, and L. Feng, Flavonols and Flavones Changes in Pomegranate (Punica granatum L.) Fruit Peel during Fruit Development. J. Agr. Sci. Tech. (2014) Vol. 16: 1649-1659, http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.1021.8526&rep=rep1&type=pdf
  3. Chen J, Xia Y, Sui X, et al. Steviol, a natural product inhibits proliferation of the gastrointestinal cancer cells intensively. Oncotarget. 2018;9(41):26299–26308. Published 2018 May 29. doi:10.18632/oncotarget.25233 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995179/
  4. J. Depew, G13. Pomegranate – Health Benefits and Preparation, effectivecare.info, https://effectivecare.info/g13-pomegranate
  5. Divya Sehgal, How does sugar act as a preservative?, sciencefocus.com, https://www.sciencefocus.com/science/how-does-sugar-act-as-a-preservative/
  6. Yu‐Jen Jou Chao‐Jung Chen Yu‐Ching Liu, et al., Quantitative phosphoproteomic analysis reveals γ‐bisabolene inducing p53‐mediated apoptosis of human oral squamous cell carcinoma via HDAC2 inhibition and ERK1/2 activation. Proteomics, 15;19, Oct 2015, pp 3296-3309, https://www.ncbi.nlm.nih.gov/pubmed/26194454