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Sulforaphane as a Treatment for COVID-19by Jihoon Kim D.C., D.A.C.N.B.(OMNS Apr 4, 2020) Recent research suggests that a compound called 'sulforaphane' may have both a prophylactic and curative benefit against ARDS and SARS-CoV-2. Sulforaphane is found in cruciferous vegetables such as broccoli and kale. It is generated by damage to the plant and is involved in protecting the plant from insect predators. In mammals it activates the Nrf2 anti-inflammatory pathway, is a potent anti-bacterial agent, and has anti-cancer properties. Recent research shows that it can modulate epigenetic pathways in mammalian cells. [1] Anti-viral propertiesSulforaphane has also been shown to have antiviral properties. Studies have shown that sulforaphane reduces viral load in the nose, increases NK cell production, displays antiviral activity against H1N1 Influenza virus, and can suppress replication of Hepatitis C Virus and inhibit HIV infection of macrophages through Nrf2. [2-5] Interestingly, heat shock proteins which are produced upon sulforaphane consumption are also known to have antiviral properties. [6] Inducer of NRF2 anti-oxidant pathwaySulforaphane may be particularly beneficial for the elderly. It is a powerful inducer of Nrf2, which regulates expression of more than 200 cytoprotective genes, including an antiviral pathway that impairs virus reproduction. [7,8] Nrf2 signaling is thought to decrease with age. According to one study, exercise induced Nrf2-signaling has been shown to be impaired in aging. [9] Sulforaphane was also shown to restore the age-related decrease of Th1 immunity in old mice. [10] Sulforaphane treats ARDSAnimal and in vitro studies have shown that sulforaphane can mitigate the inflammatory damage to the lungs in ARDS. In one study, sulforaphane doubled the survivability of rabbits with ARDS. [11,12] Sulforaphane is also a potent inhibitor of NFkB, which is a master inducer of inflammation. [13] In one study, influenza virus-induced markers of inflammation were significantly lower in smokers after consumption of broccoli sprout homogenate. [14] Protection for the lungsSulforaphane has a protective effect on the lungs. In a 12 week study in Qidong, China, consumption of sulforaphane was associated with immediate and sustained increase in urinary excretion of airborne pollutants, benzene 61% and acrolein 23%. [15] In another study, daily 100 æmol sulforaphane for 14 days was shown to improve the broncho-protective response in asthmatics. [16] Cancer, diabetesA plethora of studies have suggested sulforaphane has a mitigating effect on cancer, diabetes, and neurological disorders, all of which are risk factors of COVID-19 fatalities. [1,11,17] Preparing sulforaphaneBroccoli sprouts contain the highest levels of precursors to sulforaphane: glucoraphanin and myrosinase. However, care must be taken because myrosinase is destroyed under heat. Broccoli sprouts must be thoroughly washed to prevent contamination by E. coli and Salmonella. Addition of myrosinase in the form of daikon radish, or mustard seed powder can increase the sulforaphane content. [18] Several supplements containing sulforaphane or its precursors glucoraphanin and myrosinase have been validated by multiple studies; those containing glucoraphanin alone have an average 10% bioavailability. [19,20] The suggested minimal adult dose is 4.4mg, based on the study in Qidong China that determined the level of sulforaphane needed to excrete benzene and acrolein. [15] I am not an expert in the fields of infectious diseases or immunology and I certainly do not want to give people false hope. Currently, there are no clinical studies of sulphoraphane against COVID-19. But since there are no randomized controlled clinical trials of ANY treatment against COVID-19, we are left to utilize therapeutic approaches based on past research. Sulforaphane has been shown to be safe for consumption and is commercially available. I believe it may be an important treatment available to the average citizen in the current viral pandemic. Lastly, I hope this publication draws interest from experts and researchers in COVID-19 for further research and investigation. (Dr. Jihoon Kim is a chiropractor and a diplomate of the American Chiropractic Neurology Board. Upon returning to South Korea, he became an assistant professor at Seoul's Chaum Anti-Aging Center, and director of a facility for children with autism spectrum disorders. Dr. Kim is currently a professor at Organic Culture, also in Seoul.) References:1. Hyun TK. (2020) A recent overview on sulforaphane as a dietary epigenetic modulator. EXCLI J. 19:131-134. https://www.ncbi.nlm.nih.gov/pubmed/32194360. 2. Mller L, Meyer M, Bauer RN et al. (2016) Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study. PLoS One. 11(1):e0147742. https://www.ncbi.nlm.nih.gov/pubmed/26820305. 3. Li Z, Liu Y, Fang Z et al. (2019) Natural Sulforaphane From Broccoli Seeds Against Influenza A Virus Replication in MDCK Cells. Natural Product Communications, June 2019: 1-8. https://journals.sagepub.com/doi/pdf/10.1177/1934578X19858221. 4. Yu JS Chen WC, Tseng CK et al. (2016) Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway. PLoS One. 11(3):e0152236. https://www.ncbi.nlm.nih.gov/pubmed/27023634. 5. Furuya AK, Sharifi HJ, Jellinger RM, et al. (2016) Sulforaphane Inhibits HIV Infection of Macrophages through Nrf2. PLoS Pathog. 12(4):e1005581. https://www.ncbi.nlm.nih.gov/pubmed/27093399. 6. Tsan MF, Gao B. (2009) Heat shock proteins and immune system. J Leukoc Biol. 85:905-910. https://www.ncbi.nlm.nih.gov/pubmed/19276179. 7. Houghton CA (2019) Sulforaphane: Its "Coming of Age" as a Clinically Relevant Nutraceutical in the Prevention and Treatment of Chronic Disease. Oxid Med Cell Longev. 2019:2716870. https://www.ncbi.nlm.nih.gov/pubmed/31737167. 8. Wyler E, Franke V, Menegatti J et al. (2019) Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program. Nat Commun. 10:4878. https://www.ncbi.nlm.nih.gov/pubmed/31653857. 9. Done AJ, Gage MJ, Nieto NC, Traustad¢ttir T. (2016) Exercise-induced Nrf2-signaling is impaired in aging. Free Radic Biol Med. 96:130-8. https://www.ncbi.nlm.nih.gov/pubmed/27109910. 10. Kim HJ, Barajas B, Wang M, Nel AE. (2008) Nrf2 activation by sulforaphane restores the age-related decrease of T(H)1 immunity: role of dendritic cells. J Allergy Clin Immunol. 121:1255-1261.e7. https://www.ncbi.nlm.nih.gov/pubmed/18325578. 11. Patel V, Dial K, Wu J, Gauthier AG. (2020) Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1. Int J Mol Sci. ;21(3). pii:E977. https://www.ncbi.nlm.nih.gov/pubmed/32024151. 12. Sun Z, Niu Z, Wu S, Shan S. (2018) Protective mechanism of sulforaphane in Nrf2 and anti-lung injury in ARDS rabbits. Exp Ther Med. 15:4911-4915. https://www.ncbi.nlm.nih.gov/pubmed/29805514. 13. Heiss E, Herhaus C, Klimo K, Bartsch H, Gerh„user C. (2001) Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem. 276:32008-32015. https://www.ncbi.nlm.nih.gov/pubmed/11410599. 14. Noah TL, Zhang H, Zhou H, Glista-Baker E, et al. (2014) Effect of broccoli sprouts on nasal response to live attenuated influenza virus in smokers: a randomized, double-blind study. PLoS One. 9(6):e98671. https://www.ncbi.nlm.nih.gov/pubmed/24910991. 15. Kensler TW, Ng D, Carmella SG et al, (2012) Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. Carcinogenesis. 33:101-107. https://www.ncbi.nlm.nih.gov/pubmed/22045030. 16. Brown RH, Reynolds C, Brooker A, Talalay P, Fahey JW. (2015) Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways. Respir Res. 16:106. https://www.ncbi.nlm.nih.gov/pubmed/26369337. 17. Sun Y, Zhou S, Guo H, et al. (2020) Protective effects of sulforaphane on type 2 diabetes-induced cardiomyopathy via AMPK-mediated activation of lipid metabolic pathways and NRF2 function. Metabolism. 102:154002. https://www.ncbi.nlm.nih.gov/pubmed/31706979. 18. Fahey JW, Holtzclaw WD, Wehage SL, et al. (2015) Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase. PLoS One. 10(11):e0140963. https://www.ncbi.nlm.nih.gov/pubmed/26524341. 19. Fahey JW, Wade KL, Stephenson KK, et al. (2019) Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration. Nutrients. 11(7). pii: E1489. https://www.ncbi.nlm.nih.gov/pubmed/31261930. 20. Yagishita Y, Fahey JW, Dinkova-Kostova AT, Kensler TW. (2019) Broccoli or Sulforaphane: Is It the Source or Dose That Matters? Molecules. 24(19). pii: E3593. https://www.ncbi.nlm.nih.gov/pubmed/31590459. Nutritional Medicine is Orthomolecular MedicineOrthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org Find a DoctorTo locate an orthomolecular physician near you: http://orthomolecular.org/resources/omns/v06n09.shtml The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource. Editorial Review Board:Ilyès Baghli, M.D. (Algeria)
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