Evidence-Based, Integrative Considerations with Respect to Immune Support & COVID-19

Evidence-Based, Integrative Considerations with Respect to Immune Support & COVID-19

CAVEAT: integrative medicine measures have thus far NOT been validated in any human trials with respect to COVID-19, so in no way, shape, or form is this article specifically recommending any natural medicine treatments for COVID-19.

I had the privilege of attending National University of Natural Medicine to become a naturopathic doctor (ND), and one of my favorite professors is the brilliant Dr. Heather Zwickey, PhD, who taught us immunology and currently serves as executive program chair at NUNM and as the principal investigator at the Helfgott Research Institute. As an infectious diseases expert, she did her post-doctoral research at Yale, and one of her life purposes is to prove the efficacy of natural medicine with regard to the immunological response.

Recently, in one of my ND Facebook groups, a colleague shared Dr. Zwickey’s thoughts regarding COVID-19, with her permission, sent to her via an email exchange. Dr. Zwickey’s thoughts were then passionately shared back and forth on Facebook and in multiple groups, and as a result her email has been blowing up.

Last week, Dr. Zwickey was featured on Dr. Tyna’s Moore’s “Pain Free & Strong Radio,” in an episode entitled, “Corona Virus with Dr. Heather Zwickey: The Facts from an Immunologist and Infectious Disease Specialist, and just before that, Dr. Zwickey was on the Natural Medicine Journal podcast, discussing “Important Clarifications Regarding COVID-19 and Natural Medicine.” I highly recommend that you take the time to listen to both of these podcasts.

Here’s what Dr. Zwickey shared with her naturopathic physician colleague, verbatim:

I’m hearing a lot of misinformation floating around, so I thought I’d talk about whether or not to use herbs to prevent COVID19. (Everything is referenced.)

 

Prevention: As NDs, you are all aware of how to prevent upper respiratory infections. You’re going to increase Defensins (vitamin D) so that any virus landing on the skin or in the mouth are killed on contact. (1,2)

 

For upper respiratory herbs, I like the combo of 5.   Astragalus (for lungs) is adaptogenic. It reduces inflammation, but can also drive Th1 if you’re exposed to an infection or have lung cancer. It’s also anti-viral. (3,4)

 

Goldenseal and Oregon grape root are directly toxic to viruses (research on flu) and bacteria (think of killing secondary pneumonia). It’s also adaptogenic. It drives Tregs, but can elicit a Th1 response in the right microenvironment. (5,6,7,8,9,10)

 

Echinacea works best at the beginning of an infection and is adaptogenic. Echinacea induces inflammatory cytokines at the beginning of infection and help with resolution post infection. There’s also a meta-analysis showing that it reduces upper-respiratory infections, especially in those susceptible to them. (11,12)

 

Elderberry is also adaptogenic – increasing cytokines in some situations and decreasing them in others. The reason I include it is that it’s anti-viral. There’s research showing it blocks viral uptake. Again, so much research on this that there’s a meta-analysis. (13)

 

I actually developed a supplement with this combo. It’s called Immune and you can find it here: http://www.zamialife.com – not that anyone needs to buy it. You can combine the herbs yourself. It’s just more expensive to buy 5 bottles of herbs.   If people get an infection and you need additional support, Fungi Perfecti has a product called Comprehensive Immune Support that can further increase a Th1 response. (14,15) (The Guggenheim article is about cancer but goes through many of the Th1 stimulating studies.)

 

Do these therapies increase cytokines? Yes. But NOT to the level of cytokine storm. You have to work hard to trigger a cytokine storm. I have not yet seen a situation where an herb can trigger a cytokine storm. We see cytokine storms with super-antigens like staph enterotoxin A, or TSST-1. And in fact, the scientific literature suggests that herbs (including Echinacea) actually decrease cytokine storms. (12,16)

 

So yes, wash hands, don’t touch your face, and sneeze/cough into your elbow. And if you want to use herbs, use what you already know. There is evidence.

 

  1. Pinheiro da Silva F, Machado MCC. Antimicrobial peptides: clinical relevance and therapeutic implications. Peptides. 2012;36(2):308-314. doi:10.1016/j.peptides.2012.05.014
  2. Beard JA, Bearden A, Striker R. Vitamin D and the anti-viral state. J Clin Virol. 2011;50(3):194-200. doi:10.1016/j.jcv.2010.12.006
  3. Li X, Qu L, Dong Y, et al. A Review of Recent Research Progress on the Astragalus Genus. Molecules. 2014;19(11):18850-18880. doi:10.3390/molecules191118850
  4. Hsieh H-L, Liu S-H, Chen Y-L, Huang C-Y, Wu S-J. Astragaloside IV suppresses inflammatory response via suppression of NF-κB, and MAPK signalling in human bronchial epithelial cells. Arch Physiol Biochem. February 2020:1-10. doi:10.1080/13813455.2020.1727525
  5. Yan Y-Q, Fu Y-J, Wu S, et al. Anti-influenza activity of berberine improves prognosis by reducing viral replication in mice. Phytother Res. 2018;32(12):2560-2567. doi:10.1002/ptr.6196
  6. Kim TS, Kang BY, Cho D, Kim SH. Induction of interleukin-12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1 response. Immunology. 2003;109(3):407-414. doi:10.1046/j.1365-2567.2003.01673.x
  7. Cecil CE, Davis JM, Cech NB, Laster SM. Inhibition of H1N1 influenza A virus growth and induction of inflammatory mediators by the isoquinoline alkaloid berberine and extracts of goldenseal (Hydrastis canadensis). Int Immunopharmacol. 2011;11(11):1706-1714. doi:10.1016/j.intimp.2011.06.002
  8. Javadi B, Sahebkar A. Natural products with anti-inflammatory and immunomodulatory activities against autoimmune myocarditis. Pharmacol Res. 2017;124:34-42. doi:10.1016/j.phrs.2017.07.022
  9. Jamshaid F, Dai J, Yang LX. New Development of Novel Berberine Derivatives against Bacteria. Mini Rev Med Chem. January 2020. doi:10.2174/1389557520666200103115124
  10. Qin X, Guo BT, Wan B, et al. Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine. J Immunol Baltim Md 1950. 2010;185(3):1855-1863. doi:10.4049/jimmunol.0903853
  11. Schapowal A, Klein P, Johnston SL. Echinacea reduces the risk of recurrent respiratory tract infections and complications: a meta-analysis of randomized controlled trials. Adv Ther. 2015;32(3):187-200. doi:10.1007/s12325-015-0194-4
  12. Vimalanathan S, Schoop R, Suter A, Hudson J. Prevention of influenza virus induced bacterial superinfection by standardized Echinacea purpurea, via regulation of surface receptor expression in human bronchial epithelial cells. Virus Res. 2017;233:51-59. doi:10.1016/j.virusres.2017.03.006
  13. Hawkins J, Baker C, Cherry L, Dunne E. Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials. Complement Ther Med. 2019;42:361-365. doi:10.1016/j.ctim.2018.12.004
  14. Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. – PubMed – NCBI. https://www-ncbi-nlm-nih-gov.liboff.ohsu.edu/pubmed/26770080. Accessed March 2, 2020.
  15. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum. – PubMed – NCBI. https://www-ncbi-nlm-nih-gov.liboff.ohsu.edu/pubmed/10624872. Accessed March 2, 2020.
  16. The cytokine storm of severe influenza and development of immunomodulatory therapy. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711683/. Accessed March 2, 2020.

Here are some key take-aways and reminders:

  1. At this point (spring, 2020), there are no human trials testing natural medicines against COVID-19, nor are there any registered therapeutics approved by the FDA. (1)
  2. Viruses aren’t actually alive without the use of your cells. (2)
  3. The way that COVID-19 enters the type two pneumocyte is through its S spike protein, which binds to ACE2 receptors. (3) This differentiates it from the average flu, which binds to sialic acid receptors. (4) ACE2 is expressed, for example, in vascular endothelial cells and renal tubular epithelium, and even resides in the gastrointestinal tract and the central nervous system (CNS). (5)
  4. COVID-19 has a furin cleavage site, which allows it to gain entry easily even if a person’s pneumocytes don’t have a lot of ACE2 receptors. (6) By the way, ACE2 inhibitors appear to upregulate ACE2 receptors, though this has not been proven yet.
  5. There are three main reasons the flu is particularly problematic in the winter but this does not seem to matter with COVID-19:
    • Diminished vitamin D exposure and production in the winter (7)
    • Humans are often inside in the winter with recirculated air which increases viral spread
    • Respiratory droplets in the air last longer in cold weather (8)
  6. In the average immune response to a virus, you want a strong Th1 response, which stimulates CD8 and NK cells to kill any virally infected cells. (9,10) Then, you want your immune system to calm down, by stimulating T regulatory cells (T regs). Not having active T regs can be a problem. Hence, you want to have a healthy gut, as an optimized microbiome plays a role in the regulation of T regs early in disease. (11)
  7. Once COVID-19 enters the cell, it stimulates an inflammasome (NLRP3, in particular, with respect to COVID-19), which is the collection of proteins, receptors and mediators involved in inflammation, causing uncontrolled inflammation. (12)
  8. One reason COVID-19 is so deadly is that it causes bilateral pneumonia.
  9. Another reason COVID-19 is so deadly is that people are getting pneumonia in their lower lobes, where fluids pools and then the subsequent pulmonary edema is spiking mortality. (13)
  10. COVID-19 may impact surfactant levels in the lungs, but to what degree this is unknown. Surfactant is responsible for keeping the alveoli open as well as protecting us from secondary infections.
  11. The particular protein made in the cytokine storms that can be induced by COVID-19 is called interleukin-1 beta (IL-1 beta), which drives fever and can mediate fatigue. Coronavirus has two virulence factors, which make it especially deadly, and can lead to a cytokine storm. One of these virulence proteins can trigger the overproduction of interferon-1 beta (IF-1 beta), by basically not allowing the body to turn off the production of IL-1 beta. (14,15)
  12. Three cytokines get activated together, typically, in inflammation, in general: IL-1 beta, IL-6, and TNF-alpha. IL-1, when high, can turn on IL-6, and also it can turn on TNF-alpha. IL-6 is a very strong cytokine, and it is associated with the induction of anxiety, as well as catastrophizing. (16)
  13. According to Dr. Zwickey, some herbs known to lower IL-6 are lemon balm, passionflower, ashwhaghanda, as well as feverfew (17) I was unable to locate studies on lemon balm and passionflower with particular regard to lowering IL-6, but there is limited evidence that rosemarinic acid, which exists in lemon balm, can lower IL-6.
  14. Ibuprofen is problematic because it blocks COX-2 which is in the same pathway as the renin-angiotensin-aldosterone system, which the virus also targets. Acetaminophen (Tylenol) may decrease intracellular glutathione levels in the type II pneumocytes, which are the exact cells targeted by COVID-19. (18)
  15. Hydrotherapy, when increasing core body temperature, motivates the mobilization of immune support to other organs in the body. (19)
  16. The Th1 response responds to viruses and bacteria. But, in asthma, there is a Th2 response going on in the lung, which could potentially “hypothetically” keep the Th1 response under control. Pregnancy also drives a strong Th2 response, which could balance out a Th1 response from the virus. (20)
  17. Melatonin can shut down the inflammasome (NLRP3). (21)
  18. The envelope on the virus makes it easier to kill, because soap and water can destroy it. 70% isopropyl alcocol is better than 100%. It dries out the lipid in the membrane of the virus.
  19. COVID-19 is an RNA virus, like HIV, not a DNA virus, and hence the RNA in the virus itself is more difficult to kill despite the fact it’s lipid membranes are easier to disrupt.
  20. Ascorbic acid or Vitamin C has a ton of literature behind it with regard to respiratory infections and it may be particularly helpful when a person is infected. (22,23)
  21. There are a number of antiviral herbs that are known to be effective, but we don’t yet know if they work particularly on COVID-19.
  22. Vitamins A and D, for example, can support the immune system, and Vitamin C can reduce the specific inflammasome associated with this disease (NLRP3). Melatonin and ascorbic acid both reduce NLRP3. Melatonin levels are inversely correlated with risk, as they can decrease NF-kappa B. (Integrative Considerations during the COVID 3.18.20)

Listen to “EP 86: Corona Virus with Dr. Heather Zwickey: The Facts from an Immunologist and Infectious Disease Specialist” on Spreaker. Resources:

  1. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, Evaluation and Treatment Coronavirus (COVID-19). In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
  2. Koonin EV, Starokadomskyy P. Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question. Stud Hist Philos Biol Biomed Sci. 2016;59:125–134. doi:10.1016/j.shpsc.2016.02.016
  3. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. doi:10.1126/science.abb2507
  4. Kimble B, Nieto GR, Perez DR. Characterization of influenza virus sialic acid receptors in minor poultry species. Virol J. 2010;7:365. Published 2010 Dec 9. doi:10.1186/1743-422X-7-365
  5. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–637. doi:10.1002/path.1570
  6. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res. 2020;176:104742. doi:10.1016/j.antiviral.2020.104742
  7. Saraff V, Shaw N. Sunshine and vitamin D. Arch Dis Child. 2016;101(2):190–192. doi:10.1136/archdischild-2014-307214
  8. Lowen AC, Steel J. Roles of humidity and temperature in shaping influenza seasonality. J Virol. 2014;88(14):7692–7695. doi:10.1128/JVI.03544-13
  9. Cook KD, Waggoner SN, Whitmire JK. NK cells and their ability to modulate T cells during virus infections. Crit Rev Immunol. 2014;34(5):359–388. doi:10.1615/critrevimmunol.2014010604
  10. Pallmer K, Oxenius A. Recognition and Regulation of T Cells by NK Cells. Front Immunol. 2016;7:251. Published 2016 Jun 24. doi:10.3389/fimmu.2016.00251
  11. Pandiyan P, Bhaskaran N, Zou M, Schneider E, Jayaraman S, Huehn J. Microbiome Dependent Regulation of Tregs and Th17 Cells in Mucosa. Front Immunol. 2019;10:426. Published 2019 Mar 8. doi:10.3389/fimmu.2019.00426
  12. Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies [published online ahead of print, 2020 Mar 14]. J Biol Regul Homeost Agents. 2020;34(2):1. doi:10.23812/CONTI-E.
  13. Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer [published online ahead of print, 2020 Feb 28]. J Thorac Oncol. 2020;S1556-0864(20)30132-5. doi:10.1016/j.jtho.2020.02.010
  14. Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies [published online ahead of print, 2020 Mar 14]. J Biol Regul Homeost Agents. 2020;34(2):1. doi:10.23812/CONTI-E.
  15. Roerink ME, van der Schaaf ME, Dinarello CA, Knoop H, van der Meer JW. Interleukin-1 as a mediator of fatigue in disease: a narrative review. J Neuroinflammation. 2017;14(1):16. Published 2017 Jan 21. doi:10.1186/s12974-017-0796-7
  16. Lazaridou A, Martel MO, Cahalan CM, et al. The impact of anxiety and catastrophizing on interleukin-6 responses to acute painful stress. J Pain Res. 2018;11:637–647. Published 2018 Mar 28. doi:10.2147/JPR.S147735
  17. Pareek A, Suthar M, Rathore GS, Bansal V. Feverfew (Tanacetum parthenium L.): A systematic review. Pharmacogn Rev. 2011;5(9):103–110. doi:10.4103/0973-7847.79105
  18. Dimova S, Hoet PH, Dinsdale D, Nemery B. Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro. Int J Biochem Cell Biol. 2005;37(8):1727–1737. doi:10.1016/j.biocel.2005.03.005
  19. Mooventhan A, Nivethitha L. Scientific evidence-based effects of hydrotherapy on various systems of the body. N Am J Med Sci. 2014;6(5):199–209. doi:10.4103/1947-2714.132935
  20. Romagnani S. Th1/Th2 cells. Inflamm Bowel Dis. 1999;5(4):285–294. doi:10.1097/00054725-199911000-00009
  21. Favero G, Franceschetti L, Bonomini F, Rodella LF, Rezzani R. Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation. Int J Endocrinol. 2017;2017:1835195. doi:10.1155/2017/1835195
  22. Hemilä H, Douglas RM. Vitamin C and acute respiratory infections. Int J Tuberc Lung Dis. 1999;3(9):756–761.
  23. Vorilhon P, Arpajou B, Vaillant Roussel H, Merlin É, Pereira B, Cabaillot A. Efficacy of vitamin C for the prevention and treatment of upper respiratory tract infection. A meta-analysis in children. Eur J Clin Pharmacol. 2019;75(3):303–311. doi:10.1007/s00228-018-2601-7

 

COVID-19 and Some Evidence-Based Natural Medicine for Viral Respiratory Infections

COVID-19 and Some Evidence-Based Natural Medicine for Viral Respiratory Infections

This article takes a quick moment to review COVID-19, and some potential evidenced-based treatments to prevent or treat viral respiratory infections. However, just to be clear, there are no registered evidence-based treatments yet specifically for COVID-19.

The First Outbreak of COVID-19 and CT Findings

The first outbreak of COVID-19 (which stands for Coronavirus Disease 2019) occurred in December 2019 in Wuhan, Hubei Providence, China. Most infected patients were diagnosed with pneumonia and characteristic CT scans, therefore, CT findings are recommended as major evidence to detect early infection and for disease assessment. (1)Corona Virus COVID-19 evidence natural medicine treatment

Clinical Presentation of COVID-19

Clinical manifestations are nonspecific: runny nose, sore throat, cough, fever, and in severe cases, difficulty breathing. (2)

Transmission of COVID-19

Person-to-person transmission is thought mainly to occur much like that of influenza, that is, via respiratory droplets.

Typical CT Findings

Typical CT findings include ground-glass opacities (GGOs) which are peripherally distributed, with patchy consolidations. And posterior or lower lobe lung involvement is more common. If these GGOs are present in greater numbers or higher density, then it is indicative of disease progression. (3) The preferred type of CT is thin-slice, which is a slice thickness of 0.625 to 1.25 mm with a higher resolution, as opposed to the standard 5 mm CT imaging of the mediastinum and gross lungs. (4)

COVID-19 Viral Genome

Covid-19 virus infection natural medicineInterestingly, the viral genome of the COVID-19 shares 88% sequence identity with two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses.

Vitamin C and Viral Respiratory Infections

Because COVID-19 is a viral infection with proclivity to infect the respiratory tract, it stands to reason that vitamin C may help to prevent it.

A 1999 prospective, controlled study, from The Journal of Manipulative and Physiological Therapeutics, found that high dose vitamin C decreased the reported cold and flu symptoms of virus-induced respiratory infections by 85%. The treatment group received 1000 mg of vitamin C hourly, for the first six hours, and then three times daily thereafter. (5)

A 2017 review article in the journal, Nutrients, concluded that vitamin C plays a role in preventing and shorting diverse infections. In fact, five controlled trials found that vitamin C had significant benefit in treating pneumonia. (6)

Chinese Medicine and COVID-19

A 2020 guideline, in line with WHO standards, from the journal, Military Medical Research, details some Chinese medicine herbal protocols that might be used specifically for COVID-19 induced pneumonia: (7)

  • Moxa
  • Clove, fineleaf schizonepeta herb, Perilla frutescens, atractylodes lancea, cinnamon, biond magnolia flower, asarum sieboldii, and Elettaria cardamomum
  • Prescription of Chinese herbs for feet bath: vulgaris, carthamus, dried ginger
  • Chinese herbs for prophylaxis: Astragalus mongholicus, roasted rhizoma atractylodis macrocephalae, saposhnikovia divaricata, Cyrtomium fortunei, honeysuckle, dried tangerine or orange peel, eupatorium, and licorice

A 2020 Journal of Integrative Medicine in vitro study found 26 Chinese herbs, including licorice and gingko, used to treat viral respiratory infection with anti-COVID-19 properties. (8)

Vitamin D and Immunomodulation During Respiratory Virus Infection

Multiple studies have found that vitamin D has immunomodulatory properties that can improve the response to respiratory viruses. (9) A 2014 randomized controlled trial investigated vitamin D related respiratory disease in preschoolers, making the case that low wintertime vitamin D levels correlate with viral respiratory infections and asthma exacerbations in children. (10) Hence, bolstering up on vitamin D could lower the chances of a respiratory infection, such as COVID-19.

Selenium and Viral Infection

It’s a well known fact that selenium deficiency weakens our defense versus infectious disease agents by reducing selenoprotein expression. (11) As a key part of antioxidant defense, selenium helps to control oxidative stress, which can occur during viral respiratory infections. (12)

Zinc and Lower Respiratory Tract Infections

Zinc is a vital nutrient key to the growth and function of all cells in the human body.  According to the WHO, the fifth leading cause of mortality and morbidity in developing nations is zinc deficiency, estimated to affect one-third of the world population and accounting for 16% of lower respiratory tract infections. (13)

Summary

In summary, evidence points to vitamins C and D, zinc and selenium supplementation, and the use of Chinese herbal medicine, as possible evidence-based options for COVID-19 prevention and treatment. But it is recommended that these options are implemented only under the guidance of a board certified naturopathic doctor, or other integrative medicine physician. Also, just to reiterate, this article is not recommending treatments specifically for COVID-19, as there are as of yet no officially registered treatments back by evidence based studies.

Resources

  1. Zu ZY, Jiang MD, Xu PP, et al. Coronavirus Disease 2019 (COVID-19): A Perspective from ChinaRadiology. 2020:200490. doi:10.1148/radiol.2020200490.
  2. Raoult D, Zumla A, Locatelli F, Ippolito G, Kroemer G. Coronavirus infections: Epidemiological, clinical and immunological features and hypothesesCell Stress. 2020;4(4):66-75. doi:10.15698/cst2020.04.216.
  3. She J, Jiang J, Ye L, Hu L, Bai C, Song Y. 2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategiesClinical and Translational Medicine. 2020;9(1). doi:10.1186/s40169-020-00271-z.
  4. Zu ZY, Jiang MD, Xu PP, et al. Coronavirus Disease 2019 (COVID-19): A Perspective from ChinaRadiology. 2020:200490. doi:10.1148/radiol.2020200490.
  5. Gorton H, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infectionsJournal of Manipulative and Physiological Therapeutics. 1999;22(8):530-533. doi:10.1016/s0161-4754(99)70005-9.
  6. Hemilä H. Vitamin C and Infections. Nutrients. 2017;9(4):339. doi:10.3390/nu9040339.
  7. Jin Y-H, Cai L, Cheng Z-S, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Military Medical Research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003341/. Published February 6, 2020. 
  8. Zhang D-hai, Wu K-lun, Zhang X, Deng S-qiong, Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. Journal of Integrative Medicine. Published February 20, 2020. 
  9. Greiller CL, Martineau AR. Modulation of the immune response to respiratory viruses by vitamin D. Nutrients. Published May 29, 2015. 
  10. Maguire JL, Birken CS, Loeb MB, et al. DO IT Trial: vitamin D Outcomes and Interventions in Toddlers – a TARGet Kids! randomized controlled trial. BMC pediatrics. Published February 8, 2014.
  11. Guillin OM, Vindry C, Ohlmann T, Chavatte L. Selenium, Selenoproteins and Viral Infection. Nutrients. Published September 4, 2019. 
  12. Steinbrenner H, Al-Quraishy S, Dkhil MA, Wunderlich F, Sies H. Dietary selenium in adjuvant therapy of viral and bacterial infections. Advances in nutrition (Bethesda, Md.). Published January 15, 2015. .
  13. Gammoh NZ, Rink L. Zinc in Infection and Inflammation. Nutrients. Published June 17, 2017.
     
Three Foods for Natural Heavy Metal Chelation

Three Foods for Natural Heavy Metal Chelation

We are exposed to potential toxins, such as heavy metals, on a daily basis, no matter what we do. So why not also cook with foods that naturally help remove heavy metals from the body, a process known as chelation? This article briefly discusses heavy metal toxicity in seafood as well as three foods for natural heavy metal chelation, then combines it altogether in a recipe!

Heavy metal toxicity and fish
Seafood, and most prominently, fish, is not only an important source of protein, but also rich in essential minerals, vitamins, and unsaturated/essential fatty acids (EFAs). Yet it is just this nutrient-dense lipid content which can also pose the greatest harm.

Fish which contain the highest amounts of fat are potentially the most healthy (e.g., salmon, mackerel, herring, trout, sardines, and albacore tuna contain the highest amounts of EFAs). (1) But many of these same fish also can contain the highest heavy metal concentrations, specifically because heavy metals have an affinity for being sequestered in fat. Currently, some of the highest in methylmercury are king mackerel, marlin, orange roughy, shark, swordfish, tilefish, ahi tuna, and bigeye tuna. (2) In fact, it is recommended that women who are pregnant or trying to conceive avoid these types of fish. (3) Although the American Heart Association recommends eating fish at least twice a week to achieve recommended daily omega-3 fatty acid status, this can backfire if we aren’t careful about where we source our seafood, as well as which types we consume. (4)

The most famous heavy metal is mercury, which in its most harmful form is methylated. Methylation is a vital metabolic process which means that some carbon and hydrogen is attached to the mercury atom, making it more bioavailable to living organisms, such as fish swimming in the sea. Over time, then, this toxic methylmercury can concentrate in the fatty tissues of seafood via the ingestion of sediment, seawater, and oceanic food-chain organisms high in methylmercury. (5,6) One study found that fish muscles contained the least concentrations of heavy metals, while liver contained the highest amounts of copper, zinc, and iron, and gills contained the highest amounts of lead and manganese. (7)

Hence, it’s critical to eat sustainably harvested seafood, such as those provided by Vital Source Seafood, an inspiring company that only supplies sustainability certified fish and seafood (Marine Stewardship Council (MSC), State of Alaska, or Monterey Bay Aquarium SeafoodWatch program certified), such as wild-caught Alaskan salmon and northwest Pacific seafood, for a fair price and delivered flash-frozen to your doorstep.

Three foods that help your body remove heavy metals

1. Cilantro
The most famous herb for chelating heavy metals from the body is cilantro/coriander, or Coriandrum sativum, which has been specifically shown to help remove mercury, lead, and aluminum from the tissues. (8) Not only that, but it’s an immune-boosting herb.

2. Garlic and onions: Garlic, onion and shallot are sulfur rich foods which particularly help remove lead from the body. (9)

3. Brazil nuts: Brazil nuts contain high a

mounts of selenium, which has been shown to reduce metal toxicity. Selenium is critical for making the body’s most important antioxidant, glutathione, which protects from oxidative damage via an enzyme called gl

utathione peroxidase. (10) Selenium can actually actively bind methylmercury in the body, thereby rendering it less bioavailable and therefore less harmful. (11)

So why not cook sustainably harvested seafood with naturally chelating herbs, and feed two birds with one seed?! 🙂 I decided to sear a filet of wild-caught Alaskan Coho salmon with some of the ingredients mentioned above, and it came out wonderfully.

Recipe: Seared Coho Salmon with Cilantro and Brazil Nuts
¾ lb filet of wild-caught Alaskan Coho salmon
7 Brazil nuts, finely chopped
Cilantro, minced
1 shallot, minced
Coconut oil
Half a lemon
Freshly cracked pepper
Pinch of Maldon sea salt

Instructions
Heat cast-iron skillet on medium, adding 1 tbsp. of coconut oil in cast-iron skillet. Lightly sauté shallot for 3-4 minutes, then remove from pan. Heat pan until very hot, then add ½ tbsp. more of coconut oil. Sear salmon fillet on both sides for 2-3 minutes, until underside is lightly browned, ending with skin side down. Plate salmon, cover in sautéed shallot, sprinkle with Brazil nuts and cilantro. Add seasoning. Squeeze lemon over. Voila! 🙂

Resources:

  1. Fish and Omega-3 Fatty Acids. How Cigarettes Damage Your Body. http://www.heart.org/HEARTORG/HealthyLiving/HealthyEating/HealthyDietGoals/Fish-and-Omega-3-Fatty-Acids_UCM_303248_Article.jsp#.W1c9fthKg_U. Accessed July 24, 2018.
  2. Menon S. Mercury Guide. NRDC. https://www.nrdc.org/stories/mercury-guide. Published January 9, 2018. Accessed July 24, 2018.
  3. What You Need to Know about Mercury in Fish and Shellfish. WebMD. https://www.webmd.com/diet/mercury-in-fish#1. Accessed July 24, 2018.
  4. Kohlstadt I. Fish, mercury, and personalized medicine. Townsend Letter: The Examiner of Alternative Medicine. June 2007.
  5. How Does Mercury Get Into Fish? Scientific American. https://www.scientificamerican.com/article/how-does-mercury-get-into/. Accessed July 24, 2018.
  6. El-Moselhy KM, Othman A, El-Azem HA, El-Metwally M. Bioaccumulation of heavy metals in some tissues of fish in the Red Sea, EgyptEgyptian Journal of Basic and Applied Sciences. 2014;1(2):97-105. doi:10.1016/j.ejbas.2014.06.001.
  7. The Health Benefits of Cilantro. Dr. Group’s Healthy Living Articles. https://www.globalhealingcenter.com/natural-health/health-benefits-of-cilantro/. Published February 16, 2017. Accessed July 24, 2018.
  8. Negi, R., Satpathy, G., Tyagi, Y. K., & Gupta, R. K. (2012). Biosorption of heavy metals by utilising onion and garlic wastesInternational Journal of Environment and Pollution, 49(3/4), 179. doi:10.1504/ijep.2012.050898.
  9. Stockler-Pinto, M., Mafra, D., Farage, N., Boaventura, G., & Cozzolino, S. (2010). Effect of Brazil nut supplementation on the blood levels of selenium and glutathione peroxidase in hemodialysis patientsNutrition, 26(11-12), 1065-1069. doi:10.1016/j.nut.2009.08.006
  10. Ralston, N. V., & Raymond, L. J. (2010). Dietary selenium’s protective effects against methylmercury toxicityToxicology, 278(1), 112-123. doi:10.1016/j.tox.2010.06.004.

Zinc and The Metabolism of Alcohol

Zinc and The Metabolism of Alcohol

It’s well known that vitamin C, B complex vitamins, glutathione, and N-acetyl Cysteine (NAC) play a large role in alcohol metabolism, but zinc is rarely mentioned. However, zinc is actually a requisite cofactor in the metabolism of alcohol. (1) Zinc has not been studied extensively as a treatment for alcoholism, though alcoholics are usually zinc deficient and suffer from conditions which may benefit from zinc supplementation, such as low sperm counts and rosacea.

The body’s main enzyme for alcohol metabolism, alcohol dehydrogenase (ADH), actually contains zinc at its catalytic site. Zinc is now considered a novel therapeutic approach to alcohol liver disease (ALD). (2) ADH exists in decreased amounts in women, which contributes to less “first-pass metabolism,” and may in part explain why women are more susceptible to alcohol intoxication.

Zinc, an essential trace element, goes hand-in-hand with protein intake; in other words, poor protein intake correlates with poor zinc status. (3) Some symptoms of zinc deficiency include poor growth, infertility, skin disease, and impaired immune function.

The Epidemic of Chronic Alcoholism

Did you know that 50% of the world’s population drinks alcohol, and 5% to 10% have chronic alcoholism? In fact, over 3% of all deaths worldwide are due to alcohol. (4)

Ethanol

Ethanol is the natural product of sugar fermentation by yeasts. According to the USDA, one standard drink contains about half an ounce of ethanol. This is the equivalent of a light 12 oz beer, a 5 oz pour of wine, or 1.5 oz of an 80-proof distilled liquor. Ethanol is found in many household products, such as mouthwash, perfume, and cooking extracts.

The Metabolism of Alcohol

Alcohol is biotransformed to acetaldehyde by three main enzyme systems in the liver. (5)

  1. The first and main system lies in the cytosol of hepatocytes, where alcohol dehydrogenase (ADH) transforms ethanol to acetaldehyde. As mentioned, the ADHs are actually are actually a class of zinc enzymes!
  2. The second involves CYPs which oxidize ethanol in the microsomes of cells, known as the microsomal ethanol-oxidizing system (MEOS). Microsomes are basically fragments of hepatocellular endoplasmic reticulum.
  3. The third involves catalase in the peroxisomes, which acts upon hydrogen peroxide as substrate, metabolizing no more than 5% of all liver ethanol.

Ethanol crosses cell membranes, about 80% of its absorption occurring in the duodenum and 20% in the stomach itself. Peak blood ethanol levels are reached approximately 30 to 90 minutes after a meal. (6) Once ethanol reaches the blood, its taken up mainly by hepatocytes replete with ample quantities of ADH. ADH, however, is also available in the mucosa of the gut.

Zinc Status as a Biomarker of Chronic Alcoholism

Studies looking at evidence of the association of zinc metabolism and alcohol-associated disorders, such as those involving the liver, brain, lung, gut, and even fetal alcohol syndrome, suggest that zinc status should be used as a biomarker for alcohol abuse. (7,8) While it has been confirmed that alcohol induces autophagy in mice, a recent animal study found that adequate zinc intake is required for autophagy. (9)

Conclusion

Given that the body’s main enzyme system responsible for metabolizing alcohol in the liver is zinc-based, there appears to be enough evidence to warrant further studies in zinc supplementation for alcohol-induced diseases.

Resources

  1. Alcohol dehydrogenase. Egyptian Journal of Medical Human Genetics.
  2. Kharbanda K, Ronis M, Shearn C, et al. Role of Nutrition in Alcoholic Liver Disease: Summary of the Symposium at the ESBRA 2017 CongressBiomolecules. 2018;8(2):16. doi:10.3390/biom8020016.
  3. Gibson RS. A Historical Review of Progress in the Assessment of Dietary Zinc Intake as an Indicator of Population Zinc StatusAdvances in Nutrition. 2012;3(6):772-782. doi:10.3945/an.112.002287.
  4. Alcohol. World Health Organization. http://www.who.int/substance_abuse/facts/alcohol/en/. Published May 12, 2014. Accessed July 17, 2018.
  5. Alcohol Metabolism: An Update. National Institute on Alcohol Abuse and Alcoholism. https://pubs.niaaa.nih.gov/publications/aa72/aa72.htm. Accessed July 17, 2018.
  6. Mitchell MC, Teigen EL, Ramchandani VA. Absorption and Peak Blood Alcohol Concentration After Drinking Beer, Wine, or SpiritsAlcoholism: Clinical and Experimental Research. 2014;38(5):1200-1204. doi:10.1111/acer.12355.
  7. McClain CJ, Su LC. Zinc deficiency in the alcoholic: a review. Alcohol Clin Exp Res 1983;7:5-10.
  8. Skalny AV, Skalnaya MG, Grabeklis AR, Skalnaya AA, Tinkov AA. Zinc deficiency as a mediator of toxic effects of alcohol abuseEuropean Journal of Nutrition. 2017. doi:10.1007/s00394-017-1584-y.
  9. Liuzzi JP, Narayanan V, Doan H, Yoo C. Effect of zinc intake on hepatic autophagy during acute alcohol intoxicationBioMetals. 2018;31(2):217-232. doi:10.1007/s10534-018-0077-7.