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22 Nutrients to Support Immunity Against SARS-CoV-2

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Disclaimer: This article is intended for informational purposes only. None of the following is intended as medical advice. Please consult your doctor or nutritionist before starting a new diet, in case of food sensitivities, allergies, drug interactions, or other precautions. Please consult with an expert herbalist or mycologist before attempting to consume any foraged foods.

This review of the literature highlights a variety of naturally occurring vitamins, minerals, and polyphenols that may reduce the risk of contracting COVID-19 and/or reduce disease severity. On a biochemical level, nutrients play irreplaceable physiological roles as hormones, antioxidants, enzyme cofactors, and more. Nutrient deficiencies present real risk factors in all-cause morbidity and mortality; as such, nutrition is a critical cornerstone of any preventive lifestyle regimen.

1. Vitamin D3

Vitamin D deficiency is associated with greater susceptibility to and severity of COVID-19[1]. Vitamin D has been shown to decrease the incidence of viral respiratory tract infections and pneumonia and lower viral replication. Sufficient Vitamin D reduces your risk of catching COVID-19 by modulating the angiotensin-converting enzyme 2 (ACE2) receptor that SARS-CoV-2 uses to infiltrate cells. Specifically, it is thought to bind to ACE2 and downregulate its expression. ACE2 expression is high in the lung, heart, ileum, kidney and bladder.

Vitamin D also suppresses cytokine release and pro-inflammatory pathways, including NF-kB, IL-6, and TNF, and promotes neurotrophic factors like nerve growth factor (NGF) that help neurons survive[2].

The majority of your Vitamin D comes from UVB sunlight, not dietary sources. Vitamin D deficiency is more common in winter months. Your best bet is to spend at least 5-30 minutes in the sun every day. The most significant dietary sources are cod liver oil, wild caught salmon, mackerel, dairy products, and eggs, but vitamin D is also found in trace amounts in wild mushrooms.

Vitamin D needs vitamin K2 and magnesium to function most optimally[3]. Vitamin D is also beneficial for individuals with existing conditions fighting COVID-19, such as cardiovascular disease, acute respiratory distress, cancer, and kidney disease[4].

  • Prevention: Maybe, by downregulating ACE2

  • Treatment: Maybe

2. Melatonin

Melatonin is a neurotransmitter and potent antioxidant. It’s immunomodulatory, meaning it can be either pro-inflammatory or anti-inflammatory, with the pro-inflammatory effects associated with antiviral activity.

In terms of anti-inflammatory effects, melatonin inhibits the NLRP3 inflammasome and activates Nrf2. In the respiratory system, melatonin blocks NF-kB, upregulates C-Fos, and downregulates matrix metalloproteases-3 (MMP-3), making it anti-fibrotic and vasodilating in activity. Melatonin indeed protects against lung injury and pulmonary fibrosis in animal models, reducing swelling, pneumonitis, collagen deposition, inflammatory cell infiltration, and vascular and alveolar thickening in the lungs. Melatonin can reduce damage to lung parenchyma and increases SIRT-1 expression, giving it anti-apoptotic effects[5].

Children seem to be less affected by COVID-19, and children also have the highest secretion of melatonin.

Melatonin’s promotion of lung health warrants featuring it on this list, as the majority of melatonin in the body is produced by the pineal gland and is associated with deep, restorative sleep and glymphatic system activity. I’m not saying you should go pop some melatonin, but try to get at least 7 hours of sleep per night and take care of your sleep hygiene. Get dark shades if you need to, and turn off electronic devices after 9pm, which is around the time when pineal melatonin secretion starts. At minimum, turn off electronic devices 2 hours before bed.

  • Protection: Maybe

  • Lessen disease severity: Maybe

3. Oranges

Hesperidin and ascorbic acid (vitamin C) found in oranges fight COVID-19. Specifically, out of 1066 natural substances screened by Wu et. al against COVID-19, hesperidin was the most suitable to bind to the spike protein. Hesperidin was found to disrupt the ACE2-RBD (receptor binding domain) complex and the main SARS-CoV-2 viral protease Mpro; hesperidin had a better interaction with the Mpro enzyme than the reference drug lopinavir in a clinical trial[6].

Vitamin C-rich foods increase white blood cell production, which is key to fighting infection. Vitamin C functions in hormonal regulation, metabolic energy, and increasing collagen, promoting barrier integrity. Vitamin C inhibits NLRP3 inflammasome activation. Clinical trials have found that vitamin C shortens the frequency, duration and severity of the common cold and the incidence of pneumonia[7].

Foods rich in Vitamin C include:

  • Green and red bell peppers

  • Tomatoes

  • Cruciferous vegetables: broccoli, Brussels sprouts, cauliflower, and cabbage

  • Leafy greens: spinach and turnip greens

  • Citrus, papaya, kiwi, pineapples

  • Sweet and white potatoes

  • Winter squash

  • Reduce incidence: Maybe

  • Reduce severity: Maybe

4. Quercetin

Quercetin could prevent COVID-19 infection, specifically by inhibiting the binding of the virus to human cells. Quercetin binds readily to the viral S-protein–human ACE2 receptor interface–ligand-binding complex. These molecules significantly alter human gene expression involved in attachment of the virus to host cells. Quercetin and vitamin C have synergistic antiviral activity. Quercetin was also able to block entry of SARS-CoV-2 into Vero E6 cells in vitro[8, 9].

Rutin, which contains quercetin and the disaccharide rutinose, also bound readily to Mpro (the main, SARS-CoV-2 serine protease, also known as 3CLpro). Rutin is found in figs.

Elderberries. Image via Getty Images

Foods rich in quercetin include elderberries, lettuce, asparagus, onions, green pepper, apples[10], berries, cilantro (coriander), capers, lovage, and dill.

Another paper using in silico data argues that oral quercetin is “unlikely to be effective in clinical trials” because of its low bioavailability during digestion, specifically its biotransformation, absorption, and metabolism. The authors instead suggest researchers focus their efforts on developing and testing nasal or throat sprays for direct administration to treat COVID-19[11].

  • Prevention: Maybe

  • Treatment: Maybe, with optimized delivery

5. Black Cumin and Parsley

Polyphenols display anti-inflammatory, antioxidant, anti-cancer, and antiviral activities. Apigenin, quercetin, amentoflavone, daidzein, puerarin, epigallocatechin, epigallocatechin gallate, and gallocatechin gallate were found to inhibit the proteolytic activity of SARS-CoV-2 3C-like protease, which is vital for viral replication.

Black cumin. Image via Organic Daily Post

Part of the family of polyphenols, flavonoids induce Nrf2 expression, which is associated with antiviral effects. Among the compounds they reviewed, thymoquinone was one of the most powerful Nrf2 activators; it is present in black cumin[12, 13].

Aquilegia coerulea grows in North America. Image via Chiltern Seeds

Apigenin is abundant in parsley, celery, rosemary, oregano, thyme, basil, coriander, chamomile, cloves, lemon balm, artichokes, spinach, peppermint, red wine, and licorice[14]. It is also a bioactive ingredient in Aquilegia oxysepala (columbine)[15].

Amentoflavone is a biflavonoid present in Ginkgo biloba, Chamaecyparis obtuse (Japanese cypress), Taxus chinensis (Chinese yew), Hypericum perforatum (St John’s wort), and Byrsonima intermedia (locustberries)[16].

Gingko biloba. Image via SJG Bloom

Puerarin is most notably found in the root of Pueraria lobata (kudzu plant). Puerarin hydrolyzes into daidzein[17]. Daidzein is found in soybeans and other legumes. Despite some data that daidzein may benefit kidney and lung disease, daidzein possesses estrogenic activity with the capacity to stimulate the growth of human breast cancer cells [18] and desensitize brain tumors to chemotherapy[19].

Overall, thymoquinone, apigenin, and amentoflavone appear the most promising from this study.

  • Prevention: unknown

  • Treatment: maybe; in vivo and clinical trials needed

6. Green Tea and Black Tea

Epigallocatechin-3-gallate (EGCG) from green tea and theaflavins from black tea, specifically theaflavin-3,3′-digallate (TF3), may hold promise against SARS-CoV-2 viral activity. EGCG is a powerful Nrf2 activator.

EGCG in green tea strongly inhibited Mpro of SARS-CoV. The high structural similarity with the 2012 virus suggests potential for treating COVID-19. It even demonstrated stronger molecular docking activity than hesperidin.

TF3 in black tea has exhibited antiviral activity against hepatitis C, HIV-1, and herpes simplex virus. TF3 also inhibits complex formation of the virus with the ACE2 receptor[20].

Taken together, this evidence suggests black tea could prevent one from catching COVID-19, while green tea could improve recovery from the virus.

  • Prevention: maybe—black tea

  • Recovery: maybe—green tea

7. Grapefruit

Naringenin, a flavonoid present in grapefruit, lemons, oranges, bergamot, and tomatoes, also possess hepatoprotective effects.

Naringenin works by inhibiting:

  1. Mpro: A molecular docking analysis study demonstrated that naringenin binds to 3CLpro chains as a ligand and blocks its activity, ultimately blocking viral replication.

  2. SARS-CoV-2 binding to the ACE receptor. This lowers the virus’s ability to enter cells

Naringenin has a bioavailability of about 6% and once absorbed, it reaches the liver, cerebrum, kidney, spleen, and heart. Naringenin has demonstrated antiviral activity against hepatitis B, hepatitis, C, dengue, and zika.

Grapefruit. Image via

Naringenin is also anti-inflammatory and inhibits cytokines: It also exerts anti-inflammatory properties by activating AMPK and inhibiting NF-kB, which results in downregulation of toll like receptor 4 (TLR4), TNF‐α, IL‐1β, IL‐6, iNOS, and COX‐2. Naringenin also exhibited anti-inflammatory effects in rats with lung damage. Naringenin downregulated TNF‐α and IL-6 in a mouse macrophage cell line. Because COVID-19 patients present with a cytokine storm (e.g. TNF‐α, IL‐1β), inhibiting the cytokine storm could be a way to relieve COVID-19 symptoms[21].

As a result, naringenin made it onto the list, most notably in the form of grapefruit, for its potential to reduce the likelihood of catching COVID-19 and also to relieve COVID-19 symptoms.

  • Reduce likelihood of catching virus: maybe, more data needed

  • Relieve COVID-19 symptoms: maybe with improved bioavailability; clinical data needed

8. Radicchio

Raddichio salad. Image via Cooks Country

Radicchio is extremely rich in the polyphenol luteolin. Luteolin specifically binds to the surface spike protein of SARS‐CoV‐2 and inhibits entry of the virus into host cells. Additionally, luteolin inhibits the SARS‐CoV Mpro which is required for viral infection[22].

Eriodictyol is a structural analogue of luteolin that may enhance treatment; it’s found in yerba santa, a native North American plant, and it could prevent COVID-19 infection.

Luteolin also binds readily to viral S-protein–human ACE2 receptor interface–ligand-binding complex.

Thus, luteolin, found in high concentrations in radicchio, could prevent COVID-19 infection.

  • Prevention: Maybe

  • Treatment: Don’t know

9. Licorice Root

Licorice root (Gancao) is used in traditional Chinese medicine due to its glycyrrhizic acid (GA), a major bioactive ingredient extracted from Rhizoma glycyrrhizae. It is used clinically as an anti-inflammatory medicine against pneumonia-induced inflammatory stress. Its pharmacological properties include detoxifying, cough-relieving, anti-inflammatory, antitumor, antiviral, and antibacterial capacity[23]. Another bioactive molecule in licorice root with therapeutic potential is glyasperin A[24].

GA has been reported recently for its ability to bind to ACE2 to prevent SARS-CoV-2 infection. GA demonstrates anti-allergenic effects, restoring the imbalance of Th1/Th2 subsets, which may help regulate inflammatory and autoimmune disease. GA also alleviated inflammation via NF-kB and p38/ERK pathways, reducing cytokines including IL-6, TNF-α, IL-8, and IL-1β[25].

That is why glycyrrhizic acid, extracted from licorice root, could prevent and relieve COVID-19 infection.

  • Prevention: Maybe

  • Relief: Maybe

10. Zinc

Zinc may be proactive in preventing COVID-19[13]. Zinc deficiency is associated with susceptibility to infection. The mortality due to pneumonia has been reported to be twice as high in individuals with low zinc status versus individuals with normal zinc levels. In a randomized, double-blind, placebo-controlled study, zinc significantly reduced the duration of symptoms of the common cold, from 7.6 to 4.4 days[26]. Another randomized controlled trial of high-dose oral zinc concluded that it enhances thymic function and the output of new CD4+ naïve T cells against torquetenovirus (TTV)[27].

Foods rich in zinc include:

  • Whole grains and whole grain products

  • Dairy products

  • Oysters

  • Red meat

  • Poultry

  • Beans

  • Nuts

Coronavirus appears to be susceptible to the viral inhibitory actions of zinc. Zinc may prevent coronavirus entry into cells and appears to reduce coronavirus virulence[7]. Specifically, zinc inhibited a SARS-CoV protease called PLP2 in vitro[28]. Interestingly, a mouse coronavirus strain was found to use a zinc matrix metalloprotease to enter the cell[29]. In this specific case it appears the virus needs zinc to work and matrix metalloprotease inhibitor was offered as a potential therapeutic target.

Based on mixed preclinical data and solid clinical data, zinc might be effective as adjuvant therapy for COVID-19. Future studies are needed to confirm whether zinc protects against SARS-CoV-2.

  • Prevention: Maybe; data is mixed

  • Treatment: Maybe, as adjuvant therapy

11. Resveratrol

Resveratrol is a SIRT1 agonist that extends the lifespan of cells; it has been shown to induce autophagy. Resveratrol protects against respiratory diseases; inhaled resveratrol blocked DNA damage in lung parenchymal cells[13]. Resveratrol increases ACE2 receptor expression, which, counterintuitively has been demonstrated to reduce illness severity, potentially due to normal physiological functions of ACE2 in converting angiotensin II into angiotensin (1-7)—angiotensin causes vasoconstriction and increase in blood pressure, which can have anti-inflammatory effects and enhance blood filtration.

Resveratrol is found in:

  • Grapes

  • Red wine

  • Nuts

  • Berries

  • Chocolate

  • Prevention: Maybe, but upregulates ACE2

  • Treatment: Maybe

12. Olive Oil

Olive oil prevents respiratory syncytial virus, influenza, and parainfluenza viruses. The bioactive polyphenol in virgin olive oil and the leaves of the olive tree, hydroxytyrosol, eliminates reactive species generated by UV rays. As such, it pairs well with vitamin D exposure. Hydroxytyrosol reduces oxidative stress and hydrogen peroxide related to the respiratory burst of neutrophils. It could be a useful adjunct treatment in respiratory tract infections[13].

More evidence is needed, though, on the effects of hydroxytyrosol from olive oil on COVID-19.

  • Prevention: unknown

  • Treatment: unknown

13. Selenium

Selenium deficiency has been associated with increased mortality risk from COVID-19. That is, the people who died from COVID-19 had lower levels of selenium than those who recovered[30].

Requiring selenium for their synthesis, selenoenzymes include several antioxidants such as glutathione peroxidase (GPx), selenoprotein P, and thioredoxin reductase. One of selenium’s primary roles is its ability to quench ROS. Selenium is involved in T cell proliferation and the humoral system, especially immunoglobulin production[26]. Low selenium is associated with poor immune function and cognitive decline, while sufficient selenium has anti-viral activity[27].

Selenium is found in:

  • Vegan: nuts, whole grains, cereals, mushrooms

  • Animal products: dairy, poultry, red meat, seafood

Interestingly, a main protease of SARS-CoV-2 responsible for viral replication interacts with glutathione peroxidase 1 (GPx1). GPx mimics ebselen, a synthetic selenium compound that is a potent inhibitor of the SARS-CoV-2 main protease[31]. This is indirect evidence that selenium may inhibit Mpro.

All in all, selenium is a cofactor that is necessary to equip potent antioxidant enzymes like glutathione peroxidase to minimize oxidative damage to cells. Combined with clinical data, we can safely assume that sufficient levels of selenium reduce the risk of complications or death due to COVID-19.

  • Prevention: Don’t know

  • Treatment: Probably

14. Probiotics

Probiotics enhance gut bacterial health and gut-lung-axis respiratory fitness. In a meta-analysis, Lactobacillus and Bifidobacterium supplementation were found to reduce the severity or shorten the duration of infection with the common cold.

Three studies showed Lactobacillus was effective at treating respiratory tract viral infections.

Another study found a significant association between Bifidobacterium and increased immune function and intestinal microbiota in the elderly[27].

This makes sense because 70% of our immune system resides in our gut wall in the form of gut-associated lymphoid tissue (GALT). Gut microbes and the immune system are continually cross-talking. So yes, even though some microbes are pathogenic and can worsen disease, others are mutualistic and can boost immunity. However, species and strains are important, and the amounts of given strains do affect their beneficial or harmful effects.

All-in-all, even though there is no direct evidence to conclude probiotics are therapeutic for COVID-19, their widespread acceptance in promoting gut health, which safeguards immunity, and even multiple clinical studies showing that probiotics treat respiratory infections, make them worthwhile for further investigation.

  • Prevention: Probably; species- and strain-dependent

  • Treatment: Probably; species- and strain-dependent

15. Hen of the Woods

Basidiomycota Agaricus blazei Murill (AbM), Hericium erinaceus (lion’s mane mushroom), and Grifola frondosa (hen of the woods / maitake) have been shown to exert antimicrobial activity against viruses, Gram‐positive and Gram‐negative bacteria, and parasites in vitro and in vivo.

Hen of the woods experimentally inhibited replication of herpes simplex virus and enterovirus 71 in vitro. AbM, HE and GF stimulate strong and rapid engagement of innate immunity and subsequent skewing of adaptive immunity from Th2 towards Th1 responses in the host[32].

A polysaccharide from hen of the woods called GFP-A increased expression of CD4+ and CD8+ T cells in the spleen, as well as mRNA expression of pro-inflammatory cytokines like IL-1b, IL-2, IL-6, and IFN-gamma[33]. Polysaccharide-K from Trametes versicolor (turkey tail) also increased IL-1b expression and NLRP3 inflammasome activation[34].

Given the immunopotentiating activity of mushrooms, one source raised caution about the safety of polysaccharides isolated from mushrooms. They’re concerned about overstimulating the immune system when COVID-19 is already associated with cytokine storm in more complicated cases. Future clinical trials would help elucidate the direct role of mushrooms and their bioactive compounds in fighting SARS-CoV-2[7].

  • Prevention: Don’t know

  • Treatment: Don’t know

16. Flax Seeds

Herbacetin (rich in flax seeds), rhoifolin (rich in citrus peels), and pectolinarin (found in a weed called Lantana camara, big sage, Spanish flag, or tickberry), were found to efficiently block the enzymatic activity of SARS-CoV Mpro[35]. Thus, herbacetin, found in flax seeds, could prevent viral replication and reduce severity of SARS. More in vivo and clinical evidence is needed.

  • Prevention: Don’t know

  • Treatment: May lessen disease severity

17. Paper Mulberry

Polyphenols found in Broussonetia papyrifera (paper mulberry)—including broussochalcone A, papyriflavonol A, broussoflavan A, kazinol F and kazinol J—interacted with both the catalytic residues of SARS-CoV-2 Mpro and exhibited good binding affinity. They are potentially more potent in their anti-Mpro activity than two repurposed drugs, lopinavir and darunavir[36].

Given that these results were obtained from an in silico docking study, essentially a molecular simulation, further studies are needed to determine effects of paper mulberry polyphenols in vivo.

  • Prevention: unknown

  • Treatment: unknown

18. Swiss Chard and Cranberries

In one experiment, myricetin and scutellarein were the most potent inhibitors the ATPase activity of the NSP13 RNA helicase involved in RNA synthesis in the SARS-CoV-2 virus. That means these compounds could prevent viral replication.

Myricetin is concentrated in swiss chard, cranberries, sweet potatoes, green and hot chili peppers, garlic, and blueberries.

Scutellarein can be found in the blue skullcap (Scutellaria lateriflora), a native herb to North America, and barbed skullcap (S. barbata), native to Asia.

In another experiment, out of the tested flavonoids, isobavachalcone most actively inhibited in vitro SARS-CoV PLpro proteolytic activity[37]. It can be found in bakuchi (Psoralea corylifolia), an Ayurvedic plant used for skin conditions.

Keep in mind, these were all in vitro experiments. Other considerations, like bioavailability of compounds, pharmacokinetics, and pharmacodynamics, can only be answered with in vivo studies.

  • Prevention: Don’t know

  • Treatment: Potentially

19. Red Algae

In a review, compounds that showed promise for the inhibition of coronavirus in humans include:

  • Silvestrol

  • Tryptanthrin

  • Saikosaponin B2

  • Caffeic acid

  • Psoralidin

  • Griffithsin

Silvestrol inhibited replication of MERS-CoV, a virus with ~79% sequence similarity to SARS-CoV-2. According to Müller et. al, “Silvestrol strongly inhibits the expression of CoV structural and nonstructural proteins (N, nsp8) and the formation of viral replication/transcription complexes” [38]. It is isolated from Aglaia, a genus of 117 species of woody trees that are part of the Mahogany family that grow largely in Southeast Asia[39].

Fruit sources high in this phytonutrient are grapes, strawberries, oranges, blueberries, black currants, tangerines, apples, cranberries, mulberries, and bilberries. Other plant sources include cauliflower, broccoli, bell peppers, cabbage, Brussels sprouts, olives, avocados, sage, rosemary, mint, parsley, basil, thyme, and cacao.

Tryptanthrin is a natural alkaloid with anticancer, anti-inflammatory, antiprotozoal, antiallergic, antioxidant and antimicrobial action. In prior studies, tryptanthrin prevented the early and late stages of viral replication, particularly by blocking the viral RNA genome synthesis and protease activity. It also demonstrates strong viricidal activity directly against HCoV-NL63. The HCoV-NL63 spike protein (S protein) targets the ACE2 receptor, showing a highly conserved sequence and structural similarity to SARS-CoV-2. Tryptanthrin is found in the Chinese herb Strobilanthes cusia (Nees) Kuntze.

Saikosaponins are triterpenoid derivatives, usually present as glycosides. In particular, Saikosaponin B2 demonstrated anti-coronaviral activity and inhibited viral attachment and penetration; it also inhibits hepatitis C virus entry.

Caffeic acid is a potent antiviral that has demonstrated activity against hepatitis B. It was also found to inhibit the attachment of HCoV to host cells, indicating potential binding to S proteins. Caffeic acid is found naturally in a wide range of plants because it’s involved in biosynthesis of lignin, a woody material.

Psoralidin also showed potent anti-viral activity against SARS-CoV PLpro. It is found in the seeds of Psoralea corylifolia, a plant used in Indian and Chinese traditional medicine.

Red algae. Image via Beachcombers

Griffithsin, a lectin found in red algae, is one of the most promising inhibitors of MERS-CoV. It potently binds specifically to glycans on CoV protein spikes and inhibits viral attachment to host cells. It also has low systemic toxicity[40]. More studies are needed to understand the tissue-specific mechanisms for prevention.

  • Prevention: Maybe; more studies needed

  • Treatment: Don’t know

20. Pot Marigold

Major phytochemicals of Calendula officinals, i.e. rutin, isorhamnetin-3-O-β-D, and calendoflaside, inhibited the Mpro main protease of SARS-CoV-2 in an in-silico docking trial. Rutin is present not just in marigold but also in oranges, black tea, asparagus, buckwheat, onions, green tea, figs, and most citrus fruit. The molecular simulation simply revealed that rutin bound readily and formed a stable complex with Mpro[41]. Further laboratory-based experiments are needed.

  • Prevention: Don’t know

  • Treatment: Don’t know