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 Health.com

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