Personalized Nutrition & the COVID-19 Era

A Rapid Review for Health Professionals

Prepared by the Personalized Nutrition & COVID-19 Task Force of the American Nutrition Association

Victoria Yunez Behm MS, CNS, LDN  Jeffrey Blumberg PhD, FACN, FASN, CNS-S  Corinne Bush MS, CNS Rajesh Grover PhD  Deanna Minich PhD, FACN, CNS  Roger Newton PhD, FACN, FAHA  David Perlmutter MD, FACN, ABIHM Dana Reed MS, CNS, LDN Stephen Sinatra MD, FACC, FACN, CNS  Michael Stroka JD, MS, CNS, LDN 

Updated April 7, 2020 - 11:11am EDT

This resource is explicitly intended for health professionals only and makes no claims regarding preventing or treating COVID-19. Members of the public should consult with their health professional before undertaking any nutritional regimen. This information is not comprehensive and will be updated as new information emerges in the literature.

Introduction

Scientists are working furiously to uncover effective approaches to combat this novel coronavirus. The American Nutrition Association (ANA) recognizes the importance of personalized nutrition to support our physical, mental, and emotional resilience. 

At the moment, the nutritional strategies to deal with this infection are only supportive. In the absence of large-scale and long-term data, there is insufficient understanding of the subtle differences of specific nutrients on outcomes for individuals and populations. This task force of ANA nutrition scientists and clinicians has gathered to share collective expertise towards the potential supportive role of personalized nutrition during this challenging time for our society and our healthcare systems.

Current recommendations aim to reduce transmission and risk of infection in the community. (Source) This Task Force Statement is intended to provide a brief overview of foods, nutrients, food compounds, and supplements with research that points to optimizing immune responses and/or inhibiting viral load in general. Many of these compounds have not been tested specifically for COVID-19 or are currently undergoing clinical trials. Health professionals should use caution and best practices to determine if and when any of the following actions may be beneficial. It is imperative that practitioners understand nutrient depletions, drug-nutrient interactions, contraindications, and comorbidities that may impact their clients and patients.

Read about context, symptoms, and who is at risk.

How does this coronavirus function?

Viral Replication:

Coronaviruses are a large family of RNA viruses that cause a variety of diseases. They are characterized by the Spike proteins (Spro) on their surfaces known as the corona for which they are named. Seven coronaviruses have been identified to date. Coronaviruses like this novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicate by a unique process, summarized below. This presents potential targets for the discovery of effective therapies. (Source, Source)

  1. Virus binds to host receptor cell - In the case of SARS-CoV-2, this occurs when the Spro bonds at the angiotensin converting enzyme 2 (ACE2) receptor protein site 
  2. Virus or its genome enters the cell’s cytoplasm and fuses with the cellular membrane
  3. Virus releases its genetic material into the cell’s nucleus or cytoplasm
  4. Viral RNA is transcribed and viral mRNA directs protein synthesis (this is unique to coronaviruses)
  5. Virus replicates and assembles new virons that are released from the cell surface by exocytosis to further infect neighboring cells

The molecular bond between the SARS-CoV-2 Spro and the ACE2 receptor in human cells is similar to the binding pattern of the 2003 SARS coronavirus. However, this novel coronavirus appears to use different amino acids as the Spike protein binds to the ACE2 receptor. This may explain why the virus “sticks” about 10 times more tightly than the corresponding spike protein of the SARS coronavirus. (Source)

coronovirus

Open Source: CDC

There is no known prevention, cure, or confirmed therapy as of the writing of this report, however, researchers are exploring anti-viral therapies and vaccine trials are underway with some promising leads. (Source, Source, Source, Source, Source) Potential interventions can generally be divided into two categories: 1) interventions that act on the human immune system or human cells, and 2) interventions that act on the virus itself. (Source

Nutrition and Immune Function Generally

The following information is not intended as medical treatment, but rather a review of the current science. This information is not comprehensive and will be updated as new information emerges in the literature. The addition of any nutrient or compound may impact viral replication or human cellular function differently during prevention and over the course of disease progression. Although many substances can support the immune system and are helpful to prevent or ameliorate viral infections, practitioners should understand the unique needs of their patients and clients in order to determine whether any potential intervention is indicated, and at what stage in COVID-19 progression it may be implemented as their scope of practice allows. Additionally, it is critical for practitioners who make recommendations to understand the unique pathophysiology of this coronavirus.

Human Immune System & SARS-CoV-2:

Our innate immune response plays an important role in controlling the replication and infection of coronavirus. The virus enters into human cells via the  ACE2 receptor protein on human cell surfaces. (Source) This enzyme, found in multiple tissues throughout the body including the mucosal lining of the upper respiratory tract, lung, digestive tract, liver, kidney, brain and more. (Source) ACE2 is dependent on sodium and potassium to regulate blood pressure, however, this coronavirus inactivates the ACE2 enzyme. Thus, interventions are being considered that can inhibit the virus’ ability to replicate and block it from binding to human cell receptors. (Source

In a recent study of 175 patients hospitalized with COVID-19 in China, 93% of severe and critically ill patients had hypokalemia due to urine potassium loss with ACE2 degradation. (Source) Over the course of their hospital stay, patients were given a dose of 3 grams of potassium, which appeared to help correct deficiencies in most patients, especially as they began to recover. (Source) The physicians treating these patients have suggested that urine potassium excretion might be utilized as a biomarker signaling recovery.  

Potassium is not likely to be a preventive strategy, but potassium may play a role in the treatment of moderate to severe cases of COVID-19. Those with mild or respiratory symptoms should not necessarily be given additional potassium, as it can interact with certain drugs and health conditions. 

Inflammatory targets:
  • Inflammatory cytokines - Cytokines have been implicated in the progression of several viral infections. COVID-19 is associated with increases in interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumor necrosis factor-α (TNF-α). These may be considered therapeutic targets for COVID-19 to combat overactive inflammatory responses and cytokine storms. (Source)
     
Cytokine inhibitors that could potentially be supportive:
  • Curcumin - Shown to suppress cytokine release in cytokine storms during Ebola outbreak (Source)
  • Bergamot - Possible IL-8 mediated anti-inflammatory properties to reduce lung inflammation (Source, Source)
  • Flavonoids like resveratrol and luteolin - May generally reduce cytokine expression and secretion (Source, Source)

Mehta et. al. in Lancet "recommend identification and treatment of hyper-inflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality.” (Source)

Viral enzyme targets:

Proteases in many viruses play an important role in viral replication and are often targets for therapeutic agents. The following are likely the most important targets for the development of therapies to reduce viral load. (Source)

  • 3-chymotrypsin-like protease (3CLpro) - coronavirus main protein (Mpro)
  • Papain like protease (PLpro) - enzyme critical to coronavirus replication and infection of the host
  • RNA-dependent RNA polymerase (RdRp) - Nsp12, an RdRp, is the vital enzyme of coronavirus replication/transcription complex
  • Spike protein (Spro) - coronaviruses have spiked proteins on their surfaces that hook onto cell membranes and allow the virus’ genetic material to enter human cells
Potential viral enzyme influencers:

A recent in silico study (not peer-reviewed) assessed the structural ability of a host of flavonoids to inhibit this coronavirus by acting on the main protease 3CLpro. Researchers found that many flavonoid compounds have similar molecular structures and biological actions as nelfinavir, an antiviral drug with promise as a pharmacologic therapy for COVID-19. The researchers suggest that kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenine-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate in medicinal plants may inhibit 3CLpro. (Source)

  • Sources of kaempferol include: Spinach, cabbage, dill
  • Sources of quercetin include: Dill, fennel leaf, onion, oregano, chili pepper
  • Sources of luteolin-7-glucoside and apigenine-7-glucoside include: Olive, start fruit
  • Sources of demethoxycurumin and curcumin include: Turmeric
  • Sources of naringenin include: Citrus fruit
  • Sources of oleuropein include: Olive
  • Sources of catechin and epicatechin gallate include: Green tea


Research published in late February used computer analysis to assess which drug and natural compounds have the potential to inhibit COVID-19. (Note: these are neither in vivo nor in vitro experiments for COVID-19, although such studies are currently underway). The following is a curated list of potential inhibitors from this study. (Source)

chart

A note on hesperidin: Hesperidin may bind to Spike protein to interfere with the re-folding of Spike and inhibits the viral infection process. Oranges, grapefruit, lemon, and tangerines contain hesperidin, and it is also available in supplement form.

“...the herbal medicines containing these compounds as major components might be meaningful for the treatment of SARS-CoV-2 infections.” (Source)
 

What role does personalized nutrition play in the COVID-19 Era?

Personalized nutrition is the first line of defense against many chronic conditions including cardiovascular disease, hypertension, and diabetes. (Source) There is mounting evidence that these comorbidities predispose those infected by SARS-CoV-2 to worsened outcomes, increased symptom severity, and potentially mortality. (Source, Source, Source) Chronic and infectious diseases share several features such as inflammation and impaired immune function. (Source) These effects can be noted in metabolic conditions like diabetes whereby inflammatory mediators are released in response to immune triggers, leading to systemic inflammation and cell/tissue damage, as well as impaired immunity over time. (Source

Patients with these same chronic diseases including heart attacks, hypertension, diabetes, and others are commonly prescribed angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). As discussed, ACE2 is the primary protein receptor for this coronavirus, through which the virus gains access to human cells. Animal models suggest that ACEIs and ARBs increase ACE2 receptors in the heart and lungs, and may increase the risk of severe complications in COVID-19. (Source) Furthermore, ACE2 receptors are present throughout the human body, and are particularly prevalent in the mouth, lungs, heart, kidneys, intestines, brain, and testes. (Source, Source) The higher expression of ACE2 may make cells in these organs and tissues particularly susceptible to SARS-CoV-2 infection, replication, and spread. (Source)

Researchers assessing severely ill patients with COVID-19 in Wuhan Tongji Hospital noted the presence of comorbidities and organ damage in critical cases, suggesting that “we should pay full attention to the treatment of the original comorbidities of the individual while treating pneumonia, especially in older patients with serious comorbid conditions...” (Source) This statement, made on the front lines of this epidemic in the context of severe cases of COVID-19, may also be considered as we look at high-risk individuals who have not yet contracted the virus. Personalized nutrition plays an important role in the optimization of health and the prevention and management of comorbidities. (Source) By doing so, we can hope to support the innate immune response of individuals, especially those in high-risk groups and possibly reduce the risk of symptom severity in those who are infected.

The effects of nutritional interventions in the progression of chronic diseases can take weeks, months, and even years in some cases. We do not suggest that personalized nutrition is a magic bullet to a global viral pandemic. However, personalized nutrition strategies elucidate and beneficially influence the interplay between physiology and diet and may help to ameliorate the severity of the condition in the weeks and months to come. (Source) As such, it’s incumbent upon the personalized practitioner to evaluate available test results to understand the individual’s status including markers of inflammation, insulin regulation, and nutrient status and address any imbalances or deficiencies.

Nutrients & bioactive compounds:

The following have immune-modulating properties and many have been shown to have general anti-viral properties. Whether these are specifically effective for COVID-19 is yet to be elucidated, however, these are generally protective and can potentially help to support individuals' overall health.

Oil of oregano - Carvacrol, a compound in oil of oregano, was shown to be more effective against certain viruses on its own, oregano oil as a whole was more effective against respiratory viruses, such as flu viruses. (Source)

  • Supplementation: Oil of oregano is available as a supplement in tincture or capsule form.  
     

Quercetin - Laboratory and animal studies have shown that quercetin may inhibit a wide variety of viruses, including a coronavirus (SARS-CoV) related to COVID-19. (Source) In mice injected with influenza, quercetin was shown to restore diminished concentrations of many antioxidants in the lungs including catalase, reduced glutathione, and superoxide dismutase. Researchers concluded that quercetin taken in conjunction with viral infection may support antioxidant capacity and protect lung tissues. (Source) Note that human studies looking at quercetin and viral load in humans are limited.

  • Food: Leafy green vegetables, broccoli, red onions, peppers, apples, grapes, black tea, green tea, red wine
  • Supplementation: Quercetin is available in supplement form, and combining with bromelain or vitamin C may improve absorption.
     

Vitamin A - Vitamin A supports the health of mucosal tissues and barrier function. (Source) Retinoic acid, a metabolite of vitamin A, also helps regulate the immune system via the microbiome. (Source) Theoretically, since COVID-19 appears to impact mucosal tissues throughout the body, vitamin A could potentially be a supportive nutrient to protect barrier function. As previously discussed, ACE2 is the cellular receptor for SARS-CoV-2, and animal studies suggest that the ACE2 receptor may be upregulated by all-trans retinoic acid (ATRA), a vitamin A derivative. (Source, Source) Thus practitioners should carefully evaluate doses of vitamin A and its derivatives that exceed the recommended daily the Recommended Dietary Allowance (RDA) of 700mcg/2,333 iu Retinoic Acid Equivalent (RAE) for women and 900mcg/3,000 iu RAE for men.

  • Food: Beef liver, cod liver oil, sweet potatoes, carrots, black-eyed peas, spinach, broccoli
  • Supplementation: Vitamin A compounds with retinoic acid and the carotenoid lutein may be superior. Lutein is a potential 3CLpro inhibitor.
     

Vitamin C - Vitamin C is an important nutrient for immune health, specifically for white blood cells to fight infections. It also enhances iron absorption, and adequate iron can help protect against vulnerability to infection. 

  • Food: Guava, kiwi, bell peppers, strawberries, oranges, papaya, broccoli, tomato, kale, grapefruit, persimmon, spinach, pineapple 
  • Supplementation: Mega-doses of oral vitamin C have not been shown to protect against coronavirus, although trials are currently underway testing the ability of intravenous vitamin C to protect against the effect of a cytokine storm. (Source) Generally, vitamin C is supportive of the immune system, especially in those who are deficient. (Source) Buffered, non-acidic or Ester C supplements with bioflavonoids are superior.
     

Vitamin D - In a systematic review assessing the overall effect of vitamin D supplementation on the risk of acute respiratory tract infection, Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (over 11,000 participants ages 0-95). The most benefit was seen in those who were very vitamin D deficient and those not receiving mega-doses. (Source) Optimizing vitamin D status is likely a safe and helpful measure for protecting against respiratory infections in general. (Source) Vitamin D status should determine dosing so that optimal levels are maintained for the individual.

  • Supplementation: Most people do not have optimal levels of Vitamin D, especially in the winter. Vitamin D is not found in sufficient amounts in most foods, so exposure to sunlight is important and possibly supplementation if 25-hydroxy vitamin D levels are suboptimal.
     

Vitamin E - While not specifically an anti-viral nutrient, vitamin E is one of the most efficient antioxidants and plays an important role in lung and liver protection. As a fat-soluble nutrient, it can accumulate in lipid membranes and react quickly with free-radicals that trigger nuclear factors that produce cytokines. (Source) Deficiencies can alter immune responses and contribute to increased viral load. (Source)

  • Food: Sunflower seeds, almonds, avocados, spinach, butternut squash, kiwi, broccoli, olive oil, trout, shrimp
  • Supplementation: Vitamin E has various forms. Combined products with tocopherols and tocotrienols are superior.
     

Selenium - Selenium is a potent antioxidant and a cofactor of glutathione peroxidase, an important antioxidant enzyme. A deficiency of selenium can alter the immune response and increase the pathogenicity of a virus. (Source)

  • Food: One Brazil nut can provide the daily dose of selenium. Also tuna, shellfish, eggs, sunflower seeds, and shiitake mushrooms are good sources.
  • Supplementation: Selenium is available in supplement form, and is often included in multivitamin formulations.
     

Potassium - As previously discussed, potassium is not likely to be a preventive strategy, and may be especially beneficial in for severe cases when the patient becomes hypokalemic due to excessive potassium loss. Healthy individuals can maintain potassium levels by eating a diet that includes:

  • Food: Cooked spinach, cooked broccoli, potatoes, sweet potatoes, mushrooms, peas, cucumbers, zucchini, eggplant, pumpkins, bananas, oranges, cantaloupe, honeydew, apricots, grapefruit
  • Supplementation: Potassium supplementation is unlikely to provide protection or symptom relief to healthy adults or those with mild or respiratory symptoms. Supplementation has currently only been explored in the critically ill and those with severe cases of COVID-19 in order to replenish levels of this nutrient when ACE2 receptors are degraded by the virus.
     

Zinc - Zinc may improve the chance of avoiding respiratory tract infections in the elderly and those who are zinc deficient. (Source, Source)

  • Food: Oysters, beef, crab, and lobster, and to a lesser extent chicken, cheese, kidney beans, garbanzo beans, cashews, and almonds
  • Supplementation: Zinc can be taken alone, in a multivitamin, or as a lozenge. (Source, Source)
     

Protein - Adequate protein is critical for immune function. 

  • Food: In particular, taurine, carnosine, anserine, and creatine from animal foods like beef and lamb may promote an immunological defense against infections by bacteria, fungi, parasites, and viruses (including coronavirus) through enhancing the metabolism and functions of immune cells. (Source
  • Supplementation: These amino acids are absent from plant foods, so those who avoid meat may need supplementation as may the elderly, who are particularly at risk for protein malnutrition. Undenatured whey protein can also promote immune health by the action of naturally present compounds such as lactoferrin, which has antioxidant and antiviral properties. It has been shown to bind to viral receptor sites and inhibit in vitro growth of some viruses, and may, therefore, help to alleviate symptom severity or complications from viral infections. No trials have studied whey protein’s effects on COVID-19 to date. (Source) One serving of high-quality whey protein contains almost half of a healthy adult’s protein needs. Whey protein can be stored dry and can last several weeks, making it a great functional bulk food option.
     

Coconut oil - Generally considered anti-viral, trials have been proposed to test the ability of compounds in coconut oil such as lauric acid and the derivative monolaurin to impair viral replication and break down the lipid envelope of the virus. (Source, Source, Source, Source)

  • Food: Coconut oil is the most abundant natural source of lauric acid. (Source). It is a versatile cooking oil, however, attention should be given to the type of coconut oil (cold-pressed and unrefined products are generally preferred) and its use. For example, heating coconut oil beyond its smoke point (approximately 177 °C/350°F) may increase the formation of volatile compounds that cause negative health effects. (Source)
  • Supplementation: Monolaurin is available in supplement form.
     

Melatonin - Melatonin and its metabolites have been shown to have immunomodulatory and antioxidant properties by scavenging free radicals and by upregulating antioxidant pathways. (Source) Studies are primarily experimental animal and in vitro, however research suggests potential for human viral-induced conditions.

  • Supplementation: Melatonin is available in capsules and liquid forms with varying dosages. Studies have not been conducted in humans with regard to coronaviruses. 

Other considerations for self-care and when speaking with patients and clients:
  • Follow guidelines from the medical community - Practice good sanitation like frequent and thorough hand-washing and take social distancing seriously as long as it is recommended. The CDC now recommends the use of cloth face coverings in public. (Source)
  • Clean well and clean often - Wear gloves or wipe down shopping cart handles. Wipe down household surfaces, phones, laptops, bathrooms, doorknobs, etc. frequently with alcohol, hydrogen peroxide, and other cleaning agents. These agents can kill the virus, which can live a few days on surfaces.
  • Eat a healthy diet - Eat a healthy diet including lots of colorful vegetables & berries (frozen foods are fine and are preferable to canned foods). Recommend a diet rich in the foods outlined above. Many of those who die from various types of infections do not have adequate nutrient status, thereby impairing their body’s innate ability to fight infectious diseases.
  • Use herbs and spices liberally - Given the potential of various compounds in herbs and other medicinal plants to interfere with viral entry into cells, suggest cooking with herbs and spices as long as they are not contraindicated for the individual.
  • Drink plenty of filtered water. 
  • Cut out sugars to support immune system function - Eating sugar can suppress the action of white blood cells for hours after ingestion. 
  • Practice self-care and stress reduction: Stress is an important factor in immunity. Stress hormones such as adrenaline and cortisol weaken immune function. 
  • Get adequate sleep, exercise, and rest - Doing so may promote feelings of wellbeing and promote a parasympathetic response. Social isolation can increase fears and feelings of loneliness, acting as immunosuppressants.
  • Find ways to engage with loved ones - Share time with your favorite people, whether virtually or in-person with those in close proximity. When we feel loved, relaxed, and happy, we produce neuronal signaling molecules such as serotonin, dopamine, and relaxin which have a strengthening effect on the immune system. (Source)

The COVID-19 Era

What is happening?

Experts are estimating that up to 40-70% of the global population will contract COVID-19 (although most will not experience severe symptoms). (Source) Some have suggested that even if it is seasonal and abates over the summer, we could see a resurgence of cases in the Fall. Will it resemble seasonal flu or will it grow exponentially? Experts are not certain. (Source)

Unfortunately, containment has been ruled out as an effective strategy. (Source) In other words, we can’t stop the spread. Hygiene and social distancing measures are an attempt to slow the spread of the virus to help healthcare providers manage cases and "flatten the curve", to lower the peak of the surge of demand and to buy time as researchers work around the clock to find effective therapies.

What are the most common symptoms?

Symptoms often start with a sore throat and dry cough and/or fever two days to two weeks after exposure (Source). As the virus multiplies, neighboring cells are infected throughout the respiratory system. When the virus reaches the lungs, inflammation in the mucous membranes can cause damage to the alveoli, which then strain to supply oxygen, causing difficulty breathing. Swelling in the lungs can lead to a buildup of fluids and dead cells, and lung infections like pneumonia can occur. (Source) We are learning more about how the infection can spread throughout mucous membranes throughout the body, such as the gastrointestinal (GI) system. Some patients have reported having GI symptoms like diarrhea, indigestion, and vomiting before or concurrent with respiratory symptoms and scientists suggest that it may also be spreading through fecal-oral routes of transmission. (Source, Source)


COVID-19 has been found in the brain stems of infected patients, suggesting that it may share a trait with other coronaviruses that can spread via a synapse‐connected route from the lung and airways. (Source) The virus may also impact cells in the heart, liver, and kidney; resulting inflammatory responses (known as a cytokine storm) may cause damage throughout the body, especially in late-stages of disease progression. (Source, Source) Some who die as a result of infection with COVID-19 may succumb to virally-driven hyper-inflammation and multi-organ failure, especially those who have genetic immune factors. (Source, Source)

Who is at risk?

In addition to those with genetic mutations impacting immune function, those at highest risk are the elderly and those with compromised immune systems or secondary infection and underlying conditions such as COPD, cardiovascular disease, congestive heart failure, diabetes, and immune conditions. (Source) Serious cases and fatalities have been weighted heavily toward these populations, though there is concern that younger, “healthier” people are showing up in this cohort. (Source, Source, Source).