How to Support Your Immune Health – See What Scientific Research Showed

As we each are doing our part in slowing the spread of the coronavirus disease 2019 or COVID-19 through social distancing and hygiene protocols as recommended by national and local health authorities, it is also important to support our immune health.

By having a strong immune system, we may help to protect not just ourselves, but also our loved ones and communities, by reducing the likelihood or severity of incubating and shedding the new coronavirus (officially named SARS-Cov-2) in case we get infected.

In this new blog, I would like to share with you evidence-based information as shown by scientific research on how to support your immune health.

References to scientific journal publications are provided so that you can empower yourself, make educated decision and take charge of your health!

In addition to supporting our immune health, it is also important to examine our diet and lifestyle choices in order to prevent or manage chronic diseases and health conditions that could make us susceptible to severe complications from COVID-19. Those high-risk chronic diseases or health conditions include hypertension, heart disease, diabetes, cancers, dementia, lung disease and obesity.^1,2,73,74 Please check out my previous blogs Diets and Chronic Diseases on how certain diets can reduce the risks of many chronic diseases.

We should also remind ourselves that supporting our immune health and overall health is important not just during this trying time but should also be a long-term strategy to help us weather through any future challenges.

Some of us may have more stay-at-home time these days. Why not take the opportunity for some self-reflection and perhaps much needed self-care, and examine our diet and lifestyle choices so that we can take charge of our health!

————————————————————————————-

Note that this blog is quite long as I try to present a more comprehensive picture and provide the scientific references. If you prefer to skip all the scientific research information and just look at the recommendations, please go to the SUMMARY section.

You can also navigate to a specific section/topic by using the “Topic Navigation” bar at the top right corner – only visible if you are reading from a laptop or computer screen, or using the TOPIC LIST below.

Here is also a Facebook Live video recording where I presented a summary of the information covered in this article.

————————————————————————————-

---

Topic List

Summary: Strategies to Support Your Immune Health

Two-Tier Immune System of the Human Body – An Overview

Diet, Lifestyle and Chronic Inflammation

Vegetables, Herbs and Spices That Support Immune Defense

Gut Health and Gut Flora

Liver Health

Sleep

Exercise

Stress

Vitamin D

Magnesium

Vitamin C

Zinc

References

---

Summary: Strategies to Support Your Immune Health

Here is a highlight of strategies to support your immune health. For detailed discussion and scientific references, please go to each topic/section that follows.

♦ Adopt a nutrient-dense whole food plant-rich diet consisting of plenty of whole fruits and vegetables of a wide variety of colors, moderate amount of legumes and whole grains, and some nuts and seeds.

• Such a diet is rich in a wide range of antioxidants, fibers and other health promoting micronutrients and phytonutrients, that help to combat oxidative stress and chronic inflammation.
• Such a diet has been shown to reduce the risk of chronic diseases including diabetes, hypertension, heart disease, etc., that may increase susceptibility to severe complications from COVID-19.

♦ Make dietary choices to reduce chronic inflammation, which is a culprit to many chronic diseases and may be attributed to increased severity and complications of COVID-19.

• Avoid refined carbohydrates (e.g. white flour, white rice, refined sugars, etc.)
• Consume high ratio of unsaturated fats including monounsaturated fats (e.g. olive, avocado) and omega-3 polyunsaturated fats (e.g. cold-water fish, flaxseed, chia seed, some nuts) over saturated fats.
• Minimize or reduce consumption of foods high in saturated fats and advanced glycation end products (AGEs) such as meats especially red meats and processed meats, foods cooked in high/dry heat, and dairy products especially aged cheese.
• Avoid of immune reactive foods, i.e., foods that trigger allergies or sensitivity, which can contribute to autoimmunity and inflammation. Note that food allergies and sensitivity are highly individualized.

♦ Support gut health and healthy gut flora, both are important for immune health.

• In addition to the above-described strategies, avoid or minimize consumption of processed foods and artificial sweeteners.
• Avoid toxins in foods including pesticides, herbicides, heavy metals, food additives, chemicals and environmental pollutants, by choosing organic whole foods whenever possible.
• Consume probiotic-rich foods from a variety of fermented foods or from probiotic supplement
• Choose organic, grass-fed/pasture-raised meat that is free of antibiotics.
• Be aware that certain drugs that can damage gut lining and gut flora including antibiotics, NSAIDs, proton pump inhibitors (PPIs), and osmotic laxatives.

♦ Incorporate certain vegetables, herbs and spices in your diet that promote immune defense.

• Cruciferous vegetables, such as broccoli, cabbage, cauliflower, kale, etc.
• Mushrooms.
• Allium such as garlic, onion, leeks, shallots, scallions, chives.
• Herbs and spices.

♦ Adopt a lifestyle that helps to reduce chronic inflammation and promote immune health.

• Adopt healthy weight management regimen through nutrient-dense whole food diets and adequate physical exercise.
• Adopt stress management techniques such as yoga, Tai Chi, meditation, low-intensity exercise, music therapy, etc.
• Engage in regular and adequate level of physical exercise.
• Ensure adequate sleep.
• Minimize exposure to food and environmental toxins by choosing organic foods and toxin-free household and personal care products whenever possible.

♦ Avoid deficiency of the following important immune-supporting nutrients, primarily through a nutrient-dense whole food diet (except for vitamin D where food is not a rich source). Supplementation may be beneficial in certain cases.

• Vitamin D
• Vitamin C
• Zinc
• Magnesium

♦ Other measures to reduce chronic inflammation, and improve gut health and immune health

• Address food sensitivities which can be hidden as symptoms can be non-specific (e.g. painful joints and muscles, chronic fatigue, skin issues, etc.), as opposed to food allergies. Food sensitivities can also result in more overt symptoms associated with inflammatory diseases and autoimmune diseases. One could self-check for potential food sensitivities through an elimination diet or alternatively do a blood test that tests for IgG and IgA antibodies to certain food compounds.
• Address gut issues as gut dysfunction can impair immune function. (See more details in my previous article: Why Your Gut Feeling Matters.)
• Address hidden infections and toxicity, e.g. parasites, mold toxicity, which can produce biotoxins contributing to chronic inflammation, and heavy metal toxicity.

[Back to Topic List]

---

Two-Tier Immune System of the Human Body – An Overview³

The body has a two-tier immune system although the most often mentioned immune function to defend against infections is antibodies.

Since SARS-Cov-2 is a new strain of coronavirus that human body has not encountered before, you may have heard repeatedly that the human body does not have immunity to it. The immunity being referred to here is the antibodies in the body, wherein the body will not have developed the corresponding antibody to SARS-Cov-2, except for the people who have been infected.

Antibodies are associated with the second tier of the immune system, called the adaptive or specific immune system. Adaptive immune system not only develops corresponding antibodies after initial exposure to a specific pathogen (e.g., virus or bacteria), it also develops immune cells that can attack and kill cells infected with a specific virus. The immunity developed is specific or targeted towards a previously exposed pathogen.

When initially exposed to a new pathogen, adaptive immunity takes 7 or more days to develop and be effective. Prior to that, the first-tier immune system, called the innate or non-specific immune system plays primary role and is the first line of defense of the body against pathogens. As the name implies, the innate or non-specific immune system does not target a specific pathogen. Instead, it can provide general protection of the body from pathogens.

The innate immune system consists of:

• Physical barriers (i.e., skin, mucus membranes).
• Protective chemicals (including stomach acid, enzymes, mucus) found along the digestive tract, respiratory tract, reproductive tract and urinary tract.
• Immune cells that attack and kill or ingest pathogens, e.g. natural killer (NK) cells, macrophages.
• Inflammatory response to mobilize immune mediators and immune cells (both innate and adaptive), confine and prevent further damage, and clean out debris to set the stage for repair.
• Antimicrobial proteins, e.g. interferons.
• Fever, a natural response of the body to infections. High body temperature can promote immune defense, inhibit microbes from multiplying and enhances body repair processes.

Therefore, it is important support the health of both the innate and adaptive immune system in the body, and avoid diets and lifestyle that could compromise our immune function.

[Back to Topic List]

---

Diet, Lifestyle and Chronic Inflammation

Clinical studies from existing COVID-19 cases showed that disease complications may progress to pneumonia, and to the more severe acute respiratory distress syndrome (ARDS) and multi organ dysfunction, eventually leading to mortality.^4,5,7

Out-of-control inflammatory response and cytokine (immune mediators) storm were thought to play important roles in coronavirus disease severity, progressing from pneumonia (inflammation of the lung) to ARDS.^4,6

Out-of-control inflammatory response can be due to imbalance of pro-inflammatory cytokines and immune response versus anti-inflammatory cytokines and immune response. Although the inflammation may be localized to the lung in the case of pneumonia, systemic inflammatory response in the rest of the body can play an important mediating role that potentiates inflammation of the lung.⁸

Chronic Systemic Inflammation – The Culprit

Studies have shown that diet and lifestyle choices can contribute to oxidative stress and chronic low-grade systemic inflammation in the body. Oxidative stress and chronic inflammation often form a vicious cycle where one potentiates the other.⁷⁵

Chronic systemic inflammation (and oxidative stress) not only may potentiate out-of-control inflammation response in the lung as discussed above, it has been shown to be an important underlying disease process of many chronic degenerative diseases including diabetes, heart disease, metabolic disorders (including hypertension, elevated blood sugar, elevated triglyceride, depressed HDL (or good) cholesterol, abdominal obesity), Alzheimer’s disease and some types of cancer.^9–13,75

As discussed above, some of these chronic diseases also increase the risk of severe complications and mortality from COVID-19. One may ponder if chronic inflammation (and oxidative stress) may be an underlying linkage that associate COVID-19 disease complications with some of these chronic diseases.

Factors That Promote Oxidative Stress and Chronic Inflammation

Foods that promote chronic inflammation include:^{14,15,21,22,70,75}

• Saturated fats (e.g. meat especially red meat and processed meat).
• High ratio of omega-6 to omega-3 polyunsaturated fats (e.g., some refined vegetable oils such as corn, soybean, sunflower and cottonseed oils).
• Advanced glycation end products (AGEs), found in cooked or uncooked meat especially beef, poultry and pork, fish, and aged cheese. High and dry heat cooking increase the levels of AGEs in foods.
• High glycemic index or glycemic load carbohydrates, especially refined carbohydrates (e.g. white flour, white rice, refined sugars etc.).
• Foods that trigger immune reactions, i.e., food allergies and sensitivities. Food allergies and sensitivities can contribute to autoimmunity and inflammation. It is highly individualized and dependent on gut health (see further discussion on Gut Health below).

Other factors that contribute to oxidative stress and chronic inflammation:^9,16–18,75

• Obesity and abdominal fat.
• Dysfunction in blood sugar regulation and insulin resistance (IR), resulting in elevated blood glucose and insulin levels.
• Toxins including chemicals and heavy metals from foods and environment.
• Biotoxins from hidden infections (e.g. bacteria, virus, parasites, mold).
• Gut dysfunction (see further discussion on Gut Health below).
• Stress (see further discussion on Stress below).
• Sleep deprivation (see further discussion on Sleep below).

Diets and Lifestyle That Reduce Oxidative Stress and Chronic Inflammation

Beneficial dietary composition include:^19,20,75

• Whole food plant-rich diets consisting of plenty of whole fruits and vegetables of a wide variety of colors, moderate amount of legumes and whole grains, and some nuts and seeds. Such diets are rich in a wide range of antioxidants, fibers and other health promoting micronutrients and phytonutrients, which help to combat oxidative stress, promote anti-inflammatory response, and regulate blood sugar. Leafy greens, cruciferous vegetables, and berries are particularly beneficial.
• Avoidance of refined carbohydrates.
• High ratio of unsaturated fats including monounsaturated fats (e.g. olive, avocado) and omega-3 polyunsaturated fats (e.g. cold-water fish, flaxseed, chia seed, some nuts) over saturated fats.
• Minimum or reduced consumption of foods high in saturated fats and AGEs such as meats (especially red meats and processed meats), foods cooked in high/dry heat, and dairy products especially aged cheese.
• Avoidance of immune reactive foods, i.e., foods that trigger allergies or sensitivities, which can contribute to autoimmunity and inflammation. Food allergies and sensitivities are highly individualized.

For more details on healthy eating guideline, please check out my previous blogs: Simple Guidelines for Healthy Eating, Are Carbs and Sugars All Bad.

Beneficial lifestyle approaches include:

• Healthy weight management through nutrient-dense whole food diets (see above) and adequate physical exercise.
• Minimum exposure to food and environmental toxins by choosing organic foods and toxin-free household and personal care products whenever possible.
• Stress management techniques such as yoga, Tai Chi, meditation, low-intensity exercise, music therapy, etc. (see further discussion on Stress below)
• Adequate sleep (see further discussion on Sleep below).

[Back to Topic List]

---

Vegetables, Herbs and Spices That Support Immune Defense

In addition to a whole food plant-rich diet mentioned above to mitigate chronic inflammation and oxidative stress, and reduce the risk of developing chronic diseases, there are specific vegetables, herbs and spices that may potentiate immune defense or have anti-microbial and anti-viral properties.

Some of these vegetables/herbs/spices may be more well researched while others may not be. The list here is not meant to be exhaustive.

Generally, it is a good strategy to incorporate a wide variety of these beneficial foods as part of a nutrient-dense whole food plant-rich diet.

Cruciferous Vegetables

Cruciferous vegetables, such as broccoli, cabbage, cauliflower, kale, etc., contain sulfur-containing compounds, glucosinolates, that is converted to isothiocyanates (ITCs) when cells walls are broken by chopping or blending. ITCs have been shown to have powerful immune boosting, antioxidant, anti-inflammatory, and anti-cancer properties. More commonly studied ITCs include sulforaphane, indole-3-carbinol, and diindolylmethane.^51,52

Numerous studies, mostly laboratory and animal studies and some human studies, have shown that ITCs and other phenolic compounds found in cruciferous vegetables exhibit anti-bacterial and anti-viral properties by heightening the immune defense mechanism against these pathogens, including Streptococcus pneumoniae, Helicobacter pylori, Clostridium species, Human papilloma virus, hepatitis, etc.^51,52,53

Mushrooms

Mushrooms have long attracted a lot of attention in their nutritional and medicinal values, and have historically been used in traditional oriental therapies.

Modern research, mostly laboratory and animal studies have shown the immune-modulating mechanisms and effects of mushroom metabolites. Mushroom metabolites have been found to either stimulate immune response which can be beneficial for cancer, immunodeficiency diseases, and bacterial and viral infections; or suppress immune reactions and inflammatory response which can be useful to mitigate autoimmune diseases.^54,55

Common dietary mushrooms include white button, cremini, shiitake, enoki, maitake, oyster, portabella, morel, and chanterelle, etc. Even simple white button mushrooms were shown to have immune-modulating effects.⁵⁵

Allium

Allium is a family of vegetables that includes garlic, onion, leeks, shallots, scallions and chives. Allium has long been recognized for its medicinal values in ancient and traditional cultures.

Modern research including some human studies has shown that allium contains organosulfur compounds that exhibits anti-cancer, anti-inflammatory, antioxidant, anti-infection (incl. bacterial, viral, fungal, parasitic infections), lipid and cholesterol lowering, and heart and liver protective properties.^56,57,58

Herbs and Spices

Herbs and spices are commonly incorporated in culinary practices across many cultures around the world. Many herbs and spices have also been traditionally recognized for their therapeutic values.

Scientific studies including human studies on the health effects of herbs and spices have grown tremendously in the last few decades. Curcumin, an active compound found in turmeric, is one of the most well researched spices for human health and many health benefits have been shown. Specific to immune functions, curcumin has been shown to have antioxidant, anti-inflammatory, anti-cancer and broad spectrum anti-microbial (against wide range of bacteria, viruses, fungi, parasites) effects.^59,60

Other herbs and spices that has anti-inflammatory effects include thyme, oregano, rosemary, sage, basil, mint, dill, parsley, cinnamon, clove, nutmeg, ginger, lemongrass, chili pepper, fenugreek, and pepper. Other spices that have anti-microbial effects include ginger, black cumin seeds, cinnamon, nutmeg, tarragon, thyme, oregano, mint, cinnamon, cloves.^59,61,62

Some Commonly Used Cold and Flu Remedies

Here is what research has shown on some of the common remedies used for common colds and flu.

Black elderberry extract is one of the commonly used supplements. Laboratory studies have shown the antiviral effects of black elderberry extract on influenza virus.^63,64 Small clinical trials have shown that elderberry extract supplementation shortened the duration and severity of symptoms associated with colds and flu.^65,66

Echinacea is another commonly used herb for common colds and flu. Laboratory and animal studies have demonstrated the anti-bacterial, anti-viral, anti-inflammatory and immune-modulating effects of echinacea. On human studies, a Cochrane review of 24 clinical trials showed that echinacea may reduce the incidence of common colds when taken as a preventative measure. As a therapeutic measure, the results were mixed in terms of whether echinacea reduced the duration of symptoms of colds.⁶⁷ Some clinical trials showed the efficacy of echinacea, when administered during early symptom onset, in reducing the severity of symptoms and risk of complications of flu.^68,69

[Back to Topic List]

---

Gut Health and Gut Flora

The gut or digestive tract spans from the mouth, to the pharynx, the esophagus, the stomach, the small intestine, the large intestine, and the anus.

The immune tissue in the lining or mucosal barrier of the gut, called to gut-associated lymphoid tissue (GALT) represent almost 70% of the entire immune system of the body.²³ Therefore, a healthy gut lining is critical for a healthy immune system.

In addition, the good (symbiotic) microorganisms in the gut flora, or more technically gut microbiota play important roles in modulating the immune functions of the human host. Such immune modulation effect extends beyond the gut to other organs and tissues, including the lung.⁸ Imbalance of gut microbiota or dysbiosis (i.e. overgrowth of bad microorganisms and undergrowth of good microorganisms) not only can impair immune defense but can also promote inflammation in the body.^8,24,25

Therefore, it is imperative to have a healthy gut and gut flora.

Some strategies to promote the health and reduce damage to the gut and gut flora include:^26–31

• Avoid or minimize consumption of processed foods, artificial sweeteners, refined carbohydrates.
• Consume a whole food plant rich diet that is high in fibers and prebiotics that feed the good microorganisms.
• Avoid toxins in foods including pesticides, herbicides, heavy metals, food additives, chemicals and environmental pollutants, by choosing organic whole foods whenever possible.
• Avoid consumption of foods that trigger immune reactions and inflammation, i.e. food allergies and sensitivity, which can be highly individualized.
• Consume probiotic-rich foods from a variety of fermented foods or from probiotic supplement.
• Reduce consumption of foods high in saturated fats.
• Choose organic, grass-fed/pasture-raised meat that is free of antibiotics.
• Be aware that certain drugs that can damage gut lining and gut flora including antibiotics, NSAIDs, proton pump inhibitors (PPIs), and osmotic laxatives.

For a more detailed account of gut and digestive health, please check out my previous blogs: “Why Your Gut Feeling Matters”, and “You are What You Eat? Not Quite”.

[Back to Topic List]

---

Liver Health

Liver conducts many critical biological functions including frontline immune defense against infections and protecting our body from toxins and other harmful substances.

With its strategic location in the body, 30% of total blood volume in the body flows and filtered through the liver.^83,84

Liver receives blood through the hepatic artery.^83,84

Liver also receives blood directly from the gut through a blood vessel called the hepatic portal vein. Therefore, liver is the first line of defense against pathogens that enter the blood stream through the gut, i.e., pathogens from foods we ingest and pathogens that lives in the gut as part of gut microbiota.^83,84

Liver plays important roles in immune surveillance against blood-borne pathogens. Liver contains a large number of immune cells that can mount quick response to invading pathogens.^83,84

Failure of the liver to detect or clear blood-borne pathogens can result in systemic infections, often leading to death. In case of liver failure, the primary cause of death is infection.^83,84

Chronic liver disease may be more prevalent than one might think. More than 30% of US population are estimated to have chronic liver disease.⁸²

Therefore, it is important to support liver health as part of our strategies for healthy immunity.

For more information on rick factors for liver diseases and tips to support liver health, please check out my article: “Take Care of Your Liver for Healthy Immunity and Overall Wellness”.

[Back to Topic List]

---

Sleep

The importance of sleep can often be overlooked in our busy life. Studies have shown that sleep and the circadian rhythm (24-hour sleep-wake cycle that synchronize with daylight and nighttime) have profound impact on immune functions.^32,33

In general, sleep enhances immune defense by facilitating the initiation of adaptive immune response. The synchrony of immune function rhythm with the 24-hour sleep-wake cycle has also been demonstrated, wherein naïve and mature immune cells peak at different time of the cycle to exert efficient immune defense mechanism.^32,33

Chronic sleep deprivation induces stress similar to other stressors that result in chronic low-grade inflammation as well as immunodeficiency due to dysregulation of both innate and adaptive immune functions. Sleep deprivation was shown to increase susceptibility to viral infections.^32,33

Therefore, maintaining a healthy sleep-wake cycle by sleeping around 10-11pm to be in-sync with the natural circadian rhythm, and having adequate amount of sleep of 7-8 hours are important to support immune health.

[Back to Topic List]

---

Exercise

Adequate physical exercise was found to be beneficial for immune functions and reduce susceptibility to viral and bacterial infections. On the other hand, a long-term sedentary lifestyle has deleterious immunological and inflammatory effects.³⁴

Exercise exerts both short-term and long-term accumulative effects on immune functions in a “dose” dependent manner. ³⁴

Short-term and regular moderate-intensity exercise exerts positive effects on immune functions However, interestingly, studies showed that short-term and regular long-duration high-intensity exercise is associated with compromised immunity.³⁴

In addition, some limited evidence showed that exercise might prevent and/or delay age-associated decline of the immune system.³⁴

For more details on overall health benefits of physical exercise and the amount/type of physical exercise that are beneficial, please check out my previous blog: Health Benefits of Physical Exercise That May Surprise You.

[Back to Topic List]

---

Stress

Chronic or prolonged stress lasting hours, days or longer has many deleterious health consequences. Many of the health consequences are the results of chronically elevated levels of stress hormones and neurotransmitters including cortisol and catecholamines.³⁵

For more details on how stress affects our health, please refer to my previous article: “Why Stress is the Culprit”.

Specifically on immune health, chronic stress was found to suppress and dysregulate both the innate and the adaptive immune function, which leads to chronic inflammation and reduced function, number, and trafficking of immunoprotective cells in the body.³⁵

Therefore, chronic stress not only weakens the first line and second line of immune defense against pathogens, it also makes us more susceptible to complications from infections by potentiating out-of-control inflammatory response, as discussed above in the case of COVID-19.³⁵

At this challenging time with COVID-19 pandemic, our stress level may inevitably be further elevated on top of the stress that we have been experiencing in our regular daily life. It is more important than ever to adopt some stress management techniques that help to mitigate the negative effects of stress on our immune health and overall health.

Examples of stress management techniques diaphragmatic breathing, yoga, Tai Chi, meditation or other mindfulness practices, low-intensity physical exercise, music therapy, etc.

[Back to Topic List]

---

Vitamin D

Roles of Vitamin D in Immune Function

The multifaceted and important roles that vitamin D plays in the body are increasingly being recognized and well beyond just bone health.

The wide-ranging effects of vitamin D is due to the presence of vitamin D receptors (VDRs) in most human cells, not just organs/tissues related to bone and calcium metabolism.^36,39

Laboratory and animal studies have demonstrated the roles of vitamin D in inhibition of cancer progression, cardiovascular health, inhibition of autoimmune diseases, and modulation of immune function.³⁶

Human studies have found the association of low blood serum level of vitamin D, i.e. calcidiol or 25(OH)D, with increased risk of certain types of cancers, diabetes, glucose intolerance, hypertension, heart disease, gastrointestinal diseases, and certain autoimmune diseases (including multiple sclerosis, rheumatoid arthritis, Hashimoto’s thyroiditis).^37,38

Specific to immune function, vitamin D was found to modulate and induce both innate and adaptive immune response against pathogens (including bacteria and viruses). In addition, vitamin D can also regulate inflammatory process by preventing overactivity of inflammatory events during infection.³⁹

More specifically, for respiratory tract infections including colds, influenza and pneumonia, some human studies have shown that lower serum levels of vitamin D was associated with higher incidence of respiratory tract infections.³⁹

Vitamin D supplementation was found to exert more protective effects against respiratory tract infections among people who are vitamin D deficient, especially those with serum 25(OH)D levels < 25 nmol/L. In addition, for vitamin D supplementation to be effective, regular daily or weekly doses should be used rather than irregular bolus doses.^39,40

Adequate Vitamin D Levels

There are currently no international standardized thresholds for 25(OH)D to define vitamin D deficiency. The thresholds for vitamin D to exert protective effects on different organs and body function may differ.

The United States Institute of Medicine (IOM) defines vitamin D deficiency as serum 25(OH)D levels < 30 nmol/L. The definition is based on bone health. In addition, serum 25(OH)D levels from 30 to <50 nmol/L are generally considered inadequate for bone and overall health in healthy individuals, while ≥50 nmol/L are generally considered adequate for bone and overall health in healthy individuals.^37,41

Note that conversion of vitamin D from sunshine on the skin to the bioavailable form of vitamin D in the body, i.e., 1,25(OH)₂D or calcitriol, is a complex process that involves the skin, liver, kidneys and various tissues in the body. Even if a person gets plenty of sunshine each day, there is no assurance that the body will have sufficient 1,25(OH)₂D at tissue and cell level. For example, people with darker skin tone will have lower conversion efficiency. Compromised liver and kidney functions may also impair conversion.³⁷

In the National Health and Nutrition Examination Survey 2005 to 2006 data, the prevalence of vitamin D deficiency (i.e., 25(OH)D levels < 50 nmol/L) in the United States was found to be 41.6% of the overall population, with increased prevalence among populations with darker skin tones.⁷¹

Natural food sources of vitamin D is limited. The best sources are fatty fish (e.g. salmon, tuna) and fish liver oils.³⁷

It is important to check for vitamin D level in blood test so that one could know whether there is potential deficiency. Note that although serum 25(OH)D levels may provide some indication of potential deficiency, serum 25(OH)D levels do not directly reflect the levels of bioavailable form of vitamin D, i.e., 1,25(OH)₂D, at tissue and cell level.³⁷

If vitamin D supplementation is needed, vitamin D3 supplement should be chosen instead of vitamin D2 supplement, because vitamin D3 supplement was found to be more effective in raising serum 25(OH)D levels.⁷²

Note that the safe or Tolerable Upper Intake Level (UL) of vitamin D supplementation recommended by IOM is no more than 4000 IU (or 100 mcg) per day for adults.³⁷

[Back to Topic List]

---

Magnesium

Roles of Magnesium in Immune Function

Magnesium is a critical and the 4th most abundant mineral in our body and involves in ~80% of known metabolic functions.⁷⁶

Some of the important functions of magnesium include serving as cofactor or activator in more than 600 enzymes in the body, supporting structural development of bones, regulating blood glucose and blood pressure, and supporting antioxidant level regulation in the cell.^76–78

Specific to immune function, magnesium plays a key role in the conversion of vitamin D to its bioactive form (i.e., 1,25(OH)₂D) that is usable by cells and tissues.^77,79

As discussed above, vitamin D deficiency can impair immune function and increase the risk of infections. Magnesium deficiency can contribute to vitamin D deficiency even with adequate sun exposure and dietary supplementation.^77,79

Chronic magnesium deficiency can also contribute to chronic systemic inflammation and oxidative stress, which are major culprits to many chronic diseases and susceptibility to COVID-19 disease severity, as previously discussed.^77,79

Adequate Magnesium Levels

Despite the importance of magnesium to our health, chronic magnesium deficiency is prevalent in our society.

It is estimated that  45% of US population are magnesium deficient due to diet, lifestyle, and certain health conditions.⁷⁶

In the United States, the Recommended Dietary Allowances (RDAs) of magnesium by IOM is 400 – 420 mg/day and 310 – 320 mg/day respectively for adult males and non-pregnant, non-lactating adult females.⁷⁸

It is estimated that 60% of people do not meet their RDA of daily magnesium intake.⁷⁶

Whole plant foods are good sources of magnesium. These include leafy green vegetables, broccoli, legumes (black beans, soybeans), whole grains, nuts (almond, cashew), seeds (pumpkin, sesame, sunflower, flax), potato with skin, banana, and unrefined sea salts.^77,78,80,81

For more information on risk factors contributing to chronic magnesium deficiency and tips to support healthy magnesium levels in the body, please check out my article: “Hidden Magnesium Deficiency May be A Culprit to Your Health Challenges”.

[Back to Topic List]

---

Vitamin C

Roles of Vitamin C in Immune Function

Vitamin C is an essential micronutrient, which acts as a potent antioxidant, supports biosynthesis of certain neurotransmitters, hormones, collagen, enzymes, and L-carnitine, and is involved in protein metabolism.⁴²

Vitamin C also plays important roles in supporting various cellular functions of both the innate and adaptive immune system. Deficiency in vitamin C therefore can result in impaired immune function.⁴³

Laboratory and animal studies have shown the anti-microbial and antiviral effects of vitamin C. Vitamin C was shown to inhibit replication of influenza virus in early stage of infection, when the vitamin C dosage is sufficiently high.⁴³

Vitamin C deficiency was found to increase susceptibility to infections, in particular respiratory tract infections. In addition, patients with acute respiratory infections, e.g. pneumonia and pulmonary tuberculosis, were found to have reduced blood plasma vitamin C levels, which may be due to increased utilization of vitamin C by the immune system during infection.^45,46

Human studies have shown mixed results where efficacy may vary depending on population groups:

• Common colds: As a preventive measure for common colds, meta-analysis of numerous clinical trials has shown that daily vitamin C supplementation at 200 mg/day or more, was effective in preventing common cold mainly for people who are under physical strain. As a therapeutic measure, daily vitamin C supplementation of 200 mg to 1 g may reduce the duration of cold symptoms.^44,45,
• Pneumonia: A Cochrane review of numerous clinical trials showed that therapeutic use of vitamin C of 1 g/day or more reduced the duration and severity of pneumonia. Severity reduction was observed among patients who were severely ill. As a preventive measure, supplementation of vitamin C helped to reduce incidence of pneumonia among people who have low dietary intake of vitamin C. Among people who have adequate dietary intake of vitamin C of 100 mg/day or more, preventive supplementation with vitamin C of as high as 2 g/day also helped to reduce the incidence of pneumonia, among specific population groups, i.e. military groups in this case, rather than the general population.⁴⁵

Adequate Vitamin C Levels

Based on all these research findings, one may ask whether vitamin C supplementation is necessary.

In the United States, the RDAs of vitamin C by IOM is 90 mg and 75 mg per day respectively for adult males and non-pregnant, non-lactating adult females.⁴²

A diet rich in whole fruits and vegetables will provide abundance of vitamin C well beyond the RDAs or the 100mg/day used in clinical trials described above.

However, vitamin C deficiency may be due to reasons other than low dietary intake. These reasons include gastrointestinal disorders that impair vitamin C absorption. Because of its potent antioxidant role, vitamin C in the body can also be depleted by the occurrence of oxidative stress, chronic systemic inflammation, and other inflammatory conditions including cardiovascular disease, neurodegenerative diseases, type 2 diabetes, obesity, gastrointestinal disorders, and lung and respiratory tract inflammations.^42,43

As described above, some studies have shown the benefits of daily intake of vitamin C of 1 g/day or more, although the positive results were observed among specific population groups. As with other nutrients, one should aim to obtain abundance of vitamin C primarily through whole fruits and vegetables.

Vitamin C supplementation may be used if deemed necessary. Among healthy adults, no adverse effects have been observed with doses of up to several grams per day.⁴⁵ However, some studies have found adverse effects of high vitamin C dosage among people with certain preexisting conditions and the ULs recommended by IOM is no more than 2 g/day for adults.⁴²

[Back to Topic List]

---

Zinc

Zinc is an essential mineral that plays important roles in immune function, wound healing, protein and DNA synthesis, and cell division.⁴⁷

Roles of Zinc in Immune Function

Even mild to moderate zinc deficiency can impair both innate and adaptive immune function. Zinc deficiency has been associated with increased susceptibility to and severity of pneumonia and other infections.⁴⁷ Zinc deficiency is also associated with increased oxidative stress, elevated inflammatory response, and worsening of inflammatory diseases.⁴⁸

Results from clinical trials:

• Pneumonia: Meta-analysis of several clinical trials showed that zinc supplementation given as an adjunct therapy to the treatment of severe pneumonia was effective in reducing the mortality. Zinc supplementation used in these clinical trials has a cumulative dose that ranged from 140 to 280 mg across a duration of 7 to 14 days.⁴⁹
• Common colds: A Cochrane review of 16 therapeutic clinical trials showed that zinc supplementation at a dose of ≥75 mg/day within 24 hours of onset of symptoms significantly reduced (by days) the duration of common cold symptoms. Zinc supplementation for at least five months reduced incidence and school absences of children with the common colds.⁵⁰

Adequate Zinc Levels

In the United States, the current RDAs of zinc is 11 mg and 8 mg per day respectively for adult males and non-pregnant, non-lactating adult females.⁴⁷

Zinc is most abundantly found in shellfish especially oyster and crab, and also in beef. Other good sources of zinc include white meats, beans, pumpkin seeds, and some nuts. Depending on dietary choices and gastrointestinal health conditions that may impair absorption, many people could be unknowingly zinc deficient or borderline deficient.⁴⁷

Overall, one should aim to consume adequate amount of zinc through a whole food nutrient-dense diet. Long-term high-dose supplementation of zinc can produce adverse effects. The UL recommended by IOM is no more than 40 mg/day for adults.⁴⁷

[Back to Topic List]

---

Related Articles

Diets and Chronic Diseases

Simple Guidelines of Health Eating

Are Carbs and Sugars All Bad

Why Your Gut Feeling Matters

You are What You Eat? Not Quite

Why Stress is the Culprit

 

---

References

1. Zhou F, Yu T, Du R et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020. doi:10.1016/s0140-6736(20)30566-3
2. Centers for Disease Control and Prevention (CDC). Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-nCoV/index.html. Published 2020.
3. Marieb E, Hoehn K. Human Anatomy & Physiology. 10th ed. San Francisco: Pearson Benjamin Cummings; 2016.
4. Wu C, Chen X, Cai Y, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med.Published online March 13, 2020. doi:10.1001/jamainternmed.2020.0994
5. Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr(2020). https://doi.org/10.1007/s12098-020-03263-6
6. Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol. 2020; 92: 424– 432. https://doi.org/10.1002/jmv.25685
7. Han Q, Lin Q, Jin S, You L. Coronavirus 2019-nCoV: A brief perspective from the front line [published online ahead of print, 2020 Feb 25]. J Infect. 2020;S0163-4453(20)30087-6. doi:10.1016/j.jinf.2020.02.010
8. Quinton LJ, Walkey AJ, Mizgerd JP. Integrative Physiology of Pneumonia. Physiol Rev. 2018 Jul 1;98(3):1417-1464. doi: 10.1152/physrev.00032
9. Esser N, Legrand-Poels S, Piette J, Scheen A, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105(2):141-150. doi:10.1016/j.diabres.2014.04.006
10. Golia E, Limongelli G, Natale F et al. Inflammation and Cardiovascular Disease: From Pathogenesis to Therapeutic Target. Curr Atheroscler Rep. 2014;16(9). doi:10.1007/s11883-014-0435-z
11. Newcombe E, Camats-Perna J, Silva M, Valmas N, Huat T, Medeiros R. Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease. J Neuroinflammation. 2018;15(1). doi:10.1186/s12974-018-1313-3
12. Moss S, Blaser M. Mechanisms of Disease: inflammation and the origins of cancer. Nature Clinical Practice Oncology. 2005;2(2):90-97. doi:10.1038/ncponc0081
13. Murata M. Inflammation and cancer. Environ Health Prev Med. 2018;23(1). doi:10.1186/s12199-018-0740-1
14. Mari-Sanchis A, Gea A, Basterra-Gortari F, Martinez-Gonzalez M, Beunza J, Bes-Rastrollo M. Meat Consumption and Risk of Developing Type 2 Diabetes in the SUN Project: A Highly Educated Middle-Class Population. PLoS ONE. 2016;11(7):e0157990. doi:10.1371/journal.pone.0157990
15. Feskens E, Sluik D, van Woudenbergh G. Meat Consumption, Diabetes, and Its Complications. Curr Diab Rep. 2013;13(2):298-306. doi:10.1007/s11892-013-0365-0
16. Valko M, Jomova K, Rhodes C, Kuča K, Musílek K. Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol. 2015;90(1):1-37. doi:10.1007/s00204-015-1579-5
17. Bredesen DE. Inhalational Alzheimer’s disease: an unrecognized – and treatable – epidemic. Aging (Albany NY). 2016;8(2):304-13.
18. Li Y, Jiao Q, Xu H, et al. Biometal Dyshomeostasis and Toxic Metal Accumulations in the Development of Alzheimer’s Disease. Front Mol Neurosci. 2017;10:339. Published 2017 Oct 24. doi:10.3389/fnmol.2017.00339
19. Galland L. Diet and Inflammation. Nutrition in Clinical Practice. 2010;25(6):634-640. doi:10.1177/0884533610385703
20. Gardener SL, Rainey-Smith SR, Martins RN. Diet and Inflammation in Alzheimer’s Disease and Related Chronic Diseases: A Review. J Alzheimers Dis. 2016;50(2):301–334. doi:10.3233/JAD-150765
21. Wilders-Truschnig M, Mangge H, Lieners C, Gruber H, Mayer C, März W. IgG antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles. Exp Clin Endocrinol Diabetes. 2008;116(4):241–245. doi:10.1055/s-2007-993165
22. Karakula-Juchnowicz H, Gałęcka M, Rog J, et al. The Food-Specific Serum IgG Reactivity in Major Depressive Disorder Patients, Irritable Bowel Syndrome Patients and Healthy Controls. Nutrients. 2018;10(5):548. Published 2018 Apr 28. doi:10.3390/nu10050548
23. Vighi G, Marcucci F, Sensi L, Di Cara G, Frati F. Allergy and the gastrointestinal system. Clin Exp Immunol. 2008;153 Suppl 1(Suppl 1):3-6.
24. Morowitz MJ, Carlisle EM, Alverdy JC. Contributions of intestinal bacteria to nutrition and metabolism in the critically ill. Surg Clin North Am. 2011;91(4):771-85, viii.
25. Quigley EMM. Gut bacteria in health and disease. Gastroenterol Hepatol (N Y). 2013;9(9):560-9.
26. Mu Q, Kirby J, Reilly CM, Luo XM. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017;8:598. Published 2017 May 23. doi:10.3389/fimmu.2017.00598
27. Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015;7(3):1565-76. Published 2015 Feb 27. doi:10.3390/nu7031565
28. König J, Wells J, Cani PD, et al. Human Intestinal Barrier Function in Health and Disease. Clin Transl Gastroenterol. 2016;7(10):e196. Published 2016 Oct 20. doi:10.1038/ctg.2016.54
29. Bischoff SC, Barbara G, Buurman W, et al. Intestinal permeability–a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14:189. Published 2014 Nov 18. doi:10.1186/s12876-014-0189-7
30. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ. 2018;361:k2179. Published 2018 Jun 13. doi:10.1136/bmj.k2179
31. Foster J, Rinaman L, Cryan J. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiol Stress. 2017;7. doi:10.1016/j.ynstr.2017.03.001
32. Almeida C, Malheiro A. Sleep, immunity and shift workers: A review. Sleep Science, 2016;9(3):164-168. doi:10.1016/j.slsci.2016.10.007
33. Besedovsky L, Lange T, Born J. Sleep and immune function. Pflügers Archiv – European Journal Of Physiology, 2011;463(1):121-137. doi:10.1007/s00424-011-1044-0
34. Turner J. Is immunosenescence influenced by our lifetime “dose” of exercise?. Biogerontology. 2016;17(3):581-602. doi:10.1007/s10522-016-9642-z
35. Dhabhar FS. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res. 2014;58(2-3):193–210. doi:10.1007/s12026-014-8517-0
36. Christakos S, Hewison M, Gardner D et al. Vitamin D: beyond bone. Ann N Y Acad Sci. 2013;1287(1):45-58. doi:10.1111/nyas.12129
37. National Institute of Health. Vitamin D – Fact Sheet for Health Professionals. Ods.od.nih.gov. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/#en66. Published 2019.
38. Liontiris MI, Mazokopakis EE. A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients. Points that need more investigation. Hell J Nucl Med. 2017; 20(1):51-56. doi:10.1967/s002449910507
39. Gruber–Bzura B. Vitamin D and Influenza—Prevention or Therapy?. Int J Mol Sci. 2018;19(8):2419. doi:10.3390/ijms19082419
40. Martineau A, Jolliffe D, Hooper R et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017:i6583. doi:10.1136/bmj.i6583
41. Cashman KD, Dowling KG, Škrabáková Z, et al. Vitamin D deficiency in Europe: pandemic?. Am J Clin Nutr. 2016;103(4):1033–1044. doi:10.3945/ajcn.115.120873
42. National Institute of Health. Vitamin C – Fact Sheet for Health Professionals. Ods.od.nih.gov. https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/. Published 2020.
43. Sorice A, Guerriero E, Capone F, Colonna G, Castello G, Costantini S. Ascorbic Acid: Its Role in Immune System and Chronic Inflammation Diseases. Mini-Reviews in Medicinal Chemistry. 2014;14(5):444-452. doi:10.2174/1389557514666140428112602
44. Heimer KA, Hart AM, Martin LG, Rubio-Wallace S. Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold. J Am Acad Nurse Pract. 2009;21(5):295–300. doi:10.1111/j.1745-7599.2009.00409.x
45. Hemilä H, Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst Rev. 2013;(8):CD005532. Published 2013 Aug 8. doi:10.1002/14651858.CD005532.pub3
46. Carr AC, Maggini S. Vitamin C and Immune Function. Nutrients. 2017;9(11):1211. Published 2017 Nov 3. doi:10.3390/nu9111211
47. National Institute of Health. Zinc – Fact Sheet for Health Professionals. Ods.od.nih.gov. https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/. Published 2020.
48. Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients. 2017;9(12):1286. Published 2017 Nov 25. doi:10.3390/nu9121286
49. Wang L, Song Y. Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta-analysis of randomized, double-blind and placebo-controlled trials. Clin Respir J. 2018;12(3):857–864. doi:10.1111/crj.12646
50. Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013;(6):CD001364. Published 2013 Jun 18. doi:10.1002/14651858.CD001364.pub4
51. Kapusta-Duch J, Kopeć A, Piatkowska E, Borczak B, Leszczyńska T. The beneficial effects of Brassica vegetables on human health. Rocz Panstw Zakl Hig. 2012;63(4):389–395.
52. Romeo L, Iori R, Rollin P, Bramanti P, Mazzon E. Isothiocyanates: An Overview of Their Antimicrobial Activity against Human Infections. Molecules. 2018;23(3):624. Published 2018 Mar 9. doi:10.3390/molecules23030624
53. Yu JS, Chen WC, Tseng CK, et al. Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway. PLoS One. 2016;11(3):e0152236. Published 2016 Mar 29. doi:10.1371/journal.pone.0152236
54. Lull C, Wichers HJ, Savelkoul HF. Antiinflammatory and immunomodulating properties of fungal metabolites. Mediators Inflamm. 2005;2005(2):63–80. doi:10.1155/MI.2005.63
55. Feeney MJ, Dwyer J, Hasler-Lewis CM, et al. Mushrooms and Health Summit proceedings. J Nutr. 2014;144(7):1128S–36S. doi:10.3945/jn.114.190728
56. Antony ML, Singh SV. Molecular mechanisms and targets of cancer chemoprevention by garlic-derived bioactive compound diallyl trisulfide. Indian J Exp Biol. 2011;49(11):805–816.
57. Tapiero H, Townsend DM, Tew KD. Organosulfur compounds from alliaceae in the prevention of human pathologies. Biomed Pharmacother. 2004;58(3):183–193. doi:10.1016/j.biopha.2004.01.004
58. Mikaili P, Maadirad S, Moloudizargari M, Aghajanshakeri S, Sarahroodi S. Therapeutic uses and pharmacological properties of garlic, shallot, and their biologically active compounds. Iran J Basic Med Sci. 2013;16(10):1031–1048.
59. Rakhi NK, Tuwani R, Mukherjee J, Bagler G. Data-driven analysis of biomedical literature suggests broad-spectrum benefits of culinary herbs and spices. PLoS One. 2018;13(5):e0198030. Published 2018 May 29. doi:10.1371/journal.pone.0198030
60. Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int. 2014;2014:186864. doi:10.1155/2014/186864
61. D’Souza SP, Chavannavar SV, Kanchanashri B, Niveditha SB. Pharmaceutical Perspectives of Spices and Condiments as Alternative Antimicrobial Remedy. J Evid Based Complementary Altern Med. 2017;22(4):1002–1010. doi:10.1177/2156587217703214
62. Vázquez-Fresno R, Rosana ARR, Sajed T, Onookome-Okome T, Wishart NA, Wishart DS. Herbs and Spices- Biomarkers of Intake Based on Human Intervention Studies – A Systematic Review. Genes Nutr. 2019;14:18. Published 2019 May 22. doi:10.1186/s12263-019-0636-8
63. Zakay-Rones Z, Varsano N, Zlotnik M, et al. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med. 1995;1(4):361–369. doi:10.1089/acm.1995.1.361
64. Krawitz C, Mraheil MA, Stein M, et al. Inhibitory activity of a standardized elderberry liquid extract against clinically-relevant human respiratory bacterial pathogens and influenza A and B viruses. BMC Complement Altern Med. 2011;11:16. Published 2011 Feb 25. doi:10.1186/1472-6882-11-16
65. Zakay-Rones Z, Thom E, Wollan T, Wadstein J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J Int Med Res. 2004;32(2):132–140. doi:10.1177/147323000403200205
66. 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
67. Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold. Cochrane Database Syst Rev. 2014;2(2):CD000530. Published 2014 Feb 20. doi:10.1002/14651858.CD000530.pub3
68. Rauš K, Pleschka S, Klein P, Schoop R, Fisher P. Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial. Curr Ther Res Clin Exp. 2015;77:66–72. Published 2015 Apr 20. doi:10.1016/j.curtheres.2015.04.001
69. Hudson JB. Applications of the phytomedicine Echinacea purpurea (Purple Coneflower) in infectious diseases. J Biomed Biotechnol. 2012;2012:769896. doi:10.1155/2012/769896
70. Sharma N, Bhatia S, Chunduri V, et al. Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them. Front Nutr. 2020;7:6. Published 2020 Feb 7. doi:10.3389/fnut.2020.00006
71. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48–54. doi:10.1016/j.nutres.2010.12.001
72. Tripkovic L, Wilson LR, Hart K, et al. Daily supplementation with 15 μg vitamin D₂compared with vitamin D₃ to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial. Am J Clin Nutr. 2017;106(2):481–490. doi:10.3945/ajcn.116.138693
73. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. Published online April 22, 2020. doi:10.1001/jama.2020.6775
74. Docherty AB, Harrison EM, Green CA , et al. Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. medRxiv 2020.04.23.20076042. doi:10.1101/2020.04.23.20076042 (This article is a preprint and has not been peer-reviewed.)
75. Tan BL, Norhaizan ME, Liew WP. Nutrients and Oxidative Stress: Friend or Foe?. Oxid Med Cell Longev. 2018;2018:9719584. Published 2018 Jan 31. doi:10.1155/2018/9719584
76. Workinger JL, Doyle RP, Bortz J. Challenges in the Diagnosis of Magnesium Status. Nutrients. 2018;10(9):1202. Published 2018 Sep 1. doi:10.3390/nu10091202
77. Razzaque MS. Magnesium: Are We Consuming Enough?. Nutrients. 2018;10(12):1863. Published 2018 Dec 2. doi:10.3390/nu10121863
78. National Institute of Health. Magnesium – Fact Sheet for Health Professionals. Ods.od.nih.gov. https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/. Published 2020.
79. Uwitonze AM, Razzaque MS. Role of Magnesium in Vitamin D Activation and Function. J Am Osteopath Assoc. 2018;118(3):181-189. doi:10.7556/jaoa.2018.037
80. Ismail AAA, Ismail Y, Ismail AA. Chronic magnesium deficiency and human disease; time for reappraisal?. QJM. 2018;111(11):759-763. doi:10.1093/qjmed/hcx186
81. Tarleton EK. Factors influencing magnesium consumption among adults in the United States. Nutr Rev. 2018;76(7):526-538. doi:10.1093/nutrit/nuy002
82. American Liver Foundation. Liver Disease Statistics. American Liver Foundation. https://liverfoundation.org/liver-disease-statistics/. Published 2017.
83. Jenne CN, Kubes P. Immune surveillance by the liver. Nat Immunol. 2013;14(10):996-1006. doi:10.1038/ni.2691
84. Kubes P, Jenne C. Immune Responses in the Liver. Annu Rev Immunol. 2018;36:247-277. doi:10.1146/annurev-immunol-051116-052415