I’m writing this in the middle of the 2020 pandemic where the world has almost come to a complete standstill because of SARS CoV-2, a.k.a a new strain of a very common group of viruses called coronaviruses which can, for some, lead to a presentation of various clinical symptoms coined COVID-19.
This post will not be a commentary on the world’s response to the virus, the degree of its true threat to human health, or whether or not lockdowns and quarantines were needed or effective.
What I will be reviewing is the role of nutrition in human immunity, and how optimal nutrition is one your best defenses against any infection or pathogen; your best offense is having a robust immune system and by extension immune response.
Your other best defense for immunologic robustness is to be ‘metabolically’ healthy. This means not being insulin resistant; the signs of which are increasing fasting blood sugar, A1C, high blood pressure, or, of course, having been diagnosed with prediabetes or Type 2 diabetes.
Whether we’re talking about any viral infection including influenza, the common cold, or specifically any coronavirus, nutrition, and a healthy immune system is a must when it comes to being in the best possible position to fight viruses. Good nutrition is also important for anyone who goes on to develop COVID complications. So what are the best anti viral foods?
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Overview of the immune system
The full scope needed to cover the complexities of the immune system is beyond this post but can be found elsewhere. Your immune system protects your body against infection and disease. It’s a complex and integrated system of cells, tissues, and organs that has specialized roles in defending against foreign substances and pathogenic microorganisms, including bacteria, viruses, and fungi.
Many might be surprised to learn that their immune system also functions to guard them against cancer. We all have precancerous and cancerous cells in us all of the time but a strong immune seeks them out and destroys them, so immunity isn’t just about those damned bugs.
Cells of the immune system originate in the bone marrow and circulate to peripheral tissues through the blood and lymph. Organs of the immune system include the thymus, spleen, and lymph nodes (4). The immune system is broadly divided into two major components: innate immunity and adaptive immunity.
As your first line of immune defence, innate immunity involves immediate, nonspecific responses to foreign invaders and pathogenic microorganisms. It doesn’t involve any immunologic memory, e.g. antibodies (4).
The innate immune system is comprised of various anatomical barriers to infection, including physical barriers (e.g., the skin & the mucous lining of your nasal passages, lungs, and digestive tract), chemical barriers (e.g., the acidity of stomach secretions), and biological barriers (e.g., normal microflora (bacteria etc) of the gastrointestinal tract), as well as cells (phagocytic) such as monocytes, macrophages, and neutrophils that eat up pathogens and secrete chemical signals that induce inflammation (4).
Because of the inflammatory products of the innate immune system, there is some collateral damage to surrounding cells and tissues during the process of combating and destroying invading pathogens (4).
Adaptive immunity (also called acquired immunity) is your second line of defense and requires more time (several days or weeks) to fully develop its complex, specific responses against pathogens (4). This response is much more complex than the innate response. Exposure to a specific antigen (protein) on an invading pathogen stimulates the production of immune cells that target the pathogen for destruction.
Immunologic “memory” means that immune responses upon a second exposure to the same pathogen are faster and stronger because antigens are “remembered.” (Some of the immune cells’ job is to do nothing more than remember the identify of a given pathogen – amazing!). Primary mediators of the adaptive immune response are B lymphocytes (B cells) which produce antibodies and T lymphocytes (T cells) which are different types of white blood cells (4).
Nutrition and immunity
Your nutritional status can modulate the actions of your immune system; therefore, the sciences of nutrition and immunology are tightly linked (5). In fact, malnutrition is the most common cause of immunodeficiency in the world (6). Practically all forms of immunity are affected by protein-energy malnutrition, but non-specific defenses and cell-mediated immunity are most severely affected.
Micronutrient deficiencies, as well as functional deficiencies, impair immune function (5). The take away here is that you don’t need to be suffering from a clinical deficiency (scurvy, rickets, pellagra, etc.) before your immune system is affected; suboptimal intakes of vitamins and minerals impact immune response as well (translation, sluggish response time to a pathogen and a less than ideal/full immune response). Ensuring your body is in the best possible position to fight any infection, including SARS CoV-2, will give you the best possible fighting chance, whether or not a coronavirus infection progresses to COVID.
Protein & energy
Protein-energy malnutrition (PEM; also called protein-calorie malnutrition) is a common nutritional problem. As a clinical dietitian nutritionist, I see it in hospitalized patients and those with significant health concerns (diseases) that affect their ability to eat and/or digest and absorb nutrients. It’s not just seen in so-called impoverished nations. It’s seen in those who are food insecure, struggling with addictions, are on limited incomes, and in the elderly.
Regarding innate immunity, PEM leads to reduced production of various disease-fighting proteins and impairs phagocyte function (the process where immune cells ‘gobble’ up pathogens) (7, 9, 10). PEM negatively affects your immune-related barriers too, increasing infections of the respiratory, gastrointestinal, and urinary tracts (11). PEM causes your thymus gland to shrink (which products T cells) leading to decreased effectiveness of memory (acquired) immune response to an antigen (the unique proteins/markers on pathogens that allow your immune system to remember the invader for next time (11, 12).
Last but not least, inadequate intakes of high-quality protein and poor energy intake impairs your lymphoid tissues, including your spleen and lymph nodes, and PEM impairs antibody affinity for pathogens; overall antibody response is generally decreased as well (12).
Experimental studies have shown that several types of dietary lipids (fatty acids) can modulate the immune response (13). Fatty acids that have this role include the long-chain polyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 classes. Fatty acids get incorporated into cell membranes (like the four walls, ceiling, and floor that surrounds a room). Here fatty acids influence how your immune and other cells talk to each other and keep the inflammation in check that occurs when your innate immune system is busy fighting pathogens (14, 15, 16).
People get enough omega-6s in their diets, that’s easy breezy as is getting enough alpha-linolenic acid omega-3 (found abundantly in both plant & animal foods). Where people miss the mark is getting enough foods with EPA, DPA & DHA omega-3s, or omega-3 supplements including algal oil. Because humans don’t produce these fats efficiently, getting pre-formed versions from food and supplements is mandatory, for both general health and a for a kick-ass immune system.
Vitamin A (not beta-carotene)
One of the best-known immune-modulating and antiviral nutrients. Vitamin A and its metabolites play critical roles in both innate and adaptive immunity. Vitamin A helps to maintain the integrity of the main anti-infection barriers: your skin and mucosal membranes (lining) of your eyes, lungs, sinuses, gastrointestinal and genitourinary tracts (17).
Vitamin A is important for the normal functioning of the white blood cells that are part of the innate immune response and vitamin A is needed for the proper functioning of both T and B cells that mediate adaptive immunity which produces antibodies when they encounter pathogens (bacteria and viruses) (17, 18). The active hormone derived from vitamin A, retinoic acid, directly or indirectly regulates over 500 genes including those involved in your immune response and function (19).
Subclinical (or a functional) vitamin A deficiency might increase the risk of infection as well (20). Infections can, in turn, lead to vitamin A deficiency in a number of different ways such as reducing food intake (due to a loss of appetite, nausea), impairing vitamin A absorption, increasing vitamin A excretion, interfering with vitamin A utilization, or increasing metabolic requirements of vitamin A (20).
PRO TIP: beta-carotene IS NOT the same as vitamin A. Beta-carotene must be converted into vitamin A and about 1/3 of the population have a genetic defect making them ‘poor converters’; for this reason, it’s best to include food sources of pre-formed vitamin A for best results.
B6 is needed for the production and metabolism of amino acids (the building blocks of proteins) such as cytokines and antibodies. Animal and human studies have demonstrated that a vitamin B6 deficiency impairs aspects of adaptive immunity. This includes impairing the maturation of newly developing white blood cells leaving them underdeveloped and ineffective (21, 22, 23).
Correcting a suboptimal and/or vitamin B6 deficiency restores any negatively affected immune function which restores optimal white blood cell production (23). Ensuring an adequate vitamin B6 intake is especially important for optimal immune system function in older individuals (24, 25).
Folate (vitamin B9)
Long story short, folate is involved in a variety of important metabolic pathways (methylation, RNA & DNA and amino acids metabolism) that support immune function as it relates to immune cell production (26, 27). Clinical folate deficiency, known as megaloblastic anemia, results in impaired immune responses, primarily affecting cell-mediated immunity; correcting the vitamin deficiency with folate supplementation restores the affected immune functions (28).
Folate works with vitamins B6 and B12 especially so ensuring you get good sources of folate in your diet is crucial so these three immune system B vitamins can work effectively.
Those with vitamin B12 deficiency and insufficiency (pernicious or megaloblastic anemia), or high homocysteine, have been shown to have suppressed natural killer cell activity and decreased numbers of circulating lymphocyte (29, 30); these impaired immune effects are corrected by treating B12 deficiency (29).
The often ridiculed Linus Pauling is most known for his work in vitamin C. Vitamin C research has come a long way with respect to supporting your immune system. When it comes to respiratory infections, higher doses of vitamin C have been shown to benefit many aspects of colds and flu. Vitamin C is a potent antioxidant that protects your cells, tissues, and body against the effects of “reactive oxygen species” (hypochlorous acid and peroxynitrite) which are generated by your immune cells when fighting infections.
In simple terms, your immune cells essentially produce small amounts of bleach to kill pathogens and yes, this can cause damage that your body needs help to off-set, enter vitamin C.
Vitamin C has been shown to stimulate both the production (31, 32, 33, 34, 35) and support of white blood cells (various leukocytes such as neutrophils, lymphocytes, and phagocytes). Specific antiviral properties of the immune system needed to fight infections are stimulated with higher intakes of vitamin C (36, 37, 38, 39, 40). It’s for this reason that vitamin C is a staple in anti viral nutrition.
Many have made the argument that the current RDA of 75 to 90 mg per day is woefully inadequate; some have suggested 200 mg while other 400 mg per day as a more optimal RDA for vitamin C. Keep in mind, this is baseline nutrition, not for any amount that may be needed during acute infections.
There’s a bit of a love-hate relationship with vitamin D3. The important thing to do is not throw the baby out with the bathwater. In one camp you have people saying that vitamin D3 is a cure-all and preventative nutrient for pretty much everything under the sun whether that’s MS, cancer, diabetes, high blood pressure, mental illness, or an immune booster for acute respiratory infections, including colds, the flu. For this reason, vitamin D3 is often recommended in the fall and winter, the so-called flu season. Now vitamin D3 is being considered for a supportive role with SARS CoV-2 infection and COVID.
On the other side, you have those who say vitamin D3 offers no unique benefits beyond basic nutrition, especially where bone health (rickets mostly) is concerned. Of course, the truth is somewhere in the middle. Vitamin D3 is involved in so many aspects of health because its hormone derivative, calcitriol, is a secosteroid where it modulates about 10% of your total genome (DNA). One such function is the production of antimicrobial peptides (proteins) that directly kill pathogens (42, 43, 44, 45, 46, 47). Vitamin D3 also helps to temper immune-system associated inflammation when you’re fighting infections including the dreaded cytokine storm.
Many conservative organizations will declare that there’s not enough evidence to indicate that vitamin D3 (through sun or supplements) can prevent, or improve the course of coronavirus infection or COVID-19, and rightfully so. SARS-CoV 2 is a new virus and large-scale, randomized controlled trials haven’t been done. Because of that, many will simply not recommend vitamin D3 supplements until such studies are done.
Most (as in 90% or more) vitamin D3 studies have one significant methodological flaw. They give a dose of vitamin D3 and wait to see its impact on an outcome, e.g. the treatment group gets 1000 IU per day or maybe different groups get different amounts such as 1000 IU, 2000 IU, or 4000 IU per day respectively. Some studies will take pre/post vitamin D levels but here’s the rub, even though everyone in the treatment group is getting the same dose of vitamin D3 (1000, 2000, etc), NOT everyone’s resulting vitamin D levels will be the same and that matters.
A good vitamin D study would personalize the dose and give each person whatever amount of vitamin D was needed to raise their vitamin D to a predetermined level. After treatment of any given dose, vitamin D blood levels could vary wildly; some may achieve 50 nmol, others 75 nmol, 125 nmol, etc. Why does this matter? There’s evidence that vitamin requirements (to satisfy all enzyme requirements) are nearly fully met when vitamin D is about 100 nmol.
Further to this, any study looking at vitamin D’s role in any given health outcome would need to consider other nutrients that are needed for optimal vitamin D metabolism including vitamin A, vitamin K2 and magnesium at the very least. Other important synergistic nutrients include the minerals boron and zinc.
FUN FACT: It’s important to note that the hypothesis that vitamin D can help with SARS-CoV-2 & COVID-19 management is rooted in years of research on D3’s role on the human genome, immunity, and respiratory illnesses. It’s not some fanatical or unsustaniated idea.
Recommended ideal serum vitamin D levels vary by outcomes: bone health, heart disease risk, autoimmune disease prevention, falls risk, muscle strength, etc, and for that reason, no one can agree. But I think we can get out of the weeds and I think it’s reasonable to look at ancestral evidence to see what an ideal level might be. Evolutionary biology suggests that early humans, even with the black skin (which requires more UVB to make vitamin D) living near the equator can easily produce (and did) the equivalent of 4000-8000 IU (100-200 mcg) per day which corresponds to a blood level of 100 + nmol.
Those who’ve reviewed what studies and systematic reviews we have to date on vitamin D, respiratory infections and COVID-19 did their job well. The problem is, they were reviewing poorly designed studies so a lack of clear evidence was expected, but does that mean the public or practitioners can’t act? Of course not, vitamin D’s role in immune is settled science, recommending vitamin D3 just needs to be positioned properly.
Any suggestive evidence for a beneficial role of vitamin D3?
In one study, researchers analyzed patient data from 10 countries and found a correlation between low vitamin D levels and hyperactive immune systems (= increased inflammation, altered immune response, and risk for cytokine storm).
The researchers noted that patients from countries with high COVID-19 mortality rates, such as Italy, Spain, and the UK (end of winter, low vitamin D status), had lower levels of vitamin D compared to patients in countries that were not as severely affected (48). Another study compared those European countries that were highly severely hit to those mildly hit by COVID-19 and vitamin D levels. Higher vitamin D levels (event in countries with low UVB but whose diet is rich in vitamin D) had lower infection and death rates (49).
A retrospective study from Indonesia of 780 COVID patients was examined based on vitamin D status and disease outcome. They found that the majority of deaths were male, with several comorbidities and low vitamin D status. In fact, there was a 10x greater risk of dying with vitamin D levels < 50 nmol and 7x greater risk for those with vitamin D levels between 50 to 75 nmol (50). It’s important to note that vitamin D levels can be lower in sicker people so the low D levels could just be a marker of poor health in general which increased there a risk for dying.
Another associative study between vitamin D levels and COVID cases and deaths using data from 20 European studies. Negative associations (worse outcomes) were observed between mean vitamin D3 levels (56 nmol) in each country and the number of COVID-19 cases and mortality (51).
A retrospective multicenter study of 212 cases of SARS-CoV-2 infection was conducted. Mean serum blood levels were 60 nmol. Serum D level was lowest in critical cases but highest in mild cases. Blood levels of vitamin D were statistically significant among clinical outcomes as well. Logistic regression analysis indicated that for each standard deviation increase in serum vitamin D level, the odds of having mild clinical outcomes (complications) rather than severe clinical outcomes were about 8 x lower (52), while the odds of having mild outcomes rather than CRITICAL outcomes (worst of the worse) was an impressive 19.6 x lower.
The results suggest that an increase in serum 25(OH)D level in the body could either improve clinical outcomes or mitigate worst (severe to critical) outcomes, while a decrease in serum 25(OH)D level in the body could worsen clinical outcomes of COVID-2019 patients. Vitamin D supplementation could possibly improve clinical outcomes of patients infected with COVID-19.
One randomized controlled trial set out to determine the clinical outcomes of older COVID-19 patients (50 and older) who received a combination of supplements that included 1000 IU of D3, 150 mg of magnesium, and 500 mcg of vitamin B12 per day. Their hypothesis was that fewer patients receiving the supplements would need oxygen therapy and/or intensive care support compared to those who did not get the supplements (it’s important to note that these were not simply SARS-CoV-2 positive infections but rather those with advanced COVID-19 clinical presentation).
It was a small study but they had 17 patients who received the supplements and 26 who did not. The baseline demographics were the same between groups. Age and high blood pressure where risk factors for poorer outcomes even after adjusting for this, the Vitamin D3, magnesium, and B12 supplements provided benefit. Fewer patients who got the supplements required the initiation of oxygen therapy.
Those who got the supplements were 13% less likely to need oxygen and 20% less likely requiring intensive care support compared to the control group (those who didn’t get the supplements). Their conclusions? Vitamin D3, magnesium, and vitamin B12 supplement “combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support and/or intensive care support”.
In particular, the α-tocopherol form of vitamin E protects against peroxidation (rusting) of polyunsaturated fatty acids (in membranes that make up the outer structure of cells) which, can potentially cause cellular damage and subsequently lead to improper immune responses of immune cells (53). Several studies in animal models, as well as humans, indicate that vitamin E deficiency impairs both humoral and cell-mediated aspects of adaptive immunity, including B and T cell function (reviewed in 54).
Moreover, vitamin E supplementation in amounts greater than current intake recommendations (15 mg/day for alpha-tocopherol) has been shown to enhance immunity and decrease susceptibility to certain infections, especially in elderly individuals. The natural age-related decline of the immune function is accompanied by an increased susceptibility to infections and a poorer response to immunization (vaccination); vitamin E has been shown to enhance immune response that declines with advancing age (55).
A study that gave 200 mg per day of alpha-tocopherol (137 IU in old units) in older adults (average age 70 years), saw improvement in several parameters of immune function after just 3 months compared to baseline (before supplementation started ) (56).
A randomized, placebo-controlled trial in 617 nursing home residents (≥65 years of age) reported that daily supplementation with 200 IU of synthetic α-tocopherol ( equivalent to 90 mg of naturalα-tocopherol) for one year significantly lowered the risk of contracting upper respiratory tract infections, especially the common cold, but had no effect on lower respiratory tract (lung) infections (57, 58, 59, 60, 61, 62, 63, 64, 65, 66).
On the other hand, some studies found no overall benefit with vitamin E supplements on respiratory tract infections in older adults (59, 67, 68, 69). More research is needed to examine whether supplemental vitamin E might enhance immune function and reduce the risk of infection in older adults.
A note on vitamin E. Vitamin E is not just alpha-tocopherol. Most of the studies on vitamin E (not just for immunity) have only looked at this form of the vitamin (there are 8 found in nature). To date, we don’t know how the other 7 forms of vitamin E might affect immune function but if you want to leverage the potential of the full vitamin E family, be sure to include a variety of foods found here: Nuts & seeds as sources of alpha & gamma tocopherols .
In addition to these foods, if you opt for a vitamin E supplement, be sure to get a good quality one that has all 8 forms such as Total E by AOR Canada. For a fuller discussion on this topic, check out my post on tocotrienols which make up 4 of the 8 different forms of vitamin E.
Adequate selenium intake is essential for a proper immune response because this trace mineral is required for the optimal function of several selenium-dependent enzymes (protein-based co-factors) known as selenoproteins (70). Selenium deficiency impairs several aspects of innate and adaptive immunity (71, 72), adversely affecting both humoral immunity (i.e., antibody production) and cell-mediated immunity (73).
Selenium has been studied for its anti-viral and anti-bacterial properties with a variety of pathogens such as Coxsackie and influenza viruses, as well as HIV (74). It has also been looked at as an adjuvant therapy to enhance the response to vaccines including poliovirus, influenza A, and hepatitis C (75, 76).
Selenium deficiency also appears to enhance the virulence (the capacity of a pathogen to overcome your body’s defenses) and/or the progression of some viral infections (77, 78, 79). Selenium affects different types of immune responses in different ways (80). For example, selenium supplementation improves cell-mediated immunity in deficient individuals and enhances the immune response to viruses (80, 81).
A considerable amount of basic research also indicates that selenium plays a role in regulating the production of cytokines (immune-related proteins) and eicosanoids (molecules involved in cell to cell communications) that orchestrate the immune response (82, 83).
Zinc is critical for the normal development and function of cells that mediate both innate and adaptive immunity (84). Because zinc is not stored in the body, regular dietary intake of foods high in zinc is important to maintain zinc concentration in your cells and tissues and in maintaining the integrity of the immune system. Therefore a chronic inadequate intake can lead to zinc deficiency and compromised immune responses (Ref).
With respect to innate immunity, zinc deficiency impairs the complement system (a collection of serum proteins that function to help destroy invading microorganisms), cytotoxicity (toxin inducing properties) of natural killer cells, phagocytic activity of white blood cells (where immune cells literally engulf pathogens and destroy them), and immune cells’ ability to generate oxidants that kill invading pathogens (85, 86, 87).
Zinc is hugely important to help prevent and reverse many of the features of an aging immune system routinely seen in older adults (88). Zinc deficiency also compromises adaptive immune function, including lymphocyte number and function (89). T lymphocytes (T cells) are particularly vulnerable to zinc deficiency (90).
Even marginal zinc deficiency, which is more common than severe zinc deficiency, can suppress aspects of immunity (ref). The elderly may be particularly at risk for marginal zinc deficiency given that there is a high prevalence of inadequate dietary zinc intake among those 60 years of age and older (91, 92), use of medications that increase the risk for zinc deficiency and because of concentrations of zinc in the blood declines with age (93, 94).
It’s not known why plasma zinc declines, but impaired absorption, alterations in cellular uptake, and epigenetic dysregulation may be contributing factors (95). Several randomized controlled trials demonstrate that supplementation with low to moderate doses of zinc (ranging from 10 to 45 mg zinc/day) in healthy elderly individuals improves several aspects of immune function and reduced the incidence of infections (96, 97, 98, 99, 100, 101).
Linus Pauling Institute’s Immune Nutrition Recommendations
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Your immune system protects your body against infection and disease.
It is a complex and integrated system of cells, tissues, and organs that has specialized roles in defending against foreign substances and pathogenic microorganisms, including bacteria, viruses, and fungi.
Your immune system needs to be fed and nourished like any other tissue or organ. What you eat and drink DOES impact both the structure and function of your immunity. When your intake of nutrients is poor (suboptimal), immunity suffers.
Not enough credit is given to nutrition when it comes to fighting infections. Many think that unless you’re severely malnourished, like those living in poverty, with addictions, who are homeless or maybe isolated elderly adults living on ‘tea and toast’, then nutrition doesn’t really matter.
Nothing could be further from the truth. Even marginal nutrient deficiencies can result in a sluggish immune response, not the least of which when it comes to fighting viral infections.
Sadly, the COVID-19 discussion has only focused on reducing the risk of infection and infection spread. While important, this does nothing to help people put themselves in the best possible position to fight off any infection they may encounter. Thankfully, 98%+ of those who become infected, survive but not necessarily without complications.
Here is where good nutrition and having a robust immune system is important. If you feel that all you can do is sit tight and wait for treatment or a vaccine, you’re missing out.
This post focused on key vitamins and minerals that are needed for immunity but there’s a lot more where nutrition, physical health, and COVID are concerned.
In Part 2 I’ll be reviewing the impact of being sedentary, overweight, obese, having insulin resistance/pre-diabetes/diabetes has on SARS-CoV-2 complications, as well as, look at other supplements of interest that are being studied for their role on COVID management such as N-acetyl-cysteine (NAC), glutathione, and potentially anti virus supplements.