By Chris D. Meletis, ND, and Kimberly Wilkes, BSc
If there is one thing we have learned from the 2020/2021 viral event, it’s that outcome largely comes down to susceptibility. Morbidity risk factors such as obesity, diabetes, poor heart health, and age all make a person more susceptible to negative consequences after exposure to a viral agent. Yet, other factors such as being under constant stress, low levels of critical nutrients, and lack of RESTorative sleep can also predispose to poor outcomes after viral exposure even if you don’t suffer from underlying conditions. Combine these latter factors with any of the underlying conditions mentioned above and the result may be particularly disastrous.
This article will discuss the factors patients must control in order to be less susceptible to upper respiratory tract infections. In addition, it will address dietary supplementation that can defend the respiratory tract and minimize the effects of immunity-impairing factors such as stress or lack of sleep.
Maximizing Melatonin Levels
Research is uncovering the surprising immune-supporting effects of the hormone melatonin. Some of these effects are likely due to its ability to induce a good-night’s sleep. However, it also has other properties, including powerful antioxidant and anti-inflammatory actions, that likely play a role. Melatonin levels decline with age, which may explain why older people are often more likely to have adverse consequences after viral exposure. However, melatonin levels are often low in many people, regardless of age. This hormone is produced by the pituitary gland when the body is exposed to darkness. Exposure to light at night, especially the blue light produced when we view devices like cell phones, tablets, and televisions, can deplete melatonin levels. Even a small amount of light seeping in through gaps in window blinds or through spaces around bedroom doors can affect melatonin levels.
Melatonin protects against the acute lung injury and acute respiratory distress syndrome that can occur after exposure to respiratory viruses. Research in mice exposed to respiratory syncytial virus (RSV) found that melatonin protected against the RSV-induced inflammatory lung damage.1 Melatonin suppressed oxidative stress and the production of pro-inflammatory cytokines in the mice exposed to RSV.
Getting Enough Quality Sleep
One of the most important factors in decreasing susceptibility to respiratory infections is making sure you get enough RESTorative sleep.2,3 This is related in part to melatonin levels, as low concentrations of this hormone can impair sleep, as well as impact immunity. However, lack of sleep also directly impairs immune cells.3 In addition, not getting enough sleep is associated with an increased risk of contracting the common cold.3
One of the most important factors impacting sleep is obstructive sleep apnea. This condition not only impairs sleep and therefore directly impacts immunity, but it also weakens lung function by compromising oxygen delivery. Sleep apnea is characterized by periods of interrupted breathing while you sleep. It occurs when throat muscles relax during sleep and block the airway. Risk factors include obesity and diabetes, but you don’t have to have either of those conditions to develop the disorder. In fact, a number of Dr. Meletis’ sleep apnea patients have been a normal weight.
Obstructive sleep apnea (OSA) has been linked to reduced immunity in patients who also have chronic rhinosinusitis with nasal polyps.4 In addition, OSA causes or exacerbates cardiovascular disease and metabolic syndrome, two underlying conditions that can predispose to worse outcomes after viral exposure.4 Furthermore, lower levels of oxygen such as those that occur in sleep apnea patients lead to high CO2 in the blood, which may increase blood acidity and a greater propensity toward illness. In fact, any chronic illness that compromises oxygen delivery and overall functioning of the lungs will leave your respiratory tract susceptible to viral infection and subsequent damage.
To read more about the importance of oxygen in your health, download Dr. Meletis’ free book about oxygen at www.GodsHealthCare.com.
Making Certain the Body Is Well Nourished
Your nutrient status plays an important role in whether you contract a virus, how aggressively it flourishes in your body, and how fast you get rid of it and get on the mend. Deficiencies in nutrients can lead to epigenetic alterations. Epigenetics are changes in gene expression that occur independently of the genetic code. Instead, they’re caused by external factors that act like switches to turn your genes on and off. Epigenetics are actually the most controllable factor we have at our disposal to create a healthy immune system. Dr. Meletis always like to say that genetics load the gun but lifestyle pulls the trigger.
Certain nutrients are especially critical for respiratory health. These include zinc and vitamins D, C, and A. Immune cells are dependent upon zinc for their development and maintenance.5 This is one of the reasons zinc has been shown to play an important role in supporting immunity. For example, elderly people who are deficient in zinc have an increased risk of pneumonia.6,7 Zinc also reduces the duration of the common cold.8,9
Furthermore, there has been a lot of interest lately in zinc ionophores, which are substances that improve cells’ ability to uptake zinc. The best known ionophore is the antimalarial drug hydroxychloroquine, which suppressed the cellular replication of a number of RNA viruses in cell culture.10 When given to human patients together with zinc and an antibacterial drug, hydroxychloroquine led to more frequent hospital discharges, lower mortality, and a reduced risk of being transferred to hospice.11 Many functional medicine providers recently have employed quercetin as a zinc ionophore in lieu of the chloroquine due to preference or regulatory access to the prescription.
Vitamin D is another nutrient important for upper respiratory function. A systematic review and meta-analysis looked at 25 randomized controlled trials involving a total of 11,321 participants who were given vitamin D or a placebo.12 The review concluded that in all the participants given vitamin D as either a daily or weekly supplement, there was a lower likelihood of developing acute respiratory tract infections. Subjects with vitamin D deficiency (baseline 25-hydroxyvitamin D levels of < 25 nmol/L) experienced the strongest benefits. Vitamin D may reduce the risk of cytokine storms and acute respiratory syndrome and inhibits the renin-angiotensin system, which has been implicated in adverse effects of certain viral infections.13,14
Vitamin C is especially well-known for its ability to support upper respiratory health. It shortens the duration of respiratory tract infections.15 A systematic review of the medical literature also found that vitamin C reduced the incidence of the common cold in subjects who were undergoing physical stress, which is known to impair immunity.16 In five small trials of people under heavy physical exertion, vitamin C was associated with a statistically significant 45% to 91% reduction in incidence of the common cold. Three other studies included in the review determined that vitamin C supplementation led to a statistically significant 80% to 100% decline in the incidence of pneumonia.
Vitamin A is another vitamin that plays an important role in immune function. Cell culture studies and animal models indicate vitamin A is involved in the function of immune cells such as neutrophils, natural killer cells, monocytes, and T and B lymphocytes.17 In clinical trials, vitamin A supplementation lowered morbidity and mortality in some infectious diseases, including measles and measles-related pneumonia, human immunodeficiency virus infection, and malaria.17
Vitamin K is an important nutrient in patients with viral infections that are associated with excessive coagulation and formation of blood clots.18 Low vitamin K levels are associated with worse outcomes in these patients.18 Vitamin K’s protective effect includes the activation of matrix Gla protein (MGP), which protects against lung and vascular damage.18
The importance of nutrients in respiratory health is demonstrated by the fact that people with chronic obstructive pulmonary disease (COPD) who are malnourished are more likely to have
sarcopenia, weight loss, worse pulmonary function, decreased exercise capacity, and increased risk of exacerbations.19
Controlling Weight
We live in a world where people are overfed and undernourished. The over-dependence on a Westernized diet that includes processed food, sugar, and unhealthy fats and that is deficient in fruit and vegetables, leads to obesity and weight gain. The buildup of fat around intra-abdominal tissues can stop the lungs from fully expanding, leading to weakened respiratory function.20 Obese people have a higher rate of infections and infection-related mortality compared to normal weight people.21 Additionally, some obese children have alterations in cell-mediated immune and neutrophil functions.21 Obese subjects who went on a diet and took multivitamins had a pronounced improvement in immune function, including enhanced antibacterial activity of monocytes and natural killer cell function, as well as a significant rise in antibodies, including immunoglobulin G (IgG), IgA, and IgM.22
Gut Microbiota
Bacterial infections are common complications of respiratory viruses. An imbalance of the gut microbiota (known as dysbiosis) during an influenza A infection may lead to increased susceptibility to respiratory bacterial infections.23 Dysbiosis of the gut microbiota can be caused by a variety of factors, including eating a diet high in sugars and fats, taking antibiotics or consuming food treated with antibiotics, and mental stress. Research has shown a decrease in beneficial bacteria like Lactobacilli and Bifidobacteria and an increase in pathogenic bacteria in patients with a viral infection.24 Gut dysbiosis is associated with a greater incidence of cytokine storm and disease severity.24 On the other hand, probiotics can inhibit the ACE2 receptor on cells, potentially stopping viruses from entering the body through that receptor.24,25 Probiotics also had anti-viral actions and assisted with the elimination of viruses in mouse models of influenza and respiratory syncytial virus infections.26,27 In humans, a study of 30 healthy elderly patients found that administration of the probiotic Bifidobacterium lactis led to improved function of immune cells.28
Toxin Exposure
Environmental toxins can cause epigenetic modifications that adversely impact immunity.
One of the external epigenetic factors that we can’t completely control but we can at least minimize is exposure to environmental toxins. Exposure to bisphenol-A (BPA), a chemical found in the linings of some canned food, dental sealants, and cash register receipts, causes inflammation that leads to an increase in the susceptibility to infections.29 Additionally, exposure to air pollution can trigger excessive activation of the innate immune system along with lung inflammation and injury.30 This is likely why there is an association between living in areas with the highest levels of air pollution and higher mortality rates from certain viral infections.31 Furthermore, fine particulate matter from wildfire smoke (PM 2.5) leads to inflammation and lung injury and could increase the severity of certain viral diseases.32,33
Psychological Stress
Being under a lot of chronic stress can lead to reduced immune function. In a study of 89 women who had recently given birth, postpartum stress reduced the immunological benefits of breast milk in their infants.34 Mental stress is also thought to be the reason why some people do not develop sufficient antibodies after receiving an influenza vaccine.35 Furthermore, people who are under stress suffer from more severe upper respiratory tract infections. For example, in one study, 55 subjects were evaluated for their level of psychological stress.36 They were then infected with influenza A virus. Being under a lot of stress before being infected with the virus was linked to more symptoms, greater mucus weights, and production of the cytokine interleukin-6 (IL-6).
Additional Dietary Supplements That Enhance Respiratory Health
In addition to the dietary supplements mentioned earlier in this article—melatonin, probiotics, zinc and vitamins A, C, D, and K—a number of other supplements are often underutilized but yet extremely powerful in supporting healthy upper respiratory function.
Nicotinamide Riboside. Nicotinamide riboside (NR) is known for its ability to enhance mitochondrial health. Mitochondrial DNA (mtDNA) is involved in innate immunity,37 which serves as the initial attack against viruses and other pathogens. The release of mtDNA from the mitochondria triggers an immune response by helping cells recognize the DNA of invading pathogens and become more resistant to viruses.38,39 In fact, the influenza A viral protein PB1-F2, targets mitochondria, leading to mitochondrial fragmentation and weakened innate immunity.40
Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme and the primary electron donor in the mitochondrial respiratory chain. NAD+ supports the immune system and influences the activity of macrophages, immune cells that defend against pathogens.41 Increasing levels of NAD+ in macrophages that are aged or immune-compromised restored immune function.41 NAD+ is also critical for ATP production, which in turn is essential for a healthy immune system.42 Nicotinamide riboside enhances mitochondrial health by boosting levels of NAD+.43 In doing so, it not only supports healthy immunity but also protects against underlying conditions such as heart disease and diabetes.44-46
Nitric Oxide. Nitric Oxide (NO) is a gas naturally produced in the body that acts as a signaling molecule. NO is produced through the nitrate to nitrite to nitric oxide pathway after eating nitrate-rich vegetables. Replenishing nitric oxide levels can have beneficial effects on the immune system and support the health of people with underlying conditions. In cell culture research, NO inhibited viral replication and entry into the host cell.47,48 In patients with a viral infection, NO reduced severe hypoxia and decreased the number of patients who needed to be on ventilators.49
Studies have also shown that NO concentrations are significantly lower in patients with certain viral infections, which is thought to lead to vascular problems and inflammation in this group of people.50 Furthermore, eating a nitrate-rich diet may lead to a balanced gut microbiota and prevent gut dysbiosis and related immune dysfunction.51 Nitric oxide also has cardiovascular benefits that may be beneficial in people with underlying conditions.52 You can increase NO levels in the body by taking a nitrate-rich supplement that contains beetroot.
Cannabidiol. Cannabidiol (CBD) is a non-psychoactive component of Cannabis sativa. It can promote immune health in a number of ways. First, it has direct effects on immune health by working through the endocannabinoid system, which acts as a gatekeeper of immunity.53 Cells in the immune system express cannabinoid receptor 2 (CB2) and to a weaker extent cannabinoid receptor 1 (CB1).54 These receptors are part of the endocannabinoid system. However, CBD can also work through an expanded endocannabinoid system known as the endocannabinoidome, which includes other receptors such as transient receptor potential vanilloid 2 (TRPV2), a protein that plays a role in a healthy immune system.55 CBD can increase the activity of natural killer (NK) cells, which have powerful antiviral actions in the body.56 It also increases the activity of NK T-cells, which have immune-enhancing properties of both NK cells and T-cells.56
Furthermore, CBD can impact immune health by virtue of its effects on stress and sleep. It soothes stress as evidenced by several studies showing it can reduce anxiousness in people undergoing a simulated public speaking test.57-59 In addition, its calming effects can lead to better sleep.60,61 Another way in which CBD supports immune health is through its ability to reduce inflammation in the gut,62 which in turn suppresses gut dysbiosis. Additionally, animal studies indicate CBD decreases inflammation in the lungs.63-65
It can be advantageous to use CBD-rich hemp oils made with VESIsorb® technology, because this type of technology leads to faster and easier absorption of CBD.66 This type of CBD oil is made with a special self-emulsifying drug delivery system (SEDDS) that maximizes absorption.
N-Acetyl Cysteine. N-acetyl cysteine (NAC) is an antioxidant that decreases mucous production in the respiratory tract.67 It enhances immune health in a number of ways. It is a precursor to the antioxidant glutathione, which is low in people who suffer serious outcomes of viral infections.68 NAC works by both anti-inflammatory and antioxidant mechanisms.69 NAC can block the angiotensin-converting enzyme 2 (ACE2), inhibiting the ability of some viruses that use ACE2 receptors to enter cells.69 Researchers showed NAC’s powerful immune effects in a study of 1,200 mg/day of NAC or a placebo given to 262 elderly people.70 The study sought to determine NAC’s effects on the occurrence and severity of influenza A infections during the cold and flu season. Over six months, the participants taking the NAC supplements had fewer flu-like episodes and a pronounced reduction in symptoms and the severity of illness compared to the placebo group.
Conclusion
There is a great deal of interest these days in fortifying the respiratory tract and decreasing susceptibility to viral infections and serious adverse consequences. We have the ability to reduce the effects of various factors that impair immunity and make us more susceptible. These factors include low melatonin levels, lack of sleep and sleep apnea, making sure you’re getting enough critical nutrients, controlling your weight, balancing the gut microbiota, and reducing toxin exposure and stress. Certain dietary supplements are also highly beneficial in supporting respiratory tract health, including nicotinamide riboside, CBD, NAC, and nitrate-rich formulas that include beetroot. By fortifying your overall health, you’re more likely to thrive after being exposed to a viral threat.
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