Supporting the immune system with supplements often includes stimulatory herbs such as echinacea, andrographis, and elderberry. And these herbs are often coupled with high-dose foundational nutrients like vitamin A, vitamin D and zinc. While these combinations are well-established, they are safest and most effective when used for short-term durations. And some patients, such as those with autoimmune conditions or who are pregnant, cannot safely take them at all. 

In this article, we focus on five well-known nutrients that provide a novel approach to safe and effective long-term immune support for everyone. By looking beyond the “famous face” of each of these nutrients, we can appreciate additional immune benefits that are further enhanced with synergistic co-administration.

Can Nutrient Status Predict Immune Readiness?

The short answer? Yes. 

But how do you know if your nutrient reserves are sufficient?

It’s not always possible to measure nutrient status directly. But vitamin D and zinc are two nutrients that can be easily measured in serum and may provide meaningful insight to immune readiness, especially where respiratory health is concerned.

Mounting research shows that low levels of vitamin D are associated with incidence and severity of COVID-19 cases. While additional findings clearly indicate that a significant number of COVID-19 patients are zinc-deficient, and that zinc-deficient patients develop a greater number of complications and are more likely to have prolonged hospital stays and increased mortality. 

But it is important to note that during active infection or inflammatory responses, nutrient behavior shifts to support the body’s immune response. And that can have important implications regarding your ability to predict immune readiness as a clinician. Here are some important aspects to keep in mind regarding nutrient assessment:

Predicting Immune Readiness via Direct Testing

  • Vitamin D is converted to its active form (1,25-OH D3) at a faster rate so testing should focus on assessing vitamin D reserves (25-OH D).
  • Zinc is redistributed to the tissues resulting in decreased serum levels (hypozincemia).

Predicting Immune Readiness via Functional Testing

  • Vitamin C is difficult to monitor directly because it degrades too rapidly to be measured accurately following collection. But insufficient levels contribute to elevated 8-hydroxy-2’-deoxyguanosine (8-OHdG), the biomarker of choice for assessing oxidative stress.

Predicting Immune Readiness via Clinical Assessment

  • While direct measurement and functional lab markers can provide valuable insights into understanding a patient’s immune balance, it is the prevention of recurrent upper respiratory tract infections that is considered the most practical clinical endpoint for assessing immune health.
5 Necessary Nutrients to Safely Engineer Immune Readiness


Quercetin is best known as a bioflavonoid antioxidant, capable of scavenging free radicals. But research also shows that quercetin exhibits antiviral activity in a dose-dependent manner. More specifically, pre-treatment with quercetin may be especially helpful to inhibit entry, replication, and overall virulence of respiratory viruses. Plus, methylated quercetin metabolites help stimulate nasal epithelial cell ciliary beat frequency–the wavelike motion of respiratory cilia that move mucus and waste products out of the respiratory tract.

Vitamin C

Vitamin C is an essential vitamin necessary for the correct functioning of the immune system. And supplementation has been shown to be beneficial against many types of viral infections, from mild to severe. In fact, viral infections are associated with concomitant increased metabolism and decreased circulating levels of ascorbate, depending on their severity. This is perhaps in part because vitamin C is concentrated by macrophages where it is used to increase chemotaxis and phagocytic activity of macrophages, as well as other the granulocytes (basophils, eosinophils, neutrophils, mast cells).

N-acetyl cysteine (NAC)

NAC improves mucus clearance from the body by breaking disulfide bonds, making mucus more slippery and easy to expel. Even more importantly, NAC is the primary precursor and rate-limiting step in the formation of glutathione, the body's most powerful antioxidant. Glutathione plays a critical role in phase II detoxification. More specifically, glutathione conjugates oxidized intermediary metabolites, creating safer compounds that are easier to eliminate from the body.

Vitamin D

Vitamin D exerts wide-ranging influence on our overall health and wellbeing. But it does play a unique role in healthy respiratory and immune function. Vitamin D strengthens barrier tissue integrity by supporting healthy tight junctions between cells. And it also plays a unique role in modulating innate and adaptive immunity via antimicrobial peptides (AMPs). Vitamin D-induced AMPs not only increase the conversion of vitamin D into its active form (1,25-OH D3), but they also have antiviral properties that can shift the immune response from Th1 to Th2 and suppress immune over-reactivity preventing cytokine storm, also called cytokine release syndrome.


Zinc is essential for maintaining immune system integrity. But mild zinc deficiency, often characterized as suboptimal zinc status, goes unnoticed in most people because it is difficult to identify clinically. However, zinc deficiency results in decreased levels and dysfunction of all immune cells leading to an increased risk in developing infectious diseases and autoimmune conditions, among others. Of particular interest to immune and respiratory health, zinc plays an important role in clearing mucus from the respiratory tract, strengthening barrier tissue integrity thereby preventing pathogen entry into cells, and inhibiting viral replication.

COVID-19 Clinical Pearls: Why Combination Therapy May Be Better Than Solo-Nutrient Support

In functional medicine, natural therapeutic agents are designed to work in concert with one another for enhanced patient benefit. And it just so happens that the five nutrients we highlight here have a synergistic effect on the immune system when used together.

Quercetin + Vitamin C

Quercetin and vitamin C are a powerful duo when it comes to safely enhancing immune protection in the body. Research shows a uniquely synergistic relationship when administered together with improved anti-viral and immunomodulatory activity against multiple coronaviruses. Vitamin C further benefits quercetin’s immune enhancing properties by recycling quercetin back to its reduced form thereby increasing its antioxidant and antiviral effect in the body.

Vitamin C + Zinc

Vitamin C and zinc have not been shown to significantly shorten the duration of COVID-19 symptoms, but they do clearly shift symptomatology towards milder clinical cases. While milder cases clearly decrease patient burden and improve long-term outcomes, they also preserve medical resources for those patients with more severe disease and greatest need.

Vitamin D + Zinc

Vitamin D and zinc are used throughout the body in numerous ways and repleting these nutrients creates strong immune reserves. Not only do vitamin D and zinc coordinate anti-viral activities especially effective during active viral respiratory infections, but, as discussed above, they also have the distinct ability to predict the severity of COVID-19 clinical outcomes. Healthy reserves of these two nutrients are clearly associated with milder COVID-19 clinical presentations.

The Bottom Line

As a parting clinical pearl, keep in mind that these five nutrients provide safe and effective immune support in three essential ways: strengthening the epithelial barrier integrity, activating natural killer cell activity, and supporting the maturation of B cells and T cells, which are required for healthy antibody production and memory T-cell development. While all patients need every day immune support during this global pandemic, it is absolutely essential that we have safe and effective, long-term support available to those who are pregnant, nursing, or have autoimmune conditions.



Dr. Katrina Wilhelm is a board-certified naturopathic physician with a passion for functional medicine. With over fifteen years of clinical and industry experience, she has worked with patients and providers alike, educating them on the role that dietary supplements and personalized lifestyle medicine play in creating optimal health.