Why You Should Prescribe These 6 Immune Boosting Supplements
Why You Should Prescribe These 6 Immune Boosting Supplements
by Krista Russ
More providers and physicians are beginning to note the importance of an integrative medical approach when it comes to treating patients. As we know, chronic disease is on the rise. Many of our solutions to treating them are reactive and fail to address the root causes. This is particularly true of chronic metabolic diseases like dyslipidemia, insulin resistance, and hypertension, autoimmune diseases like M.S and lupus, and degenerative diseases like arthritis and dementia.
Our typical approach to treating all of these diseases circles almost entirely around symptom management rather than identifying and addressing causative factors. Hypertensives are given water pills and blood pressure pills; diabetics, insulin; people with dyslipidemia, statins. Oftentimes, the side effects are worse than the conditions they treat or even increase the risk of another unwanted health condition.
In actuality, a great majority of chronic diseases, especially those that characterize our current epidemic of metabolic syndrome have very similar underlying causes: namely overconsumption of highly processed, nutrient-depleted foods and sedentary lifestyle. Unfortunately, the consequences for such ailments are not merely in the future; they are right now.
And as we now know, metabolic syndrome and its related ailments (heart disease, type two diabetes, obesity, NAFLD, PCOS, etc.) are strongly associated with worse health outcomes when it comes to handling acute infection. This became perhaps most evident at the height of the COVID-19 pandemic, when such patients experienced disproportionately higher numbers of severe health complications like ARDS and deaths (according to a 2020 review ). The authors stated “Elevated risk of severe presentations of COVID-19 has been strongly associated with patients with cardiovascular disease, diabetes, hypertension, and who are overweight or obese.”
This is alarming, and calls to the importance of a different approach when it comes to treating chronic disease. While medication can be part of the picture, it can’t be the whole picture anymore. If it was, we wouldn’t have this epidemic of metabolic syndrome and surging rates of type two diabetes. If medication alone was the answer, it doesn’t explain why so many people who were treated for metabolic syndrome were still dying at much higher rates of COVID-19 and still are. So what can we, as providers, do differently?
It starts with embracing a more integrative approach–that is, focusing on a collective approach that involves diet, exercise, supplementation, sleep, mental health, and when needed, medication to treat and prevent disease rather than medication as a standalone. When patients take this approach, the results often speak for themselves. For example, when pre-diabetics were divided into groups–one who lost 5-7% of their body weight and exercised 150 minutes per week, they reduced their risk of developing type two diabetes by a whopping 58%. But pre-diabetics who took metformin alone only reduced their risk by 31% (via The American Diabetes Association).
In this blog, we will address the importance of prescribing supplements to help your patients boost their immune systems. As you will soon learn, the immune system is at the seat of both acute and chronic illness. The key to preventing serious health consequences in your most vulnerable patients (those with metabolic syndrome) who could become seriously ill if they were to contract COVID-19 this winter is to fortify their immune systems. Overall, our goal is to dispel the myth that supplements are merely “alternative” and convey what powerful, evidence-based research has to teach about these supplements and how they can help your patients.
The Immune System: A Deep Dive
Before we can get into the evidence supporting six, immune-boosting supplements, a brief refresher on the immune system is helpful.
When we think of the immune system, short-lived ailments like the common cold or flu immediately come to mind, but remember that the immune system plays a far more extensive role in our health. Most autoimmune diseases such as M.S, rheumatoid arthritis, and possibly fibromyalgia are linked to errors in the immune system. Almost all chronic diseases such as heart disease, diabetes, fatty liver, and cancer are influenced at least in part by the immune system because of the underlying inflammatory response.
Where The Immune System “Lives”
As you might recall from medical school, unlike other systems of the body that are confined to a specific area, the immune system is everywhere. Every cell of the body has the ability to detect “self” from “non-self.” When “non-self” is detected either purposefully or inadvertently, the body activates the immune response regardless.
Still, there are some organs that are especially associated with immunity such as the thymus, tonsils, and spleen because they contain lymphoid tissue. Even the humble appendix, once thought to be entirely vestigial, is abundant in lymphoid tissue. As a result, people with intact appendixes are significantly less likely to contract clostridium difficile, a serious diarrheal disease (per a 2013 study).
Actually, the whole gut plays a pivotal role in the immune system because most of the body’s lymphoid tissue is found there. This so-called gut-associated lymphoid tissue or GALT comprises several different types of immune cells such as macrophages, lymphocytes T and B, dendritic cells, and more (per Pediatric Gastrointestinal and Liver Disease 6th ed.). The GALT is found in what you might be familiar with as “Peyer’s Patches”, but it also includes lymphoid tissues outside of the membranes lining the small intestine like the tonsils, appendix, and colonic patches (per Healthline and a 2015 paper).
The fact that much of our immune system subsides in our gut should ring alarm bells when there is a problem with the immune system. Many substances can easily damage this tissue (alcohol, antibiotics, chronic use of NSAIDs, chemotherapy drugs, food allergies, etc.) leading to a condition called increased intestinal permeability or intestinal hyperpermeability, which has led many researchers to speculate there is a link between autoimmune conditions and the gut (via Cleveland Clinic).
An impaired intestinal barrier may allow toxins to enter the bloodstream such as bacteria or undigested food particles, triggering an inflammatory immune reaction. Indeed, many diseases are associated with increased permeability of the gut lining such as autoimmune disorders like IBD and celiac disease. Some researchers speculate that even seemingly non-related issues could be a product of intestinal hyperpermeability such as arthritis, asthma, chronic fatigue, eczema, and fibromyalgia (via Cleveland Clinic). We will discuss ways to help your patients repair their gut barrier in future content, which could play a key role in autoimmune and inflammatory diseases.
Inflammation and Chronic Disease
Besides gut health, recall that inflammation plays a pivotal function in the immune system. In most acute situations, inflammation is not “bad.” In fact, it’s essential to the disease-fighting and healing process. The problem lies when inflammation becomes chronic because too much inflammation retards the healing process and damages tissues. We see this in diseases like steatohepatitis. And inflammation doesn’t have to be obvious to cause serious problems.
Many diseases are now being linked to “low grade” inflammation, a subtler type of inflammation that can manifest over many years or even decades before it turns into actual disease. Obesity is a prime example of this, as obese people show higher levels of inflammatory proteins in their blood such as C-reactive protein (CRP). And obesity is just one example. A surprising number of ailments are associated with inflammation such as Alzheimer’s, Parkinsons, depression, and women’s health issues like PCOS and endometriosis, according to The University of Queensland. Even cancer is associated with inflammation as it helps tumors spread and grow. And these are not by definition the “inflammatory diseases” that most providers tend to think of–yet inflammation almost always underlies their pathology.
Taming inflammation is vital for the long-term health of your patients. Part of that equation includes minimizing harmful risk factors like smoking, drinking to excess, a high sugar diet, processed food, exposure to pesticides, and sedentary lifestyle. But because the body’s detox systems are already overburdened with the constant onslaught of pollutants, plastics, pesticides, and heavy metals in our environment and so many of your patients have metabolic syndrome, even these steps may not be enough to ward off chronic inflammation. That is where immune-modulating supplementation comes into play. It tackles two birds with one stone: boosting the immune system during these perilous times where COVID-19, RSV, and influenza are ever-present threats to our humanity and protecting against the chronic inflammation that can weaken the immune system, greatly elevating the risk for chronic disease in your patients over time.
Six Immune Boosting Supplements & What The Clinical Literature Shows Us
Vitamin C
As a provider, you’re probably familiar with the general role Vitamin C aka ascorbic acid plays in health. You know that it’s a water-soluble vitamin and antioxidant that prevents scurvy, but it’s unlikely you have learned much about its role in promoting immunity. There is much evidence to support its role in immunity, however. According to a 2017 paper out of the journal Nutrients, in addition to being an electron donor (antioxidant), it acts as a cofactor for several gene regulating enzymes. It supports both the innate and adaptive immune system. For example, its role of maintaining epithelial integrity is important for the prevention of pathogens breaching this invaluable barrier.
Vitamin C is abundant in phagocytes like neutrophils and enhances several immune processes like chemotaxis, phagocytosis, and the growth and differentiation of lymphocytes. It is vital for the clearance of used neutrophils by macrophages to prevent further tissue damage and necrosis once an infection is resolved. Vitamin C supplementation helps to prevent and accelerate the treatment of both respiratory and systemic infections. In fact, in order to prevent infection, at least 100-200 mg of vitamin C per day are required for optimal tissue levels and plasma saturation, but higher levels are required for the treatment of established infections. This is because acute infections deplete Vitamin C stores, likely because of increases in metabolic demands and increased turnover (via Vitamin C and Immunity). But Vitamin C’s importance in serving the immune system extends far beyond acute infectious disease.
It’s also important to note that poor dietary intake should not be the only cause for suspecting inadequate vitamin C status in your patients. Malnutrition, malabsorptive disorders like Crohn’s or Celiac, and various chemical dependencies (i.e- alcohol abuse) can also induce Vitamin C deficiency, and suspicion should be further raised in these patient demographics.
Zinc
The mineral zinc is well-known for its role in both wound healing and immunity, but few providers understand the astounding biochemical mechanisms that zinc supports in immunity beyond its role in serving as a cofactor to various enzymes. According to a 2017 paper out of the journal Nutrients, zinc has only been recognized as a required nutrient in humans since the 1960s. But since that time, it has become evident that zinc is crucial to supporting the immune system. In addition to possessing both anti-inflammatory and antioxidant properties, zinc ions regulate many intracellular signaling pathways that control the innate and adaptive immune system.
Because of its role in important immunological processes such as the inflammatory response and controlling oxidation, many diseases like RA, diabetes, atherosclerosis, and age-induced macular degeneration may be related to insufficient zinc consumption.
How Zinc Works (via How Zinc Helps You Fight Off Infections):
- Regulates thymus and bone marrow which make lymphocytes T and B cells.
- Plays a role in the innate (non-specific immune) immune system by making skin and other barriers more resistant to infection. It also regulates the immune cells in this location such as dendritic and mast cells.
- Controls the activity of various immune cells in the blood such as monocytes and neutrophils.
- Forms a component of proteins used by macrophages to destroy pathogens.
- Important for the adaptive immune system so that prior threats are recognized.
Like Vitamin C, this makes zinc important for not only the prevention of acute infection but potentially for the prevention of chronic diseases. Furthermore, certain populations such as the elderly, vegetarians and vegans, and patients with renal failure or chronic diarrhea are at greater risk for deficiency.
Vitamin D
While you were probably only taught that Vitamin D is needed for the absorption of calcium into bones and preventing rickets and osteomalacia, research now shows us that Vitamin D plays a key role in immunity. For instance, every 10 nM/L increase in blood Vitamin D levels reduces the risk of respiratory infections by an impressive 7% (per SOLIUS). Furthermore, a systematic review of 25 randomized and controlled trials concluded that Vitamin D supplementation greatly reduces the risk of respiratory tract infections.
Vitamin D also appears to play a role in autoimmunity. Several autoimmune diseases are associated with low Vitamin D status. For instance, adequate sunlight exposure and a Vitamin D-rich diet is associated with a lower risk for MS (per Mayo Clinic). Vitamin D has even shown to reduce Type One Diabetes progression in newly diagnosed children by enhancing clinical remission following initiation of insulin therapy (per UMass Chan Medical School). The surviving beta cells are more adequately protected with high Vitamin D status leading to lower doses of insulin being needed in the years to come and fewer serious diabetes-related complications later in life as a result.
The key takeaway is that beyond its role in maintaining bone health, Vitamin D modulates the immune and inflammatory response (per a 2014 study). For instance, it inhibits proinflammatory cytokines which is critical to the progression of all inflammatory diseases. This is also why most chronic inflammatory diseases like asthma, arthritis, nonalcoholic fatty liver, and lupus are associated with low vitamin D levels.
There has been much debate over the ideal dosage of Vitamin D. This is because the amount of Vitamin D needed to prevent acute deficiency is thought to be far less than the amount needed for ideal health by many experts. Furthermore, although 15 minutes of direct sunlight exposure to the bare skin (arms, face, etc.) can produce most of the vitamin D needed in a day for lighter complected people, this is not the case for people of color who have a higher melanin content in their skin. And with many people living in the northern hemisphere and spending much of the year covered up, with clouds blocking out much of the sunlight anyway, it is no wonder that nearly half of all Americans are Vitamin D deficient (via UT Health Houston). Fortunately, we will detail what recent research supports for optimal vitamin D dosage in The Six Key Supplements for Immunity.
Melatonin
You know that melatonin is the hormone that controls circadian rhythms and promotes sleep, but you probably didn’t know it could also boost your patients’ immune systems. Now, overwhelming evidence supports that it can.
According to a 2005 paper “Melatonin enhances both innate and cellular immunity. It stimulates the production of progenitor cells of granulocytes and macrophages and of NK cells. Production of IL-2, IL-6 and IL-12 is stimulated by melatonin. Increased T-helper production, particularly of CD4+ cells, occurs after melatonin supplementation.”
Melatonin also exhibits anti-inflammatory effects, such as reducing tissue destruction during inflammatory immune reactions (per a 2009 review). Its antioxidant role as a free radical scavenger has potential to reduce damage in all cells.
What more? According to the article Melatonin is for More than Just Sleep by Dr. Terri Deneui, leukocytes contain melatonin-specific receptors and enzymes needed for the synthesis of melatonin. And mitochondria, which produce most of the cell-damaging reactive oxygen species in the body, contain some of the highest concentrations of melatonin. Mitochondrial membranes also have special transporters that allow for rapid uptake of melatonin. The purpose? Increase melatonin’s ability to destroy free radicals where they are most needed and aid in the prevention of both acute and chronic diseases. Melatonin also triggers the growth of T-cells and enhances phagocytosis.
Numerous studies demonstrate that through its protective antioxidant effects, it helps prevent chronic inflammation. For example, it inhibits NLRP-3 inflammasomes, which are proteins that contribute to inflammation in the lungs–the same inflammation linked to the acute respiratory stress seen in some COVID-19 patients. These inflammasomes proteins can also wreak havoc in other disease states, contributing to much of the demise seen in diseases like meningitis, Parkinson’s, ischemic stroke, cerebral hemorrhage, and other types of brain damage.
Furthermore, because of its antioxidant properties, melatonin serves many protective roles beyond acute infection and may one day be used to treat diseases associated with oxidative stress such as:
- Cancers like leukemia, breast, and prostate
- Cardiovascular disease
- Diabetes
- Chronic obstructive pulmonary disease (COPD)
- HIV/AIDS
- Viral infections, including colds, influenza, and coronaviruses.
- Neurodegenerative disorders like Parkinson’s Disease, Alzheimer’s Disease, and ALS
Glutathione
By controlling levels of oxidative stress, glutathione may help reduce disease risk for conditions associated with it, which include many inflammatory conditions like diabetes, cancer, fatty liver disease, and rheumatoid arthritis.
Many autoimmune diseases cause chronic inflammation, linking the two. The added oxidative stress of autoimmune diseases can impair the function of the cells’ energy-production powerhouses–the mitochondria–but studies show glutathione can reduce oxidative stress by modulating the body’s immune response and protecting mitochondria from free radical damage. The fact is, very few diseases do not benefit from glutathione supplementation.
Glutathione is also required for the prevention of Acute Respiratory Distress Syndrome (ARDS) often seen in COVID-19 and other critically ill respiratory patients via multiple mechanisms according to the article Role of glutathione in immunity and inflammation in the lung out of the journal of Gene Medicine. This is because endogenous glutathione not only inhibits inflammation but is needed for the correct immune response to an infection, directing inflammatory neutrophils away from the lungs where they can induce ARDS and instead to the infection site to kill invading pathogens. Precisely, according to the 2011 article, “Glutathione regulates the balance between innate immunity or leukocyte infiltration at the site of infection to kill bacteria, and inflammation or leukocyte infiltration to the lung to cause organ failure.”
Without this critical balance in place, the immune system overreacts and starts damaging healthy tissues. And the importance of glutathione isn’t limited to ARDS or lung diseases either. Glutathione’s imperative role in the immune system likely plays a role in the increased susceptibility to infection in a multitude of other diseases such as AIDS, COPD, Cystic Fibrosis, influenza, and alcohol abuse. What do these seemingly unrelated illnesses have in common though? All deplete glutathione levels.
Because glutathione is poorly absorbed orally, sublingual, liposomal, or even intravenous forms are more effective since they either enhance digestive absorption or bypass the digestive tract altogether.
N-acetyl-cysteine (NAC)
With these six, evidence-supported supplements in your arsenal, your patients are sure to not only build stronger immune systems but to develop more resilience to chronic diseases as a whole.
But in order for your patients to gain the most benefit, you must know how to prescribe these supplements. You must understand which circumstances to use them for and what doses align best with those circumstances. Fortunately, we will describe what the literature shows on dosing for optimal health (as opposed to merely preventing nutritional deficiency) in The Six Key Supplements for Immunity
NAC is a precursor to glutathione. It is so effective at producing glutathione that a version of it (Acetylcysteine) is given in the emergency room to treat Tylenol overdose and its subsequent severe liver damage (per Guidelines for the Management of Acetaminophen Overdose). The primary benefit of NAC supplementation comes from its ability to upgrade endogenous glutathione production, which can help to bypass the problem of poor oral glutathione absorption. Although your patients can’t obtain NAC directly through diet, sulfur-rich foods like broccoli, garlic, and leeks can increase the body’s production of NAC.
NAC also aids the immune system directly. A 2020 review out of the journal Therapeutic Clinical Risk Management assessed multiple studies using NAC for elderly COVID-19 patients, noting limited vaccine protection against COVID-19 in elderly patients. The study aimed to look at alternative treatment modalities to help curb the associated multisystem organ dysfunction and mortality often seen in this patient demographic.
NAC was studied because it has been used in clinical practice for the treatment of critically ill or even septic patients. NAC’s documented antioxidant, anti-inflammatory, and immune-regulating effects are thought to aid in both the treatment and prevention of SARS-Cov-2. Thus, the review assessed NAC’s potential benefit to elderly, COVID-19 patients.
Amazingly, it was demonstrated that NAC could benefit such patients via numerous mechanisms. Here are just a few:
- In severe COVID-19 infections, lymphopenia is a common complication. NAC can block this process by increasing glutathione in T cells and blocking the apoptosis that viruses tend to upregulate, thus elevating glutathione levels in lymphocytes and preventing their destruction.
- Cytokine storm is strongly linked with mortality in COVID-19 patients. These cytokines produce excessive reactive oxygen species (ROS) that can injure healthy cells, but NAC acts as a powerful ROS scavenger, which could allow it to prevent both cytokine storm and its consequent pulmonary edema and lung failure.
- After 3 days of intravenous NAC treatment (40 mg/kg/day), 61 adult patients with mild to moderate lung damage experienced significant improvements in systemic oxygenation and reduced need for ventilatory support. The mortality rate was also slightly reduced, which begs the question how much could this be improved at even higher NAC doses?
- Another case report of a patient with H1N1 who was treated with NAC and oseltamivir from septic shock resulted in improved sepsis and eliminated their lung infiltrates.
What’s Next?
With these six, evidence-supported supplements in your arsenal, your patients are sure to not only build stronger immune systems but to develop more resilience to chronic diseases as a whole.
But in order for your patients to gain the most benefit, you must know how to prescribe these supplements. You must understand which circumstances to use them for and what doses align best with those circumstances. Fortunately, we will describe what the literature shows on dosing for optimal health (as opposed to merely preventing nutritional deficiency) in The Six Key Supplements for Immunity
The insight you will gain here is crucial to making the best use of these supplements in your practice. You will also learn more details like what forms are best for ideal absorption. As you know, certain medication forms are better absorbed than others for the same drug, and the same is true of supplements. This insight is indispensable for helping your patients and your practice.