Collection: IMMUNE, DETOX SUPPORT

Our immune health is inextricably tied to our overall health.  The ability to fight off a viral infection, for example, is not just a matter of having acquired serum antibodies to the viral pathogen.

Our defense begins with the innate immune system, which includes all outer and inner surfaces of our body (the skin and mucous membranes), and also scavenger white blood cells (aka phagocytes -- monocytes, neutrophils, dendritic cells, macrophages), signalling proteins (cytokines), and Natural Killer cells.

The innate immune system is fast acting and responds within minutes or hours to an infection or injury.  It responds in largely the same way, whatever the pathogen is, and has a relatively limited ability, but an ability nonetheless, to become trained by an exposure to a pathogen, so that it can to some extent 'remember' how to respond to the pathogen the next time that it encounters it.

If the innate immune system can't take care of the infection, then the adaptive, or acquired, immune system kicks in. 

The adaptive immune system can hone in more precisely on pathogens and can 'recall' in finer detail how to respond to a pathogen the next time it encounters it, via the production of acquired antibodies and memory-B and memory-T cells.  In the germinal centers of lymph nodes, acquired antibodies are tested against the invading pathogen, and only the ones with the highest binding affinity to epitopes (binding sites) on the pathogen are selected for replication.  But this training takes time, which is why the adaptive immune response to the first encounter of a pathogen takes days or weeks, rather than minutes or hours.

A robust innate immune response is the reason why most children are able to shrug off an infection by SARS-CoV-2 with mild, or no, symptoms.  Children haven't yet lived long enough for their innate immune system to have been degraded by a decline in overall health.

In particular, children have more innate, or natural, antibodies than adults do.  These are antibodies that are already present in tissues throughout the body, and do not require training by first exposure to a pathogen.  Natural antibodies can't bind as strongly to a specific pathogen as acquired antibodies to that pathogen do, because they haven't gone through the training against that pathogen that acquired antibodies undergo.  But they can bind to a broader range of pathogens than acquired antibodies do, precisely because of their lack of training against a specific pathogen.  And innate antibodies can react almost immediately upon the first exposure to a pathogen, whereas acquired antibodies need to undergo their training against it over days and weeks.

Is there anything that adults can do to make their immune system more robust and youthful?

The first thing is to improve our overall health, especially by correcting any insulin resistance that we may have.  Insulin resistance is the scourge of modernity and underlies the chronic diseases of modernity.  We can do this by exercising regularly; eating more fresh vegetables, fruits and healthy fats, including saturated fat; limiting consumption of refined carbohydrates; getting enough sleep; and thereby maintaining a healthy BMI.

There are also nutritional supplements that can boost our immune response and keep it in balance, so that inflammation, our body's initial response to injury or infection, does not get out of control.  The following are some of them:

Vitamins and minerals are essential to all aspects of human health, including immunological health, aiding in the ability to fight off infections by pathogens, clear toxins from the body, and to remain in immunological balance so that chronic inflammatory or autoimmune disorders do not develop.

The best way to obtain the vitamins and minerals necessary for proper immune functioning is through the diet:

• "The best method for obtaining the micronutrients required to improve immune system functions is through a proper diet, including the consumption of vegetables and fresh fruits [28]. For example, elderberries contain antioxidants and may help to reduce inflammation, whereas selenium and B vitamins are abundant in button mushrooms. Other foods with high selenium contents include sardines, garlic, broccoli, Brazil nuts, tuna, and barley. Zinc can be obtained from lean meats, wheat germ, oysters, crabs, poultry, chickpeas, yogurt, and baked beans, among other foods [29]. Heme is available from lean poultry and shellfish and represents the most readily absorbed source of iron. Other healthy sources of iron include broccoli, kale, and beans. Many vitamins that aid immunity can be found in foods or are added to foods, such as folic acid, which is added to several cereals, breads, pastas, and other whole grains. The natural form of folate is found in beans, peas, and green leafy vegetables [29,30]. Baked potatoes, lean chicken breast, chickpeas, cold-water fish, such as tuna, and bananas are all high in vitamin B₆. Green leafy vegetables, including spinach and kale, in addition to citrus fruits, contain vitamin C, which is also abundant in brussels sprouts, bell peppers, strawberries, and papaya [31]. Most people can obtain sufficient amounts of vitamin C without requiring supplements, as vitamin C–rich foods are easily accessible. Vitamin E is abundant in hazelnuts, peanuts, almonds, and sunflower seeds, in addition to spinach and broccoli. Choosing a range of colorful foods ensures the acquisition of sufficient dietary vitamin A amounts [3]."

However, food has become much less nutrient-dense over the past couple of generations, both because of the soil-depleted conditions under which source ingredients are grown, and the increased prevalence of highly processed foods in our diet. 

Thus it has become more difficult to rely on diet alone to support immune function, and we don't always eat as well as we should.

Quality multivitamins like Support Protocols Men's and Women's Multivitamin Softgels contain more than the US RDA of vitamin C, zinc and selenium, which are known as having immune-supporting properties. 

But vitamin C, zinc and selenium by themselves are not enough for healthy immune function:  all vitamins and many minerals play a key role too:  vitamin A, the B vitamins (B1, B2, B3, B5, B6, B7, B9, B12) vitamin C, vitamin D, vitamin E, vitamins K1 and K2, iron, iodine, magnesium, and copper.

Multivitamins are an insurance policy and safety net for the diet, to make sure that every day we are getting the micronutrients we need for peak immune performance.

In addition, the nutritional supplements below may also help maintain healthy immune system function by warding off bacterial, fungal and viral infection, aiding detoxification, and controlling inflammation.

The liver sits on the front-line of the immune system.  It detects, captures and clears pathogens and toxins from the blood, and can mount an immune response in seconds, defending the body while the adaptive immune system ramps up its response to pathogens over hours and days. 

• "The liver appears to be the most dominant organ with respect to infections...a patient with liver failure will die primarily of infections."

Keeping the liver healthy is critical to maintaining a properly functioning immune system and to controlling inflammation throughout the body.

Choline is an often overlooked, but essential, nutrient that must be obtained from the diet, and one that is involved in many critical functions in the human body: 

• Choline is the precursor for the neurotransmitter acetylcholine, which is essential for the proper functioning of the brain and both the somatic and autonomic nervous systems;
• Choline is also the precursor for the methyl-group donor betaine, and so is essential for the methylation and de-methylation reactions in the liver that regulate gene expression;
• Every cell membrane in the body requires choline.  In the liver, in particular, a deficiency of choline will cause triglycerides to accumulate in it, resulting in fatty liver disease and, if left uncorrected, cirrhosis.  In muscle cells, a deficiency of choline will cause damage and eventually cell death.

Although choline is an essential dietary nutrient, at least 75% of U.S. adults consume less than the Adequate Intake (AI) levels of 7.5 mg of choline per kg of body weight (the AI level is higher during pregnancy and lactation).  In those over the age of 71, only 4% of men and 2% of women are getting the recommended AI levels.  Note that the AI levels of choline are minimum levels that were set by the U.S. Institute of Medicine to avoid impaired liver function.  The AI levels are not optimal levels.

Glutathione is the body's 'master antioxidant' and detoxifying agent.  It is a tri-peptide (three amino acid) compound that is produced in the cytoplasm of every cell in the body, with a high concentration in the liver.  Although glutathione is made by the body, it is critical that our diet provide either glutathione precursors, or glutathione itself, in order to maintain adequate levels of glutathione.  Modern diets, because of the high prevalence of processed foods, provide only negligible amounts of glutathione.

Supplementing with N-acetyl cysteine (NAC) as a strategy to boost glutathione levels is common.  Glutathione, called the body's "master antioxidant:"

• Plays a critical role in the body's detoxification process;
• Has a central role in maintaining the function of both the innate immune system (e.g. Natural Killer cells) and the adaptive immune system (e.g. T cells);
• Relieves symptoms of respiratory conditions by reducing inflammation in lung tissue;
• Increases insulin sensitivity by reducing inflammation in fat cells and insulin receptors;
• Reduces the risk of cardiovascular disease by protecting against oxidative damage in heart tissue and by having a vasodilating effect;
• Boosts brain health by protecting against oxidative damage in brain tissue

Although NAC is commonly used because of its believed ability to boost glutathione levels, its ability to do that is not clear:

• "Three conditionally essential amino acids, glycine, cysteine, and glutamic acid combine to form glutathione in a two-step biochemical reaction.... Cysteine is frequently identified as rate-limiting, which provides the rationale of why N-acetylcysteine (NAC) is frequently studied and suggested as a supplement for glutathione support [50], yet a review of the data indicates its use may be inconclusive or equivocal.... Although NAC is promising as a supplement to both boost glutathione levels and potentially mitigate some of the issues related to oxidative stress [57,58], the research is not conclusive [59,60,61,62]"

Nevertheless, the reason that people supplement with glutathione precursors like NAC is because of glutathione's generally poor oral bioavailability. 

However, Kyowa Hakko, makers of the patented Setria form of oral glutathione, have shown in a clinical trial that Setria is able to survive the digestive system and to increase blood levels of glutathione. 

With the advent of Setria glutathione, it is possible to supplement glutathione levels directly, rather than having to rely on supplementation with NAC or other precursors to indirectly boost glutathione levels.

Vitamin D is among the most powerful of micronutrients, being involved in the cell signaling of nearly every system in the body, including the immune system.  For its active metabolite form in the body, calcitriol, it is more accurate to state that vitamin D is a hormone rather than a vitamin. 

The majority of immune cells have vitamin D receptors, reflecting the critical role that vitamin D plays in immune function:  vitamin D both strengthens the innate immune system to fight off infection by viruses and bacteria, and regulates the adaptive immune system to control inflammation and keep it from running amok.

In the current Covid-19 pandemic, "evidence of a link between low vitamin D levels and poor Covid-19 outcomes is robust, including numerous population and individual correlational studies, causal modeling, prospective cohort intervention studies, and randomized controlled trials." 

A deficiency in vitamin D leads to a decreased ability to fight off infection by the SARS-CoV-2 virus, and a greater propensity to the hyper-inflammatory and hyper-coagulability states (due to the cytokine and bradykinin storms and macrophage activation) in late-stage Covid-19 that results in severe disease and death.

Indeed, one systematic review and meta-analysis found that a Covid-19 mortality rate approaching zero could be achieved if the population's blood vitamin D3 level were raised to a minimum of 50 ng/mL:

• "Regression suggested a theoretical point of zero mortality at approximately 50 ng/mL D3. Conclusions: The datasets provide strong evidence that low D3 is a predictor rather than just a side effect of the infection. Despite ongoing vaccinations, we recommend raising serum 25(OH)D levels to above 50 ng/mL to prevent or mitigate new outbreaks due to escape mutations or decreasing antibody activity."

Magnesium:  Less well-known is magnesium's role in immune health:  it is involved in over 600 enzymatic reactions in the body, and is critical to heart, brain and musculoskeletal health.  It is difficult to get from the diet, and 60% or more of the population is estimated to be deficient in magnesium.  Magnesium modulates cellular reactions controlling inflammation and immune responses in the body -- a deficiency of magnesium will lead to increased inflammation and an over-reaction in immune responses.

Boron helps the body to use vitamin D; aids in the absorption of magnesium; works with both vitamin D and magnesium to reduce inflammation; raises levels of antioxidants such as glutathione; and aids in wound healing.  Boron deficiency has become widespread due to modern industrial agriculture, fertilizer use, and the depletion from topsoil of minerals essential to human health.

Vitamin D, magnesium and boron should be thought of as the three co-essential members of a nutritional triumvirate, and should be taken together.

The human species evolved together with certain probiotic microorganisms including Lactobacillus (L.), Bifidobacterium (B.), and Streptococcus (S.). 

Our modern diet has deprived these microorganisms residing in our gut of the nutrients they need to survive and to help calibrate our immune and metabolic functioning throughout life, and especially as we get older. 

Probiotics help maintain balance between pro-inflammatory and anti-inflammatory reactions in our gut and respiratory tract in response to both pathogens and harmless foreign substances.

In the Covid-19 pandemic, a paper published in April 2022 in BMJ found that decreased gut microbiome diversity, in particular a reduction of bifidobacterium and faecalibacterium strains, is associated with increased Covid-19 symptom severity:

"We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention [with probiotic supplements]."

Support Protocols Probiotics are a balanced spectrum of live organisms consisting of acid-resistant probiotic bacterial strains that are known to naturally colonize the human gastrointestinal tract, and are formulated to deliver a potency of at least 25 billion CFU through the Best By date.

The omega-3 fatty acids (FA) are an essential group of nutrients that must be obtained from the diet.  The liver can convert the omega-3 FA alpha-linolenic acid (ALA) -- found in seeds, nuts and vegetable oils -- into eicosapentaenoic acid (EPA), and from EPA into docosahexaenoic acid (DHA), but only very inefficiently. 

The best dietary sources of EPA and DHA are oily fish such as salmon, sardines and mackerel, or algae and plankton.  In the US and in many parts of the EU, however, the most prevalent dietary form of omega-3 FAs is ALA; DHA and EPA are consumed in insufficient amounts.

DHA and EPA have been and continue to be extensively studied for their ability to modulate inflammation. 

Inflammation is the innate immune system's first-line response to infection or injury, and is characterized by redness, heat, swelling and pain.  These are the result of white blood cells, in particular neutrophils, rushing to the site of injury or infection to do their job to defend the body against the injury or infection.

Omega-3 fatty acids, in particular EPA and DHA, are actively involved in the regulation of both the initiation and the resolution of inflammation. 

In the initiation phase, EPA and DHA can act in an anti-inflammatory role, by regulating pro- and anti-inflammatory signaling molecules (cytokines and chemokines), and by modulating gene activity involving nuclear factor-kappa B (NF-κB).

In the resolution, or healing, phase, it has been discovered in the past 20 years that EPA and DHA are precursors to the molecules actively involved with and necessary for the successful resolution of inflammation, known as Specialized Pro-resolving Mediators (SPM).  A number of these SPM have been identified:  resolvins, protectins and maresins.

These inflammation-resolving SPMs are relevant not only to acute infection and injury, but to many chronic diseases as well, because these have chronic inflammation as their underlying characteristic:  for example, cardiovascular diseases, metabolic syndrome, autoimmune diseases, and neuro-cognitive diseases.

Thus EPA and DHA may be beneficial both for recovering from acute infection or injury, and for healing many chronic conditions involving underlying unresolved inflammation.

Curcumin is the most prevalent active compound derived from the roots of the turmeric plant (curcuma longa), and is commonly used as a spice, food coloring and in ayurvedic medicine as a treatment for inflammatory diseases.  Curcumin has been shown in numerous studies to have potent anti-inflammatory and antioxidant properties: 

• It down-regulates several transcription factors, such as nuclear factor kappa beta (NF-kB), and protein kinases, such as mitogen-activated protein kinase (MAPK), involved in pro-inflammatory pathways such as those in the production of pro-inflammatory cytokines (e.g. IL-6), tumor necrosis factor alpha (TNF-a) and signal transducer and activator of transcription (STAT) proteins;
• Its chemical structure acts as an electron trap, preventing the formation of pro-oxidant reactive oxygen species (ROS);
• Its chemical structure also enables it to chelate heavy metals, thus protecting against metal-induced toxicity;
• It is ten times more powerful than vitamin E as a free-radical scavenger;
• In addition to acting as a direct scavenger of ROS, it increases levels of gluthatione, the body's master antioxidant;
• It is able to cross the blood-brain barrier, and is thus able to protect the brain from oxidative stress and inflammation
• Because of curcumin's many known anti-inflammatory properties, with potential benefit for a multitude of disease classes, it is being studied both as a prophylactic and as a treatment for Covid-19.

A computational study has shown that curcumin has antiviral activity against SARS-CoV-2, and two pilot clinical studies have shown that it resulted in improved outcomes for the treatment group versus the control group:  1, 2.

However, one challenge that must be overcome with curcumin is that its bioavailability is very low, perhaps as low as 1% for unformulated curcumin.  Support Protocols Turmeric Curcumin Phytosome, however, uses Meriva^®, a patented formulation of curcumin that uses phosphatidylcholine to increase its bioavailability 29-fold compared to unformulated curcumin.