Immune Support | A Guide To Immune System Modulation

Posted by Nootropics Depot on 29th Dec 2023

Discover the intricate workings of your immune system and expert tips on modulation from Emiel, our product specialist. This comprehensive guide is packed with an abundance of strategies to maintain peak health!

A Guide To Immune System Modulation

During the colder, and darker months of the year, the main thing that is often on our minds is our immune function. We either find ourselves in a prevention mode during this time, or we have already gotten unlucky and we are trying to speed up recovery. However, immune function is often quite misunderstood because it is an extremely complex system. When we are discussing immune function, we are oftentimes focused on the act of prevention. This act of prevention relies heavily on the innate immune system, rather than the adaptive immune system. Think of the innate immune system as airport security. The staff at airport security has many tools at their disposal to identify threats, and prevent those threats from inflicting serious damage. This approach is not very precise, yet it prevents most security threats that you would see at airports. Hopefully, airport security would catch most threats but based on the amount of staff at the airport and their skill level things could certainly be missed. For example, at an airport with a lack of adequate staff or worse yet, badly trained staff, the likelihood for a threat to make it past security is much higher. Thus, in order to increase security, proper training and staffing is paramount. The same can be said for our innate immune system, which acts as “security” for our body. We are constantly coming into contact with threats in our environments.

A Rare Newcomer In The Functional Mushroom Space

Lignosus rhinocerus, also known as tiger milk mushroom, is one of the most exciting newcomers to the functional mushroom space. This mushroom has historically been incredibly rare, with wild tiger milk mushroom being almost impossible to come by in meaningful quantities. This is largely due to the fact that tiger milk mushrooms do not grow close to each other. Instead, single mushrooms are separated by vast distances in wild jungles. This is also partially where Lignosus rhinocerus gets its ‘tiger milk mushroom’ nickname from. In folklore, it is thought that the mushroom grows on spots where drops of milk from a lactating tiger have fallen. Of course, tigers are rare and travel incredible distances everyday, so within folklore this seems like a perfectly reasonable explanation why the mushrooms grow so far apart from each other! However, this is more of an old wives tale. Tiger milk mushroom does not need to grow on the spots where a mother tiger's milk fell. Even so, the name stuck, and now everyone refers to it as tiger milk mushroom. This is very similar to how Hericium erinaceus is called lion's mane mushroom, despite not being related to lions at all. Even with tiger milk mushroom's rarity, there is a very long history of human use associated with it. Tiger milk mushroom is primarily gathered in the wild, and consumed by indigenous Malaysian people who hunt for this mushroom in the jungle. This amazing fungi is prized by many for its numerous beneficial effects!

A Guide To Immune System Modulation

What is Ashwagandha?

Ashwagandha is a herb that belongs to the night shade family of plants. The nightshade family of plants is a very interesting one and includes a lot of vegetables that make up large parts of many diets. Notable nightshade members are potatoes, tomatoes, chili peppers, goji berries and even tobacco! Another name for the nightshade family is Solanaceae. This is where Ashwagandha gets its Latin name from; Withania somnifera. Ashwagandha is a short perennial shrub, with a large root system that develops small deep orange fruits. The fruits resemble a small cherry and the leaves look frosty due to the many tiny hairs that are on them. This one of the reasons why Ashwagandha is also referred to as ‘winter cherry’. Traditionally, the Ashwagandha root is used, however new research has found high concentrations of key components in the leaves too. Various manufacturers have taken notice of this. One of the most notable being Natreon who produce a specialized extract of Ashwagandha called Sensoril. Sensoril is made from the leaves of Ashwagandha, giving it a unique chemical composition, which produces noticeable calming effects.

Throughout history, tiger milk mushroom has piqued the interest of many individuals. Most notably, the first Western reference to this mushroom was made all the way back in 1664 in the diary of English writer, John Evelyn. In a section of his diary, he describes a collection of rarities from Asia, with one of these rarities being tiger milk mushroom.

At the time, tiger milk mushroom was referred to as ‘Lac Tigridis’, which is Latin for ‘tiger milk’:

Figure 1. Tiger’s roam great distances throughout the jungle everyday, and thus a lactating tiger would leave behind drops of milk every few kilometers. This is likely where the folklore story that inspired the “tiger milk mushroom” nickname comes from, because tiger milk mushrooms grow in the same habitat Malaysian tigers reside in, and single mushrooms are usually separated by several kilometers in the wild!

Figure 1. Immune function is on many of our minds during the cold and dark winter months!

Especially at this time of the year, there are lots of people around us who are coughing and sniffling and to make matters worse we are oftentimes in poorly ventilated indoor spaces with those individuals. Yet many people make it through the winter months completely unscathed despite the fact that they are constantly being bombarded with threats to their immune system. The reason why we are not constantly under the weather is because our innate immune system is doing a fantastic job of blocking the threats before they make themselves into our body and start replicating.

Figure 2. Our innate immune system is like airport security, and acts as one of the first lines of defense against threats.

Luckily our more permeable membranes, such as our eyes, ears, nose and mouth can also neutralize most threats. For example, most mucosal membranes produce high amounts of immunoglobulin A (IgA) which acts as a strong barrier for threats. Another much more obvious example is the pH of our stomach. The pH is so low that most threats that we end up consuming orally are destroyed by the acidic environment. Moving further into the gastrointestinal system, beneficial bacteria, especially those that are good at synthesizing short chain fatty acids (SCFAs) such as butyrate, are also a major line of defense against threats.

Figure 3. Our skin is one of the main barriers utilized by our innate immune system.

Figure 2. A portrait of the English writer John Evelyn. Reportedly painted in 1689 which is 25 years after he wrote about tiger milk mushroom in his diary.

This diary entry reveals two very interesting pieces of information. First of all, the name ‘tiger milk’ has been around for at least 358 years, which means that the folklore story about how tiger milk mushrooms grow has been around for a very long time! Secondly, based on the fact that tiger milk mushroom was included in a list of spectacular rarities from Asia, it is clear that it was held in very high regard, even in 1664!

Figure 3. A picture of Henry Nicholas Ridley, who is often referred to as the father of the Malaysia rubber trade, and potentially made one of the first documented attempts at cultivating tiger milk mushroom

He noted that the tiger milk mushroom was very important to the health of indigenous communities in Malaysia, and with this in mind, he hoped to cultivate tiger milk mushroom. However, he was not successful, and this is because tiger milk mushrooms are incredibly hard to cultivate! In fact, it is so tricky to cultivate that it was only successfully cultivated more than 100 years after Henry Nicholas Ridley’s initial attempt.

When this happens, we often feel terrible. In fact, the better your innate immune system functions, the more lousy you would feel as the inflammatory and histamine response would be much stronger. At this point, we would also start to see a gradual switch from the innate immune system to the adaptive immune system. However, this takes at least a few days and sometimes even a whole week because genetic changes play a major role here and the adaptive immune system must first learn what it is actually dealing with. Thus, when we think practically about immune function and how to modulate it with supplements, we are oftentimes more focused on the much faster acting innate immune system rather than the slower adaptive immune system. Once the adaptive immune system gets kicked into gear, we start producing lots of antibodies and antigens which are much more targeted towards threats than the innate immune system. While you can think of the innate immune system as an army that indiscriminately attacks anything it deems to be a threat, the adaptive immune system is a team of highly skilled assassins that can take out threats with precision, and most importantly, memory. Even after the threat has passed, the specialized cells of the adaptive immune system such as the lymphocytes will remember what to do if the threat presents itself again. This is why a specific threat will often only affect us once.

With all of this in mind, we have a few directions to go into when choosing supplements for modulating immune function. The most direct approach is to bolster innate immune function, and in fact, most immune boosting strategies focus on the innate immune system. For example, one of the primary benefits of Epicor is that it can boost the levels of IgA, thus bolstering one of the primary protective barriers. However, lots of supplements are also important for modulating adaptive immune function. As we mentioned earlier though, the adaptive immune system takes a few days to fully ramp up so while it is important for proper recovery, it is not so important in the first few days.

Figure 4. The differences between the innate and adaptive immune systems. The innate immune system is very non-specific whereas the adaptive immune system is very precise and has a memory.

Another thing to consider with both the innate and adaptive immune system is that they both utilize inflammation and oxidation as primary tools. In fact, most inflammation is mediated through the immune system. Thus, when we are talking about inflammation, we are actually talking about a core aspect of our immune system. We often want to lower inflammation, but what we really want to do is tune inflammation to the point that we can reap its immune modulating benefits without many of the drawbacks of elevated inflammation. Thus, it is not surprising that many immune boosting supplements, such as Andrographis paniculata, are also great at balancing overall inflammation levels. It is then also not surprising that many antioxidants, such as vitamin C, also play a very important role in tuning our immune response.

Taking Action Before It Is Too Late

Our main goal when it comes to immune function modulation is to bolster our immune system to the point where we prevent the majority of threats from becoming issues. This can come in the form of behavioral adjustments such as eating healthy food, optimizing sleep quality, getting in enough exercise and modulating stress levels. With this in mind, we can consider supplements that help enhance these behavioral adjustments as “immune boosters” too because they help foster healthy behaviors. For example, supplements such as Sleep Support, Cistanche tubulosa and PanaMAX can all help enhance overall immune function both through direct mechanisms and indirect mechanisms which involve fostering healthy behaviors.

Figure 5. Optimizing healthy behaviors, such as optimizing sleep, can have very positive effects on immune function!

Vitamin D synthesis is mainly mediated through UV exposure and during the winter many of us experience drastically reduced rates of UV exposure, thus leading to major drops in vitamin D levels. This is easily adjusted for by taking a vitamin D3 supplement. Last but not least, we can supplement with various botanicals and fungi that help bolster our innate immune system. This can occur through modulation of inflammation and oxidation, but more often than not, the immune boosting effects of many botanicals and fungi can be traced back to our microbiome!

Figure 6. Unfortunately, many of us do not experience much sun exposure during the winter, and thus our vitamin D levels can drop significantly during the winter months.

The Importance Of Our Gut

Earlier in this blog we mentioned that eating healthy is a great way to bolster immune function. This is of course due to many of the micronutrients contained in food, such as vitamins and minerals, but perhaps more importantly is the large amount of prebiotics and probiotics contained within many healthy foods. In the last few decades we have started to discover more and more that our gut is very important for tuning immune function just right. The microbes in our gut are capable of producing many different immune modulators, such as the short chain fatty acids (SCFA). These SCFAs, such as butyrate, do a great job at bolstering the innate immune system. The SCFAs are mainly generated from prebiotic-like substances, such as various types of starches and fibers. In fact, the beta-glucans from mushrooms and yeast are great substrates for producing SCFA and they exert most of their immune boosting properties via this gut mediated mechanism!

Figure 7. Our microbiome plays a very important role in immune modulation!

Fermented foods also play a major role here, and thus we would encourage the inclusion of fermented foods into an immune boosting strategy. This is because fermented foods are full of beneficial probiotics, most of which are great at synthesizing SCFAs. Something as simple as daily yogurt consumption, or a bit of real fermented sauerkraut on your sandwiches can help a lot! We are also big fans of unpasteurized kombucha and kefir for this purpose. Of course probiotic supplements can be utilized here too, however, fermented foods also contain lots of prebiotics thereby helping to boost the overall effects of the probiotics they contain. Many fermented foods such as sauerkraut are also fairly enriched in SCFA!

"Research has shown that magnesium levels are decreasing in most foods... With the magnesium content decreasing in crops and the increase in the consumption of processed foods, magnesium deficiencies in the population are becoming more prevalent."

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Figure 1. Immune function is on many of our minds during the cold and dark winter months!

Hopefully, airport security would catch most threats but based on the amount of staff at the airport and their skill level things could certainly be missed. For example, at an airport with a lack of adequate staff or worse yet, badly trained staff, the likelihood for a threat to make it past security is much higher. Thus, in order to increase security, proper training and staffing is paramount. The same can be said for our innate immune system, which acts as “security” for our body. We are constantly coming into contact with threats in our environments. Especially at this time of the year, there are lots of people around us who are coughing and sniffling and to make matters worse we are oftentimes in poorly ventilated indoor spaces with those individuals. Yet many people make it through the winter months completely unscathed despite the fact that they are constantly being bombarded with threats to their immune system. The reason why we are not constantly under the weather is because our innate immune system is doing a fantastic job of blocking the threats before they make themselves into our body and start replicating.

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Figure 2. Our skin is one of the main barriers utilized by our innate immune system.

One of the main barriers that the innate immune system utilizes to keep us healthy is our skin. However, the skin is easily bypassed. For example, if we shake hands with someone they could pass a potential threat onto us. The skin of our hands does an impeccable job of preventing these threats from entering our body, but unfortunately the skin is also very easily bypassed. After shaking hands with someone, most of us end up touching a much more permeable membrane, such as our eyes or nose. Luckily our more permeable membranes, such as our eyes, ears, nose and mouth can also neutralize most threats. For example, most mucosal membranes produce high amounts of immunoglobulin A (IgA) which acts as a strong barrier for threats. Another much more obvious example is the pH of our stomach. The pH is so low that most threats that we end up consuming orally are destroyed by the acidic environment. Moving further into the gastrointestinal system, beneficial bacteria, especially those that are good at synthesizing short chain fatty acids (SCFAs) such as butyrate, are also a major line of defense against threats.

Figure 3. Immune system is like airport security, and acts as one of the first lines of defense against threats.

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Once threats do make it past some of these initial barriers, the innate immune system kicks things up a notch. The innate immune system is not at all specialized, but it can produce a very inhospitable environment for various threats by releasing histamines and inflammatory cytokines. This produces massive amounts of inflammation and oxidation, which eventually also leads to a rapid increase in body temperature. When this happens, we often feel terrible. In fact, the better your innate immune system functions, the more lousy you would feel as the inflammatory and histamine response would be much stronger. At this point, we would also start to see a gradual switch from the innate immune system to the adaptive immune system. However, this takes at least a few days and sometimes even a whole week because genetic changes play a major role here and the adaptive immune system must first learn what it is actually dealing with. Thus, when we think practically about immune function and how to modulate it with supplements, we are oftentimes more focused on the much faster acting innate immune system rather than the slower adaptive immune system.

Once the adaptive immune system gets kicked into gear, we start producing lots of antibodies and antigens which are much more targeted towards threats than the innate immune system. While you can think of the innate immune system as an army that indiscriminately attacks anything it deems to be a threat, the adaptive immune system is a team of highly skilled assassins that can take out threats with precision, and most importantly, memory. Even after the threat has passed, the specialized cells of the adaptive immune system such as the lymphocytes will remember what to do if the threat presents itself again. This is why a specific threat will often only affect us once.

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Figure 4. The differences between the innate and adaptive immune systems. The innate immune system is very non-specific whereas the adaptive immune system is very precise and has a memory.

Taking Action Before It Is Too Late

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Figure 5. Optimizing healthy behaviors, such as optimizing sleep, can have very positive effects on immune function!

Immune boosting strategies can also be much more direct, for example by topping up essential vitamins and minerals which play an important role in the innate and adaptive immune system. For example, one of the reasons we may be more susceptible to threats during the winter time is due to lower levels of circulating Vitamin D and 25-hydroxy vitamin D which play an important role in both our innate and adaptive immune system. Vitamin D synthesis is mainly mediated through UV exposure and during the winter many of us experience drastically reduced rates of UV exposure, thus leading to major drops in vitamin D levels. This is easily adjusted for by taking a vitamin D3 supplement.

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Figure 6. Unfortunately, many of us do not experience much sun exposure during the winter, and thus our vitamin D levels can drop significantly during the winter months.

Last but not least, we can supplement with various botanicals and fungi that help bolster our innate immune system. This can occur through modulation of inflammation and oxidation, but more often than not, the immune boosting effects of many botanicals and fungi can be traced back to our microbiome!

The Importance Of Our Gut

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

Figure 7. Our microbiome plays a very important role in immune modulation!

Protecting Ourselves From Our Immune System

One aspect of our immune function that is not often discussed, is that it can also be damaging to our bodies. As we have discussed throughout this blog, our immune system is set up in a way that it can inflict major damage to threats that enter our body. However, especially our innate immune system, also inflicts a lot of damage on healthy cells throughout our body. Luckily there are many systems throughout our body which can help mitigate the majority of this damage. One of the main protective systems are our antioxidant defenses, with glutathione playing a major role here. Glutathione is one of our bodies main antioxidant defenses and during ramped up immune responses we see a major uptick in oxidation. In cases where glutathione levels are low for example, this can result in very negative consequences. Thus, keeping glutathione levels topped up can be very beneficial for protecting ourselves from a full on immune response and it can actually also be very useful for dialing in both innate and adaptive immune responses. The same could be said for one of the quintessential immune boosters, vitamin C. Vitamin C helps bolster both innate and adaptive immune systems, and it also acts as a powerful antioxidant thereby protecting us from immune responses too.

Figure 8. Our immune system can also turn on us if the inflammation and oxidation it produces goes unchecked. This is why we need endogenous compounds such as glutathione, to protect ourselves from a strong immune response.

Similar things can be said for many inflammation regulating supplements too. For example, one of our favorite inflammation regulating supplements, Andrographis paniculata, can protect us from excessive levels of inflammation while also boosting overall immune function. Vignatex can also help reduce inflammatory cytokines which get ramped up during an immune response and can both help keep us safe from threats whilst also inflicting damage on normal healthy cells.

Protecting Ourselves From Our Immune System

Figure 1. Mycelium on an agar plate, where the fabled erinacine A is rumored to be hanging out!

The Year Round Strategy

Immune Stacks

Optimize Sleep: Using sleep-enhancing supplements such as Sleep Support, in order to fully reap the benefits of sleep on immune function.
Optimize Diet: Try to consume more fermented foods and foods that are high in prebiotic starches and fibers.
Exercise: Try to get a healthy amount of exercise every day. However, don’t push yourself super hard all the time because very intense exercise can also decrease overall immune function!
Cover The Basics: Optimize your micronutrient intake with supplements such as zinc, magnesium, vitamin D3 + K2, Infini-B, Infini-C, and vitamin E.
Dial In Your Defenses: Optimize immune defenses with mushroom supplements and supplements like Epicor.
Nurture An Optimal Microbiome: Pay close attention to your gut health and try to optimize gut health by eating fermented foods, and taking supplements that can enhance your microbiome such as Cistanche and Resveratrol.
Protect Yourself, Before You Wreck Yourself: Try to balance inflammatory and oxidative systems throughout the body with supplements such as glutathione and Andrographis paniculata.

Now that we have covered the basics of immune function and how to modulate it, it’s time to build up a stack!

The Simple Immune Defense Stack*

Mushroom Magic Matcha + Reduced Glutathione

This stack is very lifestyle oriented; keeping things simple yet effective. Mix up a serving of Mushroom Magic Matcha for all of your beta-glucan needs and then take a capsule of reduced glutathione in order to top up your glutathione pools!

Advanced Immune Defense Stack*

Immune Defense + Immuse + Epicor + Reduced glutathione

The advanced stack takes things to the next level, starting with our highly optimized immune boosting stack immune defense! Immune defense is further rounded out by the very unique postbiotic, immuse, and the prebiotic, Epicor. To further solidify this stack, we added some reduced glutathione to balance oxidative and inflammatory immune processes.

The Simple Immune Recovery Stack*

Microzinc (40 mg) + NAC

A higher dose of zinc joins forces here with NAC which is capable of rapidly boosting glutathione levels. Furthermore, NAC is great at thinning out mucus which can really come in handy if you are all stuffed up!

The Advanced Immune Recovery Stack*

Microzinc (40 mg) + NAC + Andrographis paniculata + Palmitoylethanolamide

The advanced recovery stack sticks with two of the same ingredients from the simple stack, zinc and NAC. This is further rounded out by Andrographis paniculata which has unique immune modulating properties and can help protect us from inflammation. Last but not least, palmitoylethanolamide, which in various studies has been found to significantly speed up recovery!

Protecting Ourselves From Our Immune System

Optimize Sleep: Using sleep enhancing supplements such as Sleep Support, in order to fully reap the benefits of sleep on immune function.
Optimize Diet: Try to consume more fermented foods and foods that are high in prebiotic starches and fibers.
Exercise: Try to get a healthy amount of exercise everyday. However, don’t push yourself super hard all the time because very intense exercise can also decrease overall immune function!
Cover The Basics: Optimize your micronutrient intake with supplements such as zinc, magnesium, vitamin D3 + K2, Infini-B, Infini-C and vitamin E.
Dial In Your Defenses: Optimize immune defenses with mushroom supplements and supplements like Epicor.
Nurture An Optimal Microbiome: Pay close attention to your gut health and try to optimize gut health by eating fermented foods, and taking supplements that can enhance your microbiome such as Cistanche and Resveratrol.
Protect Yourself, Before You Wreck Yourself: Try to balance inflammatory and oxidative systems throughout the body with supplements such as glutathione and Andrographis paniculata.

Immune Stacks

Now that we have covered the basics of immune function and how to modulate it, it’s time to build up a stack!

The Simple Immune Defense Stack*

Mushroom Magic Matcha + Reduced Glutathione

Advanced Immune Defense Stack*

Isoliquiritigenin + NALT + Sabroxy + Fenugreek

The Simple Immune Recovery Stack*

Microzinc (40 mg) + NAC

The Advanced Immune Recovery Stack*

Microzinc (40 mg) + NAC + Andrographis paniculata + Palmitoylethanolamide

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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