What is PanaMAX Optimized Ginseng?
Panax ginseng is a very popular herbal supplement that has been used for thousands of years. Its main use historically has been within Chinese traditional medicine for a wide variety of purposes. Its name loosely translates to panacea, meaning that it can heal all ailments. Even though that is hyperbole, Panax ginseng is remarkably effective at supporting a large amount bodily and cognitive functions. Panax ginseng benefits include:
● supports healthy stress levels
● supports cognitive function
● promotes a positive mood
● promotes energy levels
● supports a healthy metabolism
● supports immune function
● supports skin health
As you may have noticed, we are referring to ginseng in this article as Panax ginseng rather than just "ginseng." This is in order to differentiate between the different types of Panax species, which are also referred to (somewhat incorrectly) as "ginseng." Besides Panax ginseng, there are 11 other species in the Panax genus; the most famous of which is Panax quinquefolius. Panax quinquefolius is most often referred to as American Ginseng. American Ginseng contains similar bioactive molecules as Panax ginseng, yet the overall profile of ginsenosides is fairly different compared to Panax ginseng, which translates to a drastically different effects profile. The issue with American Ginseng is that it is much cheaper than real Panax ginseng, and thus American Ginseng is often times passed of as Panax ginseng to save on costs. The only way to verify whether or not you are dealing with real Panax ginseng is by utilizing species testing via HP-TLC. This is what Natrium Health utilizes for all of its plant extracts, so you can rest assured that we are supplying real Ginseng - the one and only Panax ginseng! There are even other “ginsengs” that are completely different plants, and are not even in the Panax genus, such as Siberian Ginseng; which is not even allowed to even be referred to as Ginseng! Now that we have that issue out of the way, let’s move on and dive deep into the world of Panax ginseng!
The Panax Ginseng Plant
The wide array of Panax ginseng benefits are predominantly produced by the ginsenosides present in the plant. Unsurprisingly, due to the wide array of effects Panax Ginseng produces, Panax ginseng also contains a wide array of ginsenosides; more than 100 in fact! The most commonly seen ginsenosides in the ginseng plant are:
● Ginsenoside Rg1
● Ginsenoside Re
● Ginsenoside Rb1
● Ginsenoside Rb2
● Ginsenoside Rc
● Ginsenoside Rd
The presence of these ginsenosides can vary widely and are dependant on what part of the plant is used (roots vs leaves), how the roots are prepared (shaved vs unshaved, steamed vs unsteamed), and how old the ginseng plant is and where it is grown. In general, we see very high levels of ginsenosides in the leaves versus the roots. However, the ginsenoside profile in the leaves are often heavily skewed towards Rg1, Re and Rd. The ginsenoside profile of the roots is often times much more balanced.
When looking at an HPLC analysis, it's clear that the total amount of ginsenosides is much higher in the leaves than they are in the root. It can also be seen that the balance of different ginsenosides is also very different in both the root and the leaf of the plant. In general, the ginseng root is the most highly praised part of the ginseng plant in Traditional Chinese Medicine, and some very old Panax ginseng roots have sold for staggering prices. In 2007, a 300 year old Panax ginseng root that was found in the Changbai mountain region in China sold for a whopping $400,000 dollars! It is thought that the older a Panax ginseng root becomes, the more “energy” it amasses. In a more scientific analysis, this “energy” is actually the amount and ratio of ginsenosides which changes as the roots age. There is weak evidence for very old Panax ginseng root being better, but we do have proof that age affects ginsenoside levels and ratios.
"In our experience, and the experience of our customers, the Panax ginseng leaf extract has a much more clear and clean stimulating effect. The root on the other hand is much more relaxing, and is much better at regulating stress."
That being said, we can clearly show that Panax ginseng leaf is much higher in ginsenosides than any Panax ginseng root in existence. So why are the leafs not as valued? Part of this is due to the balance of ginsenosides, and the effects that this balance results in. The leaf is very high in stimulating ginsenosides. We can confirm this both with analytical testing and by observing subjective effects. In our experience, and the experience of our customers, the Panax ginseng leaf extract has a much more clear and clean stimulating effect. The root on the other hand is much more relaxing, and is much better at regulating stress. The difference between the two is so large that it almost seems like the extracts are made from two completely different plants. To explain why there is such a large difference in effects between the leaf and the root, we have to do an in depth analysis of the six main ginsenosides that we listed earlier.
What is Ginsenoside Rg1?
Ginsenoside Rg1 is one of the most abundant ginsenosides in Panax ginseng. It is both highly expressed in the root system and the leaves of Panax ginseng. Alongside ginsenoside Rb1, ginsenoside Rg1 has a lot of beneficial effects on the brain. Rg1 appears to promote a positive mood, and helps boost learning and memory. It does this via a few different pathways, the first of which appears to be by boosting brain derived neurotrophic factor (BDNF) levels in key areas of the brain. BDNF is a highly important protein that plays a pivotal role in helping our brains change and adapt. This process of change and adaptation, which constantly occurs in our brain, is collectively referred to as neuroplasticity.
Ginsenoside Rg1 Structure
What is Neuroplasticity?
Neuroplasticity is a crucial factor in overall cognitive health, as many of our cognitive functions, especially memory processing are highly dependent on neuroplastic changes in our brain. Rg1, by boosting BDNF levels and supporting the activity of the signalling pathways related to BDNF, can help improve our overall cognitive health.
"Ginsenoside Rg1 appears to significantly regulate stress-related decline in BDNF levels and through this mechanism, it may be a great solution to fending off that stress-induced fogginess!"
The neuroplasticity enhancing effects of ginsenoside Rg1 come in handy especially during periods of high stress. This is due to the fact that chronic stress can lower levels of BDNF throughout the brain. This stress-related regulation in BDNF levels is especially noticeable in the hippocampus. So much so, in fact, that stress may actually cause shrinkage of the hippocampus. Hippocampal atrophy has been linked to lowered mood and decreased memory processing. This is likely why during periods of high stress, we experience a major reduction in mood and our normally clear-headedness can be replaced by foggy and slow cognitive processing. Ginsenoside Rg1 appears to significantly regulate stress-related decline in BDNF levels and through this mechanism, it may be a great solution to fending off that stress-induced fogginess!
Furthermore, ginsenoside Rg1 has some other interesting neurological effects. Research has show that ginsenoside Rg1 can help promote acetylcholine concentrations in the hippocampus. Acetylcholine is a highly important neurotransmitter in the brain that plays a major role in cognitive processing and mood. By enhancing acetylcholine release, ginsenoside Rg1 may help enhance focus, increase memory retention, and may even help boost mood. This is all on top of the BDNF effects of ginsenoside Rg1. In fact, enhanced acetylcholine signalling goes hand in hand with enhanced BDNF signalling.
Ginsensoide Rg1: A True Adaptogen Compound
Ginsenoside Rg1, besides reducing the negative effects of stress on the brain, may also help modulate stress and promote healthy stress levels. Rg1 has some very unique effects when it comes to stress hormone signalling. This is because Rg1 itself appears to bind to stress hormone receptors called glucocorticoid receptors. By binding to glucocorticoid receptors, Rg1 is able to actually produce a minor stress response. This may seem a little bit contradictory since Panax ginseng is often times promoted for stress reduction. However, having too little stress is actually a very bad thing, because we need a small amount of stress in order to stay focused and motivated. However, larger amounts of stress are very detrimental, so we want to find a balance. Ginsenoside Rg1 binds tightly to the glucocorticoid receptor, which prevents stress hormones from binding to this receptor. It then produces only a minor stress response in contrast to actual stress hormones. Due to this, it helps balance out stress levels. Ginsenoside Rg1 is truly an adaptogenic compound as it helps our bodies adapt to the effects of stress. By producing a small stress response, Rg1 may have stimulating effects, which will help us stay alert, focused, and motivated!
What is Ginsenoside Re?
Ginsenoside Re appears to exist in large amounts in the leaves of ginseng. It is a very interesting ginsenoside and has some significant stress-regulating effects. As we talked about earlier, stress can increase the expression of stress hormones, which can have potentially detrimental effects on our brains and bodies. Stress can also cause negative effects on our mind by boosting norepinephrine levels. Norepinephrine is an important neurotransmitter that helps us stay alert and focused, which is why our bodies have adapted to use it in the fight or flight response. Increased norepinephrine levels can really get us going, which in cases of extreme danger, would allow us either to fight the threat or escape from it. Increased stress levels may enhance the expression of tyrosine hydroxylase in an area of the brain called the locus coeruleus. This brain region is responsible for the bulk of norepinephrine synthesis, and one of the main driving mechanisms behind norepinephrine synthesis is the the expression of tyrosine hydroxylase. This means, that if stress increases tyrosine hydroxylase expression in the locus coeruleus, then we will experience a fairly constant state of fight or flight. This can be very unhealthy, as it is not good to constantly be in a state of hypervigilance. Luckily, ginsenoside Re appears to block the increase in tyrosine hydroxylase in the locus coeruleus. This can be majorly beneficial when we need to stay calm and relaxed.
Ginsenoside Re also has potentially significant neuroprotective effects. It achieves this through a variety of mechanisms, one of the main ones being a major reduction in malondialdehyde (MDA). MDA is a major biomarker of oxidation in the brain. When MDA levels are high, this indicates a high amount of oxidative stress in the brain. Ginsenoside Re, by decreasing MDA levels, may help to support our brains from oxidative stress. In fact, out of all of the ginsenosides, ginsenoside Re seems to be the most effective at limiting the formation of reactive oxygen species, and this is likely why such a large reduction of MDA is observed in the brain.
"Acetylcholine is a major player in cognitive function, and by enhancing the synthesis of acetylcholine, ginsenoside Re may provide a significant boost to overall cognitive function."
Ginsenoside Re and Cholinergic Signaling
When it comes to supporting cognition, ginsenoside Re also appears to be remarkably effective. Ginsenoside Re has the ability to enhance cholinergic signalling through a variety of pathways. The first of which is by enhancing the activity of an enzyme called choline acetyltransferase (ChAT). ChAT is responsible for attaching an acetyl group to choline, in order to produce the neurotransmitter acetylcholine. Acetylcholine is a major player in cognitive function, and by enhancing the synthesis of acetylcholine, ginsenoside Re may provide a significant boost to overall cognitive function. Furthermore, ginsenoside Re can also inhibit the function of another enzyme called acetylcholinesterase (AChE), which is responsible for breaking down acetylcholine. By inhibiting AChE, ginsenoside Re can further enhance acetylcholine levels in the brain. As the cherry on top, ginsenoside Re even appears to be able to enhance the activity of the vesicular acetylcholine transporter (VChAT). VChAT is required for getting acetylcholine to where it can exert its beneficial effects. This means that ginsenoside Re not only increases acetylcholine levels, it also increases cholinergic signalling by allowing the increased levels of acetylcholine to make their way to areas of the brain where they can exert their positive cognition promoting effects.
What is Ginsenoside Rb1?
Panax ginseng is highly effective in promoting a positive mood, and most of its mood-boosting effects appear to be due to its Rb1 content. Similar to ginsenoside Rg1, ginsenoside Rb1 has highly efficacious stress-regulating effects, and this is likely where a bulk of the mood-boosting effects come from. However, ginsenoside Rb1 also appears to significantly interact with the serotonergic system. Ginsenoside Rb1 appears to signal through select estrogenic pathways, and through this, causes an upregulation of the enzyme tryptophan hydroxylase.
"Serotonin is highly implicated with mood, and by enhancing serotonin levels, we may be able to promote a positive mood."
Ginsenoside Rb1 and Typtophan Hydroxylase
Tryptophan hydroxylase is responsible for taking the dietary amino acid tryptophan and turning it into 5-hydroxytryptophan, which is a direct precursor to serotonin. By up-regulating the activity of tryptophan hydroxylase, ginsenoside Rb1 can enhance the levels of serotonin in the brain. Serotonin is highly implicated with mood, and by enhancing serotonin levels, we may be able to promote a positive mood. By acting through the estrogenic system, ginsenoside Rb1, can also inhibit the function of another enzyme called monoamine oxidase (MAO). The MAO enzymes are responsible for breaking down various neurotransmitters, such as serotonin and dopamine and by inhibiting it, ginsenoside Rb1 may be able to promote healthy levels of these neurotransmitters. This may help promote a positive mood and help bolster overall cognitive health.
Whereas ginsenosides such as ginsenoside Rg1 appear to have a stimulating effect, the effects of ginsenoside Rb1 appear to be more calming. This is likely why the root extract is more calming, as it has a higher ratio of ginsenoside Rb1 than in the leaf extract. This is also likely why the combination of the leaf and root extract is so synergistic, but we’ll touch on this more later in the article.
What is Ginsenoside Rb2?
Ginsenoside Rb2 has some interesting effects on our metabolic health, as it appears to play a major role in glucose processing. It achieves these beneficial metabolic health effects mainly by activating AMPK and sirt1. AMPK activation is somewhat of a holy grail when it comes to enhancing overall health, and in the supplement industry there is always a search for the next best AMPK activator. This is not surprising, as AMPK activation causes a massive cascade of positive health effects. AMPK activation primarily helps our muscles take up and use glucose. This enhances glucose metabolism and is beneficial for overall health, as glucose accumulation comes with a whole host of problems; one of which is an accumulation of fatty tissue. AMPK activation also inhibits the synthesis of fatty acids in addition to inhibiting cholesterol and triglyceride synthesis. These are also important processes to properly regulate as an accumulation of fatty acids, cholesterol, and triglycerides can be majorly detrimental to our overall health. Furthermore, AMPK can significantly increase the uptake of fatty acids and induce beta-oxidation. During the process of beta-oxidation, fatty acids are broken down into acetyl-CoA, which can provide energy to our cells.
"AMPK activation is somewhat of a holy grail when it comes to enhancing overall health, and in the supplement industry, there is always a search for the next best AMPK activator."
Ginsenoside Rb2 and AMPK Activation
AMPK activation has even been shown to have potential life-extending effects, which is another reason why AMPK activation is so highly sought after. Sirt 1 activation also helps enhance metabolic health by helping to regulate insulin sensitivity. The regulation of insulin sensitivity is highly beneficial in maintaining optimum health and may also help slow down the process of aging. Furthermore, it is believed that sirt 1 activation is highly involved in longevity, and has been a target of interest in longevity communities. Part of the reason why sirt 1 activation appears to be able to enhance longevity is by helping to regulate long-term inflammation, which may increase as we age. Overall, activation of AMPK and sirt 1 makes ginsenoside Rb2 a highly interesting health-boosting compound. It also makes it an interesting compound for those interested in supporting their weight loss efforts, as the metabolic-regulating effects of Rb2 may help promote weight loss when paired with a healthy diet and exercise regime.
What is Ginsenoside Rc?
Ginsenoside Rc Structure
Panax ginseng has significant inflammation-regulating effects and it appears that these inflammation-regulating effects can be traced back to ginsenoside Rc. Ginsenoside Rc appears to achieve this by interacting with two pathways that are highly involved in inflammation within the body. The first of these pathways is the TBK1/IRF-3 pathway, which is highly involved with macrophages and the inflammatory and oxidative compounds that they produce. By regulating this pathway, ginsenoside Rc is able to provide a broad reduction of inflammation and oxidation throughout the body. In particular, it appears to be able to keep our joints healthy, as the TBK1/IRF-3 pathway appears to play a major role in joint inflammation. The second pathway that ginsenoside Rc regulates is the p38/ATF-2 pathway. This pathway plays a major regulatory role in the body's natural inflammatory processes in our lungs and digestive system. By regulating this pathway, ginsenoside Rc can help support our respiratory health in addition to benefiting overall digestive health.
What is Ginsenoside Rd?
Ginsenoside Rd Structure
Ginsenoside Rd appears to be another ginsenoside, much like ginsenoside Rg1, that is highly beneficial for overall neurological health. It appears that similar to ginsenoside Rg1, ginsenoside Rd can help promote BDNF levels. Furthermore, ginsenoside Rd may also help boost levels of vascular endothelial growth factor (VEGF). VEGF is an important growth factor in the brain, which as the name may suggest, helps promote the vascular system in our brain. Enhanced vascularization in the brain can be highly beneficial to overall brain function. Furthermore, VEGF appears to be able to promote neurogenesis in various areas of the brain. Moreover, it appears to be especially effective at inducing neurogenesis in the subventricular zone (SVZ). The SVZ is an interesting area of the brain that harbors high concentrations of neural stem cells. It has been found that the SVZ is responsible for the bulk of adult neurogenesis, and by specifically enhancing the SVZ, through VEGF, ginsenoside Rd may significantly boost adult neurogenesis.
Ginsenoside Rd and Neurogenesis
By enhancing neurogenesis, a whole host of benefits can be experienced. One of the major effects of adult neurogenesis is enhanced learning abilities. In addition to this, adult neurogenesis is important for promoting a positive mood. Furthermore, adult neurogenesis can be highly neuroprotective, which will help keep our brains healthy... especially as we age. Overall, it appears that ginsenoside Rd may be one of the most brain healthy ginsenosides present in Panax ginseng! Luckily for us, the ginseng leaf extract has a very high ratio of ginsenoside Rd, making it a very interesting extract for boosting overall cognitive abilities.
PanaMAX Optimized Ginseng: Combining the best of both worlds.
As can be gleaned from the detailed analysis above about the various ginsenosides, each one has a unique effect, which can have a very valuable impact on overall health and cognition. This is why we at Natrium Health decided to combine both a Panax ginseng leaf extract with a Panax ginseng root extract in our new PanaMAX formulation. This is due to the fact that the leaf extract is extremely high in a few key ginsenosides, such as Rg1, Re, and Rd while being much lower in the other ginsenosides. This is illustrated well by analytical testing data we have collected on samples of our root and leaf extracts:
As can be seen in the table above, the ginsenoside profile of the Panax ginseng leaf extract is highly unbalanced when compared to the ginsenoside profile of the root extract, which is much more balanced. Based on the discussion of the individual ginsenosides, it is now no surprise why the Panax ginseng leaf extract is very stimulating, whereas the Panax ginseng root extract is much more relaxing. We decided that we wanted the best of both worlds, and by combining the root and the leaf extract, we quite effectively balanced out the overall ginsenoside profile while keeping the ginsenoside levels very high. This balance illustrated quite well in the below table:
The Surprising, Beneficial Effects of PanaMAX Optimized Ginseng
On paper, combining the two Panax Ginseng extracts made a lot of sense to us. We predicted a very energizing extract that was a little bit smoother than just the leaf extract by itself. The results completely took us by surprise though, and we found that the combination of the two extracts was immensely calming and melted stress away. It achieved this without a hint of lethargy, an unfortunate side effect that limits the use of many stress management support supplements. In our opinions, this was the best ginseng extract we had tried, and really gave us the effects we had always looked for in a ginseng supplement.
Now that we got a taste of what was possible with PanaMAX, we decided to to see if we could make it even better. The most straightforward addition would be another ginseng extract, but we already had such a solid ginsenoside profile that it seemed like a waste to add even more ginseng to it. That’s when we stumbled on some fascinating leads from traditional Chinese medicine. In traditional Chinese medicine, it is common practice to supplement with a large combination of ingredients. In these traditional combinations, something we picked up on is that Panax ginseng is often combined with Schisandra chinensis. As you may have come to expect from our sister site Nootropics Depot, we wanted to really get to the bottom of why Panax ginseng and Schisandra chinensis were being combined. The answer we found actually has some solid scientific evidence behind it.
"The results completely took us by surprise though, and we found that the combination of the two extracts was immensely calming and melted stress away. It achieved this without a hint of lethargy, an unfortunate side effect that limits the use of many stress management support supplements or compounds."
Why Stack Panax Ginseng with Schisandra Chinensis?
Traditional Chinese medicine is quite an advanced herbal medicine system, and has been used for thousands of years. One of the main principles in traditional Chinese medicine is the concept of compatibility. This is similar to what we do when we create our stacks. Natrium Health does not just randomly combine ingredients. We take a structured approach to finding out why certain ingredients should be combined. A similar process is followed in traditional Chinese medicine, in which there is a monarch herb, minister herb, assistant herb, and messenger herb.
Monarch Herbs, Minister Herbs, Assistant Herbs, and Messenger Herbs
The monarch herb is the main herb of focus in a combination of ingredients, as it will produce most of the effects. Then, you have a minister herb, which has effects that can support the main effects of the monarch herb. A good monarch + minister combination example, would be Nootropics Depot's caffeine/L-theanine stack, in which caffeine produces the main effects (monarch) and L-theanine produces supporting effects (minister) for the caffeine. The assistant herb aims to support the effects of the minister herb, and often times also has minor effects of its own which will help enhance the overall effects. The messenger herb aims to tie all of the herbs in a formulation together and allows them to work as best as possible.
"Natrium Health does not just randomly combine ingredients. We take a structured approach to finding out why certain ingredients should be combined. A similar process is followed in traditional Chinese medicine, in which there is a monarch herb, minister herb, assistant herb and, messenger herb."
Shengmai-san - The Traditional Inspiration for PanaMAX
When it comes to Schisandra chinensis, it is often utilized as a messenger herb. In fact, there is a famous traditional Chinese medicine formulation called Shengmai-san which is used to to help promote healthy cardiovascular function. It consists of Panax ginseng (monarch herb), Ophiopogon japonicus (minister herb) and Schisandra chinensis (as both an assistant and messenger herb). So, is there any scientific proof behind this carefully constructed formula?
The Schisandra chinensis Plant
Well it turns out that Schisandra chinensis is a strong p-glycoprotein inhibitor. P-glycoprotein is, as the name might suggest, is a protein that helps clear molecules out of cells. This is a very important process in the body, and many herbal compounds are particularly sensitive to being cleared out quickly by P-glycoprotein. This appears to be especially true for the ginsenosides. Research has shown that P-glycoprotein inhibitors can help to significantly promote the absorption and utilization of ginsenosides. In fact, studies have shown that combining Panax ginseng with Schisandra chinensis significantly increases the bioavailability of the various ginsenosides. It looks like the formulators behind Shengmai-san were on to something, which can now be verified via scientific research. This is very impressive considering the formula seems to have been formulated in 1186. In other words, that means traditional Chinese medicine formulators figured out Schisandra chinensis allowed ginsenosides to be absorbed better 833 years ago! Incredible! After figuring all of this out, it was a no-brainer for us to include Schisandra chinensis in our PanaMAX formula.
"When it comes to Schisandra Chinensis, it is often utilized as a messenger herb. In fact, there is a famous traditional Chinese medicine formulation called Shengmai-san which is used to to help promote healthy cardiovascular function."
Upon adding Schisandra chinensis, a remarkable change was noticed in the already fantastic formula of Panax ginseng root and Panax ginseng leaf. As traditional Chinese medicine stipulates - a messenger herb ties all of the other components together, and we found this to be true for PanaMAX too. This is likely because different ginsenosides are more or less sensitive to P-glycoprotein efflux. This means that not only are we increasing the overall bioavailability of the ginsenosides in our bodies, we are also making sure they all stay active for a more balanced amount of time. This further capitalizes on our concept of balancing out the ginsenosides, as we are not just balancing the levels in the actual product, but also in our bodies! Schisandra chinensis in Shengmai-san is also described as an assistant herb. This means that it has some of its own minor effects that it adds to the formula. In the case of PanaMAX, this appears to be mood elevation. Panax ginseng root and Panax ginseng leaf extracts combined already provided quite a good mood boost, but adding in the Schisandra chinensis capitalized on this mood boost. Overall, we believe PanaMAX is on of the best adaptogen supplements we have come across. The stress management and mood elevation that PanaMAX can provide is really quite remarkable.
How to take PanaMAX Optimized Ginseng Capsules
We envision two ways in which PanaMAX can be used:
1. Individuals whom need consistent stress management support will benefit greatly from supplementing PanaMAX on a daily basis. This will help keep them calm, focused, and healthy. Stress also reduces immune function, and Panax ginseng helps support a healthy immune response. As discussed earlier, it also helps keep our stress levels balanced, rather than completely eliminating stress. This will help ensure that PanaMAX can decrease stress but won’t rob us of our motivation. For this use, we would suggest taking PanaMAX in the mornings so that you can experience stress support throughout the day.
2. The second way in which we can envision PanaMAX being used is as an acute stress manager. PanaMAX does not require a prolonged build up time in the body in order to provide effective stress support, so it can be taken when you have bitten off more than you can chew, and might be feeling overwhelmed. We have used PanaMAX this way throughout the office, any many of our employees have been extremely impressed with the quick relief they get. The stress management effects come on fairly quickly, and so it can be utilized as a very beneficial tool in high stress situations.