How Senactiv® Allows You To Train Hard & Recover Harder
This is second in a series of updated Blogs on Optygen & OptygenHP, long-time favorites of First Endurance users. In this blog, Dr. Bucci discusses one of the key components of OptygenHP, an adaptogen combination recently renamed as Senactiv®, previously known as ActiGin Proprietary Matrix.
Adaptogens & New Insights Hiding in Plain Sight
Senactiv® for Endurance Exercise
Senactiv® has been carefully designed and clinically studied to improve exercise recovery and thus, performance. It speeds up normal muscle repair processes after strenuous exercise and improves exercise capacity by increasing muscle energy (ATP) production. Let’s do a little digging into what Senactiv® actually is and how it produces these effects.
OptygenHP’s ActiGin® Proprietary Matrix is Now Senactiv®
Before getting into the clinical weeds, a nomenclature clarification: Senactiv® is exactly the same ingredient as the ActiGin® formerly used in OptygenHP. Only the name has changed. The supplier of Senactiv®, NuLiv Science, changed the name recently because there were too many branded ingredients with ActiWhatever names, creating confusion in the marketplace. Senactiv® keeps the ACTIVe part of the name, but makes it more specific to ginseng: ginSENg + ACTIVe = SENACTIV, or active ginseng – get it? Our website shows the name change in the Supplement Facts page for OptygenHP.
Luke Bucci PhD
Chief Scientific Officer
What is Senactiv®?
Senactiv® is a patented combination of two adaptogenic extracts – Notoginseng root (Panax notoginseng, aka san-chi ginseng) and the more familiar rose hips (Rosa roxburghii) (Kuo 2020) – that can do a lot even with a relatively paltry 50mg per serving.
Notoginseng is the forgotten ginseng behind Chinese/Korean/Siberian ginseng (Panax ginseng), Japanese ginseng (Panax japonicus) and American ginseng (Panax quinquefolium) (see Figure 1). Notoginseng has the usual spectrum of ginseng’s primary active agents – polysaccharides and saponins, specifically ginsenosides – with different ratios than the other ginsengs.
Siberian ginseng has been permanently renamed to Eleutherococcus senticosum or Eleuthero – only Panax species can be called ginseng.
Ginsenosides interact with enzymes, receptors, and sensing machinery to trigger your body to make specific signals for adapting you to stay healthy (hence “adaptogenic”). But ginsenosides can be tricky. Assuming you have the right microbiome, some of the active ginsenosides are made by your gut bacteria; however, modern sugar-fed microbiomes tend to not have the right gut bugs to convert ginsenosides into their more active forms. This explains a lot of the regional variability for results in human studies.
Notoginseng’s main claim to fame is that, with the right patented processing, it yields a concentrated extract of ginsenoside Rg1, similar to what a healthy gut biome produces (see Figure 2). This highly effective concentration is what enables the lower dose mentioned earlier (less than 50mg) than other ginseng materials, and it delivers a very active and absorbable ginsenoside before it gets to your gut bugs. In short, Notoginseng in Senactiv® is a supercharged concentrate of the best ginseng root. (More on this later in How Does Senactiv® Work?)
The second component of Senactiv® is something more familiar: rose hips. This is the bulbous thing that forms after the rose bloom falls off – it’s the seed pod (fruit) for rose bushes. But this is not your garden variety rose hip; Senactiv® uses a specific variety of antique Chestnut Rose (Rosa roxburghii) fruit from the Guizhuo province in China, widely cultivated and used as a functional food for centuries (see Figure 3).
R. roxburghii extract in Senactiv® has high levels of unique and rare molecules that are different from the vitamin C and antioxidant flavonoids in garden variety rose hips. These rare molecules are flavonoids, triterpenes, phenylpropanoids, and pyranosides. Some of these closely resemble ginsenosides, which should clue you in to what this extract can do.
Again, processing is the key to concentrating these rare molecules (most have unfathomable names, but our bodies know how to use them – good thing our bodies can’t spell). These fancy molecules act similarly to ginsenosides, but are different enough to have added or synergistic biological effects.
Figure 1: Panax notoginseng dried roots photograph (A), and illustration of entire plant (B).
Adapted from Duan 2017.
Figure 2: 2D Chemical Structure of Ginsenoside Rg1 (PubChem)
Senactiv®, Autophagy, and the Good Side of Exercise-Induced Inflammation & Muscle Damage
No Pain, No Gain
Senactiv® is much more than just a less-used type of ginseng with rose hips. It is carefully constructed to help orchestrate your body’s responses to improve muscle recovery after exercise stress by precisely regulating control signaling.
Intense, demanding exercise increases rate of fuel oxidation, which increases spinoff of free radicals in mitochondria, which causes subcellular structural damage, triggering an inflammatory response, aka Exercise-Induced Muscle Damage or EIMD. This is why you feel Delayed-Onset Muscle Soreness (DOMS) from intense, demanding exercise for a few days.
Muscle, immune and blood/lymphatic vessel cells can repair damage, survive, and thrive – they need to or else you would not survive, grow, or age. The first step in repair (and adaptive training, too) is to clear out the defective cells that have enough subcellular damage, especially the mitochondrial furnaces that generate energy from fuel. This is called autophagy (literally eating oneself), and it’s part of the circle of homeostasis, or maintaining health. It’s what all living creatures do all the time, and yes, this process is brutally induced by hard training and racing.
All cells have a well-developed system to turn over broken subcellular components, from whole organelles to individual proteins or lipids and, of course, DNA and RNA. Ultimately, damaged molecules are sent to intracellular scrap heaps and recycling centers. The resulting pieces are used to make more cell proteins, lipids, DNA, RNA, all sorts of molecules, membranes and organelles. All this intracellular traffic needs orchestration, which is accomplished by a massive signaling and receiving network inside of cells, and also outside of cells – to communicate to the rest of the body for their information and for their help.
The first step in autophagy is what we call inflammation – perfectly normal and essential for life, and more exercise causes more inflammation and results in more DOMS. Because pain is part of the massive signaling processes, and because our brains have been conditioned to not like pain, we look at inflammation as a bad thing and try to suppress it.
While pain and even inflammation can be suppressed effectively with administration of exogenous, synthetic, unnatural molecular mimics of endogenous signals (NSAIDs, opioids, corticosteroids, and more), the underlying homeostasis has already begun thanks to autophagy. EIMD speeds up the background rate of autophagy and homeostasis so muscles can repair and improve (adaptive training)2.
2Citations for autophagy, homeostasis, inflammation & EIMD during exercise: Erlich 2019; Jamart 2012; Ji 2007; Kuo 2019, 2020; Liu 2020; Martin-Tincon 2018; Schirrmacher 2021; Sousa 2014; Tipton 2018; Tota 2019.
Senactiv® Takes out the Garbage
Senactiv® interacts with, bolsters, and speeds up the normal subcellular repair processes in muscles and other organs after intense exercise. Those odd compounds from the combination of Notoginseng and rose hip concentrates, unique to Senactiv®, mimic normal signals our bodies use for constant, ongoing repair, adding to your body’s response – IF you have exercised enough to produce EIMD. These unusual benefits in exercising humans have only recently been discovered and studied.
Post-endurance exercise muscle biopsies illustrate this effect (Wu 2020). Measurement of a protein called p16INK4a is a marker for senescent cells, or cells marked for disposal. Three hours after exercise, when senescent cells peak, 5mg of ginsenoside Rg1 from Notoginseng returned the senescent cell levels back to normal. This finding is interpreted as speeding up senescent cell removal – or taking out the garbage. The difference is both clear and significant. Rg1 speeds up muscle recovery, which over time, can improve training effects and thus, performance (see Figure 4).
Though Figure 4 measures senescence three hours after three hours of cycling, other findings from the same exercise stress in shorter duration (one hour of cycling) found that ginsenoside Rg13 led to fewer free radical damage indicators (TBARS), enhanced muscle glycogen replenishment, decreased inflammatory markers4, and increased time-to-exhaustion and total work by 20%5(Hou 2015) (see Figure 5). In another, similar study, the majority of subjects (75%) bettered their time to exhaustion (Wu 2019 580).
Other findings from additional human studies after exercise using ginsenoside Rg1 found similar improvements in muscle repair after strenuous exercise, including
- reduced muscle satellite (stem) cell aging (Lee 2021);
- reduced senescent cells (Wu 2019 580, 2020);
- increased activation, proliferation, differentiation and fusion of muscle satellite cells (Wu 2019 27);
- decreased leukocyte infiltration (Wu 2019 580);
- increased macrophage presence and activities (Wu 2019 580, 2020);
- reduced apoptotic DNA fragmentation after exercise (Wu 2019 580);
- increased inducible nitric oxide synthase (iNOS) and IL-6 mRNA
- synthesis (Wu 2019 580);
- reduced IL-10 mRNA synthesis (Wu 2020), decreased collagenase activity (Wu 2019 580); and
- more myogenesis (Wu 2019 27), making muscles stronger and better trained.
3 5mg one night and one hour before exercise.
4 TNF-alpha, restored IL-10 mRNA.
5 38 vs. 32 minutes cycle ergometry at 80% VO2max and 306 vs. 254kJ.
Likewise, in a ginsenoside Rg1 study of resistance training (squats), perceived exertion, muscle cell senescence, and myeloperoxidase decreased while endothelial progenitor cells increased (Lee 2021).
Figure 6: Increased Cycling Time to Exhaustion by Unstandardized Notoginseng (adapted from Liang 2005).
Interestingly, Notoginseng studies that combine it with other ginsenosides, which have differing activities that might mute the desired effects of Rg1, still showed positive results. The first was a study with 29 subjects that found improvements in cycle ergometry exercise from 1,350mg daily Notoginseng supplementation for one month, compared to placebo (Liang 2005)(See Figure 6). The daily dose of ginsenoside Rg1 was 50mg out of 200mg of total ginsenosides. Ginsenoside Rb1 was present at the same amount, and is known to be a relaxant and central depressant (in other words, anti-ergogenic).
Another human study gave 4,000mg of unstandardized Notoginseng powder or placebo to 20 exercising men to produce delayed-onset muscle soreness by downhill running (Pumpa 2014). At two hours post-exercise, some markers of performance and recovery were significantly improved by Notoginseng, but other markers were not significantly different, even though numerically favoring Notoginseng.
This study showed a large variation in each measurement, decreasing statistical power to find meaningful differences. This study differs from the Senactiv® ginsenoside Rg1 series of studies by not determining if or how much ginsenosides were actually given, and thus, is irrelevant to the findings from Senactiv®.
These results suggested that making a Notoginseng extract rich in Rg1 without conflicting ginesenosides would be more effective, and Senactiv® was born. Ginsenoside Rg1 by itself is considered a central stimulant with anti-fatigue activity – very relevant to Senactiv® containing small doses of only Rg1 as a key for success!
What about the contribution of Rosa roxburghii? Although Chestnut Rose fruit does not have human clinicals on exercise performance itself, its traditional use for centuries has been to promote healthy aging, just like ginseng.
Rosa roxburghii fruit has flavonoids, polysaccharides, triterpenes, and lipid components that have been shown to have antioxidant, anti-apoptosis, and antistress signaling effects that are a perfect match to ginsenoside Rg1’s effects (Liu 2016; Marmaol 2017; van Rensburg 2005; Xu 2016; Zhan 2019).
The Custodian of Muscles
Every well-operating facility needs a good custodial crew. Sooner or later, all of us will confront enough stress for adaptogens to have utility by speeding up recovery processes and taking out the trash, and endurance exercise is a sure bet to get cellular stress. Just as interesting is that speeding up recovery by taking out the garbage is the same process of slowing growth and aging, which is where adaptogens got their start.
Long-term, consistent use of adaptogens helps your body resolve stress and preserve homeostasis, and Senactiv® is only one of the homeostatic adaptogens in OptygenHP. Future blogs will take a closer look at each adaptogen in Optygen and OptygenHP.
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