Nutritional value (mg) for 2 capsules

Caffshock®: 400
of which caffeine: 80
of which polyphenols: 80
of which chlorogenic acids: 60

Zynamite®: 300
of which mangiferine: 180

Ginselect ™ (ginseng extract): 200
of which ginsenosides (7%): 14

Vitamin B3: 14 or 100% of the AR *

*Reference contributions

Mental fatigue or physical fatigue? [1,2]

The feeling of energy translates into a state which allows one to be concentrated, vigilant, focused ... These are terms that also reflect the ability to memorize information, to learn or quite simply to carry out a habitual activity.

Feeling tired, as opposed to feeling energized, is a condition that is considered subjective. We must also distinguish mental or cognitive fatigue (brain, central nervous system) and physical fatigue (objective state whose seat is rather the skeletal muscle), although they are both potentially correlated.

So why do we sometimes feel tired?
Of course, sleep is essential. It is THE factor that allows us to maintain our daily activities. Sleep is the time of rest allowing to recover from the physical fatigue accumulated during the day but also from mental fatigue (concentration is paused).Attention is a brain function that allows you to select at each moment of the day what you want or need to do to achieve an achievement. It is therefore a constant and normal stress. But our attention span depends on other parameters which evolve rapidly nowadays: rapid sequence of tasks, tireless interruptions of notifications from our smartphones, irregular rhythms ... We are very familiar with these daily situations that we find in particular in the professions. with high responsibilities, precision jobs, the roles of “Super-mom”, or even studies ...Athletes can also be affected due to the need to deploy a certain will in physical effort, that is to say, a strong and prolonged concentration to optimize performance. All these environments require a particular attentional load (efforts of concentration) and can cause a feeling of mental “fog”.

Also, certain repeated actions of slow and not very stimulating tasks can lead to loss of attention due to lack of stimulation (hypovigilance). And sometimes, mental fatigue and this hypovigilance merge ...

Finally, mental load, stress, and other emotions directly influence our attentional capacity. This mental and intellectual fatigue can therefore be the cause of inadequate energy, weariness in the face of a daily action to be carried out, unavailability to complete a job and disengagement (loss of motivation) in the job. task carried out. These sensations can also lead to a feeling of physical fatigue, even if it does not come directly from muscle strain [2].

Mental fatigue and the brain, how to measure it?

The principle of cognitive fatigue is fairly simple to understand but its physiological mechanisms are much less so. The brain, representing a very small fraction of our body weight, is alone home to 20% of oxygen metabolism and is the most glucose-consuming organ (Watts, 2018). The hypothesis would therefore be as follows: an intense, prolonged and unusual work task would lead to an energy limitation in brain activity.

But what you need to know is that the brain works like a generator that is passed through by electrical signals. These are generated by movements of particles in neurons (such as dopaminergic neurons) which induce microcurrents. Brain activity is then translated into frequency waves. These waves are classified according to their intensity, from Gamma waves (intense mental activity), to Delta waves (sleep state). As a result, these are witnesses of brain activity but also of mental state [3].

Ultimately, two approaches to measuring brain activity can be used (seen in clinical studies):

• The behavioral approach which consists of observing the state of fatigue via variations in behavior ("CDR computerized assessment system"). This method includes a battery of different tests of attention, memory, responsiveness ...,
• The functional approach, which consists of measuring brain activity to deduce the state of fatigue by correlations (electroencephalogram, functional MRI). One of these methods consists, for example, in measuring brain waves during intense mental activity and in measuring its evolution over time.

How to act?

Compounds associated with beneficial effects on the brain are sometimes referred to as nootropics. This definition covers fairly broad effects on cognitive functions ranging from memory to concentration.

Regarding nutraceuticals, many compounds and active ingredients can claim this qualification: plant extracts (especially adaptogens), amino acids (and protein derivatives), fatty acids, antioxidants [5] ... Their actions can even be very specific : activators or inhibitors of certain nerve pathways, protectors of nerve cells (neuroprotection)…

Ginseng: a precious root

Ginseng is a member of the Araliaceae family, and it is one of the oldest nootropics listed. Under the generic name of “ginseng”, there are in fact several botanical species:

• Panax ginseng (Asian ginseng; from Korea or China),
• Panax japonicas (Japanese ginseng),
• Panax quinquefolius (North American, Siberian ginseng)

C.A. Meyer panax ginseng is considered the “authentic” ginseng, due to its greater decline and history of medicinal use.

Panax ginseng
Panax ginseng has been known for thousands of years in oriental medicine. It is one of the most important medicinal plants, especially in Korea, China and Japan. This plant has traditionally been used as a stimulant, but researchers have reported empirical use also in many areas including immunity [6]. Nowadays, ginseng has established itself as a reference nutraceutical with an exponential increase in its publications and in particular in clinical studies since 2005 [7]. The root of panax ginseng C.A. Meyer is composed of many bioactive compounds: polysaccharides, polyphenols and cyclic terpenes, in this case saponins including the famous ginsenosides.

White and red panax ginseng
Although they are both made from C.A. Meyer panax ginseng, white ginseng and red ginseng are not created equal. White ginseng only corresponds to the plant (root) dried without other processes, while red ginseng (also root) has undergone a maturation process, including heating which gives it its red-brown color. In addition, the roots used for red ginseng are generally older: around 6 years old instead of 3-4 years old for white ginseng. This process is absolutely ancestral and its tradition has been perpetuated for more than 1000 years in Korea. And it is not a hazard ; this additional maturation gives red ginseng a higher rate of saponins and therefore of ginsenosides, key molecules in its effectiveness. In other words, the transformation of white ginseng into red ginseng will “potentiate” its effect [7,8]. Finally, ginseng is the perfect example of the reconciliation between science and ancient traditions!

Panax ginseng and its ginsenosides
C.A. Meyer panax ginseng is primarily known for ginsenosides. These molecules belong, as we have seen, to the family of saponins (which are part of the triterpenoids). Over 50 different ginsenosides have been referenced in ginseng. The raw root of ginseng contains about 2-3% ginsenosides. The Rg1, Rc, Rd, Rb1, Rb2 and Re are the so-called “major” ginsenosides and vary according to the ginsengs, although Rb1 and Rg1 are the most abundant. Also, there are so-called “rare” ginsenosides, such as Rg2, Rg3, Rh2 and Rh3. The latter are also qualified as “noble”, because they are present in very small quantities and are only found in red ginseng. Indeed, the transformation of white ginseng into red ginseng increases the overall concentration of ginsenosides and particularly promotes the formation of rare ginsenosides [8]. Beyond this distinction between major and rare ginsenosides, Science classifies them into two categories according to their molecular structure:

• The 20 (S) -protopanaxadioles (PPD): Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2, Rh3, Rs1,
• The 20 (S) -protopanaxatrioles (PPT): Re, Rf, Rg1, Rg2, Rh1.

Note that the major ginsenosides actually have low bioavailability. On the other hand, within our organism (during digestion via the intestinal microbiota) they can be metabolized into these famous rare ginsenosides, more bioavailable and therefore more bioactive [9–11].

Panax ginseng in Nutraceuticals
In Nutraceuticals, it is the ginseng root that is of interest. It is this that will guarantee the presence of ginsenosides. In addition, panax ginseng C.A. Meyer has experienced enormous enthusiasm in the market, which has led to stricter supervision by the Korean Foods & Drugs Administration (“KFDA”, the Korean food and drug products agency). Why ? Because some Korean ginseng products contained sometimes very high amounts of ginsenosides, so high that it was suspected. Indeed, the Korean authorities quickly understood that many extracts or powders were quite simply adulterated by the addition of saponins. These saponins can be extracted from another plant (bellflower flowers) or even from ginseng leaves. It is actually easier to use the leaves than to wait 6 years to harvest the roots and mature them ... It should also be noted that this adulteration is not without risk. Ginseng leaves are not authorized in France for use in Nutraceuticals ...

To select a ginseng, it is therefore important to look at 2 main parameters, even after having checked the logistical traceability of the material:

• Check the content of ginsenosides, in particular the quantity Rb1 + Rg1, ie the two most abundant ginsenosides (measurement by chromatographic method).
• To go further and detect possible adulterations, we must also look at the ratios of ginsenosides to each other. For example, the Rb1 / Rg1 ratio makes it possible to confirm that we are indeed dealing with an extract of mature root (and not of leaves). It also helps to differentiate authentic ginseng (panax red ginseng Vs American ginseng).

Extraction of ginseng roots
Afterwards, it is the quality of the extraction and its process that will ensure a good ginseng. In this context, the standardization of panax ginseng G115 extract represents a unique process and an “ideal” example of a standardized extract. Indeed, ginseng G115 is the first to have been standardized with a well-defined level of ginsenosides, the first to have received a Marketing Authorization (Marketing Authorization) and to be registered on the European market as a medicinal plant ( In the 60s). This registration means that it is therefore listed in the European Pharmacopoeia and benefits from a monograph which defines its production framework but also its precise characteristics. The validation of this approach demonstrates irreproachable consistency in terms of quality and efficiency. G115 is thus derived from an ethanol extraction of C.A. Meyer panax ginseng roots and is standardized to 4% major ginsenosides based on an extraction ratio of 3: 1 to 7: 1. This extract is a model, and is in a way a “gold standard” for Nutraceuticals [10,12].

In Nutraceuticals, it is in fact impossible to use G115, the use of which is reserved for herbal medicines (since it is listed in the pharmacopoeia). On the other hand, it is possible to use a strictly equivalent extract: our ginseng, Ginselect ™, in all points equivalent to G115:

• Same primary material
• Same extraction ratio
• Same extraction process (method and elution)Same profile (rate and ratios) in ginsenosides

Panax ginseng in clinical studies
Ginseng has been and still is the subject of numerous clinical studies. These beneficial effects have been demonstrated on several levels, in particular on stress and on cognitive functions. It is because of these known effects on stress that ginseng is considered an adaptogenic plant. Several reviews and meta-analyzes have concluded with beneficial effects and in general, ginseng, thanks to ginsenosides and their stimulating effects, is an effective nutraceutical for mental fatigue [10,12–15]. In the case of ginseng, the variability of clinical results depends on the type of extract studied. It is therefore decisive to select an extract benefiting from a monograph or an equivalent (that is to say with a strict and repeatable production framework), this makes it possible to highlight the beneficial effects of ginseng in a more rigorous and meaningful. Today, with the many studies to the credit of the G115 and a review of more than 50 years on the market, its use is known and recognized. More precisely, from 200 mg / day (7% of ginsenosides) taken once or over several weeks (depending on the studies), a good extract of ginseng would improve: the response to cognitive tests (such as memory tests or reactivity), the activation of the neural circuits of the cerebral arousal state or the oxygenation systems in the context of physical performance [12].

The Nutri & Co choice: Ginselect ™
To select our ginseng, we have endeavored to respond to two main issues:

• Traceability excluding any risk of adulteration (100% root, no added saponins),
• Guaranteed efficiency through process control and rigorous standardization.

We have chosen the specific Ginselect ™ extract:

• The botanical species: an authentic C.A. Meyer panax ginseng extract,
• A potentiated ginseng: red ginseng,
• Full traceability: a traditional Asian origin and Italian manufacture,
• Perfect equivalence with the "Gold Standard" extract: a manufacturing process proving similarity with the process for obtaining G115,
• Rigorous identification by chromatography,
• Strict standardization at 7% of ginsenosides with specific monitoring of the level of Rg1 + Rh1.

Mangiferine: a rare polyphenol

Mangiferin (family Anacardiaceae) is a natural xanthone (a C-glycosyl xanthone) found in the mango tree (Mangifera indica). This structurally specific polyphenol has received special attention since the discovery of its very important bioactivity [16]. In addition, its structural difference suggests a mechanism of action that is distinct (and therefore potentially complementary) to that of conventional polyphenols of the flavonol type, and especially of saponins (which are not polyphenols but cyclic terpenes of the sterol family). Zynamite® is a compound standardized to more than 60% mangiferin. He has numerous publications to his credit:

• 2 preclinical studies [17,18],
• 6 clinical studies [19–24].

We selected it for the strength of its clinical data and for being the only patented active ingredient based on mangiferin that can be used in Nutraceuticals.

Caffeine: the ultimate stimulant

Caffeine falls under the category of psychotropic drugs. These are substances that can modify the physiological activity of the nervous system. The stimulating effects of caffeine on our mental activity are well known and well documented. The mechanism of action is also well known: caffeine is a natural antagonist of adenosine receptors in the brain, helping to prevent drowsiness.On the other hand, caffeine sometimes gets a bad press even if this is not justified in all aspects. Like many substances, “the dose makes the poison” (Paracelsus) and excess should be avoided. Indeed, in unreasonable amounts, caffeine has a diuretic and cardiac accelerator effect. According to scientific consensus, this upper limit is around 400 mg / day [25,26], while the positive effects on the feeling of energy are felt from 40 mg / day.

Our caffeine is found in the active Caffeshock®, a set of five plants (coffee, maca, mate, guarana, green tea), constituting a natural caffeine intake precisely dosed at 40 mg per capsule, or just as much as a whole small cup of coffee. Caffeshock® is not just about its caffeine intake since it also naturally contains polyphenols and chlorogenic acids.

The unique Nutri & Co combination

The rationale behind our formula is simple: the effectiveness is measured as much in the immediate effect of a sensation of “boost” (caffeine) as in a more prolonged effect, and especially in the absence of a sensation of "backlash" linked to the dissipation of the effect of caffeine (ginseng and mangiferine).In addition, the "stimulating nootropic" approach is comprehensive, thanks to the contribution of 3 different families of molecules (saponins, polyphenols and psychotropics) for an action on several levers of brain activity.

Publications

1. McDowd, J.M. An Overview of Attention: Behavior and Brain. J. Neurol. Phys. Ther. 2007, 31, 98–103, doi:10.1097/NPT.0b013e31814d7874.2.
2. Laurent, F. Détection de La Fatigue Mentale à Partir de Données Électrophysiologiques, Pierre et Marie Curie, 2011.3.
3. Pouch, A. LE NEUROFEEDBACK : TECHNIQUE EXPERIMENTALE DE TRAITEMENT DES MALADIES NEUROLOGIQUES COGNITIVES, Pharmacie - Aix-Marseille, 2018.4.
4. Kandlur, A.; Satyamoorthy, K.; Gangadharan, G. Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance. Front. Mol. Neurosci. 2020, 13, 41, doi:10.3389/fnmol.2020.00041.5.
5. Williams, R.J.; Mohanakumar, K.P.; Beart, P.M. Neuro-Nutraceuticals: Further Insights into Their Promise for Brain Health. Neurochem. Int. 2016, 95, 1–3, doi:10.1016/j.neuint.2016.03.016.6.
6. Smith, I.; Williamson, E.M.; Putnam, S.; Farrimond, J.; Whalley, B.J. Effects and Mechanisms of Ginseng and Ginsenosides on Cognition. Nutr. Rev. 72, 15.7.
7. He, Y.; Yang, J.; Lv, Y.; Chen, J.; Yin, F.; Huang, J.; Zheng, Q. A Review of Ginseng Clinical Trials Registered in the WHO International Clinical Trials Registry Platform. BioMed Res. Int. 2018, 2018, 1–7, doi:10.1155/2018/1843142.8.
8. Lee, S.M.; Bae, B.-S.; Park, H.-W.; Ahn, N.-G.; Cho, B.-G.; Cho, Y.-L.; Kwak, Y.-S. Characterization of Korean Red Ginseng (Panax Ginseng Meyer): History, Preparation Method, and Chemical Composition. J. Ginseng Res. 2015, 39, 384–391, doi:10.1016/j.jgr.2015.04.009.9.
9. Leung, K.W.; Wong, A.S.-T. Pharmacology of Ginsenosides: A Literature Review. 2010, 7.10.
10. EMA Assessment Report on Panax Ginseng C.A. Meyer, Radix. 2014, 124.11.
11. Shahrajabian, M.H.; Sun, W.; Cheng, Q. A Review of Ginseng Species in Different Regions as a Multipurpose Herb in Traditional Chinese Medicine, Modern Herbology and Pharmacological Science. J Med Plants Res 2019, 13, 213–226.12.
12. Bilia, A.R.; Bergonzi, M.C. The G115 Standardized Ginseng Extract: An Example for Safety, Efficacy, and Quality of an Herbal Medicine. J. Ginseng Res. 2020, 44, 179–193, doi:10.1016/j.jgr.2019.06.003.13.
13. Shergis, J.L.; Zhang, A.L.; Zhou, W.; Xue, C.C. Panax Ginseng in Randomised Controlled Trials: A Systematic Review. Phytother. Res. 2013, 27, 949–965, doi:10.1002/ptr.4832.14.
14. Bach, H.V.; Kim, J.; Myung, S.-K.; Cho, Y.A. Efficacy of Ginseng Supplements on Fatigue and Physical Performance: A Meta-Analysis. J. Korean Med. Sci. 2016, 31, 1879, doi:10.3346/jkms.2016.31.12.1879.15.
15. Jin, T.-Y. Clinical and Preclinical Systematic Review of Panax Ginseng C. A. Mey and Its Compounds for Fatigue. Front. Pharmacol. 2020, 11, 31.16.
16. Imran, M.; Arshad, M.S.; Butt, M.S.; Kwon, J.-H.; Arshad, M.U.; Sultan, M.T. Mangiferin: A Natural Miracle Bioactive Compound against Lifestyle Related Disorders. Lipids Health Dis. 2017, 16, 84, doi:10.1186/s12944-017-0449-y.17.
17. Reddeman, R.A.; Glávits, R.; Endres, J.R.; Clewell, A.E.; Hirka, G.; Vértesi, A.; Béres, E.; Szakonyiné, I.P. A Toxicological Evaluation of Mango Leaf Extract ( Mangifera Indica ) Containing 60% Mangiferin. J. Toxicol. 2019, 2019, 1–14, doi:10.1155/2019/4763015.18.
18. Dimpfel, W.; Wiebe, J.; Gericke, N.; Schombert, L. Zynamite® (Mangifera Indica Leaf Extract) and Caffeine Act in a Synergistic Manner on Electrophysiological Parameters of Rat Central Nervous System. Food Nutr. Sci. 17.19.
19. Gelabert-Rebato, M.; Wiebe, J.C.; Martin-Rincon, M.; Gericke, N.; Perez-Valera, M.; Curtelin, D.; Galvan-Alvarez, V.; Lopez-Rios, L.; Morales-Alamo, D.; Calbet, J.A.L. Mangifera Indica L. Leaf Extract in Combination With Luteolin or Quercetin Enhances VO2peak and Peak Power Output, and Preserves Skeletal Muscle Function During Ischemia-Reperfusion in Humans. Front. Physiol. 2018, 9, 15.20.
20. Gelabert-Rebato, M.; Martin-Rincon, M.; Galvan-Alvarez, V.; Gallego-Selles, A.; Martinez-Canton, M.; Vega-Morales, T.; Wiebe, J.C.; Castillo, C.F.; Castilla-Hernandez, E.; Diaz-Tiberio, O.; et al. A Single Dose of The Mango Leaf Extract Zynamite® in Combination with Quercetin Enhances Peak Power Output During Repeated Sprint Exercise in Men and Women. 2019, 17.21.
21. Gelabert-Rebato, M.; Wiebe, J.C.; Martin-Rincon, M.; Galvan-Alvarez, V.; Curtelin, D.; Perez-Valera, M.; Habib, J.J.; Pérez-López, A.; Vega, T.; Morales-Alamo, D.; et al. Enhancement of Exercise Performance by 48 Hours, and 15-Day Supplementation with Mangiferin and Luteolin in Men. 2019, 24.22.
22. Martin-Rincon, M.; Gelabert-Rebato, M.; Galvan-Alvarez, V.; Gallego-Selles, A.; Martinez-Canton, M.; Lopez-Rios, L.; Wiebe, J.C.; Martin-Rodriguez, S.; Arteaga-Ortiz, R.; Dorado, C.; et al. Supplementation with a Mango Leaf Extract (Zynamite®) in Combination with Quercetin Attenuates Muscle Damage and Pain and Accelerates Recovery after Strenuous Damaging Exercise. Nutrients 2020, 12, 614, doi:10.3390/nu12030614.23.
23. Wightman, E.L.; Jackson, P.A.; Forster, J.; Khan, J.; Wiebe, J.C.; Gericke, N.; Kennedy, D.O. Acute Effects of a Polyphenol-Rich Leaf Extract of Mangifera Indica L. (Zynamite) on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study. Nutrients 2020, 12, 2194, doi:10.3390/nu12082194.24.   
24. López-Ríos, L. Central Nervous System Activities of Extract Mangifera Indica L. J. Ethnopharmacol. 2020, 16.25.
25. Ruxton, C.H.S. The Impact of Caffeine on Mood, Cognitive Function, Performance and Hydration: A Review of Benefits and Risks. Nutr. Bull. 2008, 33, 15–25, doi:10.1111/j.1467-3010.2007.00665.x.26.
26. Pomeroy, D.E.; Tooley, K.L.; Probert, B.; Wilson, A.; Kemps, E. A Systematic Review of the Effect of Dietary Supplements on Cognitive Performance in Healthy Young Adults and Military Personnel. 2020, 32.