Nootropics

Potent psychoactive and neuroactive chemicals that play key roles in modulating receptor sites, synaptic enzymes, membrane structures, cerebral perfusion, biogenic processes, neuroendocrine regulation and more.

Coffeeberry® Whole Coffee Fruit Extract

Coffeeberry^® is made from organic coffee fruits, which are often called coffee cherries. Like cherries, coffee plants produce soft red fruits surrounding a pit or hard seed. The seed (or coffee “bean”) is roasted to make coffee. But it’s the fruit that is being used to make Coffeeberry^®. Similar to many fruits, coffee cherries are high in polyphenols. And like coffee beans, they also contain caffeine. There are more than 120 Coffea species. The most popular species is Coffea arabica (commonly known simply as "Arabica"). Coffeeberry^® is made from Arabica coffee plants grown on sustainable farms. The fruits are handpicked when they are ripe. The caffeine we get in a morning coffee, a cup of tea, or an energy drink can help us perform better physically and mentally.* It does this by promoting arousal (wakefulness), which is a necessary ingredient for being able to pay attention and react quickly. Not surprisingly, this has led to caffeine being one of the most widely used and studied substances for supporting both sports performance and brain function. While caffeine gets most of the attention, coffee polyphenols support healthy function. Most nootropics use pure caffeine; a better approach is using a coffee extract that gives caffeine and the naturally occurring coffee fruit polyphenols. 

TOP BENEFITS OF COFFEEBERRY^®

Supports cognitive performance*

Supports exercise performance*

Supports mood*

QUALIA’S COFFEEBERRY^® SOURCING

Coffeeberry^® organic whole coffee fruit extract is produced by Futureceuticals, a leader in fruit and vegetable extracts. 

Futureceuticals calls this ingredient CoffeeBerry^® Energy, because it contains a minimum of 70% caffeine, along with polyphenols from coffee cherries. 

Made from carefully selected, hand-picked, premium Arabica coffee cherries. 

Sustainably sourced from farms certified Fairtrade International & Rainforest Alliance.

Coffeeberry^® is Rainforest Alliance Certified™, Non-GMO Project Verified, gluten-free, vegan, Kosher, organic, GRAS and eco-friendly. 

COFFEEBERRY^® FORMULATING PRINCIPLES AND RATIONALE

Because of its content of caffeine, we consider Coffeeberry^® to follow hormetic dosing principles (see Qualia Dosing Principles) and to have a hormetic range (i.e., a dosing range below and above which results would be poorer). Caffeine is one of the most used, and best studied nootropic and ergogenic compounds. When used as a nootropic (i.e., to promote alertness, focus, reaction time, etc.) caffeine is typically dosed from 50 to 200 mg. When used as an ergogenic (i.e., for sports performance) just prior to exercise the upper end of the dose range can be as high as 600 mg [1]. In both of these cases, responses to caffeine tend to follow an adaptational (i.e., hormetic) curve, with low-to-moderate amounts of caffeine supporting better cognitive and sports performance, but servings above the higher end of the range hindering performance. The amount of Coffeeberry^® in a formulation will depend on whether it is being used alone or combined with other sources of caffeine, what the formula is for, and the role caffeine is supporting in a formula. *

CAFFEINE KEY MECHANISMS

Supports brain function*

Supports optimal adenosine receptor function* [2]

Optimizes, via adenosine receptor antagonism, the levels of the neurotransmitters acetylcholine, glutamate, serotonin, dopamine and norepinephrine* [3,4]

Supports healthy acetylcholine signaling* [4–7]

Supports healthy dopamine signaling* [4,8–13]

Supports healthy serotonin signaling* [4,7,14–17]

Supports healthy glutamate signaling* [4,8,9]

Supports healthy GABA signaling* [4,7]

Supports healthy noradrenaline signaling* [4,16]

Supports healthy cortical activation in the brain* [2,4]

Supports healthy cerebral metabolism* [2,4]

Promotes wakefulness* [18]

Supports cognitive function*

Supports cognitive performance* [1,4,19–22]

Supports executive function* [23–25]

Supports information processing rate* [2,26,27]

Supports simple and sustained attention* [1,23,27,28]

Supports vigilance* [1,28]

Supports reaction time* [1,21,22,27]

Supports reasoning* [20]

Supports creative thinking* [24]

Supports resistance to mental fatigue* [26,28]

Supports healthy neuroprotective functions* [29,30]

Supports a healthy mood*

Supports positive affect* [4,21,22,25,31]

Supports physical performance*

Supports healthy resistance to physical fatigue* [19,22,23,32]

Supports healthy resistance to perceived exhaustion* [1]

Supports muscle endurance and strength exercise activities* [1]

Supports speed, power, and agility during intense exercise* [1] 

Other actions*

Supports optimal metabolic rate* [33–35]

Supports healthy phosphodiesterase balance* [36]

Complementary ingredients*

L-Theanine to support cognitive performance* [26,37–40]

Choline donors (e.g., citicoline, alpha-GPC) to support attention, concentration, and working memory* [41]

L-ornithine to support enhanced mood and cognitive performance* [42]

Alpinia galanga to support cognitive performance* [43,44]

*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.

REFERENCES

[1]T.M. McLellan, J.A. Caldwell, H.R. Lieberman, Neurosci. Biobehav. Rev. 71 (2016) 294–312.

[2]G. Burnstock, Advances in Experimental Medicine and Biology 986 (2013) 1–12.

[3]B.B. Fredholm, Pharmacol. Toxicol. 76 (1995) 93–101.

[4]B.B. Fredholm, K. Bättig, J. Holmén, A. Nehlig, E.E. Zvartau, Pharmacol. Rev. 51 (1999) 83–133.

[5]E. Acquas, G. Tanda, G. Di Chiara, Neuropsychopharmacology 27 (2002) 182–193.

[6]A.J. Carter, W.T. O’Connor, M.J. Carter, U. Ungerstedt, J. Pharmacol. Exp. Ther. 273 (1995) 637–642.

[7]D. Shi, O. Nikodijević, K.A. Jacobson, J.W. Daly, Cell. Mol. Neurobiol. 13 (1993) 247–261.

[8]G. Racchetti, A. Lorusso, C. Schulte, D. Gavello, V. Carabelli, R. D’Alessandro, J. Meldolesi, J. Cell Sci. 123 (2010) 165–170.

[9]D. Quarta, J. Borycz, M. Solinas, K. Patkar, J. Hockemeyer, F. Ciruela, C. Lluis, R. Franco, A.S. Woods, S.R. Goldberg, S. Ferré, J. Neurochem. 91 (2004) 873–880.

[10]B.E. Garrett, S.G. Holtzman, Eur. J. Pharmacol. 262 (1994) 65–75.

[11]K.R. Powell, P.M. Iuvone, S.G. Holtzman, Pharmacol. Biochem. Behav. 69 (2001) 59–70.

[12]M. Solinas, S. Ferré, Z.-B. You, M. Karcz-Kubicha, P. Popoli, S.R. Goldberg, J. Neurosci. 22 (2002) 6321–6324.

[13]X. Zheng, S. Takatsu, H. Wang, H. Hasegawa, Pharmacol. Biochem. Behav. 122 (2014) 136–143.

[14]D.J. Haleem, A. Yasmeen, M.A. Haleem, A. Zafar, Life Sci. 57 (1995) PL285–92.

[15]S. Khaliq, S. Haider, F. Naqvi, T. Perveen, S. Saleem, D.J. Haleem, Pak. J. Pharm. Sci. 25 (2012) 21–25.

[16]M.D. Chen, W.H. Lin, Y.M. Song, P.Y. Lin, L.T. Ho, Zhonghua Yi Xue Za Zhi 53 (1994) 257–261.

[17]M. Okada, Y. Kawata, K. Kiryu, K. Mizuno, K. Wada, H. Tasaki, S. Kaneko, J. Neurochem. 69 (2002) 2581–2588.

[18]T. Porkka-Heiskanen, Handb. Exp. Pharmacol. (2011) 331–348.

[19]V. Maridakis, P.J. O’Connor, P.D. Tomporowski, Int. J. Neurosci. 119 (2009) 1239–1258.

[20]M.J. Jarvis, Psychopharmacology 110 (1993) 45–52.

[21]A. Nehlig, J. Alzheimers. Dis. 20 Suppl 1 (2010) S85–94.

[22]C.H.S. Ruxton, Nutr. Bull. 33 (2008) 15–25.

[23]J. Lanini, J.C.F. Galduróz, S. Pompéia, Hum. Psychopharmacol. 31 (2016) 29–43.

[24]K. Soar, E. Chapman, N. Lavan, A.S. Jansari, J.J.D. Turner, Appetite 105 (2016) 156–163.

[25]F.L. Dodd, D.O. Kennedy, L.M. Riby, C.F. Haskell-Ramsay, Psychopharmacology 232 (2015) 2563–2576.

[26]C.F. Haskell, D.O. Kennedy, A.L. Milne, K.A. Wesnes, A.B. Scholey, Biol. Psychol. 77 (2008) 113–122.

[27]S.J.L. Einöther, T. Giesbrecht, Psychopharmacology 225 (2013) 251–274.

[28]A. Smith, Food Chem. Toxicol. 40 (2002) 1243–1255.

[29]M.A. Schwarzschild, K. Xu, E. Oztas, J.P. Petzer, K. Castagnoli, N. Castagnoli Jr, J.-F. Chen, Neurology 61 (2003) S55–61.

[30]M. Kolahdouzan, M.J. Hamadeh, CNS Neurosci. Ther. 23 (2017) 272–290.

[31]S.H. Backhouse, S.J.H. Biddle, N.C. Bishop, C. Williams, Appetite 57 (2011) 247–252.

[32]J.M. Davis, Z. Zhao, H.S. Stock, K.A. Mehl, J. Buggy, G.A. Hand, Am. J. Physiol. Regul. Integr. Comp. Physiol. 284 (2003) R399–404.

[33]K.J. Acheson, B. Zahorska-Markiewicz, P. Pittet, K. Anantharaman, E. Jéquier, Am. J. Clin. Nutr. 33 (1980) 989–997.

[34]A. Astrup, S. Toubro, S. Cannon, P. Hein, L. Breum, J. Madsen, Am. J. Clin. Nutr. 51 (1990) 759–767.

[35]J. LeBlanc, M. Jobin, J. Côté, P. Samson, A. Labrie, J. Appl. Physiol. 59 (1985) 832–837.

[36]O.H. Choi, M.T. Shamim, W.L. Padgett, J.W. Daly, Life Sci. 43 (1988) 387–398.

[37]S.J.L. Einöther, V.E.G. Martens, J.A. Rycroft, E.A. De Bruin, Appetite 54 (2010) 406–409.

[38]T. Giesbrecht, J.A. Rycroft, M.J. Rowson, E.A. De Bruin, Nutr. Neurosci. 13 (2010) 283–290.

[39]G.N. Owen, H. Parnell, E.A. De Bruin, J.A. Rycroft, Nutr. Neurosci. 11 (2008) 193–198.

[40]C.N. Kahathuduwa, T.L. Dassanayake, A.M.T. Amarakoon, V.S. Weerasinghe, Nutr. Neurosci. 20 (2017) 369–377.

[41]S.E. Bruce, K.B. Werner, B.F. Preston, L.M. Baker, Int. J. Food Sci. Nutr. 65 (2014) 1003–1007.

[42]A. Misaizu, T. Kokubo, K. Tazumi, M. Kanayama, Y. Miura, Prev Nutr Food Sci 19 (2014) 367–372.

[43]S. Srivastava, M. Mennemeier, S. Pimple, J. Am. Coll. Nutr. 36 (2017) 631–639.

[44]S. Srivastava, M. Mennemeier, J.A. Chaudhary, J. Am. Coll. Nutr. 40 (2021) 224–236.

Caffeine (from Green Tea Extract)

Caffeine is a methylxanthine compound used to counter fatigue and promote alertness. It’s found in the seeds, fruits, nuts, or leaves of a number of plants native to Africa, East Asia, and South America. These include coffee beans (as well as coffee cherry fruits), cocoa beans, guarana berries, kola nuts, and leaves from tea, guayusa, and yerba mate. Caffeine is quickly absorbed in the gastrointestinal tract and is able to easily cross the blood-brain barrier to reach the brain, where it has stimulating and invigorating mechanisms. The caffeine we get in a morning coffee, a cup of tea, or an energy drink can help us perform better physically and mentally.* It does this by promoting arousal (wakefulness), which is a necessary ingredient for being able to pay attention and react quickly. Not surprisingly, this has led to caffeine being one of the most widely used and studied substances for both sports performance and brain function.* In addition to being a source of caffeine, green tea (Camelia sinensis) is rich in polyphenols with antioxidant properties, including catechins, theaflavins, tannins, and flavonoids [1].

TOP BENEFITS OF CAFFEINE

Supports cognitive performance*

Supports exercise performance*

Supports mood* 

QUALIA’S CAFFEINE SOURCING

Caffeine sourced from Green Tea Extract standardized to not less than 60% caffeine.

Caffeine from Green Tea Extract is a non-GMO, gluten-free, vegan, Kosher, and Halal certified ingredient.

CAFFEINE FORMULATING PRINCIPLES AND RATIONALE

We consider caffeine to follow hormetic dosing principles (see Qualia Dosing Principles) and to have a hormetic range (i.e., a dosing range below and above which results would be poorer). Caffeine is one of the most used, and best studied nootropic and ergogenic compounds. As a nootropic (i.e., to promote alertness, focus, reaction time, etc.) caffeine is typically used in amounts ranging from 50 to 200 mg. As an ergogenic (i.e., for sports performance) just prior to exercise, the upper end of the serving range can be as high as 600 mg [2]. In both of these cases, responses to caffeine tend to follow a hormetic curve, with low-to-moderate doses of caffeine supporting better cognitive and sports performance, but serving above the higher end of the range hindering performance. We have selected a serving of caffeine from green tea at the lower end of the range for nootropic purposes.*

CAFFEINE KEY MECHANISMS

 Supports brain function*

Supports optimal adenosine receptor function* [3]

Optimizes, via adenosine receptor antagonism, the levels of the neurotransmitters acetylcholine, glutamate, serotonin, dopamine, and norepinephrine* [4,5]

Supports healthy acetylcholine signaling* [5–8]

Supports healthy dopamine signaling* [5,9–14]

Supports healthy serotonin signaling* [5,8,15–18]

Supports healthy glutamate signaling* [5,9,10]

Supports healthy GABA signaling* [5,8]

Supports healthy noradrenaline signaling* [5,17]

Supports healthy cortical activation in the brain* [3,5]

Supports healthy cerebral metabolism* [3,5]

Promotes wakefulness* [19]

Supports cognitive function*

Supports cognitive performance* [2,5,20–23]

Supports executive function* [24–26]

Supports information processing rate* [3,27,28]

Supports simple and sustained attention* [2,24,28,29]

Supports vigilance* [2,29]

Supports reaction time* [2,22,23,28]

Supports reasoning* [21]

Supports creative thinking* [25]

Supports resistance to mental fatigue* [27,29]

Supports healthy neuroprotective functions* [30,31]

Supports a healthy mood*

Supports positive affect* [5,22,23,26,32]

Supports physical performance*

Supports healthy resistance to physical fatigue* [20,23,24,33]

Supports healthy resistance to perceived exhaustion* [2]

Supports muscle endurance and strength exercise activities* [2]

Supports speed, power, and agility during intense exercise* [2] 

Other actions*

Supports optimal metabolic rate* [34–36]

Supports healthy phosphodiesterase balance* [37]

Complementary ingredients*

L-Theanine to support cognitive performance* [27,38–41]

Choline donors (e.g., citicoline, alpha-GPC) to support attention, concentration, and working memory* [42]

L-ornithine to support enhanced mood and cognitive performance* [43]

Alpinia galanga to support cognitive performance* [44,45]

*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.

REFERENCES

[1]N. Khan, H. Mukhtar, Curr. Pharm. Des. 19 (2013) 6141–6147.

[2]T.M. McLellan, J.A. Caldwell, H.R. Lieberman, Neurosci. Biobehav. Rev. 71 (2016) 294–312.

[3]G. Burnstock, Advances in Experimental Medicine and Biology 986 (2013) 1–12.

[4]B.B. Fredholm, Pharmacol. Toxicol. 76 (1995) 93–101.

[5]B.B. Fredholm, K. Bättig, J. Holmén, A. Nehlig, E.E. Zvartau, Pharmacol. Rev. 51 (1999) 83–133.

[6]E. Acquas, G. Tanda, G. Di Chiara, Neuropsychopharmacology 27 (2002) 182–193.

[7]A.J. Carter, W.T. O’Connor, M.J. Carter, U. Ungerstedt, J. Pharmacol. Exp. Ther. 273 (1995) 637–642.

[8]D. Shi, O. Nikodijević, K.A. Jacobson, J.W. Daly, Cell. Mol. Neurobiol. 13 (1993) 247–261.

[9]G. Racchetti, A. Lorusso, C. Schulte, D. Gavello, V. Carabelli, R. D’Alessandro, J. Meldolesi, J. Cell Sci. 123 (2010) 165–170.

[10]D. Quarta, J. Borycz, M. Solinas, K. Patkar, J. Hockemeyer, F. Ciruela, C. Lluis, R. Franco, A.S. Woods, S.R. Goldberg, S. Ferré, J. Neurochem. 91 (2004) 873–880.

[11]B.E. Garrett, S.G. Holtzman, Eur. J. Pharmacol. 262 (1994) 65–75.

[12]K.R. Powell, P.M. Iuvone, S.G. Holtzman, Pharmacol. Biochem. Behav. 69 (2001) 59–70.

[13]M. Solinas, S. Ferré, Z.-B. You, M. Karcz-Kubicha, P. Popoli, S.R. Goldberg, J. Neurosci. 22 (2002) 6321–6324.

[14]X. Zheng, S. Takatsu, H. Wang, H. Hasegawa, Pharmacol. Biochem. Behav. 122 (2014) 136–143.

[15]D.J. Haleem, A. Yasmeen, M.A. Haleem, A. Zafar, Life Sci. 57 (1995) PL285–92.

[16]S. Khaliq, S. Haider, F. Naqvi, T. Perveen, S. Saleem, D.J. Haleem, Pak. J. Pharm. Sci. 25 (2012) 21–25.

[17]M.D. Chen, W.H. Lin, Y.M. Song, P.Y. Lin, L.T. Ho, Zhonghua Yi Xue Za Zhi 53 (1994) 257–261.

[18]M. Okada, Y. Kawata, K. Kiryu, K. Mizuno, K. Wada, H. Tasaki, S. Kaneko, J. Neurochem. 69 (2002) 2581–2588.

[19]T. Porkka-Heiskanen, Handb. Exp. Pharmacol. (2011) 331–348.

[20]V. Maridakis, P.J. O’Connor, P.D. Tomporowski, Int. J. Neurosci. 119 (2009) 1239–1258.

[21]M.J. Jarvis, Psychopharmacology 110 (1993) 45–52.

[22]A. Nehlig, J. Alzheimers. Dis. 20 Suppl 1 (2010) S85–94.

[23]C.H.S. Ruxton, Nutr. Bull. 33 (2008) 15–25.

[24]J. Lanini, J.C.F. Galduróz, S. Pompéia, Hum. Psychopharmacol. 31 (2016) 29–43.

[25]K. Soar, E. Chapman, N. Lavan, A.S. Jansari, J.J.D. Turner, Appetite 105 (2016) 156–163.

[26]F.L. Dodd, D.O. Kennedy, L.M. Riby, C.F. Haskell-Ramsay, Psychopharmacology 232 (2015) 2563–2576.

[27]C.F. Haskell, D.O. Kennedy, A.L. Milne, K.A. Wesnes, A.B. Scholey, Biol. Psychol. 77 (2008) 113–122.

[28]S.J.L. Einöther, T. Giesbrecht, Psychopharmacology 225 (2013) 251–274.

[29]A. Smith, Food Chem. Toxicol. 40 (2002) 1243–1255.

[30]M.A. Schwarzschild, K. Xu, E. Oztas, J.P. Petzer, K. Castagnoli, N. Castagnoli Jr, J.-F. Chen, Neurology 61 (2003) S55–61.

[31]M. Kolahdouzan, M.J. Hamadeh, CNS Neurosci. Ther. 23 (2017) 272–290.

[32]S.H. Backhouse, S.J.H. Biddle, N.C. Bishop, C. Williams, Appetite 57 (2011) 247–252.

[33]J.M. Davis, Z. Zhao, H.S. Stock, K.A. Mehl, J. Buggy, G.A. Hand, Am. J. Physiol. Regul. Integr. Comp. Physiol. 284 (2003) R399–404.

[34]K.J. Acheson, B. Zahorska-Markiewicz, P. Pittet, K. Anantharaman, E. Jéquier, Am. J. Clin. Nutr. 33 (1980) 989–997.

[35]A. Astrup, S. Toubro, S. Cannon, P. Hein, L. Breum, J. Madsen, Am. J. Clin. Nutr. 51 (1990) 759–767.

[36]J. LeBlanc, M. Jobin, J. Côté, P. Samson, A. Labrie, J. Appl. Physiol. 59 (1985) 832–837.

[37]O.H. Choi, M.T. Shamim, W.L. Padgett, J.W. Daly, Life Sci. 43 (1988) 387–398.

[38]S.J.L. Einöther, V.E.G. Martens, J.A. Rycroft, E.A. De Bruin, Appetite 54 (2010) 406–409.

[39]T. Giesbrecht, J.A. Rycroft, M.J. Rowson, E.A. De Bruin, Nutr. Neurosci. 13 (2010) 283–290.

[40]G.N. Owen, H. Parnell, E.A. De Bruin, J.A. Rycroft, Nutr. Neurosci. 11 (2008) 193–198.

[41]C.N. Kahathuduwa, T.L. Dassanayake, A.M.T. Amarakoon, V.S. Weerasinghe, Nutr. Neurosci. 20 (2017) 369–377.

[42]S.E. Bruce, K.B. Werner, B.F. Preston, L.M. Baker, Int. J. Food Sci. Nutr. 65 (2014) 1003–1007.

[43]A. Misaizu, T. Kokubo, K. Tazumi, M. Kanayama, Y. Miura, Prev Nutr Food Sci 19 (2014) 367–372.

[44]S. Srivastava, M. Mennemeier, S. Pimple, J. Am. Coll. Nutr. 36 (2017) 631–639.

[45]S. Srivastava, M. Mennemeier, J.A. Chaudhary, J. Am. Coll. Nutr. 40 (2021) 224–236.

Cognizin® Citicoline

Scientific Name:
Cytidine diphosphocholine

Polygala tenuifolia Root Extract

In Traditional Chinese Medicine, Polygala tenuifolia root is one of the most used herbs to support the brain and central nervous system. Traditionally it was often used to reduce forgetfulness and support brain performance during aging (i.e., it’s what we’d consider a nootropic today). It was also commonly used in formulas to support sleep and promote a calmer, more balanced mood. Preclinical research suggests it supports brain protection and repair processes and molecules (such as BDNF and NGF), counters chronic stress, supports sleep, and influences both adenosine signaling—a molecule involved in the sleep homeostatic drive—and GABA signaling—a neurotransmitter involved with relaxation at night and sleep. The roots have several bioactive compounds thought to be relatively unique to this plant including tenuigenin, tenuifolin, yuanzhi-1, tenuifolisides, and tenuifolioses.*

TOP BENEFITS OF POLYGALA TENUIFOLIA

Supports cognitive function*

Supports a healthy stress response*

Supports sleep*

QUALIA’S POLYGALA TENUIFOLIA SOURCING

Polygala tenuifolia root extract is a 10:1 extract, which means that 10 parts of the root are used to create 1 part of the extract. This concentrates the active compounds, so less of the herb is needed.

Polygala tenuifolia root extract is Non-GMO and Vegan.

POLYGALA TENUIFOLIA FORMULATING PRINCIPLES AND RATIONALE

Because preclinical research suggests the potential for adaptogenic properties of Polygala tenuifolia, we consider this herb to follow hormetic principles similar to herbal adaptogens (see Qualia Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. Based on human studies and traditional uses, we’d consider the serving range for concentrated extracts to be about 100-300 mg daily (about 1-3 grams of crude root powder). Our goal with P. tenuifolia, as with all ingredient choices, is to select the appropriate serving keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogens and nootropic extracts, we are likely to choose an amount of P. tenuifolia towards the lower end of the range.*

POLYGALA TENUIFOLIA KEY MECHANISMS

Supports brain function*

Supports learning and memory* [1–5]

Supports sleep* [6–8]

Supports glutamate decarboxylase (GAD) activity* [9]

Supports GABA-Glutamate signaling* [7,9–11]

Supports adenosine signaling* [12]

Supports adrenergic signaling* [3,6,7]

Supports dopamine signaling* [3,13]

Influences acetylcholinesterase (AChE) activity* [3,4,14]

Influences monoamine oxidase (MAO) activity* [4]

Supports brain-derived neurotrophic factor (BDNF)* [15,16]

Supports synaptic transmission in the hippocampus* [16]

Supports long-term potentiation (LTP)/synaptic plasticity* [14,16]

Supports the proliferation and differentiation of neural stem cells* [17,18]

Supports neuroprotective functions* [16,19–24]

Supports antioxidant defenses* [4,14,23,25]

Supports healthy stress responses*

Supports healthy behavioral and physiological responses to stress* [8,11,15]

Supports gut health*

Supports the composition of the gut microbiota* [5,26,27]

Supports gut barrier function [27]

Promotes general health and longevity*

Supports mitochondrial function* [22]

Supports healthy immune function* [28,29]

*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.

REFERENCES 

[1]J.-Y. Lee, K.Y. Kim, K.Y. Shin, B.Y. Won, H.Y. Jung, Y.-H. Suh, Neurosci. Lett. 454 (2009) 111–114.

[2]K.Y. Shin, J.-Y. Lee, B.Y. Won, H.Y. Jung, K.-A. Chang, S. Koppula, Y.-H. Suh, Neurosci. Lett. 465 (2009) 157–159.

[3]H. Zhang, T. Han, L. Zhang, C.-H. Yu, D.-G. Wan, K. Rahman, L.-P. Qin, C. Peng, Phytomedicine 15 (2008) 587–594.

[4]Z. Li, Y. Liu, L. Wang, X. Liu, Q. Chang, Z. Guo, Y. Liao, R. Pan, T.-P. Fan, Evid. Based. Complement. Alternat. Med. 2014 (2014) 392324.

[5]W. Zeng, A.G. Wu, X.-G. Zhou, I. Khan, R.L. Zhang, H.H. Lo, L.Q. Qu, L.L. Song, X.Y. Yun, H.M. Wang, J. Chen, J.P.L. Ng, F. Ren, S.Y. Yuan, L. Yu, Y. Tang, G.X. Huang, V.K.W. Wong, S.K. Chung, S.W.F. Mok, D.L. Qin, H.L. Sun, L. Liu, W.L.W. Hsiao, B.Y.K. Law, Pharmacol. Res. 170 (2021) 105697.

[6]K. Kawashima, D. Miyako, Y. Ishino, T. Makino, K.-I. Saito, Y. Kano, Biol. Pharm. Bull. 27 (2004) 1317–1319.

[7]Q. Cao, Y. Jiang, S.-Y. Cui, P.-F. Tu, Y.-M. Chen, X.-L. Ma, X.-Y. Cui, Y.-L. Huang, H. Ding, J.-Z. Song, B. Yu, Z.-F. Sheng, Z.-J. Wang, Y.-P. Xu, G. Yang, H. Ye, X. Hu, Y.-H. Zhang, Phytomedicine 23 (2016) 1797–1805.

[8]Y. Yao, M. Jia, J.-G. Wu, H. Zhang, L.-N. Sun, W.-S. Chen, K. Rahman, Pharm. Biol. 48 (2010) 801–807.

[9]C.-I. Lee, J.-Y. Han, J.T. Hong, K.-W. Oh, Arch. Pharm. Res. 36 (2013) 1244–1251.

[10]C.-Y. Chen, X.-D. Wei, C.-R. Chen, J. Pharmacol. Sci. 131 (2016) 1–5.

[11]I.-J. Shin, S.U. Son, H. Park, Y. Kim, S.H. Park, K. Swanberg, J.-Y. Shin, S.-K. Ha, Y. Cho, S.-Y. Bang, J.-H. Lew, S.-H. Cho, S. Maeng, PLoS One 9 (2014) e88617.

[12]E.-J. Shin, K.-W. Oh, K.-W. Kim, Y.S. Kwon, J.H. Jhoo, W.-K. Jhoo, J.-Y. Cha, Y.K. Lim, I.S. Kim, H.-C. Kim, Life Sci. 75 (2004) 2751–2764.

[13]H.-L. Yuan, B. Li, J. Xu, Y. Wang, Y. He, Y. Zheng, X.-M. Wang, CNS Neurosci. Ther. 18 (2012) 584–590.

[14]J.-N. Huang, C.-Y. Wang, X.-L. Wang, B.-Z. Wu, X.-Y. Gu, W.-X. Liu, L.-W. Gong, P. Xiao, C.-H. Li, Behav. Brain Res. 246 (2013) 111–115.

[15]Y. Hu, P. Liu, D.-H. Guo, K. Rahman, D.-X. Wang, T.-T. Xie, Pharm. Biol. 48 (2010) 794–800.

[16]W. Xue, J.-F. Hu, Y.-H. Yuan, J.-D. Sun, B.-Y. Li, D.-M. Zhang, C.-J. Li, N.-H. Chen, Acta Pharmacol. Sin. 30 (2009) 1211–1219.

[17]H.-J. Park, K. Lee, H. Heo, M. Lee, J.W. Kim, W.W. Whang, Y.K. Kwon, H. Kwon, Phytother. Res. 22 (2008) 1324–1329.

[18]Y. Chen, X. Huang, W. Chen, N. Wang, L. Li, Neurochem. Res. 37 (2012) 771–777.

[19]Y. Ikeya, S. Takeda, M. Tunakawa, H. Karakida, K. Toda, T. Yamaguchi, M. Aburada, Biol. Pharm. Bull. 27 (2004) 1081–1085.

[20]X.-L. Sun, H. Ito, T. Masuoka, C. Kamei, T. Hatano, Biol. Pharm. Bull. 30 (2007) 1727–1731.

[21]T. Kuboyama, K. Hirotsu, T. Arai, H. Yamasaki, C. Tohda, Front. Pharmacol. 8 (2017) 805.

[22]L. Wang, G.F. Jin, H.H. Yu, X.H. Lu, Z.H. Zou, J.Q. Liang, H. Yang, Food Funct. 10 (2019) 7453–7460.

[23]X. Li, Y. Sun, Y. Wei, L. Zhou, L. Liu, P. Yin, Y. Liu, S. Wu, J. Li, C. Lu, Curr. Neurovasc. Res. 15 (2018) 94–102.

[24]J.-H. Park, J.S. Kim, D.S. Jang, S.-M. Lee, Am. J. Chin. Med. 34 (2006) 115–123.

[25]P. Liu, Y. Hu, D.-H. Guo, B.-R. Lu, K. Rahman, L.-H. Mu, D.-X. Wang, Pharm. Biol. 48 (2010) 828–833.

[26]C.-C. Wang, J.-H. Yen, Y.-C. Cheng, C.-Y. Lin, C.-T. Hsieh, R.-J. Gau, S.-J. Chiou, H.-Y. Chang, Food Nutr. Res. 61 (2017) 1379861.

[27]C.-C. Li, F. Ye, C.-X. Xu, Q. Chang, X.-M. Liu, R.-L. Pan, J. Ethnopharmacol. 294 (2022) 115349.

[28]T. Nagai, Y. Suzuki, H. Kiyohara, E. Susa, T. Kato, T. Nagamine, Y. Hagiwara, S. Tamura, T. Yabe, C. Aizawa, H. Yamada, Vaccine 19 (2001) 4824–4834.

[29]K.-S. Kim, D.-S. Lee, G.-S. Bae, S.-J. Park, D.-G. Kang, H.-S. Lee, H. Oh, Y.-C. Kim, Eur. J. Pharmacol. 721 (2013) 267–276.

SmartSeed™ (Celastrus paniculatus seed extract)

Scientific Name:
Celastrus paniculatus Willd

Caffeine

Ginkgo Biloba Leaf Extract (24% glycosides)

Scientific Name:
Ginkgo biloba

Caffeine (from Guarana Seed Extract)

Caffeine is a methylxanthine compound used to combat fatigue and promote alertness. It’s found in the seeds, fruits, nuts, or leaves of a number of plants native to Africa, East Asia, and South America. These include coffee beans (as well as coffee cherry fruits), cocoa beans, guarana berries, kola nuts, and leaves from tea, guayusa, and yerba mate. Caffeine is quickly absorbed in the gastrointestinal tract and is able to easily cross the blood-brain barrier to reach the brain, where it typically has stimulating and invigorating effects. Caffeine can help us perform physically and mentally by promoting healthy arousal (wakefulness), which is an important part of being able to pay attention and react quickly. Not surprisingly, this has led to caffeine being one of the most widely used and studied substances for supporting both sports performance and brain function [1,2].* Paullinia cupana (i.e., guarana) has been cultivated in the Amazon river basin in South America for centuries, having a long history of use by Amazonian tribal people to promote wakefulness and help maintain alertness. Guarana seeds are a source of caffeine and other methylxanthines, saponins and tannins. Because of its caffeine content, guarana has been used for its energy-enhancing benefits. Guarana has been popularly used to support memory and to soothe mental and physical stress and fatigue [3,4].*

TOP BENEFITS OF CAFFEINE FROM GUARANA SEED EXTRACT

Supports healthy brain function and cognition*

Supports mood*

Supports mental and physical stamina*

QUALIA’S CAFFEINE FROM GUARANA SEED EXTRACT SOURCING

Guarana seed extract is standardized for 50% caffeine.

Guarana seed extract is a non-GMO, gluten-free, and vegan ingredient.

CAFFEINE FROM GUARANA SEED EXTRACT FORMULATING PRINCIPLES AND RATIONALE

We consider caffeine to follow hormetic dosing principles (see Qualia Dosing Principles) and to have a hormetic range (i.e., a dosing range below and above which results would be poorer). Caffeine is one of the most used, and best studied nootropic and ergogenic compounds. As a nootropic (i.e., to promote alertness, focus, reaction time, etc.) caffeine is typically used at amounts ranging from 50 to 200 mg. As an ergogenic (i.e., for sports performance) just prior to exercise, the upper end of the serving range can be as high as 600 mg [2]. In both of these cases, responses to caffeine tend to follow a hormetic curve, with low-to-moderate doses of caffeine supporting better cognitive and sports performance, but serving above the higher end of the range hindering performance. We use a combination of organic Coffeeberry®, guarana seed extract, and anhydrous caffeine to supply 100 mg of caffeine in a suggested serving of QUALIA MIND. So, think of these three ingredients as our caffeine blend or caffeine stack. The amount of caffeine supplied by the blend is what would be found in a small cup of coffee. This is in the middle of the range for nootropic purposes and on the lower end of what’s used for ergogenic purposes.*

KEY MECHANISMS

CAFFEINE  

Supports brain function*

Supports optimal adenosine receptor function* [5]

Optimizes, via adenosine receptor antagonism, the levels of the neurotransmitters acetylcholine, glutamate, serotonin, dopamine and norepinephrine* [6,7]

Supports healthy acetylcholine signaling* [7–10]

Supports healthy dopamine signaling* [7,11–16]

Supports healthy serotonin signaling* [7,10,17–20]

Supports healthy glutamate signaling* [7,11,12]

Supports healthy GABA signaling* [7,10]

Supports healthy noradrenaline signaling* [7,19]

Supports healthy cortical activation in the brain* [5,7]

Supports healthy cerebral metabolism* [5,7]

Promotes wakefulness* [21]

Supports cognitive function*

Supports cognitive performance* [2,7,22–25]

Supports executive function* [26–28]

Supports information processing rate* [5,29,30]

Supports simple and sustained attention* [2,26,30,31]

Supports vigilance* [2,31]

Supports reaction time* [2,24,25,30]

Supports reasoning* [23]

Supports creative thinking* [27]

Supports resistance to mental fatigue* [29,31]

Supports healthy neuroprotective functions* [32,33]

Supports a healthy mood*

Supports positive affect* [7,24,25,28,34]

Supports physical performance*

Supports healthy resistance to physical fatigue* [22,25,26,35]

Supports healthy resistance to perceived exhaustion* [2]

Supports muscle endurance and strength exercise activities* [2]

Supports speed, power, and agility during intense exercise* [2] 

Other actions*

Supports optimal metabolic rate* [36–38]

Supports healthy phosphodiesterase balance* [39]

Complementary ingredients*

L-Theanine to support cognitive performance* [29,40–43]

Choline donors (e.g., citicoline, alpha-GPC) to support attention, concentration, and working memory* [44]

L-ornithine to support enhanced mood and cognitive performance* [45]

Alpinia galanga to support cognitive performance* [46,47]

GUARANA 

Supports cognitive function*

Supports cognitive performance [48–52]

Supports alertness [48]

Supports attention [50,52]

Supports contentedness [48,52]

Supports exercise performance*

Helps combat exertion during exercise (consumed 1 h prior to exercise)* [51]

Helps combat physical fatigue* [53]

Supports healthy aging and longevity*

Supports healthy cardiometabolic parameters* [54–56]

Supports healthy antioxidant defenses and helps combat oxidative stress* [54,57–59]

REFERENCES

[1]B. Fiani, L. Zhu, B.L. Musch, S. Briceno, R. Andel, N. Sadeq, A.Z. Ansari, Cureus 13 (2021) e15032.
[2]T.M. McLellan, J.A. Caldwell, H.R. Lieberman, Neurosci. Biobehav. Rev. 71 (2016) 294–312.
[3]H. Lidilhone, V.S. Genise, T. Neusa, J. Med. Plants Res. 7 (2013) 2221–2229.
[4]L.L.M. Marques, E.D.F. Ferreira, M.N. de Paula, T. Klein, J.C.P. de Mello, Rev. Bras. Farmacogn. (2018).
[5]G. Burnstock, Advances in Experimental Medicine and Biology 986 (2013) 1–12.
[6]B.B. Fredholm, Pharmacol. Toxicol. 76 (1995) 93–101.|
[7]B.B. Fredholm, K. Bättig, J. Holmén, A. Nehlig, E.E. Zvartau, Pharmacol. Rev. 51 (1999) 83–133.
[8]E. Acquas, G. Tanda, G. Di Chiara, Neuropsychopharmacology 27 (2002) 182–193.
[9]A.J. Carter, W.T. O’Connor, M.J. Carter, U. Ungerstedt, J. Pharmacol. Exp. Ther. 273 (1995) 637–642.
[10]D. Shi, O. Nikodijević, K.A. Jacobson, J.W. Daly, Cell. Mol. Neurobiol. 13 (1993) 247–261.
[11]G. Racchetti, A. Lorusso, C. Schulte, D. Gavello, V. Carabelli, R. D’Alessandro, J. Meldolesi, J. Cell Sci. 123 (2010) 165–170.
[12]D. Quarta, J. Borycz, M. Solinas, K. Patkar, J. Hockemeyer, F. Ciruela, C. Lluis, R. Franco, A.S. Woods, S.R. Goldberg, S. Ferré, J. Neurochem. 91 (2004) 873–880.
[13]B.E. Garrett, S.G. Holtzman, Eur. J. Pharmacol. 262 (1994) 65–75.
[14]K.R. Powell, P.M. Iuvone, S.G. Holtzman, Pharmacol. Biochem. Behav. 69 (2001) 59–70.
[15]M. Solinas, S. Ferré, Z.-B. You, M. Karcz-Kubicha, P. Popoli, S.R. Goldberg, J. Neurosci. 22 (2002) 6321–6324.
[16]X. Zheng, S. Takatsu, H. Wang, H. Hasegawa, Pharmacol. Biochem. Behav. 122 (2014) 136–143.
[17]D.J. Haleem, A. Yasmeen, M.A. Haleem, A. Zafar, Life Sci. 57 (1995) PL285–92.
[18]S. Khaliq, S. Haider, F. Naqvi, T. Perveen, S. Saleem, D.J. Haleem, Pak. J. Pharm. Sci. 25 (2012) 21–25.
[19]M.D. Chen, W.H. Lin, Y.M. Song, P.Y. Lin, L.T. Ho, Zhonghua Yi Xue Za Zhi 53 (1994) 257–261.
[20]M. Okada, Y. Kawata, K. Kiryu, K. Mizuno, K. Wada, H. Tasaki, S. Kaneko, J. Neurochem. 69 (2002) 2581–2588.
[21]T. Porkka-Heiskanen, Handb. Exp. Pharmacol. (2011) 331–348.
[22]V. Maridakis, P.J. O’Connor, P.D. Tomporowski, Int. J. Neurosci. 119 (2009) 1239–1258.
[23]M.J. Jarvis, Psychopharmacology 110 (1993) 45–52.
[24]A. Nehlig, J. Alzheimers. Dis. 20 Suppl 1 (2010) S85–94.
[25]C.H.S. Ruxton, Nutr. Bull. 33 (2008) 15–25.
[26]J. Lanini, J.C.F. Galduróz, S. Pompéia, Hum. Psychopharmacol. 31 (2016) 29–43.
[27]K. Soar, E. Chapman, N. Lavan, A.S. Jansari, J.J.D. Turner, Appetite 105 (2016) 156–163.
[28]F.L. Dodd, D.O. Kennedy, L.M. Riby, C.F. Haskell-Ramsay, Psychopharmacology 232 (2015) 2563–2576.
[29]C.F. Haskell, D.O. Kennedy, A.L. Milne, K.A. Wesnes, A.B. Scholey, Biol. Psychol. 77 (2008) 113–122.
[30]S.J.L. Einöther, T. Giesbrecht, Psychopharmacology 225 (2013) 251–274.
[31]A. Smith, Food Chem. Toxicol. 40 (2002) 1243–1255.
[32]M.A. Schwarzschild, K. Xu, E. Oztas, J.P. Petzer, K. Castagnoli, N. Castagnoli Jr, J.-F. Chen, Neurology 61 (2003) S55–61.
[33]M. Kolahdouzan, M.J. Hamadeh, CNS Neurosci. Ther. 23 (2017) 272–290.
[34]S.H. Backhouse, S.J.H. Biddle, N.C. Bishop, C. Williams, Appetite 57 (2011) 247–252.
[35]J.M. Davis, Z. Zhao, H.S. Stock, K.A. Mehl, J. Buggy, G.A. Hand, Am. J. Physiol. Regul. Integr. Comp. Physiol. 284 (2003) R399–404.
[36]K.J. Acheson, B. Zahorska-Markiewicz, P. Pittet, K. Anantharaman, E. Jéquier, Am. J. Clin. Nutr. 33 (1980) 989–997.
[37]A. Astrup, S. Toubro, S. Cannon, P. Hein, L. Breum, J. Madsen, Am. J. Clin. Nutr. 51 (1990) 759–767.
[38]J. LeBlanc, M. Jobin, J. Côté, P. Samson, A. Labrie, J. Appl. Physiol. 59 (1985) 832–837.
[39]O.H. Choi, M.T. Shamim, W.L. Padgett, J.W. Daly, Life Sci. 43 (1988) 387–398.
[40]S.J.L. Einöther, V.E.G. Martens, J.A. Rycroft, E.A. De Bruin, Appetite 54 (2010) 406–409.
[41]T. Giesbrecht, J.A. Rycroft, M.J. Rowson, E.A. De Bruin, Nutr. Neurosci. 13 (2010) 283–290.
[42]G.N. Owen, H. Parnell, E.A. De Bruin, J.A. Rycroft, Nutr. Neurosci. 11 (2008) 193–198.
[43]C.N. Kahathuduwa, T.L. Dassanayake, A.M.T. Amarakoon, V.S. Weerasinghe, Nutr. Neurosci. 20 (2017) 369–377.
[44]S.E. Bruce, K.B. Werner, B.F. Preston, L.M. Baker, Int. J. Food Sci. Nutr. 65 (2014) 1003–1007.
[45]A. Misaizu, T. Kokubo, K. Tazumi, M. Kanayama, Y. Miura, Prev Nutr Food Sci 19 (2014) 367–372.
[46]S. Srivastava, M. Mennemeier, S. Pimple, J. Am. Coll. Nutr. 36 (2017) 631–639.
[47]S. Srivastava, M. Mennemeier, J.A. Chaudhary, J. Am. Coll. Nutr. 40 (2021) 224–236.
[48]C.F. Haskell, D.O. Kennedy, K.A. Wesnes, A.L. Milne, A.B. Scholey, J. Psychopharmacol. 21 (2007) 65–70.
[49]D.O. Kennedy, C.F. Haskell, B. Robertson, J. Reay, C. Brewster-Maund, J. Luedemann, S. Maggini, M. Ruf, A. Zangara, A.B. Scholey, Appetite 50 (2008) 506–513.
[50]D.O. Kennedy, C.F. Haskell, K.A. Wesnes, A.B. Scholey, Pharmacol. Biochem. Behav. 79 (2004) 401–411.
[51]R.C. Veasey, C.F. Haskell-Ramsay, D.O. Kennedy, K. Wishart, S. Maggini, C.J. Fuchs, E.J. Stevenson, Nutrients 7 (2015) 6109–6127.
[52]A. Scholey, I. Bauer, C. Neale, K. Savage, D. Camfield, D. White, S. Maggini, A. Pipingas, C. Stough, M. Hughes, Nutrients 5 (2013) 3589–3604.
[53]E.B. Espinola, R.F. Dias, R. Mattei, E.A. Carlini, J. Ethnopharmacol. 55 (1997) 223–229.
[54]R. de L. Portella, R.P. Barcelos, E.J.F. da Rosa, E.E. Ribeiro, I.B.M. da Cruz, L. Suleiman, F.A.A. Soares, Lipids Health Dis. 12 (2013) 12.
[55]C. da C. Krewer, E.E. Ribeiro, E.A.M. Ribeiro, R.N. Moresco, M.I. de U.M. da Rocha, G.F.F. dos S. Montagner, M.M. Machado, K. Viegas, E. Brito, I.B.M. da Cruz, Phytother. Res. 25 (2011) 1367–1374.
[56]J.B. Ruchel, J.F.P. Rezer, M.L. Thorstenberg, C.B. Dos Santos, F.L. Cabral, S.T.A. Lopes, C.B. da Silva, A.K. Machado, I.B.M. da Cruz, M.R.C. Schetinger, J.F. Gonçalves, D.B.R. Leal, Phytother. Res. 30 (2016) 49–57.
[57]R. Mattei, R.F. Dias, E.B. Espı́nola, E.A. Carlini, S.B.M. Barros, J. Ethnopharmacol. 60 (1998) 111–116.
[58]H. Peixoto, M. Roxo, T. Röhrig, E. Richling, X. Wang, M. Wink, Medicines (Basel) 4 (2017).
[59]A. Basile, L. Ferrara, M.D. Pezzo, G. Mele, S. Sorbo, P. Bassi, D. Montesano, J. Ethnopharmacol. 102 (2005) 32–36.

Alpha-glycerophosphocholine (Alpha-GPC)

Scientific Name:
Alpha-glycerophosphocholine

Inositol

Inositol is a family of nine different stereoisomers. This is a chemistry term. It means that all inositols share the same atoms and the sequence of how the atoms are bonded together but differ in the three-dimensional orientation of their atoms in space. An analogy would be a folding beach chair that can be put in multiple positions. The most stable form of inositol in the body is called myo-inositol. It’s also the most abundant form. The most commonly supplemented form of inositol is myo-inositol (myo-inositol is a synonym for inositol in dietary supplements). Historically, inositol was considered part of the B-complex of vitamins (it was called vitamin B8), but because we can make it in the body, it’s no longer classified as a vitamin. While lots of foods contain inositol, its bioavailability in plant foods such as seeds, beans, and grains is low. In the body, inositol is found in cell membrane phospholipids, plasma lipoproteins, and (as the phosphate form) in the cell nucleus (the home of our DNA).* 

TOP BENEFITS OF INOSITOL

Supports healthy hormone functions *

Supports brain health *

QUALIA’S INOSITOL SOURCING

Inositol is a non-GMO, gluten-free, and vegan ingredient.

INOSITOL FORMULATING PRINCIPLES AND RATIONALE

There is no recommended daily allowance for inositol. Dietary intake has been estimated as being between about  200 mg to 600 mg [1]. Inositol is generally considered to be dose-dependent (see Qualia Dosing Principles) and can be supplemented in amounts as high as several grams. For general cellular signaling purposes and brain health support, we may use a low amount to support dietary intake.*

INOSITOL KEY MECHANISMS  

Supports healthy cardiometabolic function*

Helps maintain healthy blood pressure* [2,3]

Helps maintain healthy blood triglycerides and cholesterol levels* [2–5] 

Supports healthy body weight maintenance* [2,6]

Supports healthy thyroid function* 

Inositol derivatives are second messengers in the TSH signaling pathway* [7]

Supports healthy thyroid-stimulating hormone (TSH) levels* [8–10] 

Supports healthy cellular thyroid function* [8–10] 

Supports female reproductive health*

Inositol derivatives are second messengers in the FSH signaling pathway* [11]

Supports healthy oocyte maturation* [12–15]

Supports healthy ovary function* [5,16–18]

Supports healthy gut microbiota*

Supports a balanced composition of the gut microbiome* [19]

Complementary ingredients*

Selenium in supporting healthy thyroid function* [8]

Resveratrol in supporting healthy metabolic profile* [20]

Choline and inositol are often supplemented together because they support chemical messengers that help keep the brain and central nervous system healthy*

*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.

REFERENCES
[1]A. Bevilacqua, M. Bizzarri, Int. J. Endocrinol. 2018 (2018) 1968450.
[2]A. Santamaria, D. Giordano, F. Corrado, B. Pintaudi, M.L. Interdonato, G.D. Vieste, A.D. Benedetto, R. D’Anna, Climacteric 15 (2012) 490–495.
[3]D. Giordano, F. Corrado, A. Santamaria, S. Quattrone, B. Pintaudi, A. Di Benedetto, R. D’Anna, Menopause 18 (2011) 102–104.
[4]M. Minozzi, M. Nordio, R. Pajalich, Eur. Rev. Med. Pharmacol. Sci. 17 (2013) 537–540.
[5]J.E. Nestler, D.J. Jakubowicz, P. Reamer, R.D. Gunn, G. Allan, N. Engl. J. Med. 340 (1999) 1314–1320.
[6]L. Pkhaladze, L. Barbakadze, N. Kvashilava, Int. J. Endocrinol. 2016 (2016) 1473612.
[7]S. Benvenga, A. Antonelli, Rev. Endocr. Metab. Disord. 17 (2016) 471–484.
[8]M. Nordio, S. Basciani, Eur. Rev. Med. Pharmacol. Sci. 22 (2018) 2153–2159.
[9]S.M. Ferrari, P. Fallahi, F. Di Bari, R. Vita, S. Benvenga, A. Antonelli, Eur. Rev. Med. Pharmacol. Sci. 21 (2017) 36–42.
[10]M. Nordio, S. Basciani, Int. J. Endocrinol. 2017 (2017) 2549491.
[11]P. Gloaguen, P. Crépieux, D. Heitzler, A. Poupon, E. Reiter, Front. Endocrinol. 2 (2011) 45.
[12]L. Ciotta, M. Stracquadanio, I. Pagano, A. Carbonaro, M. Palumbo, F. Gulino, Eur. Rev. Med. Pharmacol. Sci. 15 (2011) 509–514.
[13]T.T.Y. Chiu, M.S. Rogers, C. Briton-Jones, C. Haines, Hum. Reprod. 18 (2003) 408–416.
[14]T.T.Y. Chiu, M.S. Rogers, E.L.K. Law, C.M. Briton-Jones, L.P. Cheung, C.J. Haines, Hum. Reprod. 17 (2002) 1591–1596.
[15]S.G. Vitale, P. Rossetti, F. Corrado, A.M.C. Rapisarda, S. La Vignera, R.A. Condorelli, G. Valenti, F. Sapia, A.S. Laganà, M. Buscema, Int. J. Endocrinol. 2016 (2016) 4987436.
[16]E. Benelli, S. Del Ghianda, C. Di Cosmo, M. Tonacchera, Int. J. Endocrinol. 2016 (2016) 3204083.
[17]S. Gerli, M. Mignosa, G.C. Di Renzo, Eur. Rev. Med. Pharmacol. Sci. 7 (2003) 151–159.
[18]M. Nordio, E. Proietti, Eur. Rev. Med. Pharmacol. Sci. 16 (2012) 575–581.
[19]Y. Okazaki, A. Sekita, T. Katayama, Biomed Rep 8 (2018) 466–474.
[20]A. Malvasi, I. Kosmas, O.A. Mynbaev, R. Sparic, S. Gustapane, M. Guido, A. Tinelli, Clin. Ter. 168 (2017) e240–e247.

Choline Bitartrate

Choline Bitartrate is a salt of choline. Choline is an essential nutrient, fundamental for the proper functioning of the brain, liver, and muscles [1]. Choline is a building block for the neurotransmitter acetylcholine, the membrane phospholipids phosphatidylcholine and sphingomyelin, and the methyl donor betaine. Acetylcholine is central to brain neurotransmission; it plays a supportive role in attention, concentration, mental focus, and memory [2–4]. Acetylcholine is also used in both the fight or flight and rest and relax parts of the autonomic nervous system, and it is a signaling molecule for activating muscles [5]. Phosphatidylcholine is a main constituent of cell and organelle membranes and is essential for healthy cell membrane function [6,7].*

TOP BENEFITS OF CHOLINE BITARTRATE

Supports mental energy *

Supports focus and attention *

Supports brain health and cognitive performance *

QUALIA’S CHOLINE BITARTRATE SOURCING

Choline Bitartrate is a source of choline, a substance vital to brain health and energy.

Choline Bitartrate is a non-GMO, gluten-free, and vegan ingredient.

CHOLINE BITARTRATE FORMULATING PRINCIPLES AND RATIONALE

In 1998, the Institute of Medicine (IOM) recognized choline as an essential nutrient needed by humans [8]. The adequate intake (AI) recommendation for choline is 550 mg/day for men and 425 mg/day for women. Many people fail to meet this adequate intake amount. On average, men over 20 years of age (396 mg choline intake) and women (260 mg choline intake) fall short of the AI for choline. As we get older, we are even less likely to get adequate choline in the diet [9]. As many as 90% of the U.S. population may not be consuming enough choline in the diet [10]. Choline bitartrate is by weight one of the best sources of choline.* We include it in a low amount to help narrow the gap between average dietary intakes and adequate intakes.

CHOLINE BITARTRATE KEY MECHANISMS

Choline donor*

Supports healthy plasma choline levels [11,12]

Supports healthy betaine levels [11,12]

Precursor for phosphatidylcholine synthesis [13]

Precursor for acetylcholine synthesis [14]

Supports healthy brain function and cognition* 

Supports cholinergic neurotransmission [14–16]

Supports healthy brain membranes [17]

Supports cognitive performance [16]

*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. 

REFERENCES 
[1]T.C. Wallace, J.K. Blusztajn, M.A. Caudill, K.C. Klatt, E. Natker, S.H. Zeisel, K.M. Zelman, Nutr. Today 53 (2018) 240–253.
[2]M.E. Hasselmo, Curr. Opin. Neurobiol. 16 (2006) 710–715.
[3]S.F. Logue, T.J. Gould, Pharmacol. Biochem. Behav. 123 (2014) 45–54.
[4]I. Klinkenberg, A. Sambeth, A. Blokland, Behav. Brain Res. 221 (2011) 430–442.
[5]C. Sam, B. Bordoni, Physiology, Acetylcholine, StatPearls Publishing, 2023.
[6]J. Agut, E. Font, A. Sacristán, J.A. Ortiz, Arzneimittelforschung 33 (1983) 1048–1050.
[7]P. Galletti, M. De Rosa, M.G. Cotticelli, A. Morana, R. Vaccaro, V. Zappia, J. Neurol. Sci. 103 Suppl (1991) S19–25.
[8]Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline, Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, National Academies Press (US), Washington (DC), 2012.
[9]D.N. Chester, J.D. Goldman, J.K. Ahuja, A.J. Moshfegh, in: FSRG Dietary Data Briefs, United States Department of Agriculture (USDA), Beltsville (MD), 2011.
[10]M. Gossell-Williams, J. Benjamin, West Indian Med. J. 55 (2006) 197–199.
[11]K.A. Böckmann, A.R. Franz, M. Minarski, A. Shunova, C.A. Maiwald, J. Schwarz, M. Gross, C.F. Poets, W. Bernhard, Eur. J. Nutr. 61 (2022) 219–230.
[12]J.M.W. Wallace, J.M. McCormack, H. McNulty, P.M. Walsh, P.J. Robson, M.P. Bonham, M.E. Duffy, M. Ward, A.M. Molloy, J.M. Scott, P.M. Ueland, J.J. Strain, Br. J. Nutr. 108 (2012) 1264–1271.
[13]F. Gibellini, T.K. Smith, IUBMB Life 62 (2010) 414–428.
[14]S.K. Fisher, S. Wonnacott, in: S.T. Brady, G.J. Siegel, R.W. Albers, D.L. Price (Eds.), Basic Neurochemistry (Eighth Edition), Academic Press, New York, 2012, pp. 258–282.
[15]I.H. Ulus, R.J. Wurtman, C. Mauron, J.K. Blusztajn, Brain Res. 484 (1989) 217–227.
[16]S. Tabassum, S. Haider, S. Ahmad, S. Madiha, T. Parveen, Pharmacol. Biochem. Behav. 159 (2017) 90–99.
[17]S.K. Tayebati, F. Amenta, Clin. Chem. Lab. Med. 51 (2013) 513–521.

Inositols

Inositol is a family of nine different stereoisomers. This is a chemistry term. It means that all inositols share the same atoms and the sequence of how the atoms are bonded together, but differ in the three-dimensional orientation of their atoms in space. An analogy would be a folding beach chair that can be put in multiple positions. The most stable form of inositol in the body is called myo-inositol. It’s also the most abundant form. The most commonly supplemented form of inositol is myo-inositol (myo-inositol functions as a synonym for inositol in dietary supplements). Myo-inositol and the D-chiro-inositol form exist in plasma in a 40:1 ratio. This combination and ratio is complementary, producing far greater functional responses at much lower doses than myo-inositol alone [1,2]. Historically, inositol was considered part of the B-complex of vitamins (it was called vitamin B8), but because we can make it in the body, it’s no longer classified as a vitamin. While lots of foods contain inositol, its bioavailability in plant foods such as seeds, beans, and grains is low. In the body inositol is found in cell membrane phospholipids, plasma lipoproteins, and (as the phosphate form) in the cell nucleus (the home of our DNA). Our main interest in inositol is for support of hormone signaling—insulin and thyroid especially. Inositol acts as a second messenger, translating hormone messages that act on the outside of cells into intracellular signals involved in energy production, growth, and repair.*

TOP BENEFITS OF INOSITOLS

Supports thyroid function *

Supports cardiometabolic health *

Supports female reproductive health*

QUALIA’S INOSITOLS SOURCING

Our main reason for including inositol is because of its role in supporting healthy insulin and thyroid signaling functions. When these work better, cellular energy can be made more efficiently.

The most important inositol criteria is opting for complementarity and using a stack of myo-inositol and D-chiro-inositol in a 40:1 ratio. Compared to either form of inositol on its own, this ratio (1) better matches physiology, (2) produces enhanced functional responses at lower doses, and (3) overcomes interference in cellular enzyme production of D-chiro-inositol from myo-inositol that can occur with insulin resistance and aging.

Myo-inositol sourcing is focused on identifying and purchasing from a reputable supplier and ensuring the myo-inositol is non-GMO, gluten-free and vegan.

We use Chirositol^® from Bioriginal as a source of D-chiro-inositol. It is extracted without the use of solvents from carob pods (Ceratonia siliqua) and contains greater than 95% D-chiro-inositol. Chirositol^® is non-GMO Project verified, gluten-free and vegan. 

INOSITOLS FORMULATING PRINCIPLES AND RATIONALE

Inositol is generally considered to be dose-dependent (see Qualia Dosing Principles) and is often used in very high amounts, especially when trying to affect the brain and mental health. But for general cellular signaling purposes, much lower amounts can be used, especially when myo-inositol and D-chiro-inositol are included at a ratio of 40:1. This is their physiological ratio in the plasma. The stacking of myo-inositol and D-chiro-inositol is complementary at this ratio, allowing for the use of lower amounts of both [1, 2].*

INOSITOLS KEY MECHANISMS

Supports healthy cardiometabolic function*

Helps maintain healthy blood pressure* [3,4]

Helps maintain healthy blood triglycerides and cholesterol levels* [1,3–5] 

Supports healthy body weight maintenance* [3,6]

Supports healthy thyroid function* 

Inositol derivatives are second messengers in the TSH signaling pathway* [7]

Supports healthy thyroid-stimulating hormone (TSH) levels* [8–10] 

Supports healthy cellular thyroid function* [8–10] 

Supports female reproductive health*

Inositol derivatives are second messengers in the FSH signaling pathway* [11]

Supports healthy oocyte maturation* [12–15]

Supports healthy ovary function* [2,5,16,17]

Supports mitochondrial function*

D-chiro-inositol supports healthy mitochondrial structure and function [18]

D-chiro-inositol supports redox balance [19]

D-chiro-inositol supports AMPK activity through the LKB1-dependent pathway [19]

Supports healthy gut microbiota*

Supports a balanced composition of the gut microbiome* [20]

Complementary ingredients*

Selenium in supporting healthy thyroid function* [8]

Resveratrol in supporting healthy metabolic profile* [21]

*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.

REFERENCES

[1]M. Minozzi, M. Nordio, R. Pajalich, Eur. Rev. Med. Pharmacol. Sci. 17 (2013) 537–540.

[2]M. Nordio, E. Proietti, Eur. Rev. Med. Pharmacol. Sci. 16 (2012) 575–581.

[3]A. Santamaria, D. Giordano, F. Corrado, B. Pintaudi, M.L. Interdonato, G.D. Vieste, A.D. Benedetto, R. D’Anna, Climacteric 15 (2012) 490–495.

[4]D. Giordano, F. Corrado, A. Santamaria, S. Quattrone, B. Pintaudi, A. Di Benedetto, R. D’Anna, Menopause 18 (2011) 102–104.

[5]J.E. Nestler, D.J. Jakubowicz, P. Reamer, R.D. Gunn, G. Allan, N. Engl. J. Med. 340 (1999) 1314–1320.

[6]L. Pkhaladze, L. Barbakadze, N. Kvashilava, Int. J. Endocrinol. 2016 (2016) 1473612.

[7]S. Benvenga, A. Antonelli, Rev. Endocr. Metab. Disord. 17 (2016) 471–484.

[8]M. Nordio, S. Basciani, Eur. Rev. Med. Pharmacol. Sci. 22 (2018) 2153–2159.

[9]S.M. Ferrari, P. Fallahi, F. Di Bari, R. Vita, S. Benvenga, A. Antonelli, Eur. Rev. Med. Pharmacol. Sci. 21 (2017) 36–42.

[10]M. Nordio, S. Basciani, Int. J. Endocrinol. 2017 (2017) 2549491.

[11]P. Gloaguen, P. Crépieux, D. Heitzler, A. Poupon, E. Reiter, Front. Endocrinol. 2 (2011) 45.

[12]L. Ciotta, M. Stracquadanio, I. Pagano, A. Carbonaro, M. Palumbo, F. Gulino, Eur. Rev. Med. Pharmacol. Sci. 15 (2011) 509–514.

[13]T.T.Y. Chiu, M.S. Rogers, C. Briton-Jones, C. Haines, Hum. Reprod. 18 (2003) 408–416.

[14]T.T.Y. Chiu, M.S. Rogers, E.L.K. Law, C.M. Briton-Jones, L.P. Cheung, C.J. Haines, Hum. Reprod. 17 (2002) 1591–1596.

[15]S.G. Vitale, P. Rossetti, F. Corrado, A.M.C. Rapisarda, S. La Vignera, R.A. Condorelli, G. Valenti, F. Sapia, A.S. Laganà, M. Buscema, Int. J. Endocrinol. 2016 (2016) 4987436.

[16]E. Benelli, S. Del Ghianda, C. Di Cosmo, M. Tonacchera, Int. J. Endocrinol. 2016 (2016) 3204083.

[17]S. Gerli, M. Mignosa, G.C. Di Renzo, Eur. Rev. Med. Pharmacol. Sci. 7 (2003) 151–159.

[18]B. Zhang, C. Gao, Y. Li, M. Wang, J. Ethnopharmacol. 214 (2018) 83–89.

[19]B. Zhang, X. Guo, Y. Li, Q. Peng, J. Gao, B. Liu, M. Wang, Mol. Nutr. Food Res. 61 (2017).

[20]Y. Okazaki, A. Sekita, T. Katayama, Biomed Rep 8 (2018) 466–474.

[21]A. Malvasi, I. Kosmas, O.A. Mynbaev, R. Sparic, S. Gustapane, M. Guido, A. Tinelli, Clin. Ter. 168 (2017) e240–e247.

Uridine Monophosphate

Scientific Name:
Uridine Monophosphate, (UMP)

Nutricog® (Terminalia chebula fruit extract and Boswellia serrata gum resin extract)

Nutricog® is a blend of two Ayurvedic herbs: Haritaki (Terminalia chebula) and Boswellia (Boswellia serrata). It is a source of gallic acid, ellagic acid, and amyrins. The fruits of T. chebula have many traditional uses, including the support of gastrointestinal health, immune defenses, and brain health. T. chebula fruits are rich in vitamin C and polyphenols including tannins, phenolic acids, and flavonoids, all of which have antioxidant properties and support general health and protective mechanisms in several organs of the human body, including the brain [1]. The resin of Boswellia trees, which is also known as frankincense or olibanum, has been traditionally used to support musculoskeletal health, immune defenses, and respiratory health, among others. Boswellia is rich in bioactive compounds including terpenes such as boswellic acids and amyrins that can cross the blood brain barrier and support healthy brain function [2,3].* 

TOP BENEFITS OF NUTRICOG®

Supports healthy brain function and cognitive performance*

Supports healthy neuroprotective mechanisms*

QUALIA’S NUTRICOG® SOURCING

Nutricog® is a patented combination of Haritaki (Terminalia chebula) and Boswellia (Boswellia serrata), standardized for gallic acid, ellagic acid, and amyrins. 

Nutricog® is clinically-studied for the support of cognitive performance.* 

Nutricog® is non-GMO, vegan, gluten-free, Kosher, and Halal certified. 

Nutricog® is a registered trademark of PLT Health Solutions - Laila Nutraceuticals, LLC.

NUTRICOG® FORMULATING PRINCIPLES AND RATIONALE

The developers of Nutricog started by doing preclinical research. This helped them determine the amount to supplement in their human clinical study. While the human study has not been published yet, the amount supplemented was 300 mg of Nutricog. We include this 300 mg amount to be consistent with what has been studied.*

NUTRICOG® KEY MECHANISMS

Supports learning and memory ‡

Supports focus and concentration ‡

Supports healthy executive function and working memory ‡

‡ Data from an unpublished clinical study provided by the manufacturer

Terminalia chebula

Supports healthy cognitive function* [4–8]

Supports healthy cortisol levels* [9]

Supports healthy behavioral stress responses* [10] 

Supports healthy monoamine (serotonin, dopamine, norepinephrine) levels* [9,10]

Supports healthy acetylcholine signaling* [7,11,12]

Supports healthy BDNF levels* [9,13]

Supports healthy neuroprotective functions* [5–8,11,13]

Boswellia serrata

Supports healthy brain function and cognition* [14–19]

Supports healthy BDNF levels* [17,20]

Supports healthy immune signaling* [14]

Supports healthy neuroprotective functions* [19–24]

Supports healthy neuronal structure* [18,25–27]

*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.

REFERENCES

[1]M. Nigam, A.P. Mishra, A. Adhikari-Devkota, A.I. Dirar, M.M. Hassan, A. Adhikari, T. Belwal, H.P. Devkota, Phytother. Res. 34 (2020) 2518–2533.
[2]M. Abdel-Tawab, O. Werz, M. Schubert-Zsilavecz, Clin. Pharmacokinet. 50 (2011) 349–369.
[3]K. Gerbeth, J. Hüsch, G. Fricker, O. Werz, M. Schubert-Zsilavecz, M. Abdel-Tawab, Fitoterapia 84 (2013) 99–106.
[4]M. Banazadeh, M. Mehrabani, N. Banazadeh, F. Dabaghzadeh, F. Shahabi, Phytother. Res. 36 (2022) 543–550.
[5]Q. Zeng, Q. Xiong, K. Lin, Z. Liang, M. Zhou, X. Tian, C. Xu, Q. Ru, Brain Res. Bull. 184 (2022) 76–87.
[6]H. Khazani, B. Jalali Kondori, H. Sahraei, G.H. Meftahi, Brain Res. Bull. 213 (2024) 110975.
[7]M.-S. Kim, D.Y. Lee, J. Lee, H.W. Kim, S.H. Sung, J.-S. Han, W.K. Jeon, BMC Complement. Altern. Med. 18 (2018) 136.
[8]R. Kumar, R. Arora, A. Agarwal, Y.K. Gupta, J. Ethnopharmacol. 215 (2018) 124–131.
[9]Y. Chandrasekhar, G. Phani Kumar, K. Navya, E.M. Ramya, K.R. Anilakumar, J. Pharm. Pharmacol. 70 (2018) 1662–1674.
[10]V. Mani, S. Sajid, S.I. Rabbani, A.S. Alqasir, H.A. Alharbi, A. Alshumaym, Afr. J. Tradit. Complement. Altern. Med. 11 (2021) 493–502.
[11]M.E.A. El-Shamarka, W.M. Aboulthana, N.I. Omar, M.M. Mahfouz, Inflammopharmacology 32 (2024) 1439–1460.
[12]Y.-J. Li, C.-C. Liang, L. Jin, J. Chen, Spectrochim. Acta A Mol. Biomol. Spectrosc. 302 (2023) 123115.
[13]J.H. Park, H.S. Joo, K.-Y. Yoo, B.N. Shin, I.H. Kim, C.H. Lee, J.H. Choi, K. Byun, B. Lee, S.S. Lim, M.J. Kim, M.-H. Won, Neurochem. Res. 36 (2011) 2043–2050.
[14]S.M. Baram, S. Karima, S. Shateri, A. Tafakhori, A. Fotouhi, B.S. Lima, S. Rajaei, M. Mahdavi, H.S. Tehrani, V. Aghamollaii, S.H. Aghamiri, B. Mansouri, S. Gharahje, S. Kabiri, M. Hosseinizadeh, S.Z. Shahamati, A.T. Alborzi, Inflammopharmacology 27 (2019) 1101–1112.
[15]S. Kirste, M. Treier, S.J. Wehrle, G. Becker, M. Abdel-Tawab, K. Gerbeth, M.J. Hug, B. Lubrich, A.-L. Grosu, F. Momm, Cancer 117 (2011) 3788–3795.
[16]S. Meshkat, S. Mahmoodi Baram, S. Rajaei, F. Mohammadian, E. Kouhestani, N. Amirzargar, A. Tafakhori, S. Shafiee, M. Meshkat, L. Balenci, A. Kiss, A. Riazi, A. Salimi, V. Aghamollaii, F. Salmani, S. Karima, Brain Inj. 36 (2022) 553–559.
[17]M. Khalaj-Kondori, F. Sadeghi, M.A. Hosseinpourfeizi, F. Shaikhzadeh-Hesari, A. Nakhlband, M. Rahmati-Yamchi, Turk J Med Sci 46 (2016) 1573–1578.
[18]M. Hosseini-Sharifabad, R. Kamali-Ardakani, A. Hosseini-Sharifabad, Avicenna J Phytomed 6 (2016) 189–197.
[19]N. Marefati, F. Beheshti, S. Memarpour, R. Bayat, M. Naser Shafei, H.R. Sadeghnia, H. Ghazavi, M. Hosseini, Cytokine 131 (2020) 155107.
[20]N. Marefati, F. Beheshti, F. Vafaee, M. Barabadi, M. Hosseini, Neurochem. Res. 46 (2021) 2473–2484.
[21]P. Doaee, Z. Rajaei, M. Roghani, H. Alaei, M. Kamalinejad, Avicenna J Phytomed 9 (2019) 281–290.
[22]S. Shadfar, S. Khanal, G. Bohara, G. Kim, S. Sadigh-Eteghad, S. Ghavami, H. Choi, D.-Y. Choi, Mol. Neurobiol. 59 (2022) 5874–5890.
[23]A.F. Khafaga, S.E. El-Kazaz, A.E. Noreldin, Sci. Total Environ. 785 (2021) 147384.
[24]F. Forouzanfar, H. Hosseinzadeh, A. Ebrahimzadeh Bideskan, H.R. Sadeghnia, Phytother. Res. 30 (2016) 1954–1967.
[25]M. Hosseini-sharifabad, E. Esfandiari, Anat. Sci. Int. 90 (2015) 47–53.
[26]C. Jalili, M.R. Salahshoor, A. Pourmotabbed, S. Moradi, S. Roshankhah, A.S. Darehdori, M. Motaghi, Res. Pharm. Sci. 9 (2014) 351–358.
[27]O. Karima, G. Riazi, R. Yousefi, A.A.M. Movahedi, Neurol. Sci. 31 (2010) 315–320.

enXtra® Alpinia Galanga

Alpinia galanga is native to Southeast Asia, where it’s used as a food and herb [1]. It is part of the ginger family, and, similar to ginger, the rhizome, or creeping rootstalk is what’s used. The rhizome has a pungent smell reminiscent of black pepper and pine. The similarity in appearance to the ginger rhizome has led to one of its common names, Thai ginger. In some traditional medical systems, it is regarded as being superior to ginger. enXtra^® is a clinically studied and standardized Alpinia galanga rhizome extract. The research emphasis in human studies of enXtra^® has been for support of alertness and focus [2].*

TOP BENEFITS OF enXtra^®

Supports alertness and focus*

Supports brain and cognitive function*

QUALIA’S enXtra^® SOURCING

enXtra^® is standardized for total polyphenols (not less than [NLT] 4%), total flavonoids (NLT 3%), total glycosides (NLT 30%) and pyrocatecollic type tannins (NLT 1%). 

enXtra^® is responsibly sourced. It is cultivated without pesticides in hilly terrain and hand picked to ensure optimum potency. It is DNA authenticated to ensure botanical identification.

enXtra^® is GRAS affirmed, non-GMO, gluten-free, vegan, Kosher certified and Halal compliant.

Grown in India.

enXtra^® is a licensed trademark of OmniActive Health Technologies Ltd.

enXtra^® FORMULATING PRINCIPLES AND RATIONALE

In human studies, a 300 mg amount of enXtra^® has been supplemented. We consider Alpinia galanga to be in the adaptogenic herb category; following hormetic dosing principles (see Qualia Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). Depending on the role of enXtra, a formula may have either half or the full amount of this extract that has been given in the human clinical studies.*

ALPINIA GALANGA KEY MECHANISMS

Supports cognitive function*

Supports mental alertness* [2–4]

Supports attention* [5,6]

Supports memory (in animals)* [7,8]

Supports brain function*

Supports neuroprotective functions* [7–9]

CNS stimulant activity* [10]

Supports locomotor activity and motor coordination* [10]

Influences acetylcholinesterase (AChE) levels/activity in the brain* [7,8]

Influences monoamine oxidase (MAO) A and B levels/activity in the brain* [8]

Supports antioxidant defenses*

Supports antioxidant defenses in the brain* [7–9,11]

Replenishes glutathione (GSH) levels* [11]

Counters oxidative stress* [9,11]

Other actions*

Supports healthy cardiometabolic parameters* [11,12]

Supports immune system activation* [13]

*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.

REFERENCES 

[1]D. Kaushik, J. Yadav, P. Kaushik, D. Sacher, R. Rani, Zhong Xi Yi Jie He Xue Bao 9 (2011) 1061–1065.

[2]S. Srivastava, M. Mennemeier, S. Pimple, J. Am. Coll. Nutr. 36 (2017) 631–639.

[3]S. Srivastava, M. Mennemeier, J.A. Chaudhary, J. Am. Coll. Nutr. 40 (2021) 224–236.

[4]S. Shalini Srivastava, BAOJN 3 (2017) 1–10.

[5]S. Srivastava, Open Access J. Clin. Trials 10 (2018) 43–49.

[6]M.M. Eraiah, M. Kundapur, L. Joshua, J.V. Thomas, (2023).

[7]J.C. Hanish Singh, V. Alagarsamy, P.V. Diwan, S. Sathesh Kumar, J.C. Nisha, Y. Narsimha Reddy, J. Ethnopharmacol. 138 (2011) 85–91.

[8]J.C. Hanish Singh, V. Alagarsamy, S. Sathesh Kumar, Y. Narsimha Reddy, Phytother. Res. 25 (2011) 1061–1067.

[9]R. Mundugaru, S. Sivanesan, P. Udaykumar, V. Dj, S.N. Prabhu, B. Ravishankar, IJPER 52 (2018) s77–s85.

[10]S. Saha, S. Banerjee, Indian J. Exp. Biol. 51 (2013) 828–832.

[11]P. Kaushik, D. Kaushik, J. Yadav, P. Pahwa, Pak. J. Biol. Sci. 16 (2013) 804–811.

[12]R.K. Verma, G. Mishra, P. Singh, K.K. Jha, R.L. Khosa, Ayu 36 (2015) 91–95.

[13]D. Bendjeddou, K. Lalaoui, D. Satta, J. Ethnopharmacol. 88 (2003) 155–160.

Gotu Kola ( Centella asiatica ) Whole Herb Extract

In Ayurvedic medicine, gotu kola (Centella asiatica; synonym is Hydrocotyle asiatica) is considered to be a mental rejuvenator (medhya Rasayana), where it was traditionally used as a tonic herb to counter mental fatigue and improve thinking. It was thought to be particularly useful during times of increased mental demands. Other traditional uses included support of blood/circulation, skin regeneration, and general longevity. Modern science has upheld some of this reputation—gotu kola is a nootropic and supports brain repair and rejuvenation processes. It also supports healthy veins and circulation. Gotu kola, unlike many other nootropics that are best taken only at the beginning of the day, is a great fit at the end of a busy day because it is calming and supports repair and rejuvenation processes. Gotu kola contains several characteristic bioactive compounds, including asiaticoside, asiatic acid, madecassic acid, madecassoside, and centelloside. Gotu kola also contains other compounds with biological activity found in other plants such as ursolic acid, rosmarinic acid, and the flavonoids apigenin and rutin [1].*

TOP BENEFITS OF GOTU KOLA

Supports a calm mood and feelings of contentment*

Supports mental alertness and attention*

Supports a healthy stress response*

QUALIA’S GOTU KOLA SOURCING

Gotu kola is a whole herb extract. It is standardized to contain not less than 10% asiaticosides, since this group of active compounds are thought to be the main bioactives.

Gotu kola is Non-GMO and Vegan.

GOTU KOLA FORMULATING PRINCIPLES AND RATIONALE

Because gotu kola is an Ayurvedic Rasayana herb, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Qualia Dosing Principles). Herbal adaptogens tend to have a hormetic zone (or range) where there’s a favorable biological response. It’s important to be in this zone; it’s just as important not to be above it. Based on human studies, where extracts standardized for one or more of gotu kola’s asiaticosides have been used, we consider the target range of asiaticosides to be between about 12.5mg to 50mg for nootropic and mood purposes. The mg amount of gotu kola used will depend on its standardization and will be chosen to deliver an amount of asiaticosides within this range. Our goal with gotu kola, as with all ingredient choices, is to select the appropriate serving keeping in mind both the ingredient and the other ingredients being used in a formulation. In other words, if we are also supplying other adaptogens and nootropic extracts, we are likely to use less gotu kola than if the only herbal adaptogen/nootropic we were using was gotu kola.*

GOTU KOLA KEY MECHANISMS

Supports healthy mood and stress responses*

Supports a calm mood* [2–8]

Supports healthy behavioral and physiological responses to stress* [8]

Supports brain function*

Supports working memory* [4]

Supports learning and memory (in animals)* [9–15]

Supports GABAergic neurotransmission* [16–20] 

Supports glutamatergic neurotransmission* [9,21]

Influences acetylcholinesterase (AChE) activity* [14,17]

Supports synaptic density in the hippocampus and frontal cortex* [11,22]

Supports brain mitochondrial function* [10,11,14,22,23]

Supports brain-derived neurotrophic factor (BDNF)* [12,13,21,24]

Supports hippocampal long-term potentiation* [21]

Supports Nrf2 signaling and antioxidant defenses in the brain* [7,10,11,14,22,23,25]

Supports neuroprotective functions* [26]

Supports healthy immune system function*

Supports innate immunity* [27]

Supports adaptive immunity* [28,29]

*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.

REFERENCES

[1]K.J. Gohil, J.A. Patel, A.K. Gajjar, Indian J. Pharm. Sci. 72 (2010) 546–556.

[2]U. Jana, T.K. Sur, L.N. Maity, P.K. Debnath, D. Bhattacharyya, Nepal Med. Coll. J. 12 (2010) 8–11.

[3]P. Puttarak, P. Dilokthornsakul, S. Saokaew, T. Dhippayom, C. Kongkaew, R. Sruamsiri, A. Chuthaputti, N. Chaiyakunapruk, Sci. Rep. 7 (2017) 10646.

[4]J. Wattanathorn, L. Mator, S. Muchimapura, T. Tongun, O. Pasuriwong, N. Piyawatkul, K. Yimtae, B. Sripanidkulchai, J. Singkhoraard, J. Ethnopharmacol. 116 (2008) 325–332.

[5]J. Bradwejn, Y. Zhou, D. Koszycki, J. Shlik, J. Clin. Psychopharmacol. 20 (2000) 680–684.

[6]K.V. Mitha, S. Yadav, B. Ganaraja, Indian J. Physiol. Pharmacol. 60 (2016) 167–173.

[7]P. Chanana, A. Kumar, Phytother. Res. 30 (2016) 671–680.

[8]A. Wanasuntronwong, M.H. Tantisira, B. Tantisira, H. Watanabe, J. Ethnopharmacol. 143 (2012) 579–585.

[9]N.A. Binti Mohd Yusuf Yeo, S. Muthuraju, J.H. Wong, F.R. Mohammed, M.H. Senik, J. Zhang, S.R. Yusof, H. Jaafar, M.L. Adenan, H. Mohamad, T.S. Tengku Muhammad, J.M. Abdullah, Brain Behav. 8 (2018) e01093.

[10]N.E. Gray, J.A. Zweig, M. Caruso, J.Y. Zhu, K.M. Wright, J.F. Quinn, A. Soumyanath, Mol. Cell. Neurosci. 93 (2018) 1–9.

[11]N.E. Gray, J.A. Zweig, M. Caruso, M.D. Martin, J.Y. Zhu, J.F. Quinn, A. Soumyanath, Brain Behav. 8 (2018) e01024.

[12]D.C.R. Sari, N. Arfian, U. Tranggono, W.A.W. Setyaningsih, M.M. Romi, N. Emoto, Iran. J. Basic Med. Sci. 22 (2019) 1218–1224.

[13]G. Sbrini, P. Brivio, M. Fumagalli, F. Giavarini, D. Caruso, G. Racagni, M. Dell’Agli, E. Sangiovanni, F. Calabrese, Nutrients 12 (2020).

[14]A. Kumar, A. Prakash, S. Dogra, Int. J. Alzheimers. Dis. 2011 (2011) 347569.

[15]M.N. Nasir, M. Habsah, I. Zamzuri, G. Rammes, J. Hasnan, J. Abdullah, J. Ethnopharmacol. 134 (2011) 203–209.

[16]R. Awad, D. Levac, P. Cybulska, Z. Merali, V.L. Trudeau, J.T. Arnason, Canadian Journal of Physiology and Pharmacology 85 (2007) 933–942.

[17]T.K. Chatterjee, A. Chakraborty, M. Pathak, G.C. Sengupta, Indian J. Exp. Biol. 30 (1992) 889–891.

[18]M.N. Nasir, J. Abdullah, M. Habsah, R.I. Ghani, G. Rammes, Phytomedicine 19 (2012) 311–316.

[19]T.E. Ceremuga, D. Valdivieso, C. Kenner, A. Lucia, K. Lathrop, O. Stailey, H. Bailey, J. Criss, J. Linton, J. Fried, A. Taylor, G. Padron, A.D. Johnson, AANA J. 83 (2015) 91–98.

[20]K. Hamid, I. Ng, V.J. Tallapragada, L. Váradi, D.E. Hibbs, J. Hanrahan, P.W. Groundwater, Chem. Biol. Drug Des. 88 (2016) 386–397.

[21]N.E. Gray, C.J. Harris, J.F. Quinn, A. Soumyanath, J. Ethnopharmacol. 180 (2016) 78–86.

[22]N.E. Gray, J.A. Zweig, D.G. Matthews, M. Caruso, J.F. Quinn, A. Soumyanath, Oxid. Med. Cell. Longev. 2017 (2017) 7023091.

[23]M. Ar Rochmah, I.M. Harini, D.E. Septyaningtrias, D.C.R. Sari, R. Susilowati, Biomed Res. Int. 2019 (2019) 2649281.

[24]Y. Boondam, P. Songvut, M.H. Tantisira, S. Tapechum, K. Tilokskulchai, N. Pakaprot, Sci. Rep. 9 (2019) 8404.

[25]N. Haleagrahara, K. Ponnusamy, J. Toxicol. Sci. 35 (2010) 41–47.

[26]S. Chen, Z.-J. Yin, C. Jiang, Z.-Q. Ma, Q. Fu, R. Qu, S.-P. Ma, Pharmacol. Biochem. Behav. 122 (2014) 7–15.

[27]M.G. Jayathirtha, S.H. Mishra, Phytomedicine 11 (2004) 361–365.

[28]D. Arora, M. Kumar, S.D. Dubey, U. Sings, Anc. Sci. Life 22 (2002) 42–48.

[29]K. Punturee, C.P. Wild, W. Kasinrerk, U. Vinitketkumnuen, Asian Pac. J. Cancer Prev. 6 (2005) 396–400.

Saffron Stigma Extract

Scientific Name:
Crocus sativus

Saffron is a spice derived from the flowers of Crocus sativus. It’s been used and traded as a spice for at least 4000 years and is considered the world's most costly spice by weight. Saffron has had a wide range and long list of traditional uses. In Traditional Iranian Medicine saffron was thought to be useful for supporting sleep and mood, and to be a heart tonic. And in India it was used as a nerve and heart tonic, and for relaxation and sleep support. Iran produces the majority of saffron: Greece, Kashmir, Morocco, Spain and Turkey are also fairly large growers. Saffron, as a spice, refers to the deep red-maroon colored stigma and styles (called threads). Not all saffron is of the same quality and strength, with price increasing substantially for the highest grades. In general, the content of several of saffron’s active compounds are used to determine strength. A greater content of crocin (responsible for saffron's color), picrocrocin (a bitter compound giving the characteristic taste), and safranal (which gives the fragrance) would be graded as higher strength. In addition to these marker compounds, saffron also contains zeaxanthin, lycopene, and other carotenoids. Crocin also belongs to the carotenoid family. Most carotenoids only dissolve in oil (i.e., are fat-soluble). Crocin is water-soluble, which is part of the reason it is used in rice dishes and other water-based food recipes. There’s been a growing interest in the use of saffron for health purposes, including in areas such as mood, cognition, vision, sports performance, appetite regulation, metabolic function, sleep, and women’s health.*

TOP BENEFITS OF SAFFRON

Supports mood*

Supports cognitive function*

Supports vision*

QUALIA’S SAFFRON SOURCING

The saffron extract we use is standardized for 0.3% safranal.

Saffron extract used in our products is GRAS, non-GMO, gluten-free, vegan, Kosher certified and Halal compliant. 

SAFFRON FORMULATING PRINCIPLES AND RATIONALE

Some saffron studies in humans have used highly standardized extracts, with servings typically in the range of 20-30 mg per day. Many other studies have used saffron powder (unstandardized) with servings often ranging from 50-300 mg daily. We source an extract that is between these two extremes—standardized, but not as highly standardized, because we believe capturing more of the essence of whole saffron stigmas is the most suitable approach for promoting health with this ingredient. Since studies comparing multiple amounts or different standardizations have not been published, there’s no information on whether saffron has a threshold effect (i.e., an amount or range less than the full serving where the majority of the response would occur; see Qualia Dosing Principles) or how different extract strengths compare to each other or to saffron powder. However, individual (i.e. N of 1) subjective response to saffron does vary considerably, with some persons reporting noticeable differences when taking as little as 1-3 mg of a standardized saffron extract. Depending on the purpose Qualia is using saffron for, and the other ingredients it’s combined with, the recommended serving may be anywhere ranging from a more micro-serving level up (3 mg) up to a serving of 30 mg per day.*

SAFFRON KEY MECHANISMS

Supports a healthy mood*

Supports a positive mental-emotional bias* [1–10]

Supports a calm mood* [1,4,7–9]

Supports healthy acute stress responses* [11]

Supports healthy brain function*

Supports focus and attention* [12]

Supports healthy brain aging* [13–16]

Supports healthy sleep* [17–22]

Supports dopamine signaling* [23]

Supports glutamate signaling* [23]

Influences acetylcholinesterase activity* [24,25]

Supports brain-derived neurotrophic factor (BDNF) levels* [10,26,27]

Supports antioxidant and neuroprotective functions* [25,28–34]

Supports healthy vision*

Supports healthy retinal function* [30,35–42]

Supports macular health* [36,39,42]

Supports visual acuity* [39,42]

Supports protection of retinal cells from light-induced damage* [37,43–45]

Supports healthy intraocular pressure* [46]

Supports exercise performance*

Supports reaction times* [47]

Supports muscle strength* [47]

Supports muscle recovery functions* [48]

Supports antioxidant defenses*

Supports antioxidant enzymes* [25,29,41]

Supports the replenishment of glutathione (GSH) levels* [25,41]

Supports free-radical scavenging* [25,29,40,41]

Supports healthy prooxidant-antioxidant balance* [49]

*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.

REFERENCES

[1]W. Marx, M. Lane, T. Rocks, A. Ruusunen, A. Loughman, A. Lopresti, S. Marshall, M. Berk, F. Jacka, O.M. Dean, Nutr. Rev. 77 (2019) 557–571.
[2]H.A. Hausenblas, D. Saha, P.J. Dubyak, S.D. Anton, J. Integr. Med. 11 (2013) 377–383.
[3]A.L. Lopresti, P.D. Drummond, Hum. Psychopharmacol. 29 (2014) 517–527.
[4]G. Kell, A. Rao, G. Beccaria, P. Clayton, A.M. Inarejos-García, M. Prodanov, Complement. Ther. Med. 33 (2017) 58–64.
[5]S. Akhondzadeh, N. Tahmacebi-Pour, A.-A. Noorbala, H. Amini, H. Fallah-Pour, A.-H. Jamshidi, M. Khani, Phytother. Res. 19 (2005) 148–151.
[6]E. Moshiri, A.A. Basti, A.-A. Noorbala, A.-H. Jamshidi, S. Hesameddin Abbasi, S. Akhondzadeh, Phytomedicine 13 (2006) 607–611.
[7]A. Ghajar, S.M. Neishabouri, N. Velayati, L. Jahangard, N. Matinnia, M. Haghighi, A. Ghaleiha, M. Afarideh, S. Salimi, A. Meysamie, S. Akhondzadeh, Pharmacopsychiatry 50 (2017) 152–160.
[8]M. Mazidi, M. Shemshian, S.H. Mousavi, A. Norouzy, T. Kermani, T. Moghiman, A. Sadeghi, N. Mokhber, M. Ghayour-Mobarhan, G.A.A. Ferns, J. Complement. Integr. Med. 13 (2016) 195–199.
[9]A. Milajerdi, S. Jazayeri, E. Shirzadi, N. Hashemzadeh, A. Azizgol, A. Djazayery, A. Esmaillzadeh, S. Akhondzadeh, Complement. Ther. Med. 41 (2018) 196–202.
[10]E. Corridori, S. Salviati, M.G. Demontis, P. Vignolini, C. Vita, A. Fagiolini, A. Cuomo, P. Carmellini, C. Gambarana, S. Scheggi, Phytother. Res. 39 (2025) 1277–1291.
[11]C. Pouchieu, L. Pourtau, J. Brossaud, D. Gaudout, J.-B. Corcuff, L. Capuron, N. Castanon, P. Philip, Nutrients 15 (2023).
[12]B. Pazoki, N. Zandi, Z. Assaf, H.S. Moghaddam, A. Zeinoddini, M.R. Mohammadi, S. Akhondzadeh, Advances in Integrative Medicine 9 (2022) 37–43.
[13]M. Farokhnia, M. Shafiee Sabet, N. Iranpour, A. Gougol, H. Yekehtaz, R. Alimardani, F. Farsad, M. Kamalipour, S. Akhondzadeh, Hum. Psychopharmacol. 29 (2014) 351–359.
[14]S. Akhondzadeh, M.S. Sabet, M.H. Harirchian, M. Togha, H. Cheraghmakani, S. Razeghi, S.S. Hejazi, M.H. Yousefi, R. Alimardani, A. Jamshidi, F. Zare, A. Moradi, J. Clin. Pharm. Ther. 35 (2010) 581–588.
[15]S. Akhondzadeh, M. Shafiee Sabet, M.H. Harirchian, M. Togha, H. Cheraghmakani, S. Razeghi, S.S. Hejazi, M.H. Yousefi, R. Alimardani, A. Jamshidi, S.-A. Rezazadeh, A. Yousefi, F. Zare, A. Moradi, A. Vossoughi, Psychopharmacology 207 (2010) 637–643.
[16]M. Tsolaki, E. Karathanasi, I. Lazarou, K. Dovas, E. Verykouki, A. Karacostas, K. Georgiadis, A. Tsolaki, K. Adam, I. Kompatsiaris, Z. Sinakos, J. Alzheimers. Dis. 54 (2016) 129–133.
[17]A.L. Lopresti, S.J. Smith, P.D. Drummond, Sleep Med. 86 (2021) 7–18.
[18]A. Tajaddini, N. Roshanravan, M. Mobasseri, A. Aeinehchi, P. Sefid-Mooye Azar, A. Hadi, A. Ostadrahimi, Int. J. Clin. Pract. 75 (2021) e14334.
[19]A.L. Lopresti, S.J. Smith, A.P. Metse, P.D. Drummond, J. Clin. Sleep Med. 16 (2020) 937–947.
[20]B.D. Pachikian, S. Copine, M. Suchareau, L. Deldicque, Nutrients 13 (2021) 1473.
[21]M. Masaki, K. Aritake, H. Tanaka, Y. Shoyama, Z.-L. Huang, Y. Urade, Mol. Nutr. Food Res. 56 (2012) 304–308.
[22]Z. Liu, X.-H. Xu, T.-Y. Liu, Z.-Y. Hong, Y. Urade, Z.-L. Huang, W.-M. Qu, CNS Neurosci. Ther. 18 (2012) 623–630.
[23]H. Ettehadi, S.N. Mojabi, M. Ranjbaran, J. Shams, H. Sahraei, M. Hedayati, F. Asefi, JBBS 03 (2013) 315–319.
[24]G.D. Geromichalos, F.N. Lamari, M.A. Papandreou, D.T. Trafalis, M. Margarity, A. Papageorgiou, Z. Sinakos, J. Agric. Food Chem. 60 (2012) 6131–6138.
[25]S.V. Rao, Muralidhara, S.C. Yenisetti, P.S. Rajini, Neurotoxicology 52 (2016) 230–242.
[26]T. Ghasemi, K. Abnous, F. Vahdati, S. Mehri, B.M. Razavi, H. Hosseinzadeh, Drug Res. 65 (2015) 337–343.
[27]F. Vahdati Hassani, V. Naseri, B.M. Razavi, S. Mehri, K. Abnous, H. Hosseinzadeh, Daru 22 (2014) 16.
[28]S. Gudarzi, M. Jafari, G. Pirzad Jahromi, R. Eshrati, M. Asadollahi, P. Nikdokht, Nutr. Neurosci. 25 (2022) 1137–1146.
[29]B. Naghizadeh, M.T. Mansouri, B. Ghorbanzadeh, Y. Farbood, A. Sarkaki, Phytomedicine 20 (2013) 537–542.
[30]S. Purushothuman, C. Nandasena, C.L. Peoples, N. El Massri, D.M. Johnstone, J. Mitrofanis, J. Stone, J. Parkinsons. Dis. 3 (2013) 77–83.
[31]Y.S. Batarseh, S.S. Bharate, V. Kumar, A. Kumar, R.A. Vishwakarma, S.B. Bharate, A. Kaddoumi, ACS Chem. Neurosci. 8 (2017) 1756–1766.
[32]L. Tamegart, A. Abbaoui, R. Makbal, M. Zroudi, B. Bouizgarne, M.M. Bouyatas, H. Gamrani, Acta Histochem. 121 (2019) 171–181.
[33]P. Haeri, A. Mohammadipour, Z. Heidari, A. Ebrahimzadeh-Bideskan, Anat. Sci. Int. 94 (2019) 119–127.
[34]S. Soeda, K. Aritake, Y. Urade, H. Sato, Y. Shoyama, Adv Neurobiol 12 (2016) 275–292.
[35]A. Lashay, G. Sadough, E. Ashrafi, M. Lashay, M. Movassat, S. Akhondzadeh, Med Hypothesis Discov Innov Ophthalmol 5 (2016) 32–38.
[36]B. Falsini, M. Piccardi, A. Minnella, C. Savastano, E. Capoluongo, A. Fadda, E. Balestrazzi, R. Maccarone, S. Bisti, Invest. Ophthalmol. Vis. Sci. 51 (2010) 6118–6124.
[37]M. Yamauchi, K. Tsuruma, S. Imai, T. Nakanishi, N. Umigai, M. Shimazawa, H. Hara, Eur. J. Pharmacol. 650 (2011) 110–119.
[38]R. Natoli, Y. Zhu, K. Valter, S. Bisti, J. Eells, J. Stone, Mol. Vis. 16 (2010) 1801–1822.
[39]G.K. Broadhead, J.R. Grigg, P. McCluskey, T. Hong, T.E. Schlub, A.A. Chang, Graefes Arch. Clin. Exp. Ophthalmol. 257 (2019) 31–40.
[40]B. Lv, T. Chen, Z. Xu, F. Huo, Y. Wei, X. Yang, Int. J. Mol. Med. 37 (2016) 225–232.
[41]L. Chen, Y. Qi, X. Yang, Ophthalmic Res. 54 (2015) 157–168.
[42]M. Piccardi, D. Marangoni, A.M. Minnella, M.C. Savastano, P. Valentini, L. Ambrosio, E. Capoluongo, R. Maccarone, S. Bisti, B. Falsini, Evid. Based. Complement. Alternat. Med. 2012 (2012) 429124.
[43]R. Maccarone, S. Di Marco, S. Bisti, Invest. Ophthalmol. Vis. Sci. 49 (2008) 1254–1261.
[44]F.D. Marco, S. Romeo, C. Nandasena, S. Purushothuman, C. Adams, S. Bisti, J. Stone, Am. J. Neurodegener. Dis. 2 (2013) 208–220.
[45]A. Laabich, G.P. Vissvesvaran, K.L. Lieu, K. Murata, T.E. McGinn, C.C. Manmoto, J.R. Sinclair, I. Karliga, D.W. Leung, A. Fawzi, R. Kubota, Invest. Ophthalmol. Vis. Sci. 47 (2006) 3156–3163.
[46]M.H. Jabbarpoor Bonyadi, S. Yazdani, S. Saadat, BMC Complement. Altern. Med. 14 (2014) 399.
[47]A. Meamarbashi, A. Rajabi, J. Diet. Suppl. 13 (2016) 522–529.
[48]A. Meamarbashi, A. Rajabi, Clin. J. Sport Med. 25 (2015) 105–112.
[49]T. Kermani, S.H. Mousavi, M. Shemshian, A. Norouzy, M. Mazidi, A. Moezzi, T. Moghiman, M. Ghayour-Mobarhan, G. A Ferns, Avicenna J Phytomed 5 (2015) 427–433.