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.

EnXtra® Alpinia Galanga

ALPINIA GALANGA COMMON NAME

Greater Galangal | Thai Ginger | Siamese Ginger

TOP BENEFITS OF ALPINIA GALANGA

  • Sharpens alertness and focus*
  • Amplifies caffeine’s nootropic benefits*
  • Supports brain and cognitive function*

WHAT IS 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. In human studies, EnXtra® has been complementary to caffeine. In a clinical study, supplementation with EnXtra® supported alertness and focus It’s clinically proven to improve alertness and focus for up to 5 hours with and without caffeine. EnXtra® can be used as a replacement for caffeine or used with caffeine to prevent crash and prolong caffeine’s nootropic benefits. [2]

NEUROHACKER’S ALPINIA GALANGA SOURCING

EnXtra® has been used in human clinical studies, where it has enhanced alertness and focus, and amplified the nootropic response to caffeine.

EnXtra® is created by Enovate Biolife, and is standardized for total polyphenols (not less than [NLT] 3%), flavanoids (NLT 4%), polysaccharides (NLT 20%) 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 registered trademark of Enovate Bioscience. 

ALPINIA GALANGA DOSING PRINCIPLES AND RATIONALE

We consider Alpinia galanga to be in the adaptogenic herb category; following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at an amount that is consistent with the studied amount in the human clinical studies.*

ALPINIA GALANGA KEY MECHANISMS

Cognitive function

  • Supports mental alertness [2]
  • Supports attention [3]
  • Supports memory [4,5]

Brain function

  • Neuroprotective effects [4–6]
  • CNS stimulant activity [7]
  • Supports locomotor activity and motor coordination [7]
  • Downregulates acetylcholinesterase (AChE) levels/activity in the brain [4,5]
  • Downregulates monoamine oxidase (MAO) A and B levels/activity in the brain [5]

Antioxidant defenses

  • Upregulates antioxidant enzymes in the brain (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [4–6,8]
  • Replenishes glutathione (GSH) levels [8]
  • Downregulates lipid peroxidation [6,8]

Other effects

  • Supports healthy cardiometabolic parameters [8,9]
  • Immunostimulant activity [10]

Complementary ingredients

  • Caffeine — supports sustained attention [2]


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. Shalini Srivastava, BAOJN 3 (2017) 1–10.
[4] J.C. Hanish Singh, V. Alagarsamy, P.V. Diwan, S. Sathesh Kumar, J.C. Nisha, Y. Narsimha Reddy, J. Ethnopharmacol. 138 (2011) 85–91.
[5] J.C. Hanish Singh, V. Alagarsamy, S. Sathesh Kumar, Y. Narsimha Reddy, Phytother. Res. 25 (2011) 1061–1067.
[6] R. Mundugaru, S. Sivanesan, P. Udaykumar, V. Dj, S.N. Prabhu, B. Ravishankar, IJPER 52 (2018) s77–s85.
[7] S. Saha, S. Banerjee, Indian J. Exp. Biol. 51 (2013) 828–832.
[8] P. Kaushik, D. Kaushik, J. Yadav, P. Pahwa, Pak. J. Biol. Sci. 16 (2013) 804–811.
[9] R.K. Verma, G. Mishra, P. Singh, K.K. Jha, R.L. Khosa, Ayu 36 (2015) 91–95.
[10] D. Bendjeddou, K. Lalaoui, D. Satta, J. Ethnopharmacol. 88 (2003) 155–160.

Celastrus Paniculatus Seed Extract

Scientific Name:
Celastrus paniculatus Willd

CELASTRUS PANICULATUS COMMON NAME

Celastrus | Intellect Tree | Jyotishmati

TOP BENEFITS OF CELASTRUS PANICULATUS

Supports cognitive performance*

Supports mood*

Supports stress response*

WHAT IS CELASTRUS PANICULATUS?

Celastrus paniculatus is native to India, where it’s used by local healers primarily as a brain tonic for reasons that are consistent with one of its common names, “the intellect tree.” Today we’d recognize these uses as offering nootropic support. These uses include “...mental acuity, support memory and intellect as well as retention and recalling power; and to alleviate mental fatigue, stress...”*[1] It was believed that people using this plant would be able to learn new information more quickly, and more accurately and efficiently recall it later.*[1] Celastrus paniculatus seeds (and their oil) are what is used for cognitive support. The seeds contains a variety of active compounds, including sesquiterpenes such as celastrine, celapanine, celapanigine, celapagin, malkangunin and paniculatine. Celastrus paniculatus extracts have, in experimental research, positively influenced cognitive function and neuroprotective functions.*

NEUROHACKER’S CELASTRUS PANICULATUS SOURCING

Celastrus paniculatus is an alcohol extract of the seeds.

Grown in India.

Celastrus paniculatus is non-GMO, gluten-free, vegan, 

CELASTRUS PANICULATUS DOSING PRINCIPLES AND RATIONALE

One way Celastrus paniculatus was traditionally used was to have a person start by eating one seed a day in the diet, and then gradually increase by one seed a day, up to a maximum of 100 seeds daily.[1] This suggests to Neurohacker that the best way to approach dosing would be to consider Celastrus paniculatus as an adaptogenic herb; following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at a low-to-moderate amount because of both the traditional approach to use, and because of our N of 1 dosing experience in product development and testing.*

CELASTRUS PANICULATUS KEY MECHANISMS 

Brain function and cognition

Supports memory and facilitates learning [2,5,7]

Counters experimentally-induced memory and learning impairments in animals [5,8–11]

Supports the levels of monoamine neurotransmitters (noradrenaline, dopamine and serotonin) and their metabolites in the brain [2]

Interacts with dopamine-D2, serotonergic, GABAB, and NMDA receptors [3,4]

Influences brain MAO-A levels [3]

Influences acetylcholinesterase activity in the brain [5]

Supports brain content of total lipids and phospholipids [6]

Supports neuroprotective functions [4,11,13,14]

Mood and stress

Supports positive behavioral responses to stress [3,8,12]

Influences plasma corticosterone (stress hormone) levels [3]

Antioxidant defenses

Supports antioxidant defenses [7,11,13–17]

Counters oxidative stress [7,11,13–17]

Supports free-radical-scavenging activity [14,16,18]

Other effects

Supports healthy immune/cytokine signaling [17,19,20]

Supports relief of minor physical discomfort [19,20]

Supports gastroprotective functions [17]

Supports healthy cholesterol levels [21]

REFERENCES

[1]N. Arora, S.P. Rai, Int. J. Pharma Bio Sci. 3 (2012) 290–303.
[2]K. Nalini, K.S. Karanth, A. Rao, A.R. Aroor, J. Ethnopharmacol. 47 (1995) 101–108.
[3]R. Valecha, D. Dhingra, Basic Clin Neurosci 7 (2016) 49–56.
[4]P.B. Godkar, R.K. Gordon, A. Ravindran, B.P. Doctor, J. Ethnopharmacol. 93 (2004) 213–219.
[5]M. Bhanumathy, M.S. Harish, H.N. Shivaprasad, G. Sushma, Pharm. Biol. 48 (2010) 324–327.
[6]P.P. Bidwai, D. Wangoo, N.K. Bhullar, J. Ethnopharmacol. 21 (1987) 307–314.
[7]M.H.V. Kumar, Y.K. Gupta, Phytomedicine 9 (2002) 302–311.
[8]V. Bhagya, T. Christofer, B.S. Shankaranarayana Rao, Indian J. Pharmacol. 48 (2016) 687–693.
[9]M. Gattu, K.L. Boss, A.V. Terry Jr, J.J. Buccafusco, Pharmacol. Biochem. Behav. 57 (1997) 793–799.
[10]S.B. Raut, R.R. Parekar, K.S. Jadhav, P.A. Marathe, N.N. Rege, Anc. Sci. Life 34 (2015) 130–133.
[11]J. Malik, M. Karan, R. Dogra, Pharm. Biol. 55 (2017) 980–990.
[12]R. Rajkumar, E.P. Kumar, S. Sudha, B. Suresh, Fitoterapia 78 (2007) 120–124.
[13]M. Chakrabarty, P. Bhat, S. Kumari, A. D’Souza, K.L. Bairy, A. Chaturvedi, A. Natarajan, M.K.G. Rao, S. Kamath, J. Pharmacol. Pharmacother. 3 (2012) 161–171.
[14]P.B. Godkar, R.K. Gordon, A. Ravindran, B.P. Doctor, Phytomedicine 13 (2006) 29–36.
[15]G. Lekha, K. Mohan, I.A. Samy, Pharmacognosy Res. 2 (2010) 169–174.
[16]P. Godkar, R.K. Gordon, A. Ravindran, B.P. Doctor, Fitoterapia 74 (2003) 658–669.
[17]S. Palle, A. Kanakalatha, C.N. Kavitha, J. Diet. Suppl. 15 (2018) 373–385.
[18]A. Russo, A.A. Izzo, V. Cardile, F. Borrelli, A. Vanella, Phytomedicine 8 (2001) 125–132.
[19]F. Ahmad, R.A. Khan, S. Rasheed, J. Ethnopharmacol. 42 (1994) 193–198.
[20]Y.A. Kulkarni, S. Agarwal, M.S. Garud, J. Ayurveda Integr. Med. 6 (2015) 82–88.
[21]R.H. Patil, K. Prakash, V.L. Maheshwari, Indian J. Clin. Biochem. 25 (2010) 405–410.

*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.




Coffeeberry® (caffeine)

Scientific Name:
1,3,7-trimethylpurine-2,6-dione

COFFEEBERRY® COMMON NAME

Coffee Fruit | Coffee Cherry | Coffee Berry

TOP BENEFITS OF COFFEEBERRY®

  • Supports cognitive performance*
  • Supports exercise performance*
  • Supports mood*

WHAT IS COFFEEBERRY®?

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 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 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. 

NEUROHACKER’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® DOSING PRINCIPLES AND RATIONALE

Because of its content of caffeine, we consider Coffeeberry® Energy to follow hormetic dosing principles (see Neurohacker 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 doses of caffeine supporting better cognitive and sports performance, but doses above the higher end of the range hindering performance. We have selected to dose Coffeeberry® at an amount that delivers the amount of caffeine (~90 mg) 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.

COFFEEBERRY® KEY MECHANISMS

Brain function

  • Adenosine receptor antagonist [2]
  • Adenosine decreases the levels of the neurotransmitters acetylcholine, glutamate, serotonin, dopamine and norepinephrine; blocking adenosine receptors, caffeine counters those effects [3,4]
  • Upregulates acetylcholine signaling [4–7]
  • Upregulates dopamine signaling [4,8–13]
  • Upregulates serotonin signaling [4,7,14–17]
  • Upregulates glutamate signaling [4,8,9]
  • Upregulates GABA signaling [4,7]
  • Upregulates noradrenaline signaling [4,16]
  • Upregulates cortical activation in the brain [2,4]
  • Upregulates cerebral metabolism [2,4]
  • Promotes wakefulness [18]

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 task switching [27]
  • Supports reaction time [1,21,22,27]
  • Supports reasoning [20]
  • Supports creative thinking [24]
  • Protects from mental fatigue [26,28]

Neuroprotection

  • Protects against neurotoxic agents [29]
  • Protects from neurodegenerative processes [30]

Mood

  • Improves mood [4,21,22,25,31]

Physical performance

  • Protects from physical fatigue [19,22,23,32]
  • Decreases perceived exhaustion [1]
  • Supports muscle endurance and strength exercise activities [1]
  • Enhances speed, power, and agility during intense exercise [1] 

Other effects

  • Upregulates the metabolic rate [33–35]
  • Non-selective phosphodiesterase inhibitor [36]

Complementary ingredients

  • Theobromine as a CNS stimulant, with faster onset and shorter duration than Theobromine [37]
  • L-Theanine in cognitive performance [26,38–40]
  • 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]


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

NooLVL™

NooLVLTM COMMON NAME

Inositol-enhanced Bonded Arginine Silicate

TOP BENEFITS OF nooLVLTM

  • Enhances processing speed and accuracy*
  • Supports executive function*
  • Boosts energy*
  • Promotes muscle performance*

WHAT IS nooLVLTM?

nooLVLTM is comprised of two components: Bonded (inositol-stabilized) arginine silicate (Nitrosigine®) plus additional inositol. L-arginine has relatively low bioavailability (~20%) following an oral dose, so high doses are needed to significantly boost blood arginine levels.[1] Nitrosigine® and nooLVLTM have overcome this limitation by bonding the L-arginine to a silicate–inositol complex, which significantly enhances the bioavailability of L-arginine.[2–5] L-arginine is involved in promoting healthy circulation because it can be used for nitric oxide production. Blood flow to metabolically active tissues, like the brain and muscles, plays a big role in allowing these tissues to perform their functions at a high level. Bonded arginine silicate supports exercise performance and post-exercise recovery by promoting muscle blood flow.[6] It also supports brain performance, enhancing mental accuracy, focus, processing speed, and executive function.[5,7,8]

NEUROHACKER’S nooLVLTM SOURCING

nooLVLTM has been clinically studied in humans: It has boosted cognitive performance and energy in eSports athletes.

nooLVLTM is an upgraded version of Nitrosigine®, an ingredient that supports blood arginine levels and nitric oxide production, enhanced energy, promoted focus and mental acuity, and supported better muscle response following exercise. 

nooLVLTM is a patented nutritional ingredient from Nutrition 21: It contains Nitrosigine® (l-arginine bonded to silica and inositol with affirmed GRAS) plus added inositol. 

nooLVLTM is gluten-free, vegan, and non-GMO.

nooLVLTM is a trademark of Nutrition 21, LLC.

nooLVLTM DOSING PRINCIPLES AND RATIONALE

Studied dose of nooLVLTM has been 1600 mg/day: Nitrosigine® has been 1500 mg/day. Since these are the highest doses that have been given in human research, we consider them to be the upper limit we’d be comfortable with for daily dosing. Since it’s possible that the product this is included in might be used more than once a day (i.e., a person could opt to take two servings), we included a half dose per serving (i.e., 800 mg of nooLVLTM). In Neurohacker’s subjective and objective internal N of 1 testing, the half dose of nooLVLTM had additive effects when combined with other nootropic ingredients.*

nooLVLTM KEY MECHANISMS

Vascular function

  • L-arginine is the substrate for vascular nitric oxide (NO) production by NO synthase (NOS)[9]
  • Upregulates endothelial NOS (eNOS) [silicate][10]
  • Upregulates the blood levels of arginine, silicon, and NO[4]
  • Supports healthy vascular function [2]
  • Supports healthy blood pressure [arginine][11] [inositol][12,13]

Brain function

  • Upregulates dopamine release[14–16].
  • Regulates dopamine transporter (DAT) activity[17–20] 
  • Supports neurotransmitter signaling [inositol][21]

Cognitive function

  • Supports performance in complex cognitive tests requiring mental flexibility, processing speed and executive functioning[7]

Exercise performance (ergogenic effects)

  • Supports exercise performance [arginine][22]
  • Delays time to exhaustion [arginine][22]
  • Delays muscle fatigue [arginine][23]
  • Supports muscle blood flow after exercise[6]
  • Protects from muscle damage after exercise and during recovery[6]


REFERENCES

[1] O. Tangphao, M. Grossmann, S. Chalon, B.B. Hoffman, T.F. Blaschke, Br. J. Clin. Pharmacol. 47 (1999) 261–266.
[2] S.D. Proctor, S.E. Kelly, J.C. Russell, Diabetologia 48 (2005) 1925–1932.
[3] S.D. Proctor, S.E. Kelly, D.F. Vine, J.C. Russell, Metabolism 56 (2007) 1318–1325.
[4] D.S. Kalman, S. Feldman, A. Samson, D.R. Krieger, Clin. Pharmacol. 7 (2015) 103–109.
[5] J. Komorowski, S.P. Ojalvo, The FASEB Journal 30 (2016) 690.17–690.17.
[6] S. Rood-Ojalvo, D. Sandler, E. Veledar, J. Komorowski, J. Int. Soc. Sports Nutr. 12 (2015) P14.
[7] D. Kalman, P.D. Harvey, S. Perez Ojalvo, J. Komorowski, Nutrients 8 (2016).
[8] S. Sylla, S.P. Ojalvo, J. Komorowski, The FASEB Journal 32 (2018) 724.12–724.12.
[9] N.W. Rajapakse, D.L. Mattson, Clin. Exp. Pharmacol. Physiol. 36 (2009) 249–255.
[10] B. Buffoli, E. Foglio, E. Borsani, C. Exley, R. Rezzani, L.F. Rodella, Acta Histochem. 115 (2013) 418–424.
[11] J.-Y. Dong, L.-Q. Qin, Z. Zhang, Y. Zhao, J. Wang, F. Arigoni, W. Zhang, Am. Heart J. 162 (2011) 959–965.
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[13] D. Giordano, F. Corrado, A. Santamaria, S. Quattrone, B. Pintaudi, A. Di Benedetto, R. D’Anna, Menopause 18 (2011) 102–104.
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[16] A. Strasser, R.M. McCarron, H. Ishii, D. Stanimirovic, M. Spatz, Neuroreport 5 (1994) 2298–2300.
[17] T.J. Volz, J.O. Schenk, Synapse 54 (2004) 173–182.
[18] J.P. Kiss, G. Zsilla, E.S. Vizi, Neurochem. Int. 45 (2004) 485–489.
[19] J.P. Kiss, E.C. Hennings, G. Zsilla, E.S. Vizi, Neurochem. Int. 34 (1999) 345–350.
[20] V. Chaparro-Huerta, C. Beas-Zárate, M.U. Guerrero, A. Feria-Velasco, Neurochem. Int. 31 (1997) 607–616.
[21] S.K. Fisher, J.E. Novak, B.W. Agranoff, J. Neurochem. 82 (2002) 736–754.
[22] H.U. Yavuz, H. Turnagol, A.H. Demirel, Biol. Sport 31 (2014) 187–191.
[23] A. Schaefer, F. Piquard, B. Geny, S. Doutreleau, E. Lampert, B. Mettauer, J. Lonsdorfer, Int. J. Sports Med. 23 (2002) 403–407.

Alpha GPC

Scientific Name:
Alpha-glycerophosphocholine

ALPHA-GLYCEROPHOSPHOCHOLINE COMMON NAME

Alpha-GPC | Glycerophosphocholine | Choline alphoscerate | L-alpha-glycerophosphocholine

TOP BENEFITS OF ALPHA-GLYCEROPHOSPHOCHOLINE

Supports cognitive function*

Supports exercise performance* 

WHAT IS ALPHA-GLYCEROPHOSPHOCHOLINE?

Alpha-glycerophosphocholine (alpha-GPC) is a choline-containing phospholipid that can be used to augment the body and brain choline pool. In this role it serves as a precursor for both acetylcholine and phosphatidylcholine biosynthesis. Alpha-GPC and citicoline (i.e., CDP-choline) are considered the nootropic forms of choline, with both forms able to increase brain choline levels, act as building blocks for acetylcholine, and support choline-dependent neurotransmission.[1–4]* However, of the two, alpha-GPC contains a higher proportion of choline, so a lower dose of alpha-GPC gives greater choline support than a similar dose of citicoline.[5–7] This means that by weight alpha-GPC is the more efficient choline precursor. Following an oral dose, alpha-GPC metabolizes into choline and the phospholipid glycerophosphate. The choline can be used for acetylcholine synthesis and neurotransmission.[3,8–14] Acetylcholine is central to brain neurotransmission; it’s 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. Because alpha-GPC is a precursor in the biosynthesis of acetylcholine, it plays a supportive role in a variety of cognitive functions, including attention, concentration, mental focus, and memory formation and recall.[15]* Alpha-GPC also supports aspects of muscle performance, and is involved in maintaining organs and tissues.* And, because alpha-GPC can be readily metabolized into phosphatidylcholine, it can be used to support the structure and function of cell membranes. Alpha-GPC is found in low amounts in a variety of foods[16] and in breast milk.[17,18] 

NEUROHACKER’S ALPHA-GLYCEROPHOSPHOCHOLINE SOURCING

Alpha-glycerophosphocholine (Alpha-GPC) is a source of choline; it is able to influence both systemic and brain concentrations of choline.

Alpha-GPC is derived from soy.

Neurohacker uses an Alpha-GPC that is sourced to be non-GMO, gluten-free, and vegan.

ALPHA-GLYCEROPHOSPHOCHOLINE DOSING PRINCIPLES AND RATIONALE

Alpha-glycerophosphocholine (Alpha-GPC) is by weight one of the best sources of choline. While alpha-GPC is often treated as if it’s dose-dependent (i.e., a higher dose is better) and doses of 1200 mg/day have been used in some clinical studies, Neurohacker believes the evidence suggests a threshold response (see Neurohacker Dosing Principles) when alpha-GPC is given to healthy people. This means that more might not be better under all circumstances. As an example, in a study of healthy college-aged men, while the higher dose (500 mg/day) of alpha-GPC did a better job increasing free choline levels, the lower dose (250 mg/day) produced a better peak muscle force response.[19] In general, Neurohacker’s experience with alpha-GPC (as well as citicoline) indicate that when used as part of comprehensive nootropic formulations, a more modest dose is often sufficient. Alpha-GPC is a useful choline source in liquids because of its taste and solubility. In general, the best time to take alpha-GPC is early in the day.

ALPHA-GLYCEROPHOSPHOCHOLINE KEY MECHANISMS

Augments choline pool

Alpha-GPC is part of the CDP-choline (or Kennedy) pathway, which has a central role in choline homeostasis [13,14]

Supports plasma choline levels [20]

Precursor for phosphatidylcholine synthesis [3]

Precursor for acetylcholine synthesis [2,3]

Brain function

Supports memory and learning [7,27,36]

Supports attention [7,36]

Supports cognition [2,3,15,36,37]

Supports acetylcholine synthesis and release [2,3,21]

Supports vesicular acetylcholine transporter levels [21,22]

Supports high affinity choline uptake transporter levels [22]

Protects from age-related changes in cholinergic neurotransmission [23]

Supports dopamine synthesis and release [1,24]

Supports dopamine plasma membrane transporter (DAT) levels [24]

Supports serotonin synthesis [24]

Supports GABA release [25]

Supports phospholipid synthesis [9,26]

Supports phosphoinositide synthesis [26,27]

Supports protein kinase C (PKC) activation [28–30]

Supports growth hormone secretion from the pituitary gland [10,20,31]

Counters some age-related brain microstructural changes [32–35]

Supports neuroprotective functions [2,3]

Exercise performance

Supports isometric force production [38]

Supports maximum power and velocity in jump movements [19]

Complementary ingredients

CDP-choline, Uridine Monophosphate, Huperzine A, Bacopa monnieri, Celastrus paniculatus, Coleus forskohlii, Vitamin B5 in supporting cholinergic neurotransmission


REFERENCES 

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Uridine Monophosphate

Scientific Name:
Uridine Monophosphate, (UMP)

URIDINE COMMON NAME

Uridine | Uridine Monophosphate | Uridine-5'-Monophosphoric Acid | UMP | 5′-Uridylic Acid

TOP BENEFITS OF URIDINE

Supports cognitive function*

Supports sleep*

WHAT IS URIDINE?

Uridine is one of the 5 standard nucleosides; the others are adenosine, cytidine, guanosine, and thymidine. These compounds are the building blocks of the main information carrier molecules in the body (DNA and RNA), and play a central role in cellular metabolism. ATP—the “A” standing for adenosine—is known for its role in carrying packets of chemical energy needed for cellular functions. Uridine plays a similar role in two non-ATP high-energy molecules used in a subset of metabolic reactions. Uridine is needed for UTP (made from uridine instead of adenosine) as an activator of substrates in some specific metabolic reactions. Uridine can also be converted into cytidine and support CTP. In this role, it is used for the synthesis of the glycerophospholipids (including phosphatidylcholine in the Kennedy pathway) needed for healthy cell membranes throughout the body and in the brain. And uridine may support different neuroregulatory processes and neurotransmitters. Uridine also crosses the blood brain barrier [1–6]. These structural and functional roles have led to it being used as a nootropic. Uridine is considered to be one of the natural sleep-promoting substances made by the brain, acting via uridine receptors in the areas of the brain which regulate natural sleep [7,8]

NEUROHACKER’S URIDINE MONOPHOSPHATE SOURCING

Uridine is supplied in a phosphorylated form as Uridine-5'-Monophosphoric Acid because this form is more stable, helps it get past the digestive system and liver intact, and allows it to cross the blood-brain barrier.

Uridine is Non-GMO and Vegan.

URIDINE MONOPHOSPHATE DOSING PRINCIPLES AND RATIONALE

One of our dosing principles is to determine whether there is a dosing range, in which many of the benefits occur and above which there appears to be diminishing returns (i.e., a threshold), and to provide a dose within this threshold range (see Neurohacker Dosing Principles). We consider uridine to be one of these threshold compounds. Uridine is most commonly used for nootropic support. In this functional role, it is common to take a dose of between 150-250 mg in the morning. For nootropic purposes, we dose uridine in this range. For sleep support, because information is based strictly on a known functional role and preclinical research, we have opted to provide a lower amount of uridine, combined with other supportive nutrients. 

URIDINE MONOPHOSPHATE KEY MECHANISMS

Brain function

Supports memory [9]

Supports brain membrane glycerophospholipids [10–12]

Supports the Kennedy (or CDP-choline) pathway, which has a central role in choline homeostasis [2,13,14]

Supports phosphatidylcholine synthesis [2,13,14]

Supports acetylcholine synthesis [2,10,13,14]

Supports cytidine levels and brain CDP-choline [1,15]

Supports activity of GABA receptors [16,17] 

Supports GABAergic neurotransmission [18,19]

Supports dopamine release [20]

Acts as a neurotransmitter via purinergic receptors [21,22]

Supports neurite outgrowth [20,23]

Sleep

Considered an endogenous sleep-promoting substance  [7,8,24]

Supports slow wave sleep (SWS) and REM sleep [24–28] 

Other effects

Supports cardioprotective functions [29]

Complementary ingredients

DHA in supporting memory and in upregulating dendritic spine density, synaptic protein levels, and phospholipids in the brain [11,30–33]


REFERENCES 

[1] M. Cansev, C.J. Watkins, E.M. van der Beek, R.J. Wurtman, Brain Res. 1058 (2005) 101–108.

[2] F. Gibellini, T.K. Smith, IUBMB Life 62 (2010) 414–428.

[3] G.B. Weiss, Life Sci. 56 (1995) 637–660.

[4] U.I. Richardson, C.J. Watkins, C. Pierre, I.H. Ulus, R.J. Wurtman, Brain Res. 971 (2003) 161–167.

[5] I.H. Ulus, R.J. Wurtman, C. Mauron, J.K. Blusztajn, Brain Res. 484 (1989) 217–227.

[6] E.M. Cornford, W.H. Oldendorf, Biochim. Biophys. Acta 394 (1975) 211–219.

[7] Y. Komoda, M. Ishikawa, H. Nagasaki, M. Iriki, K. Honda, S. Inoue, A. Higashi, K. Uchizono, BIOMEDICAL RESEARCH-TOKYO 4 (1983) 223–227.

[8] T. Kimura, I.K. Ho, I. Yamamoto, Sleep 24 (2001) 251–260.

[9] L.A. Teather, R.J. Wurtman, J. Nutr. 136 (2006) 2834–2837.

[10] L. Wang, M.A. Albrecht, R.J. Wurtman, Brain Res. 1133 (2007) 42–48.

[11] R.J. Wurtman, I.H. Ulus, M. Cansev, C.J. Watkins, L. Wang, G. Marzloff, Brain Res. 1088 (2006) 83–92.

[12] N. Agarwal, Y.-H. Sung, J.E. Jensen, G. daCunha, D. Harper, D. Olson, P.F. Renshaw, Bipolar Disord. 12 (2010) 825–833.

[13] Z. Li, D.E. Vance, J. Lipid Res. 49 (2008) 1187–1194.

[14] P. Fagone, S. Jackowski, Biochim. Biophys. Acta 1831 (2013) 523–532.

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[19] P. Liu, X. Che, L. Yu, X. Yang, N. An, W. Song, C. Wu, J. Yang, Pharmacol. Biochem. Behav. 163 (2017) 74–82.

[20] L. Wang, A.M. Pooler, M.A. Albrecht, R.J. Wurtman, J. Mol. Neurosci. 27 (2005) 137–145.

[21] A. Brunschweiger, C.E. Müller, Curr. Med. Chem. 13 (2006) 289–312.

[22] A. Dobolyi, G. Juhász, Z. Kovács, J. Kardos, Curr. Top. Med. Chem. 11 (2011) 1058–1067.

[23] A.M. Pooler, D.H. Guez, R. Benedictus, R.J. Wurtman, Neuroscience 134 (2005) 207–214.

[24] K. Honda, Y. Komoda, S. Nishida, H. Nagasaki, A. Higashi, K. Uchizono, S. Inoué, Neurosci. Res. 1 (1984) 243–252.

[25] M. Kimura-Takeuchi, S. Inoué, Brain Res. Bull. 31 (1993) 33–37.

[26] S. Inoué, M. Kimura-Takeuchi, K. Honda, Endocrinol. Exp. 24 (1990) 69–76.

[27] S. Inoue, K. Honda, Y. Komoda, K. Uchizono, R. Ueno, O. Hayaishi, Proceedings of the National Academy of Sciences 81 (1984) 6240–6244.

[28] M. Kimura-Takeuchi, S. Inoué, Neurosci. Lett. 157 (1993) 17–20.

[29] I.B. Krylova, V.V. Bulion, E.N. Selina, G.D. Mironova, N.S. Sapronov, Bull. Exp. Biol. Med. 153 (2012) 644–646.

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[31] S. Holguin, J. Martinez, C. Chow, R. Wurtman, FASEB J. 22 (2008) 3938–3946.

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Cognizin Citicoline

Scientific Name:
Cytidine diphosphocholine

COMMON NAME

Citicoline | CDP-choline | Cytidine 5'-diphosphocholine 

TOP BENEFITS OF CITICOLINE

  • Supports mental energy *
  • Supports focus and attention *
  • Supports brain health and cognitive performance *

WHAT IS CITICOLINE?

Citicoline is a choline and cytidine-containing intermediate in the generation of phosphatidylcholine from choline. It can be used to augment the body and brain choline pool. Citicoline and Alpha-glycerophosphocholine (alpha-GPC) are considered the nootropic forms of choline, with both being able to increase brain choline levels, act as building blocks for acetylcholine, and support choline-dependent functions. Following ingestion, citicoline yields choline and cytidine [1,2], the latter being converted into uridine in humans [3]. These compounds can be used to produce the phosphatidylcholine needed for the structure and function of healthy cell membranes  [4,5]. Phosphatidylcholine can also be used for acetylcholine synthesis [6,7]. Acetylcholine is central to brain neurotransmission; it plays a supportive role in attention, concentration, mental focus, and memory. 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. Cognizin® is a branded citicoline (CDP-choline) that provides nutritional support for brain energy, attention, focus, and recall.

NEUROHACKER’S CITICOLINE SOURCING

Cognizin® is a patented and clinically studied form of citicoline, a substance vital to brain health and energy.

Cognizin® Citicoline has been used in a number of human studies. It provides nutritional support for brain energy, attention, focus, and recall.

Cognizin® Citicoline is non-GMO, vegan, Kosher, and GRAS.

Cognizin® is a registered trademark of Kyowa Hakko Bio Co.

CITICOLINE DOSING PRINCIPLES AND RATIONALE

Cognizin® Citicoline is typically dosed in amounts between 250 and 500 mg/day when used alone as a nootropic in healthy adults. Neurohacker believes the evidence suggests a threshold response (see Neurohacker Dosing Principles) for citicoline when given to healthy people, which means the majority of functional benefits occur at the lower end of the range, with a doubling of the dose from 250 to 500 mg producing only modest additional functional gains. The amount included in a formulation may be below the amount used in studies when it has been given alone, because Neurohacker Collective’s experience with citicoline is that, when used with other ingredients that influence choline levels and metabolism, a more modest dose can be sufficient.  

CITICOLINE KEY MECHANISMS

Choline donor

  • Citicoline is part of the Kennedy (or CDP-choline) pathway, which has a central role in choline homeostasis [8–10]
  • Supports plasma levels of choline [11]
  • Supports plasma levels of uridine [11]
  • Precursor for phosphatidylcholine synthesis [4,5,7]
  • Precursor for acetylcholine synthesis [6,7]

Brain and cognitive function

  • Supports memory and learning [12–18]
  • Supports working memory [18]
  • Supports attention [19,20]
  • Supports processing speed [18]
  • Supports executive function [18]
  • Supports cognitive health [12,16,17,21]
  • Supports brain energetics and ATP [22]
  • Supports acetylcholine synthesis and release [6,7,21]
  • Supports cholinergic neurotransmission [23,24]
  • Supports brain phospholipid synthesis [7,22,25–27]
  • Supports brain mitochondrial phospholipid and protein production [28,29]
  • Supports dopamine release [30,31]
  • Supports dopaminergic neurotransmission [24,32]
  • Supports brain (frontal lobe) bioenergetics [22]
  • Supports brain bioelectrical activity [12]
  • Supports cerebral blood flow [12]
  • Supports brain plasticity [33]
  • Supports neuroprotective functions [21,26,27,33–40]
  • Supports neuronal cell membrane stabilization [26,36]
  • Supports brain glutathione levels [27]
  • Supports brain SIRT1 levels [38]

REFERENCES
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[8]F. Gibellini, T.K. Smith, IUBMB Life 62 (2010) 414–428.
[9]Z. Li, D.E. Vance, J. Lipid Res. 49 (2008) 1187–1194.
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Phenylethylamine HCL

Scientific Name:
Phenylethylamine, (PEA)

Overview:
PEA is an endogenous neurotransmitter and neuroregulator that plays a key role in mood and cognition. It is associated with states of heightened arousal, euphoria, and excitation, as well as increased attention and concentration.

Scientific Name:
Phenylethylamine, (PEA)

Mechanisms:

  • Stimulates dopamine, norepinephrine, and acetylcholine levels[1]
  • Modulates receptor sensitivity and reuptake processes[1]
  • Synthesized in the body from the amino acid phenylalanine[2]
  • Psychoactive ingredient in chocolate and blue green algae[3,4]
  • Synergistic with MAO-B inhibitors like Hordenine[5]
  • Phenylethylamines are a category of empathogens and entheogens derived from PEA and that act largely on its receptor sites[1]
REFERENCES

[1] Xie Z1 & Miller GM (2008). Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther, 325(2):617-28. doi: 10.1124/jpet.107.134247
[2] Berry MD (2004). Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. J Neurochem, 90(2):257-71. doi: 10.1111/j.1471-4159.2004.02501.x
[3] Granvogl M, et al (2006). Formation of amines and aldehydes from parent amino acids during thermal processing of cocoa and model systems: new insights into pathways of the strecker reaction. J Agric Food Chem, 54(5):1730-9. doi: 10.1021/jf0525939
[4] Güven KC et al (2010). Alkaloids in marine algae. Mar Drugs, 8(2):269-84. doi: 10.3390/md8020269
[5] Cashin CH (1972). Effect of sympathomimetic drugs in eliciting hypertensive responses to reserpine in the rat, after pretreatment with monoamineoxidase inhibitors. Br J Pharmacol. 1972 Feb;44(2):203-9. doi: 
10.1111/j.1476-5381.1972.tb07256.x

Saffron Extract (Crocus sativus)

SAFFRON COMMON NAME

Saffron | Saffron Crocus

TOP BENEFITS OF SAFFRON

  • Supports mood*
  • Supports cognitive function*
  • Supports vision* 

WHAT IS SAFFRON?

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, 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.

NEUROHACKER’S SAFFRON SOURCING

There's a long history of saffron adulteration. Because of this, Neurohacker feels it is critical to use a standardized saffron extract purchased from an ingredient supplier that can authenticate quality and strength.

The saffron extract we use has been clinically studied, is DNA authenticated, and has a patented profile for marker compounds including crocin, picrocrocin and safranal.

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

SAFFRON DOSING PRINCIPLES AND RATIONALE

Most saffron studies have used standardized extracts, with doses typically in the range of 20-30 mg per day. While a few studies have used 60 mg, in general, we consider 30 mg to be at the top end of what’s needed when using saffron extracts for specific clinical reasons. Since studies comparing multiple doses or different standardizations have not been published, there’s no information of whether saffron has a threshold effect (i.e., an amount or range less than the full dose where the majority of the response would occur; see Neurohacker Dosing Principles). 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 Neurohacker is using saffron for, and the other ingredients it’s combined with, it might be dosed anywhere ranging from a more micro-dose level up (3 mg) up to a studied dose of 30 mg per day. 

SAFFRON KEY MECHANISMS

Mood

  • Supports a positive mental-emotional bias [1–9]
  • Supports a calm mood [3,4,7–9]

Brain function

  • Supports focus and attention [10]
  • Supports healthy brain aging [11–13]
  • Supports sleep [14–16]
  • Supports dopamine signaling [17,18]
  • Supports GABA-glutamate signaling [17]
  • Supports acetylcholinesterase activity [18]
  • Supports brain-derived neurotrophic factor (BDNF) levels [19,20]
  • Supports neuroprotective functions [18,21–25]
  • Supports long-term potentiation [15]

Vision

  • Supports retinal function [26–28]
  • Protects macular health [27–29]
  • Supports visual acuity [27,29]
  • Protects retinal cells against light-induced damage [30–33]
  • Protects retinal cells against damage and degeneration [22,27,29,33–36]
  • Supports healthy intraocular pressure [37]

Exercise performance

  • Enhances reaction times [38]
  • Supports muscle strength [38]
  • Supports muscle recovery functions [39]

Antioxidant defenses

  • Supports antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]) [18,21,36]
  • Replenishes glutathione (GSH) levels [18,36]
  • Supports free-radical scavenging [18,21,35,36]
  • Promotes healthy prooxidant-antioxidant balance [40]

Mitochondrial function

  • Supports the activity of mitochondrial enzymes [18]
  • Supports mitochondrial membrane potential [35]

Metabolic function

  • Supports cytokine balance [41]
  • Supports appetite regulation [42]
  • Supports healthy lipid levels and blood pressure regulation [43,44] 

References

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Gotu Kola ( Centella asiatica ) Whole Herb Extract

GOTU KOLA COMMON NAME

Gotukola | Indian Pennywort | Asiatic Pennywort

TOP BENEFITS OF GOTU KOLA

Supports a calm mood and feelings of contentment*
Supports mental alertness and attention*
Supports a healthy stress response*
Supports circulation*

WHAT IS GOTU KOLA?

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].

NEUROHACKER’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 DOSING PRINCIPLES AND RATIONALE

Because gotu kola is an Ayurvedic Rasayana herb, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker 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 dose 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

Mood and stress response
Supports a calm mood[2–8]
Supports healthy behavioral and physiological responses to stress[8]

Brain function
Supports working memory[4]
Supports learning and memory[9–15]
Supports executive function[10,11]
Supports glutamate decarboxylase (GAD) activity[16]
Supports GABAergic neurotransmission[17]
Supports GABA receptor agonist actions [asiatic acid][18–20]
Supports glutamatergic AMPA receptors [9]
Down-regulates acetylcholinesterase (AChE)[14,18]
Supports hippocampal synaptic density[11]
Supports the expression of synaptic markers in the hippocampus and frontal cortex[21]
Supports brain mitochondrial function[10,11,14,21,22]
Supports brain-derived neurotrophic factor (BDNF)[12,13,23,24]
Supports NMDA receptors[24]
Supports hippocampal long-term potentiation[24]
Supports Nrf2 signaling in the brain[10,11,21,22]
Supports antioxidant defenses[7,10,11,14,21,22,25]
Supports neuroprotective functions[26]

Immune system
Supports innate immunity[27]
Supports adaptive immunity[28,29]


REFERENCES

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Polygala tenuifolia Root Extract

POLYGALA TENUIFOLIA COMMON NAME

Polygalae Radix | Yuan zhi | Onji

TOP BENEFITS OF POLYGALA TENUIFOLIA

Supports cognitive function*
Supports a healthy stress response*
Supports sleep*
Supports mood*

WHAT IS POLYGALA TENUIFOLIA?

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.

NEUROHACKER’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 DOSING PRINCIPLES AND RATIONALE

Because preclinical research suggests the potential for adaptogenic properties of Polygala tenuifolia, we consider dosing to follow hormetic principles similar to herbal adaptogens (see Neurohacker 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 dose 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 dose 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 dose P. tenuifolia towards the lower end of the range. 

POLYGALA TENUIFOLIA KEY MECHANISMS

Brain function

Supports learning and memory [1–4]

Supports sleep [5–7]

Supports glutamate decarboxylase (GAD) activity [8]

Supports GABA-Glutamate signaling [6,8–10]

Supports adenosine signaling [11]

Supports adrenergic signaling [3,5,6]

Supports dopamine signaling [3,12]

Downregulates acetylcholinesterase (AChE) activity [3,4,13]

Downregulates monoamine oxidase (MAO) [4]

Supports brain-derived neurotrophic factor (BDNF) [14,15]

Supports synaptic transmission in the hippocampus [15]

Supports long-term potentiation (LTP)/synaptic plasticity [13,15]

Supports the proliferation and differentiation of neural stem cells [16,17]

Supports neuroprotective functions

Protects against neurotoxic agents [18–20]

Protects from cognitive impairments [15,18–23]

Supports antioxidant defenses [4,13,20,24]

Stress

Supports healthy behavioral and physiological responses to stress [7,10,14]

Gut microbiota

Supports the composition of the gut microbiota [25]

Immune System

Supports adaptive immunity [26]

Supports macrophage functions [27]

Healthy aging and longevity

Supports mitochondrial function [22]

REFERENCES 

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Caffeine

COMMON NAME

Caffeine 

TOP BENEFITS OF CAFFEINE

Supports cognitive performance*

Supports exercise performance*

Supports mood* 

WHAT IS CAFFEINE?

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. 

NEUROHACKER’S CAFFEINE SOURCING

We use anhydrous caffeine, a dehydrated form of caffeine (the word “anhydrous” means without water) that is highly concentrated.

Caffeine is classified by the US Food and Drug Administration as generally recognized as safe (GRAS).

Caffeine is non-GMO, gluten-free, and vegan.

CAFFEINE DOSING PRINCIPLES AND RATIONALE

We consider caffeine to follow hormetic dosing principles (see Neurohacker 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 a hormetic curve, with low-to-moderate doses of caffeine supporting better cognitive and sports performance, but doses above the higher end of the range hindering performance. We have selected to dose caffeine at the amount 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.

CAFFEINE KEY MECHANISMS

Brain function and cognition

Promotes wakefulness [2]

Supports cognitive performance [1,3–7]

Supports executive function [8–10]

Supports information processing rate [11–13]

Supports simple and sustained attention [1,8,13,14]

Supports vigilance [1,14]

Supports task switching [13]

Supports reaction time [1,6,7,13]

Supports reasoning [5]

Supports creative thinking [9]

Supports resistance to mental fatigue [12,14]

Adenosine receptor antagonist [11]

Supports acetylcholine signaling [3,15–17]

Supports dopamine signaling [3,18–23]

Supports serotonin signaling [3,17,24–27]

Supports glutamate signaling [3,18,19]

Supports GABA signaling [3,17]

Supports noradrenaline signaling [3,26]

Supports cortical activation in the brain [3,11]

Supports cerebral metabolism [3,11]

Supports neuroprotective functions [28,29] 

Mood

Supports positive affect [3,6,7,10,30] 

Physical performance

Supports resistance to physical fatigue [4,7,8,31]

Supports resistance to exhaustion [1]

Supports muscle endurance and strength exercise activities [1]

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

Other effects

Supports metabolic rate [32–34]

Non-selective phosphodiesterase inhibitor [35]

Complementary ingredients

Theobromine as a CNS stimulant, with faster onset and shorter duration than Theobromine [36]

L-Theanine in cognitive performance [12,37–40]

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 for cognitive performance [43,44]


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

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Ginkgo Biloba Leaf Extract (24% glycosides)

Scientific Name:
Ginkgo biloba

COMMON NAME

Ginkgo | Maidenhair tree

TOP BENEFITS OF GINKGO BILOBA

  • Supports brain health and cognitive performance *
  • Supports neuroprotection *
  • Supports mood *
  • Supports vascular function *

WHAT IS GINKGO BILOBA?

Ginkgo biloba is one of the most widely used and researched herbs for brain health. G. biloba has been used in Traditional Chinese Medicine for several hundred years. Standardized extracts of G. biloba have been used since the mid-1960’s. The Ginkgo biloba tree is native to China and has been called a living fossil because it is the only surviving species of the order Ginkgoales that existed on earth 190 million years ago. The trees are very long-lived, with some specimens claimed to be as much as 1,500 years old. It contains several bioactive substances, including flavonoid glycosides such as quercetin, kaempferol and isorhamnetin, and terpene lactones such as ginkgolides A, B and C, and bilobalide. Through the action of these compounds, Ginkgo is able to support several neurotransmitter systems, support neurogenesis, and promote healthy vascular function and cerebral blood flow. G. biloba is best known for supporting attention, concentration, memory and mood [1].

NEUROHACKER’S GINKGO BILOBA SOURCING

Ginkgo biloba extract is made from plants harvested in China and uses a 35:1 (or greater) herb to extract ratio.

Ginkgo biloba extract  is standardized to contain 24% flavone glycosides and 6% terpene lactones. 

Ginkgo biloba Leaf Extract is non-GMO and vegan.

GINKGO BILOBA DOSING PRINCIPLES AND RATIONALE

We consider Ginkgo biloba to be an herbal adaptogen, so expect it to follow hormetic 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 (see Neurohacker Dosing Principles). Therefore, it’s important to identify the lowest dose that can produce the desired responses when using Ginkgo biloba. In clinical trials, standardized Ginkgo biloba leaf extracts have most commonly been used at doses ranging from 120 mg to 240 mg/day. When used in combination with other ingredients, standardized Ginkgo biloba leaf extracts have been used at lower doses, most commonly between 50 and 120 mg/day. Since we’re using a standardized Ginkgo biloba leaf extract as part of a combination of ingredients with which it may have additive effects, we chose a dose in the range used in combination studies. 

GINKGO BILOBA KEY MECHANISMS

Brain and cognitive function

  • Supports memory [2–6]
  • Supports working memory [3,7,8]
  • Supports attention [9,10]
  • Supports information processing speed [7,11]
  • Supports executive function [7]
  • Supports cognitive health [12–14]
  • Supports healthy cerebral blood flow [15–17]
  • Supports acetylcholine levels [18]
  • Influences anticholinesterase activity [19]
  • Supports dopamine levels [20,21]
  • Supports noradrenaline levels [20]
  • Supports serotonergic neurotransmission [22–24]
  • Supports neurogenesis [25–27]
  • Supports synaptogenesis [25]
  • Supports brain-derived neurotrophic factor (BDNF) [24,25,28,29]
  • Supports cyclic-AMP response element binding protein (CREB) activity [26]
  • Supports neuronal membrane fluidity [30]
  • Supports neuroprotective functions [31–35]

Mood and stress response

  • Supports a calm mood and positive affect [24,36–39]
  • Supports healthy stress responses and stress hormone levels (adaptogenic) [40,41]
  • Modulates the hypothalamic-pituitary-adrenal (HPA) axis [42]

Vascular health

  • Supports healthy blood flow [43–46]
  • Supports endothelial function [47–51]
  • Supports vascular function [52–54]
  • Influences platelet-activating factor (PAF) activity [55–57]
  • Supports blood antioxidant capacity [29]

Healthy aging and longevity

  • Supports mitochondrial function [47,50,58–60]
  • Supports mitochondrial responses to age-related oxidative stress [61]

Complementary ingredients

  • Ginger for mood support [62–65]
  • Ginseng for cognitive performance [66–71]
  • Rhodiola for cognitive performance [72]
REFERENCES
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Bacopa monnieri Leaf Extract

Scientific Name:
Bacopa monnieri

COMMON NAME:

Bacopa | Brahmi | Water Hyssop

TOP BENEFITS OF BACOPA MONNIERI:

  • Supports brain function and cognitive performance *
  • Supports a calm mood *
  • Supports healthy stress responses *
  • Supports antioxidant defenses *
  • Supports neuroprotection *
  • Supports vascular function *

WHAT IS BACOPA MONNIERI?:

Bacopa monnieri has been used in Ayurvedic medicine for almost 3000 years. One of its main traditional uses has been as a neural tonic to support intelligence, cognitive performance, nervous system rejuvenation, and brain function. These traditional uses have made it a favorite nootropic herb. Scientific studies on B. monnieri have focused primarily on cognitive function and mood. B. monnieri has also shown adaptogenic properties, supporting the brain and nervous system during stress. B. monnieri contains saponins called bacosides. These compounds, most notably  bacosides A and B, are believed to underlie the plant’s nootropic reputation [1,2]. B. monnieri also has strong antioxidant properties that may contribute to neuroprotective functions in the brain.

NEUROHACKER’S BACOPA MONNIERI SOURCING

Bacopa monnieri Leaf Extract is made from aerial parts of the plants harvested in India and uses a 10:1 herb to extract ratio.
Bacopa monnieri Leaf Extract is standardized to contain 20% bacosides, calculated as the sum of bacopaside I, bacoside A3, bacopaside II, jujubogenin isomer of bacopasaponin C and bacopasaponin C.
Bacopa monnieri Leaf Extract is NON-GMO and vegan.

BACOPA MONNIERI DOSING PRINCIPLES AND RATIONALE

Clinical studies using standardized Bacopa monnieri extracts typically use between 250-640 mg of these concentrated extracts. These doses have been equivalent to 3000 to 9000 mg of the dried herb. We consider B. monnieri to be in the adaptogenic herb category, following hormetic dosing principles (see Neurohacker Dosing Principles) with a high likelihood of having a hormetic range (i.e., a dosing range below and above which results could be poorer). We have selected to dose this at an amount that is consistent with the studied amount in the human clinical studies for supporting cognitive function and mood.*

BACOPA MONNIERI KEY MECHANISMS 

Brain and cognitive function

  • Supports learning and memory [3–8]
  • Supports attention [9]
  • Supports working memory [10]
  • Supports executive function [6,11]
  • Supports alertness [11]
  • Supports cognitive health [12–14]
  • Supports acetylcholine levels [12]
  • Influences acetylcholinesterase activity [15–17]
  • Supports choline acetyltransferase activity [15]
  • Supports dopamine levels [18,19]
  • Supports tryptophan hydroxylase activity [18]
  • Supports serotonin levels [12,18,19]
  • Supports GABAergic neurotransmission [20–22]
  • Supports dendritic growth and branching [23,24]
  • Supports healthy brain cytokine signaling [25]
  • Supports neuroprotective functions [16,26–34]
  • Counters neuronal reactive oxygen species (ROS) levels and oxidative stress [16,31,33,34]
  • Supports neuronal antioxidant defenses [16,26–28,33–35]
  • Supports neuronal mitochondrial function [33,34,36]

Stress and mood

  • Supports a calm mood [6,11]
  • Supports healthy stress responses and stress hormone levels [19,37–39]
  • Regulates stress-induced changes in dopamine and serotonin levels [19]
  • Supports positive affect [7,40,41}

Vascular health

  • Supports vascular function [42]
  • Supports healthy cerebral blood flow [43]

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Mucuna pruriens Seed

Scientific Name:
Mucuna pruriens, L-3,4-dihydroxyphenylalanine

COMMON NAME

Velvet bean | Monkey tamarind | Cowage | Cowitch | Lacuna bean | Lyon bean

TOP BENEFITS OF MUCUNA PRURIENS

  • Supports brain function *
  • Supports neuroprotection *
  • Supports antioxidant defenses *

WHAT IS MUCUNA PRURIENS?

Mucuna pruriens, also known as velvet bean, is a legume that is used as food in some parts of Southeast Asia and has been used in Unani and Ayurvedic traditional medicine. M. pruriens seeds (i.e., the beans) contain flavonoids, saponins, lectins, and alkaloids. The beans are one of the best sources of the amino acid L-3,4-dihydroxyphenylalanine (L-DOPA). Fava beans and green beans are other food sources of L-DOPA. Because L-DOPA is the direct precursor of the neurotransmitter dopamine, M. pruriens has been used as a nootropic for brain support. Dopamine is one of the main neurotransmitters in the brain. It participates in several important brain functions, most notably reward, motivation, pleasure, focus, cognitive flexibility, emotional resilience, and motor control. Healthy functioning of dopamine signaling is fundamental for healthy cognitive function and emotional drive [1–3]. 

NEUROHACKER’S MUCUNA PRURIENS SOURCING

Mucuna Pruriens Seed Extract is standardized to contain 50% L-DOPA. 

Mucuna Pruriens Seed Extract is non-GMO, Kosher, Halal, gluten-free, and vegan. 

MUCUNA PRURIENS DOSING PRINCIPLES AND RATIONALE

The dose of Mucuna pruriens extract was selected based on the dose of L-DOPA we wanted to include in our formulation. This extract is standardized for 50% L-DOPA, meaning that each 100 milligrams of M. pruriens seed extract provides 50 milligrams of L-DOPA. This amount of dietary L-DOPA is less than what would be consumed by eating a small serving of Fava or green beans [4]. Neurohacker Collective believes M. pruriens may be complementary with other ingredients used with it for supporting dopamine signaling and brain health. 

MUCUNA PRURIENS KEY MECHANISMS

Brain function

  • Supports dopamine levels and dopaminergic neurotransmission [3,5]
  • Supports noradrenaline levels [3,5]
  • Supports serotonin levels [3,5]
  • Supports cognitive health [6]
  • Supports neuroprotective functions [6–9]
  • Supports neural antioxidant defenses [10]
  • Counters neural ROS levels and oxidative stress [7,11] 
  • Supports growth hormone levels [12] 
  • Supports neural immune signaling [9,13,14]

Stress and mood

  • Supports healthy behavioral and physiological stress responses [9,15]
  • Supports healthy stress hormone levels [12,16]
  • Supports healthy behavioral responses [9,17]

General health

  • Supports healthy blood pressure [18,19]
  • Supports healthy blood glucose levels [20–22]
  • Supports mitochondrial function [5,23,24]
  • Supports antioxidant defenses [6,10,11,15,23,24] 

Male reproductive health

  • Supports healthy testosterone levels [25,26]
  • Supports sperm count and motility [15,23–25,27]

REFERENCES

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Huperzia serrata Leaf extract (1% Huperzine A)

Scientific Name:
Huperzine A extracted  from Huperzia serrata

COMMON NAME

Toothed Clubmoss | Chinese Club Moss | Huperazon 

TOP BENEFITS OF HUPERZINE A

  • Supports cholinergic neurotransmission *
  • Supports brain function and cognitive performance *
  • Supports neuroprotection *

WHAT IS HUPERZINE A?

Huperzia serrata (synonym Lycopodium serratum) is a species of fir clubmoss that has been used in Traditional Chinese Medicine (as Qian Ceng Ta). Huperzia serrata has several bioactive compounds, including lycopodium alkaloids, triterpenes, flavones and phenolic acids. The most important and widely studied of these is the alkaloid huperzine A, which indirectly supports healthy acetylcholine levels in the brain. Acetylcholine is a neurotransmitter and neuromodulator that plays important roles in cognitive function, most notably, in the neural mechanisms of memory [1], but also in executive function, alertness, attention, and learning. Acetylcholine supports different types of memory, from working memory to long-term memory, and different phases of memory, from memory formation to consolidation and retrieval. By supporting acetylcholine signaling, huperzine A supports cognitive function. Huperzine A has also been shown to support brain antioxidant defenses and neuroprotective functions [2,3].

NEUROHACKER’S HUPERZINE A SOURCING

Huperzia serrata leaf extract is made from the aerial parts of the plant. It is standardized for 1% Huperzine A.

Huperzia serrata leaf extract is non-GMO, gluten-free and vegan.

HUPERZINE A DOSING PRINCIPLES AND RATIONALE

Persons using huperzine A as a nootropic typically take a dose ranging from 50 to 200 μg. Neurohacker Collective uses an amount consistent with the lowest end of this range (50 μg). On Qualia products, the labeled amount (e.g., Huperzia serrata Leaf Extract (1% Huperzine A) is 5 mg ) refers to the amount of the Huperzia serrata Leaf extract not to the amount of huperzine A. Because the extract is standardized for 1% huperzine A, and each miligram of H. serrata leaf extract provides 10 μg of huperzine A, a 5 mg dose of the extract supplies 50 μg of huperzine A. We opted for a dose at the low end of the range because we believe huperzine A is additive with other ingredients used in our formulation for supporting brain health. 

HUPERZINE A KEY MECHANISMS

Brain and cognitive function

  • Supports memory and learning [4–9]
  • Supports cognitive health [4–6,8–16]
  • Supports task switching [15]
  • Supports long-term potentiation (LTP) [17]
  • Supports acetylcholine levels [2,4,5,10,18–22]
  • Supports choline acetyltransferase activity [10–13]
  • Supports dopamine release [4,19,20,22]
  • Supports noradrenaline release [4,20,22]
  • Influences NMDA glutamate receptor activity [4,23–26]
  • Supports the levels of neurotrophic factors (BDNF, NGF) [27]
  • Supports hippocampal neurogenesis [28]
  • Supports neuroprotective functions [3,4,11–13,17,20,21,27,29–35]
  • Supports brain antioxidant defenses [3,12,30–34,36]
  • Supports neurovascular health [37]
  • Supports blood-brain barrier function [37]
  • Influences neural cytokine signaling [10,37–39]

REFERENCES
[1]M.E. Hasselmo, Curr. Opin. Neurobiol. 16 (2006) 710–715.
[2]X. Ma, C. Tan, D. Zhu, D.R. Gang, P. Xiao, J. Ethnopharmacol. 113 (2007) 15–34.
[3]R. Wang, X.C. Tang, Neurosignals 14 (2005) 71–82.
[4]R. Wang, H. Yan, X.-C. Tang, Acta Pharmacol. Sin. 27 (2006) 1–26.
[5]D.H. Cheng, H. Ren, X.C. Tang, Neuroreport 8 (1996) 97–101.
[6]J. Li, H.M. Wu, R.L. Zhou, G.J. Liu, B.R. Dong, Cochrane Database Syst. Rev. (2008) CD005592.
[7]Q.Q. Sun, S.S. Xu, J.L. Pan, H.M. Guo, W.Q. Cao, Zhongguo Yao Li Xue Bao 20 (1999) 601–603.
[8]J.W. Ye, Y.Z. Shang, Z.M. Wang, X.C. Tang, Acta Pharmacol. Sin. 21 (2000) 65–69.
[9]S.S. Xu, Z.X. Gao, Z. Weng, Z.M. Du, W.A. Xu, J.S. Yang, M.L. Zhang, Z.H. Tong, Y.S. Fang, X.S. Chai, Zhongguo Yao Li Xue Bao 16 (1995) 391–395.
[10]S.-Z. Zhu, W.-P. Huang, L.-Q. Huang, Y.-L. Han, Q.-P. Han, G.-F. Zhu, M.-Y. Wen, Y.-Y. Deng, H.-K. Zeng, Neurosci. Lett. 631 (2016) 70–78.
[11]R. Wang, H.Y. Zhang, X.C. Tang, Eur. J. Pharmacol. 421 (2001) 149–156.
[12]L.M. Wang, Y.F. Han, X.C. Tang, Eur. J. Pharmacol. 398 (2000) 65–72.
[13]J. Zhou, H.Y. Zhang, X.C. Tang, Neurosci. Lett. 313 (2001) 137–140.
[14]L.Y. Ou, X.C. Tang, J.X. Cai, Eur. J. Pharmacol. 433 (2001) 151–156.
[15]A. Gul, J. Bakht, F. Mehmood, J. Chin. Med. Assoc. 82 (2019) 40–43.
[16]Z.-Q. Xu, X.-M. Liang, Juan-Wu, Y.-F. Zhang, C.-X. Zhu, X.-J. Jiang, Cell Biochem. Biophys. 62 (2012) 55–58.
[17]L. Ye, J.-T. Qiao, Neurosci. Lett. 275 (1999) 187–190.
[18]X.C. Tang, P. De Sarno, K. Sugaya, E. Giacobini, J. Neurosci. Res. 24 (1989) 276–285.
[19]Y.-Q. Liang, X.-C. Tang, Acta Pharmacol. Sin. 27 (2006) 1127–1136.
[20]Y.Q. Liang, X.T. Huang, X.C. Tang, Cell. Mol. Neurobiol. 28 (2008) 87–101.
[21]L.S. Tonduli, G. Testylier, C. Masqueliez, G. Lallement, P. Monmaur, Neurotoxicology 22 (2001) 29–37.
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[23]J.M. Zhang, G.Y. Hu, Neuroscience 105 (2001) 663–669.
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[27]Z.-F. Wang, L.-L. Tang, H. Yan, Y.-J. Wang, X.-C. Tang, Pharmacol. Biochem. Behav. 83 (2006) 603–611.
[28]T. Ma, K. Gong, Y. Yan, L. Zhang, P. Tang, X. Zhang, Y. Gong, Brain Res. 1506 (2013) 35–43.
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Pterostilbene as pTeroPure

Scientific Name:
3′,5′-Dimethoxy-4-stilbenol

Overview:
Pterostilbene is a powerful cerebral antioxidant and neuroprotectant found naturally in blueberries. Research indicates that pterostilbene may reduce age-related cognitive decline, improving memory, concentration, and learning.

Scientific Name:
3′,5′-Dimethoxy-4-stilbenol

Mechanisms:


    • Powerful antioxidant and anti-inflammatory compound[1]
    • Higher bioavailability, half-life and potency than resveratrol – crosses the blood brain barrier efficiently to act as a cerebral antioxidant[1]
    • Inhibits the synthesis of pro-inflammatory molecules such as PGE2[1]
    • Decreases neuroinflammation by inhibiting IkBα
    • Decreases age-related cognitive decline – possibly through protecting dopamine levels[1]
    • Modifies AMPK levels and activates SIRT1 genes associated with caloric restriction and life extension[1]
    • Anxiolytic effects through regulation of ERK phosphorylation[2]
    • Lowers blood glucose and cholesterol levels[3]
REFERENCES

[1] Poulose SM, et al (2015). Effects of pterostilbene and resveratrol on brain and behavior. Neurochem Int, 89:227-33. doi: 10.1016/j.neuint.2015.07.017
[2] Al Rahim M, et al (2013). Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation. Planta Med, 79(9):723-30. doi: 10.1055/s-0032-1328553
[3] Estrela JM, et al (2013). Pterostilbene: Biomedical applications. Crit Rev Clin Lab Sci, 50(3):65-78. doi: 
10.3109/10408363.2013.805182

Theobromine

Scientific Name:
3,7-dimethylxanthine extracted from Theobroma Cacao

COMMON NAME

Theobromine

TOP BENEFITS OF THEOBROMINE

  • Supports brain function and cognitive performance *
  • Supports neuroprotection *

WHAT IS THEOBROMINE?

Theobromine is a bitter compound found in high amounts in cocoa beans (and hence chocolate) and in much lower amounts in tea, yerba mate, guarana and guayusa. Its name comes from the botanical name for the cocoa bean, Theobroma cacao. The amount of theobromine in cocoa powders can vary about 5-fold, from between 2 to 10%. Darker chocolate generally has more theobromine than milk chocolate. Theobromine belongs to a class of alkaloid molecules called methylxanthines, which also includes caffeine. Like caffeine, it supports alertness processes in the brain by influencing the adenosine neurotransmitter system. Theobromine has somewhat similar effects to caffeine in supporting the sensation of being alert or having energy, but with slower onset and longer duration of activity [1–4]. It can be thought of as being a weaker cousin to caffeine, influencing similar brain processes but not quite as strongly. 

NEUROHACKER’S THEOBROMINE SOURCING

Theobromine is non-GMO and vegan.

THEOBROMINE DOSING PRINCIPLES AND RATIONALE

A 2 ounce serving of milk chocolate contains approximately 120 mg of theobromine, while the same amount of dark chocolate contains about 400 mg. Similar to caffeine, theobromine is not a “more is better” ingredient when it comes to being a nootropic. As an example, in a study that compared theobromine doses of 250, 500, and 1000 mg, the lowest dose produced the best subjective experience [5]. This indicates that there’s a high likelihood theobromine may follow hormetic dosing principles (see Neurohacker Dosing Principles), i.e., have a dosing range below and above which results could be poorer. Furthermore, because Neurohacker Collective believes theobromine may have additive effects with other ingredients, especially caffeine, we have selected to dose theobromine at an amount that occurs with dietary intake of chocolate. 

THEOBROMINE KEY MECHANISMS

Brain and cognitive function

  • Supports memory and learning [6–8]
  • Supports cognitive health [7]
  • Influences adenosine receptor activity [2,3,9]
  • Supports dopamine levels [10]
  • Supports noradrenaline levels [10]
  • Supports brain-derived neurotrophic factor (BDNF) [6,8]
  • Supports antioxidant defenses [10]

Cellular function

  • Influences phosphodiesterase (PDE) activity and intracellular cAMP levels [6,9]
  • Influences mTOR signaling [11] 

Complementary ingredients

  • Caffeine in supporting energetic arousal, reaction time and information processing [12]

REFERENCES 

[1]B. Gottwalt, P. Tadi, in: StatPearls, StatPearls Publishing, Treasure Island (FL), 2020.

[2]H.J. Smit, Handb. Exp. Pharmacol. (2011) 201–234.

[3]R. Franco, A. Oñatibia-Astibia, E. Martínez-Pinilla, Nutrients 5 (2013) 4159–4173.

[4]E. Martínez-Pinilla, A. Oñatibia-Astibia, R. Franco, Front. Pharmacol. 6 (2015) 30.

[5]M.J. Baggott, E. Childs, A.B. Hart, E. de Bruin, A.A. Palmer, J.E. Wilkinson, H. de Wit, Psychopharmacology 228 (2013) 109–118.

[6]M. Yoneda, N. Sugimoto, M. Katakura, K. Matsuzaki, H. Tanigami, A. Yachie, T. Ohno-Shosaku, O. Shido, J. Nutr. Biochem. 39 (2017) 110–116.

[7]J. Mendiola-Precoma, K. Padilla, A. Rodríguez-Cruz, L.C. Berumen, R. Miledi, G. García-Alcocer, J. Alzheimers. Dis. 55 (2017) 1273–1283.

[8]R. Islam, K. Matsuzaki, E. Sumiyoshi, M.E. Hossain, M. Hashimoto, M. Katakura, N. Sugimoto, O. Shido, Nutrients 11 (2019).

[9]I. Cova, V. Leta, C. Mariani, L. Pantoni, S. Pomati, Psychopharmacology 236 (2019) 561–572.

[10]L. Fernández-Fernández, G. Esteban, M. Giralt, T. Valente, I. Bolea, M. Solé, P. Sun, S. Benítez, J.R. Morelló, J. Reguant, B. Ramírez, J. Hidalgo, M. Unzeta, Food Funct. 6 (2015) 1251–1260.

[11]N. Sugimoto, M. Katakura, K. Matsuzaki, E. Sumiyoshi, A. Yachie, O. Shido, Basic Clin. Pharmacol. Toxicol. 124 (2019) 575–581.

[12]H.J. Smit, E.A. Gaffan, P.J. Rogers, Psychopharmacology 176 (2004) 412–419.

Pure Energy (Pterostilbene bound to Caffeine)

Scientific Name:
1,3,7-trimethylxanthine

PureEnergy®

Caffeine-pTeroPure® Co-crystal

Overview:
PureEnergy is a patented compound binding caffeine with the potent antioxidant pterostilbene. Binding caffeine with pterostilbene significantly slows the absorption rate of caffeine lengthening its half life and delivering up to 30% more total effect while reducing typical caffeine crash symptoms.

Caffeine

Overview:
Caffeine is a methylxanthine found in coffee beans, cocoa beans and in tea. Research shows that caffeine is a brain stimulant that increases alertness, wakefulness, attention, working memory, and motor activity.

Scientific Name:
1,3,7-trimethylxanthine

Mechanisms:

  • Adenosine receptor antagonist[1]
  • Affects neurotransmitters modulated by Adenosine: Noradrenaline, Dopamine, Serotonin, Acetylcholine, Glutamate, and GABA[1]
  • Phosphodiesterase inhibitor[2]
  • Increases motor activity through inhibition of acetylcholinesterase
  • Increases cortical activation in the brain[1]
  • Increases information processing rate and concentration[1]
  • Increases cerebral metabolism[1]

More Info:


REFERENCES

[1] Burnstock G (2013). Introduction to purinergic signalling in the brain. Adv Exp Med Biol, 986:1-12. doi: 10.1007/978-94-007-4719-7_1
[2] Essayan DM (1999). Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol, 57(9):965-73. doi: 
10.1016/S0006-2952(98)00331-1