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.
Greater Galangal | Thai Ginger | Siamese Ginger
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 humans studies, EnXtra® has been synergistic with 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]
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.
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.*
Cognitive function
Brain function
Antioxidant defenses
Other effects
Synergies
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.
Scientific Name:
Uridine Monophosphate, (UMP)
Uridine | Uridine Monophosphate | Uridine-5'-Monophosphoric Acid | UMP | 5′-Uridylic Acid
Supports cognitive function*
Supports sleep*
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].
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.
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.
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]
Synergies
With DHA in supporting memory and in upregulating dendritic spine density, synaptic protein levels, and phospholipids in the brain [11,30–33]
REFERENCES
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[10] L. Wang, M.A. Albrecht, R.J. Wurtman, Brain Res. 1133 (2007) 42–48.
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Scientific Name:
Celastrus paniculatus Willd
Celastrus | Intellect Tree | Jyotishmati
Supports cognitive performance*
Supports mood*
Supports stress response*
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.*
Celastrus paniculatus is an alcohol extract of the seeds.
Grown in India.
Celastrus paniculatus is non-GMO, gluten-free, vegan,
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.*
Brain function and structure
Supports memory and facilitates learning [2,5,7]
Reverses 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]
Downregulates brain MAO-A levels [3]
Downregulates 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 mood [3,8,12]
Downregulates plasma corticosterone (stress hormone) levels [3]
Antioxidant defenses
Supports brain antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]) [7,11,13–17]
Replenishes glutathione (GSH) levels [7,11,15]
Downregulates lipid peroxidation [7,11,13–17]
Supports Free-radical-scavenging activity [14,16,18]
Other effects
Modulates cellular signaling [17,19,20]
Supports relief of minor physical discomfort [19,20]
Gastroprotective effect [17]
Supports healthy cholesterol levels [21]
REFERENCES
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[18] A. Russo, A.A. Izzo, V. Cardile, F. Borrelli, A. Vanella, Phytomedicine 8 (2001) 125–132.
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Scientific Name:
1,3,7-trimethylpurine-2,6-dione
Coffee Fruit | Coffee Cherry | Coffee Berry
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.
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.
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.
Brain function
Cognitive function
Neuroprotection
Mood
Physical performance
Other effects
Synergies
REFERENCES
[1] T.M. McLellan, J.A. Caldwell, H.R. Lieberman, Neurosci. Biobehav. Rev. 71 (2016) 294–312.
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Inositol-enhanced Bonded Arginine Silicate
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]
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.
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.*
Vascular function
Brain function
Cognitive function
Exercise performance (ergogenic effects)
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Scientific Name:
Alpha-glycerophosphocholine
Alpha-GPC | Glycerophosphocholine | Choline alphoscerate | L-alpha-glycerophosphocholine
Supports cognitive function*
Supports exercise performance*
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]
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 (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.
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]
Synergies
CDP-choline, Uridine Monophosphate, Huperzine A, Bacopa monnieri, Celastrus paniculatus, Coleus forskohlii, Vitamin B5 in supporting cholinergic neurotransmission
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Scientific Name:
Cytidine diphosphocholine
Overview:
CDP Choline is a compound made up of choline and cytidine with neuroprotective and nootropic activity. CDP Choline decreases age-related memory impairment and cognitive decline, and enhances attention, learning and memory.
Scientific Name:
Cytidine diphosphocholine
Mechanisms:
More Info:
[1] Weiss GB1 (1995). Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci. 1995;56(9):637-60. doi: 10.1016/0024-3205(94)00427-T
[2] Levin ED (2013). Complex relationships of nicotinic receptor actions and cognitive functions. Biochem Pharmacol, 86(8):1145-52. doi: 10.1016/j.bcp.2013.07.021
[3] Tayebati SK, et al (2013). Modulation of monoaminergic transporters by choline-containing phospholipids in rat brain. CNS Neurol Disord Drug Targets, 12(1):94-103. doi: 10.2174/1871527311312010015
[4] Fagone P & Jackowski S (2012). Phosphatidylcholine and the CDP-choline cycle. Biochim Biophys Acta, 1831(3):523-32. doi: 10.1016/j.bbalip.2012.09.009
[5] Dempsey RJ & Raghavendra Rao VL (2003). Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats. J Neurosurg, 98(4):867-73. doi: 10.3171/jns.2003.98.4.0867
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:
More Info:
[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 | Saffron Crocus
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.
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.
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.
Mood
Brain function
Vision
Exercise performance
Antioxidant defenses
Mitochondrial function
Metabolic function
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Gotukola | Indian Pennywort | Asiatic Pennywort
Supports a calm mood and feelings of contentment*
Supports mental alertness and attention*
Supports a healthy stress response*
Supports circulation*
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].
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.
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.
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]
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Polygalae Radix | Yuan zhi | Onji
Supports cognitive function*
Supports a healthy stress response*
Supports sleep*
Supports mood*
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.
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.
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.
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]
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Scientific Name:
Ginkgo biloba
Overview:
Ginkgo biloba is a plant with neuroprotective, nootropic and adaptogenic effects. Ginkgo biloba can delay aging, improving memory and attention.
Scientific Name:
Ginkgo biloba
Mechanisms:
[1] van Beek TA (2002). Chemical analysis of Ginkgo biloba leaves and extracts. J Chromatogr A, 16;967(1):21-55. doi: 10.1016/S0021-9673(02)00172-3
[2] Ponto LL, Schultz SK (2003). Ginkgo biloba extract: review of CNS effects. Ann Clin Psychiatry, 15(2):109-19. doi: 10.1023/A:1024688326023
[3] Ahlemeyer B, Krieglstein J (2003). Neuroprotective effects of Ginkgo biloba extract. Cell Mol Life Sci, 60(9):1779-92. doi: 10.1007/s00018-003-3080-1
[4] Yamamoto Y, et al (2007). Ginkgo biloba extract improves spatial memory in rats mainly but not exclusively via a histaminergic mechanism. Brain Res, 1129(1):161-5. doi: 10.1016/j.brainres.2006.08.102
[5] Tchantchou F, et al (2009). Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. J Alzheimers Dis. 2009;18(4):787-98. doi: 10.3233/JAD-2009-1189
[6] Liao HJ, et al (2011). Two new ginkgolides from the leaves of Ginkgo biloba. Planta Med, 77(16):1818-21. doi: 10.1055/s-0030-1271153
[7] Kanowski S, et al (1996). Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry, 29(2):47-56. doi: 10.1016/S0944-7113(97)80021-9
[8] Rapin JR, et al (1994). Demonstration of the “anti-stress” activity of an extract of Ginkgo biloba (EGb 761) using a discrimination learning task. Gen Pharmacol, 25(5):1009-16. doi: 10.1016/0306-3623(94)90111-2
[9] Eckert A, et al (2003). Effects of EGb 761 Ginkgo biloba extract on mitochondrial function and oxidative stress. Pharmacopsychiatry, 36 Suppl 1:S15-23. doi: 10.1055/s-2003-40449
Scientific Name:
Bacopa monnieri
Overview:
Studies indicate that Bacopa monnieri has neuroprotective, nootropic and adaptogenic effects. Research shows that it can improve memory formation and recall.
Scientific Name:
Bacopa monnieri
Mechanisms:
[1] Aguiar S, Borowski T (2013). Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res, 16(4):313-26. doi: 10.1089/rej.2013.1431
[2] Sivaramakrishna, C, et al (2005). Triterpenoid glycosides from Bacopa monnieri. Phytochemistry, 66: 2719–2728. doi: 10.1016/j.phytochem.2005.09.016
[3] Rauf K, et al (2012). Effect of acute and sub-chronic use of Bacopa monnieri on dopamine and serotonin turnover in mice whole brain. AJPP. 2012;6:2767–2774. doi: 10.5897/AJPP12.244
[4] Chowdhuri DK, et al (2002). Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res, 16(7):639-45. doi: 10.1002/ptr.1023
[5] Chatterjee M, et al (2010). Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice. Indian J Exp Biol, 48(3):306-13. PMID: 21046986
[6] Bhaskar M, Jagtap AG (2011). Exploring the possible mechanisms of action behind the antinociceptive activity of Bacopa monniera. Int J Ayurveda Res, 2(1):2-7. doi: 10.4103/0974-7788.83173
[7] Anbarasi K, et al (2006). Cigarette smoking induces heat shock protein 70 kDa expression and apoptosis in rat brain: Modulation by bacoside A. Neuroscience, 138(4):1127-35. doi: 10.1016/j.neuroscience.2005.11.029
[8] Velmurugan K, et al (2009). Synergistic induction of heme oxygenase-1 by the components of the antioxidant supplement Protandim. Free Radic Biol Med, 46(3):430-40. doi: 10.1016/j.freeradbiomed.2008.10.050
Scientific Name:
Mucuna pruriens, L-3,4-dihydroxyphenylalanine
Overview:
Mucuna pruriens is a bean with neuroprotective and adaptogenic effects. Mucuna pruriens is a mood enhancer and increases focus and motivation.
Scientific Name:
Mucuna pruriens, L-3,4-dihydroxyphenylalanine
Mechanisms:
[1] Pulikkalpura H, et al (2015). Levodopa in Mucuna pruriens and its degradation. Sci Rep, 5:11078. doi: 10.1038/srep11078
[2] Misu Y, et al (1996). Neurobiology of L-DOPAergic systems. Prog Neurobiol, 49(5):415-54. doi: 10.1016/0301-0082(96)00025-1
[3] Das Gupta V, Gupta A (1980). Effect of pyridoxal 5-phosphate on carbidopa and decarboxylation of levodopa. J Pharm Sci, 69(10):1145-8. doi: 10.1002/jps.2600691005
[4] Rana DG, Galani VJ (2014). Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu, 35(1):90-7. doi: 10.4103/0974-8520.141949
[5] Shukla KK, et al (2007). Mucuna pruriens Reduces Stress and Improves the Quality of Semen in Infertile Men. Evid Based Complement Alternat Med, 7(1):137-44. doi: 10.1093/ecam/nem171
[6] Lampariello LR, et al (2012). The Magic Velvet Bean of Mucuna pruriens. J Tradit Complement Med, 2(4):331-9. PMID: 24716148
[7] Chihara K, et al (1986). L-dopa stimulates release of hypothalamic growth hormone-releasing hormone in humans. J Clin Endocrinol Metab, 62(3):466-73. doi: 10.1210/jcem-62-3-466
Scientific Name:
Huperzine A extracted from Huperzia serrata
Overview:
Huperzine A is a potent natural synaptic enzyme modulator. Studies indicate its ability to support learning, memory, neuroplasticity, and executive function.
Scientific Name:
Huperzine A extracted from Huperzia serrata
More Info:
[1] Wang R, et al (2006). Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin, 27(1):1-26. doi: 10.1111/j.1745-7254.2006.00255.x
[2] Ma T, et al (2013). Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res, 1506:35-43. doi: 10.1016/j.brainres.2013.02.026
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:
[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
Scientific Name:
3,7-dimethylxanthine extracted from Theobroma Cacao
Overview:
Theobromine is a methylxanthine related to caffeine extracted from cocoa (Theobroma Cacao) beans. Studies show that theobromine increases alertness, attention, and executive function.
Scientific Name:
3,7-dimethylxanthine extracted from Theobroma Cacao
Mechanisms:
More Info:
[1] Franco R, et al (2013). Health benefits of methylxanthines in cacao and chocolate. Nutrients, 18;5(10):4159-73. doi: 10.3390/nu5104159
[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
[3] 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
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:
More Info:
[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