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    What Makes Cognamind
The Best Nootropic Available?

Expert
Development Team

HackStacks’ team of scientists, experts in biochemistry, medicine, nutritional supplements, and most importantly — human performance — chose each ingredient in the Cognamind stack for a singular purpose: to bring you the very best, most effective mental support system possible.

Research Based

We based Cognamind’s formula on solid research. Human clinical trials show that ingredients in Cognamind significantly improve brain performance, speed, recall, along with other critical mental functions in healthy adults.

Full Transparency

It’s important for you to know exactly what substances you’re putting in your body. That’s why we didn’t use a “proprietary blend” to hide the details of our formula. Instead, we’ve listed the precise weights for each of COGNAMIND’s active ingredients in milligrams or micrograms so you get the information you need to make the right decisions for your health and your performance .

What's in Cognamind?

Cognamind™ is a precise combination of nootropic
ingredients carefully selected and blended to deliver
maximum benefits of mental energy, sustained
focus and improved memory.

Neurofactor™ Whole Fruit Coffee Extract

Neurofactor is an all-natural product extracted from the whole fruit of the coffee plant, Coffea Arabica. Human clinical research has shown that whole fruit coffee concentrates significantly raise levels of brain-derived neurotrophic factor (BDNF). Higher levels of BDNF support a wide array of cognitive benefits including growth of new neurons, support for healthy neurons, and cognitive functions including memory, learning and thinking. John J. Ratey, author of “Spark, The Revolutionary New Science of Exercise and the Brain,” calls BDNF “Miracle-Gro” for your brain.

Neurofactor is a patented extract derived from the whole fruit of the coffee plant, (Coffee Arabica), also called the coffee cherry or coffee berry (1).

According to ancient folklore, a 9th-century Ethiopian goatherd named Kaldi discovered the coffee fruit who saw his goats eating red berries from a tree. After eating the berries, Kaldi’s goats started acting erratically, becoming energized and refusing to sleep. Curious, Kaldi brought some fruit back to his local monastery which he and the monks ate. During evening prayers, they were unusually alert and energized and couldn't sleep.

Typically, the outer flesh of the coffee fruit is discarded in favor of the caffeine and antioxidant-rich inner seed. The seed is fermented and roasted to become what we usually think of as coffee beans. Recently, research has shown the fleshy outer fruit is potent with antioxidants, polyphenols, and procyanidins, which may have significant neuroprotective benefits for the brain (2).

Neurofactor is extracted from the entire coffee fruit – the outer flesh, as well as the inner bean and thus contains all of coffee’s active substances. Research shows Neurofactor conferring a range of neuroprotective benefits and neuro-stimulatory effects primarily because of its impact on brain-derived neurotrophic factor, or BDNF. BDNF is a large protein found in various tissues in the body that plays a role in multiple pathways and mechanisms related to brain health and cellular signaling. BDNF binds to receptors in the brain involved in nerve growth, it plays a direct role in neurogenesis (creation of new neurons), and is involved in neurotransmitter signaling, including glutamatergic and GABAergic, among others. BDNF combined effects play a central role in learning, memory, mood, and well-being (4, 11, 12, 13, 14). Inadequate BDNF levels have been linked to several cognitive disorders including depression, obsessive-compulsive disorder, Alzheimer’s disease, dementia, and Parkinson’s disease (5, 6, 7, 8).

When compared with green coffee caffeine, green coffee bean powder, and grape seed extract, whole coffee fruit concentrate outperformed all three compounds in its ability to stimulate BDNF serum levels (9). In a clinical study, Neurofactor supplementation has shown to increase BDNF as much as 143% (3).

Given coffee fruit’s involvement in a wide variety of brain pathways and mechanisms, it should be expected to have synergistic effects when combined with other ingredients that affect similar pathways. While the research on whole coffee fruit is in the early stage, it may combine well with GABA sources like PharmaGaba, choline sources such as citicholine, and bacopa. Much like resveratrol, whole coffee fruit extract seems like a promising addition to any nootropic stack in supporting long-term cognition, neuroprotection, and healthy aging.

References

  • Coffee bean, the free encyclopedia
  • Reyes, I. T., Nemzer, B., Shu, ., Huynh, L., Argumedo, R., Keller, R., & Pietrzkowski, . (2013). Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects. (Vol. 110(3), ). Br J Nutr.. pubmed/23312069
  • Fujinami, A., Ohta, K., Obayashi, H., Fukui, M., Hasegawa, G., Nakamura, N., Kozai, H., Imai, S., & Ohta, M. (2008). Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance. (Vol. (10-11), ). Clin Biochem..
  • Yamada, K., & Nabeshima, T. (2003). Brain-derived neurotrophic factor/TrkB signaling in memory processes. (Vol. 91(4), ). J Pharmacol Sci.. pubmed/12719654
  • Brunoni , A., Lopes, M., & Fregni, F. (2008). A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. (Vol. 11(8), ). Int J Neuropsychopharmacol.. pubmed/18752720
  • Zuccato, C., & Cattaneo, E. (2009). Brain-derived neurotrophic factor in neurodegenerative diseases. (Vol. 5(6), ). Nat Rev Neurol.. pubmed/19498435
  • Arancio, O., & Chao, . (2007). Neurotrophins, synaptic plasticity and dementia. (Vol. 17(3), ). Curr Opin Neurobiol.. pubmed/17419049
  • Fumagalli, F., Racagni, G., & Riva, M. (2006). Shedding light into the role of BDNF in the pharmacotherapy of Parkinson's disease. (Vol. 6(2), ). Pharmacogenomics J.. pubmed/16402079
  • Reyes, I. T., Nemzer, B., Shu, ., Huynh, L., Argumedo, R., Keller, R., & Pietrzkowski, . (2013). Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects. (Vol. 110(3), ). Br J Nutr.. pubmed/23312069
  • Heimbach, J., Marone, P., Hunter, J., Nemzer, B., Stanley, S., & Kennepohl, E. (2010). Safety studies on products from whole coffee fruit. (Vol. 48(8-9), ). Food Chem Toxicol.. pubmed/20600539%20?iframe=true&width=100%&height=100%
  • Bekinschtein, P., Cammarota, M., Katche, C., Slipczuk, L., Rossato, J. I., Goldin, ., Izquierdo, I., & Medina, J. H. (2008). BDNF is essential to promote persistence of long-term memory storage (Vol. 105(7), ). Proc Natl Acad Sci U S A.. pmc/articles/PMC2268201/
  • Zigovaa, T., Penceaa, V., Wiegandb, S. J., & Luskina, M. B. (1998). Intraventricular Administration of BDNF Increases the Number of Newly Generated Neurons in the Adult Olfactory Bulb (Vol. Volume 11, Issue 4, ). Molecular and Cellular Neuroscience. science/article/pii/S1044743198906844
  • Makoto, M., Kiyofumi, Y., Jue, H., Akira, N., & Toshitaka, N. (2003). Involvement of BDNF Receptor TrkB in Spatial Memory Formation (Vol. 10(2), ). Learn Mem.. pmc/articles/PMC196664/
  • Brunoni, A. R., Lopes, M., & Fregni, F. (2008). A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression (Vol. 11 (8), ). Int J Neuropsychopharmacol. content/11/8/1169
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Theacrine

Theacrine is an alkaloid compound similar to caffeine but with novel differences. Like caffeine, theacrine promotes energy, alertness, and focus, and it also reduces occasional fatigue. But unlike caffeine, the effects taper off gradually and last longer, and – surprisingly – theacrine seems to have a relaxing and anti-stress effect. Also important is that tolerance to theacrine develops slowly if at all. Theacrine’s benefits are enhanced when it is combined with caffeine.

Theacrine is a naturally occurring alkaloid molecule similar in structure to caffeine (1). The compound is found in significant amounts only in Camellia Assamica, a small shrub in the same family as green tea whose leaves are used to make Kucha(2). The plant originated in East Asia and is cultivated around the world, especially in subtropical climates (3).

Kucha tea leaves have been used in Traditional Chinese Medicine for centuries to treat conditions like asthma and heart diseases including angina. Drinking tea made from steeped Kucha leaves provides a variety of mild health benefits, but the theacrine extracted from those leaves delivers a much more potent ingredient.

Theacrine has over twice the potency of caffeine and has a strong positive effect on mood (4, 5, 6). In fact, theacrine is synthesized directly from caffeine in certain plants (7). Compared to caffeine, theacrine is longer lasting and offers benefits beyond stimulation: elevated mood, relaxation and mental clarity (8). The effects of theacrine taper off slowly rather than abruptly as a “caffeine crash.”

Theacrine effects vary and seem to be dose dependent. At higher doses, it is used mainly as a stimulant, increasing alertness, energy and cognition, though taken at smaller doses it has mild sedative and relaxing properties (8). Separately, research shows that theacrine may have anti-inflammatory and analgesic (pain-relieving) properties as well. Preliminary data from studies suggest theacrine's pain reduction value may be comparable to indomethacin, a nonsteroidal anti-inflammatory drug used to treat various types of arthritis, bursitis, and tendonitis (9).

Molecularly, theacrine is identical to caffeine with the additions of a methyl group and a ketone group (10). Like caffeine, theacrine appears to act on adenosinergic and dopaminergic neurotransmission pathways (11).

Theacrine is effective when stacked with other nootropic ingredients like caffeine, bacopa monniera, huperzine A, vitamin B12 (12).

References

  • Feduccia, A., Wang, Y., Simms, J., Yi , H., Li, R., Bjeldanes, L., Ye, C., & Bartlett, S. (2012). Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors. (Vol. 102(2), ). Pharmacol Biochem Behav.. pubmed/22579816
  • Zheng, X., Y, C., Kato, M., Crozier, A., & Ashihara, H. (2002). Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha). (Vol. 60(2), ). Phytochemistry.. pubmed/12009315
  • (J.W. Mast.) Kitam. Camellia sinensis var. assamica.
  • Grassi, D., Desideri, G., Di Giosia, P., De Feo, M., Fellini, E., Cheli, P., Ferri, L., & Ferri, C. (2013). Tea, flavonoids, and cardiovascular health: endothelial protection. (Vol. 98(6 Suppl), ). Am J Clin Nutr.. pubmed/24172308
  • Weil-Malherbe, H.(1946). The solubilization of polycyclic aromatic hydrocarbons by purines. Weil-Malherbe H1. (Vol. 40(3), ). Biochem J.. pubmed/16748014
  • Neish, W.(1948). On the solubilisation of aromatic amines by purines (Vol. Volume 67, Issue 5, ). WILEY-VCH Verlag GmbH & Co. . doi/10.1002/recl.19480670505/abstract
  • Zheng, Z., Ye, C., Kato, M., Crozier, A., & Ashihara, H. (2002). Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha). (Vol. 60(2), ). Phytochemistry.. pubmed/12009315
  • Daniel, J., Kuhman,, , Keanan, J., Joyner, , & Bloomer, R. J. (2015). Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women (Vol. 7(11), ). Nutrients. . /pmc/articles/PMC4663612/
  • Kuhman, D., Joyner , K., & Bloomer, R. (2015). Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women. (Vol. 7(11), ). Nutrients.. pubmed/26610558
  • Kihlman, B.(1977). 1,3,7,9-tetramethyluric acid--a chromosome-damaging agent occurring as a natural metabolite in certain caffeine-producing plants. (Vol. (3-4), ). Mutat Res.. pubmed/331090
  • Feduccia, A., Wang, Y., Simms, J., Yi, H., Li, R., Bjeldanes, L., Ye, C., & Bartlett, S. (2012). Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors. (Vol. 102(2), ). Pharmacol Biochem Behav.. pubmed/22579816
  • Kuhman, D., Joyner, K., & Bloomer, R. (2015). Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women. (Vol. 7(11), ). Nutrients.. pubmed/26610558
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Cognizin® CDP-Choline

Cognizin is a patented form of cytidine diphosphate-choline or CDP, also called citicholine. Citicholine is naturally occurring in the cells of human and animal tissue. Studies show that citicholine supplements help improve focus and mental energy, along with memory. CDP-choline supplementation increases dopamine receptor densities, increases cerebral blood flow, supports improved glucose metabolism, and reduces oxidative stress.

Cognizin is a patented form of cytidine diphosphate-choline, also called CDP-choline or citicholine, an organic component made up of choline and cytidine and found in every cell in the human body, particularly the brain. It is an intermediate in the synthesis of choline, essential to overall health, and neural health, in particular.

Choline’s importance became evident during the mid-1800’s when scientists independently identified molecules which later turned out to be various forms of choline. (4, 5). In 1865 Oscar Liebreich, working on a human brain declared he’d found “the mother-substance of all” (6) and named it Choline, recognizing it as essential for cell signaling and human life (7).

Choline itself plays a key role in cell structure, cell messaging, fat transport and metabolism and DNA synthesis. It is considered to have both nootropic and neuroprotective properties and specifically impacts memory and attention as well as overall cognition. (2, 3, 8, 9, 10). Studies have also demonstrated that citicholine may be useful in promoting memory formation and recall in older adults, and is associated with improve recovery after stroke (11, 12).

Once ingested, citicholine breaks down into choline and cytidine, which breaks down into uridine (13). Choline is regarded as the “learning neurotransmitter,” and supplementation is used primarily to improve cognitive function (14). Uridine, the byproduct of cytidine, is another neurotransmitter associated with cognitive function, playing a role in the synthesis of cellular membranes and other neurological properties in the brain (15).

The clinically effective dose for citicholine ranges between 500 mg - 2,000 mg, ideally divided into two doses/day. Doses above 2,000 mg show no additional benefits for cognition. Citicholine may work well with other cholinergic ingredients such as alpha-GPC, caffeine, huperzine-A, and Bacopa, that stimulate choline receptors and promote circulating choline in the brain.

References

  • Bracken, B., Penetar, D., Rodolico, J., Ryan, E., & Lukas, S. (2011). Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults. (Vol. 98(4), ). Pharmacol Biochem Behav.. pubmed/21397626
  • Erin, M., Allison, L., Julia, ., Toshikazu, K., Masahiko, M., Koji, M., Yoichiro, S., & Deborah, Y. (2012). Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women (Vol. Vol.3 No.6, ). FNS. PaperInformation.aspx?paperID=19921
  • Alvarez, X., Laredo, M., Corzo, D., Fernández-Novoa, L., Mouzo, R., Perea, J., Daniele, D., & Cacabelos, R. (1997). Citicoline improves memory performance in elderly subjects. (Vol. 19(3), ). Methods Find Exp Clin Pharmacol. pubmed/9203170
  • Théodore, G.(2008). Recherches chimiques sur les oeufs de carpe, lues à l'Académie nationale de médecine (). Harvard University: Imprimé par E. Thunot. Recherches_chimiques_sur_les_oeufs_de_ca.html?id=nE89AAAAYAAJ
  • Adolph, S.(1862). Ueber einige neue Bestandtheile der Schweinegalle (). Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA. doi/10.1002/jlac.18621230310/abstract
  • Steven, Z. H. (2012). A brief history of choline (Vol. 61(3), ). Ann Nutr Metab. pmc/articles/PMC4422379/
  • Lin, C., & Wu, . (1986). Choline oxidation and choline dehydrogenase (Vol. Volume 5, Issue 3, ). Journal of Protein Chemistry. article/10.1007/BF01025488
  • Erin, M., Allison, L., Julia, H., Toshikazu, K., Masahiko, M., Koji, M., Yoichiro, S., & Deborah, Y. (2012). Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women (Vol. Vol.3 No.6, ). FNS. journal/PaperInformation.aspx?paperID=19921
  • Parisi, V., Coppola, G., Centofanti, M., Oddone, F., Angrisani, A., Ziccardi, L., Ricci, B., Quaranta, L., & Manni, G. (2008). Evidence of the neuroprotective role of citicoline in glaucoma patients. (). Prog Brain Res. pubmed/18929133
  • Alvarez, X., Laredo, M., Corzo, D., Fernández-Novoa, L., Mouzo, R., Perea, J., Daniele, D., Cacabelos, R., & (1997). Citicoline improves memory performance in elderly subjects. (Vol. 19(3), ). Methods Find Exp Clin Pharmacol. pubmed/9203170
  • Alvarez, X., Laredo, M., Corzo, D., Fernández-Novoa, L., Mouzo, R., Perea, J., Daniele, D., Cacabelos, R., & (1997). Citicoline improves memory performance in elderly subjects. (Vol. 19(3), ). Methods Find Exp Clin Pharmacol. pubmed/9203170
  • Saver, .(2008). Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair. (Vol. 5(4), ). Rev Neurol Dis. pubmed/19122569
  • Bracken, B., Penetar, D., Rodolico, J., Ryan, E., & Lukas, S. (2011). Eight of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults. (Vol. 98(4), ). Pharmacol Biochem Behav.. pubmed/21397626
  • Choline, 38 unique references to scientific papers
  • Wurtman, .(2008). Synapse formation and cognitive brain development: effect of docosahexaenoic acid and other dietary constituents. (Vol. 57 Suppl 2, ). Metabolism. pubmed/18803968
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Natural Caffeine (from Green Tea)

Caffeine is the world’s best known central nervous system stimulant and is the world’s most consumed psychoactive substance. The caffeine contained in COGNAMIND is completely natural and extracted from Green Tea.

Caffeine is probably the world’s best-known stimulant.

It occurs naturally in coffee beans, several types of tea and at least 60 other different plants. Caffeine is also synthesized in the laboratory, though all forms have the same chemical composition, they may have subtly different effects.

According to ancient Chinese folklore, caffeine was first discovered when the Chinese emperor Shennong accidentally discovered tea by boiling certain leaves in water, resulting in a “fragrant and restorative drink” (1). Coffee is believed to have first been drunk in the middle east during the fifteenth century, and it soon spread throughout the world as a popular energy-boosting beverage. Caffeine as a separate chemical compound was isolated in 19th century France (2).

Caffeine is currently the most widely consumed psychoactive compound in the world. A powerful stimulant, it is used to promote wakefulness as well as to enhance alertness and physical performance (3). Research suggests that steady caffeine use may provide long-term health benefits including reducing the risk of Alzheimer’s Disease, cirrhosis and liver cancer (4, 5).

Caffeine is absorbed through the intestines and acts upon adenosinergic pathways in the central nervous system (6). In normal conditions, adenosine causes relaxation and sedation, but caffeine occupies the adenosine receptors and prevents this action (7). Optimal doses of caffeine range widely between 100mg and 500mg, the exact amount determine by an individual’s weight, sensitivity, and habituation (8). Steady caffeine often results in tolerance, thus requiring higher doses to achieve the desired effect. Depending on the delivery method, caffeine reaches its peak of effect between 15 minutes and 2 hours after ingestion (9).

Caffeine is effective alone, though it is often combined with other ingredients depending on the application. As mentioned above it is often used as a stimulant for mental alertness, energy, and focus, as a performance-enhancer for vigorous exercise, and is also used to support fat-burning (10, 11, 12). Caffeine can be combined with theanine to increase a broad range of cognitive functions. (13, 14).

References

  • JOHN, E. C. (1992). Tea in China: The History of China's National Drink (Contributions to the Study of World History) (Vol. 33, ). Praeger. ref=sr_1_1?ie=UTF8&qid=1480606775&sr=8-1&keywords=tea+in+China%3A+The+History+of+China%27s+National+Drink
  • Jonn's Berzelius (1824), Annual report on the advances of chemistry and mineralogy
  • Caffeine All Essential Benefits/Effects/Facts & Information, 446 unique references to scientific papers
  • Prediger, R.(2010). Effects of caffeine in Parkinson's disease: from neuroprotection to the management of motor and non-motor symptoms. (Vol. 20 Suppl 1, ). J Alzheimers Dis.. pubmed/20182024
  • Guerciolini, R., Szumlanski, C., & Weinshilboum Weinshilboum, R. (1991). Human liver xanthine oxidase: nature and extent of individual variation. (Vol. 50(6), ). Clin Pharmacol Ther.. pubmed/1752110
  • Bonati, M., Latini, R., Galletti, F., Young, J., Tognoni, G., & Garattini, S. (1982). Caffeine disposition after oral doses. (Vol. 32(1), ). Clin Pharmacol Ther.. pubmed/7083737
  • Bertil, F. B., Karl, B., Janet, H., Astrid, N., & Edwin, . E. (1999). Actions of Caffeine in the Brain with Special Reference to Factors That Contribute to Its Widespread Use (Vol. 51 (1), ). Pharmacological Reviews. content/51/1/83.short
  • Gummadi, S., Bhavya, B., & Ashok, . (2012). Physiology, biochemistry and possible applications of microbial caffeine degradation. (Vol. 93(2), ). Appl Microbiol Biotechnol..
  • Conway, K., Orr, R., & Stannard, S. (2003). Effect of a divided caffeine dose on endurance cycling performance, postexercise urinary caffeine concentration, and plasma paraxanthine. (Vol. 94(4), ). J Appl Physiol (1985). pubmed/12482764
  • Astorino TA, T., Terzi, M., Roberson, D., & Burnett, T. (2010). Effect of two doses of caffeine on muscular function during isokinetic exercise. (Vol. 42(12), ). Med Sci Sports Exerc. pubmed/20421833
  • Childs, E., & de Wit, H. (2006). Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users. (Vol. 185(4), ). Psychopharmacology (Berl). pubmed/16541243
  • Astrup, A., Toubro, S., Cannon, S., Hein, P., Breum, L., & Madsen, J. (1990). Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. (Vol. 51(5), ). Am J Clin Nutr. pubmed/2333832
  • Olson, C., Thornton, J., Adam, G., & Lieberman, H. (2010). Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and mood. (Vol. 30(5), ). J Clin Psychopharmacol. pubmed/20814335
  • Owen, G., Parnell, H., De Bruin, E., & Rycroft, J. (2008). The combined effects of L-theanine and caffeine on cognitive performance and mood. (Vol. 11(4), ). Nutr Neurosci.. pubmed/18681988
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Huperzine A

Huperzine A (often just called Huperzine), is an alkaloid substance extracted from the Huperziceae herb that has been used for centuries to help with alertness and memory. Huperzine A works as a cognitive booster and memory enhancer. It helps prevent the breakdown of acetylcholine known as the learning transmitter, thus improving mental performance and supporting healthy brain function. Huperzine is known to work synergistically with Caffeine and Choline.

Huperzine-A is extracted from the Huperzia Serrata plant, a type of moss native to India and Southeast Asia. Huperzia has a long history in Traditional Chinese Medicine to treat age-related cognitive disorders and memory impairment (1).

Huperzine-A is an acetylcholinesterase inhibitor which stops that enzyme from breaking down “the learning neurotransmitter,” acetylcholine (2). Preventing acetylcholine’s breakdown results in increased levels of choline (acetylcholine) in the brain, which in turn enhances cognitive function and synthesis of neural membranes, offering neuroprotective effects.

The main benefits of huperzine-A supplementation are improved memory and overall mental function, along with neuroprotection. Additionally, research suggests that huperzine-A may ameliorate consequences of Alzheimer’s disease and other related neurological disorders, though more evidence is needed to confirm these findings (3, 4). Huperzine-A may also offer neuroprotection against beta-amyloid pigmentation (involved in the pathogenesis of numerous brain disorders, including Alzheimer’s), glutamate (known to induce cell death) and certain other types of toxicity (5, 6).

The common dose range of huperzine-A is 50 - 200 mcg/day in one dose or divided into several smaller ones throughout the day (7). It is a water-soluble compound, so it does not need to be taken with food.

Huperzine A’s primary action is to increase brain levels of choline or acetylcholine. Scientists refer to this action as cholinergic. It synergizes with other known cholinergics such as alpha-GPC, and citicholine, as well as compounds that enhance cognitive function or alertness like caffeine or theacrine (8) to help increase choline in the brain.

References

  • Alan , K. P., & Werner, T. (1999). Chemistry, Pharmacology, and Clinical Efficacy of the Chinese Nootropic Agent Huperzine A (Vol. 32 (8), ). Acc. Chem.. doi/abs/10.1021/ar9800892?journalCode=achre4
  • Andrea, Z.(2003). The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease (Vol. Volume 75, Issue 3, ). Cognitive Drug Research science/article/pii/S0091305703001114
  • Wei-Han, L., Jason Q. D., G., Ashley, F. R., Joseph A.M., H., & Ian, W. E. (2010). Huperzine alkaloids from Australasian and southeast Asian Huperzia (Vol. Volume 48 Issue 9, ). Pharmaceutical Biology. doi/abs/10.3109/13880209.2010.485619
  • Guoyan, Y., Yuyi, W., Jinzhou, T., & ian-Ping, L. (2013). Huperzine A for Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (Vol. 8(9), ). PLoS One. pmc/articles/PMC3781107/
  • Ved, H., Koenig, M., Dave, ., & Doctor, B. (1997). Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. (Vol. 8(4), ). Neuroreport.. pubmed/9141073
  • Rui, W., Han, Y., & Xi-can, . (2006). Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine (Vol. 27, ). Acta Pharmacologica Sinica. aps/journal/v27/n1/abs/aps20061a.html
  • Rui, W., Han, Y., & Xi-can, . (2006). Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine (Vol. 27, ). Acta Pharmacologica Sinica. aps/journal/v27/n1/abs/aps20061a.html
  • Andrew, S. A. (1997). Old Chinese Herbal Medicine Used for Fever Yields Possible New Alzheimer Disease Therapy (Vol. 277(10), ). JAMA. journals/jama/article-abstract/414496
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Bacopa Monnieri

Bacopa monniere is a medicinal herb used for hundreds of years in traditional Ayurvedic medicine. Called "Brahmi" after Brahmā, the creator God of the Hindu pantheon, Bacopa has a history as a potent cognitive enhancer, stress reliever, and brain supporter. More recently, bacopa is used to improve memory formation and recall speed, make learning faster and easier, enhance clarity of thought, and augment overall brain function. Bacopa is also useful for reducing stress, and inducing a sense of calm and tranquility and reducing feelings of stress. Users report that it is an excellent general relaxant and can improve the quality of sleep, so they wake feeling rested and refreshed.

Bacopa Monniera, or water hyssop, is a perennial, creeping herb native to the wetlands of southern and Eastern India, Australia, Europe, Africa, Asia, and North and South America. [2]

It is known in India as Brahmi after Brahma, the Hindu creator god. The plant was first described 1500 years ago in Sanskrit texts as being valuable for sharpening the intellect and addressing mental defects. It has been used in traditional Ayurveda medicine to treat a wide range of conditions including inflammation, fever, coughing, poisoning, various blood disorders, as an astringent and a laxative, as well as to treat epilepsy (1). More recently, Bacopa is used primarily as a nootropic to improve mental acuity and memory and to reduce stress (2, 3).

Bacopa has repeatedly been shown to improve cognitive function, aid in memory formation, and reduce both stress and anxiety (4, 5, 6). Studies indicate that anti-anxiety effects occur almost immediately, whereas the cognitive enhancing effect may take longer, perhaps weeks. (7, 8). Unlike some other compounds, Bacopa works for both the elderly and young people.

Bacopa may also have specific neuroprotective properties: it shows promise in reducing oxidative damage from aluminum and preventing iron toxicity in the brain (9).

Bacopa contains 14 biologically active compounds collectively called Bacopasides (10). Bacopa primarily interacts with the dopamine and serotonergic pathways involved with stress and anxiety reductions, and may affect the cholinergic system, delivering benefits to enhanced cognitive function (11, 12). Bacopa’s impact on memory improvement is believed to derive from enhanced neuronal transmission and signaling (13).

The standard effective dose of Bacopa is 300 mg (14), at which level it induces relaxation. It is often paired with stimulants such as caffeine or theacrine to mitigate the herb's potential drowsiness. Bacopa is a fat-soluble supplement and should be taken with meals to avoid stomach upset or cramping.

References

  • Shinomol, G., & Muralidhara, ( 2011). Bacopa monnieri modulates endogenous cytoplasmic and mitochondrial oxidative markers in prepubertal mice brain. (Vol. 18(4), ). Phytomedicine. pubmed/20850955
  • Dr. Ajay Padmawar, Bacopa Moniera
  • Pase , M., Kean, J., Sarris, J., Neale, C., Scholey, A., & Stough, C. (2012). The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. (Vol. 18(7), ). J Altern Complement Med.. pubmed/22747190
  • Stough, C., Downey, L., Lloyd, J., Silber, B., Redman, S., Hutchison, C., Wesnes, K., & Nathan, P. (2008). Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double-blind placebo-controlled randomized trial. (Vol. 22(12), ). Phytother Res.. pubmed/18683852
  • Raghav, S., Singh, H., Dalal, P., Srivastava, J., & Asthana, O. (2006). Randomized controlled trial of standardized Bacopa monniera extract in age-associated memory impairment. (Vol. 48(4), ). Indian J Psychiatry.
  • Rai, D., Bhatia, G., Palit, G., Pal, R., Singh, S., & Singh, H. (2003). Adaptogenic effect of Bacopa monniera (Brahmi). (Vol. 75(4), ). Pharmacol Biochem Behav.. pubmed/12957224
  • Stough, C., Lloyd, J., Clarke, J., Downey, L., Hutchison, C., Rodgers, T., & Nathan, P. (2001). The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. (Vol. 156(4), ). Psychopharmacology (Berl). pubmed/11498727
  • Raghav, S., Singh, H., Dalal, P., Srivastava, J., & Asthana, O. (2006). Randomized controlled trial of standardized Bacopa monniera extract in age-associated memory impairment. (Vol. 48(4), ). Indian J Psychiatry. pubmed/20703343
  • Tripathi, S., Mahdi, A., Hasan, M., Mitra, K., & Mahdi, F. (2011). Protective potential of Bacopa monniera (Brahmi) extract on aluminum induced cerebellar toxicity and associated neuromuscular status in aged rats. (Vol. 57(1), ). Cell Mol Biol (Noisy-le-grand). pubmed/21366957
  • Srivastava, P., Raut, H., Puntambekar, H., & Desai, A. (2012). Stability studies of crude plant material of Bacopa monnieri and quantitative determination of bacopaside I and bacoside A by HPLC. (Vol. 23(5), ). Phytochem Anal. pubmed/22259163
  • Rajan, K., Singh, H., Parkavi, A., & Charles, . (2011). Attenuation of 1-(m-chlorophenyl)-biguanide induced hippocampus-dependent memory impairment by a standardised extract of Bacopa monniera (BESEB CDRI-08). (Vol. 36(11), ). Neurochem Res. pubmed/21735137
  • Saraf, M., Prabhakar, S., Khanduja, K., & Anand, A. (2011). Bacopa monniera Attenuates Scopolamine-Induced Impairment of Spatial Memory in Mice. (Vol. 2011, ). Evid Based Complement Alternat Med.. pubmed/21607013
  • Pase, M., Kean , J., Sarris , J., Neale, C., Scholey, A., & Stough, C. (2012). The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. (Vol. 18(7), ). J Altern Complement Med.. pubmed/22747190
  • Morgan, A., & Stevens, J. (2010). Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. (Vol. 16(7), ). J Altern Complement Med.. pubmed/20590480
  • Velmurugan, K., Alam, J., McCord, J., & Pugazhenthi, S. (2009). Synergistic induction of heme oxygenase-1 by the components of the antioxidant supplement Protandim. (Vol. 46(3), ). Free Radic Biol Med..
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L-Theanine

L-Theanine is a naturally occurring amino acid found in green tea leaves. Its chemical structure is similar to the neurotransmitter Glutamate. L-Theanine's similarity to Glutamate, one of the two key compounds responsible for signal transmission in the brain, makes L-Theanine valuable as a nootropic supporting overall learning, focus, and memory. L-Theanine is also shown to increase the brain’s levels of dopamine and serotonin, reducing feelings of stress and enhancing general well-being. L-Theanine combines well with caffeine, boosting the combination’s effect on focus and alertness while decreasing jittery and stressful effects.

Sensoril® Ashwagandha Extract

Sensoril is a patented extract of both the root and leaf of the Ashwagandha plant. A traditional herb with an ancient history, experts classify "The King of Ayurveda" as an adaptogen, a natural substance considered to help the body adapt to stress and normalize bodily processes. Ashwagandha is not typically thought of as a nootropic because it has so many documented effects on other body systems. It has positive effects on supporting healthy systemic inflammation, sleep quality, cortisol levels, cholesterol, blood pressure, physical power output, and the immune system, along with an extensive list of other effects. As a nootropic, ashwagandha supplementation impacts the GABA and serotonin neurotransmitters. It is commonly used to reduce stress and fatigue, as well as to improve mood and motivation.

Sensoril® is a patented, full-spectrum standardized root and leaf extract of Ashwagandha, or Withania Somnifera, a popular herb in Auyervedic medicine that has been used for centuries. Because of its long history and numerous applications, Ashwagandha is commonly referred to by practitioners as the King of Ayurveda.

Ashwagandha translates from Sanskrit as “smell of horse” referring to the distinctly horsey, farmhouse odor, and according to folklore it is thought eating the herb delivers the strength and vitality of a horse (5).

Ashwagandha is considered an adaptogen, a substance that helps the body adapt to anxiety and stress on both physiological and psychological levels (7). Today, ashwagandha is mainly known for its positive effects on helping the body cope with stress, increase endurance, and enhance cognitive function, which seems to be a result of the herbs effect on stress and anxiety. (6). Ashwagandha has been shown to alleviate insomnia and effects from stress-related depression (8). It can directly reduce levels of the stress hormone, cortisol, leading to reductions in the immunosuppressive effects of stress (9). As a cognitive enhancing supplement, ashwagandha may be effective in treating Alzheimer’s disease as well as improving new memory formation (10).

Also, Ayurveda uses Ashwagandha to treat tumors and ulcers (3), to enhance virility, as an aphrodisiac, as a rejuvenating agent, to treat inflammation, fatigue, stress, diabetes, cardiovascular disease, and other illnesses (4). Outside of Ayurveda, it is thought to confer neuroprotective benefits (2). The herb also has some interesting implications as an anti-cancer treatment, and new research suggests it may serve as an effective adjuvant therapy used alongside other primary forms of cancer treatment (11).

Ashwagandha contains many biologically active compounds including polyphenols, antioxidants, and other molecules that act upon different mechanisms and enzymatic pathways in the body (12). Ashwagandha supports mechanisms that suppress metastasis and angiogenesis, it acts upon various neuroprotective and neurotransmission pathways in the brain such as the cholinergic system, dopaminergic, and glutaminergic system, and it interacts with proteins and enzymes involved in reducing inflammation and maintaining cellular integrity (13, 14, 15, 16). Though we know many of the pathways ashwagandha acts upon, many have yet to be elucidated by scientific investigation.

Clinical studies have shown Sensoril to reduce circulating levels of cortisol and C-Reactive Protein, and important marker for systemic inflammation. It has also demonstrated lower pulse rates and blood pressure compared to a placebo, as well as increases in DHEA (an important hormone related to memory and mood) and hemoglobin. Compared to control groups, subjects have reported fewer headaches, less fatigue, muscle pain, sleeplessness, forgetfulness, and irritability, along with improved appetite and concentration. In all the research, there are no reports of adverse side effects. The clinical dose of Sensoril to achieve these results is 125mg.

References

  • Singh, B., Saxena, A., Chandan, B., Gupta, D., Bhutani, K., & Anand, K. (2001). Adaptogenic activity of a novel, withanolide-free aqueous fraction from the roots of Withania somnifera Dun. (Vol. 15(4), ). Phytother Res..
  • Singh, B., Chandan, B., & Gupta, D. (2003). Adaptogenic activity of a novel withanolide-free aqueous fraction from the roots of Withania somnifera Dun. (Part II). (Vol. 17(5), ). Phytother Res.. pubmed/12748992
  • Mirjalili, M. H., Moyano, E., Bonfill, M., Cusido, R. M., & Palazón, J. (2009). Steroidal Lactones from Withania somnifera, an Ancient Plant for Novel Medicine (Vol. 14(7), ). Molecules. 1420-3049/14/7/2373
  • Widodo, N., Priyandoko, D., Shah, N., Wadhwa, R., & Kaul , S. (2010). Selective killing of cancer cells by Ashwagandha leaf extract and its component Withanone involves ROS signaling. (Vol. 5(10), ). PLoS One.. pubmed/20975835
  • Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. (Vol. 34(3), ). Indian J Psychol Med.. pubmed/23439798
  • Mishra, L., Singh, B., Dagenais, S., & (2000). Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. (Vol. 5(4), ). Altern Med Rev.. pubmed/10956379
  • Bharavi, K., Reddy, A., Rao, G., Kumar, P., Kumar, D., & Prasadini, P. (2011). Prevention of cadmium bioaccumulation by herbal adaptogens. (Vol. 43(1), ). Indian J Pharmacol.. /pubmed/21455421
  • (2004). Monograph. Withania somnifera. (Vol. 9(2), ). Altern Med Rev. . pubmed/15253680
  • Chandrasekhar, K., Kapoor, J., Anishetty, S., & (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. (Vol. 34(3), ). Indian J Psychol Med.. pubmed/23439798
  • Chandrasekhar, K., Kapoor, J., Anishetty, S., & (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. (Vol. 34(3), ). Indian J Psychol Med.. pubmed/23439798
  • Deocaris, C., Widodo, N., Wadhwa, R., & Kaul , S. (2008). Merger of ayurveda and tissue culture-based functional genomics: inspirations from systems biology. (). J Transl Med.. pubmed/18348714
  • Mishra, L., Singh, B., Dagenais, S., & (2000). Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. (Vol. 5(4), ). Altern Med Rev.. pubmed/10956379
  • Yang, Z., Garcia, A., Xu, S., Powell, D., Vertino, P., Singh, S., & Marcus, A. (2013). Withania somnifera root extract inhibits mammary cancer metastasis and epithelial to mesenchymal transition. (Vol. 8(9), ). PLoS One. pubmed/24069380
  • Bhattacharya, S., Bhattacharya, A., Sairam, K., & Ghosal, S. (2000). Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. (Vol. 7(6), ). Phytomedicine.. pubmed/11194174
  • Modak, M., Dixit, P., Londhe, J., Ghaskadbi, S., & Devasagayam, T. (2007). Indian herbs and herbal drugs used for the treatment of diabetes. (Vol. 40(3), ). J Clin Biochem Nutr.. pubmed/18398493
  • Karin, M., & Delhase, M. (2000). The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. (Vol. 12(1), ). Semin Immunol.. pubmed/10723801
  • Karin, M., & Delhase, M. (2000). The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. (Vol. 12(1), ). Semin Immunol.. pubmed/10723801
  • Ramanathan, M., Balaji, B., & Justin, A. (2011). Behavioural and neurochemical evaluation of Perment an herbal formulation in chronic unpredictable mild stress induced depressive model. (Vol. 49(4), ). Indian J Exp Biol.. pubmed/21614890
  • Maity , T., Adhikari, A., Bhattacharya, K., Biswas, S., Debnath, P., & Maharana, C. (2011). A study on evalution of antidepressant effect of imipramine adjunct with Aswagandha and Bramhi. (Vol. 13(4), ). Nepal Med Coll J.. pubmed/23016473
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Methylcobalamin

Methylcobalamin is the “active” form of vitamin B12. It is almost identical to the more common form of B12 with the addition of one methyl group. Vitamin B12 is essential to human health, specifically allowing for the efficient operation of the central nervous system as well as all neurological tissues.

Methylcobalamin is one of the two common forms of Vitamin B12, the other being Cyanocobalamin. B12 is a water-soluble nutrient vital to human health and is found naturally only in animal products like meat, fish, eggs and dairy. First discovered in the 1800s, it was identified as a compound found in the liver that could be used to treat pernicious anemia (1). Adequate levels of B12 have been associated with increased mood and well-being, and is involved in healthy neuronal functioning and neurotransmission, and is believed to play a role in overall brain and nerve health (2, 8). B12 deficiencies are associated with numerous diseases and disorders including depression, fatigue, increased risk of stroke and Alzheimer’s Disease (5, 6, 7).

Since the discovery of B12's chemical structure, it has been identified as an enzyme cofactor for DNA synthesis and energy production and has been called “the Energy Vitamin.” It is believed to play a role in brain and nerve health(2).

B12 supplementation is considered necessary to increase cellular energy as well as aiding in the metabolism of fat, protein, and carbohydrate (3). It has effects on decreasing plasma homocysteine (a biomarker of inflammation) and converting various enzymes that support energy metabolism (4). B12 is involved in the methylation process, as it can contribute methyl groups to other molecules to support various metabolic processes (11, 12).

Vitamin B12 is absorbed through the intestines and carried in the bloodstream where it binds to transporter proteins (9). Methylcobalamin the active form of B12; it has the greatest bioavailability and can cross the blood-brain barrier freely (10).

References

  • G. , . H., F. , R. S., & C., H. W. (1920). BLOOD REGENERATION FOLLOWING SIMPLE ANEMIA (Vol. 53, ). American Journal of Physiology. content/53/2/236
  • O'Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. (Vol. 2(3), ). Nutrients. pubmed/22254022
  • O'Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. (Vol. 2(3), ). Nutrients. pubmed/22254022
  • O'Leary, F., & Samman, S. (2010). Vitamin B12 in health and disease. (Vol. 2(3), ). Nutrients. pubmed/22254022
  • Penninx, B., Guralnik, ., Ferrucci, L., Fried, ., Allen, R., & Stabler, S. (2000). Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study. (Vol. 157(5), ). Am J Psychiatry.. pubmed/10784463
  • Coppen, A., & Bolander-Gouaille, C. (2005). Treatment of depression: time to consider folic acid and vitamin B12. (Vol. 19(1), ). J Psychopharmacol. pubmed/15671130
  • Huijts, M., Duits, ., Staals, J., & van Oostenbrugge, R. J. (2012). Association of Vitamin B12 Deficiency with Fatigue and Depression after Lacunar Stroke (Vol. 7(1), ). PLoS One.
  • Gupta, . K. (2015). Potential Benefits of Methylcobalamin: A Review (Vol. 3, ). Austin J Pharmacol Ther.. pharmacology-therapeutics/fulltext/ajpt-v3-id1076.pdf
  • Carmel, R.(2003). Mild transcobalamin I (haptocorrin) deficiency and low serum cobalamin concentrations. (Vol. 49(8), ). Clin Chem..
  • Gupta, . K. (2015). Potential Benefits of Methylcobalamin: A Review (Vol. 3, ). Austin J Pharmacol Ther.. pharmacology-therapeutics/fulltext/ajpt-v3-id1076.pdf
  • Bottiglieri, T.(2013). Folate, vitamin B₁₂, and S-adenosylmethionine. (Vol. 36(1), ). Psychiatr Clin North Am. pubmed/23538072
  • https://examine.com/supplements/Vitamin+B12/
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Trans-Resveratrol

Trans-Resveratrol is the bioactive form of resveratrol, a polyphenol produced in a variety plants, especially berries and grapes and it is thought to be responsible for the reported health benefits of red wine. It is classified as an ampakine and seems to adjust certain neuroreceptors in the brain, along with being a powerful antioxidant. Resveratrol supplementation can boost dopamine production, BDNF, and blood flow in the brain.

Trans-resveratrol is a phytoalexin, a natural plant phenol found in fruits and berries including grapes, which helps protect the plant from various types of environmental stress. It was discovered in wine several thousand years ago and in Ayurveda is called “draksha”, meaning fermented grape juice (3). Today resveratrol is found in significant amounts in red wine(1). Resveratrol is popularly considered to be an anti-aging, life-extending substance and is responsible for the belief that red wine consumption is healthful. (4).

Research has shown resveratrol to have a protective effect on cardiovascular health, improve insulin sensitivity, and add to lifespan in individuals who are otherwise healthy (2). With respect to cognition and neurology, research shows that resveratrol supplementation may increase blood flow to the brain, may interfere with mechanisms involved in beta-amyloid accumulation (implicated in the pathogenesis of Alzheimer’s disease), and may increase intercellular signaling between neurotransmitters in the glutaminergic pathway (5, 6, 7). It is also thought to be involved in many enzymatic processes related to neuroprotection, though more research is needed to confirm (10, 11, 12).

Concerning longevity, resveratrol acts primarily upon the Sirtuin system, which is involved in maintaining cellular integrity and thus directly related both longevity and how the body reacts to various stressors (8, 9). The research is not conclusive, but long-term supplementation of resveratrol appears to support both cardiovascular health and insulin sensitivity.

Resveratrol doses range from a low of 5 - 10 mg/day, though larger doses in the range of 150 - 445 mg/day have been used (13).

References

  • Milosz, J., Lidia, J., & Marcin, O. (2013). Resveratrol in prostate diseases – a short review (Vol. 66(2), ). Cent European J Urol.. pmc/articles/PMC3936154
  • de Gaetano, G., De Curtis, A., di Castelnuovo, A., Donati, M., Iacoviello, L., & Rotondo, S. (2002). Antithrombotic effect of polyphenols in experimental models: a mechanism of reduced vascular risk by moderate wine consumption. (Vol. 957, ). Ann N Y Acad Sci.. pubmed/12074971
  • Divya, P., & Nancy, P. (2016). Determination of Quality Standards for Draksharishta, a Polyherbal Ayurvedic Formulation (Vol. 78(1), ). Indian J Pharm Sci.. pmc/articles/PMC4852562/
  • Catalgol, B., Batirel, S., Taga, Y., & Ozer, N. (2012). Resveratrol: French paradox revisited. (Vol. 3, ). Front Pharmacol.. pubmed/22822401
  • Matés, J., Pérez-Gómez, C., Núñez de Castro, I., Asenjo, M., & Márquez, J. (2002). Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death. (Vol. 34(5), ). Int J Biochem Cell Biol.. pubmed/11906817
  • Matés, J., Pérez-Gómez, C., Núñez de Castro, I., Asenjo, M., & Márquez, J. (2002). Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death. (Vol. 34(5), ). Int J Biochem Cell Biol.. pubmed/11906817
  • Porquet, D., Casadesús, G., Bayod, S., Vicente, A., Canudas, A., Vilaplana, J., Pelegrí, C., Sanfeliu, C., Camins, A., Pallàs, M., & del Valle, J. (2013). Dietary resveratrol prevents Alzheimer's markers and increases life span in SAMP8. (Vol. 35(5), ). Age (Dordr).. pubmed/23129026
  • Kelly, G.(2010). A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 1. (Vol. 15(3), ). Altern Med Rev. . pubmed/21155626
  • Kelly, G.(2010). A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 2. (Vol. 15(4), ). Altern Med Rev.. pubmed/21194247
  • Moldzio, R., Radad, K., Krewenka, C., Kranner, B., Duvigneau, J., & Rausch, W. (2013). Protective effects of resveratrol on glutamate-induced damages in murine brain cultures. (Vol. 120(9), ). J Neural Transm (Vienna).. pubmed/23459926
  • Bobermin, L., Quincozes-Santos, A., Guerra, M., MC, , Souza, D., Gonçalves, C., & Gottfried, C. (2012). Resveratrol prevents ammonia toxicity in astroglial cells. (Vol. 7(12, ). PLoS One. . pubmed/23284918
  • Chow, H., Garland, L. L., Hsu, C., Vining, D. R., Chew, W. M., Miller, J. A., Perloff, M., Crowell, J. ., & Alberts, D. . (2010). Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a Healthy Volunteer Study (Vol. Volume 3, Issue 9, ). AACRvPublications. content/3/9/1168
  • Mukherjee, S., Dudle, J., & Das, D. (2010). Dose-dependency of resveratrol in providing health benefits. (Vol. 8(4), ). Dose Response.. pubmed/21191486
  • Malhotra, A., Nair, P., & Dhawan, D. (2011). Curcumin and resveratrol synergistically stimulate p21 and regulate cox-2 by maintaining adequate zinc levels during lung carcinogenesis. (Vol. 20(5), ). Eur J Cancer Prev.. pubmed/21633290
  • Kwon, K., Kim, J., Kim, M., Lee, J., Ignarro, L., Kim, H., Shin, C., & Han, S. (2011). Melatonin synergistically increases resveratrol-induced heme oxygenase-1 expression through the inhibition of ubiquitin-dependent proteasome pathway: a possible role in neuroprotection. (Vol. 50(2), ). J Pineal Res. pubmed/21073519
  • Kowalczyk, M., Kowalczyk, P., Tolstykh, O., Hanausek, M., Walaszek, Z., & Slaga , T. (2010). Synergistic effects of combined phytochemicals and skin cancer prevention in SENCAR mice. (Vol. 3(2), ). Cancer Prev Res (Phila).. pubmed/20103723
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PharmaGABA® GABA

GABA is one of the two main “inhibitory” neurotransmitters responsible for reducing stimulation of nerve cells, inducing relaxation as a result. PharmaGABA is a natural form of GABA produced by a fermentation process by the same bacteria used to manufacture traditional Korean kimchi. PharmaGABA is distinct from normal GABA in that it can cross the blood-brain barrier, producing clinical effects in smaller quantities. PharmaGABA contributes as a nootropic by lowering stress and inducing relaxation. It is also valuable for smoothing out potential side-effects of caffeine and other stimulants.

GABA (Gamma-AminoButyric Acid) is a depressive neurotransmitter, responsible for regulating many depressive and sedative actions in the brain. GABA plays a role in reducing neuronal excitability and therefore is critical for relaxation and sleep.

GABA activity in the brain was first recognized in the 19th century when barbiturates were first used to reduce anxiety and treat epileptic seizures (1). Barbiturate use spawned a wide variety of pharmacological drugs that were all found to mediate GABA receptors in the brain. Originally GABA wasn’t used directly as a supplement; rather, GABA was targeted as an important neurotransmitter to reduce stress and anxiety (2).

The main reported benefits of increased GABA levels are reduced anxiety and stress, along with greater overall well-being (3, 4). GABA may stimulate Growth Hormone secretion to promote the growth of lean muscle, fat-burning, and stabilization of blood pressure (5, 6).

GABA is naturally produced in the body, though plant-derived supplements are commonly available. Uptake into the brain is more efficient with low doses, and less efficient at higher concentrations (7). This is because GABA can tightly regulate itself: it blocks its own transport when too much is present ensuring neurological levels of GABA remain constant (8).

PharamGABA is a patented, natural form of GABA, produced by a fermentation process by the same bacteria used in manufacturing traditional Korean kimchi. Regular GABA supplements are not absorbed efficiently into the bloodstream and don’t cross the blood-brain barrier well. PharmaGABA’s unique molecule does cross the blood brain barrier and have much more pronounced effects including decreases in sleep onset time, improved sleep quality, improved test taking scores, reductions in cortisol levels, increases in Growth Hormone, increased lean body mass as well as other effects.

GABA is often used in nootropic supplements along with other ingredients such as l-theanine and bacopa, which work together to increase GABA synthesis in the brain to induce the desired effects of elevated mood, reduced stress, and anxiety (11).

References

  • N G, B., & T G, S. (2006). GABA and glycine as neurotransmitters: a brief history (Vol. 147(Suppl 1), ). Br J Pharmacol. pmc/articles/PMC1760744/
  • N G, B., & T G, . (2006). GABA and glycine as neurotransmitters: a brief history (Vol. 147(Suppl 1), ). Br J Pharmacol. pmc/articles/PMC1760744/
  • Foster, A., & Kemp, J. (2006). Glutamate- and GABA-based CNS therapeutics. (Vol. 6(1), ). Curr Opin Pharmacol. pubmed/16377242
  • Foster, A., & Kemp, J. (2006). Glutamate- and GABA-based CNS therapeutics. (Vol. 6(1), ). Curr Opin Pharmacol. pubmed/16377242
  • Cavagnini, F., Invitti, C., Pinto, M., Maraschini, C., Di Landro, A., Dubini, A., & Marelli, A. (1980). Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man. (Vol. 93(2), ). Acta Endocrinol (Copenh). pubmed/7376786
  • Powers, M., Yarrow , J., McCoy, S., & Borst, S. (2008). Growth hormone isoform responses to GABA ingestion at rest and after exercise. (Vol. 40(1), ). Med Sci Sports Exerc.. pubmed/18091016
  • Löscher, W., & Frey, H. (1982). Transport of GABA at the blood-CSF interface. (Vol. 38(4), ). J Neurochem. pubmed/6801203
  • Löscher , W.(1979). GABA in plasma and cerebrospinal fluid of different species. Effects of gamma-acetylenic GABA, gamma-vinyl GABA and sodium valproate. (Vol. 32(5), ). J Neurochem. pubmed/374686
  • Petroff , O.(2002). GABA and glutamate in the human brain. (Vol. 8(6), ). Neuroscientist. pubmed/12467378
  • Shyamaladevi, N., Jayakumar, A., Sujatha, R., Paul, V., & Subramanian, E. (2002). Evidence that nitric oxide production increases gamma-amino butyric acid permeability of blood-brain barrier. (Vol. 15;57, ). Brain Res Bull. pubmed/11849830
  • Bartholini, G.(1985). GABA receptor agonists: pharmacological spectrum and therapeutic actions. (Vol. 5(1), ). Med Res Rev.. pubmed/2984490
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BioPerine® Black Pepper Extract

BioPerine is a patented extract taken from the black pepper fruit. Black pepper has been used in many traditional health systems including Ayurveda and Traditional Chinese Medicine and is considered in those systems as essential to human health. BioPerine is used to enhance bioavailability and multiply the effect of other nootropic ingredients.

BioPerine® is a patented extract obtained from black pepper fruits (Piper nigrum) standardized minimum to 95% Piperine, the active ingredient in the fruit.

Black Pepper has been part of the human diet since ancient times and has been used to treat human ailments for almost as long. Historically it has been used to treat a variety of gastrointestinal disorders, “imbalances” and dental or oral discomfort. Ayurvedic medicine considers black pepper as one of the three foundational ingredients in many prescritpions and formulations.

Throughout Asia, black pepper is thought to be a powerful medicinal plant where it is used to support healthy aging, liver health, circulation, and digestion (3). In modern nutritional supplements formulation, Piperine extract is used to enhance “bioavailability” or absorption of other ingredients by blocking the process of absorption and excretion in the liver and urine (4).

Piperine has been shown to modify the metabolism of various drugs and supplements. It works by downregulating the release of an enzyme in the liver that processes compounds before urinary excretion (7, 8). Drugs and supplements that are processed in the liver stimulate a process called glucoronidation, which binds to compounds which are then signaled for urinary secretion (9). Piperine has been shown to halt this process of excretion, which in turn, alters the metabolism of these compounds, and can enhance their bioavailability and activity in the body.

As an separate ingredient, studies suggest piperine may enhance cognitive function, mood, and decrease symptoms of depression (5). Early evidence suggests that piperine may also act upon neurotransmitter activities involved in thought formation and memory retention (10).

Bioperine is used in various nootropic stacks to enhance both the absorption in the small intestine and increase the effects of other ingredients. (11, 12).

References

  • Srinivasan, K.(2007). Black pepper and its pungent principle-piperine: a review of diverse physiological effects. (Vol. 47(8), ). Crit Rev Food Sci Nutr.. pubmed/17987447
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