Deep Dive into the Science Behind Nucleus Stack

Deep Dive into the Science Behind Nucleus Stack

The Nucleus Stack represents the ultimate in high-performance, functional nootropic formulations. If you are a gamer, coder, or you trade the stock or crypto markets, you know you need to be at your very best to compete and perform. “Bad days” won’t work for you, period! That’s why we developed Nucleus Alpha, Beta and Gamma – to give you the edge you need to be the very best.

Modern activities, particularly those that require the use of a computer, place tremendous demands on your mind and body, as they require a great deal of sustained concentration. Gaming in particular necessitates strong motor skills, tactical understanding, and hand-eye coordination. Coding and trading the markets requires often rapid decision-making, strategic thinking, and intense problem-solving skills. The Nucleus Stack is a 1-2-3 punch that can dramatically improve your day-to-day performance!

Toss the potentially harmful and addictive substances like Adderall, energy drinks and artificial stimulants that could be wrecking your physical and mental health.

Suggested reading: Why You Should Come Off Adderall (and Ritalin) and What to Do Instead

1. Nucleus Alpha

Alpha is the foundation to the stack. It is perfect for enhancing focus, concentration and working memory, involved in reasoning and decision making.

  • Enhances brain function*
  • Facilitates clearer thinking*
  • Improves reaction time*
  • Reduces fatigue*
  • Reduces stress*
  • Regulates pain*
  • Sharpens focus*

Alpha leverages the benefits of some of the most highly regarded plants and natural compounds so you can perform at your very best, whether you are a weekend warrior or a pro.

Caffeine is a well-known nootropic, especially when combined with L-Theanine giving you vigor and calm focus. The carefully chosen Cannabinoids work synergistically together, providing clear, calm focus and supporting learning and memory. Cordyceps improves energy, focus, learning and memory, and protects nerve cells from damage. GABA provides a calm focus for the stress of mental tasks. Ginkgo supports working memory, which is involved in reasoning and decision making, improves attention and the retrieval of learned facts. Gotu Kola has long been used as a general health tonic. It improves working memory (involved in reasoning and decision making), improves mood, calms anger, decreases anxiety and improves alertness. Lemon Balm has been said to “completely revivify a man”. It Improves cognitive performance and mood, improves working memory and mathematical processing and decreases stress. Lion’s Mane has long been used to improve vigor and strength. It improves both physical and cognitive performance. Vitamin B3 is essential to the function of all cells. It has been used in orthomolecular medicine as a calming agent, improving focus without decreasing cognitive function. Vitamin D3 and K2 work synergistically together supporting brain health. Vitamin D protectes nerve cells and is critical to the formation of neurotransmitters, the chemical signals that make the brain work. Vitamin K2 supports overall brain function via it’s anti-oxidant, anti-inflammatory effects and via its roles cell membrane metabolism.

Read more about each ingredient:

Caffeine Anhydrous

The Anhydrous Caffeine (caffeine with the water removed) used in Nucleus Alpha is extracted from plants. Unlike many other supplements the Caffeine in Nucleus Alpha is not synthetic, nor is it made from urea. While we think of Caffeine as coming from coffee or tea, it is actually found in over 60 plants.1 Caffeine’s stimulant effect on the Central Nervous System has been known for centuries and is generally accepted to be the most commonly consumed psychostimulant in the world.2

Mechanisms of action

Amongst other effects, Caffeine stimulants arousal in the Central Nervous System, mainly by blocking Adenosine receptors.3

When energy is used from ATP (Adenosine Tri-phosphate), the main energy molecule in the body, the Adenosine accumulates. By night time the accumulated Adenosine induces sleep.4 Caffeine blocks Adenosine receptors, not only inhibiting the action of Adenosine but also leading to an increase in Dopamine, Norepinephrine and Glutamate.5

Efficacy

Caffeine has been well-studied as an enhancer in physical pursuits.6 The cognitive effects of Caffeine are still being worked out, vary from person to person and may be more pronounced in those who do not regularly consume this.5

However, Caffeine has been shown to

  • increase attention, wakefulness, vigor and efficient information processing7
  • improve motor skills and decreases perception of effort8
  • improves reaction time, especially when sleep deprived9
  • improve the response to stress10

Safety

When ingested in amounts typically found in food and beverages, Caffeine is relatively safe.11

In some individuals Caffeine may cause elevated blood pressure, irregular heartbeat, stomach irritation and vomiting, anxiety, restlessness and psychosis. 11

In Nucleus Alpha, a small amount of Caffeine has been added to work synergistically with the L-Theanine, 12 as is unlikely to be well tolerated.

References

1. Lee, R.A. & Balick, M.J. Rx: Caffeine. Explore (NY) 2, 55-59 (2006).

2. Porciúncula, L.O., Sallaberry, C., Mioranzza, S., Botton, P.H. & Rosemberg, D.B. The Janus face of caffeine. Neurochem Int 63, 594-609 (2013).

3. Ferré, S. Role of the central ascending neurotransmitter systems in the psychostimulant effects of caffeine. J Alzheimers Dis 20 Suppl 1, S35-49 (2010).

4. Bjorness, T.E. & Greene, R.W. Adenosine and sleep. Curr Neuropharmacol 7, 238-245 (2009).

5. Cappelletti, S., Piacentino, D., Sani, G. & Aromatario, M. Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol 13, 71-88 (2015).

6. Graham, T.E. Caffeine and exercise: metabolism, endurance and performance. Sports Med 31, 785-807 (2001).

7. Lorist, M.M. & Tops, M. Caffeine, fatigue, and cognition. Brain Cogn 53, 82-94 (2003).

8. Meeusen, R. & Decroix, L. Nutritional Supplements and the Brain. Int J Sport Nutr Exerc Metab 28, 200-211 (2018).

9. Kamimori, G.H., et al. Caffeine improves reaction time, vigilance and logical reasoning during extended periods with restricted opportunities for sleep. Psychopharmacology (Berl) 232, 2031-2042 (2015).

10. Kasimay Cakir, O., et al. Protective effect of low dose caffeine on psychological stress and cognitive function. Physiol Behav 168, 1-10 (2017).

11. Temple, J.L., et al. The Safety of Ingested Caffeine: A Comprehensive Review. Front Psychiatry 8, 80 (2017).

12. Kahathuduwa, C.N., Dassanayake, T.L., Amarakoon, A.M.T. & Weerasinghe, V.S. Acute effects of theanine, caffeine and theanine-caffeine combination on attention. Nutr Neurosci 20, 369-377 (2017).

L-Theanine

L-Theanine, an amino acid found in green tea, is a great addition to a Nootropic stack as it improves focus and calmness at the same time.

While L-Theanine has been shown to be enhance brain function on its own, when stacked with Caffeine it may further increase the focus that Caffeine provides1 while calming the jitteriness that often accompanies Caffeine intake.

Mechanism of Actions

The mechanisms of actions of L-Theanine are still being worked out. However, it is well-established that L-theanine increases alpha brainwaves,2 and stimulates the growth of brain cells.3

Alpha brainwaves are associated with “wakeful relaxation as well as increased creativity, better performance under stress, and improved learning and concentration, as well as decreased anxiety.”4
L-theanine’s actions are likely to be related it its effect in increasing Dopamine (reward signaling), Serotonin (mood signaling) and GABA (calm signaling) and possibly inhibiting Glutamate (excitability signaling) in the brain.5

Efficacy

L-theanine has been shown to help:

  • Mitigate the physical effects of stress, lowering blood pressure,6 heart rate and improving heart rate variability.7
  • Decrease the psychological effect of stress8
  • Along with Caffeine, improves attention9 and decreases distractibility when performing a task.10
  • Improves learning and memory11

Safety

L-Theanine has been shown to be safe with few side-effects.12

References

1. Kahathuduwa, C.N., Dassanayake, T.L., Amarakoon, A.M.T. & Weerasinghe, V.S. Acute effects of theanine, caffeine and theanine-caffeine combination on attention. Nutr Neurosci 20, 369-377 (2017).

2. Juneja, L.R., Chu, D.-C., Okubo, T., Nagato, Y. & Yokogoshi, H. L-theanine—a unique amino acid of green tea and its relaxation effect in humans. Trends in Food Science & Technology 10, 199-204 (1999).

3. Katasonov, A.B. [Neurobiological effects of theanine and its possible use in neurology and psychiatry]. Zh Nevrol Psikhiatr Im S S Korsakova 118, 118-124 (2018).

4. Lardner, A.L. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutr Neurosci 17, 145-155 (2014).

5. Nathan, P.J., Lu, K., Gray, M. & Oliver, C. The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother 6, 21-30 (2006).

6. Yoto, A., Motoki, M., Murao, S. & Yokogoshi, H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol 31, 28 (2012).

7. Kimura, K., Ozeki, M., Juneja, L.R. & Ohira, H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol 74, 39-45 (2007).

8. Hidese, S., et al. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients 11(2019).

9. Dietz, C. & Dekker, M. Effect of Green Tea Phytochemicals on Mood and Cognition. Curr Pharm Des 23, 2876-2905 (2017).

10. Kahathuduwa, C.N., et al. l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study. Nutrition research (New York, N.Y.) 49, 67-78 (2018).

11. Park, S.K., et al. A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. Journal of medicinal food 14, 334-343 (2011).

12. Hidese, S., et al. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr 29, 72-79 (2017).

Cannabinoids

Cannabis sativa aerial parts

Cannabis is one of the most ancient non-food crops cultivated by humans. It has been used in the Traditional Medicines of South Africa, South America, Turkey, Egypt and many regions of Asia.1 Only two to three generations ago, Cannabis was routinely used in Europe and the USA to treat a variety of conditions, from migraine to nausea to Parkinson’s disease.2

Constituents & Mechanism of Actions

The Cannabis sativa plant contains over 500 known compounds. 3 The most well-known group of these compounds are the phytocannabinoids, of which there are over 100 different types. These phytocannabinoidss can broadly divided into:

  • Psychoactive compounds such as Tetrahydrocannabinol (THC)
  • Non-psychoactive compounds including Cannabidiol (CBD), Cannabigerol (CBG) and other plant chemicals such as Cannabis terpenes.4

The phytocannabinoids all have an effect on the body’s own cannabinoid system, binding to the Endocannabinoid receptors found throughout the body.5

Nucleus Alpha uses the THC-free Cannabinoids, CBD (Cannabidiol) and CBG (Cannabigerol), as well as Cannabis Terpenes in a synergistic mix.

The actions of CBD and CBG include:1

  • Neuroprotection (protecting nerves against damage) via anti-oxidant, anti-inflammatory, and immune mechanisms1,6 as well as increasing glucose uptake by the neurons.7
  • Pain-relief
  • Anti-nausea
  • Anti-psychotic
  • Immune support
  • Reduction of the effects of stress8
  • Anti-anxiety effects9
  • Anti-inflammatory4
  • Sleep induction10

Plant terpenes have diverse effects11 including:

  • Anti-anxiety
  • Immune enhancing
  • Inhibition of the breakdown of Acetylcholine – pivotal to focus, learning and memory

The Cannabinoids and other plant compounds such as the Terpenes work synergistically together in the plant and when consumed by humans.4

Efficacy

CBD shows promise in treating anxiety, depression and psychosis.12 CBD may potentially also treat disorders of the central nervous system such as Alzheimer’s disease, Parkinson’s disease, Multiple Sclerosis and Epilepsy.1

Research on CBD, CBG and Cannabis Terpenes as nootropics are yet to be done. However, these cannabinoids are likely to improve brain health by

  • Decreasing anxiety
  • Protecting neurons
  • Regulating mood
  • Supporting a healthy stress response

Safety

CBD (without THC) is considered safe and well tolerated.13

References

1. Giacoppo, S., Mandolino, G., Galuppo, M., Bramanti, P. & Mazzon, E. Cannabinoids: new promising agents in the treatment of neurological diseases. Molecules 19, 18781-18816 (2014).

2. Russo, E.B. History of cannabis and its preparations in saga, science, and sobriquet. Chem Biodivers 4, 1614-1648 (2007).

3. Solymosi, K. & Köfalvi, A. Cannabis: A Treasure Trove or Pandora’s Box? Mini Rev Med Chem 17, 1223-1291 (2017).

4. Russo, E. Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British journal of pharmacology 163, 1344-1364 (2011).

5. Russo, E. & Guy, G.W. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 66, 234-246 (2006).

6. Gugliandolo, A., Pollastro, F., Grassi, G., Bramanti, P. & Mazzon, E. In Vitro Model of Neuroinflammation: Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid. Int J Mol Sci 19(2018).

7. Köfalvi, A., et al. Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer’s disease. Neuropharmacology 110, 519-529 (2016).

8. Akirav, I. Cannabinoids and glucocorticoids modulate emotional memory after stress. Neuroscience and biobehavioral reviews 37, 2554-2563 (2013).

9. Campos, A.C. & Guimarães, F.S. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl) 199, 223-230 (2008).

10. Babson, K.A., Sottile, J. & Morabito, D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep 19, 23 (2017).

11. Andre, C.M., Hausman, J.F. & Guerriero, G. Cannabis sativa: The Plant of the Thousand and One Molecules. Front Plant Sci 7, 19 (2016).

12. Campos, A.C., Moreira, F.A., Gomes, F.V., Del Bel, E.A. & Guimarães, F.S. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci 367, 3364-3378 (2012).

13. Iseger, T.A. & Bossong, M.G. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophrenia research 162, 153-161 (2015).[/ultimate_modal] were carefully chosen to work synergistically together, providing clear, calm focus and support learning and memory.

Cordyceps

Cordyceps militaris fruiting bodies

Cordyceps is a type of fungus that parasitizes insects. It is found throughout the world and is especially abundant in tropical forests and humid regions.1

Cordyceps has been used for centuries in Traditional Chinese Medicine for the treatment of fatigue, low libido, as a recovery aid after illness, and to enhance physical strength and endurance.2 While there are many species of Cordyceps, C. sinesis and C. militaris have been the most used and the most studied with C. militaris being considered a suitable substitute for the more extensively studied C. sinesis.3

Constituents & Mechanism of Actions

Cordyceps species contain a wide variety of compounds including polysaccharides, sterols, and amino acids. However, it is thought that nucleosides including cordycepsin (3’-deoxyadenosine), adenine and inosine acting on the purinergic receptors are responsible for most of the effects in the human body.3

The compounds in Cordyceps have, amongst other actions been shown to be:1,3

  • Anti-inflammatory, Anti-oxidant, Immune enhancing
  • Anti-tumor
  • Anti-diabetic
  • Anti-aging4
  • Energy enhancing5

In the laboratory, (in vitro) Cordyceps has also been shown to

  • Inhibit the breakdown of Acetylcholine6 – critical for focus, learning and memory
  • Increase BDNF, promoting the survival of nerve cells7

While the exact mechanism are still being worked out, it is likely that all of these actions contribute to Cordyceps’ effects as a nootropic.8

Efficacy

Cordyceps has a long traditional use as a “powerhouse of energy.”9 However, modern clinical trials are only just starting to be done and indicate that in humans, Cordyceps

  • Increases aerobic capacity10,11

In animal studies, Cordyceps has been shown to

  • Improve cognitive function12,13
  • Improve learning and memory14
  • Improve the response to stress15

Safety

Cordyceps is generally well tolerated. Mild side-effects such as nausea and diarrhoea have been described.16

References

1. Liu, Y., et al. The Chemical Constituents and Pharmacological Actions of Cordyceps sinensis. Evid Based Complement Alternat Med 2015, 575063 (2015).

2. Lin B, L.S. Cordyceps as an Herbal Drug. in Herbal Medicine: Biomolecular and Clnical Aspects (ed. Benzie IFF, W.-G.S.) (CRC Press/Taylor & Francis, Boca Raton (Fl), 2011).

3. Olatunji, O.J., et al. The genus Cordyceps: An extensive review of its traditional uses, phytochemistry and pharmacology. Fitoterapia 129, 293-316 (2018).

4. Ji, D.B., et al. Antiaging effect of Cordyceps sinensis extract. Phytother Res 23, 116-122 (2009).

5. Dai, G., Bao, T., Xu, C., Cooper, R. & Zhu, J.S. CordyMax Cs-4 improves steady-state bioenergy status in mouse liver. J Altern Complement Med 7, 231-240 (2001).

6. Tsai, C.H., Yen, Y.H. & Yang, J.P. Finding of polysaccharide-peptide complexes in Cordyceps militaris and evaluation of its acetylcholinesterase inhibition activity. J Food Drug Anal 23, 63-70 (2015).

7. Lee, S.H., et al. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils. J Exerc Rehabil 12, 69-78 (2016).

8. Shashidhar, M.G., Giridhar, P., Udaya Sankar, K. & Manohar, B. Bioactive principles from Cordyceps sinensis: A potent food supplement – A review. J Funct Foods 5, 1013-1030 (2013).

9. Ashraf, S.A., et al. Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Cordyceps Medicinal Fungus and Its Nutraceutical and Therapeutic Potential. Molecules 25(2020).

10. Steinkraus, D.C. & Whitfield, J.B. Chinese Caterpillar Fungus and World Record Runners. American Entomologist 40, 235-239 (1994).

11. Xiao, Y., et al. Increased aerobic capacity in healthy elderly humans given a fermentation product of Cordyceps CS-4. Medicine and Science in Sports and Exercise – MED SCI SPORT EXERCISE 31(1999).

12. He, M.T., et al. Protective role of Cordyceps militaris in Aβ(1-42)-induced Alzheimer’s disease in vivo. Food Sci Biotechnol 28, 865-872 (2019).

13. Cai, Z.L., et al. Effects of cordycepin on Y-maze learning task in mice. European journal of pharmacology 714, 249-253 (2013).

14. Gong, M.F., Xu, J.P., Chu, Z.Y. & Luan, J. [Effect of Cordyceps sinensis sporocarp on learning-memory in mice]. Zhong Yao Cai 34, 1403-1405 (2011).

15. Koh, J.H., Kim, K.M., Kim, J.M., Song, J.C. & Suh, H.J. Antifatigue and antistress effect of the hot-water fraction from mycelia of Cordyceps sinensis. Biol Pharm Bull 26, 691-694 (2003).

16. Hu, R., et al. Comparison of drug safety data obtained from the monitoring system, literature, and social media: An empirical proof from a Chinese patent medicine. PloS one 14, e0222077 (2019).

GABA

Gamma-aminobutyric acid

GABA is a (non-protein forming) amino acid found throughout the body. Most of the research has been done on GABA’s functions in the brain and the pancreas.1 In the brain, GABA is an important neurotransmitter (chemical signal) that is made directly in the neurons from Glutatmate2 and is critical to the functioning of the central nervous system.3

GABA also exists naturally in food such as tea, tomato, soybean,4 and in uncooked spinach.5 More interestingly (for the nerds at Omic anyway), GABA is made by bacteria such as Lactobacillus and Bifidobacterium species in fermented foods6 and in fact, in our own guts7.

Mechanism of Actions

GABA is the main “inhibitory” neurotransmitter in the brain and Glutamate is the main “excitatory” neurotransmitter. These compounds control many of the brain’s processes.2

While inhibition may not sound great, inhibitory processes are essential to optimal brain function.8 In worst case scenarios a lack of inhibition can lead to epilepsy and stiff person syndrome.2 More commonly, too little GABA activity (not enough inhibition) results in anxiety;9 and we all know how difficult it is to concentrate and perform when we are anxious. GABA prevents us from generating inappropriate emotional and behavioral responses to stress. However, stress decreases GABA activity in the brain.10

While the ability of GABA taken orally to cross the blood-brain-barrier has been questioned, emerging research indicates that substantial amounts of GABA may cross the blood-brain-barrier into the brain.11 Furthermore, while research is still early, the GABA in the gut may be able to communicate with the brain via the Vagus nerve.12 Super cool!

GABA decreases the action of norepinephrine13 and is thought to be involved in a large range of behaviors, including confidence, stress regulation and memory enhancement.14

Efficacy

Most trials in humans involve pharmaceuticals, for treatment of anxiety and epilepsy, that attach to the GABA receptors.15 However, early clinical trials using supplemental GABA indicate it is effective in:

  • Improving relaxation16
  • Decreasing anxiety16
  • Enhancing immunity when under stress16
  • Reducing the stress of mental tasks14
  • Improving energy17
  • Improving task-solving ability17
  • Decreasing the negative effects of stress in the body3
  • Lowering blood pressure18

Safety

GABA is likely to be safe when used as a supplement.16

References

1. Jewett BE, S.S. Physiology, GABA. in StatPearls (StatPearls [Internet], Treasure Island, Florida, 2020).

2. Hampe, C., Mitoma, H. & Manto, M. GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets. (2018).

3. Hepsomali, P., Groeger, J.A., Nishihira, J. & Scholey, A. Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Front Neurosci 14, 923 (2020).

4. Diana, M., Quílez, J. & Rafecas, M. Gamma-aminobutyric acid as a bioactive compound in foods: a review. Journal of Functional Foods 10, 407-420 (2014).

5. Oh, S.-H., Moon, Y.-J. & Oh, C.-H. γ -Aminobutyric Acid (GABA) Content of Selected Uncooked Foods. Preventive Nutrition and Food Science 8(2003).

6. Boonstra, E., et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol 6, 1520 (2015).

7. Duranti, S., et al. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep 10, 14112 (2020).

8. Cuypers, K., Maes, C. & Swinnen, S.P. Aging and GABA. Aging (Albany NY) 10, 1186-1187 (2018).

9. Nemeroff, C.B. The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull 37, 133-146 (2003).

10. Jie, F., et al. Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases. Front Neurosci 12, 562 (2018).

11. Takanaga, H., Ohtsuki, S., Hosoya, K. & Terasaki, T. GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier. J Cereb Blood Flow Metab 21, 1232-1239 (2001).

12. Schmidt, C. Mental health: thinking from the gut. Nature 518, S12-15 (2015).

13. Hayakawa, K., Kimura, M. & Kamata, K. Mechanism underlying γ-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats. European journal of pharmacology 438, 107-113 (2002).

14. Yoto, A., et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids 43, 1331-1337 (2012).

15. Rashmi, D., Zanan, R., John, S., Khandagale, K. & Nadaf, A. Chapter 13 – γ-Aminobutyric Acid (GABA): Biosynthesis, Role, Commercial Production, and Applications. in Studies in Natural Products Chemistry, Vol. 57 (ed. Atta ur, R.) 413-452 (Elsevier, 2018).

16. Abdou, A.M., et al. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors 26, 201-208 (2006).

17. Kanehira, T., et al. Relieving occupational fatigue by consumption of a beverage containing γ-amino butyric acid. J Nutr Sci Vitaminol (Tokyo) 57, 9-15 (2011).

18. Nishimura, M., et al. Effects of white rice containing enriched gamma-aminobutyric acid on blood pressure. Journal of Traditional and Complementary Medicine 6, 66-71 (2016).

Ginkgo

Ginkgo biloba Leaf

Ginkgo is one of the most commonly used herbs used in Europe1 and is listed in the German Commission E monographs for the treatment of cognitive disorders. It is frequently prescribed in the United States.2 The Ginkgo tree is a native of China where it has been used for thousands3 of years to treat various disorders. More recently, Ginkgo has been suggested as a nootropic agent.4

Constituents & Mechanism of Actions

Ginkgo contains a number of different phyto-chemicals. However, the active compounds are the terpene trilactones known as ginkgolides and the flavonoids nl. quercetin, kaempferol and isorhamnetin.5

These compounds have been shown to cross the blood brain barrier where they protect the cellular mitochondria from damage, ensuring the continued supply of ATP.6 ATP is the form of energy that is made in the mitochondria of human cells. The more ATP you have, the better you function.

The Ginkgo compounds are anti-oxidants that have been shown to quench free radicals. Ginkgo decreases inflammation, and blood clotting, increasing blood flow to the brain, while protecting the brain by decreasing the death of brain cells and the accumulation of plaque that is associated with Alzheimer’s disease.6

Ginkgo extracts have been shown to increase

  • Norepinephrine – supporting mood and cognition7
  • Dopamine – supporting learning and attention7
  • Acetylcholine – supporting focus, learning and memory8

Efficacy

Most of the studies on the effects of Ginkgo in the brain have been done on preventing and treating dementia.9

However, in healthy people, there is evidence that Ginkgo

  • Improves working memory10 which is involved in reasoning and decision making
  • Improves attention11
  • Improves retrieval of learned facts12
  • Improves symptoms of ADHD13

Safety

Although increased bleeding is associated with Ginkgo use, the evidence for this is equivicol.14 While rare side-effects such as nausea and diarrhea have been reported, Ginkgo is generally well tolerated.15

References

1. Roland, P.D. & Nergård, C.S. [Ginkgo biloba–effect, adverse events and drug interaction]. Tidsskr Nor Laegeforen 132, 956-959 (2012).

2. Diamond, B.J., et al. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 81, 668-678 (2000).

3. Dubey, A.K., Shankar, P.R., Upadhyaya, D. & Deshpande, V.Y. Ginkgo biloba–an appraisal. Kathmandu Univ Med J (KUMJ) 2, 225-229 (2004).

4. Arushanian, E.B. & Beĭer, E.V. [Ginkgo Biloba as a cognitive enhancer]. Eksp Klin Farmakol 71, 57-63 (2008).

5. Shi, C., Liu, J., Wu, F. & Yew, D.T. Ginkgo biloba extract in Alzheimer’s disease: from action mechanisms to medical practice. Int J Mol Sci 11, 107-123 (2010).

6. Ude, C., Schubert-Zsilavecz, M. & Wurglics, M. Ginkgo biloba extracts: a review of the pharmacokinetics of the active ingredients. Clin Pharmacokinet 52, 727-749 (2013).

7. Fehske, C.J., Leuner, K. & Müller, W.E. Ginkgo biloba extract (EGb761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment. Pharmacol Res 60, 68-73 (2009).

8. Zhang, L., et al. Identification of Human Acetylcholinesterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations. Comb Chem High Throughput Screen 21, 41-49 (2018).

9. Nguyen, T. & Alzahrani, T. Ginkgo Biloba. in StatPearls (StatPearls Publishing

Copyright © 2020, StatPearls Publishing LLC., Treasure Island (FL), 2020).

10. Silberstein, R.B., et al. Examining brain-cognition effects of ginkgo biloba extract: brain activation in the left temporal and left prefrontal cortex in an object working memory task. Evid Based Complement Alternat Med 2011, 164139 (2011).

11. Kennedy, D.O., Scholey, A.B. & Wesnes, K.A. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl) 151, 416-423 (2000).

12. Kaschel, R. Specific memory effects of Ginkgo biloba extract EGb 761 in middle-aged healthy volunteers. Phytomedicine : international journal of phytotherapy and phytopharmacology 18, 1202-1207 (2011).

13. Shakibaei, F., Radmanesh, M., Salari, E. & Mahaki, B. Ginkgo biloba in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. A randomized, placebo-controlled, trial. Complementary therapies in clinical practice 21, 61-67 (2015).

14. Kellermann, A.J. & Kloft, C. Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy 31, 490-502 (2011).

15. Sierpina, V.S., Wollschlaeger, B. & Blumenthal, M. Ginkgo biloba. Am Fam Physician 68, 923-926 (2003).

Gotu Kola

Centella asiatica leaves

Gotu Kola is used extensively in India by traditional healers and the general population as a general cognitive enhancer,1 health tonic, and for the treatment for infections such as leprosy, tuberculosis, and dysentery.2

Constituents & Mechanism of Actions

The phyto-chemicals in Gotu Kola that are likely to be responsible for its cognitive enhancing effects, include terpenes (Asiatic acid, Madecassoside, Asiaticoside) and flavonoids (Quercetin, Kaempferol, Leutolin, Naringin, Apigenin).3,4

These compounds

  • Protect brain cells from damage possibly due it’s anti-oxidant activity
  • Enhance Acetylcholine – supporting focus, learning and memory3
  • Possibly enhance GABA – pivotal to calm focus5
  • Enhance the tree-like structure of brain cells, resulting in the formation of memories3
  • May have anti-aging effects, by increasing Telomerase – an enzyme that increases the health of DNA6
  • Support the population of “good” bacteria in the gut, that produce Butyrate – a brain enhancing fat7

Efficacy

The effect of Gotu Kola has been largely been studied in animals, indicating enhanced learning and memory effects.8

In humans, Gotu Kola has been shown to improve Mild Cognitive Impairment in the elderly.9

In a healthy population without cognitive impairment, Gotu Kola was shown to

  • Improve working memory – involved in reasoning and decision making
  • Improve mood10
  • Improve alertness
  • Calm anger 11
  • Decrease anxiety.12

Safety

Gotu Kola is generally well tolerated.13

References

1. Mannangatti, P. & Naidu, K.N. Indian Herbs for the Treatment of Neurodegenerative Disease. Adv Neurobiol 12, 323-336 (2016).

2. Panmei, R., Gajurel, P.R. & Singh, B. Ethnobotany of medicinal plants used by the Zeliangrong ethnic group of Manipur, northeast India. J Ethnopharmacol 235, 164-182 (2019).

3. Uddin, M.S., et al. Nootropic and Anti-Alzheimer’s Actions of Medicinal Plants: Molecular Insight into Therapeutic Potential to Alleviate Alzheimer’s Neuropathology. Mol Neurobiol 56, 4925-4944 (2019).

4. Brinkhaus, B., Lindner, M., Schuppan, D. & Hahn, E.G. Chemical, pharmacological and clinical profile of the East Asian medical plant Centella asiatica. Phytomedicine : international journal of phytotherapy and phytopharmacology 7, 427-448 (2000).

5. Kardani, A., Soltani, A., Sewell, R.D.E., Shahrani, M. & Rafieian-Kopaei, M. Neurotransmitter, Antioxidant and Anti-neuroinflammatory Mechanistic Potentials of Herbal Medicines in Ameliorating Autism Spectrum Disorder. Curr Pharm Des 25, 4421-4429 (2019).

6. Tsoukalas, D., et al. Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives. Molecular medicine reports 20, 3701-3708 (2019).

7. Peterson, C.T., et al. 16S rRNA gene profiling and genome reconstruction reveal community metabolic interactions and prebiotic potential of medicinal herbs used in neurodegenerative disease and as nootropics. PloS one 14, e0213869 (2019).

8. Nasir, M.N., et al. Effects of asiatic acid on passive and active avoidance task in male Spraque–Dawley rats. Journal of Ethnopharmacology 134, 203-209 (2011).

9. Tiwari, S., Singh, S., Patwardhan, K., Gehlot, S. & Gambhir, I. Effect of Centella asiatica on mild cognitive impairment (MCI) and other common age-related clinical problems. Digest Journal of Nanomaterials and Biostructures 3, 215-220 (2008).

10. Wattanathorn, J., et al. Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. Journal of Ethnopharmacology 116, 325-332 (2008).

11. Puttarak, P., et al. Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis. Sci Rep 7, 10646 (2017).

12. Bradwejn, J., Zhou, Y., Koszycki, D. & Shlik, J. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 20, 680-684 (2000).

13. Songvut, P., Chariyavilaskul, P., Tantisira, M.H. & Khemawoot, P. Safety and Pharmacokinetics of Standardized Extract of Centella asiatica (ECa 233) Capsules in Healthy Thai Volunteers: A Phase 1 Clinical Study. Planta medica 85, 483-490 (2019).

Lemon Balm

Melissa officinalis whole plant

Lemon Balm has been used in European and Middle Eastern Traditional Medicine for thousands years to treat a variety of conditions including neurological and mental disorders,1 for the enhancement of memory and to “completely revivify a man.”2 It is currently used for its calming, anti-anxiety effects.3 Unlike pharmaceuticals which impair cognitive performance,4 Lemon Balm can actually induce calm and enhance cognitive performance.3

Constituents & Mechanism of Actions

Lemon Balm contains various terpenes (ursolic acid, oleanolic acid), phenols (luteolin, naringin) and volatile essential oils (citronellal, geraniol).1

While still being studied, it appears that Lemon Balm’s cognitive-enhancing effects are partially due to its effect in:

  • Binding to Acetylcholine nicotinic receptors in the brain that
    • Protect brain cells, increasing their survival5
    • Support the release of neurotransmitters including5:
      • Dopamine – supporting learning and attention
      • GABA – pivotal to calm focus
  • Binding to Acetylcholine muscarinic receptors in the brain,6 which play an essential role in learning and memory.7
  • Increasing GABA by inhibiting its breakdown8
  • Anti-oxidation effects, protecting brain cells from damage9

Efficacy

Early human studies indicate that Lemon Balm

  • Improves cognitive performance and mood10
  • Improves working memory and mathematical processing3
  • Decreases stress11

Safety

Lemon Balm is generally well tolerated. However theoretically, those with hypothyroidism and glaucoma may need to monitor their conditions if using Lemon Balm regularly.1

References

1. Shakeri, A., Sahebkar, A. & Javadi, B. Melissa officinalis L. – A review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 188, 204-228 (2016).

2. Kennedy, D.O. & Scholey, A.B. The psychopharmacology of European herbs with cognition-enhancing properties. Curr Pharm Des 12, 4613-4623 (2006).

3. Scholey, A., et al. Anti-stress effects of lemon balm-containing foods. Nutrients 6, 4805-4821 (2014).

4. Thompson, J.M., et al. Cognitive properties of sedation agents: comparison of the effects of nitrous oxide and midazolam on memory and mood. Br Dent J 187, 557-562 (1999).

5. Zoli, M., Pucci, S., Vilella, A. & Gotti, C. Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors. Curr Neuropharmacol 16, 338-349 (2018).

6. Wake, G., et al. CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. J Ethnopharmacol 69, 105-114 (2000).

7. Thomsen, M., Sørensen, G. & Dencker, D. Physiological roles of CNS muscarinic receptors gained from knockout mice. Neuropharmacology 136, 411-420 (2018).

8. Awad, R., Muhammad, A., Durst, T., Trudeau, V.L. & Arnason, J.T. Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Phytother Res 23, 1075-1081 (2009).

9. Hohmann, J., et al. Protective effects of the aerial parts of Salvia officinalis, Melissa Officinalis and Lavandula angustifolia and their constituents against enzyme-dependent and enzyme-independent lipid peroxidation. Planta medica 65, 576-578 (1999).

10. Kennedy, D.O., et al. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology 28, 1871-1881 (2003).

11. Kennedy, D.O., Little, W. & Scholey, A.B. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med 66, 607-613 (2004).

Lion’s Mane

Hericium erinaceus fruiting body

Lion’s mane is a fungus that grows on old or dead broadleaf trees. It is used as food and medicine in Asia and has a long history of use in traditional Chinese and Japanese Medicine as a restorative, promoting vigor and strength.1

Constituents & Mechanism of Actions

Lion’s Mane contains a large amount of different bioactive compounds2 including polysaccharides (e.g. β-glucan), terpenoids (e.g. hericenones, erinacines) and sterols1

The actions of these compounds include:

  • Protection of nerves cells and stimulation of nerve growth3
  • Anti-oxidation1
  • Anti-inflammatory2
  • Anti-cancer effects4
  • Anti-biotic properties2
  • Anti-aging5
  • Beneficial effects on glucose and fat metabolism2

While the exact mechanisms are still unknown, ut is likely that the neuroprotective, anti-inflammatory and anti-oxidation effects of Lions’ Mane contribute to its actions in the brain.6

Efficacy

While further clinical studies are needed to confirm the actions in the body of Lion’s Mane, Animal studies have shown that Lion’s Mane can

  • Increase physical performance7
  • Improve the functioning of the hippocampus, a region of the brain responsible for processing memories and emotional responses8,9

Early studies in humans, indicate that Lion’s Mane can

  • Reduce anxiety and depression6
  • Improve cognitive function in those with mild cognitive impairment10

Safety

Lion’s mane is well tolerated and no adverse events have been reported, although those with mushroom allergy may need to avoid this.1

References

1. Spelman, K., Sutherland, E. & Bagade, A. Neurological Activity of Lion’s Mane ( Hericium erinaceus ). Journal of Restorative Medicine 6, 19-26 (2017).

2. Friedman, M. Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion’s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive Compounds. J Agric Food Chem 63, 7108-7123 (2015).

3. Lee, K.F., et al. Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine. Int J Mol Sci 15, 15073-15089 (2014).

4. Zan, X., et al. Hericium erinaceus polysaccharide-protein HEG-5 inhibits SGC-7901 cell growth via cell cycle arrest and apoptosis. Int J Biol Macromol 76, 242-253 (2015).

5. Noh, H.J., et al. Chemical constituents of Hericium erinaceum associated with the inhibitory activity against cellular senescence in human umbilical vascular endothelial cells. J Enzyme Inhib Med Chem 30, 934-940 (2015).

6. Nagano, M., et al. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Biomed Res 31, 231-237 (2010).

7. Liu, J., Du, C., Wang, Y. & Yu, Z. Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus. Exp Ther Med 9, 483-487 (2015).

8. Brandalise, F., et al. Dietary Supplementation of Hericium erinaceus Increases Mossy Fiber-CA3 Hippocampal Neurotransmission and Recognition Memory in Wild-Type Mice. Evid Based Complement Alternat Med 2017, 3864340 (2017).

9. Ryu, S., Kim, H.G., Kim, J.Y., Kim, S.Y. & Cho, K.O. Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain. Journal of medicinal food 21, 174-180 (2018).

10. Mori, K., Obara, Y., Moriya, T., Inatomi, S. & Nakahata, N. Effects of Hericium erinaceus on amyloid β(25-35) peptide-induced learning and memory deficits in mice. Biomed Res 32, 67-72 (2011).

Vitamin B3

Niacinamide

Vitamin B3 is actually not a Vitamin (as it can be made in the body from Tryptophan) and usually refers to 3 (or sometimes 4) compounds in food that in the body go on to become NAD (nicotinamide adenine dinucleotide). These dietary compounds are Nicotinic acid (also called Niacin), Nicotinamide (also call Niacinamide), Nictoniamide Riboside (and the amino acid Tryptophan). Vitamin B3 was first discovered as by-product of nicotine and is sometimes just called Niacin.1

Niacinamide may cause flushes which are harmless and may in fact help with sleep. Non-flushing Vitamin B3 products may not be as effective across the board.

Mechanisms of Action

Over 400 enzymes in the body require Vitamin B3. Vitamin B3 is essential to the way your body makes energy from food in the mitochondria and is thus essential to the function of all your cells whether they be skin cells or brain cells.2

In a scientific paper from 1979, Vitamin B3 is described as having a benzodiazepine like action, which may indicate that it has an effect similar to that of the calming neurotransmitter GABA.3 In a case report Vitamin B3 was shown to alleviate anxiety.4

More recently dietary intake of Vitamin B3 is thought to protected against age-related cognitive decline.5 Animal studies indicate that treatment with Vitamin B3 slows cognitive decline by preserving mitochondria and autophagy6 and improved behavior following head injury.7

Efficacy

There are few interventional trials looking at Vitamin B3 directly as a nootropic.

However there is some indication that Vitamin B3 is useful in diverse neurological conditions such as Tinnitus, Migraine and Multiple Sclerosis,8 as well as in certain psychiatric conditions such as Bipolar Disorder,9 anxiety4 and depression.10

Safety

The main side effects of Vitamin B3 are flushing and redness of the skin that may be mistaken for an allergic reaction. The extended-release forms of Vitamin B3 may be associated with liver problems. This form is not used in Omic products. In very high doses (1000-3000mg / day), Vitamin B3 can cause low blood pressure, insulin resistance and gastric upset.11

References

1. Makarov, M.V., Trammell, S.A.J. & Migaud, M.E. The chemistry of the vitamin B3 metabolome. Biochem Soc Trans 47, 131-147 (2019).

2. Jacobson, M.K. & Jacobson, E.L. Vitamin B3 in Health and Disease: Toward the Second Century of Discovery. Methods Mol Biol 1813, 3-8 (2018).

3. Möhler, H., Polc, P., Cumin, R., Pieri, L. & Kettler, R. Nicotinamide is a brain constituent with benzodiazepine-like action. Nature 278, 563-565 (1979).

4. Prousky, J. Niacinamide’s potent role in alleviating anxiety with its benzodiazepine-like properties: A case report. Journal of Orthomoleculular Medicine 19, 104-110 (2004).

5. Morris, M.C., et al. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline. J Neurol Neurosurg Psychiatry 75, 1093-1099 (2004).

6. Liu, D., et al. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol Aging 34, 1564-1580 (2013).

7. Hoane, M.R., Akstulewicz, S.L. & Toppen, J. Treatment with vitamin B3 improves functional recovery and reduces GFAP expression following traumatic brain injury in rats. J Neurotrauma 20, 1189-1199 (2003).

8. Prousky, J. Efficacy of Vitamin B 3 and Its Related Coenzymes for the Treatment of Bell’s Palsy, Huntington’s Disease, Migraine and Chronic Tension-Type Headaches, Multiple Sclerosis, Parkinson’s Disease, and Tinnitus. Journal of Orthomolecular Medicine 27, 69-86 (2012).

9. Jonsson, B.H. Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II Disorder: A Case of Vitamin Dependency. Nutrients 10(2018).

10. Tonge, W.L. Nicotinic acid in the treatment of depression. Ann Intern Med 38, 551-553 (1953).

11. Niacin. in NI National Institutes of Health Office of Dietary Supplements (NIH, 2020).

Vitamin K2

Vitamin K1 is known as a blood coagulator and there is cross-over in the effects of Vitamin K1 and K2. Vitamin K1 is found in green leafy plants and is recycled in the body. Vitamin K2 is made in the human gut from bacteria and is also obtained from meats, eggs and cheese.1 Vitamin K2 comes in various forms from MK-1 to MK-14. MK-4 and MK-7 are the most common.

Mechanisms of Action

Vitamin K2 is essential in the brain where it is involved in2

  • Sphingolipids, fats that are major components of cells especially in the brain
  • Improving the health of the blood vessels in the bran
  • Improving nerve growth
  • Increasing anti-oxidants
  • Supporting proteins that are neuroprotective and anti-inflammatory in the brain

Animal studies have indicated that

  • Vitamin K2 decreases anxiety and depression in rats with pre-diabetes3
  • Rats with Vitamin K deficiency exhibit general malaise and a lack of exploratory behavior4
  • Vitamin K2 may be able to treat cognitive impairment due to anesthetic5

Efficacy

While interventional trials are lacking, population studies have indicated that:

  • Low Vitamin K intake is lower in elderly with Alzheimer’s disease.6
  • Higher Vitamin K levels are associated with better verbal memory performances7 and overall cognition8

Safety

Vitamin K2 is generally well tolerated with occasional mild gastric upset resorted. However, individuals on blood thinners should consult with their medical practitioner before commencing Vitamin K2 supplements.1

References

1. Salminen, W., Agbaje-Williams, M. & Ajayi, F.O. A Unique Formulation of Cardioprotective Bio-Actives: An Overview of Their Safety Profile. Medicines (Basel) 6(2019).

2. Ferland, G. Vitamin K and brain function. Semin Thromb Hemost 39, 849-855 (2013).

3. Gancheva, S.M. & Zhelyazkova-Savova, M.D. Vitamin K2 Improves Anxiety and Depression but not Cognition in Rats with Metabolic Syndrome: a Role of Blood Glucose? Folia Med (Plovdiv) 58, 264-272 (2016).

4. Cocchetto, D.M., Miller, D.B., Miller, L.L. & Bjornsson, T.D. Behavioral perturbations in the vitamin K-deficient rat. Physiol Behav 34, 727-734 (1985).

5. Miao, H., et al. Anesthetic Isoflurane or Desflurane Plus Surgery Differently Affects Cognitive Function in Alzheimer’s Disease Transgenic Mice. Mol Neurobiol 55, 5623-5638 (2018).

6. Presse, N., Shatenstein, B., Kergoat, M.J. & Ferland, G. Low vitamin K intakes in community-dwelling elders at an early stage of Alzheimer’s disease. J Am Diet Assoc 108, 2095-2099 (2008).

7. Presse, N., et al. Vitamin K status and cognitive function in healthy older adults. Neurobiol Aging 34, 2777-2783 (2013).

8. McCann, A., et al. Exploratory analysis of covariation of microbiota-derived vitamin K and cognition in older adults. Am J Clin Nutr 110, 1404-1415 (2019).

Vitamin D3

Cholecalciferol

Vitamin D, the sunshine Vitamin is made in your skin when the sun ray’s come into contact with cholesterol-like molecules in the skin-cells. We hope you are getting outdoors without screen!

Small amounts of Vitamin D can also be obtained from food such as fatty fish (salmon, mackerel), beef liver, cheese, egg yolks and mushrooms.

Mechanisms of Action

Vitamin D is involved throughout the body and brain, affecting everything from bone health, to immunity, heart health, insulin secretion and is important in the synthesis and modulation of neurotransmitters such as Acetylcholine (learning and memory), Dopamine (learning, attention and reward) and Serotonin (mood).1

Vitamin also exhibits neuroprotective effects possibly via supporting brain detoxification pathways.2 Vitamin D and its receptors in the brain are pivotal to learning and memory.3

Low Vitamin D is associated with depression4 and lower cognitive performance.5

Animal studies indicate that Vitamin D supplementation may decrease age-related memory impairment via it’s anti-inflammatory actions.6

Efficacy

Research on the effects of Vitamin D supplementation to improve cognition are mixed.7 However, Vitamin D may be useful in the treatment of depression,8 as well as improving cognitive function in ADHD.9 Vitamin D supplementation may also improve higher level cognitive functioning such as visual memory.10

Safety

It is generally recommended that Vitamin D intake is kept below 4000iu / 100mcg daily.11

References

1. Naumović, N. [Vitamin D–physiological importance]. Med Pregl 63, 301-304 (2010).

2. Wrzosek, M., et al. Vitamin D and the central nervous system. Pharmacol Rep 65, 271-278 (2013).

3. Stephenson, A., Mamo, J.C.L., Takechi, R., Hackett, M.J. & Lam, V. Genetic, environmental and biomarker considerations delineating the regulatory effects of vitamin D on central nervous system function. Br J Nutr, 1-38 (2019).

4. Anglin, R.E., Samaan, Z., Walter, S.D. & McDonald, S.D. Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry 202, 100-107 (2013).

5. Wilkins, C.H., Sheline, Y.I., Roe, C.M., Birge, S.J. & Morris, J.C. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry 14, 1032-1040 (2006).

6. Briones, T.L. & Darwish, H. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J Neuroinflammation 9, 244 (2012).

7. Byrn, M.A., Adams, W., Penckofer, S. & Emanuele, M.A. Vitamin D Supplementation and Cognition in People with Type 2 Diabetes: A Randomized Control Trial. J Diabetes Res 2019, 5696391 (2019).

8. Spedding, S. Vitamin D and depression: a systematic review and meta-analysis comparing studies with and without biological flaws. Nutrients 6, 1501-1518 (2014).

9. Elshorbagy, H.H., et al. Impact of Vitamin D Supplementation on Attention-Deficit Hyperactivity Disorder in Children. Ann Pharmacother 52, 623-631 (2018).

10. Pettersen, J.A. Does high dose vitamin D supplementation enhance cognition?: A randomized trial in healthy adults. Exp Gerontol 90, 90-97 (2017).

11. Vitamin D Fact Sheet for Health Professionals. in NIH National Institutes of Health Office of Dietary Supplements (NIH, 2020).

2. Nucleus Beta

Nucleus Beta is designed to be taken as a stack with Nucleus Gamma but can also be taken on it’s own or in fact, with Nucleus Alpha.

  • Further improvement in memory and attention*
  • Enhanced visual processing*
  • Enhanced focus*

Nucleus Beta provides the brain with the building blocks for optimal function: Choline, GABA and Vitamin B3. Add to this the memory boosting and focusing properties of Bacopa and you will be unstoppable.

What you can expect from the Nucleus Alpha, Beta combination…

  • Further boosts to energy levels*
  • Improved memory and attention*
  • Enhanced information processing*
  • Supports brain health*

Bacopa is an ancient herb used to improve cognition and nourish the nervous system, improving spatial learning, visual processing, focus, and attention. Choline L-Bitartrate provides the brain with a source of Choline that the it uses to repair cell membrains and to make Acetylecholine an important neurotransmitter in focus, learning and memory. GABA provides a calm focus for the stress of mental tasks. Vitamin B3 is essential to the function of all cells. It has been used in orthomolecular medicine as a calming agent, improving focus without decreasing cognitive function.

Read more about each ingredient:

Bacopa

Bacopa monnieri aerial parts

Bacopa, a native of India and Australia, also known as Brahmi, has been used in Ayurvedic medicine for centauries as a medical plant that rejuvenates intellect and memory.1 Recent research indicates that Bacopa may improve brain function involved in processing environmental inputs and enhancing learning and memory.2

Constituents & Mechanisms of Action

The main nootropic constituents of Bacopa are thought to be saponins known as bacosides.3 Other compounds include alkaloids, D-mannitol and apigenin.4

Bacopa exhibits multiple mechanisms by which it nourishes neurons, enhancing cognitive function.

One of the more interesting mechanisms is via increasing the number of connections between dendritic neurons in the brain.1 Dendritic neurons have a major role in integrating and processing incoming information,1 basically helping your brain to work better.

Bacopa also works to protect neurons via:

  • anti-oxidant effects5,6
  • supporting the production of Aceytlcholine6 and preventing its breakdown;7 Acetylcholine is pivotal to focus, learning and memory
  • elevating levels of serotonin and dopamine6
  • protecting against neurotoxins such as methylmercury,8 paraquat,9 acrylamide10
  • increasing ATP (energy) in the brain11
  • improving blood flow to the brain12

In animal studies, Bacopa has been shown to improve:

  • spatial learning performance1
  • learning and Memory retention1,13
  • mood14
  • the response to stress15

Bacopa also displays longevity potential6

Efficacy

Early human trials in healthy volunteers have indicated that Bacopa may decrease anxiety2 and improve:

  • speed of visual information processing2
  • rate of learning2
  • memory consolidation2,16 and recall17,18
  • Decreases anxiety2
  • working memory7
  • attention and cognitive processing7

Safety

Side effects to Bacopa are rare.4 While long term studies are needed, the most common side effect of Bacopa is mild gastrointestinal upset.2

References

1. Vollala, V.R., Upadhya, S. & Nayak, S. Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats. Clinics (Sao Paulo) 66, 663-671 (2011).

2. Stough, C., et al. The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl) 156, 481-484 (2001).

3. Sivaramakrishna, C., Rao, C.V., Trimurtulu, G., Vanisree, M. & Subbaraju, G.V. Triterpenoid glycosides from Bacopa monnieri. Phytochemistry 66, 2719-2728 (2005).

4. Aguiar, S. & Borowski, T. Neuropharmacological review of the nootropic herb Bacopa monnieri. Rejuvenation Res 16, 313-326 (2013).

5. Anbarasi, K., Vani, G., Balakrishna, K. & Devi, C.S. Effect of bacoside A on brain antioxidant status in cigarette smoke exposed rats. Life Sci 78, 1378-1384 (2006).

6. Rastogi, M., et al. Prevention of age-associated neurodegeneration and promotion of healthy brain ageing in female Wistar rats by long term use of bacosides. Biogerontology 13, 183-195 (2012).

7. Peth-Nui, T., et al. Effects of 12-Week Bacopa monnieri Consumption on Attention, Cognitive Processing, Working Memory, and Functions of Both Cholinergic and Monoaminergic Systems in Healthy Elderly Volunteers. Evid Based Complement Alternat Med 2012, 606424 (2012).

8. Sumathi, T., Shobana, C., Christinal, J. & Anusha, C. Protective effect of Bacopa monniera on methyl mercury-induced oxidative stress in cerebellum of rats. Cell Mol Neurobiol 32, 979-987 (2012).

9. Singh, M., Murthy, V. & Ramassamy, C. Standardized extracts of Bacopa monniera protect against MPP+- and paraquat-induced toxicity by modulating mitochondrial activities, proteasomal functions, and redox pathways. Toxicol Sci 125, 219-232 (2012).

10. Shinomol, G.K., Raghunath, N., Bharath, M.M. & Muralidhara. Prophylaxis with Bacopa monnieri attenuates acrylamide induced neurotoxicity and oxidative damage via elevated antioxidant function. Cent Nerv Syst Agents Med Chem 13, 3-12 (2013).

11. Liu, X., et al. Neuroprotective effects of bacopaside I in ischemic brain injury. Restor Neurol Neurosci 31, 109-123 (2013).

12. Kamkaew, N., Norman Scholfield, C., Ingkaninan, K., Taepavarapruk, N. & Chootip, K. Bacopa monnieri increases cerebral blood flow in rat independent of blood pressure. Phytother Res 27, 135-138 (2013).

13. Singh, H.K. & Dhawan, B.N. Effect of Bacopa monniera Linn. (brahmi) extract on avoidance responses in rat. J Ethnopharmacol 5, 205-214 (1982).

14. Sairam, K., Dorababu, M., Goel, R.K. & Bhattacharya, S.K. Antidepressant activity of standardized extract of Bacopa monniera in experimental models of depression in rats. Phytomedicine : international journal of phytotherapy and phytopharmacology 9, 207-211 (2002).

15. Sheikh, N., et al. Effect of Bacopa monniera on stress induced changes in plasma corticosterone and brain monoamines in rats. J Ethnopharmacol 111, 671-676 (2007).

16. Morgan, A. & Stevens, J. Does Bacopa monnieri improve memory performance in older persons? Results of a randomized, placebo-controlled, double-blind trial. J Altern Complement Med 16, 753-759 (2010).

17. Pase, M.P., et al. The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. J Altern Complement Med 18, 647-652 (2012).

18. Neale, C., Camfield, D., Reay, J., Stough, C. & Scholey, A. Cognitive effects of two nutraceuticals Ginseng and Bacopa benchmarked against modafinil: a review and comparison of effect sizes. Br J Clin Pharmacol 75, 728-737 (2013).

Choline

Choline Bitartrate is a precursor to choline that is essential to many functions in the body.

Choline is an essential dietary nutrient that is obtained mainly from beef, eggs, salmon, and almonds.1 While the body makes a small amount of choline, this is not sufficient for its needs.

Mechanisms of Action

Choline is used in the body:

  • To produce Acetylcholine (a critical neurotransmitter required for focus, learning and memory)1
  • As part of cell membranes, which are critical to cell functioning2
  • As part of the membrane sheath around neurons3 which is crucial to their functioning
  • To produce betaine, a methyl donor1 central to methylation
    • Methylation is involved in everything from the formation of neurotransmitters (including Dopamine and Serotonin) to the repair of DNA, immune function, energy production and detoxification.4 Optimal methylation is crucial in gene expression, the so-called turning on and off of genes.5

So, choline is pretty much involved in almost all functions of the body.

Choline is well known to be essential for the brain development in the developing fetus. It is now also considered a neuro-protectant in adults and is essential for staving off cognitive decline.5 Choline is important in memory, learning and cognitive function.

Deficiency of choline is strongly associated fatty infiltration of the liver and cognitive decline.6

Animal studies have indicated that supplementation with choline:

  • Significantly reduced the brain changes that lead to Alzheimer’s disease7
  • Improved spatial7 and recognition memory8
  • Improved brain pasticity9
  • Improved cognitive and motor performance10

Efficacy

Human studies have shown

  • Improved cognitive function of Choline combined with Ginkgo11 (both in the Nucleus stack)
  • Improvement in Motor Speed and Attention12 after 28 days of supplementation but not after a single dose.2
  • Higher choline intake is associated with better cognitive performance13

While interventional trials have not yet been done, it is suggested that supplementing with Choline alongside a nootropic such as Bacopa or Aniracetam will have synergistic effects.

Safety

Choline is considered safe in doses up to 3500mg daily.14 Occasional mild side effects such as an upset stomach15 and a fish odor have been reported.16

References

1. Wiedeman, A.M., et al. Dietary Choline Intake: Current State of Knowledge Across the Life Cycle. Nutrients 10(2018).

2. Lippelt, D.P., van der Kint, S., van Herk, K. & Naber, M. No Acute Effects of Choline Bitartrate Food Supplements on Memory in Healthy, Young, Human Adults. PloS one 11, e0157714 (2016).

3. Skripuletz, T., et al. Pivotal role of choline metabolites in remyelination. Brain 138, 398-413 (2015).

4. Yasko, A. Autism: Pathways to Recovery, (Neurological Research Institute, 2009).

5. Bekdash, R.A. Neuroprotective Effects of Choline and Other Methyl Donors. Nutrients 11(2019).

6. Zeisel, S.H., Klatt, K.C. & Caudill, M.A. Choline. Adv Nutr 9, 58-60 (2018).

7. Velazquez, R., et al. Lifelong choline supplementation ameliorates Alzheimer’s disease pathology and associated cognitive deficits by attenuating microglia activation. Aging Cell 18, e13037 (2019).

8. Moreno, H., Hall, G., Gallo, M. & de Brugada, I. Dietary choline supplementation in adult rats improves performance on a test of recognition memory. Behav Brain Res 353, 210-217 (2018).

9. Jadavji, N.M., Emmerson, J.T., MacFarlane, A.J., Willmore, W.G. & Smith, P.D. B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke. Neurobiol Dis 103, 89-100 (2017).

10. Tabassum, S., Haider, S., Ahmad, S., Madiha, S. & Parveen, T. Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats. Pharmacol Biochem Behav 159, 90-99 (2017).

11. Lewis, J.E., et al. A double-blind, randomized clinical trial of dietary supplementation on cognitive and immune functioning in healthy older adults. BMC Complement Altern Med 14, 43 (2014).

12. McGlade, E., et al. The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males. J Atten Disord 23, 121-134 (2019).

13. Poly, C., et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr 94, 1584-1591 (2011).

14. Yates, A.A., Schlicker, S.A. & Suitor, C.W. Dietary Reference Intakes: the new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 98, 699-706 (1998).

15. Mehta, A.K., Singh, B.P., Arora, N. & Gaur, S.N. Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma. Immunobiology 215, 527-534 (2010).

16. Wozniak, J.R., et al. Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability. Nutrition research (New York, N.Y.) 33, 897-904 (2013).

GABA

Gamma-aminobutyric acid

GABA is a (non-protein forming) amino acid found throughout the body. Most of the research has been done on GABA’s functions in the brain and the pancreas.1 In the brain, GABA is an important neurotransmitter (chemical signal) that is made directly in the neurons from Glutatmate2 and is critical to the functioning of the central nervous system.3

GABA also exists naturally in food such as tea, tomato, soybean,4 and in uncooked spinach.5 More interestingly (for the nerds at Omic anyway), GABA is made by bacteria such as Lactobacillus and Bifidobacterium species in fermented foods6 and in fact, in our own guts7.

Mechanism of Actions

GABA is the main “inhibitory” neurotransmitter in the brain and Glutamate is the main “excitatory” neurotransmitter. These compounds control many of the brain’s processes.2

While inhibition may not sound great, inhibitory processes are essential to optimal brain function.8 In worst case scenarios a lack of inhibition can lead to epilepsy and stiff person syndrome.2 More commonly, too little GABA activity (not enough inhibition) results in anxiety;9 and we all know how difficult it is to concentrate and perform when we are anxious. GABA prevents us from generating inappropriate emotional and behavioral responses to stress. However, stress decreases GABA activity in the brain.10

While the ability of GABA taken orally to cross the blood-brain-barrier has been questioned, emerging research indicates that substantial amounts of GABA may cross the blood-brain-barrier into the brain.11 Furthermore, while research is still early, the GABA in the gut may be able to communicate with the brain via the Vagus nerve.12 Super cool!

GABA decreases the action of norepinephrine13 and is thought to be involved in a large range of behaviors, including confidence, stress regulation and memory enhancement.14

Efficacy

Most trials in humans involve pharmaceuticals, for treatment of anxiety and epilepsy, that attach to the GABA receptors.15 However, early clinical trials using supplemental GABA indicate it is effective in:

  • Improving relaxation16
  • Decreasing anxiety16
  • Enhancing immunity when under stress16
  • Reducing the stress of mental tasks14
  • Improving energy17
  • Improving task-solving ability17
  • Decreasing the negative effects of stress in the body3
  • Lowering blood pressure18

Safety

GABA is accepted as safe when used as a supplement.16

References

1. Jewett BE, S.S. Physiology, GABA. in StatPearls (StatPearls [Internet], Treasure Island, Florida, 2020).

2. Hampe, C., Mitoma, H. & Manto, M. GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets. (2018).

3. Hepsomali, P., Groeger, J.A., Nishihira, J. & Scholey, A. Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Front Neurosci 14, 923 (2020).

4. Diana, M., Quílez, J. & Rafecas, M. Gamma-aminobutyric acid as a bioactive compound in foods: a review. Journal of Functional Foods 10, 407-420 (2014).

5. Oh, S.-H., Moon, Y.-J. & Oh, C.-H. γ -Aminobutyric Acid (GABA) Content of Selected Uncooked Foods. Preventive Nutrition and Food Science 8(2003).

6. Boonstra, E., et al. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol 6, 1520 (2015).

7. Duranti, S., et al. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABA. Sci Rep 10, 14112 (2020).

8. Cuypers, K., Maes, C. & Swinnen, S.P. Aging and GABA. Aging (Albany NY) 10, 1186-1187 (2018).

9. Nemeroff, C.B. The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull 37, 133-146 (2003).

10. Jie, F., et al. Stress in Regulation of GABA Amygdala System and Relevance to Neuropsychiatric Diseases. Front Neurosci 12, 562 (2018).

11. Takanaga, H., Ohtsuki, S., Hosoya, K. & Terasaki, T. GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier. J Cereb Blood Flow Metab 21, 1232-1239 (2001).

12. Schmidt, C. Mental health: thinking from the gut. Nature 518, S12-15 (2015).

13. Hayakawa, K., Kimura, M. & Kamata, K. Mechanism underlying γ-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats. European journal of pharmacology 438, 107-113 (2002).

14. Yoto, A., et al. Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. Amino Acids 43, 1331-1337 (2012).

15. Rashmi, D., Zanan, R., John, S., Khandagale, K. & Nadaf, A. Chapter 13 – γ-Aminobutyric Acid (GABA): Biosynthesis, Role, Commercial Production, and Applications. in Studies in Natural Products Chemistry, Vol. 57 (ed. Atta ur, R.) 413-452 (Elsevier, 2018).

16. Abdou, A.M., et al. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors 26, 201-208 (2006).

17. Kanehira, T., et al. Relieving occupational fatigue by consumption of a beverage containing γ-amino butyric acid. J Nutr Sci Vitaminol (Tokyo) 57, 9-15 (2011).

18. Nishimura, M., et al. Effects of white rice containing enriched gamma-aminobutyric acid on blood pressure. Journal of Traditional and Complementary Medicine 6, 66-71 (2016).

Vitamin B3

Niacinamide

Vitamin B3 is actually not a Vitamin (as it can be made in the body from Tryptophan) and usually refers to 3 (or sometimes 4) compounds in food that in the body go on to become NAD (nicotinamide adenine dinucleotide). These dietary compounds are Nicotinic acid (also called Niacin), Nicotinamide (also call Niacinamide), Nictoniamide Riboside (and the amino acid Tryptophan). Vitamin B3 was first discovered as by-product of nicotine and is sometimes just called Niacin.1

Niacinamide may cause flushes which are harmless and may in fact help with sleep. Non-flushing Vitamin B3 products may not be as effective across the board.

Mechanisms of Action

Over 400 enzymes in the body require Vitamin B3. Vitamin B3 is essential to the way your body makes energy from food in the mitochondria and is thus essential to the function of all your cells whether they be skin cells or brain cells.2

In a scientific paper from 1979, Vitamin B3 is described as having a benzodiazepine like action, which may indicate that it has an effect similar to that of the calming neurotransmitter GABA.3 In a case report Vitamin B3 was shown to alleviate anxiety.4

More recently dietary intake of Vitamin B3 is thought to protected against age-related cognitive decline.5 Animal studies indicate that treatment with Vitamin B3 slows cognitive decline by preserving mitochondria and autophagy6 and improved behavior following head injury.7

Efficacy

There are few interventional trials looking at Vitamin B3 directly as a nootropic.

However there is some indication that Vitamin B3 is useful in diverse neurological conditions such as Tinnitus, Migraine and Multiple Sclerosis,8 as well as in certain psychiatric conditions such as Bipolar Disorder,9 anxiety4 and depression.10

Safety

The main side effects of Vitamin B3 are flushing and redness of the skin that may be mistaken for an allergic reaction. The extended-release forms of Vitamin B3 may be associated with liver problems. This form is not used in Omic products. In very high doses (1000-3000mg / day), Vitamin B3 can cause low blood pressure, insulin resistance and gastric upset.11

References

1. Makarov, M.V., Trammell, S.A.J. & Migaud, M.E. The chemistry of the vitamin B3 metabolome. Biochem Soc Trans 47, 131-147 (2019).

2. Jacobson, M.K. & Jacobson, E.L. Vitamin B3 in Health and Disease: Toward the Second Century of Discovery. Methods Mol Biol 1813, 3-8 (2018).

3. Möhler, H., Polc, P., Cumin, R., Pieri, L. & Kettler, R. Nicotinamide is a brain constituent with benzodiazepine-like action. Nature 278, 563-565 (1979).

4. Prousky, J. Niacinamide’s potent role in alleviating anxiety with its benzodiazepine-like properties: A case report. Journal of Orthomoleculular Medicine 19, 104-110 (2004).

5. Morris, M.C., et al. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline. J Neurol Neurosurg Psychiatry 75, 1093-1099 (2004).

6. Liu, D., et al. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol Aging 34, 1564-1580 (2013).

7. Hoane, M.R., Akstulewicz, S.L. & Toppen, J. Treatment with vitamin B3 improves functional recovery and reduces GFAP expression following traumatic brain injury in rats. J Neurotrauma 20, 1189-1199 (2003).

8. Prousky, J. Efficacy of Vitamin B 3 and Its Related Coenzymes for the Treatment of Bell’s Palsy, Huntington’s Disease, Migraine and Chronic Tension-Type Headaches, Multiple Sclerosis, Parkinson’s Disease, and Tinnitus. Journal of Orthomolecular Medicine 27, 69-86 (2012).

9. Jonsson, B.H. Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II Disorder: A Case of Vitamin Dependency. Nutrients 10(2018).

10. Tonge, W.L. Nicotinic acid in the treatment of depression. Ann Intern Med 38, 551-553 (1953).

11. Niacin. in NI National Institutes of Health Office of Dietary Supplements (NIH, 2020).

3. Nucleus Gamma

Nucleus Gamma is a very powerful nootropic that we stack with Nucleus Beta. It can however also be stacked with Nucleus Alpha, to bring your performance to the very highest level! Focus longer, be sharper and feel happier and confident.*

Aniracetam belongs to a class of pharmaceuticals known as Racetams. The first Racetam, Piracetam was developed in the late 1960s. A number of other Racetams followed with Aniracetam being launched by Roche in 1993. It is thought that Aniracetam modulates neurotransmitters, supporting memory, the learning of abstract concepts, vision and creativity.

  • Sharpens memory*
  • Increases focus and alertness*
  • Supports healthy mood*
  • May improve cognitive health*
  • Improves learning

Read more about the ingredient:

Aniracetam

Aniracetam belongs to a class of pharmaceuticals known as Racetams. The first Racetam, Piracetam was developed in the late 1960s. A number of other Racetams followed with Aniracetam being launched by Roche in 1993.1 Aniracetam is available in the US without a prescription but is not approved by the FDA for the treatment of any medical condition.

Racetams are modulators of brain function that are used to improve memory and cognitive function, treat epilepsy, and neuro-degenerative disorders such as Alzheimer’s disease and to decrease stress and anxiety.2

Mechanisms of Action

The Racetam class of drugs all share a pyrrolidone ring (see above).

The Racetams exhibit overlapping modes of actions and effects.2 However, the way the Racetams work have still not been elucidated. A number of theories exist, with the majority of research has been done on Piracetam.

The Racetams appear to positively affect the levels of neurotransmitters in the brain possibly by changing the electrical charge across neurons,3 or by enhancing the production of proteins in the brain.4 In particular the Acetylcholine1 and Glutamate5,6 systems are thought to be involved.

Other mechanisms that may also be involved are:

  • Increasing oxygen utilization in the brain for energy7
  • A GABA like action, improving calm focus8
  • An anti-oxidant effect, protecting neurons from damage9
  • Increasing Acetylcholine receptors and supporting the Cholinergic system, 10,11 which is central to learning and memory.1
  • Positively modulating the Dopamine and Serotonin systems12

Animal studies are conflicting, with some studies showing no effect,13 while other studies indicating that Aniracetam may be useful to

  • Increase attention and vigilance14
  • Improve motivation15
  • Decrease depression16 and anxiety17
  • Improve learning and memory18

Efficacy

While the Racetams have shown a clinical effect, due to the difficulty of working out a mechanism of action, combined with lack of side-effects, research has paradoxically petered out.1

However, there are some human trials indicating that Aniracetam may be helpful in:

  • The treatment of Alzheimer’s disease19
  • Mitigating mild cognitive decline20,21

Despite the paucity of clinical trials, Aniracetam has been described as having a “well-known effect on learning and memory.”22 Furthermore, Aniracetam has been suggested as a treatment for the inattention, hyperactivity and impulsivity seen in ADHD, as well as the associated anxiety and depression.12

Safety

The Racetams are generally well tolerated with few side-effects although long term effects of use have not been explored.1,2 The Racetams do not appear to be habit forming.23

References

1. Gualtieri, F., Manetti, D., Romanelli, M.N. & Ghelardini, C. Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs. Curr Pharm Des 8, 125-138 (2002).

2. Malykh, A.G. & Sadaie, M.R. Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. Drugs 70, 287-312 (2010).

3. Gouliaev, A.H. & Senning, A. Piracetam and other structurally related nootropics. Brain Res Brain Res Rev 19, 180-222 (1994).

4. Lucchi, L., Pascale, A., Battaini, F., Govoni, S. & Trabucchi, M. Cognition stimulating drugs modulate protein kinase C activity in cerebral cortex and hippocampus of adult rats. Life Sci 53, 1821-1832 (1993).

5. Pittaluga, A., et al. Activity of putative cognition enhancers in kynurenate test performed with human neocortex slices. J Pharmacol Exp Ther 290, 423-428 (1999).

6. Copani, A., et al. Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures. J Neurochem 58, 1199-1204 (1992).

7. Grau, M., Montero, J.L. & Balasch, J. Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat. Gen Pharmacol 18, 205-211 (1987).

8. Wischer, S., Paulus, W., Sommer, M. & Tergau, F. Piracetam affects facilitatory I-wave interaction in the human motor cortex. Clin Neurophysiol 112, 275-279 (2001).

9. Horvath, B., et al. In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine. Clin Neuropharmacol 25, 37-42 (2002).

10. Pepeu, G. & Spignoli, G. Nootropic drugs and brain cholinergic mechanisms. Prog Neuropsychopharmacol Biol Psychiatry 13 Suppl, S77-88 (1989).

11. Mondadori, C. In search of the mechanism of action of the nootropics: new insights and potential clinical implications. Life Sci 55, 2171-2178 (1994).

12. Nakamura, K. Aniracetam: its novel therapeutic potential in cerebral dysfunctional disorders based on recent pharmacological discoveries. CNS Drug Rev 8, 70-89 (2002).

13. Elston, T.W., et al. Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice. PloS one 9, e104443 (2014).

14. Nakamura, K. & Kurasawa, M. Serotonergic mechanisms involved in the attentional and vigilance task performance of rats and the palliative action of aniracetam. Naunyn Schmiedebergs Arch Pharmacol 361, 521-528 (2000).

15. Nakamura, K. & Kurasawa, M. Aniracetam restores motivation reduced by satiation in a choice reaction task in aged rats. Pharmacol Biochem Behav 68, 65-69 (2001).

16. Nakamura, K. & Tanaka, Y. Antidepressant-like effects of aniracetam in aged rats and its mode of action. Psychopharmacology (Berl) 158, 205-212 (2001).

17. Nakamura, K. & Kurasawa, M. Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. European journal of pharmacology 420, 33-43 (2001).

18. Cumin, R., Bandle, E.F., Gamzu, E. & Haefely, W.E. Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents. Psychopharmacology (Berl) 78, 104-111 (1982).

19. Senin, U., et al. Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study. Eur Neuropsychopharmacol 1, 511-517 (1991).

20. Canonico, V., et al. [Efficacy and tolerance of aniracetam in elderly patients with primary or secondary mental deterioration]. Riv Neurol 61, 92-96 (1991).

21. Koliaki, C.C., Messini, C. & Tsolaki, M. Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study. CNS Neurosci Ther 18, 302-312 (2012).

22. Galeotti, N., Ghelardini, C. & Bartolini, A. Piracetam and aniracetam antagonism of centrally active drug-induced antinociception. Pharmacology, biochemistry, and behavior 53, 943-950 (1996).

23. Coper, H. & Herrmann, W.M. Psychostimulants, analeptics, nootropics: an attempt to differentiate and assess drugs designed for the treatment of impaired brain functions. Pharmacopsychiatry 21, 211-217 (1988).

Leave a Reply

Your email address will not be published.Required fields are marked *

Wishlist 0
Open wishlist page Continue shopping