Introduction: What Are Nootropics?
One of the fastest growing categories of supplements in the market today, both sports nutrition and general use is that of nootropics. ‘Brain boosters’, if you will, nootropics is an umbrella term used to classify a wide category of chemicals, both natural and synthetic, that provide positive cognitive benefits to the human brain. The term was coined by a Roman psychologist, Dr. Corneliu E. Guirgea, who is considered the father of nootropics and godfather of brain pharmacology. The word nootropics originates from the Greek word noos (mind) and tropein (towards) (1).
His formal description of the category states that “Nootropics are drugs which ameliorate the functional “plasticity” of the central nervous system. The nootropic drug acts at the telencephalic level through a series of bioenergetic, hemorheological, microcirculatory and neurochemical mechanisms. As to this, recent data show a facilitation by piracetam, of the efficiency of the central cholinergic system.” (2) He is most famous for being the first to synthesize what is considered the first man-made nootropic, Piracetam in 1964 (3). To summarize Dr. Guirgea’s definition of what classifies a substance as a nootropic, it must meet the following criteria:
- Possess little to no side-effects and be non-toxic
- Protect the brain from chemical and physical assaults
- Increase the efficacy and efficiency of neuronal firing control mechanisms
- Enhance memory and the ability to learn
- Help the brain function under disruptive conditions
While the above list is a pretty stringent classification standard for any substance, the term nootropic has been used more loosely in today’s world, often describing any substance that offers a cognitive benefit. These more loosely defined substances are ones that do such things as improve concentration, increase processing speed and improve memory.
Legality: Who Regulates Nootropics?
As you can imagine, both natural and synthetic nootropics have gained popularity and for good reason. There are some that are perfectly fine for over the counter sale and use, while some aren’t allowed to be sold as dietary supplements. This is often considered a gray area as there is no single governing body that holds an identical definition of what a constitutes an approved nootropic. A vast majority of governing bodies consider nootropics dietary supplements.
The fine line comes when they are synthetically produced at which point you must consider: Is the nootropic controlled which requires a prescription or age restriction for purchase, or is it scheduled which means it is ranked by its risk for abuse. Like most drugs, the schedule of a drug influences the control very closely: The higher the risk, the more control there is over the substance.
With this article, we will examine herbal extract, dietary supplement nootropics, and synthetic/semi-synthetic nootropics and see what the research says.
When we are referring to synthetic nootropics, we are talking about a category known as racetams which is a category of nootropic that works by prevents the degradation and increases production of the neurotransmitter acetylcholine. Some racetams work to improve the functionality of acetylcholine receptors while other variations adjust the production to scale up or lastly can prevent the breakdown of acetylcholine. This is important as acetylcholine is vital for everything including decision making, focus, memory, and other cognitive based effects (4). Unfortunately, many of these are considered to be drugs and therefore cannot be purchased OTC or as supplements. However, in some markets they can be purchased as research chemicals.
Regarded as the first nootropic drug to be invented by Dr. Guirgea, Piracetam continues to be a very popular choice for those that utilize nootropics and is often viewed as a ‘beginner’ nootropic for those new to experimenting with such a drug. Also known as Nootropyl or UCB6215, it works via stimulation of acetylcholine receptors, increasing their production. Research has also revealed that it increases glucose and oxygen consumption in the brain which precedes cognitive improvement (4).
One of the most thoroughly studied racetams, Piracetam has been shown that in young and otherwise healthy adults to provide cognitive enhancement, though the benefits are greater and more pronounced in populations which may have cognitive impairment such as aging (5). Also promising is that research seems indicative that Piracetam can help improve cognitive function in those with degenerative cognitive function (6). As a whole, with the real-world trials and research available, Piracetam is considered to generally be more of a preventative mechanism for reducing cognitive aging vs. a short-term agent for improving immediate cognitive enhancement. The recommended daily dosage is 800mg, three times a day. The half-life is approximately 5 hours following oral on intravenous administration with the half-life in cerebrospinal fluid lasting around 8.5 hours (7).
Synthesized from the parent nootropic Piracetam, this compound has modifications within the similar structure. First synthesized in 1984, the primary purpose would be best suited for anti-amnesiac properties. There isn’t a large body of evidence available for its efficacy, especially in humans, however, the potential reported benefits include improved cognitive ability for those with brain trauma and improvement in memory formation in elderly populations (8). The ideal scenario for dosing is 400mg three times a day or 600mg twice a day.
Perhaps the most closely related member of the racetam family to Piracetam, Phenylpiracetam is Piracetam with an additional phenyl group added to its structure. Also known as Phenotropil and Carphedon, this synthetic nootropic is rapidly and well absorbed via its enhanced lipophilicity. Compared to the parent drug Piracetam, it has an enhanced anti-amnesiac and neuroprotective effect (9).
Like something out of the 1980’s Rocky IV movie, there is a relatively large body of research on Phenylpiracetam in Russia, but unfortunately most of it isn’t published online for use outside of the country. From these studies, it is said that there is strong evidence for attenuating and treating cognitive decline. Aside from the neuroprotective effects, there is published data for Phenylpiracetam having an apparent anti-depression mechanism as well as psychostimulatory properties that inhibit sleep (10) (11). General dosing guidelines suggest that 100mg a day are adequate as it is relatively conservative in the dosing needed. Users can increase usage with experience.
A fat-soluble nootropic that needs to be ingested with fatty acids, Aniracetam is a cholergenic compound. Yet another stemming from Piracetam, it is the Piracetam molecule with an amine replaced with a methylated phenyl group. Its mechanism of action is that of a positive modulator of AMPA receptors (12). It has a prolonged, yet controlled effect of neurological stimulation and can decrease the rate of receptor desensitization. It is considered to be 5 times stronger than the parent Piracetam, however it takes significantly longer to break down completely in the body with the tradeoff of being longer lasting in effect.
There appears to be a neuroprotective effect from Aniracetam as research has shown it can help alleviate memory and learning impairment caused by damage such as blunt trauma and cerebral ischemia (13). Regarding learning in general, there has also been a specific effect in receptor desensitization, translating to potential benefit in memory formation (14). There is also a notable increase in judgment due to a significant increase in dopamine and serotonin which also doubles as an anti-depressant (15). Typical recommended dosage is 750mg up to three times a day. It has a short half-life of around 2 hours so it is ideally consumed on an evenly spaced basis (16).
Last but not least, stemming also from Piracetam is Oxiracetam. It is structurally similar to Piracetam featuring the same structure with the inclusion of a single hydroxyl group (17). Oxiracetam is known as a GABA analog that supports phospholipid metabolism as well as influencing a positive modulation of AMPA receptors and helps influence neurotransmitter release, very similar but markedly more potently than its parent compound Piracetam (18).
Oxiracetam is similar to the effect of Aniracetam in that it appears to increase long-term potentiation of acetylcholine release while not modifying the resting acetylcholine concentrations in the brain (19) (20). When it comes to memory formation, the data is positive but considered unreliable, however, it has a more pronounced effect in regard to having anti-amnesiac properties (21) (22). Psychostimulatory properties have been noted with Oxiracetam use, however to a small degree and there is no negative impact on sleep quality, though it can increase the time required to fall asleep (23).
In summation, there is an apparent implication for increasing memory in otherwise healthy subjects, though it appears there is a 5-day loading period required for maximum efficacy (24). Perhaps the wisest range of recommended dosing, the range can go from 700mg a day all the way to 2,400mg, taken at 6-hour intervals. It is best dosed approximately an hour before desired effects. The half-life is approximately 8 hours in healthy individuals with a huge range of 10-68 hours in individuals with renal dysfunction (25).
Which Synthetic Nootropic is Best?
There are potential benefits to each of the racetams listed above. Each is good in its own respect, so the best approach is to evaluate what you are trying to achieve and use trial an error with the given dosage guidelines to see what works for you. As with any substance, everyone has a unique biochemistry, so there is no cookie-cutter approach for which is ‘best’.
Dietary Supplement/Herbal Nootropics
Now that we’ve covered the various synthetic versions of nootropics, let’s examine the more natural side of things that are available over the counter for use as a dietary supplement. As with the synthetic nootropics we just discussed, you should select natural nootropics based on what you are trying to achieve, and the best method is to try them out and see what works best for your individual biochemistry. With that being said, let’s examine some of the most popular ‘nootropic’ supplements:
A compound found naturally in plants such as Club Moss, Huperzine A is a very common nootropic. Commonly altered to create the nootropic form, it has been regarded as a premier cognitive enhancer due to the high purity of the substance it produces. It is known for its action as an acetylcholinesterase inhibitor (26). It also has properties for neuroprotection and can block NMDA receptor without the negative side effects of other such compounds (27). In a simple summary of effects, it inhibits enzymes that degrade neurotransmitters and is being researched as a potential compound for reducing cognitive decline in elderly populations. Standard dosing is 50-200mcg per day and has a half-life of 10-14 hours (28).
Bacopa leaf extract, also commonly listed as Bacopa monnieri is a creeping marsh plant and regarded as an Ayurvedic herb that has been used primarily for neurological regeneration, memory enhancement and anxiety (29). It has also been used in traditional medicine for depression, learning, various neuropharmacological disorders (30). Bacopa monnieri also possesses properties of anti-inflammatory, antipyretic and acts as an astringent (31). There appear to be up to 14 compounds found within this extract with them being generally referred to simply as Bacoside A & B at up to 8% of the dry leaf content (32).
Bacopa monnieri has a variety of promising applications supported in literature, and one of the main mechanisms of action being the interaction with dopamine and serotonergic systems and neuron communication via the increased growth of dendrites (33). Supplementation has shown to improve overall mental cognition in subjects by way of reduced anxiety and is often used for nootropic purposes (34). In regard to dosage, the standard dosage in literature is 300mg with an assumed bacoside content of 55% or higher and it should be consumed with a lipoid transporter as it is fat soluble (35).
A naturally occurring cholinergic compound alpha-glycerphosphocholine, known as Alpha-GPC for short. Classified as a choline-containing phospholipid and an intermediate of lecithin metabolism or simply a lecithin molecule with two less fatty acids, it’s a choline pro-drug, and is known to be a precursor to acetylcholine and phosphatidylcholine in the body following ingestion (36). Alpha-GPC is as a naturally occurring constituent of red meat and organ tissue for dietary sources, but for the most part is scarce in appreciable amounts in naturally occurring sources (37). Supplemental Alpha-GPC is typically made synthetically through enzymatic creation via egg or soy lecithin (38).
Alpha-GPC has been shown in research studies to have a variety of positive effects. Brain detoxification is one potential benefit as various studies have supported this with improvement in cognitive deficits (39), decreases in mental fatigue and reduction in metabolic stress of exercise (40). Alpha-GPC has also been shown to support healthy brain aging as various studies have supported findings that deterioration was less in groups supplemented with Alpha-GPC (41), therapeutic benefits in recovery from stroke (42), and significant improvements in most neuropsychological parameters tested (43). Lastly from a performance perspective, Alpha-GPC has the potential to increase growth hormone output, however there is currently only a single study so this area of research interest is considered ongoing (44). Recommended dosage is 600mg at bare minimum with the research supporting cognitive benefits coming at 1200mg.
Choline Bitartrate is the salt form of choline with bitartrate being added to stabilize and help with absorption and contains approximately 41% choline by molecular weight (45). Choline is a direct precursor of the neurotransmitter acetylcholine and plays a vital role in the body with aiding in nerve signaling, cell membrane maintenance, triglyceride transportation from the liver as the primary sports nutrition purpose of a neurotransmitter vital to nerve and muscle function and normal liver metabolism (46). Though there is no conclusive evidence for supplementation of choline bitartrate as research is still being conducted, there has been a wide array of potential benefits hypothesized from supplementation, stemming from having additional choline available to act as a neurotransmitter.
Known formally as Yamabushitake, Lion’s Mane is a dietary mushroom that has recently emerged as a nootropic supplement. This particular mushroom grows in Japan and China from old or dead broadleaf trees. Ingestion of Lion’s Mane appears to increase nerve growth factor (NGF) levels and secretion (47). An analogue contained within, 3-hydroxyhericenone, has been shown to prevent neuron death induced by stress and to enhance myelination of neurons as well (48). One specific study using 98% pure Lions Mane powder showed significant improvements on a rating scale in individuals with dementia and cognitive decline by increasing cognition relative to control (49). Additionally, there has been noted decreases in anxiety and depressive symptoms with supplementation (50). Based on research, the ‘optimal’ dosage of Lion’s Mane isn’t known, however the studies referenced for cognitive improvements used 1,000mg taken three times per day.
A fat-soluble amino acid, phosphatidylserine is a naturally occurring phospholipid that exists in all species, and comprises a portion of the phospholipid pool. Specifically, it is particularly concentrated in the human brain (15%), lungs (7.4%), testes (6.4%), kidneys (5.7%), liver (3.8%), skeletal muscle (3.3%), heart (3.2%) and blood plasma (0.2%) (51). Phosphatidylserine can be found in soy lecithin, bovine brain, Atlantic mackerel, chicken heart, Atlantic herring and in smaller amounts in chicken leg and liver (52). The first supplemental form of phosphatidylserine was from the bovine cortex, and while this form appears to be superior in the effects of proposed cortisol reduction compared to soy-based supplementation, the source from bovine brain is no longer used due to concerns over Creutzfeldt–Jakob disease (53).
Phosphatidylserine has been shown in research to possess a variety of positive benefits when supplemented. One of the primary positive benefits of phosphatidylserine supplementation is improved mental cognition as well as prevention of cognitive decline with such supporting studies specifically finding that supplementation has been shown to significantly reduce symptoms of Alzheimer’s disease and dementia. These studies also supported a positive increase in global glucose utilization in the brain of up to 14.8% (54). There has also been a documented decrease in exercise-induced cortisol with phosphatidylserine supplementation, though the efficacy of the form derived from soy doesn’t appear to have the same supporting data as the bovine source (55). Dosage is a standard 100mg divided in 3 total doses for the day for preventing cognitive decline.
N-Acetyl Tyrosine is a modified version of the amino acid L-tyrosine. It has the active compound acetic acid added to enhance the bioavailability and absorption as a whole and in theory, increase the supporting functions of tyrosine within the body (56). Tyrosine is an amino acid that is used to produce the catecholamines noradrenaline through the catecholamine pathway. Tyrosine undergoes a series of conversions with the rate-limiting step in the overall process being the enzyme tyrosine hydroxylase (57). Supplementation with tyrosine appears to have anti-stress mechanisms for acute stressors and may also preserve stress-induced memory deficits (58).
Research has shown tyrosine supplementation to effectively improve cognition as well as cause a reduction in blood pressure during acute stress situations (59) (60). There are also marked increases in subjective well-being and improvements in working memory, though the data is inconclusive and research is ongoing for the latter (59) (61).
L-Theanine, known by the technical name r-glutamylethylamide is a nondietary amino acid derived primarily from the natural source of Camellia sinesis. The theanine content of these leaves is approximately 0.9-3.1% of the dry weight of the leaves and said to range from 25-60mg per 200mL serving of tea (2.5g of dried tea leaves) (62). It is structurally similar to glutamine and is known as a relaxation agent without sedation with the proposed mechanism being a reduced perception of stress and slight improvements in attention (63).
Regarded as a relaxation agent without sedation and appears to act via blocking the effects of glutamate in the brain as well as stimulating the production of the inhibitory, relaxing neurotransmitter GABA (64). There is also a marked increase in alpha waves in the frontal and occipital lobes of the brain (65) and has research support in reducing stress perception and improvements in attention (66). Interestingly, there also appears to be a protective measure from theanine supplementation when taken before stressful situations in preventing the elevation of stress hormones and oxidative damage (67). Also of interest is that theanine has been shown in studies to significantly improve nitric oxide production in endothelial cells (68). L-theanine is generally taken in the dosage of 100-200mg per day and is commonly paired with caffeine.
As you can see, there are quite a few ‘natural’ nootropics on the market that have benefits aside from just cognitive enhancement. If you are looking for a cognitive advantage without negative sides you have plenty to pick from and the cool part is there are some other positive effects that can come with their use. On the natural side, this makes it especially true that if you are looking to try a nootropic, don’t just look at the cognitive side, but the other potential benefits.
Suppz Recommended Nootropic Supplements
- The “nootropic” approach to the pharmacology of the integrative activity of the brain. Giurgea, C.2, Apr-Jun 1973, Cond Reflex, Vol. 8, pp. 108-15.
- Nootripic drugs and aging. Giurgea, CE.4, July-Aug 1983, Acta Psychiatr Belg, Vol. 83, pp. 349-58.
- Li, Jie.Drug Discovery: Practices, Processes and Perspectives. s.l. : John Wiley & Sons, 2013.
- Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. Malykh, A.3, February 12, 2010, Drugs, Vol. 70, pp. 287-312.
- Piracetam-induced improvement of mental performance. A controlled study on normally aging individuals. Mindus, P.2, Aug 1976, Acta Psychiatr Scand, Vol. 54, pp. 150-60.
- Clinical efficacy of piracetam in cognitive impairment: a meta-analysis. Waegmans, T.4, 2002, Dement Geriatr Cogn Disord, Vol. 13, pp. 217-24.
- National Center for Biotechnology Information.Piracetam. PubChem Compound Database. [Online] June 13, 2018. https://pubchem.ncbi.nlm.nih.gov/compound/4843. CID=4843.
- Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia. McLean, A.4, Oct-Dec 1991, Brain Inj, Vol. 5, pp. 375-80.
- Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia. Tiurenkov, I.2, Mar-Apr 2007, Eksp Klin Farmakol, Vol. 70, pp. 24-9.
- The phenotropil treatment of the consequences of brain organic lesions. Savchenko, A.12, 2005, Zh Nevrol Psikhiatr Im S S Korsakova, Vol. 105, pp. 22-6.
- Investigation into stereoselective pharmacological activity of phenotropil. Zvejniece, L.5, November 2011, Basic Clin Pharmacol Toxicol, Vol. 109, pp. 407-12.
- Aniracetam. An overview of its pharmacodynamic and pharmacokinetic properties, and a review of its therapeutic potential in senile cognitive disorders. Lee, C.3, March 1994, Drugs Aging, Vol. 4, pp. 257-73.
- Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents. Cumin, R.2, Berlin : s.n., 1982, Psychopharmacology, Vol. 78, pp. 104-11.
- Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam. Ito, L.May 1990, J Physiol, Vol. 424, pp. 533-43.
- Aniracetam enhances cortical dopamine and serotonin release via cholinergic and glutamatergic mechanisms in SHRSP. Shirane, M.1-2, October 19, 2001, Brain Res, Vol. 916, pp. 211-21.
- National Center for Biotechnology Information.Aniracetam. PubChem Compound Database. [Online] June 13, 2018. https://pubchem.ncbi.nlm.nih.gov/compound/2196. CID=2196.
- Chemistry and pharmacology of nootropics. Nicolaus, B.5, 1982, Drug Development Research, Vol. 2, pp. 463-74.
- Cyclic GABA-GABOB analogues. IV. Activity on learning and memory. Banfi, S.1, January 1984, Farmaco Sci, Vol. 39, pp. 16-22.
- Aniracetam augments, and midazolam inhibits, the long-term potentiation in guinea-pig hippocampal slices. Satoh, M.2, July 1986, Neurosci Lett, Vol. 68, pp. 216-20.
- Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine. Spignoli, G.3, July 1987, Pharmacol Biochem Behav, Vol. 27, pp. 491-5.
- The memory-enhancing effects of the piracetam-like nootropics are dependent on experimental parameters. Mondadori, C.1, May 1, 1989, Behav Brain Res, Vol. 33, pp. 79-82.
- Avoidance facilitation by nootropics. Sansone, M.Suppl, 1989, Prog Neuropsychopharmacol Biol Pshychiatry, Vol. 13, pp. S89-97.
- Relationships between arousal and cognition-enhancing effects of oxiracetam. Cavoy, A.2, February 1994, Pharmacol Biochem Behav, Vol. 47, pp. 283-7.
- (S)-Oxiracetam is the Active Ingredient in Oxiracetam that Alleviates the Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats. Li, Wan.10052, August 2017, Sci Rep, Vol. 7.
- Piracetam and other structurally related nootropics. Gouliaev, A.2, May 1994, Brain Research Reviews, Vol. 19, pp. 180-22.
- Effects of huperzine A on acetylcholinesterase isoforms in vitro: comparison with tacrine, donepezil, rivastigmine and physostigmine. Zhao, Q.2-3, November 29, 2002, Eur J Pharmacol, Vol. 455, pp. 101-7.
- The NMDA receptor ion channel: a site for binding of huperzine A. Gordon, R.S1, 2001, Journal of Applied Toxicology, Vol. 21, pp. S47-S51.
- Pharmacokinetics of huperzine A following oral administration to human volunteers. Li, Y.Oct-Dec 2007, Eur J Drug Metab Pharmacokinet, Vols. 32-4, pp. 183-7.
- Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monniera Linn. Singh, H.5, 1997, Indian Journal of Pharmacology, Vol. 29, pp. 359-65.
- Bacopa monnieri modulates endogenous cytoplasmic and mitochondrial oxidative markers in prepubertal mice brain. Shinomol, G.4, February 2011, Phytomedicine, Vol. 18, pp. 317-26.
- Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Chowdhuri, D.7, November 2002, Phytotherapy Research, Vol. 16, pp. 639-45.
- Bacosterol glycoside, a new 13,14-seco-steroid glycoside from Bacopa monnier. Bhandari, P.2, 2006, Chem Pharm BUll, Vol. 54, pp. 240-1.
- Enhancement of basolateral amygdaloid neuronal dendritic arborization following Bacopa monniera extract treatment in adult rats. Vollalla, V.4, Sao Paulo : s.n., April 2011, Clinics, Vol. 66, pp. 663-71.
- Chronic effects of Brahmi (Bacopa monnieri) on human memory. Roodenry, S.2, August 2002, Neuropsychopharmacology, Vol. 27, pp. 279-81.
- Neuropharmacological Review of the Nootropic Herb Bacopa monnieri. Aguiar, S.4, August 2013, Rejuvination Res, Vol. 16, pp. 313-26.
- Revisiting choline alphoscerate profile: a new, perspective, role in dementia? Scapicchio, P.7, July 2013, INt J Neurosci, Vol. 123, pp. 444-9.
- Purification of L-alpha glycerylphosphorylcholine by column chromatography. Zhang, K.January 13, 2012, J Chromatogr A, Vol. 1220, pp. 108-14.
- Simplified preparation of L-alpha-glyceryl phosphoryl choline. Brockerhoff, H.10, October 1965, Can J Biochem, Vol. 43, p. 1777.
- Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial. Malaguarnera, M.4, December 2011, Metab Brain Dis, Vol. 26, pp. 281-9.
- Oral acetyl-L-carnitine therapy reduces fatigue in overt hepatic encephalopathy: a randomized, double-blind, placebo-controlled study. Malaguarnera, M.4, Aprill 2011, American Journal of , Vol. 93, pp. 799-808.
- Efficacy and tolerability of choline alphoscerate (cereton) in patients with Parkinson’s disease with cognitive disorders. Levin, O.11, 2009, Zh Nevrol Psikhiatr Im S S Korsakova, Vol. 109, pp. 42-6.
- alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Barbagallo, S.June 30, 1994, Ann N Y Acad Sci, Vol. 717, pp. 253-69.
- Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among patients with probable senile dementia of Alzheimer’s type. Parnetti, L.2, Mar-Apr 1993, Drugs Aging, Vol. 3, pp. 159-64.
- Acute supplementation with alpha-glycerylphosphorylcholine augments growth hormone response to, and peak force production during, resistance exercise. Ziegenfuss, T.Suppl 1, September 2008, Journal of the International Society of Sports Nutrition, Vol. 5.
- Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women. Wallace, J.7, October 2012, British Journal of Nutrition, Vol. 108, pp. 1264-1271.
- Effects of choline on health across the life course: a systematic review. Leemakers, ET and Moreira, EM.8, August 2015, Journal of Nutrition Review, Vol. 73, pp. 500-522.
- Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Mori, K.9, September 2008, Biol Pharm Bull, Vol. 31, pp. 1727-32.
- An endoplasmic reticulum (ER) stress-suppressive compound and its analogues from the mushroom Hericium erinaceum. Ueda, K.21, 2008, Vol. 16.
- Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Mori, K.3, March 2009, Phytoher Res, Vol. 23, pp. 367-72.
- Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake. Nagano, M.4, August 2010, Biomed Res, Vol. 31, pp. 231-7.
- Brain cephalin, a mixture of phosphatides, separation from it of physphatidylserine, phosphatidylethanolamine and a fraction containing an inositol phophatide. August 1942, pp. 34-44.
- Phospholipids and sports performance. Jager, R. 5, July 2007, Journal of the International Society of Sports Nutrition, Vol. 4.
- Pharmacological effects of phosphatidylserine enzymatically synthesized from soybean lecithin on brain functions in rodents. Sakai, M. 1, Tokyo : s.n., February 1996, J Nutr Sci Vitaminol, Vol. 42, pp. 47-54.
- Effect of Phosphatidylserine on Cerebral Glucose Metabolism in Alzheimer’s Disease. Klinkhammer, P. 4, 1990, Dementia and Geriatric Cognitive Disorders, Vol. 1.
- Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Monteleone, P. 4, 1992, Eur J Clin Pharmacol, Vol. 42, pp. 385-8.
- Tryptophan and tyrosine ratios to neutral amino acids in endogenous depression. Relation to antidepressant response to amitriptyline and lithium + L-tryptophan. Maller, S. 1, February 1983, J Affect Disord, Vol. 5, pp. 67-69.
- Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines. Nakashima, A. 11, Nov 2009, J Neural Transm (Vienna), Vol. 116, pp. 1355-62.
- Tyrosine improves working memory in a multitasking environment. Thomas, JR and Lockwood, C. 3, November 1999, Pharmacol Biochem Behav, Vol. 64, pp. 495-500.
- Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Banderet, L. 4, April 1989, Brain Res Bull, Vol. 22, pp. 759-62.
- Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Deijen, J. 2, January 1999, Brain Res Bull, Vol. 48, pp. 203-9.
- Tyrosine reverses a cold-induced working memory deficit in humans. Shurtleff, D. 4, April 1994, Pharmacol Biochem Behav, Vol. 47, pp. 935-41.
- L-theanine, a natural constituent in tea, and its effect on mental state. Nobre, AC. 2008, Asia Pac J Clin Nutr, Vol. Suppl, pp. 167-168.
- L-theanine—a unique amino acid of green tea and its relaxation effect in humans. Jneja, L. 6-7, JUne 1999, Trends in Food Science & Technology, Vol. 10, pp. 199-204.
- The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent. Nathan, PJ. 2, ` : s.n., 2006, J Herb Pharmacotherapy, Vol. 6, pp. 21-30.
- Effects of Theanine on the Release of Brain Alpha Wave in Adult Male. Song, CH and Jung, J. 9, November 2003, Korean Journal of Nutrition, Vol. 36, pp. 918-23.
- Effects of l-theanine on attention and reaction time response. Higashiyama, A and Hitay, H. 3, July 2011, Journal of Functional Foods, Vol. 3, pp. 171-76.
- Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Tian, X. 2013, Brain Research, Vol. 1503, p. 2432.
- L-theanine promotes nitric oxide production in endothelial cells through eNOS phosphorylation. Siamwala, J. 3, 2013, J Nutr Biochem, Vol. 24, pp. 595-605.