Too often we focus on food for the body while we neglect the vital nutrients and antioxidants that are crucial for the brain to be healthy and operate at optimum level. Not all nutrients and antioxidants for the brain are equal. We need nutrients and antioxidants for the brain that have neuroprotective qualities. Why? Our brain operates under tremendous amount of activity and stress. The brain needs extra neuroprotection not only to fight against free radical and oxidative cell damage but also to mitigate and to reduce the declines in cognitive function, memory, energy, and passion that are brought on with age.

Cerebral PRIME and Cerebral SLEEP contain powerful Neuroprotection that can improve not only brain health but also mood, creativity, endurance, and anti-fatigue. Cerebral Prime also enhances Neurotransmitters which increase Mental and Physical Performance - cognitive function, mental speed, focus, motivation, energy, memory, data processing, and physical reaction time. Cerebral SLEEP enhances REM sleep and Deep sleep so you can get more out of your sleep. REM sleep consolidates memory and rejuvenates the brain while Deep sleep heals and revitalizes the body.

Since brain health and mental performance are of critical importance, we procure the best ingredients with the highest quality. Cerebral PRIME and Cerebral SLEEP contain ingredients that work synergistically to improve brain health, to increase daytime performance and to enhance REM and Deep sleep.

Below are just a few of the many ingredients that are contained in our proprietary nootropic formula/stacks. Together with the way we process and enhance them, we have increased their ability to work even more synergistically and to produce much greater benefits and results for both brain health and for increasing mental and physical performance. The research on these ingredients are exciting and quite promising.

N Acetyl L-Tyrosine

Tyrosine can increase levels of neurotransmitters dopamine and adrenaline, which can help improve reasoning, memory and performance especially in stressful situations. Tyrosine also produces other important brain chemicals that help nerve cells communicate and can improve alertness, attention, focus, and endurance. During periods of acute stress and sleep deprivation, Tyrosine can help improve performance. A study found that cadets, who were supplemented with Tyrosine during a week-long intensive combat training session, experienced less stress and fatigue compared to those without Tyrosine.[1] The study also noted that Tyrosine not only has some protection against acute stress but also reduces blood pressure which helps to improve cognitive performance during and after stressful periods.[1]

N Acetyl L-Tyrosine

Besides stress, not getting enough sleep and having to stay awake for an extended time period can negatively affect one’s cognitive performance in a dramatic way. A study that supplemented people who were sleep deprived and experiencing “extended wakefulness” with Tyrosine found that Tyrosine was able to lessen or “attenuate the decrease in cognitive performance that was associated with sleep deprivation”.[2] Furthermore, Tyrosine can improve cognitive performance during sleep deprivation without significantly affecting sleep function.[2] In other studies, Tyrosine has demonstrated to improve not only cognitive function (various cognitive tests) but also global ratings on mood and happiness (assessed by Clyde Mood Scale and Profile of Mood states).

Phosphatidylserine (PS)

Phosphatidylserine (PS) has a long researched history of improving brain functions such as focus, cognition, engagement, memory and feeling clear-headed in both the young and the old.[3] PS supplementation in healthy young adults showed a significant improvement in cognitive and mental “processing speed (20%) and accuracy (13% more correct responses, 39% less wrong responses)” in acute tests and exercises.[4] Besides mental data processing speed and memory, there are improvements in free speech and logic speaking;[5] thoughts are smoother and more connected which makes it easier to find the right words to speak and to communicate. Additionally, Phosphatidylserine has been reported to improve long-term memory and long-term recognition.[5]

With Phosphatidylserine supplementation, it has also been observed that the interest in the environment and the attention span were increased while loss of motivation, socialization and initiative were reduced, which implies a higher level of interest, mental engagement and social engagement, in present activities.

Other numerous clinical trials with Phosphatidylserine and the elderly have shown “improvements in memory tasks such as name-face delayed recall, facial recognition, telephone-number recall and misplaced-objects recall”.[6] Additionally, It is noted that the interest in the environment and the attention span were increased as well.[6] In others words, PS can help one to become more engaging with people and activities while improving memory recall.

Phosphatidylserine (PS)

Besides mental improvements, PS supplementation improved physical exercise capacity in a research study and suggests that it might “possess potential ergogenic properties”.[7] In a moderate intensity cycling study, participants who took PS over a placebo (in a double-blind manner) recorded an average increase in exercise time to exhaustion from 7:51 minutes to 9:51 minutes.[7] This is a 29% increase in endurance or time to exhaustion/fatigue.

In summary, Phosphatidylserine (PS) supplementation has been observed to improve mental processing speed, cognitive capacity, memory, engagement as well as physical endurance. It can be used as a daily preventative against cognitive decline.

Dimethylaminoethanol (DMAE)

As Dimethylaminoethanol (DMAE) is a compound that is known as a "smart drug," its molecules can cross the blood-brain barrier to improve cognitive and mental abilities by converting the choline into Acetylcholine, which is a neurotransmitter. DMAE helps the vital function of forming new connections between neurons and enhances the process of impulse transmission. It optimizes brain activity and increases neurons’ functions for reasoning, focus, concentration, logic learning, memory formulation and connected thoughts.[8] By increasing the levels of Acetylcholine in the brain, DMAE can improve memory by enhancing the brain’s ability to remember, to recall, and to learn new memories better. Thus, DMAE is explored for its potential use as a memory enhancer, brain "booster," and "smart drug."

The Acetylcholine neurotransmitters also help the neurons’ synapses by increasing their ability to transfer messages from the brain to the entire body more efficiently.[8] DMAE lengthens attention span, focus, concentration, and can be helpful for people suffering from a cholinergic deficit and attention-related conditions. Students with increased levels of acetylcholine in the neurons have experienced an increase not only in their memory and focus but also creativity and associative thinking. It also improved their ability to concentrate more effectively during activities that required intense focus. Additionally, DMAE promotes calming effects and reduces stress and anxiety.

Dimethylaminoethanol (DMAE) is also known as a brain/mind health compound because it reduces the buildup of the “age pigment,” which impairs cognitive function and is linked to cognitive decline with age.[9] DMAE not only can increase levels of compounds involved with memory such as acetylcholine, but also can synthesizes Centrophenoxine, which has been noted to have the potential to repair brain damage in Alzheimer’s patients. Regarding people who have suffered strokes, the Acetylcholine Neurotransmitter attaches to neuron membranes and causes membrane depolarization effects that improve sustaining memories.

Dimethylaminoethanol (DMAE)

Additionally, DMAE has neuroprotective qualities for the brain and protects neurons and other cells from harmful effects of certain types of oxidation by embedding itself in the structure of the cell and acting as an anti-oxidant.[10] DMAE has neuroprotective qualities that are much needed by the brain for optimum brain health.

Besides improving memory and other cognitive functions of an aging brain, DMAE is reported to have anti-aging benefits for the skin as well. The antioxidant properties provide numerous benefits for the skin including firming it. It aids the skin to look more youthful by reducing blemishes, inflammation wrinkles and other signs of aging by preventing the production of arachidonic acid.

Alpha-GPC

Alpha-glycerophosphocholine (Alpha-GPC) is a cholinergic compound that is used for its cognitive-promoting properties and to enhance power output in athletes. Although the evidence is preliminary, a pilot study recorded that supplementation of Alpha-GPC prior to a power test (bench throws) reported a 14% power output improvement relative to placebo when taken 45 minutes prior to activity.[11]

Another research study noted that Alpha-GPC supplementation can increase growth hormone secretion and hepatic fat oxidization (fat burning) with increases in serum acetoacetate and 3-hydroxybutyrate levels.[12]

Alpha-GPC appears to be neuroprotective.[13] When it was given immediately following a stroke or ischemia attack for a period of 5 months, the study recorded consistent improvement in function.[14]The study also noted that the long term general usage of Alpha-GPC against cognitive disorders of degenerative or vascular origin (Alzheimer's, dementia, stroke, transitory ischemic attack) resulted in fairly consistent improvements on MMSE scores in the range of 10-26% (degenerative disorder origin) and 8-30% (vascular origin).[14]

In short, Alpha-GPC appears to support cellular membranes and may aid in preventing cognitive decline.[15] Athletes are at times interested in Alpha-GPC due to its ability to enhance growth hormone production and power output. Growth hormone secretion in response to stimulation (via GHRH) is amplified with administration of Alpha-GPC, and although it is effective in both youth and elderly it seems that elderly persons experience a greater relative increase (due to having less output initially).[16]

Ginkgo Biloba Extract

For centuries, Ginkgo Biloba has been used to treat various neurological conditions and to improve cognitive performance. Ginkgo Biloba is commonly supplemented for brain health, cognitive enhancement and to alleviate cognitive decline due to its neurotrophic and neuroprotective effects, which may extend to dopaminergic neurons. Ginkgo Biloba extract has been reported to not only protect neurons against oxidative stress and to have a “neuroprotection [quality] against free radical damage and excitotoxicity,” but also may “protect neurons from oxidative cell death”.[17] [18] Ginkgo Biloba’s antioxidative effects are extremely important for maintaining optimum brain health and reducing declines in cognition and memory.

Furthermore, Ginkgo Biloba appears to have “neuroprotective effects against β-amyloid proteins,” which is of interest to the pathology of “chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer's disease”.[18] In persons already experiencing cognitive decline, Ginkgo Biloba supplementation appears to have some therapeutic benefit in “improving cognitive performance and social functioning,” and the degree of improvement on cognitive performance were of “sufficient magnitude” and significant enough to be noticed by caretakers.[19] [20] The result of Ginkgo Biloba supplementation is an improvement in the quality of life for both the patients and the caregivers.[19]

Besides its cognitive and mental enhancements, Ginkgo Biloba can increase oxygen carrying capacity in persons especially at high altitudes who have no previous high-altitude experience.[21] Ginkgo Biloba supplementation can help reduce acute mountain sickness (AMS) which occurs when one ascends from a low altitude or sea level upwards, most commonly seen in mountain climbers and thought to be related to low blood oxygen concentrations.[21] This increase oxygen carrying capacity quality of Ginkgo Biloba might also be useful for exercise, physical activity, physical training, and sports.

Ornithine Hydrochloride (Ornithine HCl)

Ornithine is one of the three amino acids involved in the Urea cycle, alongside L-Arginine and L-Citrulline. When supplemented, Ornithine appears to reduce elevated ammonia levels in the blood which can be caused by prolonged exercise or extended physical work. This ability to reduce elevated ammonia concentration in the blood suggests that it can enhance performance and endurance in prolonged exercises (45 minutes or more). This anti-fatigue effect appears during prolonged exercise, which correlates with the time when ammonia would normally cause problems. This anti-fatigue quality was noticeable in a study in which athletes who were supplemented with Ornithine recorded a fatigue rating that was 52% compared to those with a placebo.[22] Within the same study, it noted that besides long distance runners, even 10-second sprinters benefited from supplementing with Tyrosine.[22] Tyrosine's anti-fatigue effect improved endurance and performance mentally and physically.

Ornithine HCI

Green Tea Extract (Polyphenols, Catechins, EGCG)

Green Tea Extract (Camellia Sinensis) has been implicated in benefiting many organ systems in the body. The benefits of Green Tea Extract are attributed to its flavonoids - polyphenols, catechins, and EGCG, which have been shown to protect brain cells from oxidative stress.[23] This protection can help reduce brain damage that could lead to mental decline and brain diseases like Parkinson's, Alzheimer's, and dementia. Green Tea Extract can also decrease the action of heavy metals like iron and copper, both of which can damage brain cells. There are even studies that suggest that there is a reduced risk of cardiovascular events and stroke observed among tea drinkers.[24]

Green Tea Extract (Polyphenols, Catechins, EGCG)

Green Tea Extract has demonstrated to be beneficial for cognition. Another research study noted that Green Tea Extract (Polyphenols, Catechins, and EGCG) was able to increase brain activity up to 2 hours after supplementation.[25] It's been shown to improve task performance and help memory as well, by enhancing the connection between different parts of the brain. Along with improving and modulating brain activity, a separate study found that those who consumed these flavonoids in Green Tea were more able to be in a relaxed and attentive state.[23]

Besides these cognitive and mental aspects, green tea has physical benefits as well. It is able to enhance stamina and endurance, the time to exhaustion, during endurance event.[26] Another amazing attribute of Green Tea Extract is its ability to stimulate thermogenesis, or fat burning with higher metabolism.[27] [28] Reports have shown that the polyphenols and catechin epigallocatechin gallate in Green Tea Extract is associated with increased weight loss due to diet-induced thermogenesis which “could be of value in assisting the management of obesity”.[27] [28] [29]

L-Theanine

Within 30-45 minutes of supplementation of L-Theanine, it has been noted to increase the production of alpha-1 waves which are associated with selective attention mechanisms[30] and arousal/mental alertness. [31] This increase in alpha-1 waves production is highly associated with promoting attention and memory while having a reduction in anxiety and stress.[32] [33] [34]

Structurally, L-Theanine is similar to Glutamine and both neurotransmitters that are produced from it (GABA and glutamate).[35] L-Theanine has been found to cross the blood brain barrier via the leucine-preferring transport system (the neutral amino acid transport).[36] [37]

L-Theanine

L-Theanine works synergistically with caffeine to improve rapid visual information processing (RVIP), reaction time, alertness, accuracy and attention while reducing fatigue.[38] [39] [40] [41] Our proprietary nootropic formula takes the synergistic effects between L-Theanine and caffeine and brings it up to a much higher level to increase mental speed, data processing, energy, physical reaction time, and endurance.

5-Hydroxytryptophan (5-HTP)

5-Hydroxytryptophan (5-HTP) can cross the blood brain barrier easily and has the sole fate of serotonin synthesis. It is more effective and reliable in increasing serotonin levels than tryptophan.[42] Proper levels of serotonin are important for the feeling of well-being and mood stability. The lack of or lower levels of serotonin, 5-HTP and tryptophan can cause depression and mood instability.

5-Hydroxytryptophan (5-HTP) has been associated with a decrease in appetite and food intake (resulting in weight loss) without significantly affecting mood state.[43] There are at least two studies that noted that 5-HTP reduces all caloric intake indiscriminately while another study suggests 5-HTP reduces the cravings for carbohydrates. At least one study noted that supplementation of 5-HTP can help with increasing satiety and reducing binge eating tendencies, which accounted for improved weight loss results.[44]

Supplementation of 5-HTP has been noted to decrease the time required to fall asleep as assessed by the Pittsburgh Sleep Quality Index (PSQI).[45]

5-Hydroxytryptophan (5-HTP)

Grape Seed Extract

Grape Seed Extract (GSE) has been demonstrated to have neuroprotective qualities for the brain and to protect cells from cytotoxicity.[46] Grape Seed Extract contains proanthocyanidin/procyanidin molecules which exert anti-oxidative effects in neurons.[47]

Besides neuroprotective qualities for the brain, a study noted that Grape Seed Extract improves cognitive functions.[48] The same study also said “our study suggests that grape seed-derived polyphenolics may be useful agents to prevent or treat Alzheimer’s disease (AD).”[48]

Grape Seed Extract (GSE) can reduce oxidative damage. It is believed that GSE's flavonoids' combination of antioxidant and anti-inflammatory properties are thought to delay or reduce the onset of neurodegenerative diseases like Alzheimer's disease and dementia.[49] One study noted that daily intake of GSE improved attention, language, and both immediate and delayed memory.[50]

Besides enhancing cognitive functions, the antioxidant activity of Grape Seed Extract is associated with a reduced risk of various cancers.[51] In lab studies, GSE has been shown to inhibit cancer in various human cell types such as human breast, lung, gastric, oral squamous cell, liver, prostate, and pancreatic cell lines.[52] [53] [54] [55] GSE also appears to have a protective effect on your liver. In test-tube studies, GSE reduced inflammation, recycled antioxidants, and protected against free radical damage during toxin exposure.[56] [57] [58]

Pine Bark Extract

Studies have noted that taking Pine Bark Extract (Pycnogenol) have improved cognitive function, attention, focus, concentration, memory and mental performance. One study states that students taking Pine Bark Extract had reduced rate of test failures and reported “improved sustained attention, memory, executive functions and mood ratings.”[59]

In another study, 61 children with confirmed ADHD took Pine Bark Extract daily for 4 weeks showed that it “caused significant reduction of hyperactivity, improves attention and visual-motoric coordination and concentration in children with ADHD.”[60] Pine Bark Extract has also demonstrated that it improves mental performance, focus, memory function and cognitive function.

Besides its cognitive benefits, Pine Bark Extract contains procyanidins which produce benefits such as increased blood flow and improved blood glucose control which appears to be anti-diabetic.[61] Pine Bark Extract is being investigated for its benefits related to healthy aging, wound healing, Alzheimer's disease, attention deficit hyperactivity disorder (ADHD), improved cognition and athletic performance.[62] [63] [64] [65] [66] [67]

Pine Bark Extract has anti-aging benefits and its antioxidants protect tissue and organs against damaging free radicals.[62] The antioxidants in Pine Bark Extract contain bioflavonoids, catechins, epicatechins, procyanidins and phenolic acids—some of these antioxidants are unique to Pine Bark Extract. Pine Bark Extract's antioxidants properties help protect the collagen and elastic tissue from oxidative damage, the primary cause of skin aging.[62] Pine Bark Extract can also improve wound healing and strengthen the immune system.

Procyanidins

Neuroprotective for the Brain & Performance Enhancing

As stated above, too often we focus on food for the body while we neglect the vital nutrients and antioxidants that are crucial for the brain to be healthy and to operate at optimum level. We need nutrients and antioxidants for the brain that have neuroprotective qualities. The brain needs extra neuroprotection not only to fight against free radicals and oxidative cell damage but also to mitigate and to reduce the declines in cognitive function, memory, energy, and passion that are brought on with age.

Our proprietary nootropic formula/stacks contain all the above-mentioned ingredients along with many more ingredients. Together with the way we process and enhance them, we have increased their ability to work even more synergistically and to produce much greater benefits and results for both brain health and for increasing mental and physical performance.

Our proprietary nootropic formulas contain powerful neuroprotection to improve brain health and to fight against oxidative cell death and cognitive decline brought upon by stress and aging. Our proprietary formulas also enhance cognitive function, attention, concentration, alertness, spatial awareness, interest (mental and social engagement), passion and increase in REM and deep sleep for memory consolidation, brain rejuvenation, immune system, recover, bodily/physical healing, wound healing, tissue repair, and anti-aging.

A Healthier Brain is a Happier Life!!!

REFERENCES

[1] Deijen JB, et al. Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Res Bull. (1999)

[2] Neri DF, et al. The effects of tyrosine on cognitive performance during extended wakefulness. Aviat Space Environ Med. (1995)

[3] Benton D, Donohoe RT, Sillance B, Nabb S: The Influence of Phosphatidylserine Supplementation on Mood and Heart Rate when Faced with an Acute Stressor. Nutr Neurosci. 2001, 4 (3): 169-178.

[4] Parker AG, et al. The effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exercise. J Int Soc Sports Nutr. (2011)

[5] Louis-Sylvestre J: Phosphatidylserine and memory problems in aged subjects. Cah Nutr Diet. 1999, 34 (6): 349-357.

[6] Crook TH, Tinklenberg J, Yesavage J, Petrie W, Nunzi MG, Massari DC: Effects of Phosphatidylserine in age-associated memory impairment. Neurol. 1991, 41: 644-649

[7] Kingsley MI, et al. Effects of phosphatidylserine on exercise capacity during cycling in active males. Med Sci Sports Exerc. (2006)

[8] Perry E, et al. Acetylcholine in mind: a neurotransmitter correlate of consciousness?. Trends Neurosci. (1999)

[9] Nagy I, Nagy K. On the role of cross-linking of cellular proteins in aging. Mech Ageing Dev. (1980)

[10] Nagy I, Nagy K. Electron spin resonance spectroscopic demonstration of the hydroxyl free radical scavenger properties of dimethylaminoethanol in spin trapping experiments confirming the molecular basis for the biological effects of centrophenoxine. Arch Gerontol Geriatr. (1984)

[11] Ziegenfuss, Tim et al Alpha-GPC and power output; growth hormone. Journal of the International Society of Sport Nutrition. 17 September 2008 5(Suppl 1):P15

[12] Kawamura T, et al Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults. Nutrition. (2012)

[13] Barbagallo Sangiorgi G, et al Alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci. (1994)

[14] Parnetti L, Amenta F, Gallai V Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev. (2001)

[15] De Jesus Moreno Moreno M Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther. (2003)

[16] Ceda GP, et al. alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Horm Metab Res. (1992)

[17] Saleem S, et al. Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury. Stroke. (2008)

[18] Zhuang H, et al. Induction of heme oxygenase 1 by Ginkgo biloba in neuronal cultures and potential implications in ischemia. Cell Mol Biol (Noisy-le-grand). (2002)

[19] Herrschaft H, et al. Ginkgo biloba extract EGb 761® in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. J Psychiatr Res. (2012)

[20] Le Bars PL, Kieser M, Itil KZ A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract EGb 761 in dementia. Dement Geriatr Cogn Disord. (2000)

[21] Moraga FA, et al. Ginkgo biloba decreases acute mountain sickness in people ascending to high altitude at Ollagüe (3696 m) in northern Chile. Wilderness Environ Med. (2007)

[22] Sugino T, et al. L-ornithine supplementation attenuates physical fatigue in healthy volunteers by modulating lipid and amino acid metabolism. Nutr Res. (2008)

[23] Scholey A, et al. Acute neurocognitive effects of epigallocatechin gallate (EGCG). Appetite. (2012)

[24] Ras RT, Zock PL, Draijer R Tea consumption enhances endothelial-dependent vasodilation; a meta-analysis. PLoS One. (2011)

[25] Suganuma M, et al. Wide distribution of {3H}(-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis. (1998)

[26] Murase T, et al. Green tea extract improves endurance capacity and increases muscle lipid oxidation in mice. Am J Physiol Regul Integr Comp Physiol. (2005)

[27] Shixian Q, et al. Green tea extract thermogenesis-induced weight loss by epigallocatechin gallate inhibition of catechol-O-methyltransferase. J Med Food. (2006)

[28] Diepvens K, Westerterp KR, Westerterp-Plantenga MS Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea. Am J Physiol Regul Integr Comp Physiol. (2007)

[29] Dulloo AG, et al. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord. (2000)

[30] Kelly SP, et al. Increases in alpha oscillatory power reflect an active retinotopic mechanism for distracter suppression during sustained visuospatial attention. J Neurophysiol. (2006)

[31] Klimesch W, et al. Induced alpha band power changes in the human EEG and attention. Neurosci Lett. (1998)

[32] Sandi C. Glucocorticoids act on glutamatergic pathways to affect memory processes. Trends Neurosci. (2011)

[33] Garcia R. Stress, hippocampal plasticity, and spatial learning. Synapse. (2001)

[34] Tamano H, et al. Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory. Brain Res Bull. (2013)

[35] Başkan MH, Aydın M. Electron paramagnetic resonance studies of gamma-irradiated dl-alanine ethyl ester hydrochloride, l-theanine and l-glutamic acid dimethyl ester hydrochloride. Spectrochim Acta A Mol Biomol Spectrosc. (2013)

[36] Yokogoshi H, et al. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. (1988)

[37] Christensen HN. Developments in amino acid transport, illustrated for the blood-brain barrier. Biochem Pharmacol. (1979)

[38] Owen GN, et al. The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci. (2008)

[39] Giesbrecht, et al. The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutr Neurosci. (2010)

[40] Foxe JJ, et al. Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology. (2012)

[41] Haskell CF, et al. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol. (2008)

[42] Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. (1998)

[43] Ceci F, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm. (1989)

[44] Rondanelli M, et al. Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration. Eat Weight Disord. (2012)

[45] Shell W, et al. A randomized, placebo-controlled trial of an amino acid preparation on timing and quality of sleep. Am J Ther. (2010)

[46] Ono K, et al. Effects of grape seed-derived polyphenols on amyloid beta-protein self-assembly and cytotoxicity. J Biol Chem. (2008)

[47] Kim Y, et al. Antioxidant and cytoprotective effects of oligomeric and polymeric procyanidin fractions from defatted grape seed in PC12 cells. J Med Food. (2012)

[48] Wang J, et al. Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease. J Neurosci. (2008)

[49] Solanki I, et al. Flavonoid-Based Therapies in the Early Management of Neurodegenerative Diseases. Front Pharmacol. (2017)

[50] Calapai G, et al. A Randomized, Double-Blinded, Clinical Trial on Effects of a Vitis vinifera Extract on Cognitive Function in Healthy Older Adults. Adv Nutr. (2015)

[51] Bagchi D, et al. Free radical scavenging, antioxidant and cancer chemoprevention by grape seed proanthocyanidin: an overview. Mutation Research. (2014)

[52] Yang N, et al. Grape seed proanthocyanidins inhibit the proliferation, migration and invasion of tongue squamous cell carcinoma cells through suppressing the protein kinase B/nuclear factor-κB signaling pathway. Int J Mol Med. (2017)

[53] Derry M, et al. Differential Effects of Grape Seed Extract against Human Colorectal Cancer Cell Lines: The Intricate Role of Death Receptors and Mitochondria. Cancer Lett. (2013)

[54] Prasad R, et al. Grape seed proanthocyanidins inhibit migration potential of pancreatic cancer cells by promoting mesenchymal-to-epithelial transition and targeting NF-κB. Cancer Lett. (2013)

[55] Hamza A, et al. Molecular characterization of the grape seeds extract's effect against chemically induced liver cancer: In vivo and in vitro analyses. Sci Rep. (2018)

[56] Nuttal S, et al. An evaluation of the antioxidant activity of a standardized grape seed extract. Clinical Trial. (1998)

[57] Facino R, et al. Sparing effect of procyanidins from Vitis vinifera on vitamin E: in vitro studies. Planta Med. (1998)

[58] Fujishita K, et al. Grape seed extract acting on astrocytes reveals neuronal protection against oxidative stress via interleukin-6-mediated mechanisms. Cell Mol Neurobiol (2009)

[59] Luzzi R, et al. Pycnogenol® supplementation improves cognitive function, attention and mental performance in students. Panminerva Med. (2011)

[60] Trebatická J, et al. Treatment of ADHD with French maritime pine bark extract, Pycnogenols. Eur Child Adolesc Psychiatry. (2006)

[61] Zibadi S, et al. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Nutr Res. (2008)

[62] Rohdewald P. Pleiotropic Effects of French Maritime Pine Bark Extract to Promote Healthy Aging. Rejuvenation Res. (2017)

[63] Ono K, et al. Pine Bark Polyphenolic Extract Attenuates Amyloid-β and Tau Misfolding in a Model System of Alzheimer's Disease Neuropathology. J Alzheimers Dis. (2020)

[64] Anheyer D, et al. Herbal medicines in children with attention deficit hyperactivity disorder (ADHD): A systematic review. Complement Ther Med. (2017)

[65] Belcaro G, et al. The COFU3 Study. Improvement in cognitive function, attention, mental performance with Pycnogenol® in healthy subjects (55-70) with high oxidative stress. J Neurosurg Sci. (2015)

[66] Belcaro G, et al. Pycnogenol® improves cognitive function, attention, mental performance and specific professional skills in healthy professionals aged 35-55. J Neurosurg Sci. (2014)

[67] Vinciguerra G, et al. Evaluation of the effects of supplementation with Pycnogenol® on fitness in normal subjects with the Army Physical Fitness Test and in performances of athletes in the 100-minute triathlon. Controlled Clinical Trial. (2013)