Mind, Memory, Focus (25)

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Cerebra-GPC is 100% Purified PhosChol with the fatty acids removed. It is a simple formulation of purified GPC and water, which comes together as a clear, concentrated, sweet tasting solution that is easy to administer to adults and children. What is Cerebra GPC? GPC is a safe, stable, and rapidly absorbed source of free choline, which easily enters the brain and has many functions in the body. It is important for the structural integrity of cell membranes, cholinergic neurotransmission, transmembrane signalling, methyl metabolism, and lipid-cholesterol transport and metabolism. Choline is a precursor for phosphatidylcholine, sphingomyelin, platelet-activating factor, betaine, and other phospholipids. A Positive Influence on Neurotransmission Acetylcholine decline coincides with advancing age, and is a hallmark of neurodegenerative disease. Even in the absence of diseases such as Alzheimer's and vascular dementia, aging brains lose cholinergic receptors; structures within the nerves that receive and propagate the messages transmitted by acetylcholine. Evidence suggests that by increasing levels of acetylcholine in the brain, cognitive deficits and brain structure changes related to ageing may be reversed. GPC is believed to prevent and ameliorate dementia, memory loss and learning difficulties because it accelerates the biosynthesis of acetylcholine and phosphatidylcholine. Additionally, GPC may protect and facilitate communication between nerves through its effect on receptors for nerve growth factor. GPC has been shown to stimulate the release of the neurotransmitter, GABA (gamma-aminobutyric acid). And, administration of GPC was influential in making more GABA available to brain cells. In various studies, GPC has been directly compared to some popular nootropic substances such as oxiracetam and acetyl-L-carnitine. Cognitive improvement among GPC patients was similar to those seen in patients taking oxiracetam. Tests directly comparing the GPC to acetyl-L-carnitine demonstrated that GPC delivers superior cognitive benefits. Conclusions Supplementation of GPC provides a good source of safe, stable, and readily absorbed choline for enhancing cholinergic metabolic functions such as neurological and mental performance. GPC should be considered as an essential nutrient in any integrated anti-ageing and/or brain restoration protocol. At this time there are no known side effects, contraindications or interactions. Ingredients are GRAS and should be well tolerated even with long term use. GPC is a nutrient present in all mammalian cells and other life forms. It is a rapidly absorbed source of choline, which easily enters the brain and has many functions in the body. Choline is important for the structural integrity of cell membranes, cholinergic neurotransmission, transmembrane signalling, methyl metabolism, and lipid-cholesterol transport and metabolism [1]. Choline is a precursor for phosphatidylcholine, sphingomyelin, platelet-activating factor, betaine, and other phospholipids (Food and Nutrition Board (FNB) 1998). Choline speeds the synthesis and release of acetylcholine, an important neurotransmitter involved in numerous important functions in the body. Choline is an essential nutrient since the de novo synthesis of choline is not always sufficient to meet human requirements for choline. The FNB established various Adequate Intake levels (AI) for choline based on gender/age groups. Table 1 lists the AI levels established by the Food and Nutritional Board. The Adequate Intake for pregnancy and lactation was established as 450 mg/day and 550 mg/day, respectively (FNB, 1998). Table 1 shows that the Adequate Intake of choline is about 550 mg/day for men and 425 mg/day for women. Choline in the diet is available as free choline or is bound as esters such as phosphocholine, GPC, sphingomyelin, or phosphatidylcholine. It should be noted that foods that are good sources of choline and choline esters are typically higher in fat and/or cholesterol. Many Americans, in view of recommendations from various private and government public health organizations, are decreasing fat, saturated fat, and cholesterol in their diet. The consumption of less fat, saturated fat, and cholesterol will lead to a concomitant decrease in choline intake. The de facto intake of choline and choline compounds were examined during the Framingham Offspring Study in several thousand men and women and showed that the general dietary intake of choline as free form and as compounds is about 312 mg/day for men and 314 mg/day for women [2]. Total choline intake was calculated as the sum of intake from free choline, phosphocholine, glycerophosphocholine, phosphatidylcholine and lecithin. Thus, the addition of choline and choline precursors to certain foods may compensate for a possible deficit in choline. Choline is a vitamin-like, essential nutrient. But free choline is poorly bioavailable and unstable in the water phase. GPC is a physiological form of choline in the body. Figure 2 shows the metabolic pathway of choline and GPC. Cerebra GPC is water soluble and able to efficiently increase choline levels in the blood and the brain. Cerebra GPC is recommended at 500mg to 1000mg of pure GPC per day, which is equivalent to 200 - 400 mg free choline. Safety of GPC GPC is a choline precursor like lecithin and choline salts. Commercial lecithin, phosphatidylcholine, choline bitartrate, and choline chloride are also precursors of choline and are all generally recognized as safe (GRAS) (21 CFR � 182,184). GPC is a naturally occurring food component. Table 2 lists the content of free choline, GPC, and other naturally present choline esters in common foods (mg choline moiety per 100 g food) [6]. Table 2 shows that GPC is the predominant choline component in foods such as milk, dairy products (e.g., cheese), olive oil, oat bran, and bananas. The average intake of GPC in the subjects participating in the Framingham Offspring Study was 54�21 mg/day [2]. Additional GPC is formed in the body by hydrolysis of phosphatidylcholine from food by phospholipase A in the gut mucosa. GPC is also an important component in human milk, with a concentration of 362�70 �mol/l as derived by the mean of 16 women [3]. GPC is a nutrient present in all mammalian cells and other life forms. It is a rapidly absorbed source of choline, which easily enters the brain and has many functions in the body. Choline is important for the structural integrity of cell membranes, cholinergic neurotransmission, transmembrane signalling, methyl metabolism, and lipid-cholesterol transport and metabolism [1]. Choline is a precursor for phosphatidylcholine, sphingomyelin, platelet-activating factor, betaine, and other phospholipids (Food and Nutrition Board (FNB) 1998). Choline speeds the synthesis and release of acetylcholine, an important neurotransmitter involved in numerous important functions in the body. Choline is an essential nutrient since the de novo synthesis of choline is not always sufficient to meet human requirements for choline. The FNB established various Adequate Intake levels (AI) for choline based on gender/age groups. Table 1 lists the AI levels established by the Food and Nutritional Board. The Adequate Intake for pregnancy and lactation was established as 450 mg/day and 550 mg/day, respectively (FNB, 1998). Table 1 shows that the Adequate Intake of choline is about 550 mg/day for men and 425 mg/day for women. Choline in the diet is available as free choline or is bound as esters such as phosphocholine, GPC, sphingomyelin, or phosphatidylcholine. It should be noted that foods that are good sources of choline and choline esters are typically higher in fat and/or cholesterol. Many Americans, in view of recommendations from various private and government public health organizations, are decreasing fat, saturated fat, and cholesterol in their diet. The consumption of less fat, saturated fat, and cholesterol will lead to a concomitant decrease in choline intake. The de facto intake of choline and choline compounds were examined during the Framingham Offspring Study in several thousand men and women and showed that the general dietary intake of choline as free form and as compounds is about 312 mg/day for men and 314 mg/day for women [2]. Total choline intake was calculated as the sum of intake from free choline, phosphocholine, glycerophosphocholine, phosphatidylcholine and lecithin. Thus, the addition of choline and choline precursors to certain foods may compensate for a possible deficit in choline. Choline is a vitamin-like, essential nutrient. But free choline is poorly bioavailable and unstable in the water phase. GPC is a physiological form of choline in the body. Figure 2 shows the metabolic pathway of choline and GPC. Figure 2: Metabolic pathway of GPC [3]. Cerebra GPC is water soluble and able to efficiently increase choline levels in the blood and the brain. Cerebra GPC is recommended at 500mg to 1000mg of pure GPC per day, which is equivalent to 200 - 400 mg free choline. Safety of GPC GPC is a choline precursor like lecithin and choline salts. Commercial lecithin, phosphatidylcholine, choline bitartrate, and choline chloride are also precursors of choline and are all generally recognized as safe (GRAS) (21 CFR � 182,184). GPC is a naturally occurring food component. Table 2 lists the content of free choline, GPC, and other naturally present choline esters in common foods (mg choline moiety per 100 g food) [6]. Table 2: Choline concentrations in common food in mg choline moiety/100 g food [6]. food Choline GPC Phospho- choline Phosphatidyl- choline Total choline 2 % milk 2.82 9.98 1.58 1.15 16.40 Cheese half & half 3.92 8.48 1.17 1.71 16.82 Sour cream 4.73 8.08 1.26 3.51 20.33 Yoghurt, plain 2.32 9.10 1.65 1.04 15.20 Olive oil 0.02 0.28 ND ND 0.29 Bananas 3.20 5.60 0.51 0.44 9.76 Fin fish � Atlantic cod 17.73 30.04 1.57 32.90 83.63 Oat bran, raw 4.41 33.25 0.68 20.23 58.57 Beef liver 56.67 77.93 11.77 247.75 418.22 Table 2 shows that GPC is the predominant choline component in foods such as milk, dairy products (e.g., cheese), olive oil, oat bran, and bananas. The average intake of GPC in the subjects participating in the Framingham Offspring Study was 54�21 mg/day [2]. Additional GPC is formed in the body by hydrolysis of phosphatidylcholine from food by phospholipase A in the gut mucosa. GPC is also an important component in human milk, with a concentration of 362�70 �mol/l as derived by the mean of 16 women [3].Metabolic Studies The bioavailability of choline and choline esters from milk was studied in a rat-pup model [7]. 15-day-old rat pups were fed infant formula, labeled with approximately 15,725 Bq of either 14C-choline, 14C-phosphocholine, 14C-GPC, or 14C-phosphatidylcholine. Stomach content, blood, and tissues were analyzed for the different choline species at different time points. The disappearance of the radiolabel in the stomach was similar for choline, phosphocholine and GPC. There was a 3-fold decrease in all labels at 30 min post incubation. At 4 h post incubation there was essentially no label present in the stomach contents. Disappearance of phosphatidylcholine-derived label in stomach contents was slower than for the other three labels. It took 8 h before a 3-fold decrease was observed and more than 12 h before this label disappeared from the stomach contents. In the GI tract, choline-, GPC-, and phosphocholine-derived labels were similar, and the total area under the curves were significantly different from the phosphatidylcholine-derived label. The labeled choline compounds were absorbed and distributed to the GI tract, liver, blood, and brain of the rat pups. The appearance and disappearance of choline-, GPC-, and phosphatidylcholine-derived labels were similar. In the liver, phosphocholine appeared and disappeared more rapidly than did the other labels. Labels from all of the water-soluble forms of choline reached maximum levels within 4 h; phosphocholine label did so by 1 h. Phosphatidylcholine appeared much more slowly than did the other labels and was still accumulating at 24 h post dose. In the liver, the total area under the curve was significantly different for each label over the time periods studied. Different choline-containing compounds were formed in liver from choline-, phosphocholine-, GPC-, and phosphatidylcholine-radio labeled infant formula. In liver at 4 h post treatment, choline (Table 3), phosphocholine-, and GPC-derived label were present in the greatest amount as betaine, with phosphocholine being the next most common metabolite formed. Phosphatidylcholine-derived label was principally associated with phosphatidylcholine in liver. By 24 h in liver (Table 4), choline and phosphocholine label was mainly present as betaine, with a small amount of phosphatidylcholine formed. No choline- and phosphocholine-derived label was present as choline, GPC, or phosphocholine. GPC-derived label was present as betaine, with some choline, GPC and phosphatidylcholine also being formed. Phosphatidylcholine-derived label was present mainly as phosphatidylcholine in liver with some betaine and phosphocholine formed. These data indicate that in liver GPC was metabolized differently than free choline and phosphatidylcholine. GPC seems to offer a sustained liberation of choline for further metabolism. The absorption, distribution, and excretion after single doses of radio labeled GPC ([14G]-GPC, labeled in the glycerol part of the molecule, and [14C]-GPC, labeled in the choline-part of the molecule) were also extensively studied in rats [8]. The blood and plasma kinetics and the excretion and tissue distribution of GPC were investigated after oral (100-300 mg GPC/kg) and i.v. (10 mg GPC/kg) uptake. The blood and plasma concentration of [14G]-GPC reached a maximum between 2-4 h after oral intake of 100 mg/kg. For [14C]-GPC, the peak concentration was obtained after 24 h. The GPC concentrations for both labeled forms stayed above the baseline during the 72 h of investigation. The tissue distribution of radioactivity was examined 3 h and 72 h after oral administration. After 3 h the radioactivity of [14G]-GPC peaked in the gut, corresponding to 18-20 % of the administered dose. The concentration in liver and kidney were respectively about twice the concentration of the blood levels, equivalent to 2-6 % of the dose. Furthermore, 3 h after oral intake of [14C]-GPC, the liver contained the highest level of radioactivity (5-11 % of the dose). Other tissues with radioactivity levels higher than blood were the kidneys (1-1.5% of the dose), spleen and lung. The total radioactivity in the gut was 2-3 % of the administered dose. Brain radioactivity was about half that found in blood. After 72 h the total remaining radioactivity for both labeled GPC-forms was spread over most tissues and organs, but values higher than blood levels were found in liver, kidneys, lung, and spleen. The brain-to-blood distribution of radioactivity was also measured time-dependently. After [14G]-GPC, the time courses of blood and brain concentrations were almost parallel within 32 h of dosing. For [14C]-GPC, brain radioactivity increased slowly up 24 h and then remained constant up to the end of the experiment. Within this plateau it amounted about 50 % of blood radioactivity. Another experiment, with 300 mg/kg GPC orally administrated showed that the radioactivity was registered in the brain as phosphatidylcholine. This suggests that choline from GPC enters the brain and is reused for biosynthesis of phospholipids. The excretion of labeled GPC during 72 h was also investigated. Renal and fecal excretion was comparable to the G- and C-labeled compounds, but low (10 % of the dose). By far the largest part of the administered radioactivity was exhaled as 14CO2, in accordance with established catabolic pathways of glycerol and choline degradation. This study showed that in the rat, GPC is hydrolyzed to choline and glycerol-3-phosphate. Some metabolic studies in men from the literature will be described:A comparative study of free plasma choline levels following intramuscular administration of l-alpha-glycerylphosphorylcholine and citicoline in normal volunteers [9] l-alpha-glycerylphosphorylcholine (alpha-GPC) is a recently developed cognitive enhancer whose mode of action is considered to involve the release of free choline, which is then utilized for acetylcholine and phosphatidylcholine biosynthesis in the brain. The purpose of this study was to evaluate the profile of free plasma choline levels following a single i.m. dose of alpha-GPC in 12 normal volunteers. Citicoline (CTC), which also acts as a choline precursor, was included for comparison purposes. Each subject was studied on three randomized occasions, (i) on a control day in the absence of drug administration (to evaluate the plasma level profile of endogenous choline); (ii) after i.m. alpha-GPC (1,000 mg); and (iii) after i.m. CTC (1,000 mg), respectively, with a washout period of at least 1-week between sessions. Blood samples for plasma choline HPLC determinations were collected at regular intervals over a 6-h period. In the control session, plasma choline levels remained stable during the sampling period. The administration of alpha-GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of CTC, plasma choline levels showed a similar time course, but were considerably lower than those observed after the administration of alpha-GPC.Pharmacokinetics of choline alfoscerate in the healthy volunteer [10] This was a pharmacokinetic study of i.m., i.v., and oral dosing with GPC. Four healthy volunteers aged 19-24 years received GPC 1000 mg i.v., then subsequently i.m., then by mouth, then received a placebo by mouth, in four separate sessions separated by 1-week washouts. During each session blood was sampled periodically over 10 hours. With i.v. administration of GPC, plasma total choline peaked at 5 minutes and returned to baseline by 4 hours. With i.m. administration, plasma total choline peaked at 0.5 hours and returned to baseline by 6 hours. With oral GPC, plasma total choline peaked at 3 hours, at a concentration slightly less than half that reached by i.m. administration. But with oral GPC, the plasma total choline remained above baseline at 10 hours. The investigators concluded that i.v. and i.m. GPC both delivered virtually identical total plasma doses (AUC, area under the curve), and that oral administration delivered about half this amount. Clinical Studies Several clinical studies showed that the tolerability of GPC was very good, even when administered in very high doses for a long term. Numerous clinical studies have described the effects of high oral or parenteral doses of GPC on several neuronal disorders:Multi-center study of l-alpha-glyceryl-phosphorylcholine vs. ST200 among patients with probable senile dementia of Alzheimer's type [11] A multi-center, randomized, controlled study compared the efficacy of l-alpha-glyceryl-phosphorylcholine (alpha-GPC) and ST200 (acetyl-l-carnitine) among 126 patients with probable senile dementia of Alzheimer's type (SDAT) of mild to moderate degree. Efficacy was evaluated by means of behavioural scales and psychometric tests. The results showed significant improvements in most neuropsychological parameters in the alpha-GPC recipients. Improvements also occurred in the ST200 recipients, but to a lesser extent. Tolerability was good in both groups. These positive findings require replication in larger, double-blind, longitudinal studies coupling clinical and biological evaluations.Multi-center clinical study of efficacy and tolerability of choline alfoscerate in patients with deficits in higher mental function arising after an acute ischemic cerebrovascular attack [12] A total of 320 patients suffering mental decline after a cerebral ischemic attack received GPC 1000 mg i.m. once daily for 28 days, then 1200 mg by mouth for another 20 weeks. GPC significantly improved neurologic measures by week 4 (p<0.0001). By week 24, the various cognitive and global clinical assessment scales showed a �large improvement� of the mental status of the patients.Clinical study of the therapeutic effectiveness and tolerability of choline alfoscerate in 15 subjects with compromised cognitive functions subsequent to acute focal cerebral ischemia [13] This was a small open trial that followed the usual GPC stroke protocol. Eleven patients of average age 74 years received GPC 1000 mg i.m. once daily for 28 days, then 1200 mg orally daily for at least another 20 weeks. On various rating scales (Mathew, MMSE, SCAG, the Psychic Evaluation Scale), GPC significantly improved results with regard to memory, anxiety, emotional lability, sociability, spatial orientation, aspects of language, eye deviation, confusion, vigilance, and general mental sharpness. Two patients complained of slight, transitory heartburn but did not withdraw from the trial. At 6 months the physicians judged 10/11 of the patients as showing results excellent to fairly good, while 10/10 patients judged themselves as having excellent to fairly good. Thus, in 5 open trials completed with 2,972 patients variously afflicted by stroke, a regimen of 1 month of intramuscular GPC followed by 5 months of oral intake produced clinically remarkable improvement. Given that the patients were generally too ill to be given placebos, the degrees of clinical improvement over the 6-month trial periods were well above those predictable as placebo effects. Many patients showed accelerated improvement within the first 2-4 weeks and continued to improve over the remaining 5 months. The physicians as well as the patients uniformly judged GPC to be very well tolerated.Effect of l-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine [14] The present study was carried out to test the effects of l-alpha-glycerylphosphorylcholine (l-alpha-GFC) on memory impairment induced by scopolamine in human subjects. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten-day pre-treatment with either l-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection, the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by l-alpha-glycerylphosphorylcholine, a cholinomimetic drug [15] The present study investigates the cholinomimetic properties of the drug l-alpha-glycerylphosphorylcholine (alpha-GPC) at the CNS level. Experiments using tritium-labelled alpha-GPC indicate that the drug reaches the brain after i.p. and p.o. administration. In order to study the cholinomimetic properties of this drug, an indirect functional index of cholinergic activation was used. In fact cholinergic agonists induce an activation of striatal dopaminergic output. Administration of alpha-GPC, both i.p. and p.o., increased striatal dihydroxyphenylacetic acid (DOPAC) content. In addition, the in vitro K+-stimulated dopamine release was increased in rats treated in vivo with alpha-GPC. Since alpha-GPC has a weak displacing activity in QNB binding, the in vivo cholinergic activity might be due to the fact that this drug may increase the availability of choline for acetylcholine synthesis leading to increased acetylcholine production. This activity may be useful in those situations such as aging in which cholinergic activity is deficient.Choline alfoscerate in the treatment of mental disorder after acute cerebrovascular accident [16] An Italian multi-center trial involved 425 patients aged 45-85 years, who were recruited from 44 centers distributed throughout the country. All the patients had suffered cerebral ischemic attacks (stroke, TIA, or acute cerebral ischemia) within the previous 10 days. It was another open trial, since the patients were too severely afflicted to be subjected to placebo treatment. Patients who scored 35 or below on the Mathew Scale were eligible for the trial, but comatose patients were not, nor were those not expected to live or judged unable to comply over the 6-month period of the trial. As per the typical GPC stroke protocol, treatment proceeded in two phases, first by giving GPC 1000 mg i.m. in-hospital daily for 28 days, then switching to GPC 1200 mg by mouth for 5 more months (400 mg 3 times per day). Upon completion of the GPC i.m. phase, there was an average improvement on the Mathew Scale of 18.56 % (11.5 points, from 62.02 to 73.53). This was statistically highly significant over baseline. A 20 % or greater improvement was seen in 168 (39.5 %) of the patients. By this measure the more impaired, older patients (65-85 years) were more likely to benefit than were the younger patients 45-64 years). During the second phase, after discharge (GPC oral, for 5 months), evaluation was based on clinical interviews and three assessment scales were used. On the MMSE for cognitive functions, there was a 12.3 % improvement (from 21.53 at week 5 to 24.19 at 6 months). A 20 % or greater improvement was seen in 126 patients (29.7 %). On the Global Deterioration Scale, there was an average 20.2 % improvement. A 20 % or greater improvement was seen in 180 patients (42.3 %). On the Crichton Geriatric Rating Scale, which assesses mainly behavioural functioning, there was an average 19.5 % improvement. A 20 % or greater improvement was seen in 166 patients (39.1 %). The researchers judged GPC to be effective and well tolerated both parenterally and orally. They noted that despite the many drugs with which GPC was co-administered, no single GPC-drug interaction was observed clinically or in laboratory tests. GPC's benefits were consistent, and spanned functional state as well as performance and social behavior. With the possible exception of the MMSE (at 12.3 %), the degrees of improvement from GPC on the various scales were well above that expected from a placebo, namely 12 % in at least 20 % of such patients.Conclusion Glycerophosphocholine is a natural, physiological, water-soluble and stable precursor of choline. It is part of the daily nutrition and its levels are reduced on account of changed dietary composition. The fortification of different foods with GPC can supply GPC and choline as readily absorbed nutrients for enhancing cholinergenic metabolic functions such as neurological and mental performance. References: [1] Canty D.J., Zeisel S.H., Jolitz A.J., Lecithin and Choline � Research Update on Health and Nutrition. [2] Cho E., Zeisel S.H., Jaques P., Selhub J., Dougherty L., Colditz G.A., Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study, Am. J. Clin. Nutr. 2006, 83: 905-911. [3] Holmes-McNary M.Q., Cheng W.-L., Nar M.-H., Fussell S., Zeisel S.H., Choline and choline esters in human and rat milk and in infant formulas. Am. J. Clin. Nutr. 1996, 64: 572-576. [4] Howe J.C., Williams J.R., Holden J.M., Zeisel S.H., Mar M.-H., USDA Database for the Choline Content of Common Foods, March 2004. [5] Koc H., Mar M.-H., Ranasinghe A., Swenberg J.A., Zeisel S.H., Quantitation of Choline and Its Metabolites in Tissues and Foods by Liquid Chromatography(Electrospray Ionization-Isotope Dilution Mass Spectrometry, Analytical Chemistry 2002, 74(18): 4734-4740. [6] Zeisel S.H., Mar M.-H., Hove J.C., Holden J.M., Concentrations of Choline-Containing Compounds and Betaine in Common Foods. Human Nutrition and Metabolism 2003: 1302-1307. [7] Cheng W.-L., Holmes-McNary M.Q., Mar M.-H., Lien E.L. Zeisel S.H., Bioavailability of choline and choline esters from milk in rat pups, Nutritional Biochemistry 1996, 7: 457-464. [8] Abbiati G., Fossati T., Lachmann G., Bergamaschi M., Castiglioni C., Absorption, tissue distribution and excretion of radiolabeled compounds in rats after administration of [14C]-l-a-glycerylohosphorylcholine, Euro. J. Drug Metabol. Pharma 1993, 18(2): 173-180. [9] Gatti J. et al., A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers, Int. J. Clin. Pharmacol. Ther. Toxicol. 1992, 30(9): 331-335. [10] De Moliner et al., Pharmacokinetics of choline alsphscerate in the healthy volunteer, Le Basi Raz. Ter. 1993, 23, Suppl. 3, 75. [11] Parnetti L,. Avate G., Bartorelli L., Cucinotta D., Cuzzupoli M., Maggioni M., Villardita C., Senin U., Multicenter Study of l-a-Glyceryl-Phosphorylcholine vs ST200 among Patients with Probable Senile Dementia of Alzheimer�s Type, Drugs & Aging 1993, 3(2): 159-164. [12] Gambi D., Onofrj M., Multicenter clinical study of efficacy and tolerability of choline alfoscerate in patients with deficits in higher mental function arising after an acute ischemic cerebrovascular attack, Geriatrica 1994, 6:91. [13] Tomasina C. et al., Clinical study of the therapeutic effectiveness and tolerability of choline alfoscerate in 15 subjects with compromised cognitive functions subsequent to acute focal cerebral ischemia, Rivista Neuropsi. Sci. Affini. 1996, 3(7): 21. [14] Canal et al., Effect of L-alpha-glycerylphosphorylcholine on amnesia caused by scopolamine. Int. J. Clin. Pharmacol. Ther. Toxico. 1991, 29(3): 103-107. [15] Trabucchi et al., Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by l-alpha-glycerylphosphorylcholine, a cholinomimetic drug, Farmaco. Sci. 1986, 41(4): 325-334. [16] Aguglia E. et al., Choline alfoscerate in the treatment of mental pathology following acute cerebrovascular accident. Funct. Neurol. 1993; 8 (Suppl):5.

Would you like… To Focus more Easily Improved Cognition Better Brain Function Improved Memory Sharper Thinking Increased Alertness Improved Mood If so, you may want to give our Brain Boost Plus, Neuro Brain and Focus Formula a try!The combinations of ingredients found in this supplement can potentially also give you: Antioxidant support Anti-inflammatory support Increased energy Improved skin health Improved eye health Blood pressure support Improved heart health Boosted immunity Better bone health Blood sugar regulation Why is it important to support your brain?The brain is arguably the most important organ in your body - without it, we wouldn’t be able to carry out any of our daily functions.The brain controls our motor skills, vision, temperature, hunger, emotions, touch, thought and just about every process that helps to maintain and regulate our bodies [1].There are a variety of factors that can lead to your brain ageing prematurely, or becoming ‘unhealthy’, such as: Lack of good quality sleep [2] Poor diet & overeating [3] Not enough exercise [4] Smoking [5] Obesity [6] High blood pressure [7] High cholesterol levels [8] Social isolation [9] Spending too much time in dimly lit environments [10] Often overlooked, Deficiency or suboptimal levels of nutrients that are important to the brain will also contribute to inferior brain health. Can you test for an ‘unhealthy’ brain?There are a variety of tests that can be used in different situations to help determine if something serious is going on with your brain.Some of these include:Balance testCT scan (computed tomography)EEG (electroencephalography)ElectromyographyMRI (magnetic resonance imaging)MRA (magnetic resonance angiography - a type of MRI scan)And more.However, as these tests are generally expensive and hard to get, most people rely on evaluating symptoms such as decreased memory, focus and clarity of thinking.Speak to your physician to determine the best course of action if you have any concerns.The Top 9 Ways to Support Your Brain:To keep your brain functioning at optimal capacity, there are some lifestyle changes that you can make: Get enough good quality sleep, every night. For most adults, this is 7-8 hours of deep uninterrupted sleep. If sleep is something you struggle with, check out our Sleep Aid Ultra page. Eat an organic diet with plenty of high nutrient density foods. This will provide your brain with most of the nutrients and minerals it needs for optimal function. Exercise regularly. Half an hour of physical activity most days, or around 150 minutes a week. Stop smoking.   Maintain a healthy weight, and don’t overeat. Even too much healthy food can lead to weight gain. Minimize stress and lower your blood pressure. Meditating is a great way to reduce stress, and try natural supplements, such as our 5 HTP, Serenity Anti-Stress Support, Saffron Pure Extract OR Organic Ashwagandha with Black Pepper. Socialize more often. Spend more time in natural light and brighter lit rooms earlier in the day. Provide your brain with minerals and vitamins that are essential for it to function optimally: Vitamin A - Vitamin A is crucial to brain function, behavior and learning [11].Vitamin C - Your brain requires huge amounts of oxygen to function, which means it is extremely susceptible to oxidative stress. Vitamin C is a powerful antioxidant and helps to reduce oxidative stress [12].Calcium - Calcium is essential for optimal blood flow to the brain [13].Vitamin D - Essential for brain health, deficiency in Vitamin D can contribute to brain fog, low mood and can impact cognitive health [14].Magnesium - Optimal levels of magnesium in the body is crucial for brain health. Deficiency of magnesium (or low levels of) is commonly found in people who are stressed [15].Vitamin B1 - A deficiency of thiamine (vitamin B1) can contribute to increased confusion, can be of detriment to your ability to think clearly as well as reducing your awareness of your surroundings [16].Vitamin B2 - Riboflavin vitamin b2) can help to reduce inflammation and oxidative stress to nerves in the brain, both of which can contribute to headaches and migraines [17].Vitamin B3 - Niacin (vitamin B3) is another B vitamin that plays an important role in the health of your brain. It’s involved in making and repairing DNA, cell signaling and acts as an antioxidant [18].Folate - Suboptimal mental function can be linked to low folic acid (folate) levels in the blood.A randomized controlled trial over 2 years showed that 400mg folic acid supplementation improved measures of brain function and decreased blood levels of proteins that are linked to Alzheimer’s disease [19].Selenium - Selenium is a powerful antioxidant [20], and people with Alzheimer’s have been found to have lower levels of selenium in their blood [21].Copper - Essential for brain function, too much or too little copper in the body can be linked with neurodegeneration [22].Manganese - Manganese is required for many functions in the body, which includes normal brain and nervous system function.It’s another powerful antioxidant (potentially one of the most important) [23] that can help to protect your brain against free radicals, as well as improving your brain function [24].Potassium - Potassium plays an important role in the cardiovascular system, helping to get blood to the brain [25].Choline - Choline is needed to produce a neurotransmitter called acetylcholine, which is crucial to regulate intelligence, mood and memory [26].Grape Seed Extract - Grapes contain flavonoids, which possess powerful antioxidants and anti-inflammatory properties. Studies have shown that grape seed extract may help to improve cognitive status and antioxidant levels in the brain, while preventing memory loss [27].GABA - GABA (gamma aminobutyric acid) is an amino acid that functions as a neurotransmitter in the brain. When GABA attaches to a GABA receptor in the brain, it has a calming effect [28].Bilberry Fruit Extract - Bilberry fruit extracts have been shown to help improve memory (both working and long-term) in older adults [29].And many more!We understand that it’s not always easy, nor is it practical to implement a variety of lifestyle changes at once.We’d advise that you make as many of those changes listed further up this page as possible, but to do so 1 or 2 at a time, make sure they stick and then implement a couple more.In the meantime, you can support your body with the essential nutrients and minerals it needs that can help you to boost your brain's function.That’s why we’ve included the above ingredients into our Brain Boost Plus formula, and included other minerals and vitamins that we think are worth taking to support the health of your brain, such as: Vitamin E [30], Iron [31], Biotin [32], Vitamin B5 [33], Vitamin B6 [34], Zinc [35], Chromium [36], Molybdenum [37], DMAE Bitartrate [38], L-glutamine [39], Green Tea Extract [40], Bacopa Extract [41], Inositol [42], N-Acetyl L-Tyrosine [43], Olive Leaf [44], Cinnamon Bark Extract [45], Licorice Root Extract [46], Boron [47], DHA [48], Vanadyl [49], Phosphatidylserine [50], Huperzine A [51]. By combining the ingredients listed on this page, with our unique proprietary blend in an easy to swallow capsule, we’ve taken the stress out of buying each of these ingredients separately, researching and experimenting how much of each you should take and then incorporating them into your diet/supplement regime.Here at Feel younger, we believe in providing strong doses at reasonable prices. Our Brain Boost Plus capsules provide a 1,004 mg dose that will cost you no more than $29, with discounts available on multiple bottle and subscription purchases.How Do You Take Feel Younger® Brain Boost Plus, Neuro Brain and Focus Formula?Take two capsules a day with your morning meal.Any Cautions?ALWAYS consult a healthcare professional before taking any new supplements. Scientific References https://www.ncbi.nlm.nih.gov/books/NBK279302/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143346/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437759/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258000/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543069/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598577/ https://www.health.harvard.edu/heart-health/blood-pressure-and-your-brain https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844833/ https://www.nia.nih.gov/news/social-isolation-loneliness-older-people-pose-health-risks https://pubmed.ncbi.nlm.nih.gov/32933226/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3169332/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649700/ https://www.medschool.umaryland.edu/news/2021/University-of-Maryland-School-of-Medicine-Study-Finds-Calcium-Precisely-Directs-Blood-Flow-in-the-Brain.html https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970300/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761127/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659035/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/ https://pubmed.ncbi.nlm.nih.gov/26828517/ https://pubmed.ncbi.nlm.nih.gov/29255930/ https://pubmed.ncbi.nlm.nih.gov/19033020/ https://pubmed.ncbi.nlm.nih.gov/24668390/ https://www.sciencedirect.com/science/article/pii/S0301008214000124 https://pubmed.ncbi.nlm.nih.gov/22072939/ https://pubmed.ncbi.nlm.nih.gov/12505649/ https://pubmed.ncbi.nlm.nih.gov/23558164/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252552/ https://pubmed.ncbi.nlm.nih.gov/21871550/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231020/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024810/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276978/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789770/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772032/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728061/ https://pubmed.ncbi.nlm.nih.gov/20423560/ https://pubmed.ncbi.nlm.nih.gov/15207438/ https://pubmed.ncbi.nlm.nih.gov/864168/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760805/ https://pubmed.ncbi.nlm.nih.gov/28899506/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153866/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554709/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6084775/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074804/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466762/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974064/ https://pubmed.ncbi.nlm.nih.gov/7889884/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772061/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077345/ https://clinicaltrials.gov/ct2/show/NCT04920305 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930088/

BENEFITS OF Helps maintain healthy brain inflammation levels* Encourages new brain cell growth* Supports healthy neurons for better memory power* Protects the brain from free radical damage* Aids healthy blood flow & oxygen levels* Promotes a calm, focused mind & balanced moods* PRODUCT DETAILS 8-in-1 complete brain health supplement Made from wild-sourced and organic brain-boosting botanicals Formulated by natural health visionary “Amazon John” Easterling Ingredients responsibly sourced from a nature preserve in the Amazon rainforest Non-GMO; No artificial flavors, preservatives, colors, fillers, or additives  3rd-Party Tested to ensure free from pesticides, glyphosate, and heavy metals Ingredients Organic Cat’s Claw Powder This ancient herbal remedy has been used for 2,000 years as a potent antioxidant and anti-inflammatory. Studies show it can help repair damaged DNA and strengthen the communication (synapses) between neurons. Plus, it can also help grow new brain cells by boosting brain-derived neurotrophic factor (BDNF).   Organic Bacopa Monnieri Powder An amazing natural brain booster that speeds up reaction time and improves memory, bacopa also helps improve mood by decreasing feelings of anxiety and depression. It’s been shown to help increase BDNF for new brain cell growth and reduce amyloid plaque (a hallmark of Alzheimer’s disease) in the brain.   Organic Pau d’Arco A powerful antifungal, pau d’arco contains a compound called lapachol that can be deadly against certain viruses, bacteria, fungi (including Candida), parasites, and more. It’s also a major anti-inflammatory that helps protect brain cells by blocking key enzymes that can contribute to brain inflammation.   Dragon’s Blood Resin Extract Beneficial for banishing brain fog and improving memory recall, dragon’s blood is a dark red, thick tree sap that’s one of the most powerful antioxidants in the world. Research shows it’s an amazing brain protector and neurogenic inflammation fighter, meaning it helps keep brain inflammation levels low.   Organic Camu Camu Powder Camu camu contains one of the highest levels of vitamin C of any plant. Not only is vitamin C a powerful antioxidant that helps prevent free radical damage, it’s also essential for the “synthesis” of other important substances in the body – including brain neurotransmitters.   Organic Cinnamon Not just a flavorful culinary spice, cinnamon is a real antioxidant powerhouse that is best known for helping to normalize blood sugar and reducing inflammation and pain. It contains two unique compounds: epicatechin and cinnamaldehyde, which have been shown to protect against age-related memory loss.   Organic Cacao Powder Cacao is considered a mood-lifter as well as a “brain-builder” as it contains neurotransmitters that are associated with pleasure as well as motivation. It’s also a rich source of resveratrol, a powerful antioxidant that helps to remove amyloid plaque from the brain.   Organic Guayusa Extract With twice as many antioxidants as green tea and containing the neuroprotective amino acid L-theanine, guayusa improves age-related cognitive decline, protects brain cells against free radical damage, and reduces anxiety. It also contains small amounts of caffeine, which can produce a “calm focus” in individuals.

Serotonin Brain Food™ highlights: ● Happier, more stable moods● Improved gut health, digestion and physical wellbeing● No artificial ingredients, no GMOs, no gluten. What is “brain food”? Neurochemistry - the chemical patterns and processes that cause your brain to function as it does - is highly complex. It varies significantly between individuals, and is heavily influenced by a large range of factors. Your diet, exercise habits, sun exposure, social group and genetics all have a role to play in your brain’s chemical behaviour. Most of us do not get enough of everything we need every day to keep our brain function 100% optimized. That’s why supplementing with brain food can give you such an edge. Brain food are natural nutrients that act as fuel for specific neurotransmitters in the brain. They can be taken daily to boost various states of optimal performance. By addressing any deficiencies or imbalances in the delicate neurological system, you can increase your ability to concentrate, regulate your energy, and balance your mood. The importance of Serotonin Serotonin is a neurotransmitter that is associated with a sense of wellbeing and happiness, as well as a healthy appetite and digestive system, constricting smooth muscles, and transmitting impulses between nerve cells. Abnormal serotonin levels can cause serious problems, such as osteoporosis, poor libido, nausea, migraines, obesity and Parkinson’s disease. Low levels are associated with depression, anxiety, and obsessive compulsive behavior. Getting your serotonin levels balanced and in an optimal range can have a profound influence on your health and quality of life. When your serotonin is being produced at the optimal pace, you will feel calm and healthy. Your mood will be positive, stable, and well balanced. Complete Neurotransmitter Support The best way to optimize serotonin levels is to ensure that the necessary precursors and cofactors are available. These precursors and cofactors pave the way for your brain to produce and then use serotonin at an optimal rate for your particular physiology. Serotonin Brain Food™ provides these essential compounds. It contains an amino acid precursor (L-Tryptophan), serotonin metabolism cofactors (Vitamin B-3, Zinc, & Magnesium), and an herbal extract to reduce cortisol (Rhodiola Rosea). For A Positive Mood SUGGESTED USE: Take a serving of 2-3 capsules to support a positive mood, during situations of stress or irritability, or as directed by a healthcare practitioner. Avoid use in the evening. Do not exceed 2 servings per day. U.S.A manufactured in a cGMP facility. Natural Stacks proudly uses only the highest quality ingredients. L-Tryptophan As a precursor to serotonin, this essential amino acid is directly converted into 5-HTP. It’s found in many foods such as egg whites, soybean, and turkey. Vitamin B-3 (Niacinamide) An essential vitamin that is also a necessary cofactor for the proper catabolism of fat, carbohydrate, protein, and alcohol. It’s also closely involved in cell signaling and DNA repair. It’s used most extensively in the brain, gut and skin, which have a high cellular turnover rate. Our Vitamin B-3 source is a niacinamide, which has been carefully selected to be non-flushing - many other Vitamin B-3 sources are niacin, which can cause uncomfortable skin flushing. Magnesium (Magnesium Glycinate) Magnesium glycinate has a positive impact on attention, memory, and stress reduction. Utilizing the essential amino acid glycine, this form of magnesium has a calming effect on the brain. Zinc (Zinc Glycinate) Zinc glycinate is a critical factor in maintaining a healthy immune system. It supports optimal cell division and replication, improves healing times, and ensures proper growth patterns and sensory development. Rhodiola Rosea An herb native to the Arctic and northernmost parts of Europe and Central Asia, Rhodiola Rosea has been used in herbal medicine for many years. It’s associated with improvements in mood, reduced stress and depression, and overall increases in physical and mental well being and performance. Serotonin Metabolism, by Abelard Lindsay Serotonin is a neurotransmitter responsible for mood[1], fear[2], aggression[3] and anxiety[4]. It plays a large part in the digestive process as it interacts with neurons present in the gut[5]. Healthy serotonin levels allow one to be in the moment instead of becoming drawn into negative thought patterns. Where does serotonin come from? It starts with tryptophan. Tryptophan is an essential amino acid that is a precursor to serotonin. It is found in many foods such as egg whites, soybean and turkey and is also available as a nutritional supplement[6]. It is converted into 5-HTP by the enzyme tryptophan hydroxylase(TH). TH is a key rate limiting enzyme that controls the production of 5-HTP in the body. TH comes in two variants. TPH1, which is present in the gut and the peripheral nervous system, and TPH2, which is primarily expressed in the central nervous system[7]. Serotonin outside the CNS is not particularly interesting for cognitive enhancement. It is however suspected that a lack or excess of serotonin in the digestive tract can lead to irritable bowel syndrome. Some drugs with antidepressant effects are actually used to control certain intractable digestive problems, presumably by having an effect on the neurochemical aspects of digestion[8]. Serotonin is an agonist for many different serotonin receptors in the brain. Many antidepressant drugs developed over the past 30 years, known as SSRIs, have been developed in order to keep serotonin active in the synaptic cleft by reducing the activity of the SERT enzyme[9]. The theory behind this is that stimulating serotonin receptors via increased synaptic serotonin will improve and alleviate depression[10]. Exercise, a well studied treatment for depression[11], has been investigated as a serotonin production enhancer through various mechanisms[12]. Serotonin is broken down and then processed into melatonin via methylation[13]. Melatonin is crucial for sleep. Methylation is also active in the dopamine system and breaks down norepinephrine to epinephrine. Supplementation of melatonin has been shown to increase serotonin in animal models[14]. Seasonal affective disorder, a form of depression caused by lack of sunlight in winter months, is tied to serotonin deficiency[15]. This is possibly due to excess melatonin production from serotonin as melatonin production is controlled by light exposure and the circadian rhythms[16]. Another system that has a profound effect on serotonin metabolism is regulated by the hormone cortisol. Cortisol pathways, which are induced by stress, cause an increase in serotonin reuptake, possibly contributing to depression[17]. Increased cortisol also may increase the production of N-formyl-L-kynurenine by increasing the activity of tryptophan 2,3-dioxygenase[18]. This pathway uses up L-Tryptophan in the eventual production of niacin instead of serotonin. Niacin is produced from tryptophan in competition with the serotonin pathway[19]. Supplementing niacin thus may free up tryptophan to be processed into serotonin. Magnesium is important in processing serotonin[20]. A correlation has been shown between low magnesium levels and depression[21]. Experimental evidence has also shown that magnesium is needed as a cofactor of tryptophan hydroxylase, which converts tryptophan into 5-HTP, a serotonin precursor, and magnesium is also needed for binding serotonin[22]. It also increases activity at the 5-HT1A serotonin receptor.[23] Zinc also enhances outcomes in unipolar depression[24]. The mechanism of action on serotonin is that it modulates uptake of serotonin into cells[25]. Herbs that have exhibited serotonin reuptake inhibition activity like St. John’s Wart[26] and herbs with observed MAO-A inhibition activity like resveratrol[27] are powerful increasers of serotonin and should only be used in situations where there is a significant deficiency. Berberine heavily influences the 5-HTT transporter[28] while having positive health benefits and being well tolerated over long periods of time. Serotonin is a regular and reliable system that responds to supplementation and has positive effects on mood and energy. There’s a huge difference between low levels of serotonin and optimal levels in how you think, feel and perform.