Nutrasal
Nutrasal Cerebra GPC (60ml) 2fl oz
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.
