A Unique Smart Nutrient to Enhance Your

Mental Function Now ...

While Helping to Repair Brain Cell Membranes for Long Term Health

 Improve immediate recall, reaction time, and mood

 Protect delicate brain cells and membranes

 Support optimal brain function

 Help counteract cognitive impairment such as: Alzheimer's disease, brain injuries,
stroke, vascular dementia, and Parkinson's disease

GPC: The new choline that enhances cognition in the young, middle-aged, and
elderly

We are continually learning about how the brain functions, environmental and dietary factors
that contribute to brain aging—and enhancement—and how it's possible to increase your
intelligence and sensory perception beyond the predictors of aging, genetics, and IQ tests.

Alpha Glycerylphosphorylcholine (GPC), a form of choline, is an exciting nutrient recently

developed as a cognitive enhancer. But GPC is not the ordinary form of choline we've been
hearing about (or even taking) for years. GPC is a source of phospholipids (the prime building
blocks of life) and choline, which is utilized for phosphatidylcholine biosynthesis in the brain,
and for the neurotransmitter acetylcholine—one of the chemicals that enable brain cells to
communicate with each other. Although GPC has all the benefits of choline, it is much more
effective at increasing acetylcholine and phosphatidylcholine production.

Acetylcholine is essential for cognitive function, and is responsible for storing and recalling
memories. It is vital for communication between neurons, and in two Italian studies
supplementation with GPC indicated an increase in brain function directly related to a healthy
supply of acetylcholine.

In the two controlled trials, daily doses of 1200 mg of GPC improved the immediate recall and
attention in a group of young adult males (ages 19-38) compared with a placebo.1,2 In middle-
aged and elderly subjects, GPC supplementation improved reaction time by supporting energy
generation and electrical coordination in the brain.3,4

In studies of older patients with vascular dementia, 1200 mg per day of GPC helped improve
cognition, as well as emotional state, confusion, and apathy.5

Why is choline important to brain functioning?

Choline is the important B vitamin that fuels tissue renewal and helps build acetylcholine. It is so
vital to thought and nerve function that, without it, we couldn't move, think, sleep or remember
anything.

Choline is also responsible for synthesizing phosphatidylcholine (PC), a component of the

membrane of every cell in your body, including brain cells. In addition to its role as a structural
element in cell membranes, PC acts as a choline reservoir for synthesizing more acetylcholine
when needed.6

Because phosphatidylcholine is a common component of cell membranes, it is distributed

throughout the body. Also, as we age, choline levels decline and it is unable to get into the brain
efficiently.7,8 For years, lecithin was a popular supplement thought to supply choline, but a
review of randomized trials did not find lecithin to be more beneficial than placebo in the
treatment of patients with dementia or cognitive impairment.9

GPC is a "next generation" supplement that effectively supplies choline, stimulates membrane
repair and benefits cognitive function.

GPC has been proven extremely effective, both in the elderly for brain decline linked to poor
circulation and Alzheimer's disease, and for enhancing mental performance in healthy young
adults.

GPC has been shown to:

 Help brain recovery following injury, coma, and surgery

 Improve memory and cognitive performance in patients with Alzheimer's dementia 10

 Improve memory and learning ability in laboratory animals 11-13

 Counteract brain aging in rats by increasing cholinergic receptor sites,14,15 restoring the
bioavailability of acetylcholine,16,17 increasing nerve growth factor receptors in the
brain,18 and slowing down undesirable structural changes in the brain 19,20

 Counter the age-related loss of nerve cells and fibers in the brain

 Protect the brain and other organs against toxic waste buildup

 Increase growth hormone secretion in both the young and the old 21,22

 Support patients recovering from cerebral ischemic attacks 23

 Increase the release of dopamine, the neurotransmitter that plays a major role in
Parkinson's disease 24,25

How does GPC work?

GPC is water-soluble and after it is ingested it quickly enters the brain, where it protects neurons
and improves signal transmission, and supports brain function and learning processes by directly
increasing the synthesis and secretion of acetylcholine, as your body needs it. Instead of being a
precursor to phosphatidylcholine (PC), GPC is actually a metabolite of PC.

In other words, after phosphatidylcholine is metabolized and stripped of its fatty acids, GPC—a
glycerin molecule bound to phosphocholine—is what remains. This is a source of choline in the
same form that a cell would obtain from scavenging its own membranes. And this is exactly the
form of choline that neurons prefer to use for synthesizing acetylcholine during times of choline
scarcity.

Also, GPC is very good at repairing and maintaining brain cell membranes. What most people
don't understand is that a cell membrane is living fluid. If you were able to watch the activity in a
cell membrane in real time, it would be like watching a fireworks display with a million things
happening at once. Neurotransmitters are released through the membrane, which needs to be
instantly repaired. As we age, the mechanism that allows the membrane to be repaired becomes
compromised, which is another reason to take GPC as a nutritional supplement.

GPC helps increase growth hormone

The decline of growth hormone (GH) levels as we age is believed to contribute to decreases in
bone mass, muscle mass, and strength. The decrease in GH is also associated with age-related
cognitive impairment.26 Interestingly, the cholinergic system helps regulate GH through the
release of growth hormone-releasing hormone, which in turn triggers secretion of GH from the
pituitary gland.27

In one study, in order to learn the effect that GPC had on GH secretion, GH-release hormone
(GHRH) was given to young and old human volunteers, with or without the addition of GPC.
The younger subjects showed a higher level of GH secretion than the older individuals, and both
groups had a greater growth hormone response to the GHRH plus GPC than to GHRH alone.
The ability of GPC to increase GH secretion was more pronounced in the older subjects.

The results showed that supplementation with GPC enhances the release of growth hormone
(GH),28 indicating that it can help counteract aging in the elderly and help build muscle mass
and strength in the young.

GPC and Citicoline: Cutting-edge choline supplements

As you might imagine, the maintenance of membranes requires much more than just a source of
choline. GPC appears to be a particularly effective form of choline, but if it were possible to
further stimulate the natural process of membrane repair, even greater beneficial effects could be
obtained. Scientists have long known that the conversion of choline to a compound called
citicoline is an essential step for phospholipid production and membrane repair.

Citicoline occurs naturally in the body and works by supplying cytidine and choline to the cells.
Cytidine (a nucleic acid) helps promote the conversion of choline into membranes, an essential
step for cellular function. Choline is also necessary in order to get the full effect of cytidine.
Because of this, citicoline was developed as a neuroprotective and cognitive enhancing drug in
Europe and Japan. The research on citicoline has found that it is helpful in:

 Stroke29

 Brain injury30,31

 Neurodegeneration, such as glaucoma32

 Parkinson's disease

 Cardiovascular disease

 Alzheimer's disease33

 Learning and memory

 Cholinergic stimulation34

Numerous studies on humans and rats have shown that ingestion of citicoline helps reverse age-
related changes in the brain. In a study at Harvard Medical School healthy, older subjects who
took 500 mg of citicoline for six weeks had an increase of phosphotidylcholine in the brain and
improved their scores on the California Verbal Learning Test.35

Another study done at the Massachusetts Institute of Technology, Cambridge, Massachusetts,

tested the verbal memory of older volunteers who were given citicoline. In the initial study, a
group of 47 women and 48 men, 58-85 years of age, were given 1000 mg of citicoline a day.
After three months, the men and women with inefficient memories showed an improvement in
delayed recall on logical memory tests. In a crossover study in which the group was given a
placebo and a higher dosage of citicoline the results indicated a clear improvement in immediate
and delayed logical memory. The study concluded that citicoline may prove effective in treating
age-related cognitive decline that may be the precursor of dementia.36

Citicoline converts to uridine

When citicoline is ingested it is broken down into cytidine and choline. The cytidine portion is
rapidly converted to uridine. Uridine—another nucleic acid— is the form that is apparently
transported in blood37, and cytidine is what is used on a cellular level. It appears that uridine can
supercharge the beneficial effects of choline, so the functionality of citicoline can be attributed to
uridine.

The latest research shows that supplementation with uridine and GPC provides the optimal
source of choline and co-factors for cognitive enhancement, membrane repair, and
neuroprotection.
The GPC form of choline is much more effective at increasing blood levels of choline as
compared to choline or citicoline.38 Since the combination of uridine and GPC provides the
ingredients needed for optimal cell membrane repair, it makes sense to take a nutritional
supplement that includes both.

What causes brain aging?

Ten to twelve percent of the brain is composed of lipids,39 which insulate the electrical
pathways enabling healthy neurotransmission. These lipids, however, are highly susceptible to
oxidative damage. Brain cells are delicate and susceptible to free radical damage from stress,
pollutants, drugs, poor diet, inadequate blood supply, alcohol, and other factors.

Additionally, there are three theories that explain why memory and cognitive function diminish
over time.

1. According to the cholinergic theory, neurological function diminishes when brain cells
lose their ability to produce adequate amounts of neurotransmitters. The theory was
developed in 1982 when scientists reported that the number of cholinergic neurons in the
basal forebrain was substantially lower in Alzheimer's disease patients than in healthy
individuals.40,41

The decline in numbers and the shriveling in size of these cholinergic cells is partly the
result of defective cell membranes caused by a decreased availability of choline and an
increased breakdown of phosphatidylcholine.42-46 When choline is in short supply and
cholinergic cells are active, any available choline goes to make more acetylcholine at the
expense of building membranes. Eventually, enough choline is withdrawn from the
membrane so that the amount of PC in a cell actually decreases, a process known as
autocannibalism.47 It is believed that this disruption in normal membrane structure in
brain cells is a major cause of brain aging.

2. A second theory ties the decline of cognitive function and memory to the actual structure
of the brain. Over time, brain cells die, the brain shrinks, and there is a decrease in
synaptic density affecting the brain's capacity to process and store information.

3. The membrane hypothesis, which was developed in the late 1970s on the basis of a series
of biological experiments, asserts that the lipid composition of cells changes due to the
accumulation of cholesterol in cell membranes. Consequently, membrane fluidity
decreases, leading to less enzyme activity and a decrease in neurotransmission, which
negatively impacts cognitive function.48,49

The good news is Alpha Glycerylphosphorylcholine (GPC) and Uridine have been shown to
protect and repair delicate brain cells and membranes—and consequently help slow down brain
aging, and support memory and cognitive function.

Avoiding the Alzheimer's epidemic

Losing your mental faculties is one of the greatest fears of the elderly. But because of the
alarming rate at which Alzheimer's disease and other forms of dementia are increasing, baby
boomers are beginning to worry too—and with good reason.

Approximately 4 million Americans currently suffer from Alzheimer's. In a 1993 national

survey, 19 million Americans said they had a family member with the disease, and 37 million
said they knew someone with Alzheimer's. The disease is increasing so fast that experts predict
by 2025 more than 22 million people worldwide will be affected unless a cure or prevention is
found.50

The only way to avoid the epidemic, research scientists say, is to accelerate the search for a way
to delay, prevent, or cure the disease. But "large scale trials are expensive—$15 to $20 million
each—and they take at least five years to get results," says Dr. Steven DeKosky of Pittsburgh, a
national leader in Alzheimer research and chair of the Alzheimer's Association's Medical and
Scientific Advisory Council.51

Since scientists now know that brain cells begin to change at least ten years before the symptoms
of Alzheimer's appear, baby boomers will reach the age of highest risk in about 2010, adds
DeKosky. "We do not have enough time left to do these five-year trials one at a time. Scientists
have many more good ideas for effective treatments than they can test with current funding," he
says.52

One of the good ideas that is showing positive results for Alzheimer's disease, other forms of
dementia and cognitive problems, and as a general cognitive enhancer is nutritional
supplementation with GPC and Uridine.

Conclusion

Although there is much more research to be done into the effects GPC and Uridine on human
subjects, the results of studies so far are extremely encouraging. Safe and without side effects,
GPC and Uridine are nutritional supplements that provide a superior form of choline to the brain
and have been shown to protect cell membranes, enhance cognition by supporting
neurotransmitters, and provide an overall anti-aging effect for brain cells.

GPC offers tremendous potential for preventing Alzheimer's disease, as does citicoline and
uridine. Autocannabalism of membrane phosphatidylcholine to make acetylcholine seems to
explain the unique vulnerability of cholinergic neurons to age-related decline. It is thought that
changes in the cell membrane due to phosphatidylcholine depletion impair normal processing of
amyloid precursor protein by the membrane bound proteases. The problem is, once you have
Alzheimer's, you already have massive brain cell loss, which nothing can reverse. So treatment is
much more difficult than prevention.

If you or someone you love would like the support of a superb cognitive enhancer, are concerned
about the threat of Alzheimer's disease, vascular dementia, or suffer from a brain injury due to
accident, illness or stroke, try GPC and Uridine—the "next generation" cognitive enhancers.
See Other Articles of Interest From
Smart Publications Health & Wellness Update

You Can be Much Smarter than You are Now, in Just Weeks.

Bacopa: The Powerful Cognitive Enhancer for People of All Ages

References:

1. Canal N, et al. Effect of L-glyceryl-phosphorylcholine on amnesia caused by

scopolamine. Intl J Clin Pharmacol Ther Toxicol 1991;29;103-7
Abstract

2. Canal N, et al. Comparison of the effects of pretreatment with choine alfoscerate,

idebenone, aniracetam and placebo on scopolamine-induced amnesia. Le Basi Razionali
della Terapia 1993;23:102-7.

3. Moglia A, Bergonzoli S, de Moliner P. Effect of aGPC in brain mapping changes in

patients with age associated memory impairment (AAMI). Le Basi Razionali della
Terapia 1990;20:83-9.

4. Sicurella L, et al. Changes in VEP in subjects treated with alphaGFC. Preliminary study.
Le Basi Razionali della Terapia 1990;29(3 Suppl.1):91-3.

5. Parnetti, L, Amenta F, Gallai V. choline alfoscerate in cognitive decline and in acute

cerebrovascular diseases: an analysis of published clinical data. Mechs Ageing
Development 2001;122:220-55.
Abstract

6. Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic
neurons. Trends Neuroscience. 1992;15 (4):117-22.

7. Mooradian AD. Blood-brain barrier transport of choline is reduced in the aged rat. Brain
Res. 1988;440(2):328-32.
Abstract

8. Cohen BM, Renshaw PF, Stoll AL, Wurtman RJ, Yurgelun-Todd D, et al. Decreased
brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy
study. JAMA. 1995;274(11):902-7.
Abstract

9. Higgins JP, Flicker L. Lecithin for dementia and cognitive impairment. Cochrane
Database Syst Rev. 2000;(4):CD001015.
Abstract

10. Parnetti L, Abate G, Bartorelli L, Cucinotta D, Cuzzupoli M, Maggioni, M, Villardita C,

Senin U. Multicentre study of l-alpha-glyceryl-phosphorylcholine vs ST200 among
 patients with probable senile dementia of Alzheimer's type. Drugs Aging 1993 Mar-
Apr;3(2):159-64
Abstract

11. Drago F, Mauceri F, Nardo L, Valerio C, Lauria N, Rampello L, Guidi G. Behavioral

effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the
rat. Pharmacol Biochem Behav 1992 Feb;41(2):445-8.
Abstract

12. Schettini G, Ventra C, Florio T, Grimaldi M, Meucci O, Scorziello A, Postiglione A,

Marino A. Molecular mechanisms mediating the effects of L-alpha-
glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and
biochemical parameters in young and aged rats. Pharmacol Biochem Behav 1992
Sep;43(1):139-51.
Abstract

13. Lopez CM, Govoni S, Battaini F, Bergamaschi S, Longoni A, Giaroni C. Effect of a new
cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia
and brain acetylcholine. Pharmacol Biochem Behav 1991 Aug;39(4):835-40.
Abstract

14. Amenta F, Liu A, Zeng YC, Zaccheo D. Muscarinic cholinergic receptors in the
hippocampus of aged rats: influence of choline alphoscerate treatment. Mech Ageing Dev
1994 Oct 1;76(1):49-64
Abstract

15. Amenta F, Franch F, Ricci A, Vega JA. Cholinergic neurotransmission in the

hippocampus of aged rats: influence of L-alpha-glycerylphosphorylcholine treatment.
Ann N Y Acad Sci 1993 Sep 24;695:311-3
Abstract

16. Bronzetti E, Felici L, Amenta F. Effect of ipsilateral lesioning of the nucleus basalis
magnocellularis and of L-alpha-glyceryl phosphorylcholine treatment on choline
acetyltransferase and acetylcholinesterase in the rat fronto-parietal cortex. Neurosci Lett
1993 Dec 24;164(1-2):47-50
Abstract

17. Trabucchi M, Govoni S, Battaini F. Changes in the interaction between CNS cholinergic
and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a
cholinomimetic drug. Farmaco [Sci] 1986 Apr;41(4):325-34
Abstract

18. Vega JA, Cavallotti C, del Valle ME, Mancini M, Amenta F. Nerve growth factor
receptor immunoreactivity in the cerebellar cortex of aged rats: effect of choline
alfoscerate treatment. Mech Ageing Dev 1993 Jun;69(1-2):119-27.
Abstract
19. Amenta F, Ferrante F, Vega JA, Zaccheo D.Long term choline alfoscerate treatment
counters age-dependent microanatomical changes in rat brain. Prog
Neuropsychopharmacol Biol Psychiatry. 1994 Sep;18(5):915-24.
Abstract

20. Neuropsychopharmacol Biol Psychiatry 1994 Sep;18(5):915-24. Amenta F, Del Valle M,

Vega JA, Zaccheo D. Age-related structural changes in the rat cerebellar cortex: effect of
choline alfoscerate treatment. Mech Ageing Dev 1991 Dec 2;61(2):173-86
Abstract

21. Ceda GP, Ceresini G, Denti L, Marzani G, Piovani E, Banchini A, Tarditi E, Valenti G.
alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of
young and elderly subjects. Horm Metab Res 1992 Mar;24(3):119-21
Abstract

22. Ceda GP, Ceresini G, Denti L, Magnani D, Marchini L, et al. Effects of cytidine 5'-
diphosphocholine administration on basal and growth hormone-releasing hormone-
induced growth hormone secretion in elderly subjects. Acta Endocrinol (Copenh).
1991;124(5):516-20.
Abstract

23. Barbagallo Sangiorgi G, Barbagallo M, Giordano M, Meli M, Panzarasa R. Alpha-

Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. Ann N Y
Acad Sci 1994 Jun 30;717:253-69
Abstract

24. Trabucchi M, Govoni S, Battaini F. Changes in the interaction between CNS cholinergic
and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a
cholinomimetic drug. Farmaco [Sci]. 1986;41(4):325-34.
Abstract

25. Agut J, Ortiz JA, Wurtman RJ. Cytidine (5')diphosphocholine modulates dopamine K(+)-
evoked release in striatum measured by microdialysis. Ann N Y Acad Sci. 2000;920:332-
5.
Abstract

26. van Dam PS, Aleman A, de Vries WR, Deijen JB, van der Veen EA, et al. Growth
hormone, insulin-like growth factor I and cognitive function in adults. Growth Horm IGF
Res. 2000;10 Suppl B:S69-73.
Abstract

27. Giusti M, Marini G, Sessarego P, Peluffo F, Valenti S, et al. Effect of cholinergic tone on
growth hormone-releasing hormone-induced secretion of growth hormone in normal
aging. Aging (Milano). 1992;4(3):231-7.
Abstract

28. Ceda GP, Ceresini G, Denti L, Marzani G, Piovani E, et al. alpha-

Glycerylphosphorylcholine administration increases the GH responses to GHRH of
 young and elderly subjects. Horm Metab Res. 1992;24(3):119-21.
Abstract

29. Stroke: D'Orlando KJ, Sandage BW Jr. Citicoline (CDP-choline): mechanisms of action
and effects in ischemic brain injury. Neurol Res 1995 Aug;17(4):281-4.

30. Levin HS. Treatment of postconcussional symptoms with CDP-choline. J Neurol Sci
1991 Jul;103 Suppl:S39-42
Abstract

31. Spiers PA, Hochanadel G. Citicoline for traumatic brain injury: report of two cases,
including my own. J Int Neuropsychol Soc 1999 Mar;5(3):260-4
Abstract

32. Grieb P, Rejdak R. Pharmacodynamics of citicoline relevant to the treatment of

glaucoma. J Neurosci Res 2002 Jan 15;67(2):143-8
Abstract

33. Farber SA, Slack BE, Blusztajn JK. Acceleration of phosphatidylcholine synthesis and
breakdown by inhibitors of mitochondrial function in neuronal cells: a model of the
membrane defect of Alzheimer's disease. FASEB J 2000 Nov;14(14):2198-206
Abstract

34. Weiss GB. Metabolism and actions of CDP-choline as an endogenous compound and
administered exogenously as citicoline. Life Sci 1995;56(9):637-60
Abstract

35. Babb SM, Wald LL, Cohen BM, Villafuerte RA, Gruber SA, Yurgelun-Todd DA,
Renshaw PF. Chronic citicoline increases phosphodiesters in the brains of healthy older
subjects: an in vivo phosphorus magnetic resonance spectroscopy study.
Psychopharmacology (Berl) 2002 May;161(3):248-54
Abstract

36. Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves
verbal memory in aging. Arch Neurol 1996 May;53(5):441-8
Abstract

37. Wurtman RJ, Regan M, Ulus I, Yu L. Effect of oral CDP-choline on plasma choline and
uridine levels in humans. Biochem Pharmacol 2000 Oct 1;60(7):989-92
Abstract

38. Gatti G, Barzaghi N, Acuto G, Abbiati G, Fossati T, Perucca E. 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 Sep;30(9):331-5.
Abstract
39. Int J Clin Pharmacol Ther Toxicol 1992 Sep;30(9):331-539. McIlwain, H. and Bachelard,
H.S., Biochemistry and the Central Nervous System, Edinburgh: Churchill Livingstone,
1985.

40. Whitehouse et al. 1982. Science 215:1237.

41. Gallagher M, Colombo PJ. Ageing: the cholinergic hypothesis of cognitive decline. Curr
Opin Neurobiol. 1995;5(2):161-8.
Abstract

42. Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic
neurons. Trends Neurosci. 1992;15(4):117-22

43. Beninger RJ, Wirsching BA, Jhamandas K, Boegman RJ. Animal studies of brain
acetylcholine and memory. Arch Gerontol Geriatr Suppl. 1989;1:71-89.
Abstract

44. Gallagher M, Colombo PJ. Ageing: the cholinergic hypothesis of cognitive decline. Curr
Opin Neurobiol. 1995;5(2):161-8.
Abstract

45. Muller WE, Stoll L, Schubert T, Gelbmann CM. Central cholinergic functioning and
aging. Acta Psychiatr Scand Suppl. 1991;366:34-9.
Abstract

46. Nitsch RM, Blusztajn JK, Pittas AG, Slack BE, Growdon JH, et al. Evidence for a
membrane defect in Alzheimer disease brain. Proc Natl Acad Sci U S A.
1992;89(5):1671-5.
Abstract

47. Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic
neurons. Trends Neurosci. 1992;15(4):117-22.

48. I. Zs.-Nagy, (1979) The role of membrane structure and function in cellular aging: a
review. Mech. Ageing Dev. 9, 237-246.
Abstract

49. I. Zs.-Nagy, (1978) A membrane hypothesis of aging. J. Theoretical. Biol. 75, 189-195.

50. Alzheimer's Association

51. "Race Against Time: Alzheimer's Epidemic Hits as America Ages" News Release, 3-27-
2000. AlzheimerSupport.com

52. Ibid.