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Clinical Review:An abbreviated look at the science supporting the memory, brain energy and focus benefits of Cognizin® citicoline

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Introducing Cognizin® citicolineCognizin is a branded form of pure, stable citicoline—an organic molecule produced endogenously and found in every living cell. This molecule is needed to build cell membranes throughout the body, but its cognitive health benefits have been studied repeatedly. This paper introduces some of the more important studies pertaining to citicoline’s ability to support cognitive health in three areas:

1 Healthy memory function*2 Brain metabolism and energy*3 Focus and attention*

CiticolineCiticoline is an important building block that is synthesized into two types of compounds vital to healthy brain function:

Phospholipids Phospholipids are essential constituents of cell membranes—including phosphotidylcholine, phosphatidylserine and phosphatidyl-ethanolamine. Because cell membranes have a very high turnover rate, these phospholipids must be continuously synthesized to ensure adequate function of cells.

Neurotransmitters Neurotransmitters, including acetylcholine, dopamine and noradrenaline, all play a role in healthy brain function, including the formation of new memories, focus and attention.

The scientific name for citicoline is cytidine 5’-diphosphocholine

ChemistryMolecular formula: C14H26N4O11P2

Structural formula

Natural aging and decrease of phosphatidylcholineThe synthesis of citicoline into phosphotidylcholine supports healthy aging, as phosphotidylcholine levels in the brain tend to decline with age4 (phosphotidylcholine makes up approximately 30% of brain tissue). In a human clinical trial, older subjects who received 500mg citicoline for six weeks showed a 7.3% increase in phosphorus metabolites over the placebo group. The researchers concluded that the increase in phosphodiesters seen in the study indicated that phospholipid synthesis and resulting cell membrane turnover were stimulated by oral citicoline supplementation, suggesting that oral citicoline

may be of use in mitigating changes in the brain relating to phosphotidylcholine decline.5

Healthy memory functionAs a choline donor, citicoline has been shown to increase levels of several neurotransmitters, including acetylcholine, that affect memory and overall cognitive function. A meta-analysis of double-blind, randomized human trials on the effects of citicoline on cognitive performance concluded that citicoline modestly improves memory.11 In addition, Cognizin citicoline has been shown to support the activity of nerves that respond to acetylcholine, helping to raise activity levels in the brain’s learning and memory circuits.

Citicoline immediate and short-term memory functionA 4-week study conducted on 24 older adults (with memory deficits and without dementia) measured memory performance. Results indicated that supplementation with citicoline significantly improved immediate and short-term memory on free recall tasks, suggesting that citicoline supplementation has beneficial effects on the underlying cognitive processes of memory retrieval and storage.3

Citicoline supports memory performance in elderly subjects3

Placebo Citicoline (1000mg)

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Citicoline improves verbal memory in aging adultsA randomized, double-blind, cross-over study on 47 female and 48 male aging (50-85 years of age) subjects tested the effect of citicoline supplementation (1000mg) on verbal memory. Memory scores were correlated with plasma choline concentrations. Results positively correlate citicoline supplementation with improved verbal memory.12

Brain metabolism and energyThe brain makes up only two percent of a person’s body weight, yet it consumes roughly 20 percent of the body’s energy when at rest.6 Citicoline helps keep the brain’s metabolic activity at healthy levels.

Animal studies on brain metabolismCognizin citicoline has been shown to support the health of mitochondrial functioning in animal brains, which resulted in higher levels of ATP in brain cells.7, 8

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Cognizin cellular synthesis and brain energyA study on the effects of Cognizin citicoline on brain cellular metabolism in humans was conducted. The study quantified the effects of citicoline on high-energy phosphate metabolites and constituents of cellular membrane synthesis in the frontal lobe of 16 healthy men and women. The data show that citicoline improves frontal lobe bioenergetics and alters phospholipid cell membrane turnover.7

The Anterior CingulateCortex (ACC) is thearea of the brainactivated with Cognizin

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Cognizin® citicoline cellular synthesis and brain energy 9

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Cellular Synthesis Cellular Energy

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PE: PhosphoethanolamineData represent mean ±SD metabolite ratios relative to the total 31P siganl at each visit.

Focus and attentionAdequate energy reserves serves a critical role in healthy brain function across the lifespan.

Cognizin improves attentional performanceA double-blind, randomized, placebo-controlled study conducted on 60 healthy, middle-aged women found that citicoline supplementation was associated with improved attentional focus and inhibition. After 28 days of supplementation, the women were evaluated using the Continuous Performance Test II (CPT-II), a measure that quantified both attentional errors of commission and omission. The subjects were divided into three groups: 250mg daily dose, 500mg daily dose and placebo. Both the 250mg and 500mg groups showed significantly better ability to produce correct responses, likely due to both improved focus and inhibition of other stimuli.10

Researchers suggested that the observed improvement in performance might be related to increased dopaminergic uptake. Previous investigations have shown that citicoline increases dopamine and dopamine receptor densities as well as aiding in the protection of neurons related to dopamine.

General brain health benefits The biochemical support provided by citicoline suggests general benefits relating to the cognitive functioning of aging adults. A review of citicoline supplementation with elderly subjects resulted in improvements in a wide range of cognitive and behavioral measures, including memory, attention, behavior, reaction time, relational life, independence and cooperation.13

What structure/function claims can Cognizin products make? The following claims are provided for informational purposes and should be reviewed by your legal counsel prior to use in marketing materials, including product labels.

•Supportsmemoryfunctionandhealthycognition*5, 13, 14, 15,

•Providesthecompoundneededforthesynthesisofphosphatidylcholine,amajor constituent of brain tissue* 1, 2, 5, 14, 15

•Enhancescommunicationbetweenneuronstosupportvisualfunction*11, 12

•Helpsprotectneuralstructuresfromaccumulatingfree-radicaldamage*15

•Supportsbrainperformancebyenhancingmetabolismandhealthybrainactivity* 9, 11, 16

•Assistsinsustaininghealthymitochondriainthebrain,theenergyfactoriesinside brain cells* 9, 11, 16

•Supportshealthybrainmetabolismbynourishingandmaintainingbraincell phospholipids* 5, 14, 15

•Helpsmaintainnormallevelsofacetyl-choline,achemicalthathelpsregulate memory and cognitive function* 11, 12

•Supportstheactivityofnervecellsthatrespondtoacetylcholine*15

•Helpsmaintainbraincellmembranesinahealthycondition*13


Improved attentional performance following citicoline supplementation10

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Data from measurement at end of treatment period


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Cognizin is easy to use Manufacturers and formulators will love the more practical benefits of Cognizin. This ingredient is: •Pure. Cognizin contains no food additives, artificial flavors or

preservatives.

•Stable. Cognizin is stable in liquids and to high heat.

•Water-soluble. Water-soluble Cognizin is easy to use in beverages and liquids.

•Neutral in taste. Cognizin’s neutral and slightly acidic taste compliments numerous product flavors.

•GRAS.Cognizinachievedself-affirmedGRASstatusandisconsideredsafe for food and beverage applications.

•Vegetarian. No animal origin material is used in Cognizin.

•Allergen-free. Cognizin is considered allergen-free.

•Kosher. Cognizin is a certified Kosher ingredient.

•Patented. Cognizin is produced by a patented fermentation process.

Cognizin product applications Cognizin is suitable for use in:

•Dietarysupplements

•Beveragesandbeveragebases

•Breakfastcereals

•Chewinggum

•Dairyproductanalogs

•Frozendairydesserts

•Hardandsoftcandies

•Milkandmilkproducts

•Processedfruitsandfruitjuices

References 1 Wurtman RJ et al. Biochem Pharmacol. 2000; 60(7): 989–92. 2 Rao AM et al. J Neurosci Res. 1999; 58(5): 697–705. 3 Alvarez XA et al. Meth Find Exp Clin Pharmacol. 1997; 19(3): 201–10.4 Cohen,BruceM.,etal.“Decreasedbraincholineuptakeinolderadults:anin

vivo proton magnetic resonance spectroscopy study.” Jama 274.11 (1995): 902-907.

5 BabbSMet al. Psychopharmacology, 2002; 161(3): 248–54.6 Drubach,Daniel.The Brain Explained. New Jersey: Prentice-Hall, 2000. 7 Hurtado O et al. Neurobiol Dis. 2005; 18: 336–45.8 Kakihana M et al. Jpn Pharmacol Ther. 1985; 13(9): 241–53.9 SilveriMMet al. NMR Biomed. 2008; 21(10): 1066–75.10 McGladeEet al. Food and Nutr. Sciences. 2012; 3(6): 769–773.

doi: 10.4236/fns.2012.36103. 11 Fiorvanti M, Yanagi M. The Cochrane Library,Oxford,England.2006;Issue4.12 SpiersPAet al. Arch of Neuro. 1996; 53(5): 441–8. 13 SecadesJJ,LorenzoJL.Meth Find Exp Clin Pharmacol.

2006;27(SupplB):1–56.14 Lopez-CoviellaIetal.J Neurochem. 1995; 65(2):889-94.15 ConantR,SchaussAG.Alt Med Rev. 2004; 9:1, 17-31.16 WatanabeSetal.Folia Psychiatr Neurol Jpn. 1975; 29(1):67-76.


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Cognizin®isatrademarkofKYOWAHAKKOBIOCO.,LTD.

Copyright©2014KYOWAHAKKOBIOCO.,LTD.AllRightsReserved.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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This information is being provided to you for educational and informational purposes only. This information is not intended to be used as marketing materials to consumers.


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