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Liposomal Citicoline

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INTRODUCTION

One of the major health concerns for our aging population today is declining brain health with its affect on memory, mental focus, and learning ability. Maintaining a sharp, attentive mind and strong cognitive ability is something that everyone needs and desires, irrespective of age, so a person can live a mentally active and productive life. Unfortunately, the brain is under constant assault from many factors including environmental radiation, heavy metal pollution, toxins in our food, and daily stress. Poor lifestyle choices and dietary deficiencies can also contribute to a weakening brain.

As a result, occasional memory loss is becoming very common as people pass into their senior years such that they find themselves forgetting where they last put their glasses, smartphone or keys. The Trending Machine National Poll (2013) showed 39% of Americans report forgetting or misplacing an everyday item in the last week. It also showed that women are generally more likely to forget or misplace their everyday items compared to men (43% vs. 31%), and that this is now a problem affecting the younger generation as well. Millennials between the ages of 18-34 are just as likely to have memory lapses as their senior counterparts when it comes to recalling what day it is, where they put their keys, or recalling key important dates.

It can be said that the major cause of forgetfulness in seniors and the loss of brain function may be due to the stresses of aging. But Business Wire (2013) published a press release where Patricia Gutentag, a leading family and occupational therapist, claims the major causes are due to multitasking, lack of sleep and the stress of class exams, job interviews, and personal relationships. Stress often leads to forgetfulness, low mood, and poor judgment according to Gutentag. She also reported that they are finding higher rates of neurodivergences in young adults. (Business Wire, 2013).

There is a product now available which will help keep your brain functioning at maximum capacity, no matter what your age. Citicoline is a nutritional product that research and clinical studies have revealed will help individuals maintain optimum brain function.* The nutritional supplement Liposomal Citicoline (Cognizin brand) from Davinci Laboratories may be a great option for those experiencing occasional memory loss due to aging.*

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What is Citicoline

Citicoline is a neurotransmitter that can boost brain and neurological function and protect the structure of the brain from the stresses of aging. Published studies have found that it can support mental acuity, memory, cognition, and focus.* (McGlade et al., 2012). These studies have shown that this nutrient can have a positive influence on brain cellular metabolism and neurological activity.* (Özay et al., 2007). Citicoline can also help protect neurons from degradation and provide improved bioenergetics in the brain.* (Parisi, Manni, Colacino & Bucci, 2008).

Citicoline can support healthy brain functions and structure, especially in the aging population.* Citicoline is a natural intermediate found in all human cells and animal tissues, especially in the brain, heart, liver, and other organs in the body.

It is now available as a supplement in over 70 countries, including the US, showing its worldwide acceptance as a viable and useful nutritional product. Its scientific name is cytidine diphosphate –choline or cytidine 5’-diphosphocholine (CDP-choline). Its structure is shown below.

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National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 25202509, CDP-choline. Retrieved October 14, 2021 from https://pubchem.ncbi.nlm.nih.gov/compound/CDP-choline.

Its primary function in the body is to act as a precursor to acetylcholine, which is a vital component of cell membranes and a primary executive neurotransmitter in the human brain. Supplementation with Citicoline increases the amount of choline available for the synthesis of acetylcholine, for neuronal membrane repair, and for the rebuilding of membrane phospholipid stores after depletion.* (Agut, López-Coviella, Ortiz & Wurtman, 1993; D’Orlando & Sandage, 1995). When ingested, Citicoline is broken down to form choline and cytidine in the intestines. (Wurtman, Regan, Ulus & Yu, 2000). After being hydrolyzed into choline and cytidine, these components are readily distributed throughout the body for utilization in many biosynthetic pathways. (Wurtman et al., 2000) Once these components cross the blood brain barrier, they reform Citicoline by the action of the enzyme, CTP-phosphocholine cytidyltransferase. (Alvarez et al., 1999).

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Mechanism of Action

Citicoline primary mechanism of action focuses on its ability to boost choline and acetylcholine levels in the brain and to act as an essential intermediate in the synthesis of the major phospholipid, phosphatidylcholine found in cell membranes produced by the so-called Kennedy pathway. Several studies have shown that Citicoline can increase phosphatidylcholine levels in the brain.* (Babb, 2002; Lopez-Covielia, 1995). When a person ages, the level of phosphatidylcholine drops significantly, causing a loss of verbal learning aptitude, an important measure of cognitive impairment. Tests on older people who have used Citicoline have shown better focus, memory, and recall of words and objects. (Alvarez et al., 1999)

Citicoline may have neuroprotective effects due to its ability to preserve cardiolipin, sphingomyelin, and the arachidonic acid content of phosphatidylcholine and phosphatidylethanolamine in cell membranes.* (Saver, 2008). Acting as an antioxidant, it is able to stimulate glutathione synthesis, thereby increasing protection against destructive hydroxyl free radicals.* As mentioned, Citicoline can protect neuronal membranes by increasing the levels of their phospholipids and by decreasing the activity of phospholipases.* (Adibhatla & Hatcher, 2003).

Citicoline can enhance cellular communication by increasing the availability of the neurotransmitters acetylcholine, norepinephrine, and dopamine.* Acetylcholine is the main neurotransmitter in the human brain and trials have found that supplementation with Citicoline may help with attention, focus, and learning in large part due to the increase in acetylcholine levels.* (Tardner, 2020)

By increasing dopamine and dopamine receptor sites, Citicoline will help improve performance on working memory and executive tasks requiring attention.* (Nieoullon, 2002).

Citicoline has been found to lower glutamate concentration levels following an ischemia event which provides an additional neuroprotective effect for the brain.* It can also raise ATP levels which shows that the supplement is able to support brain bioenergetics.* (Silveri et al., 2010)

Additional work has shown that Citicoline can also stimulate the synthesis of SAMe, the active trans-methylation agent in the body, which provides neuronal membrane stabilization and reduction of arachidonic acid.* This is very important following an ischemia event when arachidonic acid levels are elevated. (Rao, Hatcher & Dempsey, 2000).

Citicoline can help restore both membrane phospholipid structure and neurological functions caused by the normal aging process.* One study showed that Citicoline may even have a positive effect in modulating appetite, which would be an aid in managing proper body weight.* (Killgore et al., 2010)

 

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Research Studies

There are many published studies that serve to support the reported claims for the nutritional benefits of taking Cognizin Citicoline. Cognizin® is the registered trademark of Kyowa Hakko Bio Co.,Ltd. These studies demonstrate that Cognizin Citicoline can help with the effects of declining brain function caused by a person’s negative lifestyle choices, poor diet, environmental toxins, and stress.* This product helps the brain maintain optimum sustainability of its metabolic environment and to retain a person’s ability to think cognitively and to have improved memory, focus and attention.* A review of the following studies below gives evidence that Citicoline can support and improve brain function and structure due to its metabolic and regenerative properties.*

 

The Product

The Liposomal Citicoline product from Davinci Laboratories is a liquid-based product and delivers 250 mg of Cognizin brand Citicoline per ml of product. It is a vegetarian, gluten and soy-free product made with Non-GMO ingredients. The recommended use is to take one or two mls per day or as directed by your healthcare provider.

Davinci’s Liposomal Citicoline product is a uniquely designed product to improve uptake and bioavailability of Citicoline using liposomal technology which carries Citicoline within a lipid bilayer. A liposome is a spherical vesicle consisting of at least one outer bilayer of phospholipids on its surface which effectively captures the active ingredient within. This technology is especially important as a dietary supplement delivery vehicle for those ingredients that are poorly absorbed because of its size or lipid makeup. The liposome easily carries ingredients like Citicoline through the gut membrane and greatly increases the bioavailability of this active ingredient in the body.

References:

  1. Adibhatla, R. M., & Hatcher, J. F. (2003). Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia. Journal of neuroscience research, 73(3), 308–315. https://doi.org/10.1002/jnr.10672
  2. Agut, J., Lopez G-Coviella, I., Ortiz, J. A., & Wurtman, R. J. (1993). Oral cytidine 5'-diphosphate choline administration to rats increases brain phospholipid levels. Annals of the New York Academy of Sciences, 695, 318–320. https://doi.org/10.1111/j.1749-6632.1993.tb23075.x
  3. Alvarez, X. A., Laredo, M., Corzo, D., Fernández-Novoa, L., Mouzo, R., Perea, J. E., Daniele, D., & Cacabelos, R. (1997). Citicoline improves memory performance in elderly subjects. Methods and findings in experimental and clinical pharmacology, 19(3), 201–210.
  4. Babb, S. M., Appelmans, K. E., Renshaw, P. F., Wurtman, R. J., & Cohen, B. M. (1996). Differential effect of CDP-choline on brain cytosolic choline levels in younger and older subjects as measured by proton magnetic resonance spectroscopy. Psychopharmacology, 127(2), 88–94. https://doi.org/10.1007/BF02805979
  5. Babb, S., Wald, L., Cohen, B., Villafuerte, R., Gruber, S., Yurgelun-Todd, D., & Renshaw, P. (2002). Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: An in vivo phosphorus magnetic resonance spectroscopy study. Psychopharmacologia,161(3), 248-254.
  6. Business Wire (2013, August 1). Survey Shows Millennials Are More Forgetful Than Seniors [Press release]. Retreived from https://www.businesswire.com/news/home/20130801006048/en/Survey-Shows-Millennials-Are-More-Forgetful-Than-Seniors.
  7. D'Orlando, K. J., & Sandage, B. W., Jr (1995). Citicoline (CDP-choline): mechanisms of action and effects in ischemic brain injury. Neurological research, 17(4), 281–284. https://doi.org/10.1080/01616412.1995.11740327
  8. Fioravanti, M., & Buckley, A. E. (2006). Citicoline (Cognizin) in the treatment of cognitive impairment. Clinical interventions in aging, 1(3), 247–251. https://doi.org/10.2147/ciia.2006.1.3.247
  9. Killgore, W. D., Ross, A. J., Kamiya, T., Kawada, Y., Renshaw, P. F., & Yurgelun-Todd, D. A. (2010). Citicoline affects appetite and cortico-limbic responses to images of high-calorie foods. The International journal of eating disorders, 43(1), 6–13. https://doi.org/10.1002/eat.20658
  10. López-Coviella, I., Agut, J., Savci, V., Ortiz, J. A., & Wurtman, R. J. (1995). Evidence that 5'-cytidinediphosphocholine can affect brain phospholipid composition by increasing choline and cytidine plasma levels. Journal of neurochemistry, 65(2), 889–894. https://doi.org/10.1046/j.1471-4159.1995.65020889.x
  11. McGlade, E., Agoston, A., DiMuzio, J., Kizaki, M., Nakazaki, E., Kamiya, T., & Yurgelun-Todd, D. (2019). The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males. Journal of Attention Disorders,23(2), 121-134.
  12. McGlade, E., Locatelli, A., Hardy, Julia., Kamiya, T., Morita, M., Morishita, K., & Yurgelun-Todd, D. (2012) Improved Attentional Performance Following Citicoline Administration in Healthy Adult Women, Food and Nutrition Sciences 3, 769.
  13. Nieoullon, A. (2002). Dopamine and the regulation of cognition and attention. Progress in neurobiology, 67(1), 53–83. https://doi.org/10.1016/s0301-0082(02)00011-4
  14. Özay, R., Bekar, A., Kocaeli, H., Karlı, N., Filiz, G., & Ulus, I. H. (2007). Citicoline improves functional recovery, promotes nerve regeneration, and reduces postoperative scarring after peripheral nerve surgery in rats. Surgical neurology, 68(6), 615–622. https://doi.org/10.1016/j.surneu.2006.12.054
  15. Parisi, V., Manni, G., Colacino, G., & Bucci, M. G. (1999). Cytidine-5'-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology, 106(6), 1126–1134. https://doi.org/10.1016/S0161-6420(99)90269-5
  16. Rao, A. M., Hatcher, J. F., & Dempsey, R. J. (2000). Lipid alterations in transient forebrain ischemia: possible new mechanisms of CDP-choline neuroprotection. Journal of neurochemistry, 75(6), 2528–2535. https://doi.org/10.1046/j.1471-4159.2000.0752528.x
  17. Saver J. L. (2008). Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair. Reviews in neurological diseases, 5(4), 167–177.
  18. Silveri, M., Dikan, J., Ross, A., Jensen, J., Kamiya, T., Kawada, Y., . . . Yurgelun-Todd, D. (2008). Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy. NMR in Biomedicine,21(10), 1066-1075.
  19. Spiers, P. A., Myers, D., Hochanadel, G. S., Lieberman, H. R., & Wurtman, R. J. (1996). Citicoline improves verbal memory in aging. Archives of neurology, 53(5), 441–448. https://doi.org/10.1001/archneur.1996.00550050071026
  20. Tardner, P. (2020). The use of citicoline for the treatment of cognitive decline and cognitive impairment: A meta-analysis of pharmacological literature.
  21. Wurtman, R. J., Regan, M., Ulus, I., & Yu, L. (2000). Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochemical pharmacology, 60(7), 989–992. https://doi.org/10.1016/s0006-2952(00)00436-6

 
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