In the realm of cognitive health and brain function enhancement, substances like Citicoline and Choline have gained attention for their potential benefits. Both are crucial for brain health, but they differ in their forms, functions, and mechanisms of action. Understanding their distinctions can assist in making informed decisions about their usage and dosage.
With competitive price and timely delivery, Witspower sincerely hope to be your supplier and partner.
Here, we&#;ll break down the differences in Citicoline vs Choline and their different benefits, dosage thresholds, and side effects. Let&#;s jump in:
Citicoline and various choline supplements offer distinct pathways to support cognitive health and brain function.
While Citicoline excels in targeted brain delivery and neuroprotection, choline variants like Alpha-GPC showcase unique, promising nootropic effects.
Embracing this diversity allows for tailored approaches to cognitive enhancement through choline supplements.
Citicoline, also known as CDP-Choline, is a naturally occurring compound found in every cell of the body. It plays a vital role in the production of phospholipids in cell membranes, particularly in brain cells. This compound is a precursor to both choline and cytidine, which are essential for neurotransmitter synthesis.
Choline is a micronutrient that acts as a precursor to acetylcholine, a neurotransmitter vital for brain and nervous system function. It's found in various foods like eggs, meat, fish, and certain vegetables. Choline is necessary for several physiological processes, including cell membrane structure and neurotransmitter synthesis.
Citicoline and Choline differ primarily in their forms and functions. Citicoline, a compound naturally present in cells, serves as a precursor to choline and cytidine, aiding in neurotransmitter synthesis and cellular repair, making it potent for cognitive enhancement and neuroprotection.
On the other hand, choline is a vital micronutrient found in various foods, essential for brain health, cellular structure, and liver function.
While both contribute to cognitive well-being, many sources claim that Citicoline may offer a more bioavailable form of choline and crosses the blood-brain barrier effectively, targeting brain health directly. Choline, on the other hand, is often obtained through diet or supplementation and fulfills daily nutrient needs for overall bodily functions.
Of course, some choline supplements are well-known nootropics, as well, so it&#;s not so clear cut. Let&#;s dig deeper into the brain-boosting potential of each:
In the realm of cognitive enhancement and brain health, both Citicoline and Choline supplements stand as essential contributors. While Citicoline offers notable neuroprotective properties and efficient delivery of choline to the brain, various choline supplements, particularly Alpha-GPC, showcase promising nootropic effects worth exploring.
Citicoline, known for its neuroprotective benefits and efficient conversion to choline, has gained attention for supporting cognitive function and structural brain integrity. Its ability to cross the blood-brain barrier effectively makes it a valuable compound for those seeking targeted cognitive enhancement.
Contrary to the notion of one being superior to the other, choline supplements like Alpha-GPC reveal intriguing nootropic potential. Alpha-GPC, with its high bioavailability and efficient penetration of the blood-brain barrier, stands out among choline variants. It has shown promising effects on cognitive performance, memory enhancement, and overall brain health.
Understanding that individual responses and preferences vary is crucial. Citicoline might suit some seeking direct brain-focused benefits, while choline supplements, especially Alpha-GPC, offer a unique avenue for nootropic enthusiasts exploring a broader spectrum of cognitive enhancements.
Citicoline is commonly available as CDP-Choline (Cytidine Diphosphate-Choline) or as Citicoline Sodium. These forms ensure better absorption in the body, facilitating the delivery of choline and cytidine for brain health support and cognitive enhancement.
Choline comes in various supplement forms like choline bitartrate, choline citrate, and alpha-GPC (Alpha-Glycerylphosphorylcholine). Each form differs in bioavailability and absorption rates, influencing how effectively the body utilizes choline for its diverse functions, including brain health and cellular structure maintenance.
Let&#;s break them down:
Each of these forms varies in how effectively they deliver choline to the body and brain. Understanding these differences can help individuals select the most suitable form based on their specific needs and desired outcomes, whether it's cognitive support, cellular maintenance, or overall brain health.
Typical daily doses range from 250mg to 2,000mg, though individual needs may vary based on age, health status, and purpose of use.
Here's a more detailed breakdown of Citicoline dosage recommendations based on specific purposes:
However, it's crucial to note that individual responses and needs can vary based on factors such as age, health status, and the specific purpose of use. Consulting a healthcare professional or a qualified practitioner is advisable to determine the most suitable dosage tailored to individual requirements and health conditions.
The recommended Adequate Intake (AI) for choline varies by age and gender, with ranges between 125 mg to 550 mg per day. However, specific health conditions may require higher doses.
Here's a more specific breakdown of choline dosage recommendations based on age and gender:
Note that most children get enough choline from a balanced diet. It&#;s important to note that children should not take supplements unless directed by their doctor.
These values provide a general guideline for adequate choline intake, but individual needs may vary based on factors such as pregnancy, lactation, specific health conditions, or dietary preferences. In some cases, higher doses may be recommended, especially for pregnant or lactating women or individuals with certain health concerns where additional choline intake could be beneficial.
Consulting a healthcare professional can help determine the most appropriate dosage based on individual circumstances.
Certainly, here's a section covering precautions and potential side effects for both Citicoline and Choline:
Citicoline is generally considered safe for most individuals when taken within recommended dosages. However, some individuals might experience mild side effects such as headaches, insomnia, nausea, or gastrointestinal discomfort. People with certain medical conditions, pregnant or breastfeeding individuals, or those on specific medications should consult a healthcare professional before supplementation.
Choline supplements are typically well-tolerated but might cause side effects such as gastrointestinal distress, fishy body odor, or low blood pressure in some individuals. Extremely high doses may lead to adverse effects like liver toxicity. Individuals with liver or kidney conditions, allergies to choline compounds, or those taking certain medications should consult a healthcare provider before starting supplementation.
It's crucial to adhere to recommended dosages and seek guidance from healthcare professionals, particularly for those with pre-existing medical conditions or undergoing specific treatments, to mitigate potential risks and ensure safe usage of Citicoline and choline supplements.
Citicoline is ideal for individuals seeking cognitive enhancement and neuroprotective effects. It's a more bioavailable form of choline and crosses the blood-brain barrier effectively.
Choline is suitable for those aiming to meet daily choline needs through diet or supplementation. It's available in various forms like choline bitartrate, citrate, and others.
Both Citicoline and Choline are crucial for brain health and cognitive function. Citicoline offers the advantage of being readily absorbed and converted into choline in the body, making it a potent option for cognitive enhancement. Meanwhile, choline, obtained through diet or supplementation, fulfills daily nutrient requirements and supports various bodily functions.
When considering supplementation, consulting a healthcare professional is advisable to determine the most appropriate form and dosage based on individual needs and health conditions.
Understanding the differences between Citicoline and Choline can empower individuals to make informed choices regarding their cognitive health and overall well-being.
Lucid beverages contain a blend of brain-boosting nootropics + powerful mushrooms designed to unlock your brain's full potential so you can zone in on what's important.
Ready to become lucid? Check out our starter kit.
Is citicoline different from choline?
Yes, citicoline (CDP-choline) is different from choline. Citicoline is a compound that contains choline and cytidine. When ingested, it breaks down into choline and cytidine, which are then used by the body to produce phosphatidylcholine, a key component of cell membranes, and to support brain function. Choline is a nutrient that serves as a precursor to the neurotransmitter acetylcholine and is essential for liver function, brain development, and muscle movement.
What is the best form of choline to take?
The best form of choline depends on your specific health needs. Common forms include:
Choline bitartrate: Affordable and effective for general supplementation.
Citicoline (CDP-choline): Known for its potential cognitive benefits and brain health support.
Alpha-GPC: Highly bioavailable and often used for cognitive enhancement and athletic performance. Each form has its advantages, so it's best to choose based on your health goals.
What are the negative side effects of citicoline?
Citicoline is generally well-tolerated, but some potential side effects can include:
Are you interested in learning more about Citicoline Vs CDP Choline? Contact us today to secure an expert consultation!
Headaches
Insomnia
Digestive issues: Such as nausea and diarrhea
Restlessness These side effects are typically mild and occur infrequently.
Is citicoline worth taking?
Citicoline can be worth taking for its potential cognitive benefits, including improved memory, attention, and overall brain function. It is often used to support recovery from stroke and other brain injuries, and some studies suggest it may be beneficial for age-related cognitive decline and neurodegenerative conditions. However, individual results can vary, so it's important to consult with a healthcare provider to determine if it's right for you.
What to avoid when taking citicoline?
When taking citicoline, it&#;s advisable to:
Avoid excessive caffeine and other stimulants: To reduce the risk of increased restlessness and insomnia.
Consult with a healthcare provider: If you are taking other medications or supplements to avoid potential interactions.
Monitor for side effects: Especially if you have a history of digestive issues or insomnia.
Does citicoline cause weight gain?
There is no evidence to suggest that citicoline causes weight gain. It is primarily used for cognitive health and does not typically influence body weight. However, individual responses can vary, so monitoring your body's reaction when starting any new supplement is always a good idea.
What foods have citicoline in them?
Citicoline itself is not found in foods, but choline, its precursor, is present in many foods, including:
Eggs
Meat and poultry
Fish
Dairy products
Soybeans
Brussels sprouts
Broccoli
Nuts and seeds
Is citicoline safe for kidneys?
Citicoline is generally considered safe for most people, including those with kidney conditions. However, there is limited specific research on citicoline's effects on kidney health. If you have existing kidney issues, it's important to consult with a healthcare provider before starting any new supplement.
Does citicoline give you energy?
Citicoline is not a stimulant, so it does not directly provide energy in the way caffeine does. However, by supporting brain health and cognitive function, it may help improve mental energy and reduce fatigue, indirectly contributing to a sense of increased energy and alertness.
Medicines containing citicoline (cytidine-diphosphocholine) as an active principle have been marketed since the s as nootropic and psychostimulant drugs available on prescription. Recently, the inner salt variant of this substance was pronounced a food ingredient in the major world markets. However, in the EU no nutrition or health claim has been authorized for use in commercial communications concerning its properties. Citicoline is considered a dietetic source of choline and cytidine. Cytidine does not have any health claim authorized either, but there are claims authorized for choline, concerning its contribution to normal lipid metabolism, maintenance of normal liver function, and normal homocysteine metabolism. The applicability of these claims to citicoline is discussed, leading to the conclusion that the issue is not a trivial one. Intriguing data, showing that on a molar mass basis citicoline is significantly less toxic than choline, are also analyzed. It is hypothesized that, compared to choline moiety in other dietary sources such as phosphatidylcholine, choline in citicoline is less prone to conversion to trimethylamine (TMA) and its putative atherogenic N-oxide (TMAO). Epidemiological studies have suggested that choline supplementation may improve cognitive performance, and for this application citicoline may be safer and more efficacious.
Keywords: citicoline, choline, health claims, toxicity, trimethylamine oxide, procognitive effects
Citicoline is the international nonproprietary name (INN) for cytidine-diphosphocholine (CDP-Cho). The substance is commercially available in two forms, sodium salt and inner salt. Citicoline sodium salt, classified as a nootropic and psychostimulant [1], is an active principle of a variety of prescription drugs, either injectables or oral formulations. In in the USA, citicoline (inner salt) was self-affirmed by the Japanese company Kyowa-Hakko as GRAS (generally regarded as safe) [2], and in it was announced as a novel food ingredient by the appropriate Implementing Decision of the Commission of the European Union [3].
The aforementioned EU Implementing Decision states that citicoline may be placed on the EU market, where it is intended to be used in food supplements aimed at a target population of middle-aged to elderly adults at a maximum level of 500 mg/day, and in dietary foods for special medical purposes with a maximum dose of 250 mg per serving and with a maximum daily consumption level of mg from these types of foods.
Classifying citicoline as a food ingredient suitable for food supplements should make it widely available, but in the highly regulated market of the European Union its marketing is problematic. According to the EU Regulation EC No / [4], all nutrition and health claims made in commercial communications concerning food supplements must be formally authorized following scientific assessment performed by the European Food Safety Agency (EFSA). Citicoline does not have any nutrition or health claim authorized up to date. Moreover, application for authorization of a health claim (related to citicoline and maintenance of normal vision) was turned down by the EFSA because it was concluded that a cause and effect relationship has not been established between the consumption of citicoline and the maintenance of normal vision [5]. Does this mean that, although it is legal to introduce citicoline to the EU market in a food supplement, information provided about this supplement should not contain any information about its specific nutritional and/or functional value?
Looking through the positive EFSA Scientific Opinion on citicoline issued prior to the aforementioned implementing decision [6], we find the reference to the observation that, both in humans and in rats, upon ingestion citicoline undergoes quick hydrolysis, breaking down to choline and cytidine [7], which then undergo further metabolism and incorporation into normal pathways of metabolism [8]. Cytidine, a pyrimidine nucleoside which in humans interconverts with uridine [9], undergoes intracellular phosphorylations to cytidine triphosphate (CTP), which participates in phospholipids synthesis via the Kennedy pathway, and may also be incorporated into nucleic acids. Choline is either phosphorylated to phosphocholine and participates in phosphatidylcholine synthesis, or oxidized to betaine, which serves as a methyl donor in the betaine-homocysteine methyltransferase reaction. Also, in cholinergic neurons, choline is acetylated to form the neurotransmitter acetylcholine.
We may, therefore, consider citicoline as a source of choline and cytidine. Whereas there is no nutrition or health claim authorized for cytidine either, there are three such claims authorized for choline. These are so-called functional claims relating to the beneficial effects of a nutrient on certain normal bodily functions. The first two state that choline contributes to normal lipid metabolism and to the maintenance of normal liver function. These claims were accepted because they were substantiated by observations that choline deficiency is associated with signs of liver damage (elevated serum alanine aminotransferase activity) and the development of fatty liver (hepatosteatosis) in humans fed choline-free total parenteral nutrition solutions, whose effects can be reversed by the administration of dietary choline [10,11]. The third claim, stating that choline contributes to normal homocysteine metabolism, was substantiated by the observations that choline-depleted diets tend to increase plasma concentrations of homocysteine [12], whereas human observational [13,14] as well as intervention [15] studies supported the inverse association between dietary choline and blood concentrations of homocysteine. Of note is that in the aforementioned intervention study, choline was supplied orally in the form of phosphatidylcholine (lecithin).
At the same time, health claims stating that choline contributes to the maintenance of normal neurological function and normal cognitive function were rejected by the EFSA because cause and effect relationships have not been established between the consumption of choline and the claimed effects [16]. One of the reasons was that some references that presented support for the claimed effects described studies that did not evaluate choline, but, for example, citicoline. A possible explanation of this paradox is that at the date of issuing scientific opinion on the health claims concerning choline (i.e., year ), citicoline was not yet appreciated by EFSA experts as the dietary source of choline. Indeed, natural foods do not contain any significant amount of this substance.
There is no direct proof that citicoline intake can reverse either elevated serum alanine aminotransferase activity or the development of fatty liver in people who are choline-deficient. There is also no direct proof that citicoline intake may lower homocysteine in blood. On the contrary, single oral administration of a high dose of citicoline (1 g/kg b.w.) to rats resulted in a transient increase of plasma homocysteine, but when a lower dose was supplemented in the diet for two months, plasma homocysteine remained unchanged [17]. At the same time there is no reasonable doubt that oral intake of citicoline is a safe and efficient method of delivery of choline to the human body.
It might perhaps be concluded that the issue of the applicability to citicoline of health claims pertaining to choline (and apparently also to some of its derivatives, such as phosphatidylcholine) is merely a legal problem that shall be settled accordingly by the appropriate authorities. On the other hand, a health claim authorized almost a decade ago may not be supported in its entirety by the contemporary scientific data. Current guidelines for the management of fatty liver do not mention supplementation with choline or its derivatives [18]. Likewise, folic acid, vitamin B6, vitamin B12, and betaine, but not cholines, are listed among nutrients that may counteract hyperhomocysteinemia [19].
It is well established that following ingestion citicoline is fully absorbed and catabolized to cytidine and choline, which enter their respective metabolic pools in the body [20,21,22]. However, the particulars of its absorption, hydrolysis, and dephosphorylation(s) are a bit unclear. Citicoline contains equimolar amounts of choline and cytidine. Following citicoline ingestion in rats, the increase in both plasma cytidine and choline occurred quickly, but the molar increase in plasma choline was markedly smaller [23]. In a human study [24], oral citicoline resulted in increases in plasma choline and uridine that were similar in timing and magnitude, but in the other human study, the increase in plasma choline following citicoline ingestion was biphasic and delayed [25]. It has been suggested that citicoline is absorbed intact and its hydrolysis occurs in the liver and is coupled with a selective withdrawal of choline from blood [26]. Following oral citicoline intake in humans, the quantitative transformation of cytidine to uridine occurring in the intestine or liver was also postulated [24].
Absorption of intact citicoline molecules from the intestine to blood could also be helpful for explaining differences of acute toxicity of citicoline versus choline upon different routes of administration (Figure 1).
Median lethal dose of choline chloride and citicoline in mice (A,B) and rats (C,D) expressed in milligrams (A,C) or in millimoles (B,D) per kilogram body weight, depending on the route administration. Data compiled from refs. [27,28,29,30,31]. Abbreviations used: i.v., intravenous; i.p., intraperitoneal; ND, no data available.
The classical measure of acute toxicity is LD50, the median lethal dose of the tested compound expressed in milligrams per kilogram body weight. The lower the LD50 value, the more toxic the substance. For any route of administration (oral, intraperitoneal, intravenous), the LD50 of citicoline is higher than the corresponding LD50 of choline, indicating that citicoline is much less toxic than choline. This difference is certainly not unexpected when we consider that the molecular weight of choline moiety (MW = 104) contributes less than 30% to the molecular weight of citicoline (MW = 489), whereas the acute toxicity of cytidine is probably lower than that of choline. However, when we express the aforementioned LD50 values on a molar basis, citicoline is still substantially less toxic than choline. The difference in molar toxicity between citicoline and choline is more than 20-fold when the substances are applied intravenously. Apparently intact citicoline molecules do not evoke acute cholinergic toxicity, probably because they are not substrates for acetylcholine synthesis.
When the compounds are given per os, the difference in toxicity is several times lower, but it still is quite significant. Two possible explanations can be proposed for the aforementioned differences. One could be that when cytidine appears in blood concomitantly with choline, it somehow attenuates acute choline toxicity. The other, which seems more plausible, could be that upon oral application choline is not liberated from citicoline in the intestinal lumen, preventing its conversion to TMA. Compared with phosphatidylcholine and other choline derivatives encountered in food (e.g., carnitine, glycerophosphocholine), citicoline may be less prone to enzymatic hydrolysis inside the intestinal lumen because it is the only compound containing pyrophosphate group (it should, however, be noted that according to one study [32], the distribution of radioactivity in tissues, urine, and expired air following oral and intravenous administration of methyl-14C-labeled citicoline in rats showed metabolic differences which suggested that the compound is, at least partially, metabolized to TMA prior to its gastrointestinal absorption).
The issue of hypothetical citicoline resistance to intraintestinal hydrolysis is of importance when we consider that the intestinal microbiome metabolizes a significant fraction of choline and its derivatives to trimethylamine (TMA), a gaseous metabolite readily taken up and oxidized in the liver to its N-oxide, TMAO.
TMAO has been implicated in the etiology of various diseases, such as kidney failure, diabetes, and cancer [33]. There is a large and growing amount of literature on the atherogenicity of TMAO resulting in increased incidence of myocardial infarction, stroke, or death [34]. A meta-analysis published recently led to the conclusion that higher plasma TMAO correlates with a 23% increase in risk for cardiovascular events and a 55% increase in all-cause mortality [35]. Two recent reports showed that higher TMAO levels were associated with increased risk of first ischemic stroke and worse neurological deficit [36], and that patients suffering from atrial fibrillation who developed cardiogenic stroke displayed approx. 4 times higher TMAO levels in plasma than patients with atrial fibrillation who did not develop stroke [37]. Another recent report suggested a link between TMAO and Alzheimer&#;s disease [38]. It has even been suggested that supplementation with choline esters prone to be metabolized to TMA and TMAO, such as phosphatidylcholine, may be dangerous to human health [39].
On the other hand, several observations cast doubt on the pivotal role of TMAO in atherosclerosis. First of all, nutritional intakes of TMAO and its precursors do not always correlate with cardiovascular disease risk. For example, high fish intake increases TMA/TMAO while being cardioprotective. Some hypotheses have been proposed recently to resolve this paradox, employing inter alia a phenomenon of reverse causality, a possible role of insulin resistance and diabetes mellitus in activating N-oxidation of TMA, etc. [40].
Nonetheless, many authors still take it as having been proven that TMAO is a causative factor in the development of atherosclerosis and cardiovascular diseases. For example, in a recent review on TMAO and stroke [41], several reports are quoted that show the importance of TMAO as a risk factor and prognostic marker for this disease, and indicate the pathomechanisms involved. These include increased TMAO generation promoting atherosclerosis, platelet activation, and inflammation. The author concludes that TMAO may be a central molecule in the relationship of diet, genetics, the gut microbiota, and cardiovascular disease.
It may be concluded that until the place of TMAO in the chain of events leading to cardiovascular diseases and mortality is ultimately clarified, citicoline could be a more reasonable choice than other choline compounds, when choline supplementation is indicated.
In two population studies, significant associations were found between choline intake or free choline level in blood and the cognitive performance of adult and elderly people. In a community-based population of non-demented individuals ( subjects, mean age 60.9 years), higher concurrent choline intake was related to better cognitive performance [42] (Figure 2). In another cross-sectional study ( subjects aged 70&#;74 years), low plasma free choline concentrations were associated with poor cognitive performance [43]. A possible explanation for the effect of choline intake on cognition in adults has been sought in its function as a precursor of phosphatidylcholine (PC), a major constituent of all biological membranes, and acetylcholine, a neurotransmitter involved in cognition [44].
Dose&#;response relationship between the average daily choline intake and verbal and visual memory performance in non-demented adults. Black lines indicate the mean score and red lines indicate 95% confidence interval. Figure reproduced from [44].
Therefore, it might be expected that supplementation with choline will improve cognitive performance. However, trials in which the effects of oral supplementation of humans with choline or phosphatidylcholine on cognition were investigated yielded mixed, mostly negative results (see [45] and references cited therein). On the other hand, in a recent small placebo-controlled study, adolescent males treated with citicoline showed improved attention and psychomotor speed and reduced impulsivity [46]. In other recent controlled studies, citicoline seemed to be efficacious in adult patients suffering from cognitive impairments, especially of vascular origin [47]. These newer studies corroborated results obtained previously when citicoline as a prescription drug had been tested in several placebo-controlled trials for cognitive impairment due to chronic cerebral disorders in the elderly. The review of those early trials led to the conclusion that there was some evidence of a positive effect of citicoline on memory and behavior in at least the short to medium term [48]. Moreover, it was recently shown that in patients suffering from dementia concomitant oral intake of citicoline improved the efficacy of cholinesterase inhibitors [49,50].
Altogether, whereas the jury may still be out on the issue whether, or to what extent, citicoline taken orally is metabolized to TMA and TMAO, there are reasons to believe that procognitive effects of citicoline supplementation are superior over those of choline or phosphatidylcholine.
P.G. and K.S. wrote the paper.
This research received no external funding.
The authors declare no conflict of interest.
Contact us to discuss your requirements of Does Citicoline Work. Our experienced sales team can help you identify the options that best suit your needs.