When it comes to smart drugs—also known as brain supplements or nootropics—there’s no doubt you want to find use the best combination of brain-optimizing ingredients. But that requires informed decision-making, which naturally necessitates some research. There is a lot of confusion surrounding CDP choline (citicoline) and Alpha GPC. What are they really, what are the differences, and are either superior to the other? This article will delve into each one separately to give a complete background, and then compare the two.
Cholinergic Compounds: What Are They?
What are Cholinergic Compounds? Cholinergic Compounds are a key component of any nootropic stack. This is because they help increase acetylcholine levels in your body. Acetylcholine is a neurotransmitter that plays an important role in all humans’ brain functioning. It is associated with all the good stuff you’re looking to improve—motivation, mood, attention and memory.
The most basic cholinergic is choline bitartrate, but it is actually not as effective as some other supplements (like Centrophenoxine, DMAE, CDP-Choline and Alpha-GPC). There are plenty of discussions in the nootropic community about the positive and negative qualities of these cholinergics and which substances work the best at boosting brain health.
A common debate is whether to use CDP-Choline or Alpha-GPC in smart drugs. Both of these are considered great ways to supplement choline. But which should you choose?
Citicoline (CDP Choline)
Citicoline also goes by the name CDP-choline (Cytidine-5’-diphosphate choline or cytidine diphosphate choline). It’s a complex organic molecule that participates as an intermediary in cell membrane phospholipid biosynthesis.
Its major function is in the Kennedy pathway, where it acts as an intermediate compound in phosphatidylcholine biosynthesis (a membrane phospholipid).
CDP-choline is made up of pyrophosphate, ribose, cytosine, and choline. This compound belongs to the nucleotides group, a collection of biomolecules found in living systems that participate in cell metabolism.
In the small intestine, CDP-choline is hydrolyzed into choline and Cytidine. Cytidine is further metabolized into the amino acid uridine in the body. These by-products are easily and quickly absorbed then distributed throughout the body. They are necessary in phospholipid synthesis to promote membrane formation and repair.
Citicoline supplementation has been shown to offer the human body neuroprotective and cholinergic benefits. It enhances the neuronal membrane structural integrity and functionality, aiding membrane repair. The by-products of Citicoline can get into the brain by crossing the blood brain barrier. There, they are synthesized back into CDP-choline.
Citicoline is used to rehabilitate ischemic stroke patients, to improve cognitive insufficiency, and to treat neurological diseases such as spinal cord and brain injuries. This natural supplement has also been used in the treatment of head trauma, eye conditions, Alzheimer’s Disease and age-related cognitive deterioration.
Product Name: CDP-choline, Citicoline
Chemical Name: Cytidine-5’-diphosphate choline
Molecular Weight: 488.33; Monosodium Salt of CDP-Choline: 510.31
The Chemical Structure of Citicoline (CDP-choline)
The chemical structure of CDP-choline is one Cytidine molecule attached to a choline molecule through two phosphate groups (pyrophosphate). Choline contains a trimethylated nitrogenous base and is categorized with the B vitamins.
This compound is involved in three primary metabolic pathways. First, through phosphorylcholine, it participates in phospholipid synthesis. It also takes part in the synthesis of acetylcholine and is involved in the oxidation process resulting in betaine, which becomes a methyl donor.
Within the body, Citicoline formation from choline in the synthesis of phosphatidylcholine is the rate-limiting step. Phosphatidylcholine is a major membrane phospholipid. Exogenous Citicoline is hydrolyzed in the small intestine to generate choline and cytidine which is further metabolized to Uridine.
A primary RNA component, cytidine is converted to cytidine triphosphate (CTP) in the cytoplasm. The enzyme choline kinase catalyzes choline in the brain, resulting in phosphorylcholine which combines with CTP to form citicoline in the citicoline metabolic pathway.
With choline phosphotransferase as the reaction’s enzyme catalyst, Citicoline combines with diacylglycerol (DAG) to form phosphatidylcholine in the Kennedy biosynthetic pathway.
Citicoline seems to have a sparing effect on the body’s choline reserves. It prevents membrane phospholipids breakdown and offers cytidine, which replaces citicoline in the various biosynthetic pathways that require it as an intermediate.
CDP-choline is a water-soluble compound with over 90-percent bioavailability. Metabolism of Citicoline takes place in the intestinal wall and liver. The by-products are cytidine and choline, which increases plasma choline. One hour after oral ingestion, the plasma levels peak. A larger second peak occurs 24 hours after consumption.
Cytidine is minimally transported across the blood-brain barrier. Consumption of CDP-choline increases uridine instead of cytidine levels. This may be due to the ready conversion of cytidine into circulating uridine. Uridine can cross the blood-brain barrier through an unsaturated transport system and be transformed into uridine triphosphate (UTP).
The CTP synthase enzyme UTP can convert UTP to cytidine triphosphate (CTP). Uridine can also be converted directly to CTP in the PC-12 cells. The synthesis of brain phosphatidylcholine (PC) makes use of the uridine from CDP-choline metabolism and the choline obtained from that CDP-choline.
A Citicoline oral dose is absorbed rapidly. Upon absorption, cytidine and choline are distributed throughout the body. Uridine and choline then enter systemic circulation to be used in various biosynthetic pathways. In the brain, they can be resynthesized into Citicoline after crossing the blood-brain barrier. Afterwards, it is excreted through respiration as CO2, through urine, and less than one percent is excreted via feces.
How Citicoline Works
CDP choline is a precursor to phosphatidylcholine biosynthesis. This is a phospholipid component essential to all cell membranes in the PNS2 and CNS. To synthesize acetylcholine, your brain prefers to use choline, which restricts the amount available phosphatidylcholine synthesis.
Citicoline supports neuron membrane health by offering the components necessary for phospholipid synthesis. By increasing the availability of norepinephrine, acetylcholine, and dopamine neurotransmitters, Citicoline promotes cellular communication.
Citicoline supplementation may enhance the choline levels available for acetylcholine synthesis. It increases the synthesis of brain phospholipid. This can support the buildup of membrane phospholipid stores following depletion. Choline is also found naturally in some foods, such as eggs.
When acetylcholine needs to be increased, or there’s low choline availability, choline containing phospholipids like phosphatidylcholine and sphingomyelin may be catabolized from neuronal membranes. Supplementing with Citicoline inhibits neural membrane degradation by offering extra choline.
Citicoline increases the synthesis of phosphatidylcholine by stimulating SAMe synthesis. This reduces arachidonic acid levels and supports membrane stabilization necessary after an ischemia. It also transforms 1,2-diacylglycerols into phosphatidylcholine.
Citicoline offers neuroprotective benefits by partially restoring phosphatidylcholine levels and preserving phosphatidylcholine arachidonic acid content. It stimulates glutathione reductase activity and glutathione synthesis. Citicoline also reduces phospholipase A2 activity and preserves cardiolipin.
Citicoline serves as an intermediary in sphingomyelin production, preserving the membrane phospholipid. In patients who have gotten an ischemic stroke, this natural supplement restores sphingomyelin to pre-stroke levels.
Citicoline and Stroke Recovery
CDP-Choline may aid in recovery from stroke by acting as a membrane stabilizer. There are several ways how this occurs. Citicoline maintains the activity of acetylcholinesterase, sphingomyelin, ATP synthase, and cardiolipin. It also reduces apoptosis, stimulates glutathione activity, and prevents damaged neurons from releasing fatty acids.
Citicoline is used for the management of cerebrovascular disorders. In Japan and Europe, it is used as a prescription drug to treat stroke.
Citicoline may help in recovery from ischemic stroke. Recovery rates differ depending on the quantity of nootropic administered. 500-2000 mg of Citicoline administered orally every day to stroke patients increases the likelihood of a full recovery within three months.
Citicoline raises lowered ATP concentrations and decreases increased glutamate concentrations stimulated by ischemia. It enhances the expression of the EAAT2 glutamate transporter, leading to increased glutamate uptake.
Citicoline can lower phospholipase stimulation which reduces hydroxyl radicals produced by ischemia. It inhibits the catabolism of cardiolipin by phospholipase A2.
Studies done on rats indicate that infusions of CDP-Choline given at the onset of experimental stroke can bestow protective effects. This includes reducing infarct size in a synergistic manner with SIRT1 activators and growth factors.
Improving Cognitive Functions
A 2006 study concluded that Citicoline is a suitable option for chronic cerebrovascular disorders and memory problems. Its neuroprotective effects prevent harmful compounds and toxins from causing damage to the brain, promoting a healthy brain.
By enhancing phospholipid metabolism, CDP choline initiates better neuron communication, which leads to effective and efficient brain performance. The conversion of cytidine to uridine enhances cognition. Uridine is a nucleotide base essential for neural membrane synthesis.
Citicoline affects the cholinergic system, increasing your brain’s choline levels. It also influences the dopamine and norepinephrine neurotransmitters within the brain. Dopamine is connected to cognition, your reward system, learning, and attention. Citicoline intake results in enhanced cognitive function and improved mood.
Raised Noradrenaline levels increase your brain’s energy. As a result, you have sufficient energy to function throughout the day. By increasing the body’s metabolism, Citicoline enhances the brain’s oxygen supply and stimulates its uptake of glucose.
Citicoline supplementation has been shown to improve verbal memory in patients with cognitive impairment and age-associated memory loss. It can also improve learning and memory.
Citicoline and Alzheimer’s
Due to its ability to prevent memory loss and enhance memory, CDP choline is linked to anti-aging and used to treat Alzheimer’s disease. The supplement increases frontal lobe bioenergetics, positively influencing mental energy and preventing age-associated cognitive decline.
In the clinical study linked above, in a condition such as Alzheimer’s disease, Citicoline enhances concentration ability for longer periods or the completion of mentally demanding activities. When used together with Piracetam, this brain supplement delays the onset of cognitive deterioration associated with Alzheimer’s disease.
Oral Citicoline intake may lead to improved cognitive function in patients with mild or moderate Alzheimer’s disease. The supplement may also counteract a neurotoxic protein deposit that contributes to the disease’s development.
Citicoline and Glaucoma
Glaucoma is a neurodegenerative disease and one of the leading causes of blindness in the elderly. It is typically characterized by retinal ganglion cells apoptosis. Usually, retina damage can occur before vision loss is detected. A sluggish neural conduction within the brain’s visual pathways is considered a factor in glaucoma’s visual effects.
Glaucoma patients who take Citicoline daily may improve their visual and retinal function. This natural supplement can also boost visual acuity and nerve function in glaucomatous eyes.
Citicoline’s Side Effects
According to research, Citicoline is relatively safe and has no serious side effects. Since it is well tolerated by the body’s cholinergic system, its consumption is linked to low toxicity. However, a daily dose of over 2000 mg may result in higher chances of negative effects.
Some unpleasant effects described by users include headaches, vomiting, indigestion, diarrhea, and insomnia. Others are tachycardia, bradicardia, and hypotension. It is recommended that pregnant or breastfeeding women do not consume CPD choline. This is because no studies have been conducted for this group.
Although Citicoline’s benefits may outweigh its risks, it is best to take it responsibly and monitor any reactions.
Alpha GPC is also known as Alpha-glycerophosphocholine or choline alfoscerate. It is a cholinergic supplement that contains choline that occurs naturally in the body – in small quantities. It is a precursor necessary for the synthesis of the acetylcholine neurotransmitter and a requirement for phosphatidylcholine formation essential for cell membrane manufacture.
Alpha GPC has a higher bioavailability compared to other choline sources for the brain. As a natural supplement, it’s derived from purified soy or sunflower lecithin extract. It is commonly preferred by users because, unlike other choline supplements, it crosses the blood-brain barrier easily. In the brain, it increases the accessibility of choline.
In the United States, this brain supplement can be purchased over the counter. It has been certified as Generally Recognized As Safe (GRAS) by the FDA. In Europe, it is regulated and prescribed for Alzheimer’s disease. It is sold under Delecit and Gliatilin brand names.
When taken orally, Alpha GPC supplies choline to neural tissues, raising acetylcholine levels. This results in increased brain and systemic choline concentrations. The brain supplement plays a key role in reducing cognitive decline and enhancing cognitive performance. It also increases the production of human growth hormone and enhances physical performance.
Research and Studies on Alpha GPC
Alpha GPC is an endogenous acetylcholine precursor and a choligernic dietary supplement. It’s a natural phospholipid that contains choline. In the brain, it’s also a precursor to phosphatidylcholine synthesis. It occurs naturally in the body as a lecithin metabolism intermediate.
It is available from food sources such as organ meats, cheese, milk, eggs, yogurt, oats, and wheat germ. However, the amounts of Alpha GPC in food sources are much lower than those in premium dietary supplements. Due to this, supplementation has been shown to help alpha GPC work better.
Alpha GPC Chemical Structure
The chemical structure of Alpha GPC includes a choline molecule attached to a glycerol molecule via a phosphate group. It is a phosphatidylcholine lecithin molecule devoid of two fatty acids. It is comprised of 40% choline, hence 1,000 mg of Alpha GPC contains 400mg free choline.
Alpha GPC is a phospholipid that is cholinergic, or choline’s primary storage form. Due to this, the brain supplement is frequently compared to Citicoline (CDP Choline). Citicoline is another natural choline source for the brain. However, Citicoline offers 21% choline, almost half of what Alpha GPC offers.
In clinical studies, Alpha GPC has been shown to be more potent and effective than CDP Choline or choline. Consuming similar dosages of Alpha GPC and Citicoline leads to higher levels of serum choline in the people who took Alpha GPC.
Pharmacology of Alpha GPC
During the conversion of lecithin to Choline, Alpha GPC acts as an intermediary. Therefore, a few of the same enzymes are used for its metabolism and ultimate absorption.
Lecithin is metabolized to lysolecithin from pancreatic phospholipase. Metabolism of lecithin further occurs when lysolecithin is exposed to phospholipase B, resulting in the formation of alpha-glycerophosphorylcholine.
The intestinal mucosal cells hydrolyze this Alpha GPC to form glycerophosphate and free choline. In the brain’s neural tissue, this first step can be avoided and choline can be generated when lecithin undergoes processing by Phospholipase D. This process directly converts lecithin to choline and glycerophosphate.
When two lysolecithin molecules reconfigure to a lecithin molecule, Alpha GPC can be formed as a byproduct. But this requires the presence of high lysolecithin concentrations.
Alpha GPC, ingested orally or administered intramuscularly, increases choline concentrations in plasma and becomes readily integrated to brain tissue. Studies done on rats indicate that within 24 hours, Alpha GPC is incorporated into brain phospholipids.
One large dose of Alpha GPC can consistently influence your brain for a period of 24 hours Acetylcholine release from stimulated neurons remains highest 1-3 hours after ingestion.
At this time, concentrations of glycerophosphocholine in the brain are almost equivalent to blood concentrations. This reveals a high intensity of penetration through the blood-brain barrier. Glycerophosphocholine and Phosphocholine concentrations are reasonably higher in neural tissue than acetylcholine or free choline combined.
Alpha GPC’s Mechanism of Action
The Alpha GPC supplement is water soluble, highly bioavailable, and fast-acting, particularly when taken orally. Its effects are experienced within an hour, because soon after consumption, it crosses the blood-brain barrier. After getting absorbed, it is metabolized into choline and glycerophosphate, a byproduct.
Alpha GPC’s major action is enhancing cholinergic neurotransmission. If your body has insufficient choline, the brain is unable to synthesize adequate acetylcholine that receptor sites require.
As a neural membrane phospholipid precursor, this supplement promotes neuronal functioning through enhanced neuronal membrane fluidity. It’s also an acetylcholine precursor and boosts the neurotransmitter which is essential for optimal brain function.
Alpha GPC enhances the efficiency of inter-neuron communication within your brain which boosts learning, memory, mental clarity, and cognitive processing. Studies show that it is beneficial for some mental and physical performance tasks.
In the cerebral cortex, this focus supplement directly influences the growth of cell membranes. This is the brain’s processing center that controls motor function, intelligence, and personality.
In addition to maintaining the brain’s plasticity, Alpha GPC is thought to play a role in new brain cell formation,. These functions are necessary for helping in the prevention of aging effects on the brain. The supplement may also act as a neuroprotectant, preventing neuronal damage and maintaining neuron health. It also seems to enhance synaptic signaling.
In the brain, Alpha GPC has been shown to stimulate an increase in choline transporter (CHT) expression and vesicular acetylcholine transporter (VAChT) expression. These are presynaptic cholinergic transporters essential for sustained ACh synthesis and neuron release.
Alpha GPC: Memory and Learning
When 600mg/kg of Alpha GPC was orally administered to rats, it stimulated PKC translocation in the cortex, peaking an hour after administration. PKC (Protein Kinase C) is an enzyme linked to memory formation and long-term memory potentiation.
The activation of PKC appears to be connected to the phospholipid component. One known PKC activator is diacylglyceride. In a clinical research conducted on dementia patients, four doses of 300 mg were given daily to treat cognitive decline. When the same dosage was given to healthy younger people, it prevented scopolamine-related memory and attention impairment.
In a study done on rats, 100-200mg/kg intraperitoneal injections of Alpha GPC were given for 21 days, two hours before training. They were linked to improved performance in both passive and active avoidance learning tasks. These tasks are commonly used for memory and cognition assessment.
Alpha GPC: Dopamine and Serotonin
In another study, a 150mg/kg Alpha GPC dose administered orally was observed to enhance levels of serotonin and dopamine in the frontal cortex and cerebellum. At the same time, the brain supplement increased the dopamine transporter expression.
Alpha GPC has also been shown to boost the release of dopamine due to potassium impact, possibly due to cellular membrane interactions. When consumed orally, it doesn’t change the expression of the serotonin transporter (SERT).
Alpha GPC: Human Growth Hormone
Alpha GPC works together with the pituitary gland to activate the production of human growth hormone (HGH). This hormone is responsible for reproduction of cells, growth, and repair. It also seems to possess anti-aging and longevity properties. An increase in the hormone occurred 45-60 minutes after ingestion of the supplement.
Athletes prefer Alpha GPC because it increases lean muscle mass and strength, resulting in improved recovery time. A 600 mg dose consumed prior to exercise has been shown to enhance growth hormone release and power output. The effects of Alpha GPC may be more pronounced in the elderly as HGH secretions decrease with age and before physical exercise.
Alpha GPC and Alzheimer’s Disease
In Alzheimer’s disease, there seems to be an increased rate of degradation to the cellular membrane that consists of choline-containing phospholipids. Patients may also manifest compromised presynaptic cholinergic function.
This may be due to increased choline requirements, since choline metabolism is enhanced by the disease. β-amyloid proteins, the biomarker of Alzheimer’s disease, can activate phospholipase A2 in the neurons, resulting in an accelerated phospholipid degradation.
A 400 mg dose of Alpha GPC, given orally three times a day for 180 days to patients with mild-to-moderate Alzheimer’s, caused a significant improvement in one study. 1,000 mg intramuscular injections of Alpha GPC have also been shown to improve memory, behavioral, and verbal symptoms in patients with vascular dementia over a period of 90 days.
Feeding your brain with phospholipid-containing choline supplements, such as Alpha GPC, may decrease additional neuronal membrane degeneration through increased cholinergic neuron viability. Cholinesterase inhibitors treatment has also been observed to raise acetylcholine concentrations, hence decreasing memory impairments.
Please note that the science here is still very much being explored. Definitely do not think for a second that Alpha GPC will truly delay or prevent any diseases. This is definitely still science that is in it’s infancy.
Alpha GPC and Neuroprotection
Research shows that Alpha GPC may help reverse cognitive decline after a stroke when given for a six-month period. The supplement also seems to be neuroprotective when administered immediately after a stroke or ischemia attack as a result of acute cerebrovascular disease. Alpha GPC also has anti-aging properties.
Alpha GPC Dosage
The recommended dosage for adults varies. A dosage of 300-600 mg, taken once or twice daily, is recommended for beginners and can be increased depending on need. This is also the standard dosage on most supplement labels.
For elderly people attempting to reduce dementia and cognitive decline symptoms, a total dose of 1200 mg per day, split into three 400 mg doses, is advised. For sportspeople, an 800 mg dose is recommended: 400 mg in the morning and another 400 mg 15 to 30 minutes prior to exercise.
Alpha GPC Safety and Side Effects
Alpha GPC is considered safe and is well tolerated by many healthy adults. This natural supplement is on the FDA’s GRAS supplement list. When consumed accurately, side effects are few and rare. Supplementing with higher doses can cause several adverse effects.
Users have reported diarrhea, fatigue, nausea, headaches, nervousness, and gastrointestinal distress. These are usually indicators that there are high levels of choline in the body. Other side effects include heartburn, confusion, vomiting, and erythema. You may experience insomnia if you take Alpha GPC at night because it gives an energy boost.
If you are susceptible to hypotension, consult a healthcare professional before taking it. Its use may cause low blood pressure and dizziness in some people. Avoid this supplement if you are taking scopolamine. Scopolamine is used to treat irritable bowel syndrome, post-operative nausea, and motion sickness.
Pregnant and breastfeeding women should not take this natural supplement as very few studies have been done on this group.
So, let’s summarize what we know from above…
How does CDP-Choline Work?
It’s kind of complicated, but we’ll stick to the basics: The body breaks CDP-Choline into cytidine and choline. The choline is then metabolized into phosphatidylcholine, which helps with brain cell membrane formation. Yes—you absolutely want healthy, optimal brain cell membrane formation for an optimal, healthy brain.
Clinically Supported Benefits of CDP-Choline
CDP-Choline has plenty of clinically backed benefits. For one, it is able to cross the blood-brain barrier, which means it can increase choline levels in your brain quickly and efficiently! CDP-Choline has been used both as a method of memory-loss prevention for aging individuals as well as a treatment for persons suffering from memory-related illnesses. Because it improves acetylcholine and phosphatidylcholine synthesis, it enhances brain health, memory and concentration. Not bad, right?
How does Alpha-GPC Work?
Alpha-GPC is a by-product of phosphatidylcholine and also aids in the brain’s production of acetylcholine. Part of Alpha-GPC is glycerophosphate, which is considered helpful to the maintenance of the healthy cell membranes we mentioned before. You can find Alpha-GPC in natural foods such as oats, wheats and milk. Because the amount of Alpha-GPC obtained from food consumption can be fairly minimal, supplementation is recommended to achieve noticeable cognitive improvement.
One study found that Alpha-GPC improved the cognitive abilities of participants with Alzheimer’s disease, while studies done on rats concluded that supplementing with Alpha-GPC improves learning abilities and short-term memory function. The hope—and hypothesis—is that it does the same for us humans.
The Negative Aspects of Using Alpha-GPC
A drawback of Alpha-GPC is that it has some mixed reviews from users. Many individuals have seen great results from taking Alpha-GPC, while others experienced negative aspects from the drug. People who take Alpha-GPC find the smart drug to be rather unpredictable—they’ve had good experiences and bad experiences with the compound. This lack of knowing whether the smart drug will improve their concentration or disrupt it makes Alpha-GPC a risky choice.
The Verdict on Brain Supplements: CDP-Choline or Alpha-GPC?
In summary, CDP-Choline and Alpha-GPC are different compounds that cause different chemical reactions in our bodies. But, they also have something very important in common: they both have positive effects on our cognitive abilities.
Because users have different experiences with CDP-Choline and Alpha-GPC, a valuable method for finding the nootropic that works for you would be experimentation. We’re not talking about treating your body like a science project—we’re just recommending that you do your research to find the right smart drugs for you. This way, you will find the nootropic that works best for you and your unique brain!