Citicoline as a Nootropic, and in Stacks with ALCAR and Phosphatidylserine
CDP-Choline, aka Citicoline
Citicoline, officially named Cytidine diphosphate-choline (CDP-Choline) or cytidine 5′-diphosphocholine occurs naturally in the brain and is available OTC in over 70 countries under names such as Ceraxon, Cognizin, NeurAxon, Somazina, and Synapsine. Citicoline is a popular “choline” supplement for use in racetam stacks.
Basics of Citicoline
Among choline sources, Citicoline is unique, for supplying another useful brain nutrient known as uridine (the brain converts cytidine to uridine). Uridine itself has nootropic qualities, which compliment choline. Uridine promotes neurogenesis or “neurite outgrowth”  and may balance dopamine levels .
Hormonal Benefits of Citicoline
CDP elevates Adrenocorticotropic hormone (ACTH) and Corticotropin-releasing hormone (CRH), which may improve bone health, increase VEGF, and ease adrenal insufficiency.
Like other sources of choline, CDP may improve HPA axis status, including levels of Luteinizing hormone, a precursor to testosterone.
Metabolism of Citicoline
Within the brain, CDP is metabolized. It is broken down to choline and cytidine groups:
- Choline catalyzes the formation of phosphatidylcholine (PC) and acetylcholine,
- Cytidine is converted to uridine (UDP).
From here, each molecule goes its separate way, to serve its separate function.
Benefits of Choline
Glutathione and methionine status are modulated via choline . Glutathione is a chief brain antioxidant, and elevated or diminished glutathione status is typically a marker of adjustment to increased oxidative stress.
Reduced methionine, an amino acid and intermediate to cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids, has been linked to increased graying of hair .
Increased acetylcholine improves dementia status, hippocampal and prefrontal cortical transmission/function, improves muscular output, but may cause lucid dreaming.
It facilitates communication between the spinal cord and the organs, and between the vagus nerve and the immune system. So it may worsen autoimmune conditions, but in the case of myasthenia gravis (Graves’ disease, malformed antibodies mistakenly clog acetylcholine nicotinic receptors), increased acetylcholine improves transmission.
Graves’ disease, like other autoimmune diseases, is routinely treated with acetylcholinesterase inhibitors.
Benefits of Uridine
Uridine intake has been studied, with mixed or incongruent results on the effect on dopamine release (increased and decreased). Modulation of dopamine transmission may explain studies’ reports of improved mood and motivation.
Uridine has diverse nootropic effects, including improved working memory, fluid intelligence, and creativity. This may be in part due to increased NGF.
Uridine for Depression or Bipolar
Uridine has been studied for depression and bipolar disorder, but according to examine.com, results are inconclusive or conflicting. Other OTC supplements or prescribed medicines may be more effective.
UDP and UMP act as precursors or catalysts to phosphatidylcholine and phosphatidylserine synthesis which may offer some antidepressant effects.
Choline also has benefits for depression, such as improving neurogenesis status, which is impaired in depressed patients . But too much choline can contribute to depression (see this source for a list of symptoms of excess acetylcholine) .
Stacks with Citicoline
A healthy fish choice, such as sardines, wild salmon, or immature tuna, supplies DHA, which has numerous synergistic effects with citicoline.
Standalone nootropics ALCAR (Acetyl-L-carnitine) and phosphatidylserine are acetyl and phosphatidyl donors, and stack well with CDP. Acetylcholine levels can be boosted dramatically with this combination.
Phosphatidylcholine levels are also boosted; low phosphatidylcholine is associated with nerve death. It is vital for nerve health; composing up to 20% of the cell membrane or phospholipid bilayer. On the contrary, too much phosphatidylcholine increases triglycerides [diacylglycerol] and contributes to atherosclerosis.
The benefits of such stacks are cumulative with healthy diets and regular exercise, which exert cholinergic and neuroprotective effects.
Serine levels also increase, which may improve cognition and schizophrenia . Serine itself is being researched as a nootropic, in particular, the D-serine isomer.
Standalone nootropics huperzine and especially galantamine have interesting secondary and tertiary mechanisms in addition to their primary of increasing acetylcholine by inhibiting acetylcholinesterase.
Galantamine improves α7 receptor transmission and modulates kynurenic acid levels, so it may improve cognitive function in the healthy, and across several illnesses such as ADD, dementia, depression, and others. This promising nootropic is approved for prescription and OTC.