Citicoline supplement: does it improve memory?

ElaineD

Dear Alzfriends:  I was doing a research articles search for medications/supplements that actually help improve memory for dementia (and stroke) patients.

I came across several research articles showing positive results with the supplement citicoline.

Does anyone here have experience or knowledge to share?

I've placed an order and DH has expressed a desire to try it!  But I do wonder what the wonderful, knowledgeable and experienced people here have to say.

Elaine

Lane Simonian

I have no personal experience with citicoline, but found this interesting article regarding its effects on stroke:

Citicoline, or cytidine 5'-diphosphocholine (CDP-choline), a drug that combines neurovascular protection and repair promoting effects, has been used to treat acute ischemic stroke and other neurological disorders, and it has an excellent safety profile (59). Citicoline is a water-soluble compound, and pharmacokinetic studies on healthy adults have shown good absorption with both oral and intravenous routes of administration (60). Once absorbed, Citicoline is converted to choline and cytidine, which enter the systemic circulation and crosses the blood-brain barrier, where it is resynthesized into citicoline in the brain. Citicoline has been shown to possess several protective functions including promoting membrane stability, and inhibiting glutamate excitotoxicity, apoptosis, and oxidative stress (61, 62).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513624/

One of the problems in Alzheimer's disease at least is the impaired transport of choline.  I am not sure how much this would affect the effectiveness of citicoline supplementation.

Lane Simonian

Here is some additional information about citicoline this time for Alzheimer's disease:

However, some points need to be further stressed regarding the possible actions of citicoline, resulting in its successful use in combined treatment in AD. As reported in the above-mentioned study [1], it can work at a biochemical, cellular, and clinical level, but an essential condition is closely linked to its chronic administration (from three months on) [8]. Citicoline is able to increase phosphatidylcholine and other cell membrane phospholipids, to enhance acetylcholine synthesis, as well as other neurotransmitters such as dopamine and noradrenaline [9, 10], to prevent the accumulation of free fatty acids and the generation of free radicals at the site of ischemia [9]. It also inhibits apoptosis and promotes mitochondria energy metabolism by preventing the loss of cardiolipin [8, 11], thus having neuroprotective effects and promotes synaptogenesis, neurogenesis, and gliagenesis [12, 13]. Furthermore, it decreases neuronal glutamate efflux and stimulates glutathione synthesis, a powerful antioxidant [12, 13]. At a clinical level, citicoline is effective in cognitive impairment of diverse etiology, including AD, MD, vascular cognitive impairment, as well as glaucoma, ambliopia, and head trauma [8, 10], and improves the immediate and delayed recall of words and objects [14].

https://www.j-alz.com/content/role-combined-treatment-citicoline-alzheimers-disease

Citicoline appears to work best when it is combined with other drugs or natural products that further reduce the effects of glutamate efflux.  Among these are treatments that reduce inducible nitric oxide synthase.

https://pubmed.ncbi.nlm.nih.gov/29154836/

Deficiency of iNOS substantially protected the AD-like mice from premature mortality, cerebral plaque formation, increased beta-amyloid levels, protein tyrosine nitration, astrocytosis, and microgliosis. Thus, iNOS seems to be a major instigator of beta-amyloid deposition and disease progression. Inhibition of iNOS may be a therapeutic option in AD .

https://pubmed.ncbi.nlm.nih.gov/16260491/

One of the best pairs for citicoline is likely panax ginseng because it not only inhibits inducible nitric oxide synthase it also scavenges the subsequently produced nitro-oxidant peroxynitrite.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659628/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659550/

I  am not sure if there are any negative side effects of combining these treatments.  Panax ginseng along can potentially cause insomnia, stomach upset, and a temporary rise in blood pressure.

Lane Simonian

As a lark, I looked to see if there were any studies using a combination of citicholine and panax ginseng.  I found only one which was for healthy adults:

Panax ginseng led to an improvement in most components of the psychomotor performance measures, arousal function and visual working memory accuracy (p<0.05), but did not significantly affected recognition reaction time (RRT) and 1-back working memory accuracy (p>0.05). Regarding citicoline treatment, it led to an improvement in psychomotor performance measures and visual working memory accuracy (p<0.05), but did not markedly changed arousal and vigilance (p>0.05). When citicoline and Panax ginseng were used in combination, a marked improvement in both psychomotor performances and visual working memory accuracy on healthy volunteers were stated (p<0.01). Panax ginseng and citicoline act synergistically on human psychomotor performance and visual working memory in normal healthy volunteers.

https://www.authorea.com/users/470961/articles/562860-cognitive-enhancer-effect-of-citicoline-alone-or-in-combination-with-panax-ginseng-a-prospective-human-psychometric-study

I would be surprised if citicoline and panax ginseng did not work synergestically in people with Alzheimer's disease.