Citicoline and memory in old age: what research has proven

Citicoline and memory in older age is the subject of clinical studies in which researchers tested specific memory skills, rather than the general ability to "think better." The most widely discussed study is a 2021 study involving people aged 50–85 that found positive results for certain episodic memory tests. However, an independent 2024 EFSA assessment did not find the body of evidence sufficient to establish a cause-and-effect relationship between citicoline consumption and improved or preserved memory.

To properly understand these findings, it is important to distinguish between age-related complaints of forgetfulness, computer-based test results, and clinical memory impairment. These are not the same conditions, and the results of one study cannot be automatically transferred to people of a different age or to those with a diagnosed disease.

What are age-related memory changes?

As a person ages, they may notice that it takes them longer to remember names, new information, or details of a recent conversation. Such complaints do not in themselves indicate dementia. Their severity depends not only on age, but also on sleep, psychological state, medications, comorbidities, and other factors. If the changes are noticeably progressive or affect daily independence, this is a reason for a medical examination, not for choosing a supplement on your own.

The term age-associated memory impairment (AAMI) is used in citicoline studies. This is a characteristic of the sample, not a universal name for all memory problems after age 50.

What types of memory were tested in citicoline studies?

Memory is not a single function. A person may be good at holding a few numbers for a few seconds, but worse at remembering where and when they saw a certain object. That's why scientific conclusions are tied to specific tests.

• Episodic memory is the recall of events, images, and the connections between them, such as pairs of objects that were shown previously.
• Short-term memory is the temporary retention of a small amount of information, such as a sequence of numbers.
• Working memory is the retention of information while simultaneously using it in a task.

A better score on one test does not confirm improvement in all of these functions. Similarly, a statistically significant difference between groups does not necessarily mean that participants experienced a noticeable change in their daily lives.

Nakazaki et al.'s study (2021): what the results showed

A randomized, double-blind, placebo-controlled study by Nakazaki et al. (2021) enrolled 100 men and women aged 50 to 85 years with age-related memory complaints. Participants were assigned to citicoline (49 subjects) and placebo (51 subjects). The protocol used 500 mg of citicoline per day for 12 weeks. These figures describe the conditions of the research study only and are not a recommendation for supplementation.

At 12 weeks, the researchers found a greater change in episodic memory scores in the citicoline group than in the placebo group: in the pair-matching test, the mean changes were 0.15 versus 0.06 (p = 0.0025). For the composite score of the four tests, a statistically significant difference was also obtained: 3.78 versus 0.72 (p = 0.0052). Both results related to the secondary outcomes of the study.

However, no convincing effect was found for tests of short-term and working memory. This distinction is important: the study did not show an overall improvement in each aspect of memory measured. The paper also notes the connections of some of the authors to the manufacturer of the studied ingredient; this context should be taken into account when assessing the independence of the evidence.

Why one positive study is not enough

The strength of a scientific conclusion is determined not only by whether the p-value is below a set threshold. The preliminary definitions of the main result, the number of participants, the reproducibility of the effect in independent studies, and its practical significance are important.

In the Nakazaki et al. study, differences were observed in selected secondary endpoints. The composite score, which also improved, may largely reflect changes in episodic memory. The study was conducted over 12 weeks and does not address whether the results were maintained after the end of the study or whether participants' daily skills changed.

Previous studies have also been mixed. Alvarez et al. (1997) assessed a recall task in 24 older adults with memory impairment but no dementia. However, the small sample size, open-label design, and other methodological limitations do not allow these results to be considered strong independent evidence. In another study reviewed by EFSA, the effect on memory was not replicated using a different protocol.

A scientific panel of the European Food Safety Authority (EFSA) reviewed the studies submitted to support the memory support claim for citicoline. The assessment did not focus on a single test, but rather on the body of evidence in middle-aged and older people with age-related memory complaints.

EFSA noted a positive result for episodic memory in Nakazaki et al. (2021), but found insufficient support in other studies. The panel also did not find a convincing mechanism by which additional intake of citicoline, in addition to the body's own synthesis of the corresponding compounds, would provide this clinical effect.

EFSA conclusion (2024): A cause-and-effect relationship has not been established between the consumption of citicoline and the improvement, maintenance or reduction of memory loss in this population. This does not mean that all the individual study results are wrong. It means that the available data are insufficient to make a general, substantiated claim about the benefits for memory.

How to read the results correctly: a brief comparison

It is not correct to compare studies by dose without considering sample composition, test type, and design. The doses listed in the table are characteristics of the study protocols and do not constitute instructions for self-administration.

What these results mean for an older person

The existence of isolated positive results provides grounds for further scientific research, but does not make citicoline a proven way to preserve memory in older age. Researchers still need to clarify for which groups the observed changes may be relevant, whether they are independently reproducible, and whether they are noticeable outside of laboratory tests.

It is also important not to confuse age-related complaints with dementia or other clinical disorders. Research involving relatively healthy people does not prove effectiveness in established diseases. If forgetfulness is new, rapidly increasing, or interferes with daily activities, it is appropriate to consult a doctor to find out the causes. When taking medication, during pregnancy or breastfeeding, the issue of using supplements also requires individual consultation.

Frequently asked questions

Is citicoline proven to improve memory after age 50?
No, a general cause-and-effect relationship has not been established. A separate study showed positive results for episodic memory, but EFSA considered the body of evidence insufficient.

What was the age of the participants in the main study?
The work of Nakazaki et al. (2021) involved people aged 50–85 with age-related memory complaints.

What is episodic memory?
This is the ability to remember and recall events and the connections between their details. In research, it is assessed with special tasks, in particular, the reproduction of pairs of objects.

Have studies shown an effect on working memory?
A key 2021 study found no statistically significant effect on working memory tests compared to placebo.

Can the research results be transferred to people with dementia?
No. Studies in relatively healthy people with age-related complaints do not confirm efficacy in diagnosed dementia.

Do the doses from the publications represent the recommended dosage of the supplement?
No. These are parameters of specific research protocols, not instructions for self-administration.

What to do if memory noticeably deteriorates?
You should see a doctor, especially if the changes are progressive or affect your daily activities. The causes cannot be determined by describing the symptoms alone.

Sources

• Nakazaki E., Mah E., Sanoshy K., Citrolo D., Watanabe F. (2021). Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. The Journal of Nutrition , 151(8), 2153–2160. PubMed .
• EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA). (2024). 'Citicoline' and support of the memory function: Evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA Journal , 22(7), e8861. PubMed .
• Alvarez XA et al. (1997). Citicoline improves memory performance in elderly subjects. Methods and Findings in Experimental and Clinical Pharmacology . PubMed .

Dietary supplement. Not a medicine. Consult a doctor before use.