Do plasmalogen supplements improve cognitive function and memory?

Answer:

Plasmalogens, a type of phospholipid (i.e., a compound made up of a fat and a phosphate group), are marketed as supplements to improve cognitive function and focus, support memory, and reduce brain fog, especially in older adults. While there is some preliminary evidence that plasmalogens play a role in brain function, the evidence for it being useful as a supplement for people is very limited, as discussed below.

What are plasmalogens?

Plasmalogens are a type of naturally occurring phospholipid. Plasmalogen make up as much as 18% of phospholipids in human cell membranes (Lee, Biochm Biophys Acta 1998). There are two main types of plasmalogens: ethanolamine plasmalogens and choline plasmalogens. Ethanolamine plasmalogens make up a significant portion of the phospholipids in the brain (Su, Lipids Health Dis 2019).

What do plasmalogens do?

Along with providing cell membrane structure, plasmalogens — particularly ethanolamine plasmalogens — are thought to play a role in brain function. Test tube studies and animal research suggest that certain plasmalogens, particularly those containing docosahexaenoic acid (DHA), may have neuroprotective effects and reduce brain inflammation (Hossain, PLoS One 2013; Ifuku, J Neuroinflammation 2012). Loss of ethanolamine plasmalogens has been linked with aging, as well as Alzheimer's disease, with greatest decreases observed in the areas of the brain most affected by this disease (Pradas, Redox Biol 2019; Ginsberg, Brain Res 1995). In some cases, the decrease in ethanolamine plasmalogens has been linked with the severity of cognitive decline in people with Alzheimer's disease (Su, Lipids Health Dis 2019).

Based on the possible link between plasmalogens and brain function, there is interest in plasmalogen supplements to help improve cognitive function and memory. However, research supporting such benefits is limited, as discussed below.

Brain function

Taking plasmalogens might, at best, slightly improve memory or cognitive function in older, healthy adults who are forgetful, but it doesn't seem to improve their attention. Plasmalogen supplementation doesn't seem to offer much benefit for adults with cognitive impairment or with Alzheimer's or for young adults.

In healthy adults
A study in Japan among healthy adults (average age 46) with self-reported slight forgetfulness showed that taking a capsule containing 1 mg of plasmalogens isolated from ascidians (sea squirts) once daily for 12 weeks slightly improved composite memory and visual memory, but did not significantly improve reaction time, attention or other measures of cognitive function compared to placebo. Plasmalogens from ascidians are known to contain eicosapentaenoic acid (EPA), DHA, oleic acid, and arachidonic acid. The supplement used in the study was from Nihon Pharmaceutical Co., which conducted the study (Watanabe, J Oleo Sci 2020). Another study in the U.S. among 30 adults (average age 65) with possible cognitive decline or risk factors for cognitive decline showed that taking one capsule of Daiwa Brain Health standardized to 0.5 mg of plasmalogens daily for about 13 weeks improved cognition by 0.5 points based on one 10-point scale (the Abbreviated Mental Test Score) and by 1.3 points based on a 30-point scale (the Mini-Mental State Examination Score) compared to baseline, and these improvements were statistically significant compared to another group that was given one capsule of Prevagen daily and showed no significant improvement in either measure of cognition. However, this study lacked a placebo group, which is needed to prove a benefit, and the participants and the investigator knew which supplements were given to the participants (Pescatore, Altern Ther Health Med 2024).

In contrast, a study in Japan among 75 healthy adults (average age 58) with self-reported cognitive difficulties showed that taking capsules providing 0.25 or 0.5 mg of plasmalogens isolated from chicken (by P-Solution Inc., which funded and conducted the study) daily for 12 weeks did not significantly improve cognitive function based on the Mini Mental State Examination or Uchida-Kraepelin test compared to placebo (Najima, Shinryo to Shinyaku 2016).

Research has not shown significant benefit of plasmalogen on cognitive function in young adults. A study among 40 healthy young adults (average age 20) showed that taking 1 mg of a scallop-derived plasmalogen twice daily for 4 weeks did not significantly improve cognitive function (based on the Uchida-Kraepelin Test), although supplementation slightly improved negative mood states (such as anger/hostility and fatigue) compared to placebo (Fujino, Front Cell Dev Biol 2022). The study was funded by the Japanese Plasmalogen Society, which received donations from B&S Corporation, the manufacturer of the plasmalogen used in this study.

In adults with mild cognitive impairment, dementia or Alzheimer's disease
A study funded by the Japanese Plasmalogen Society among 276 adults (average age 76) with mild Alzheimer's disease or mild cognitive impairment in Japan showed that 1 mg of plasmalogen extracted from scallops (by B&S Corporation), taken in two divided doses daily for 24 weeks, did not significantly improve cognitive function or memory compared to placebo (Fujino, EBioMedicine 2017).

Although a small study published in 2022 suggested cognitive improvements with a high dose of plasmalogen, the study was only preliminary and does not prove a benefit. In the study, 22 older adults (average age 67) took 900 mg of a synthetic DHA plasmalogen (ProdromeNeuro by Prodrome Sciences, which conducted the study) daily for 1 month, then increased the daily dose by 900 mg every month for an additional 3 months (final daily dose during month 4 was 3,600 mg). Blood levels of phospholipid derivatives of DHA plasmalogen increased compared to baseline, and about 41% of the participants reportedly showed improvements in cognitive function compared to baseline. However, the same percentage (41%) of participants showed no improvement and 18% showed cognitive decline. Furthermore, the researchers defined improvement as a "change in CDR [Clinical Dementia Rating level] of one or more units" but the average change in score was not reported for the study participants and the statistical significance of the change was based on a comparison with predicted responses rather than a placebo control group (Goodenowe, Front Cell Dev Biol 2022).

Safety of plasmalogens

Plasmalogen supplements have been safely used in the studies described above, with no serious side effects attributed to plasmalogens (Fujino, Front Cell Dev Biol 2022; Goodenowe, Front Cell Dev Biol 2022; Fujino, EBioMedicine 2017; Najima, Shinryo to Shinyaku 2016; Watanabe, J Oleo Sci 2020). Keep in mind that all of the studies have generally been small and short-term, so long-term safety and possible rare side effects are unknown.

Theoretically, people allergic to the raw materials from which plasmalogens are derived (such as scallops) may have an allergic response to the corresponding plasmalogen.

Cost

Plasmalogen supplements (usually sold as capsules or softgels) are typically expensive (about $2.55 or more per daily serving) and may not be worth the cost based on the limited evidence of benefit.

For instance, NeuroREGAIN by LABO Nutrition costs about $2.55 per 1-mg of plasmalogens and Daiwa Brain Health softgels cost about $2.69 per 1-mg of plasmalogens. Two other products, each from Prodrome Sciences, cost even more per serving, and the amount of plasmalogens per serving of these products is unclear. ProdromeGlia costs $99 for 30 servings ($3.30 per serving), while ProdromeNeuro costs a whopping $199.00 for 30 servings ($6.63 per serving). Both products, which are synthesized in a lab rather than derived from animals, are listed as providing 900 mg of omega-3 plasmalogen oil per 2-capsule serving, which seems to be significantly higher than the amount in other products. However, it is not clear what percentage of plasmalogen oil is plasmalogens.

Are foods good sources of plasmalogens?

Many animal-based foods are good sources of plasmalogens, with some providing more per serving than the 1 to 2 mg generally been used in clinical studies per day. As shown below, meats and poultry contain greater amounts than seafoods, although ethanolamine plasmalogens (the type found in particularly in the brain) tend to make up a greater percentage of total plasmalogens in seafood compared to meat and poultry (Wu, Foods 2021).