High-Plasmalogen Diets May Help Mild Cognitive Impairment

High plasmalogen diets may help mild cognitive impairment | MCI 911 Mild Cognitive Impairment

by Carissa Perez Olsen, PhD

Mild cognitive impairment (MCI) is associated with changes in a certain type of fats in our bodies, plasmalogens. These are a specialized type of phospholipids, which are the molecules that build our cellular membranes. In fact, plasmalogens make up more than 20 percent of phospholipids in humans, and are particularly plentiful in the nervous system.1

We do not yet have a full understanding of the roll of plasmalogens in biology, but it is clear they are important for the ability of our cells to survive in stressful conditions, particularly when there are high levels of chemically reactive molecules that can damage cellular components. It is not yet known how plasmalogens exert these protective effects, but it is clear that when they are absent, the cells die more often.1,2 This cell-protection role suggests that replenishing decreased levels of them in patients would have a benefit.

The Takeaway:

Increasing a patient’s intake of mussels, scallops, other types of seafood or by taking a daily plasmalogen supplement could help with MCI.
If lipids are deficient in one’s diet, they can be provided as supplements. A common example is taking fish oil for its content of omega fatty acids. Although plasmalogens are not yet a commonly known supplement, increasing their levels may be important to prevent or ameliorate the progression of MCI and Alzheimer’s disease (AD).

Plasmalogens in MCI

More particularly, the advent of mass spectrometry-based measurements has allowed for the comparison of the molecules that are altered during MCI and all stages of AD.3 One such change is a consistent depletion in plasmalogens. In MCI patients, their levels are decreased by up to 40 percent.4,5

Thus, restoring plasmalogen levels may be an important way to improve impaired cognitive function in MCI patients and, potentially, delay or prevent the onset of AD.

Dietary Supplements Improve Cognitive Function

Unlike other macromolecules such as protein and DNA, lipid composition can be altered through dietary changes, which presents a unique opportunity for intervention.

Lab studies

Studies in mice and other models demonstrated a therapeutic benefit in providing plasmalogens to the diet in mitigating memory loss.6

Human studies

Foods that are high in plasmalogens, like scallops, have been shown to improve cognitive function in early stages of AD in a Japanese study of 328 patients by Fujino and colleagues.7 Due to the safety and ease of administration of dietary supplements, plasmalogens were added to the diet of patients with early AD—and cognitive improvement was seen in mild cases.

The subjects received either 1 mg/day of plasmalogens purified from scallops or a placebo. In mild AD patients, measures of memory (WMS-R test) improved significantly in the treatment group among females and those younger than 77 years old. There was no statistically significant improvement in more advanced patients, suggesting that early intervention is critical.

Additionally, the supplementation of these lipids can be tailored to individuals by adjusting dosage according to body weight. There are no studies of how much plasmalogen supplementation would be needed for maximum benefit.

Sources of plasmalogens

There have been efforts to identify sources of plasmalogens in food. In one study, the highest levels of plasmalogens were found in ascidians, also called sea squirts, mussels, and scallops.8 There are also significant levels in pork and beef.

Supplements available are derived from scallops and at similar concentrations as provided to the individuals in the study described above. It is important to note that they have not been specifically tested and are fairly expensive per dose . Also, studies have not yet determined if particular types of plasmalogens would have a greater benefit than others.


The clinical studies that have been completed thus far have been limited to general plasmalogen supplements that were purified from scallops. There is significant potential to improve efficacy by testing more specific plasmalogen combinations. Model systems can be useful in determining the supplementation with the most promise for clinical trials.

In summary, a decrease in plasmalogens may be a way to identify MCI before symptoms are noticeable. If the level is reduced, intervention can occur earlier to correct the deficit. Thus, there may be significant potential to make dietary changes to help people with MCI or mild AD improve their cognitive functions.

Increasing a patient’s intake of mussels, scallops, other types of seafood or by taking a daily plasmalogen supplement is a relatively simple way to get started.

There are even “scallop-derived” supplements already available on Amazon, at $85 to $90 for a month’s supply, but we have no experience with these, and we found no studies proving their efficacy.


1. Braverman NE, Moser AB. Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta. 2012;1822(9):1442-1452. doi: 10.1016/j.bbadis.2012.05.008.

2. Sindelar PJ, et al. The protective role of plasmalogens in iron-induced lipid peroxidation. Free Radic Biol Med. 1999;26(3-4):318-324. doi: 10.1016/s0891-5849(98)00221-4.

3. Wood PL, et al. Circulating plasmalogen levels and Alzheimer disease assessment scale-cognitive scores in Alzheimer patients. J Psychiatry Neurosci. 2010;35(1):59-62. doi: 10.1503/jpn.090059.

4. Han X, et al. Plasmalogen deficiency in early Alzheimer’s disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J Neurochem. 2001;77(4):1168-1180. doi: 10.1046/j.1471-4159.2001.00332.x.

5. Marin R, et al. Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer’s and Parkinson’s diseases. Neurobiol Aging. 2017;49:52-59. doi: 10.1016/j.neurobiolaging.2016.08.027.

6. Hossain MS, et al. Oral ingestion of plasmalogens can attenuate the LPS-induced memory loss and microglial activation. Biochem Biophys Res Commun. 2018;496(4):1033-1039. doi: 10.1016/j.bbrc.2018.01.078.

7. Fujino T, et al. Efficacy and blood plasmalogen changes by oral administration of plasmalogen in patients with mild Alzheimer’s disease and mild cognitive impairment: a multicenter, randomized, double-blind, placebo-controlled trial. EBioMedicine. 2017;17:199-205. doi: 10.1016/j.ebiom.2017.02.012.

8. Yamashita S, et al. Analysis of plasmalogen species in foodstuffs. Lipids. 2016;51(2):199-210. doi: 10.1007/s11745-015-4112-y.

Additional Reading
Olsen CP. Cognitive health: high-plasmalogen diets and Alzheimer’s. Today’s Dietitian. 2019;21(10):12.

Su XQ, et al. Plasmalogens and Alzheimer’s disease: a review. Lipids Health Dis. 2019;18(1):100. doi:10.1186/s12944-019-1044-1.

About the Author

MCI 911 Contributor Biochemist Dr. Carissa Perez Olsen


Dr. Carissa Perez Olsen is a biochemistry researcher and an Assistant Professor of Chemistry and Biochemistry at Worcester Polytechnic Institute in Worcester, Massachusetts. She received her PhD from the University of Washington in Seattle and started an independent research group with an Early Independence Award from the National Institutes of Health. She is passionate about understanding how lipids impact human disease and in finding new approaches to promote healthy aging.