Research Progress of Plasmalogen

Research Progress of Plasmalogen

The strong correlation between plasmalogens and Alzheimer’s disease had already been confirmed decades ago. However, these studies had made very little progress. The main reason for the slow progression was due to extraordinary amount of time and money required for plasmalogen extraction and detection. In addition, there was no high-volume extraction technology available for animal testing and clinical trial. However, a research team in Japan chaired by Takehiko Fujino, Emeritus Professor of Kyushu University has successfully established a patented high-volume plasmalogen extraction method with 92% purity and a simple plasmalogen detection method. These discoveries have led to a major breakthrough in plasmalogen research.

Research Progress of Plasmalogen


In parallel with the clinical trial which commenced in November 2014, another large-scale clinical trial (open trial) was carried out in January 2015 to study the effect of test food containing Scallop-derived-PLASMALOGEN on cognitive function in 225 patients with moderate and severe dementia (Alzheimer’s dementia, Lewy body dementia, cerebrovascular dementia and semantic dementia) (60 – 85 years old). In this clinical trial, participants were divided into two groups and test food containing 0.5mg or 1.0mg Scallop-derived PLASMALOGEN were administered to each group for 3 months. Changes of MMSE were observed and caregivers’ evaluations were taken. This trial had completed in April 2016 and the data is expected to be published late 2016 or 2017.
The clinical data from 44 patients who had completed the trial was reported. Scallop-derived PLASMALOGEN has improved cognitive function such as memory and concentration, emotion, hallucination, delusion, facial expression, as well as the concentration of plasmalogens in the membranes of patients’ red blood cells. (UMIN test ID: UMIN000016008)


High-purity plasmalogen in large amount was successfully extracted from scallop (Scallop-derived PLASMALOGEN).
Based on the results of the small-scale study conducted in 2013, a large-scale clinical trial (double-blind) was conducted in November 2014 to study the effect of test food containing Scallop-derived PLASMALOGEN on the cognitive function in 328 patients with mild Alzheimer’s disease or mild cognitive impairment (60 – 85 years old). In this clinical trial, test food containing 0.5 mg of plasmalogen or placebo food were given to the patients twice a day for 6 months and changes of MMSE and other medical indices [Wechsler Memory Scale-Revised, blood plasmalogen and geriatric depression scale (short version)] were observed. This trial had completed in April 2016 and the data is expected to be published late 2016 or 2017. (UMIN test ID: UMIN000014945)


Small-scale clinical trial (single-blind trial) was conducted to evaluate the effect of plasmalogens (derived from chicken) on the improvement of cognitive function and the effect of plasmalogen hemodynamic alteration by 6-month administration of plasmalogen-containing drink to 40 patients with mild to moderate Alzheimer’s disease (60 years old or above). In this trial, test food (drink containing either 0.5mg, 2.5mg or 5mg of plasmalogens) and placebo food were given twice a day to Alzheimer’s disease patients for 6 months and the changes of MMSE and other medical indices (levels of plasmalogen in red blood cells, blood chemical and blood pressure) were observed. (UMIN test ID: UMIN000009898)
Research was conducted on two shellfish with the aim to search for a better source of plasmalogens.


Completion of safety test of plasmalogens.

Research proved that patients with Alzheimer’s disease have lower levels of plasmalogen in their erythrocytes (Oma S et al., 2012).
Another research proved that orally administered plasmalogens (chicken skin) in rat increased the levels of plasmalogen in the erythrocytes (Mawatari S et al., 2012).

Administration of plasmalogens (chicken breast muscle) in animal model was proven to increase plasmalogen content in the brain and suppress neuroinflammation and accumulation of amyloid β proteins induced by lipopolysaccharide (LPS) (Katafuchi T et al., 2012; Masataka I et al., 2012).


Oral administration of plasmalogens to the dozens of Alzheimer’s patients was implemented in a private medical institution. The safety and efficacy of plasmalogens were tested in patients with dementia of Alzheimer’s type (2009 – Present).


Simplified and sophisticated method to separate plasmalogens from all other phospholipids was established [2-day work has been shortened to 1 hour with high performance liquid chromatography (HPLC) method] (Mawatari S et al., 2007).


A method to extract high purity (92%) plasmalogens in high-volume from chicken was established. In this method, extracted phospholipids were treated with certain enzyme and only plasmalogens remained in the end. This method was easy, fast and affordable (Mawatari S et al., 2009).

Before 2006

“Brain Fatigue” theory established in 1997 was the clue to the study of plasmalogens. BOOCS (Brain Oriented Oneself Control System) theory is the “Brain Fatigue” removal method to prevent fatigue from generating in the brain. This BOOCS theory was then progressed towards a significant relationship between Alzheimer’s dementia and plasmalogens as Alzheimer’s would be one of the results from brain fatigue and plasmalogens have efficacy for Alzheimer’s disease.

Strong correlation between plasmalogens and Alzheimer’s dementia had already been confirmed in other studies (Ginsberg L et al., 1995 and Guan Z et al., 1999)

However, these studies have made very little progress. The main reason was the extraction of plasmalogens requires huge amount of time and money. In addition, there was no high-volume plasmalogen extraction technology available for animal testing and clinical trial.


Publication Number: 2006-232967

Development of a technique capable of simple and mass production of sphingolipid and plasmalogen-type glycerophospholipid and functional food materials containing them.

Publication Number: 2008-179588

Development of a simple method to extract high-purity sphingomyelin and plasmalogen-type glycerophospholipid from chicken epidermis in good yield.

Publication Number: WO/2012/039472

Development of a novel therapy comprising plasmalogen, to ameliorate central nervous system inflammation. The plasmalogen is extracted from a biotissue (preferably an avian tissue) containing ethanolamine plasmalogen and choline plasmalogen.