The effect of plasmalogen precursor supplementation on blood plasmalogen and C‐reactive protein levels and cognition in cognitively impaired persons

Abstract Background Decreased blood and brain plasmalogens levels are associated with decreased cognition in humans. 1‐O‐alkyl‐2,3‐diacylglycerol (ADG) plasmalogen precursors containing docosahexaenoic acid (DHA) at the sn‐2 position have been shown to increase blood plasmalogens and to be neuroprotective in animal models of neurodegeneration. The goal of this study was to evaluate the effect of dietary DHA‐ADG supplementation on blood plasmalogen and C‐Reactive Protein (CRP) levels and cognition in cognitively impaired persons. Method Twenty persons (9M/11F), aged 37‐81 (average = 68) with mild to moderate cognitive impairment [CDR: 13(0.5); 3(1); 4(2)] were administered an escalating dose of DHA‐ADG [1.0ml/day for 30 days; 2.0ml/day for 60 days; 4.0ml for 30 days]. Blood plasmalogen and CRP levels and cognitive status were measured at baseline and the end of each month. Cognitive status was determined using the Quick Dementia Rating System (QDRS), which was used to derive the participant’s Clinical Dementia Rating (CDR). Result Overall, maximum average DHA ethanolamine plasmalogen levels were achieved by the end of the 2 nd month [224% of baseline, 95%CI = 173‐273%] and this level of elevation was sustained for the duration of the study. Of the 20 participants, 14 (70%) exhibited robust and sustained plasmalogen elevations (>150%, >2 months, ADG Responder). Of the 14 ADG responders, 10 exhibited improvements on QDRS and 6 of these 10 exhibited improvements of at least one CDR level. Of the 14 ADG responders, 4 had baseline CRP levels >1.0. In each of these 4 subjects, CRP levels decreased by >0.5 by the end of the 4 th month. DHA‐ADG was well tolerated at all dosages and no adverse reactions were observed. No cognitive improvement was observed in any of the ADG non‐responders. Conclusion DHA‐ADG was effective at elevating blood plasmalogen levels at the dosages studied. 10/14 (71%) of cognitively impaired persons experienced improved levels of cognition when blood DHA‐plasmalogens were elevated by >150%. In all persons with elevated baseline CRP levels, DHA‐plasmalogen elevation was associated with a decrease in blood CRP. This analysis suggests that DHA‐ADG supplementation may be beneficial for patients with mild to moderate cognitive impairment.