High-dose triglyceride DHA supplementation increases plasma and cerebrospinal fluid phospholipid DHA species.

Abstract

It is not clear whether triglyceride DHA-based formulations (TG-DHA) can sufficiently enrich brain DHA. Animal studies suggest that phosphatidylcholine (PC) and lyso-phosphatidylcholine (LPC) lipids might be preferred brain DHA substrates. The goal of this study is to assess the effect of high-dose TG-DHA supplementation on DHA-containing PC (PC-DHA) and LPC (LPC-DHA) lipid species in plasma and total cerebrospinal fluid (CSF) DHA as a surrogate for brain DHA incorporation. We conducted a randomized clinical trial stratified by DHA treatment (n=14) and placebo (n=14) status in non-demented older participants (CDR ≤ 0.5, age ³ 55 years old). Participants were provided 2,040 mg DHA daily in the form of TG-DHA for six months. Plasma and CSF were obtained at baseline and after supplementation. Participants were also stratified by ApoE ε4 status, an allele known to increase Alzheimer's disease (AD) risk. PC and LPC lipid species from plasma and CSF were isolated and examined by LC/MS-MS. Total fatty acids in CSF were measured via GC/MS-MS. Among all participants, PC-DHA represented 39% of total DHA in plasma, while LPC-DHA represented 1.8% of total DHA. PC-DHA increased by 69% and 19% in plasma and CSF, respectively, following supplementation compared to placebo (p<0.0001 for both). Plasma LPC-DHA increased by 140% in the treatment group compared to placebo (p<0.0001). Increases in plasma PC-DHA and LPC-DHA were both significantly correlated to changes in total DHA in CSF (R=0.8 and 0.57, respectively, p<0.003 for both). A trend toward greater increases in PC-DHA in non-ApoE ε4 carriers compared to carriers were also observed. Our data indicate that high-dose TG-DHA supplementation effectively increases DHA phospholipid incorporation in plasma and CSF. We acknowledge that CSF may not exactly reflect brain lipid uptake but provides useful information on brain DHA bioavailability. Our findings support that high-dose TG DHA supplementation are brain penetrant and can help answer whether enriching brain DHA can slow down cognitive decline in patients at risk of AD.