Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography

Abstract

Docosahexaenoic acid (DHA; 22:6n-3) is a critical constituent of the brain, but its metabolism has not been measured in the human brain in vivo. In monkeys, using positron emission tomography (PET), we first showed that intravenously injected [1-11 C]DHA mostly entered nonbrain organs, with ?0.5% entering the brain. Then, using PET and intravenous [1-11 C]DHA in 14 healthy adult humans, we quantitatively imaged regional rates of incorporation (K*) of DHA. We also imaged regional cerebral blood flow (rCBF) using PET and intravenous [15 O]water. Values of K* for DHA were higher in gray than white matter regions and correlated significantly with values of rCBF in 12 of 14 subjects despite evidence that rCBF does not directly influence K*. For the entire human brain, the net DHA incorporation rate J in , the product of K*, and the unesterified plasma DHA concentration equaled 3.8 6 1.7 mg/day. This net rate is equivalent to the net rate of DHA consumption by brain and, considering the reported amount of DHA in brain, indicates that the half-life of DHA in the human brain approximates 2.5 years. Thus, PET with [1-11 C]DHA can be used to quantify regional and global human brain DHA metabolism in relation to health and

Higher RBC EPA + DHA corresponds with larger total brain and hippocampal volumes

“…DHA brain metabolism was studied in 14 healthy adult men and Figure 2 Mean normal hippocampal brain volume in cubic centimeters by omega-3 index using linear regression with 95% confidence bands The fully adjusted model has a slightly attenuated slope compared with the unadjusted model, but reduced variability; a 3.2% greater omega-3 index is correlated with 100 mm women between 19 and 64 years of age using radiolabeled DHA and PET. 36 The net rate of human brain DHA uptake was 3.8 6 1.7 mg/d, which implied a 2.5-year half-life assuming 5 g of total DHA in the brain. To the extent that incorporation of DHA into neuronal membranes is important in maintaining cognitive function, future supplementation studies may need to be several years long.…”

Imaging decreased brain docosahexaenoic acid metabolism and signaling in iPLA2β (VIA)-deficient mice

“…* P < 0.05; ** P < 0.01; *** P < 0.001; iPLA 2 (18)(19)(20)(21)(22) ). This could be tested directly by quantitatively imaging regional brain DHA incorporation in these patients with positron emission tomography ( 67 ).…”

[P3–317]: DHA BRAIN UPTAKE AND APOE4 STATUS: A PET STUDY WITH [1‐11C]‐DHA

“…From plasma samples collected at 0, 3,7,10,15,20,40, and 60 minutes after infusion of [1-11 C]-DHA, total lipids were extracted into chloroform:methanol (1:1) as previously described [24].…”