Phospholipid class-specific brain enrichment in response to lysophosphatidylcholine docosahexaenoic acid infusion

This project was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) [482597] and from the Canadian Institutes of Health Research (CIHR) [497215] to Dr. R.P. Bazinet and by a NSERC studentship to Dr. C.T. Chen.Peer reviewedPostprin

Disturbance in uniformly 13C-labelled DHA metabolism in elderly human subjects carrying the apoE ε4 allele

Carrying the apoE ε4 allele (E4+) is the most important genetic risk for Alzheimer's disease. Unlike non-carriers (E4 − ), E4+ seem not to be protected against Alzheimer's disease when consuming fish. We hypothesised that this may be linked to a disturbance in n-3 DHA metabolism in E4+. The aim of the present study was to evaluate [13C]DHA metabolism over 28 d in E4+v. E4 − . A total of forty participants (twenty-six women and fourteen men) received a single oral dose of 40 mg [13C]DHA, and its metabolism was monitored in blood and breath over 28 d. Of the participants, six were E4+ and thirty-four were E4 − . In E4+, mean plasma [13C]DHA was 31 % lower than that in E4 − , and cumulative β-oxidation of [13C]DHA was higher than that in E4 − 1–28 d post-dose (P≤ 0·05). A genotype × time interaction was detected for cumulative β-oxidation of [13C]DHA (P≤ 0·01). The whole-body half-life of [13C]DHA was 77 % lower in E4+ compared with E4 − (P≤ 0·01). In E4+ and E4 − , the percentage dose of [13C]DHA recovered/h as 13CO2 correlated with [13C]DHA concentration in plasma, but the slope of linear regression was 117 % steeper in E4+ compared with E4 − (P≤ 0·05). These results indicate that DHA metabolism is disturbed in E4+, and may help explain why there is no association between DHA levels in plasma and cognition in E4+. However, whether E4+ disturbs the metabolism of 13C-labelled fatty acids other than DHA cannot be deduced from the present study

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787–0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576–0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556–0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620–1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818–0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383–1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449–0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475–1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD

Retroconversion is a minor contributor to increases in eicosapentaenoic acid following docosahexaenoic acid feeding as determined by compound specific isotope analysis in rat liver

Abstract Dietary docosahexaenoic acid (DHA, 22:6n-3) not only increases blood and tissue levels of DHA, but also eicosapentaenoic acid (EPA, 20:5n-3). It is generally believed that this increase is due to DHA retroconversion to EPA, however, a slower conversion of α-linolenic acid (ALA, 18:3n-3) derived EPA to downstream metabolic products (i.e. slower turnover of EPA) is equally plausible. In this study, 21-day old Long Evans rats were weaned onto an ALA only or DHA + ALA diet for 12 weeks. Afterwards, livers were collected and the natural abundance 13C-enrichment was determined by compound specific isotope analysis (CSIA) of liver EPA by isotope ratio mass-spectrometry and compared to dietary ALA and DHA 13C-enrichment. Isotopic signatures (per mil, ‰) for liver EPA were not different (p > 0.05) between the ALA only diet (−25.89 ± 0.39 ‰, mean ± SEM) and the DHA + ALA diet (−26.26 ± 0.40 ‰), suggesting the relative contribution from dietary ALA and DHA to liver EPA did not change. However, with DHA feeding estimates of absolute EPA contribution from ALA increased 4.4-fold (147 ± 22 to 788 ± 153 nmol/g) compared to 3.2-fold from DHA (91 ± 14 to 382 ± 13 nmol/g), respectively. In conclusion, CSIA of liver EPA in rats following 12-weeks of dietary DHA suggests that retroconversion of DHA to EPA is a relatively small contributor to increases in EPA, and that this increase in EPA is largely coming from elongation/desaturation of ALA