DHA Cycling Halves the DHA Supplementation Needed to Maintain Blood and Tissue Concentrations via Higher Synthesis from ALA in Long–Evans Rats

Abstract

Background Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) recommendations are frequently stated at 500 mg/d; however, adherence to these recommendations would result in a large global commercial EPA/DHA production deficit. Previously, our laboratory demonstrated that acute DHA intake in rats can increase the capacity for synthesis-secretion of n–3 (ω-3) polyunsaturated fatty acids (PUFAs). Objective We aimed to investigate the utility of a dietary DHA cycling strategy that employs 2 wk of repeated DHA feeding for a total of 3 cycles over 12 wk. Methods Male Long–Evans rats were fed a 10% fat diet by weight comprised of either 1) a 2-wk, 2% α-linolenic acid (ALA, DHA-ALA group 18:3n–3) diet followed by a 2-wk, 2% DHA + 2% ALA diet over 3 consecutive 4-wk periods (“DHA cycling,” DHA-ALA group); 2) a 2% DHA + 2% ALA diet (DHA group) for 12 wk; or 3) a 2% ALA-only diet (ALA group) for 12 wk. At 15 wk old, blood and tissue fatty acid concentrations and liver mRNA expression and 13C-DHA natural abundances were determined. Results DHA concentrations in plasma, erythrocytes, and whole blood between the DHA-ALA group and the DHA groups were not different (P ≥ 0.05), but were 72–110% higher (P < 0.05) than in the ALA group. Similarly, DHA concentrations in liver, heart, adipose, and brain were not different (P ≥ 0.05) between the DHA-fed groups, but were at least 62%, 72%, 320%, and 68% higher (P < 0.05) than in the ALA group in liver, heart, adipose, and skeletal muscle, respectively. Compound-specific isotope analysis indicated that 310% more liver DHA in the DHA-ALA group compared with the DHA group is derived from dietary ALA, and this was accompanied by a 123% and 93% higher expression of elongation of very long-chain (Elovl)2 and Elovl5, respectively, in the DHA-ALA group compared with the ALA group. Conclusions DHA cycling requires half the dietary DHA while achieving equal blood and tissue DHA concentrations in rats. Implementation of such dietary strategies in humans could reduce the gap between global dietary n–3 PUFA recommendations and commercial production.

Higher Increase in Plasma DHA in Females Compared to Males Following EPA Supplementation May Be Influenced by a Polymorphism in ELOVL2: An Exploratory Study

“…The plasma δ 13 C of FAME was determined by GC‐IRMS, as previously described by our laboratory (Giuliano et al, 2018; Lacombe et al, 2017, 2018; Metherel et al, 2017, 2019a, b). Briefly, the δ 13 C of plasma fatty acids collected by IRMS was normalized and converted to the international reference scale (Vienna Peedee Belemnite) by multipoint linear normalization and reported in mUr.…”

Overview of how N32 and N34 elovanoids sustain sight by protecting retinal pigment epithelial cells and photoreceptors

“…However, it is now recognized that both senescence programming and inflammaging occur at all stages of life span, including early development, cell differentiation, and in many pathological DHA esterified into phospholipids is most abundant in photoreceptors and synaptic membranes DHA (22:6, omega-3 or n-3) is an essential fatty acid family member highly concentrated in and required for the biogenesis of synaptic membranes and other membranes of the CNS, including PRC membranes (5). Dietary DHA is supplied or synthesized from dietary linolenic acid in the liver (18:3,n-3) (6). DHA supplied by the liver (7) is taken up from the neurovascular unit (bloodbrain barrier or blood-inner retina barrier) or from the choriocapillaris (beneath the retina) by the RPE.…”

Membrane‐type frizzled‐related protein regulates lipidome and transcription for photoreceptor function

“…Polymorphisms of this receptor have been found in age‐related macular degeneration (AMD) as well as in other forms of retinal degenerations. 22:6 is an omega‐3 (n‐3) essential fatty acid highly enriched in and required for the biogenesis of PRC membranes and is supplied either directly by diet or synthesized from dietary linolenic acid in the liver (18:3,n‐3) . 22:6 supplied by the liver is taken up from the choriocapillaris by the RPE and then delivered to the PRC inner segments .…”

“…13,14 Polymorphisms of this receptor have been found in age-related macular degeneration (AMD) 15 as well as in other forms of retinal degenerations. 17 22:6 supplied by the liver 18 is taken up from the choriocapillaris by the RPE and then delivered to the PRC inner segments. 17 22:6 supplied by the liver 18 is taken up from the choriocapillaris by the RPE and then delivered to the PRC inner segments.…”

“…22:6 is an omega-3 (n-3) essential fatty acid highly enriched in and required for the biogenesis of PRC membranes 16 and is supplied either directly by diet or synthesized from dietary linolenic acid in the liver (18:3,n-3). 17 22:6 supplied by the liver 18 is taken up from the choriocapillaris by the RPE and then delivered to the PRC inner segments. 16,19 Here, it is incorporated at the sn-2 position of the glycerol backbone, especially in phosphatidylcholine (PC), which comprises more than 50% of PRC phospholipids 20 mainly used for the biogenesis of PRC outer segments.…”