Compound-specific isotope analysis reveals no retroconversion of DHA to EPA but substantial conversion of EPA to DHA following supplementation: a randomized control trial

Metherel, Adam H.; Irfan, Maha; Klingel, Shannon L.; Mutch, David M.; Bazinet, Richard P.

doi:10.1093/ajcn/nqz097

Cited by 65 publications

(82 citation statements)

References 53 publications

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“…Both DHA (22:6ω3) and EPA (20:5ω3) contributed to this increase in total ω-3 PUFA. The increase in EPA observed with DHA supplementation is consistent with published studies performed in vitro and in vivo [47,48].…”

Section: Dha Intake Increases ω-3 Pufa Content In Red Blood Cells Andsupporting

confidence: 91%

Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice

et al. 2020

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Lupus is a debilitating multi-organ autoimmune disease clinically typified by periods of flare and remission. Exposing lupus-prone female NZBWF1 mice to crystalline silica (cSiO 2), a known human autoimmune trigger, mimics flaring by inducing interferon-related gene (IRG) expression, inflammation, ectopic lymphoid structure (ELS) development, and autoantibody production in the lung that collectively accelerate glomerulonephritis. cSiO 2-triggered flaring in this model can be prevented by supplementing mouse diet with the ω-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). A limitation of previous studies was the use of purified diet that, although optimized for rodent health, does not reflect the high American intake of saturated fatty acid (SFA), ω-6 PUFAs, and total fat. To address this, we employed here a modified Total Western Diet (mTWD) emulating the 50 th percentile U.S. macronutrient distribution to discern how DHA supplementation and/or SFA and ω-6 reduction influences cSiO 2-triggered lupus flaring in female NZBWF1 mice. Six-week-old mice were fed isocaloric experimental diets for 2 wks, intranasally instilled with cSiO 2 or saline vehicle weekly for 4 wks, and tissues assessed for lupus endpoints 11 wks following cSiO 2 instillation. In mice fed basal mTWD, cSiO 2 induced robust IRG expression, proinflammatory cytokine and chemokine elevation, leukocyte infiltration, ELS neogenesis, and autoantibody production in the lung, as well as early kidney nephritis onset compared to vehicle-treated mice fed mTWD. Consumption of mTWD containing DHA at the caloric equivalent to a human dose of 5 g/day dramatically suppressed induction of all lupus-associated endpoints. While decreasing SFA and ω-6 in mTWD modestly inhibited some disease markers, DHA addition to this diet was required for maximal protection against lupus development. Taken together, DHA supplementation at a translationally relevant dose was highly effective in

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Section: Dha Intake Increases ω-3 Pufa Content In Red Blood Cells Andsupporting

confidence: 91%

Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice

et al. 2020

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“…However, evidence from both rats and human indicates that the increase in EPA is more likely because of a slower turnover of EPA in the plasma and liver, rather than the retro-conversion pathway of DHA to EPA [33,34]. Nevertheless, DHA feeding may slow the conversion of EPA to downstream metabolic products in the liver, with a concomitant decrease of DPA levels seen after DHA supplementation [33][34][35]. Taken together, the current data may suggest that the antidepressant-like effects of EPA better than DHA were possibly not through DHA, but rather due to EPA own function, either directly or via its metabolite DPA.…”

Section: Discussionmentioning

confidence: 99%

EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression

Peng

Cai

Yan

et al. 2020

IJMS

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Clinical evidence indicated that eicosapentaenoic acid (EPA) was more effective than docosahexaenoic acid (DHA) in depression treatment. However, possible mechanisms remain unclear. Here, a chronic unpredictable mild stress (CUMS)-induced model of depression was used to compare EPA and DHA anti-depressant effects. After EPA or DHA feeding, depression-like behavior, brain n-3/n-6 PUFAs profile, serum corticosterone and cholesterol concentration, hippocampal neurotransmitters, microglial and astrocyte related function, as well as neuronal apoptosis and survival signaling pathways were studied. EPA was more effective than DHA to ameliorate CUMS-induced body weight loss, and depression-like behaviors, such as increasing sucrose preference, shortening immobility time and increasing locomotor activity. CUMS-induced corticosterone elevation was reversed by bother fatty acids, while increased cholesterol was only reduced by EPA supplement. Lower hippocampal noradrenaline and 5-hydroxytryptamine concentrations in CUMS rats were also reversed by both EPA and DHA supplement. However, even though CUMS-induced microglial activation and associated increased IL-1β were inhibited by both EPA and DHA supplement, increased IL-6 and TNF-α levels were only reduced by EPA. Compared to DHA, EPA could improve CUMS-induced suppressive astrocyte biomarkers and associated BDNF-TrkB signaling. Moreover, EPA was more effective than DHA to attenuate CUMS-induced higher hippocampal NGF, GDNF, NF-κB, p38, p75, and bax expressions, but reversed bcl-2 reduction. This study for the first time revealed the mechanisms by which EPA was more powerful than DHA in anti-inflammation, normalizing astrocyte and neurotrophin function and regulating NF-κB, p38 and apoptosis signaling. These findings reveal the different mechanisms of EPA and DHA in clinical depression treatment.

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“…Retro‐conversion of DHA is more common in non‐neural cells than neural cells (Park et al, 2016). However, recently it was shown that increased plasma level of EPA in human following DHA supplementation did not occur via retro‐conversion rather a result of slowed metabolism and/or accumulation of plasma EPA (Metherel et al, 2019). During the last 30 years or so, the increasing incidence of several metabolic diseases are thought to be due to the results of high dietary intake of n‐6 fatty acid containing foods and oils compared with n‐3 fatty acids, thus increased the ratio of n‐6:n‐3 fatty acids (20:1) intake to a much higher level than the recommended ratio for optimal health benefits (Simopoulos, 2016).…”

Section: Dietary and Metabolic Sources Of Dha And Its Worldwide Consumentioning

confidence: 99%

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

Mallick

Basak

Duttaroy

2019

Intl J of Devlp Neuroscience

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Docosahexaenoic acid,22:6n-3 (DHA) and its metabolites are vital for the structure and functional brain development of the fetus and infants, and also for maintenance of healthy brain function of adults. DHA is thought to be an essential nutrient required throughout the life cycle for the maintenance of overall brain health. The mode of actions of DHA and its derivatives at both cellular and molecular levels in the brain are emerging. DHA is the major prevalent fatty acid in the brain membrane. The brain maintains its fatty acid levels mainly via the uptake of plasma free fatty acids. Therefore, circulating plasma DHA is significantly related to cognitive abilities during ageing and is inversely associated with cognitive decline. The signaling pathways of DHA and its metabolites are involved in neurogenesis, antinociceptive effects, anti-apoptotic effect, synaptic plasticity, Ca 2+ homeostasis in brain diseases, and the functioning of nigrostriatal activities. Mechanisms of action of DHA metabolites on various processes in the brain are not yet well known. Epidemiological studies support a link between low habitual intake of DHA and a higher risk of brain disorders. A diet characterized by higher intakes of foods containing high in n-3 fatty acids, and/or lower intake of n-6 fatty acids was strongly associated with a lower Alzheimer's Disease and other brain disorders. Supplementation of DHA improves some behaviors associated with attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior, as well as cognition. Nevertheless, the outcomes of trials with DHA supplementation have been controversial. Many intervention studies with DHA have shown an apparent benefit in brain function. However, clinical trials are needed for definitive conclusions. Dietary deficiency of n-3 fatty acids during fetal development in utero and the postnatal state has detrimental effects on cognitive abilities. Further research in humans is required to assess a variety of clinical outcomes, including quality of life and mental status, by supplementation of DHA.

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Compound-specific isotope analysis reveals no retroconversion of DHA to EPA but substantial conversion of EPA to DHA following supplementation: a randomized control trial

Cited by 65 publications

References 53 publications

Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice

Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice

EPA is More Effective than DHA to Improve Depression-Like Behavior, Glia Cell Dysfunction and Hippcampal Apoptosis Signaling in a Chronic Stress-Induced Rat Model of Depression

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

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