Carlon Elite EPA (EPA-only) on iHerb can be shipped to HK: https://hk.iherb.com/pr/carlson-elite-epa-gems-1-000-mg-120-soft-gels/13839
Otherwise, Vascepa is approved in HK: NAVLIN DAILY
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GPR120 internalization: a key mechanism for EPA in antidepressant action
The incidence of depression is on the rise, and currently available antidepressants often exhibit limited efficacy in many patients. Additionally, the underlying mechanisms of depression remain poorly understood. Research has shown that neuroinflammation, driven by M1 microglial phenotypic polarization, contributes to neuronal abnormalities implicated in the development of depression. Eicosapentaenoic acid (EPA) has emerged as a promising therapeutic agent for depression. However, the specific target of EPA’s anti-stress effects is yet to be identified. This study aimed to explore the pathogenesis of depression and elucidate the central regulatory mechanisms underlying EPA’s antidepressant efficacy. In this study, mice were orally administered EPA for five consecutive weeks. During this period, they were subjected to daily chronic unpredictable mild stress (CUMS) and treated with lipopolysaccharide (LPS, 0.5 mg kg−1, intraperitoneally) every other week. The results demonstrated that EPA significantly alleviated neuronal degeneration in the medial prefrontal cortex. Furthermore, EPA improved synaptic plasticity impairments induced by CUMS combined with LPSs, as indicated by the increased protein levels of Nlgn1, PSD95, GAP43, and Syn. EPA also reduced neuroinflammation by inhibiting M1 microglial polarization and NLRP3 inflammasome activation. Notably, EPA exerted antidepressant-like effects by modulating GPR120. These findings suggest that EPA intake can mitigate abnormal mood and behavior induced by elevated immune-inflammatory signals. These findings suggest that EPA intake can attenuate abnormal moods and behaviors induced by elevated immune-inflammatory signals. Therefore, EPA may be a promising strategy for the clinical treatment of inflammatory depression.
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The results of several meta-analyses suggest that eicosapentaenoic acid (EPA) supplementation is therapeutic in managing the symptoms of major depression. It was previously assumed that because EPA is extremely low in the brain it did not cross the blood-brain barrier and any therapeutic effects it exerted would be via the periphery. However, more recent studies have established that EPA does enter the brain, but is rapidly metabolised following entry. While EPA does not accumulate within the brain, it is present in microglia and homeostatic mechanisms may regulate its esterification to phospholipids that serve important roles in cell signaling. Furthermore, a variety of signaling molecules from EPA have been described in the periphery and they have the potential to exert effects within the brain. If EPA is confirmed to be therapeutic in major depression as a result of adequately powered randomized clinical trials, future research on brain EPA metabolism could lead to the discovery of novel targets for treating or preventing major depression.
The potential effect of DHA feeding to slow the conversion of EPA to downstream metabolic products in the liver could explain some of the differences between EPA and DHA on major depression outcomes.
But, more surprisingly, we observed that EPA and DHA entered the brain at similar rates in the in situ model, raising the question that if EPA and DHA entered the brain at a similar rate, why were EPA concentrations 250 – 300 times lower than DHA? We found, that even in situ and in under 45 seconds, EPA appeared to undergo rapid metabolism, including beta-oxidation. By using radiolabelled EPA in an in vivo infusion model developed by Stanley Rapoport, we assessed the kinetics of EPA uptake into the brain (Chen et al., 2013). Consistent with our in situ 8 findings, the incorporation coefficient (a marker of the brains capacity for taking up a fatty acid) was similar for EPA and DHA in vivo. Any differences in their rates of uptake could not explain their massive difference in brain concentrations, a finding that was confirmed by Igarashi and colleagues (Igarashi et al., 2013)
We and others have observed that DHA supplementation increases EPA levels (Conquer and Holub, 1996; Metherel et al., 2017; Metherel et al., 2019; Rey et al., 2019; Schuchardt et al., 2016). While this is commonly referred to as retroconversion, a process by 16 which DHA is enzymatically converted "back” to EPA, we have recently reported that the increase in EPA is predominately due to a decrease in its metabolism relative to its synthesis (Metherel et al., 2017; Metherel et al., 2019). While it is not exactly clear which metabolic pathways are involved in the DHA-induced increases in EPA, DHA does appear to be blocking aspects of EPA metabolism.
Brain eicosapentaenoic acid metabolism as a lead for novel therapeutics in major depression 2019
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Thanks. The case against DHA is becoming stronger everyday…
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I’m compelled to reply because I have been looking for someone else with this experience for years.
I used to take what I now recognize was a low-quality rancid omega-3 supplement, and it did not make me depressed, it made me a jerk. Irritable, snappy, impatient, judgemental, and downright angry, and the effect was fairly immediate. I’m e3/e4 and really wanted to be able to supplement but just could not tolerate how it affected my mood and personality.
Fast forward a few years and I’m now taking a high quality supplement and have none of these effects.
But having spent most of the morning reading on this forum I’m now seriously doubting my high-dose high-DHA strategy. I’m new to this forum although not new to the subject matter. I’m learning a ton, the level of science here is much superior to most of the Internet.
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I can agree with that.
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I’m so glad that you felt compelled to respond. Your description of how you responded to supplementation exactly matches my experience, but you described it even better than I had! It’s oddly comforting and satisfying to compare notes and know someone truly understands!
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What are some of the good epa only supplements? I’m finding that even the ones marketed as “epa” contain a small amount of dha. There’s the Carlson one but the label doesn’t specify the entire composition of the fish oil.
I take Ingennus Pharmepa Restore 1000mg Pure EPA Fish Oil High Absorption rTG Omega-3 IFOS Certified
Readily available on Amazon. I like that it’s IFOS certified, as I’m worried about contaminants. However I only take 500mg dose three times a week. My OmegaCheck reading in April was 5.5 % by wt., according to their range, right at the limit of Relative Risk: LOW. Some people advocate 8 as a minimum, but I’m comfortable at 5.5. YMMV.
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I’m reconsidering this, but I take daily:
1400 mg TG-ALA
1688 mg TG-EPA
210 mg LPC-EPA
1313 mg TG-DHA
105 mg LPC-DHA
Which is two capsules Nature Made Flaxseed Oil Extra Strength, three capsules Nordic Naturals Ultimate Omega 2x, and two capsules Fenix Accentrate Omega Max.
My Omega3 Index is 12.8%
Now I’m wondering if I’m getting too much DHA and disturbing the downstream metabolism and neuronal incorporation. My interest is in AD prevention, I have my lipids dialed in with ezetimibe and low-intensity statin.
Unsure why. Have you ever tried plasmologen omega 3?
The best is to take pharma-grade Vazkepa (also branded as Vascepa in some countries). EPA-only, validated in large clinical trials, proven to improve cardiovascular health. However, it may be expensive or unavailable where you live.
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I take this
https://www.amazon.co.uk/dp/B01LF2WAJA
Healthspan Elite Omega 3 Pure EPA 1g
I don’t know how it compares, but it is just EPA.
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