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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Breaking news:
I thought you’d be interested to know that Matt K said as a result of someone who watches his podcast, he is starting to think you should take more EPA than DHA
Minute 48
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There are a lot of people who suggest higher EPA Omega 3s. I heard it first from Dr. Stanfield years ago.
Now if Kaeberlein said he was stopping Omega 3s due to DHA being linked to depression, then that would probably be @adssx
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O3:
Below you’ll find three parts:
-
Tidy (lightly‑edited) transcript – all the original ideas are retained, but I’ve pulled out filler words, removed timestamps, normalised punctuation, added clear speaker labels, and split very long turns for readability.
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Executive summary – a concise, thematic overview of the conversation.
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Critique – strengths, gaps and cautions, plus a few evidence links should you want to dig deeper.
1. Tidy transcript
(≈19 min read – open/close to expand)
Click to show / hide
Matt (host):
Welcome to the OptiSpan podcast. I’m with Dr Nicole Burn (“Nikki”) and Dr Kevin White. Both started in acute‑care medicine and migrated to what we call Health‑span Medicine. Today we’ll dig into the diagnostics we use at OptiSpan—especially blood work—and how to turn results into actionable strategy.
ORIGINS & DEFINITIONS
Kevin:
I trained in emergency and trauma. After a while I realised most visits were late‑stage chronic disease. I watched peers my own age show up with heart attacks and thought, I don’t want that future. That pivoted me toward prevention.
Nikki:
My father was a dermatologist who actually prescribed exercise and diet. Later, as a hospitalist, I admitted an 80‑year‑old ultra‑fit woman whose “longevity doctor” tried to make every lab “match a 25‑year‑old.” That’s when I thought, pregnancy biology isn’t longevity biology; we can do this better.
Matt:
Quick refresher: lifespan is how long you live; health‑span is the portion you stay healthy and independent. Most people actually care about health‑span.
THE FOUR PILLARS
We organise care around Eat, Move, Sleep, Connect.
EAT
Nikki:
Whole, minimally processed foods first. We target 0.7–1 g protein per lb of ideal bodyweight, plus 25‑35 g of fibre. A high‑protein, low‑carb first meal steadies glucose.
Kevin:
Lean muscle is the “currency of ageing.” CGMs teach people fast—my first big spike was from a “healthy” potato‑corn soup.
Matt:
Spikes aren’t always bad, but repeated large swings matter. We use CGMs for four weeks: two weeks of normal eating, two weeks of N=1 experiments.
MOVE
Kevin:
“The best exercise is the one you’ll do.” Consistency over perfection. Resistance training preserves lean mass; zone‑2 cardio and VO₂‑max training predict resilience. Weighted‑vest walking (“rucking”) and balance drills are underrated.
Nikki:
150 min/week of zone‑2 is our baseline prescription; we add bone‑loading and balance, especially for post‑menopausal women.
SLEEP
Kevin:
Poor sleep drives inflammation and dementia risk. My non‑negotiables: morning light, evening screen‑curfew, an Eight‑Sleep cooling mattress. 4‑7‑8 breathing knocks me out when I wake at 3 a.m.
Nikki:
My Oura ring showed me it took 45 minutes to fall asleep after late‑night laptop work, but only 10 minutes if I swapped for reading. Alcohol predictably trashes Oura scores.
CONNECT
Nikki:
Blue‑zone data are clear: sustained social integration and a sense of value lengthen life. We ask about pets, volunteering, purpose.
Kevin:
New relationships drive neuro‑plasticity. We coach reframing stress rather than “eliminating” it.
KEY BLOOD & IMAGING MARKERS
(Selected highlights; full panel discussed in depth)
| Domain | Marker | OptiSpan “good” cut‑offs |
|---|---|---|
| Lipids | Apo‑B, LP (a) | Apo‑B < 80 mg/dL; LP (a) < 30 mg/dL |
| Metabolic | Fasting insulin < 8 µIU/mL, C‑peptide < 2.5 ng/mL, A1c ≈5 % | Early insulin resistance often shows before A1c rises |
| Inflammation | hs‑CRP < 1 mg/L, IL‑6 low, ferritin 30‑150 ng/mL (context) | ESR less useful for low‑grade inflammation |
| Nutrients | 25‑OH vitamin D 50‑80 ng/mL, Omega‑3 index ≥ 6 % | Most Seattle clients need supplementation |
| Organ‑specific | ALT ≈20 U/L, Cystatin‑C for GFR if muscular | Point‑of‑care ultrasound confirms fatty‑liver suspicions |
They also order Galleri multi‑cancer screening, Dexa, CCTA + Cleerly, and selective genetics/polygenic‑risk scores.
HORMONES
Men (Kevin):
Look at total/ free testosterone, SHBG and estradiol; fix root causes (sleep, alcohol, obesity) before scripts.
Women (Nikki):
Perimenopause labs swing wildly; dose HRT to symptoms and bone‑protective estradiol ≈60 pg/mL. Modern trans‑dermal oestrogen plus oral/vaginal progesterone beats the dated WHI fear narrative. Early HRT lowers fracture, CVD and cognitive‑decline risk.
COMMUNITY REFLECTIONS
- Annoyance: “Magic‑bullet” seekers and fringe hype give the field a bad name.
- Excitement: Rapid data flow, AI‑driven personalisation, and the intellectual puzzle of integrating biomarkers with lifestyle.
## 2. Executive summary (≈350 words)
Podcast premise – Former ER & hospital physicians Dr Kevin White and Dr Nicole Burn join host Matt to describe how OptiSpan’s “health‑span medicine” uses advanced diagnostics and coaching to delay chronic disease.
1. Why they left acute care
Both were tired of patching up late‑stage illness and wanted to prevent it. A stroke in a hyper‑supplemented 80‑year‑old and endless repeat ER visits were tipping points.
2. Four‑pillar framework
Eat – whole foods, high protein (0.7–1 g/lb), ≥25 g fibre; CGMs for real‑time education.
Move – resistance training for “muscle currency,” 150 min zone‑2 cardio, VO₂‑max tests (treadmill or resting device), plus balance & weighted‑vest walking.
Sleep – strict evening routine, temperature control, breathing drills; alcohol and blue light clearly harm metrics.
Connect – social integration and stress relationship re‑framing; new friendships foster neuro‑plasticity.
3. Diagnostics hierarchy
- Metabolic axis: fasting insulin, C‑peptide, A1c, CGM.
- CVD axis: Apo‑B, LP (a), NMR lipoprotein size, CCTA + Cleerly plaque imaging.
- Inflammation: hs‑CRP, IL‑6, ferritin (dual role).
- Organ health: ALT for fatty liver, cystatin‑C for kidney in muscular clients.
- Nutrients & toxins: vitamin D, omega‑3 index, lead & mercury.
- Cancer‑screening: Galleri liquid biopsy, whole‑body MRI case‑by‑case.
- Genetics: limited polygenic‑risk scores; APOE‑ε4 always checked.
4. Hormone management
- Men: optimise lifestyle first, then judicious TRT.
- Women: early, individualised HRT (trans‑dermal oestrogen + progesterone) for bone, brain and CV protection; doses titrated to estradiol ≈ 60 pg/mL.
5. Community commentary
Biggest frustration is public demand for single‑pill solutions and sensationalist fringe claims; biggest excitement is accelerating science plus AI‑enabled personalisation.
Bottom line – OptiSpan blends rigorous biomarker tracking with lifestyle coaching; no silver bullets, but compound gains across eat‑move‑sleep‑connect pillars, hormone optimisation and early detection can meaningfully bend the health‑span curve.
## 3. Critique
| Aspect | Strengths | Caveats / Opportunities |
|---|---|---|
| Framework | The four‑pillar model is memorably simple; emphasises behaviour before prescriptions. | Connect pillar is conceptually broad; could benefit from clearer, measurable targets (e.g. validated social‑isolation scores). |
| Diagnostics | Fasting insulin, Apo‑B, LP (a) and Cleerly imaging place them at the evidence‑based forefront of CVD prevention. | Heavy panel risks information overload and cost. No discussion of cost‑effectiveness or insurance realities. |
| CGM use | Pragmatic four‑week protocol (baseline + experiments) balances learning with device fatigue. | Glucose “spikes” framed as inherently ageing; physiological spikes after mixed meals are normal. The nuance was mentioned but could have been emphasised more. |
| Hormone views | Nuanced take on female HRT: timing, route and target estradiol rooted in modern data; recognition that WHI fear still lingers. | Male TRT section was thin; skipped discussion of erythrocytosis monitoring, fertility impact, or long‑term cardiovascular uncertainty. |
| Evidence literacy | They acknowledge WHI limitations, cite PCSK9 data on LP (a), and call out false‑positive rates for Galleri. | Several claims lacked direct citation (e.g. concrete thresholds for ALT ≈ 20 U/L or vitamin D 60 ng/mL). Including references would strengthen credibility. |
| Patient communication | Emphasis on personalised N‑of‑1 testing, shared visuals (ultrasound, CGM graphs) and motivational framing is patient‑centred. | Could further address socio‑economic barriers to high‑protein diets, CGMs, Dexa, CCTA and Galleri—tools not universally accessible. |
| Longevity‑community stance | Healthy scepticism toward “hack” culture and biological‑age hype; highlights iterative science. | Brief dismissal of epigenetic clocks may overlook research‑grade clocks (GrimAge, DunedinPACE) that are showing predictive validity in cohorts. |
| Overall | A balanced, clinical voice that grounds longevity enthusiasm in internal‑medicine pragmatism. | Needs deeper engagement with cost, access inequities and stronger referencing to avoid sliding into expert‑opinion territory. |
How to use this
- Practitioners: borrow the four‑pillar teaching script and the staged CGM protocol; cross‑check lab cut‑offs with latest guidelines.
- Individuals: start with one pillar (usually sleep!), get a baseline fasting insulin + Apo‑B, and build from there—no magic bullets needed.
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I get irrational fear/anxiety from fish oil supps.
I tried the vegan brand Bryan Johnson is using and also tried NOW fish oil capsules in the past.
Both give me anxiety.
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I’ll probably be run off this site for saying this, but I gotta say… I was extremely depressed by that video. I totally respect MK, don’t get me wrong. But I’ve frequently been utterly flabbergasted by the low quality of some of his guests, random influencers and borderline scammers. And - apologies ahead of time - Dr. Kevin White… what is the point of featuring this barely awake guy, who strikes me as an inert substance in human form… he never says anything with a pulse or point. Why not stick to top guys like Brian Kennedy? And then we have a doctor who is apparently on staff of the Optispan organization. How do I put it diplomatically - it does the opposite of encouraging me to sign up with that joint. They go over some extremely basic nostrums about diet and exercise, so basic 100% of it is a waste of time - everyone and their dog heard this a trillion times. Then we get to the blood tests, and it’s a horror show. Anyone who knows the first thing about any of this would be astounded by the evidence free assertions and recommendations based on nothing more than “feels” (the ‘how low an ApoB’ is good), blissful lack of any awareness of the complexity of EPA/DHA/ALA nexus of controversy and subsequent blithe recommendations and so on down the line, super shallow discussions of insulin and glucose and so on. Horrifying.
I had naively imagined, based on MK’s involvement that Optispan would be a collection of top world authorities and scientists in diet, cholesterol, metabolism, and so on with many specialties. Meanwhile it’s like stepping into a gym expecting to be guided by the world’s top exercise scientists, and being met by the average meathead “personal trainer” full of the usual misconceptions and bro science. SMH.
That show is more mixed up than a dog’s breakfast.
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There is a difficulty in terms of producing videos of needing quantity. Hence there will be limits on quality.
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