I was thinking about melatonin and astaxanthin together. Is there a potential synergy or is this overkill? There is the obvious evidence with astaxanthin and the ITP and melatonin has it’s advantages as well. Anyone taking both of these together? In full disclosure l am taking around 120 mg of astaxanthin in the morning and currently around 60 mg melatonin at night.
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Ean, I take 8x12mg=96mg of astaxanthin a day. I settled on the brand Bulk Supplements. What brand do you take?
When I first started about a year ago, I tried several different brands that were obviously bogus. I thought they were bogus due to the color and viscosity of the liquid in the caps and the color of my feces. Now, my hands and feet have a nice pinkish flamingo hue. (and my poop is dark purple)
The astaxanthin is suspended in maybe 100mg of sunflower oil. I also take fish oil, so I need to space it throughout the day due to potential GI overload. With meals, I add psyllium husk for bulk, and that eliminates the GI issues.
In an earlier thread, RapaAdmin had calculated the mouse/human equivalent as around 3.5 grams per day. If I put my mind to it, I could take 200mg of the pills, but I would have to rearrange and properly schedule my food intake around my astaxanthin pill routine. Plus, that’s a lot of sunflower oil to consume. In the current available formulations, I can’t see getting to a 3.5gr dose. Impurities make salmon and flamingo food additives a no-go. If one of the bulk supplement companies comes out with kilo bags, I’d experiment with much higher doses.
Oh, the most important point: it was fantastic on helping my hip joint pain, a game-changer. It was one of the very few supplements from which I felt an almost immediate striking effect. I quit ibuprofen, 1800mg/day, which was starting to give me an ulcer.
Astaxanthin is one of the few things I will mention/recommend to my reqular acquaintances. I have mentioned the anti-inflammatory effects that I experienced to various nurses/doctors I run into, but of course, they are just mildly annoyed at my “hallucinations/delusions”. Oh well, I felt it was my moral duty to report this important anecdotal experience to the “authorities”, so I did, to no avail.
As for melatonin, I take 6-10mg at night when I use the bathroom to put me back to sleep. I’ve read some good things about it, but 10mg takes care of my immediate sleeping needs.
Best Wishes, TC
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I take bulk supplements astaxanthin as well(at least for the moment). I am impressed that you have benefited so much from taking it. I have not perceived any benefits but l will still continue. I think l may adopt your 8 pill strategy. I should have read the ingredients better l didn’t realize it was dissolved in sunflower oil. I will probably switch to NOW after my supply runs out. Thanks for the info
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From what little I know sunflower is not a terrible oil, and I just guestimated the amount, still it adds up. I know the annual productions levels of asta must be at industrial scale because most farmed salmon are fed asta. With thousands of tons of raw bulk asta floating about the free market you’d think I could score a couple keys of high quality powder, but I haven’t found any (yet)
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If you come across a reliable bulk supplier, please let know.
In brief → When your bloodstream, tissues, and lipoproteins are already saturated with carotenoids/vitamin A, extra astaxanthin or lutein is still absorbed and useful, but the incremental longevity‑or antioxidant payoff falls off sharply because (i) intestinal uptake and conversion are feedback‑limited, (ii) xanthophyll‑binding sites in retina, brain, and membranes plateau, and (iii) any further free‑radical scavenging is governed by “first radicals, then antioxidants.” Below are the main biological choke‑points and what the human data show.
1. Built‑in feedback: high vitamin A/carotenoids dial down uptake
- Negative‑feedback loop via ISX. When retinol/retinoic‑acid signalling is ample, the intestine‑specific homeobox (ISX) transcription factor represses the scavenger receptor SR‑BI and BCO1 (β‑carotene oxygenase‑1). Result: less chylomicron loading of all carotenoids and almost no conversion of the provitamin ones to retinol.(Cambridge University Press & Assessment)
- Transporter crowding. Even without ISX, carotenoids share the same micelles, SR‑BI/CD36 entry ports, and chylomicron surface area. In vitro, adding β‑carotene cut lutein uptake by ≈20 %.(PMC) Similar competition is seen for lycopene, α‑carotene, and astaxanthin in Caco‑2 and mouse models.
- Plateau kinetics. Plasma lutein typically plateaus once it rises to ≈0.6–0.8 µmol/L; above that, doubling the dose barely nudges the curve because intestinal efflux and hepatic clearance accelerate.
2. Tissue “parking spots” fill up
| Tissue target | Main binding proteins (capacity) | What happens when they’re full |
|---|---|---|
| Macula | StARD3 + GSTP1 bind ≈1 µg lutein/zeaxanthin per gram retina | Macular‑pigment optical density (MPOD) plateaus ~0.9 D.U.; extra oral lutein raises serum but hardly budges MPOD in high‑baseline eyes. Subjects with low starting MPOD gain ~2–3 × more.(PLOS) |
| Neurons/mitochondria | Membrane phospholipids + carotenoid–cholesterol complexes (esp. for astaxanthin) | Once membranes are saturated, further carotenoids stay in LDL/HDL; antioxidant protection against singlet‑oxygen in situ no longer increases linearly. |
| Adipose & skin | Passive storage; half‑life 30–60 days | Acts as a buffer; large existing pool slows the rise (and fall) of plasma xanthophylls after new doses. |
3. What the intervention trials actually show
(Selected human (or closest animal) data that measured baseline status and response)
| Study | Baseline status | Supplement & duration | Outcome | Who benefitted most |
|---|---|---|---|---|
| LISA‑Austria RCT | Mean MPOD 0.21 D.U. | Lutein 20 mg/d × 24 wk | ↑ MPOD by 27 % overall | Participants in lowest tertile at baseline showed +0.10 D.U.; highest‑tertile rose only +0.02.(PLOS) |
| Dose‑response serum study | Serum lutein 0.18 → 0.80 µmol/L at plateau | 5, 10, 20 mg/d × 140 d | Serum rises were dose‑linear, but MPOD increase explained only 29 % of variance; “high carriers” showed diminishing return beyond 10 mg.(PubMed) | |
| Healthy smokers vs. non‑smokers | Smokers: high oxidative stress, low baseline carotenoids | Astaxanthin 5–40 mg/d × 3 wk | −25 % F₂‑isoprostane, +~14 % SOD in smokers; no change in non‑smokers with already good antioxidant status | Smokers (low baseline)(PubMed) |
| Firefighters (RCT, 2024) | Baseline TAC normal | Astaxanthin 12 mg/d × 4 wk | Small ↓ CRP and MDA (NS after covariate adjustment) | Biggest drops seen in those with highest starting MDA; others unchanged.(Taylor & Francis Online) |
| Arterial‑stiffness RCT, 2023 | Middle‑aged adults, normal oxidative markers | Astaxanthin 8 mg/d, 12 mo | No effect on oxidative stress or PWV | Baseline‐adequate group showed null result.(ScienceDirect) |
Pattern: the farther you are from sufficiency—low MPOD, low serum xanthophylls, high oxidative load—the larger the delta from supplementation. Once the “redox reserve” is healthy, extra milligrams move the needle little or not at all.
4. Does that mean “don’t bother” if you’re already carotenoid‑replete?
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Not exactly. Astaxanthin and lutein have specialised roles (mitochondrial membrane stability; blue‑light filtering; up‑regulating NRF2). Those niche benefits may persist even when broad‑spectrum antioxidant capacity is topped up.
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But expect a logarithmic benefit curve. Going from “low” to “normal” gives the biggest longevity/antioxidant bang; going from “normal” to “very high” gives a sliver.
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Possible downsides of mega‑dosing:
- Displacement of other fat‑soluble nutrients in chylomicrons.
- Carotenodermia or, with pre‑formed vitamin A, outright hypervitaminosis A (hepatic, osteologic).
- Blunting of exercise‑induced hormesis if antioxidant load is too high.
5. Practical take‑aways for tweaking your stack
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Measure, don’t guess. Serum lutein/zeaxanthin, plasma astaxanthin (if available), retinol, and MPOD optical scan tell you where you sit on the curve.
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Aim for “sweet‑spot” ranges.
- Serum lutein ≈ 0.4–0.6 µmol/L
- Serum astaxanthin ≈ 0.05–0.12 µmol/L (typical after 6–12 mg/d)
- MPOD ≥ 0.5 D.U.
Going far above confers little extra benefit and may just fatten lipoproteins.
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If you’re already high, cycle or micro‑dose. Two 6‑mg lutein softgels per week often keep MPOD steady; likewise 4–6 mg astaxanthin every other day maintains plasma levels once tissue pools are loaded.
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Leverage co‑factors, not more milligrams. Carotenoid uptake doubles with 5–10 g mixed dietary fats; add mixed tocopherols or vitamin C to spare carotenoids instead of piling on more.
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Watch vitamin A pre‑formed intake. If retinol (or high‑dose cod‑liver oil) is already >3 000 µg RAE/d, expect tighter ISX repression; provitamin carotenoid conversion (β‑carotene → retinol) may fall by >50 %.(EFSA Journal)
Bottom line
Both astaxanthin and lutein still work when you’re carotenoid‑rich, but their marginal returns flatten once transporters, binding proteins, and membrane seats are occupied and overall oxidant pressure is low. If your labs and MPOD are already at the upper end of physiological norms, dialing back to a maintenance dose—or focusing on other, non‑redundant longevity levers—will likely give you more risk‑adjusted benefit than chasing ever‑higher carotenoid numbers.
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That’s what Brian Kennedy means when he cautions that we don’t know the effects of popping dozens of drugs/supplements as they don’t even have to be necessarily additive. Any supplement likely has a saturation point in the body, and the various interactions are going to be complicated and perhaps counterintuitive.
I can well imagine that if you are getting saturation effects in carotenoids, you might be getting them in other phytonutrients. Perhaps the same obtains for the various polyphenols that folks like Dr. Greger like to champion in the high consumption of fruits and vegetables. Maybe the benefits top out - or even reverse - with x cups of bluberries on top of y cups of strawberries etc.
I supplement with lutein, zeaxanthin, meso-zeaxanthin, astaxanthin. I frequently thought about how they interact and saturate various tissues - I’ve posted studies regarding that in other threads. If we believe these are consequential doses, then the effects could be anywhere along the spectrum. More is not always better. YMMV.
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Thanks for the deep analysis! Directly consuming Retinol seems like the safest option if you high dose Astaxanthin. Maybe low dose liver?
Besides, normal carotenes are much more pro-oxidatory than the stable astaxanthin once they are in the cell wall.
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