It has been increasingly clear to me, that though both are important, anti-inflammatories are probably more important as we age. That is another reason I don’t discount the use of metformin for those who don’t have type II diabetes.
“We conclude that the anti-inflammatory properties of metformin are exerted irrespective of diabetes mellitus status. This may accelerate the investigation of drug utility in nondiabetic cardiovascular disease groups.”
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Possible methods of action for Astaxanthin in terms of the lifespan improvement effects:
Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector.
and
I did read that in a human study of Astaxanthin, 40 mg daily achieved a better result than 10 mg. However I don’t know how scalable that is. That may be a good set point for most?
Its interesting… the results we’ve seen so far are somewhat similar to what we see with rapamycin; the greater the dose (so far, in all animals tested) the greater the benefit in terms of healthspan and lifespan. In the NIA ITP program they were testing 4,000ppm, and I’ve seen studies in mice as high as 15,000ppm in their feed with no problems. I’m sure at some point the researcher will reach a point of diminishing returns, but they have not found that point yet with regard to astaxanthin.
So far, other than turning the color of a flamingo, there seem to be no deleterious side effects. There is no known LD50 for this compound (Lethal dose statistic).
Given the universal safety profile across organisms (up to 750mg/kg dosing in rats during cycle of pregnancy with no ill effects for mother or babies), as well as no reported side effects in humans, seem to suggest a very strong human safety profile.
I’m wondering if a pulsed, or cycling, dosing strategy might be best with regard to minimizing the most significant downside of this molecule, which is making your skin go pink/orange if continuous dosing at a high level.
Given that astaxanthin is included as feed for farm-raised salmon (for the color), I have to believe the bulk cost of it is very low. I’m researching this now.
My personal approach is to increase dosing until I get obvious skin discoloration, then test different cycling on/off protocols to see what might work to minimize this issue.
And do regular blood work to track if there is any change in any key metrics.
Can anyone find any research data that would suggest this strategy with astaxanthin is risky?
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Ah. I see. But how will your co-workers react to a pink version of you? Although you could blame it on a sunburn.
Right now, I see the biggest side-effect of high dosage Astaxanthin is the shrinkage of the bank account. I think that for this to be a viable high dosage supplement, we will need to find a way to bulk buy it. Maybe from a salmon feed store! Please keep us informed. I would probably be willing to try a large bulk purchase as well and ramp up my dosage as well.
However, with my luck, I’ll only get up to 20 mg a day after I buy 100 lbs of the stuff…
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If Astaxanthin’s key to success is by activating the FOX03 gene in humans, that’s a homerun right there! Humans with an activated FOXO3 gene were routinely found amongst centenarian cohorts…
A genetic variation within FOXO3 was first reported to be associated with human longevity in a study of an American cohort of Japanese ancestry with a mean age of 97.9 years [35].
FOXO3 on the Road to Longevity: Lessons From SNPs and Chromatin Hubs - PMC.
German researchers at the Christian Albrechts University in Kiel recently confirmed that variants of the FOXO3A gene are a common characteristic for many people who live past 100. The CAU team studied 380+ centenarians, more than 600 people in their 90s, and more than 700 60-75 year olds to determine how prevalent these gene variations were. They found that not only were certain FOXO3A variants very common in 90 year olds, they were even more common in 100 year olds, emphasizing the importance of genetics for aging well.
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I read anecdotal data for years from people using it to enhance their skin tone or tan. I have never seen any photographic evidence of anyone significantly changing their skin color even though using very high doses.
This quote was disturbing. So most of the “Astaxanthin” bulk powder is actually a petrochemical and not from the algae…
“Naturally-sourced astaxanthin is available — but it’s four times as expensive. According to one of the world’s leading manufacturers, AlgaTech, “essentially all” astaxanthin used in aquaculture is a petrochemical product. Scientists say it is not the same for salmon as eating krill and may not react the same way in our bodies as a natural carotenoid.”
Maybe the best way is to contact the ITP for their source?
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Ah - most of the astaxanthin for human consumption (perhaps all) is natural:
Will get back to you when I hear more on pricing.
I think this is a cautionary tale not to buy Chinese ‘Astaxanthin’ as you will probably get the petrochemical version as they run at dirt cheap prices. Most people would not assume that there are un-natural sources of Astaxanthin and would naively beleive it all comes from algae.
Just like me 5 minutes ago…
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I’m going to try to pull together the research on the potential benefits and risks of higher Astaxanthin doses. Ideally we’d identify some biomarkers we can use to see if the compound is providing us the benefits we hope for, while allowing early identification of any of the negatives side effects.
If you have time, please search around on Pubmed and post additional information relevant to this compound. Obviously, top priority is for human clinical trials, and the longer the better.
Here is my start:
Potential Benefits of Astaxanthin:
In double-blind, randomized controlled trials (RCTs), astaxanthin lowered oxidative stress in overweight and obese subjects and in smokers. It blocked oxidative DNA damage, lowered C-reactive protein (CRP) and other inflammation biomarkers, and boosted immunity in the tuberculin skin test. Astaxanthin lowered triglycerides and raised HDL-cholesterol in another trial and improved blood flow in an experimental microcirculation model. It improved cognition in a small clinical trial and boosted proliferation and differentiation of cultured nerve stem cells. In several Japanese RCTs, astaxanthin improved visual acuity and eye accommodation. It improved reproductive performance in men and reflux symptoms in H. pylori patients. In preliminary trials it showed promise for sports performance (soccer). In cultured cells, astaxanthin protected the mitochondria against endogenous oxygen radicals, conserved their redox (antioxidant) capacity, and enhanced their energy production efficiency.
Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism.
LDL cholesterol and ApoB were significantly lower after treatment with astaxanthin, compared with the start of administration, whereas none of the lipid profiles was changed in the placebo group. At the baseline, all four biomarkers were not significantly different between the two groups. Compared with the placebo group, MDA and ISP were significantly lower, but TAC was significantly higher in the astaxanthin group at 12 weeks. These results suggest that supplementary astaxanthin has positive effects by improving the LDL cholesterol, ApoB, and oxidative stress biomarkers.
Long-term 1 mg ASTA/kg body weight (BW) supplementation in Wistar rats (for 45 days) significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP) and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion.
Conclusions: our results suggest that ASTX may have preventive effects against diabetes and atherosclerosis and may be a novel complementary treatment option for the prevention of diabetes in healthy volunteers, including subjects with prediabetes, without adverse effects.
Owing to its ability to cross the blood‑brain barrier, astaxanthin has received attention for its protective effects against neurological disorders, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, cerebral ischemia/reperfusion, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, cognitive impairment and neuropathic pain. Previous studies on the neurological effects of astaxanthin are mostly based on animal models and cellular experiments. Thus, the biological effects of astaxanthin on humans and its underlying mechanisms are still not fully understood.
Potential Risks of Astaxanthin
Canthaxanthin Retinopathy
Not specific to Astaxanthin, but Canthaxanthin is another Carotenoid, and since there are issues with dosing Canthaxanthin at extremely high doses (10X to 20X higher than the 3grams/day Astaxanthin that is the human equivalent to what the NIA ITP is giving their mice) for long periods of time, it seems that there could be a small but possible risk of similar issues with Astaxanthin.
In high doses it seems Canthaxanthin can accumulate in the eye and cause crystals, which impair vision. When the person stops taking Canthaxanthin generally the crystals degrade / dissolve over time by themselves.
Apparently, some people take Canthaxanthin at high doses to get the desired change in skin color, this supplement is marketed as a “tanning supplement” because it gives people’s skin a brown/orange tint.
Canthaxanthin and other carotenoids locate in biological lipid membranes and based on their orientation and location can influence membrane properties such as permeability and fluidity. They are powerful antioxidants due to their radical scavenging and singlet oxygen-quenching properties [6]. However, in vitro studies have actually demonstrated prooxidant effects of carotenoids at higher concentrations [6]. In the setting of canthaxanthin retinopathy, it is thought that damage occurs at the level of the macular vascular system around areas of canthaxanthin-lipoprotein complex deposits, which comprise the visible crystals [7]. It is proposed that vascular dysfunction occurs due to aggregation of these complexes in vessel lipid layers, which modify and disrupt lipid membrane properties [7].
Incidence and prevalence are difficult to predict due to the generally asymptomatic course of canthaxanthin retinopathy. Some reports state an incidence between 12 and 14% [8, 9]. Harnois et al. [9] noted that crystal appearance follows a dose-dependent correlation, seen with 50% of patients ingesting a total dose of 37 g and with 100% ingesting greater than 60 g.
…
Treatment for canthaxanthin retinopathy is immediate discontinuation of the drug as soon as crystals are identified, even if the patient is asymptomatic. Prognosis is very good with complete recovery occurring in the vast majority of patients. Hueber et al. [16] followed five patients for 16–24 years and no long-term adverse effects were found, and fluorescein angiography results were normal, although complete resolution of golden particle appearance took up to 20 years.In summary, canthaxanthin retinal crystal deposition is a very common finding in patients with prolonged use of the drug. Symptomatic visual loss is less common and correlates with total dosage and possibly patient age. Even with profound visual loss, prognosis for improvement is very good with recognition and discontinuation of the drug.
Source Paper: Canthaxanthin Retinopathy with Visual Loss: A Case Report and Review
Related Paper: Canthaxanthin Retinopathy: Anatomic and Functional Reversibility | JAMA Ophthalmology | JAMA Network
Summary
So - there seems to be a small risk of the reversible condition similar to what is called Canthaxanthin Retinopathy. It is seen in humans who take 37 to 60 grams of Canthaxanthin (which is in the same family of molecules as astaxanthin).
However, the amount of astaxanthin that is being discussed is the human equivalent of the dosing used in the ITP Mouse Studies. The mice receive 4,000ppm of Astaxanthin. This is equivalent to about 3.6 grams/day (by our calculation) in human terms. This is still only 10% of the dosing of Canthaxanthin dosing levels that are seen to cause Canthaxanthin Retinopathy.
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Great stuff! Actually, it sounds like a lot of what GLYNAC does, but without the side effects of NAC. The downside is not that bad since they mitigate with time.
Make sure to include the FOX03 activation data in your summary. I think that’s a key longevity factor.
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Interestingly, FOX03 seems to be most helpful to females. A new study:
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OK. How do we activate or deactivate each one to obtain maximum longevity?
The only one I know for Sirt6 is the Sirt6 Activator by Do Not Age.
Sirt6 activator by Do Not Age, is simple Bladder Wrack seaweed (Focus Vestculosus). Many companies offer that, for a fraction of the price of Do Not Age. Do Not Age don’t want you to know that.
If you want to activate Sirtuin 1,3 and 6 at the same time in a natural way, eat a cup of Black/Blue berries a day.
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Article title talks about f. distichus. But the table shows highest sirt6 activation from f vesiculosus (bladderwrack). Activation involves sirt1, sirt6 and srt7.
Thank you.
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I found this Bladderwrack supplement:
https://hk.iherb.com/pr/nature-s-way-bladderwrack-580-mg-100-vegan-capsules/1844?gclid=CjwKCAjwvNaYBhA3EiwACgndgg5wcUV-DTh0YQMwKwln6Srwp6cBBT8J35iDSjHbDL_le4KyjMLm1hoCSOgQAvD_BwE&gclsrc=aw.ds
Also, I have heard that f vesiculosus varies greatly in the amount of Sirt6 activation from a lot to almost nothing depending on the batch. Of course that comes from the scientists at DoNotAge saying why their supplements have to be rigorously tested and why their supplement is so expensive…
Also Bladderwrack has a high concentration of iodine. You wouldn’t want to take too much of this. Does the iodine activate Sirt6?
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Think?
Is the iodine in the bladderwrack, stimulating the thyroid and activating sirt1, sirt6 and srt7?
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