#104

Guacamole! I actually had that with chips prior to my last Rapamycin dose for good fat content.

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#105

Iā€™m up to 144mg of Astaxanthin per day, no noticeable side effects, or any effects at all really, other than pinkish stools.

More good news on Astaxanthin:

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#106

Got the following new information from Richard Miller at the NIA ITP program (I asked him more questions about the Astaxanthin study they are doing).

In the recent interview Richard Miller stated that astaxanthin is, in preliminary results, showing longevity benefits for male mice.

Here is his response:

We analyze survival data twice, once when half the controls of each sex have died at each site, and then again when 90% of the controls have died. The C2019 mice have reached the first milestone and not the second. The attached slides show the outcome at the 50% point. I think they are promising, but they are far from definitive, particularly because we did not yet have any data at all on mice older than 1050 days, and since we had many live mice between ages 900 - 1050. Still, it appears the Asta (and possibly meclizine) may turn out to be beneficial for at least male mice.

When we get to the 90th percentile, in a couple of months, we will then do the definitive analysis and start to prepare a publication.

ā€¦ I think you should feel free to mention that the studies of Asta are ongoing and incomplete, but so far show suggestive evidence of a benefit in males.

Since Asta (and meclizine for that matter) are available OTC, it may turn out that they would be safer for long-term use in humans. Of course we do NOT know if they have any health benefits in humans, or, if they did, what the best dose would be, or what harmful side effects they might have if used for long periods rather than short-term courses. Still, they may turn out to have fewer side effects than Rapamycinā€¦

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#107

Indeed, thatā€™s down right sexist!

The study has to run out and see where those curves land.

The TJL males site went really south for ASTA?

Need to wait until I see the full final studyā€¦maybe the ASTA mice are so sick of seeing their littermates red, it ruins their appetite, so they eat less, while the control mice keep chowing away and dying early!

Remind me the human dose equivalent and how red is your poop currently, ergo, what dose are you at?

Hmmmā€¦thinking about being ā€œred manā€ for halloween by injecting a liquid version of Asta. :wink:

Wait, is this Richard Miller of the ITP making this statement?? Pretty much everyone on this forum thinks the ITP is the ā€œgold standardā€ for HUMAN lifespan translation interventions?

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#108

Great news! I can tell my mother to stop taking Astaxanthin and full speed ahead for my Dad. :slight_smile:

Still fighting the intestinal pain and bloating issue before upping my dosage.

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#109

I really have a hard time believing the issues you are having around intestinal pain and bloating is the astaxanthin. Iā€™m at 120mg and feel nothing. I may bump it up to 200mg next week. Iā€™m just testing high doses to see if its reasonable to try to scale up to the ITP dosing equivalent in humans - which seems to be in the low gram levels.

Astaxanthin is available in powder form, probably fairly inexpensively in bulk I suspect. If its cost effective that might make sense to look into for some of us. consuming 100s of mg of astaxanthin doesnā€™t make sense in terms of the typical consumer 10mg capsules available today on the market.

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#110

I am starting to agree with you, but every time I up the dosage, the pain gets worse. Different folks, different strokes. Maybe I am allergic to it? Actually, I am pretty sure most of the pain and bloating came from the oatmeal I used to eat daily. I am now cycling my breakfasts on a 3 day cycle to see how that helps. And when I run out of oatmeal, I will replace it with scrambled eggs. Maybe then I can up the dosage to see what happens.

#111

As I have gotten older I have found that almost any kind of grain increases gas and bloating.
You might try going on a very low-carb diet for a few days. If you drink milk switch to lactose-free milk such as Lactaid.
I didnā€™t choose to go on a low carb grain-free diet, my body did and I feel so much better.

5 Likes
#112

Homemade milk kefir can also aid in digesting lactose (as well as the many other health benefits)

#113

Thanks guys for all the help. I truly appreciate it. I will solve this problem!

(Cycling the breakfasts has helped. Iā€™m 90% sure itā€™s the oatmeal now. Who knew?)

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#114

Full Paper (PDF) Here: Sci-Hub | Astaxanthin: How much is too much? A safety review | 10.1002/ptr.6514

eight human studies were conducted to look specifically at safety of high doses of natural AX, ranging from 8 to 45 mg/day and over 4 to 12 weeks (Aquasearch, 1999; Kajita et al., 2010; Kajita, Tsukahara, Kato, & Yoshimoto, 2009; Matsuyama et al., 2010; Ohgami et al., 2005; Satoh et al., 2009; Spiller & Dewell, 2003; Tsukahara et al., 2005). Twenty-eight studies were found, which used daily doses of at least 12-mg natural AX over a period of at least 4 weeks. These were general efficacy studies where adverse events were monitored.

No serious adverse events were observed in any of the clinical studies listed above, even at the highest dose tested (45 mg in 15 patients; Kajita et al., 2010). In one study, a red coloration of the stool was noted at a dose of 30 mg (Kajita et al. 2009b; Tsukahara, Kato, & Yoshimoto, 2009). This was also observed at a dose of 20 mg (Choi, Kim, et al., 2011) and an increased frequency in bowel movement in two patients (of 14). Kupcinskas et al. (2008) recorded 36 adverse events (in 131 patients taking 16 or 40 mg AX or placebo); however, compared with placebo, fewer events took place in the higher dose group.

No changes in liver parameters in humans have been reported.

Natural AX has shown an excellent clinical safety profile at short-term daily doses up to 100 mg and long-term daily doses averaging between 8 and 12 mg.

In the Fajita et al, 2010 study at up to 50mg a day:

Physiological, biochemical, hematological, and No adverse effects reported 12 weeks urinary markers were analyzed at baseline, 4, 8, and 12 weeks. No clinical changes were observed over the study period

Human studies have not identified any significant toxicity at any doses over any length of time for natural AX in at least 87 clinical trials involving 2,000+ participants using short-term daily doses (up to 100 mg) and long-term daily doses averaging between 8 and 12 mg. No severe adverse events were recorded. No indicators of liver toxicity (such as elevated enzymes) were reported in any clinical studies. Reddening of stool is a minor adverse event occurring at high doses.

3 Likes
#115

Iā€™m continuing on my testing of higher doses, now up to 200mg/day. Reddening of stool is the only change Iā€™ve noticed - positive or negative.

#116

It seems that high dosing is extremely non-toxic in mammals.

Safety Assessment of Astaxanthin - Subchronic Toxicity Study in Rats

Astaxanthin, a naturally occurring xanthophyll, is commercially used as a colouring agent in salmon feed, but also marketed as a dietary supplement. The objective of this study was to investigate the subchronic toxicity of synthetic [3S, 3ā€™S]-Astaxanthin in rats. A powder formulation containing approximately 20% [3S, 3ā€™S]-Astaxanthin was administered via the diet to groups of 10 male and 10 female Wistar rats at concentrations of 5,000, 15,000 and 50,000 ppm for a period of 13 weeks. A formulation of comparable composition but without [3S, 3ā€™S]-Astaxanthin served as a placebo control. There were no effects observed on survival, clinical examinations, clinical pathology, estrous cycle as well as on sperm parameters. At terminal necropsy, a macroscopically visible brown-blue discoloration of the gastrointestinal contents was noted which was considered to be secondary to the violet-brown color of the test material. No other significant or dose-related abnormalities were found in the tissues collected at termination. Our observations support that ingestion of [3S, 3ā€™S]-Astaxanthin of up to 700 - 920 mg/kg bw/day in rats in a gelatin/carboydrate formulation is without adverse effects

Astaxanthin Toxicity Discussionā€¦

In our study, the only treatment related effect of the ASTX containing formulation was a brown-blue discoloration of the content in the gastrointestinal tract noted in treated rats after 13 weeks of exposure. This observation was considered to be associated with the intensive coloration of the tested product and was not an adverse toxicological effect. No biologically significant differences in food consumption, body weights, body weight gain, gross findings at necropsy or the histopathological investigation of isolated tissues were associated in a dose related manner with exposure to the test material or the formulation matrix for up to 13 weeks of dosing. Clinical chemistry, hematology, blood clotting times and urinalysis evaluations showed no toxicologically relevant, dose-related effects in group of animals treated with the test article or the formulation matrix relative to the vehicle control group at any study period examined. Results from the functional observational battery conducted during the final week of the study showed no signs of test-substance-related effects in behavior or sensorimotor tests.

The results of this study indicate that ingestion of the [3S, 3ā€²S] isomer of astaxanthin of up to 700 and 920 mg ASTX/kg bw/day in a gelatin/carbohydrate formulation is without adverse effect when given orally to rats for 13 weeks of continuous exposure

Full Research paper (PDF) here: Sci-Hub | Safety assessment of [3S, 3ā€²S]-astaxanthin ā€“ Subchronic toxicity study in rats | 10.1016/j.fct.2015.04.017

Similarly - no detectable toxicity in mice:

In the repeat-dose toxicity test, 100, 250 and 500 mg/kgĀ·bw astaxanthin showed no abnormalities in terms of body and organ weight as well as hematological and biochemical parameters in clinical observation throughout the pregnancy. During pregnancy, the liver accumulated the highest content of astaxanthin, while the eye exhibited the least. The results indicated that administration of astaxanthin from H. pluvialis throughout pregnancy had no adverse effect on mice.

and a 90 day toxicology study in rats yielded not noticeable toxicity:

Both male and female Sprague-Dawley (SD) rats (12 for each gender) receiving the astaxanthin crystal at 1.2, 240.0, or 750.0 mg/kg/day in olive oil via oral gavage for 90 days showed no changes in body weight gains, hematology and serum chemistry values and hepatic enzyme stability, organ integrity and organ weight. Except the higher food consumption observed in rats receiving 750.0 mg/g astaxanthin crystal, administration of the astaxanthin crystal to 25-27 pregnant female rats in each group throughout the period of organogenesis (G6-G15) produced no adverse effects on fetal organogenesis. Based on the results, we propose that the no-observable-adverse-effect level (NOAEL) of the astaxanthin crystal extracted from genetically modified E. coli K-12 is 750.0 mg/kg bw/day.

Full research Paper (PDF) Here: Sci-Hub | Safety assessment of astaxanthin derived from engineered Escherichia coli K-12 using a 13-week repeated dose oral toxicity study and a prenatal developmental toxicity study in rats | 10.1016/j.yrtph.2017.05.003

1 Like
#117

Then the question is what dose should be taken to get the maximum result? You could chow down a lot of this stuff for very little extra effect. Any thoughts about this? 10 mg? 20 mg? 100 mg a day? Supplements could get expensive quickly at high dosesā€¦

#118

The bigger issue is at what point your skin turns red (similar to the issue with beta-carotene).

ā€œStudies have shown supplementation of astaxanthin to be incredibly safe, with no significant side effectsā€”although, like other carotenoids, it has the potential to affect the colour of the skin if taken at high doses for prolonged periods. That being said, such an effect has only been observed in animals, and doses of up to 100 mg as a single event and 40 mg daily for four weeks in humans were well tolerated with no skin changes or other adverse events reported.ā€

Iā€™m checking on costs of bulk powder astaxanthin. You are right, the typical consumer product is too expensive for higher dosing I think.

Note: arotenoids are fat soluable. They are absorbed best if dissolved in fat. So take it with a fatty meal, or drink some olive oil or MCT oil I guess.

The ITP fed the mice a human equivalent of about 3.64g of astaxanthin per day (4000ppm). This is 100x the dose used in human studies!

Here is the math:

4000ppm is 0.4%. A typical mouse weighs about 0.025kg and eats about 4g of food per day, so 0.4% is 16mg of astaxanthin for the mouse per day. That is a dose of 16mg/0.025kg=640mg/kg. Divide by 12.3 to allometrically scale to humans, to get a human equivalent dose of (640mg/kg)/12.3=52mg/kg. So for a 70kg human, that would be 3.64g of astaxanthin.

It appears that a higher proportion of ASX is absorbed when is delivered in an oil-based formulation. In an open parallel study, eight healthy male volunteers received a single dose of 40 mg of ASX as three different lipid-based formulations (n = 8 for each group). All three lipid-based formulations enhanced the bioavailability of ASX, but the highest bioavailability was observed with the formulation containing the highest content of the hydrophilic synthetic surfactant. Therefore, these results suggest that ASX should be consumed together with dietary fats to optimize bioavailability

Source: Astaxanthin in Skin Health, Repair, and Disease: A Comprehensive Review - PMC

2 Likes
#119

This article from Blagosklony gives me some concern over high dose astaxanthin.

doi: 10.18632/oncotarget.27882

Failure of anti-oxidants

The goal of longevity research is life extension. Instead, most studies are focused on life-shortening. Many things can shorten lifespan without causing normal aging. For example, car accidents shorten lifespan, but they do not cause aging. Knockout of antioxidant enzymes can shorten lifespan. But antioxidants do not extend lifespan [3ā€“12]. Furthermore, antioxidants increase mortality in humans [13ā€“17]. Clinical trials of antioxidants have been terminated because of increased cancer incidence [13ā€“17]. In agreement, antioxidants promote cancer in mice [18, 19]. Yet, thousands of publications describe mechanisms of life extension by the exact same antioxidants that do not extend lifespan. To study mechanisms of life extension, there must be life extension at least.

Certainly, reactive oxygen species (ROS) cause molecular damage, and this damage would eventually kill the organism. But no organism lives long enough to die from accumulation of molecular damage because hyperfunctional (in part, mTOR-driven) aging terminates life first [9]. If artificially accelerated by knocking out genes, molecular damage may become life limiting. But in normal animals and humans, it is not. We cannot extend life by targeting a non-life-limiting process.

#120

I agree with Blagosklonny and many other geoscientists ; the anti-oxidant / ROS / redox theory of aging has largely failed. But Iā€™m also not going to say that NIA ITP results are not good studies. Perhaps astaxanthinā€™s primary method of operation in longevity is one of the other pathways?

We have already seen successful ITP-validated lifespan improvements via Protandim. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Andā€¦ protandim is marketed as an anti-oxidant by the company (which of course, means nothing other than that they think people buy some supplements because they think anti-oxidants are good).

Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation, astaxanthin has gained growing interest as a multi-target pharmacological agent against various diseases. In the current review, the anti-inflammation mechanisms of astaxanthin involved in targeting for inflammatory biomarkers and multiple signaling pathways, including PI3K/AKT, Nrf2, NF-ĪŗB, ERK1/2, JNK, p38 MAPK, and JAK-2/STAT-3, have been described. Furthermore, the applications of anti-inflammatory effects of astaxanthin in neurological diseases, diabetes, gastrointestinal diseases, hepatic and renal diseases, eye and skin disorders, are highlighted. In addition to the protective effects of astaxanthin in various chronic and acute diseases, we also summarize recent advances for the inconsistent roles of astaxanthin in infectious diseases, and give our view that the exact function of astaxanthin in response to different pathogen infection and the potential protective effects of astaxanthin in viral infectious diseases should be important research directions in the future.

2 Likes
#121

IMO, Dr B is over-simplifying the term ā€œantioxidantsā€ in his sweeping generalization that they donā€™t work for aging. Heā€™s referring to the studies which used high doses of specific compounds which directly neutralize free radicals (Vit C, E, beta carotene, etc). I think the jury is still out when it comes to other, more balanced approaches to reducing free radicals, especially in a system where free radicals are elevated (illness vs health). Some food-based compounds work together in synergy to neutralize radicals and then regenerate each other. Some are hormetic antioxidants which actually work as weak PRO-oxidants which stimulate our cellular antioxidant enzymes such that thereā€™s a net antioxidant effect. Taking an extract of grape seed, which contains a spectrum of different ā€œantioxidantsā€ is very different than taking high-dose alpha tocopherol. Iā€™m not ready to just give up on antioxidants altogether, even though itā€™s clear that pushing the dial too far towards ā€œreductive stressā€ isnā€™t good either.

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#122

Anti-oxidants may help in specific disease conditions, but the general consensus related to the Free Radical Theory of Aging is:

#123

Oh, I wasnā€™t claiming that the antioxidant theory of aging is true, just that oxidative damage and antioxidants shouldnā€™t be entirely discounted as playing a role. I agree completely with the authorā€™s statement from the above paper:

ā€œOxidative damage would contribute to the aging process only as a subset of total damage. It may be more relevant to regulating lifespan under some conditions, but less relevant under other conditions.ā€

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