Astaxanthin, Natural vs. Synthetic - Your Thoughts?

[RapAdmin]

As I reported earlier and was discussed in the earlier Astaxanthin thread here, the National Institutes on Aging, ITP program is having good success with median lifespan extension with Astaxanthin at 4,000ppm, with preliminary results (not final) of a median lifespan increase of about 12%. The 4,000ppm dosing in the mouse studies, translates to something like 3.5 grams per day in human dosing.

In this NIA ITP study I think they may be using the synthetic version of Astaxanthin called AstaSana manufactured by DSM nutritional products, a Dutch company.

So, this study and the good results in terms of healthspan / lifespan extension brings up a number of issues.

Right now - the Astaxanthin supplements market is virtually entirely “natural” astaxanthin produced by Algae. This production method is very expensive and the resulting supplements are very expensive even at a low dose of 12mg/day. At the level of dosing used in the NIA ITP Study it would cost about $4,500 per month to get the 3.5 grams per day of Astaxanthin that resulted in the 12% lifespan extension. Obviously this pricing level is not acceptable for most people.

There is of course, the question of how likely it is that the AstaSana synthetic astaxanthin mouse study translates with similar results to humans?

There is the added issue and question as to whether the NIA ITP study using synthetic astaxanthin translates to natural astaxanthin (in humans)?

There is research that suggests that the synthetic astaxanthin is more bioavailable than the natural astaxanthin, so it may be that the natural astaxanthin does not provide the same longevity & health benefits that the synthetic astaxanthin does:

Study on Bioavailability of synthetic Asta:

Plasma appearance of unesterified astaxanthin geometrical E/Z and optical R/S...

Cost / Benefit and Risk/Reward:

So, there are a number of considerations when thinking about taking Astaxanthin for its lifespan extending properties.

1. The Cost/Safety/Efficacy of Natural Astaxanthin. Natural Astaxanthin is very expensive, and has a long history of use in humans and has an excellent safety profile. But, Does Natural Astaxanthin provide the same level of health / longevity benefits that the Synthetic Astaxanthin has shown in the mouse longevity studies by the NIA ITP? We just don’t know.

2. The Cost/Safety/Efficacy of Natural Astaxanthin. The Synthetic Astaxanthin (at equivalent doses) is roughly 75% to 80% cheaper than the Natural Astaxanthin, and is showing excellent results in the NIA ITP studies, but this type of Astaxanthin has not been sold much as a human supplement yet. (but it is easily purchased from suppliers).

Following is the informational and safety data from DSM on their AstaSana synthetic Astaxanthin product, which is manufactured in Spain. Please let me know your thoughts…

PDS_5016378.pdf (85.0 KB)

EFSA 2019 - Safety of astaxanthin for its use as a novel food.pdf (1.0 MB)

AstaSana - GRAS notice.pdf (1.3 MB)

[Jensen_Achilles]

I’ve been taking astaxanthin for years. I always aim natural as I read natural is more potent at removing free radicals (reactive species) but I’m not sure how natural vs synthetic when it comes to lifespan.
Good question!

[RPS]

All farmed salmon is fed synthetic astaxanthin to give it its expected colour (otherwise it would be grey and no-one would buy it).
One can conclude then that the synthetic stuff does no harm.
As far as I am aware, chemically it is identical. Therefore I would say there is a high probability it is doing what it should do once ingested (whatever that may be), so on a cost/ benefit view, the synthetic is the obvious choice.

[RapAdmin]

Actually, the molecules are not identical. Its a chiral molecule (left/right hand molecular architecture) so they are not actually identical, just extremely similar.

From ConsumerLab:

[RapAdmin]

@Jensen_Achilles

I read natural is more potent at removing free radicals (reactive species)

What is the source of this information? (note: I see one source listed in the ConsumerLabs write-up above).

It seems that there is a bit of a war on between the natural astaxanthin companies and the synthetic astaxanthin companies, and given that the cost of the synthetic is about 80% cheaper, they are afraid of losing their market and spreading all kinds of information which may or may not be accurate. So - I’m thinking we need to very carefully evaluate all the claims from both sides of this issue. I don’t have a horse in this race - I just want to figure out the best option for cost-effective and biologically effective astaxanthin.

Moreover - not all synthetic astaxanthin versions are the same - each company may have a different manufacturing approach, and a slightly different molecule, and / or “packaging” approach (of the molecule) - so without good information you are really jumping to conclusions without good data and your conclusions are likely wrong.

[JuanDaw]

Twelve percent? How many mice were tested?

Calcium pantothenate provided an extension of 18.72%, which is fifty percent greater than the effect of astaxanthin. The mice which took calcium pantothenate were 33, versus 41 control mice. Dosage was modest - 300 μg of calcium pantothenate daily in drinking water.

https://journals.sagepub.com/doi/abs/10.3181/00379727-99-24442

Am taking both. But my dosage of astaxanthin is a modest 12 mg. I might have greater mileage with 500 mg calcium pantothenate.

[RapAdmin]

This is the National Institutes of Aging ITP program. The protocol for their studies is the same for each study. They have three simultaneous studies going on at the same time for every compound they test.

Approximately 50 male mice and 50 female mice are getting the drug/supplement at each of the 3 test sites (The Jackson Laboratory [TJL], University of Michigan [UM], and University of Texas Health Science Center at San Antonio [UT]). Each site also enrolled approximately 100 male and 100 female control mice, which also served as the control group for the other drugs tested.

So, approximately 900 mice total.

Its a much more rigorous process than the odd small individual lifespan studies that some groups do. I wouldn’t trust a single lab’s result.

This compares to the study you referenced where they had:

Thirty-three young male and female C-57 black mice were given approximately 300 μg of calcium pantothenate daily in drinking water. Forty-one control mice did not receive the vitamin supplement.

So - three simultaneous studies each with 300 mice, vs. one study with around 74 mice. A huge difference.

There is a good video on the National Institutes of Aging ITP (Intervention Testing Program) here:

Webinar | Drugs That Slow Aging in Mice: the NIA Interventions Testing Program

[DeStrider]

I have been to the testing site at the University of Michigan when I go to visit family. It’s a top notch facility at a top notch university! Next time I go, probably summer of 2023, I’ll try to arrange lunch with Dr. Miller or his associates.

[Kandice]

Synthetic astaxanthin (S-AX) was tested against natural astaxanthin from Haematococcus pluvialis microalgae (N-AX) for antioxidant activity. In vitro studies conducted at Creighton University and Brunswick Laboratories showed N-AX to be over 50 times stronger than S-AX in singlet oxygen quenching and approximately 20 times stronger in free radical elimination.

https://www.researchgate.net/publication/263169974_Synthetic_astaxanthin_is_significantly_inferior_to_algal-based_astaxanthin_as_an_antioxidant_and_may_not_be_suitable_as_a_human_nutraceutical_supplement

[RapAdmin]

Kandice, the paper you site above is produced by a natural astaxanthin consultant and a company (Cyanotech Corp.) that is a leader in the natural astaxanthin industry - so not exactly an unbiased source of information.

I suspect that its not the anti-oxidant effect of the synthetic astaxanthin that is resulting in the lifespan increase of 12% that is being seen in the NIA ITP studies…

If the above study is representative of lifespan improvement then theoretically the ITP would see a 20 to 50 times improvement in the lifespan extension with the natural version, compared to that which is being seen with the synthetic astaxanthin… and I doubt the National Institute on Aging’s ITP program would have used the synthetic version of astaxanthin if they read the above research, believed it, and though that the synthetic astaxanthin was going to be 20 to 50 times less effective at lifespan extension.

More broadly, I think the anti-oxidant / free radical theory of aging is largely dead now in the geroscience community (though not in the popular press or lay community, sadly). So I think the paper is a red herring in that sense - it “sounds good” and may even be true, but in reality it has no impact at all on longevity. In all the longevity science meetings, nobody is talking about anti-oxidants anymore and I don’t think any geoscientist is looking at anti-oxidants as a key factor in longevity any longer (though I know the public still thinks that anti-oxidants are health-promoting, and many companies continue to market to that belief and encourage it).

Most antioxidants don’t extend lifespan

In the past two decades, many large studies found that antioxidants do not slow down aging and don’t reduce mortality (R,R,R).

One large meta-analysis consisting of 230,000 people even found that some antioxidants are associated with an increased risk of dying (R): vitamin A, vitamin E and beta-carotene intake was associated with slightly increased mortality.

Of course, many arguments can be brought up to counter these findings: in many studies the wrong form of antioxidants are given, or too low doses, or too late.

Still, both animal and human studies have painted a disappointing picture about the role of antioxidants in longevity. Animals have been given all kinds of antioxidant cocktails, but they didn’t live longer. At least according to well-conducted studies; there are many low-quality studies that sometimes do show that antioxidants slow down aging. But often, when these studies are reproduced by other research groups no longevity effects are seen.

Why antioxidants don’t really work to extend lifespan

Research shows that most antioxidants do not extend lifespan.

And if some antioxidants do extend lifespan, it’s often not because of their antioxidant activity, but because of other mechanisms, such as their anti-inflammatory, epigenetic or mitochondrial activity.

Why Antioxidants Don't Slow Down Aging & What Really Works

Is the Free-Radical Theory of Aging Dead?

Antioxidants Are Unlikely To Prevent Aging, Study Suggests

Against the oxidative damage theory of aging: superoxide dismutases protect...

In conclusion, current evidence does not allow to recommend antioxidant supplementation as a useful mean to prevent age-related pathophysiological modifications and clinical conditions. Several concerns are present not only about their efficacy, but also on their safety. No recommendation will be made until a clearer picture of 1) mechanisms underlying the aging process, 2) the network existing among the different antioxidant molecules, 3) the relationship between pro-oxidant and antioxidant factor, 4) the pathogenesis of the oxidative damage-related disease, and 5) reliable markers of oxidant and antioxidant levels, will be provided.

Effects of antioxidant supplementation on the aging process

Free-radical theory of aging | Challenges to the theory

[RapAdmin]

Here is my question to people: Given what you know about natural and synthetic astaxanthin as shown in this post (above)…

Which Version of Astaxanthin Would You Buy?

• Natural Astaxanthin, at the typical Amazon.com Price of $4.15 per 100mg
• Synthetic Astaxanthin at a price of approx. $1.00 per 100mg

[RapAdmin]

Mikhail V. Blagosklonny

Mikhail V. Blagosklonny

Mikhail V. Blagosklonny

[DeStrider]

So are you going to stop using Asta because of this? Vitamin C, NAC, are also antioxidants…

[JuanDaw]

Response from a certain Alex, on Blagoklonny’s Twitter account.

To clarify, too many human trials focus on the same tired, small group like beta carotene, dl-alpha tocopherol, vitamin c, NAC. And then reviews take these and apply to all antioxidants. Waiting for human trials are many herbal and natural antioxidants w/ anticancer properties.

[JuanDaw]

Blag quoted Dr. Michael Ristow. Below is an interview of Dr. Ristow.

Free radicals are not your enemy | An interview with Dr. Michael Ristow (part...

Another problem is that there are different types of antioxidants, and the public can’t distinguish between them. There are direct antioxidants that really react with free radicals, like vitamin C and E and a few others, and then there are indirect antioxidants, which actually induce oxidative stress. A prime example is polyphenols, like EGCG from green tea, or the compounds that make berries blue or purple or red, which are all pro-oxidants because they cause oxidative stress. So these guys induce antioxidant defense in the body like exercise does, and they really are healthy. But since they’re all called antioxidants, the average consumer doesn’t distinguish between them and can’t tell the good from the bad.

Nuance matters.

[JuanDaw]

In the interview, Dr. Ristow quotes a study by Christian Gluud, stating that “antioxidants increase all mortality”.

Below is the abstract.

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007176.pub2/abstract

Goran Bjelakovic, Dimitrinka NikolovaLise, Lotte Gluud, Rosa G Simonetti, Christian Gluud

Authors’ conclusions

We found no evidence to support antioxidant supplements for primary or secondary prevention. Beta‐carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing.

Dr. Ristow:

"The message I want to get across here is that the best case for antioxidant supplements is that they’re harmless, like vitamin C. If you have too much vitamin C, you’ll just excrete it through the kidneys and no damage is done. But other antioxidants like vitamin E, vitamin A, beta-carotene, these can become a problem, and they’ve been repeatedly shown to increase cancer, to cause cardiac problems like heart attack, and to reduce lifespan.

[RapAdmin]

@DeStrider

So are you going to stop using Asta because of this? Vitamin C, NAC, are also antioxidants…

Not at all. The data behind astxanthin looks good. I am just saying that merely because something is an antioxidant or in this case just because the natural version of astxanthin had a higher ORAC or antioxidant rating doesn’t mean it has greater health or longevity value for people.

The synthetic version of astxanthin is what is producing the 12% median lifespan increase in the ITP study. It seems reasonably likely it has nothing to do with the antioxidant rating or level as was mentioned in the study above by Kandice.

[Tree_Slayer]

Some antioxidant’s metabolites are pro oxidant. Which has to be taken into account with any antioxidant, also why large doses may not be practical with some things

[LeeJohn]

The question is how to get synthetic Astaxanthin?

I go to the website of AstaSana as RapAdmin mentioned, it looks like they don’t sell the product to the personal use, have you or anyone ever bought AstaSana?

I can’t find synthetic Astaxanthin in the market, there are all natural Astaxanthin, where to buy synthetic Astaxanthin? and how to buy it? If anyone has experience, please share more information to us.

AstaSana™ | DSM Human Nutrition & Health

[RapAdmin]

I don’t think anyone sells it yet. I couldn’t find any companies.