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Astaxanthin prevents fish oil induced oxidative stress


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#1 ikaros

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Posted 27 June 2011 - 07:41 PM


Pharmacol Biochem Behav. 2011 May 17;99(3):349-355. [Epub ahead of print]

Astaxanthin limits fish oil-related oxidative insult in the anterior forebrain of Wistar rats: Putative anxiolytic effects?

Mattei R, Polotow TG, Vardaris CV, Guerra BA, Leite JR, Otton R, Barros MP.


Source

Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), ZIP 04023062, São Paulo, SP, Brazil.


Abstract

The habitual consumption of marine fish is largely associated to human mental health. Fish oil is particularly rich in n-3 polyunsaturated fatty acids that are known to play a role in several neuronal and cognitive functions. In parallel, the orange-pinkish carotenoid astaxanthin (ASTA) is found in salmon and displays important antioxidant and anti-inflammatory properties. Many neuronal dysfunctions and anomalous psychotic behavior (such as anxiety, depression, etc.) have been strongly related to the higher sensitivity of cathecolaminergic brain regions to oxidative stress. Thus, the aim of this work was to study the combined effect of ASTA and fish oil on the redox status in plasma and in the monoaminergic-rich anterior forebrain region of Wistar rats with possible correlations with the anxiolytic behavior. Upon fish oil supplementation, the downregulation of superoxide dismutase and catalase activities combined to increased "free" iron content resulted in higher levels of lipid and protein oxidation in the anterior forebrain of animals. Such harmful oxidative modifications were hindered by concomitant supplementation with ASTA despite ASTA-related antioxidant protection was mainly observed in plasma. Although it is clear that ASTA properly crosses the brain-blood barrier, our data also address a possible indirect role of ASTA in restoring basal oxidative conditions in anterior forebrain of animals: by improving GSH-based antioxidant capacity of plasma. Preliminary anxiolytic tests performed in the elevated plus maze are in alignment with our biochemical observations.

Copyright © 2011 Elsevier Inc. All rights reserved.


What's interesting is that fish oil alone appears to be deleterious to the brain. Another hype-myth proven to result in opposite to health claims?

#2 david ellis

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Posted 27 June 2011 - 09:11 PM

My problem is that I wonder why the Yup'ik Alaskan eskimos who eat 20 times as much fish oil are very healthy. Many native peoples are troubled by high rates of metabolic syndrome and the Yup'ik have significantly low rates of metabolic syndrome.

If something is bad for us, shouldn't taking 20 times as much be very bad?

I, too, have read that fish oil oxidizes easily and is bad for us. It is true that fish oil oxidizes quickly, but I have not yet read an explanation of why the fish oil studies are wrong.

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#3 niner

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Posted 28 June 2011 - 02:43 AM

My problem is that I wonder why the Yup'ik Alaskan eskimos who eat 20 times as much fish oil are very healthy. Many native peoples are troubled by high rates of metabolic syndrome and the Yup'ik have significantly low rates of metabolic syndrome.

If something is bad for us, shouldn't taking 20 times as much be very bad?

I, too, have read that fish oil oxidizes easily and is bad for us. It is true that fish oil oxidizes quickly, but I have not yet read an explanation of why the fish oil studies are wrong.

I bet these eskimos are not megadosing on fish oil that they ordered from iherb. I bet they are getting it from the fish they eat. The previous post suggests that the astaxanthin in salmon is beneficial. This paper looked at levels of EPA and DHA in blood cells, and comes to the conclusion that people should take fish oil, presumably a lot of it. I think that's the wrong conclusion. What they were looking at wasn't a marker of fish oil consumption, it was a marker of having a particular sort of diet. Maybe the conclusion should have been that people should eat a high-fish paleo diet, or whatever it was. The native peoples who are suffering from high rates of metabolic syndrome are eating crappy industrial diets. A crappy industrial diet plus fish oil is still crappy.
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#4 david ellis

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Posted 28 June 2011 - 04:18 PM

I bet these eskimos are not megadosing on fish oil that they ordered from iherb. I bet they are getting it from the fish they eat. The previous post suggests that the astaxanthin in salmon is beneficial. This paper looked at levels of EPA and DHA in blood cells, and comes to the conclusion that people should take fish oil, presumably a lot of it. I think that's the wrong conclusion. What they were looking at wasn't a marker of fish oil consumption, it was a marker of having a particular sort of diet. Maybe the conclusion should have been that people should eat a high-fish paleo diet, or whatever it was. The native peoples who are suffering from high rates of metabolic syndrome are eating crappy industrial diets. A crappy industrial diet plus fish oil is still crappy.



It is not about diet, it is about the level of EPA/DHA in the blood. Bottom line, the Inuits had 20 times the level of EPA/DHA. EPA/DHA is supposed to be dangerous because it oxides easily. They had 20 times as much EPA/DHA, so if EPA/DHA is dangerous why was their health superior? Why aren't they showing the ill effects of 20 times as much dangerous malondialdehyde?

I take more than one gram of EPA/DHA a day. My lipid peroxide levels* are .88 nmol/mL. That is pretty good, close to the healthiest fifth of the reference range. Despite their low level of EPA/DHA intake, cronies have high levels of lipid peroxidation. I don't know why their levels are high, but my level of peroxidation is low.

TBARS test -HPLC measuring malondialdehyde removing most non-specific effects. (thiobarbituric acid reactive substance)

I have read the explanations why EPA/DHA is bad, and I am unable to refute them. I am an accountant, not a biochemist. But, I need to understand why all of the studies about beneficial effects of EPA/DHA are mistaken. The Inuit study is a recent example of many studies about fish oil, and high levels of EPA/DHA in the blood are shown to be beneficial, not problematic. Why don't the theoretical effects of malondialdehyde show up in these studies? If peroxidation is a problem why don't the fish oil studies find it?

#5 ikaros

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Posted 28 June 2011 - 04:44 PM

It is not about diet, it is about the level of EPA/DHA in the blood. Bottom line, the Inuits had 20 times the level of EPA/DHA. EPA/DHA is supposed to be dangerous because it oxides easily. They had 20 times as much EPA/DHA, so if EPA/DHA is dangerous why was their health superior? Why aren't they showing the ill effects of 20 times as much dangerous malondialdehyde?

I take more than one gram of EPA/DHA a day. My lipid peroxide levels* are .88 nmol/mL. That is pretty good, close to the healthiest fifth of the reference range. Despite their low level of EPA/DHA intake, cronies have high levels of lipid peroxidation. I don't know why their levels are high, but my level of peroxidation is low.

TBARS test -HPLC measuring malondialdehyde removing most non-specific effects. (thiobarbituric acid reactive substance)

I have read the explanations why EPA/DHA is bad, and I am unable to refute them. I am an accountant, not a biochemist. But, I need to understand why all of the studies about beneficial effects of EPA/DHA are mistaken. The Inuit study is a recent example of many studies about fish oil, and high levels of EPA/DHA in the blood are shown to be beneficial, not problematic. Why don't the theoretical effects of malondialdehyde show up in these studies? If peroxidation is a problem why don't the fish oil studies find it?


It's also important to note here that this study examined only a very specific part of the human organism, i.e. brain (and more specifically anterior forebrain). You can't biopsy the brain in human studies.
The situation in blood plasma could be a different story as this is biochemically a different environment. Malondialdehyde and other oxidative stress markers could be totally normal in the plasma of heavy dose fish oil consumers.

Whatever the situation I find that the most important conclusion from the study is that if supplementing fish oil alone one should definately add a lipid soluble antioxidant to the diet. The double bonds in EPA and DHA are very susceptible to oxidation unless there's a quencher present. Astaxanthin is one good example as it has a very low potential for auto-oxidation unlike beta-carotene. The astaxanthin + fish oil combo would equate very well to eating actual salmon.

Edited by ikaros, 28 June 2011 - 04:48 PM.


#6 nameless

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Posted 28 June 2011 - 04:51 PM

This may be simplistic and am only guessing, but could the fish oil used in the studies themselves account for the variability regarding peroxidation markers?

I've gotten bad fish oil before, and sometimes get 'iffy' fish oil... typically noticed if shipping fish oil over the Summer months. Some fish oils contain vitamin E + antioxidants, some don't. Some are high concentrates (which I am guessing would oxidize faster), some are low. And cheaper fish oils tend to have higher oxidation markers than more expensive ones.

So was wondering, could it be as simple as the fact that some studies use lousy fish oil without any antioxidants present?

#7 Robert C

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Posted 28 June 2011 - 07:03 PM

The New Chapter fish oil contains the natural astaxanthin from the salmon. It is much darker than normal fish oils. I have no way to prove it but it seems and tastes fresher to me.
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#8 hollywood_69

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Posted 28 June 2011 - 10:03 PM

Would Algal Oil fall into this category, it contains 900mg DHA? Thinking about going to 1g krill oil with asta. Or might just take 4mg of Asta and leave the oils all alone. This is very perplexing, because fish oils were suppose to be some of the most proven supplements. I'll never get this stuff right.

The New Chapter fish oil contains the natural astaxanthin from the salmon. It is much darker than normal fish oils. I have no way to prove it but it seems and tastes fresher to me.



#9 nameless

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Posted 28 June 2011 - 10:40 PM

There is only an tiny, tiny bit of astaxanthin in most salmon oils, including the New Chapter one. I think is has something like 3mcg per gel? I wouldn't expect that to offer much oxidation protection. The rosemary and mixed Es with the product are what would help, I'd think.

----

Hollywood_69:

And I don't see why algae DHA would differ from fish oil as far as oxidation goes. If anything, it may oxidize faster due to DHA being more prone to oxidation than EPA is. It should have some Vit E or other antioxidants in the product itself, so it'd protect against oxidation at least somewhat.
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#10 Robert C

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Posted 28 June 2011 - 11:30 PM

Yes there is 3 mcg of astaxanthin per gel in the New Chapter fish oil. I agree that it does not seem like much but I don't know the order of magnitude of an effective amount. The oil is noticably darker than other fish oils. New Chapter claims the pigment is from the astaxanthin. If that is true one would think that if there was enough to contribute to a dark pigment there might be enough to help with oxidation. Just a guess though.

I agree that it is hard to get this stuff right! I'm 52 years old and have been interested in health and fitness as long as I can remember. I have seen many health fads come and go. It often seems like what is good for you one decade is bad for you the next decade. I remember reading somewhere that human brains are programed to extrapolate. So I think we tend to be quick to extrapolate things like in vitro to in vivo, rat to human, and if a little bit of something is good for you a lot must be better. Also, most studies tend to be narowly focused on one aspect of health without looking for side effects. I believe in embracing the latest health information only so far. I like to be conservative with my supps and limit most things to close to natural levels.

IMO fish oil is the best form of omega 3 fatty acids which are considered by most to be a required nutrient. I'm a lazy guy and don't cook a lot of wild caught oily fish so I supplement to the extent to get the DHA plus EPA that the American Heart Association suggests for all Americans (about 0.5 mg DHA plus EPA per day). I figure I can't be too wrong with this approach.

#11 hollywood_69

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Posted 29 June 2011 - 12:17 AM

Hey I googled krill oil and i looked it up on pub med (just typed krill oil) and it seems great! Who knows 5-10 years from now though. I'm 33 yro m that is very active, not to mention a hypocrondiac! Ijust tried canned Alaskan Salmon, ewww I still ate it though. Just going to stick with supps.

I'm trying to limit my regime to Vit D3, multi, resveratrol every 2 days and oil. Not sure which one though. Still leaning towards krill. Or as I posted asta, it seems to do almost all the things for the heart as oils do. I just hope when I'm much older that all this doesn't come out to be awful afterall.

#12 niner

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Posted 29 June 2011 - 12:39 AM

I remember reading somewhere that human brains are programed to extrapolate. So I think we tend to be quick to extrapolate things like in vitro to in vivo, rat to human, and if a little bit of something is good for you a lot must be better. Also, most studies tend to be narowly focused on one aspect of health without looking for side effects.

Yup, these are the most common errors we make. Very succinctly put! Another common error, particularly around here, is to ignore the importance of dosage. Dosage at the receptor site is the difference between working great, doing nothing, or killing you.

IMO fish oil is the best form of omega 3 fatty acids which are considered by most to be a required nutrient. I'm a lazy guy and don't cook a lot of wild caught oily fish so I supplement to the extent to get the DHA plus EPA that the American Heart Association suggests for all Americans (about 0.5 mg DHA plus EPA per day).

Half a milligram? Are you sure that's not half a gram?

#13 niner

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Posted 29 June 2011 - 01:13 AM

I bet these eskimos are not megadosing on fish oil that they ordered from iherb. I bet they are getting it from the fish they eat. The previous post suggests that the astaxanthin in salmon is beneficial. This paper looked at levels of EPA and DHA in blood cells, and comes to the conclusion that people should take fish oil, presumably a lot of it. I think that's the wrong conclusion. What they were looking at wasn't a marker of fish oil consumption, it was a marker of having a particular sort of diet. Maybe the conclusion should have been that people should eat a high-fish paleo diet, or whatever it was. The native peoples who are suffering from high rates of metabolic syndrome are eating crappy industrial diets. A crappy industrial diet plus fish oil is still crappy.

It is not about diet, it is about the level of EPA/DHA in the blood. Bottom line, the Inuits had 20 times the level of EPA/DHA. EPA/DHA is supposed to be dangerous because it oxides easily. They had 20 times as much EPA/DHA, so if EPA/DHA is dangerous why was their health superior? Why aren't they showing the ill effects of 20 times as much dangerous malondialdehyde?

I think that the only reason they have that level of EPA/DHA in their blood is because they eat what is essentially a fish-based paleo diet. The people with metabolic syndrome are getting it from industrial diets that don't provide these lipids. Further, if the healthy people are eating a lot of salmon, then the astaxanthin is protecting them from the lipid oxidation products. Fundamentally, I contend that the vast majority of the health markers discussed in the paper were good because of the diet, not because of the fish oil. As far as the malondialdehyde question, maybe it doesn't effect the health markers they looked at, though it still may be doing damage. Or maybe the astaxanthin took care of it. Or maybe it's a second-order effect that just isn't as important as the macronutrient ratios of your diet.

#14 Robert C

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Posted 29 June 2011 - 01:46 AM

Oops! Yes I meant to say that the American Heart Association recommends about 0.5 GRAMS of DHA plus EPA per day for all Americans.

#15 nameless

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Posted 29 June 2011 - 09:34 PM

Yes there is 3 mcg of astaxanthin per gel in the New Chapter fish oil. I agree that it does not seem like much but I don't know the order of magnitude of an effective amount. The oil is noticably darker than other fish oils. New Chapter claims the pigment is from the astaxanthin.

Well, it won't hurt, but just not sure it is doing much.

As a comparison, a serving of Atlantic salmon has around 1-2mg of astaxanthin.

Sockeye has 4mg per serving. And most astaxanthin supplements are 4 mg.

Note the difference is quite large... mcg vs mg. I wouldn't worry about it though, as there are other antioxidants in the product too and your dose is reasonable.

#16 nameless

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Posted 06 July 2011 - 07:18 PM

I bet these eskimos are not megadosing on fish oil that they ordered from iherb. I bet they are getting it from the fish they eat. The previous post suggests that the astaxanthin in salmon is beneficial.
---
Further, if the healthy people are eating a lot of salmon, then the astaxanthin is protecting them from the lipid oxidation products.


Does anyone happen to know of any studies looking at the the avg. astaxanthin intake by either Eskimo or Japanese populations?

I'm curious as to what supplemental dose would equate to dietary levels. I stated the approx. astaxanthin equivalent to a serving of salmon above in this thread, but I have no idea how much salmon certain fish-eating populations eat.

I'm wondering if perhaps a low-dose astaxanthin supplement, maybe taken every other day (think it has around a 20hr or so half-life), would equate to dietary intakes of fish eating populations.

Edited by nameless, 06 July 2011 - 07:20 PM.


#17 david ellis

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Posted 07 July 2011 - 08:15 PM

Does anyone happen to know of any studies looking at the the avg. astaxanthin intake by either Eskimo or Japanese populations?

I'm curious as to what supplemental dose would equate to dietary levels. I stated the approx. astaxanthin equivalent to a serving of salmon above in this thread, but I have no idea how much salmon certain fish-eating populations eat.

I'm wondering if perhaps a low-dose astaxanthin supplement, maybe taken every other day (think it has around a 20hr or so half-life), would equate to dietary intakes of fish eating populations.

With the dietary intake of EPA/DHA grams in the study linked above you might be able to estimate how much fish they ate, and thus how much astaxanthin was in their diet.
From the study linked in my post above.
3.7 (eskimos) compared with 0.14 g/d in men (US)
2.4 (eskimos) compared with 0.09 g/d in women (US)

The protective effect of 4 mg of my daily astaxanthin could explain why my consumption of one gram of EPA/DHA was not harmful. My malondialdehyde levels were low because astaxanthin protected EPA/DHA from oxidation. Apparently it is safe to supplement fish oil if you also supplement astaxanthin.

#18 nameless

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Posted 07 July 2011 - 09:13 PM

With the dietary intake of EPA/DHA grams in the study linked above you might be able to estimate how much fish they ate, and thus how much astaxanthin was in their diet.
From the study linked in my post above.
3.7 (eskimos) compared with 0.14 g/d in men (US)
2.4 (eskimos) compared with 0.09 g/d in women (US)

The protective effect of 4 mg of my daily astaxanthin could explain why my consumption of one gram of EPA/DHA was not harmful. My malondialdehyde levels were low because astaxanthin protected EPA/DHA from oxidation. Apparently it is safe to supplement fish oil if you also supplement astaxanthin.


Thing is, I'll assume they also ate other fish too besides salmon, so I'm not sure how to figure out astaxanthin content just based on their Omega 3 levels.

4mg would equate to 1-4 servings of Atlantic salmon daily, which would seem at least semi-reasonable for an eskimo, I guess? Again, not sure. Maybe they don't eat salmon year-round?

And it could even be possible vitamin E or other antioxidants protect against oxidation as well as astaxanthin. At least most fish oils contain various antioxidants already. A fish oil + astaxanthin supplement could make sense though, if trying to mimic salmon consumption -- assuming algae astaxanthin is the same as what appears in food.

#19 david ellis

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Posted 07 July 2011 - 10:01 PM

And it could even be possible vitamin E or other antioxidants protect against oxidation as well as astaxanthin. At least most fish oils contain various antioxidants already. A fish oil + astaxanthin supplement could make sense though, if trying to mimic salmon consumption -- assuming algae astaxanthin is the same as what appears in food.


I am having trouble thinking globally, I should have also disclosed that I take 300 mg of Rosemary extract, and 500 mg of Gamma E powder (slightly less than 1/2 of BAC's recomended dose) and 133 mg of Tocotrienol Beadlets (of which BAC recommends a 666 mg dose) and 500 mg of Vitamin C for a total list of my antioxidants. At age 72, I think these are reasonable amounts. All of the powders are taken mixed with coconut oil.

#20 nupi

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Posted 08 July 2011 - 11:14 AM

So would we still get the benefits from supplementing Astaxanthin individually or are we more worried about oxidation before it enters our body? In any case, Astaxanthin seems to be a rather pricy single antioxidant (like 20 cent per 4mg pill...)

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#21 pycnogenol

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Posted 08 July 2011 - 03:00 PM

So would we still get the benefits from supplementing Astaxanthin individually or are we more worried about oxidation before it enters our body?
In any case, Astaxanthin seems to be a rather pricy single antioxidant (like 20 cent per 4mg pill...)


Astaxanthin isn't too pricey; I spent $46 for a 300-day supply. I take my Astaxanthin with Omega-3.

http://www.iherb.com...gels/30648?at=0

Comes to around 15 cents per day which is reasonable.

Edited by pycnogenol, 08 July 2011 - 03:02 PM.





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