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ALA blocks CR Life extension


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#1 Matt

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Posted 25 May 2008 - 07:54 PM


"An intriguing observation from this study is that alpha-lipoic acid can
continue to block the effect of DR feeding to extend survival for over a
year after its removal from the diet."


Well i never took ALA before going CR, but I was shocked by this result. ALA prevented the extension of lifespan from CR if it was taken prior to going on the diet, and the effect lasted a year? Maybe someone can do a good analysis of this paper?

Merry BJ, Kirk AJ, Goyns MH.
Dietary lipoic acid supplementation can mimic or block the effect of dietary
restriction on life span.
Mech Ageing Dev. 2008 Apr 22;129(6):341-348. [Epub ahead of print]
PMID: 18486188

Abstract

Dietary restriction feeding extends survival in a range of species but a
detailed understanding of the underlying mechanism is lacking. There is
interest therefore in identifying a more targeted approach to replicate this
effect on survival.

We report that in rats dietary supplementation with alpha-lipoic acid, has
markedly differing effects on lifetime survival depending upon the dietary
history of the animal. When animals are switched from DR feeding to ad
libitum feeding with a diet supplemented with alpha-lipoic acid, the
extended survival characteristic of DR feeding is maintained, even though
the animals show accelerated growth. Conversely, switching from ad libitum
feeding a diet supplemented with alpha-lipoic acid to DR feeding of the
non-supplemented diet, blocks the normal effect of DR to extend survival,
even after cessation of lipoic acid supplementation. Unlike the dynamic
effect of switching between DR and ad libitum feeding with a
non-supplemented diet where the subsequent survival trajectory is determined
by the new feeding regime, lipoic acid fixes the survival trajectory to that
established by the initial feeding regime.

Ad libitum feeding a diet supplemented with lipoic acid can therefore act as
mimetic of DR to extend survival.

Edited by Matt, 25 May 2008 - 08:03 PM.


#2 digfarenough

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Posted 25 May 2008 - 09:06 PM

That is indeed weird.

They used 12 groups of rats. All rats entered the experiment at age 2 months. A control group of 102 rats were fed ad libitum throughout their lives. Two large groups of dietary-restricted (DR) rats (75 rats/group) were food restricted to weight 55% of their age-matched controls: one of these two groups was supplemented with lipoic acid at 1.5g/kg body weight.
The other 9 groups (~25 rats per group) were started on one of the above, then switched to another at age 6 or 12 months.

The 6 month groups (4 groups) were:
ad lib -> DR
DR -> ad lib
ad lib + LA -> DR
DR -> ad lib + LA

The 12 month groups (5 groups) were the same as the above, plus one extra:
DR -> DR + LA

Results highlights:
* DR rats lived longer than ad lib rats (approx. 12% longer) regardless of whether LA was used in either group
* ad lib -> DR at 12 months of age showed essentially the same lifespan as DR rats (i.e. it didn't matter that they didn't start on dietary restriction until 12 months, they got basically the same benefit as if they had been on DR since 2 months old); DR -> ad lib at 12 months of age rats lost most of the benefits of DR (but there was a small residual benefit)
* ad lib + LA -> DR at 12 months rats did not gain the benefits of DR, ad lib + LA -> DR at 6 months did gain some of the benefits of DR
* DR -> ad lib + LA at 12 months had lifespans as if they were always DR, DR -> ad lib + LA at 6 months had lifespans of intermediate length (so partial continuing effects of DR)

They conclude that LA's effect might be described as locking in the survival trajectory of the animal, but they don't know why. They suggest it is not related to the anti-oxidant properties of LA. Possible mechanisms they mention: it has been implicated that LA can modify gene expression, LA regulates a number of transcription factors, LA can bind to DNA directly, and a few others.

One quote I found interesting: "Although DR feeding regimes have previously been considered to slow the accumulation of tissue damage, probably as a result of oxidative stress, the survival data from this study with that of Mair et al. (2003) and Spindler (2005) suggests strongly that DR feeding induces a state change in the organism that is associated with extended survival, rather than inducing a slower rate of damage accrual. Little or no memory effect on survival is seen when switching from a DR feeding regime to control feeding.

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#3 niner

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Posted 26 May 2008 - 04:29 AM

This is indeed weird. I have one question: Was it 1.5g/kg body weight, or was it 1.5g/kg food? Often when animals are dosed in their food, the dosage is described by the fraction of food weight. This would make a large difference, as 1.5g/kg body weight would be like a human taking over 100g ALA per day. At that level, there's no telling what might be going on.

#4 digfarenough

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Posted 26 May 2008 - 01:53 PM

This is indeed weird. I have one question: Was it 1.5g/kg body weight, or was it 1.5g/kg food? Often when animals are dosed in their food, the dosage is described by the fraction of food weight. This would make a large difference, as 1.5g/kg body weight would be like a human taking over 100g ALA per day. At that level, there's no telling what might be going on.


Oh, you might be right. I'm used to automatically reading things as a function of body weight. The relevant quote from the paper is: "The lipoic acid supplemented diet was the CRM diet enriched with a racemic mixture of dl-thioctic acid (Posted Image-lipoic acid) obtained from Fisher Scientific U.K., Limited, at 1.5 g/kg by the Special Diet Systems Division of Dietex International."

So your interpretation does fit that a bit better.

#5 niner

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Posted 27 May 2008 - 05:54 AM

Ok, so it sounds like the rats were taking a dose of LA that's comparable to what we take, then. That's worrisome.

My next question would be: What are the error bars on this data? Are they overstating things?

#6 Matt

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Posted 27 May 2008 - 12:38 PM

I have the paper here if anyone interested.

Edited by Matt, 27 May 2008 - 12:40 PM.


#7 steelheader

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Posted 28 May 2008 - 04:26 PM

For those of us who want to make a rational decision about continuing to use lipoic acid and Alcar, what are the current pros and cons? Is there a significant risk that lipoic acid with Alcar might work at cross purposes to resveratrol?

Thanks.

#8 Ghostrider

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Posted 28 May 2008 - 07:25 PM

Is there an anti-oxidant equally powerful to ALA? Or would substitute have the same effect? What extends life more: CR or anti-oxidant therapy?

#9 Guest_Kismet_*

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Posted 29 May 2008 - 04:09 PM

Is there an anti-oxidant equally powerful to ALA? Or would substitute have the same effect? What extends life more: CR or anti-oxidant therapy?

Counterquestion, did anyone ever extend life span using anti-oxidant therapy in any type of animal? (I am really curious myself!)

Michael implied (in a thread about deprenyl) the question is 'no' in otherwise healthy, well cared for animals and everything I've ever read points in the same direction.
Some feasible interventions that increase max. life span known to me include: CR, methionin restriction and IF/deprenyl/resveratrol (to some [minor] extent have shown max. life span extension, but the studies are very inconclusive and no definite evidence exists).
However, the case in humans may be MUCH more complicated and the 'conjectures' that anti-oxidants can extend max. life span *might* be true in humans?

Edited by Kismet, 29 May 2008 - 04:10 PM.


#10 edward

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Posted 30 May 2008 - 05:45 PM

I wonder if somehow the ALA is preventing some of the hormetic effect of CR


Edit: as in the protective effects of ALA prevent the body's own natural up-regulation of the systems that would protect it under the stress of Calorie Restriction... ie, the ALA tricks the body into thinking everything is ok so no need to adapt

Note also that humans have much better antioxidant and repair systems than rats and thus a little ALA might just be a drop in the bucket for us and may not make that much difference in terms of the over all "everything is ok"...

Edited by edward, 30 May 2008 - 06:14 PM.


#11 edward

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Posted 30 May 2008 - 06:08 PM

Matt,

Can you post a link to the paper or upload it?

#12 Matt

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Posted 31 May 2008 - 12:46 PM

Matt,

Can you post a link to the paper or upload it?


Email me at matt AT matthewlake.plus.com

and i'll send it.

#13 edward

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Posted 31 May 2008 - 05:54 PM

email sent
from itsmeithink AT gmail

#14 edward

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Posted 02 June 2008 - 04:45 AM

Here is the article

Compliments of Matt

I haven't read through all of it as it is rather dense but I will and anyone else who wants to plow through it some opinions would be beneficial as I think this is an important issue

Attached Files



#15 edward

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Posted 07 June 2008 - 05:29 AM

badump...

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#16 Mortuorum

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Posted 08 July 2009 - 09:01 PM

Here is the article

Compliments of Matt

I haven't read through all of it as it is rather dense but I will and anyone else who wants to plow through it some opinions would be beneficial as I think this is an important issue



Perhaps we should just take a lot of better researched compounds like NAC and other anti-aging substances instead of lipoics for now, as with all else, it's all so fickle, atop that RLA is so $$$$$$$$?!!........I wonder if the Sustained Release forms of NAC bear with them the same potential controversy of problematic that GeroNova and AOR were bickering over concerning QR and SR Lipoics a while back? Doesn't NAC actuate some similar mechanisms to Lipoics, anyway? Interesting as well to potentially note regarding AOR and GeroNova bickering a while ago over the efficacy of supplementing with the reduced form of RLA directly (DHLA) or taking RLA alone and allowing the body to convert it on its own that NAC is much more efficacious than supplementing with Reduced Glutathione. Any thoughts?

I don't think ALCAR is absolutely essential nor for everyone, some don't respond well to doses even after experimental variations of incrementation, there are certainly other alternatives to mitochondrial "charging"........



- M.

Edited by Mortuorum, 08 July 2009 - 09:05 PM.





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