23 replies to this topic

[nootropi]

Link

[brooklynjuice]

We had this up on our site YEARS ago. We even studied the addition of other key anti-oxidants and came up with quite a stack (that many sites then stole for profit) by adding green tea extract and CLA and/or proper ration fish oils.

[drmz]

does one really need ®-alpha-lipoic acid with ALCAR if you're also taking 3gr Vit C and Theanine as an anti-oxidant ?

[lynx]

Yeah, you need a mitochondrial anti-oxidant. The ones tested by Ames so far that were effective were NAC, ALA, PBN, NtBHA.

[scottl]

Lynx,

NAC works as a mitochondrial anti-oxidant i.e. it could be used alone with ALCAR without taking any of the above?

[nagaki]

The function of RLA is not only as an antioxidant, it has so many other functions that are equally, if not more, important.

[lynx]

Lynx,

NAC works as a mitochondrial  anti-oxidant i.e. it could be used alone with ALCAR without taking any of the above?

Yeah, I read it over at Avant, Spook posted it.

Then I checked pubmed and it works in the mitochondria as well as interstitially and intracellularly.

One thing about NAC is that it is best to use 3:1 Ascorbic Acid/NAC. Ascorbic acid assists in reducing NAC so that it can get back in the battle and also so that it doesn't become a prooxidant.

Biochemistry. 2004 Jul 6;43(26):8494-502. Related Articles, Links 

 
Modulation of mitochondrial complex I activity by reversible Ca2+ and NADH mediated superoxide anion dependent inhibition.

Sadek HA, Szweda PA, Szweda LI.

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.

Complex I, a key component of the mitochondrial respiratory chain, exhibits diminished activity as a result of cardiac ischemia/reperfusion. Cardiac ischemia/reperfusion is associated with increases in the levels of mitochondrial Ca(2+) and pro-oxidants. In the current in vitro study, we sought evidence for a mechanistic link between Ca(2+), pro-oxidants, and inhibition of complex I utilizing mitochondria isolated from rat heart. Our results indicate that addition of Ca(2+) to solubilized mitochondria results in loss in complex I activity. Ca(2+) induced a maximum decrease in complex I activity of approximately 35% at low micromolar concentrations over a narrow physiologically relevant pH range. Loss in activity required reducing equivalents in the form of NADH and was not reversed upon addition of EGTA. The antioxidants N-acetylcysteine and superoxide dismutase, but not catalase, prevented inhibition, indicating the involvement of superoxide anion (O2(*-)) in the inactivation process. Importantly, the sulfhydryl reducing agent DTT was capable of fully restoring complex I activity implicating the formation of sulfenic acid and/or disulfide derivatives of cysteine in the inactivation process. Finally, complex I can reactivate endogenously upon Ca(2+) removal if NADH is present and the enzyme is allowed to turnover catalytically. Thus, the present study provides a mechanistic link between three alterations known to occur during cardiac ischemia/reperfusion, mitochondrial Ca(2+) accumulation, free radical production, and complex I inhibition. The reversibility of these processes suggests redox regulation of Ca(2+) handling.

PMID: 15222760 [PubMed - indexed for MEDLINE]

Also, check out this cool study of how Ascorbic Acid, once oxidized can boost Glutathione. Also ascorbic acid can diffuse into mitochondria.

http://www.fasebj.or...full/14/10/1352

[lynx]

does one really need ®-alpha-lipoic acid  with ALCAR if you're also taking 3gr Vit C and Theanine as an anti-oxidant ?

It appears that I could have been wrong in saying you need a mito anti-ox, as Vit C diffuses into mitochondria.

[stellar]

One thing about NAC is that it is best to use 3:1 Ascorbic Acid/NAC. Ascorbic acid assists in reducing NAC so that it can get back in the battle and also so that it doesn't become a prooxidant.

Does it have to be that form? What about Calcium ascorbate ("Ester C")?

That is the same ratio that Durk and Sandy recommend for preventing hangovers, 200mg NAC and 600mg Calcium Ascorbate per drink.

[stellar]

So is it possible to use Vitamin C and NAC along with ALCAR instead of ALA?

[lynx]

Ester C will work fine, in your stomach it dissociates from the calcium.

Regarding Lipoic acid, as someone pointed out there are a lot of other good reasons to use ALA.

[stellar]

Is Glutathione a mitochondrial antioxidant? I ask this because both ALA and NAC raise glutathione, and both are mitochondrial antioxidants. It's likely quite possible to use NAC+Vitamin C along with ALCAR instead of ALA. One other interesting thing, Rhodiola Rosea is a mitochondrial antioxidant as well....or says LEF. I could have sworn I read that in one of their recent magazines, in an ad for Mitochondrial Energy Optimizer. I just looked online at their website and the information wasn't in the ad. The online ad may be outdated, because in the magazine it has the "SOD zyme" which is missing online.

I've grown tired of the whole ALA vs R-ALA vs K-R-ALA thing so I'm staying away from purchasing any until a later date.

As stated before, I wonder if Garlic boosts glutathione (sulfur)?

[stellar]

Hmm...I guess this answers my question about Garlic and Glutathione!!


1: Toxicology. 1999 Feb 15;132(2-3):215-25. Related Articles, Links

Treatment with aged garlic extract protects against bromobenzene toxicity to precision cut rat liver slices.

Wang BH, Zuzel KA, Rahman K, Billington D.

School of Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

Precision-cut liver slices from phenobarbital-induced rats were incubated for 6 h with the model hepatotoxin bromobenzene (BB) at a final concentration of 1 mM. Severe toxicity was indicated by a decreased K+, adenosine triphosphate and glutathione (GSH) content of the slices, increased release of alanine aminotransferase and lactate dehydrogenase into the medium, and increased formation of thiobarbituric acid reacting substances. Pretreatment of animals for 7 days with aged garlic extract (AGE) (Kyolic) at doses of 2 and 10 ml/kg/day dramatically reduced the toxicity of BB in a dose-dependent manner. The GSH content of liver slices from rats treated with AGE at 2 or 10 ml/kg/day increased by 50 and 80%, respectively. The BB-induced decrease in GSH content was less in slices derived from AGE-treated rats compared with slices from control rats. Pretreatment with AGE did not affect cytochrome P450 when assayed as 7-ethoxycoumarin O-deethylase and 7-pentoxyresorufin O-depentylase activities in hepatic microsomes. Thus, the mechanism by which pretreatment with AGE protects against BB hepatotoxicity involves both an elevation of hepatic GSH content, and a GSH sparing effect, possibly due to conjugation of organosulphur compounds in AGE with toxic BB metabolites. Only this GSH sparing effect was seen in our earlier study on the in vitro hepatoprotective effect of AGE [Wang et al., 1998. Toxicology 126, 213-222].

PMID: 10433384 [PubMed - indexed for MEDLINE]

[Chip]

There appears to be lots of in vitro and animal studies cited to support the claims of ALCAR and ALA. Any one got some direct links to the studies on humans? Bruce Ames refers to a couple at the close of the following November 2004 abstract but I've yet to get any closer to looking at the original research. Maybe I could find them via the citations at Ames web site?

Abstract located at Pub-Med http://www.ncbi.nlm....trez/query.fcgi?
Original source cited as Ann N Y Acad Sci. 2004 Nov;1033:108-16

Delaying the mitochondrial decay of aging with acetylcarnitine.

Ames BN, Liu J.

Nutritional Genomics Center, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. bames@chori.org

Oxidative mitochondrial decay is a major contributor to aging. Some of this decay can be reversed in old rats by feeding them normal mitochondrial metabolites, acetylcarnitine (ALC) and lipoic acid (LA), at high levels. Feeding the substrate ALC with LA, a mitochondrial antioxidant, restores the velocity of the reaction (K(m)) for ALC transferase and mitochondrial function. The principle appears to be that, with age, increased oxidative damage to protein causes a deformation of structure of key enzymes with a consequent lessening of affinity (K(m)) for the enzyme substrate. The effect of age on the enzyme-binding affinity can be mimicked by reacting it with malondialdehyde (a lipid peroxidation product that increases with age). In old rats (vs. young rats), mitochondrial membrane potential, cardiolipin level, respiratory control ratio, and cellular O(2) uptake are lower; oxidants/O(2), neuron RNA oxidation, and mutagenic aldehydes from lipid peroxidation are higher. Ambulatory activity and cognition decline with age. Feeding old rats ALC with LA for a few weeks restores mitochondrial function; lowers oxidants, neuron RNA oxidation, and mutagenic aldehydes; and increases rat ambulatory activity and cognition (as assayed with the Skinner box and Morris water maze). A recent meta-analysis of 21 double-blind clinical trials of ALC in the treatment of mild cognitive impairment and mild Alzheimer's disease showed significant efficacy vs. placebo. A meta-analysis of 4 clinical trials of LA for treatment of neuropathic deficits in diabetes showed significant efficacy vs. placebo.

[lemon]

Aside from being a universal antioxidant (fat & water soluble whilst regenerating other antioxidants and boosting the most powerfull endogenous antioxidants) lipoic acid is capable of de-oxidizing cellular and intracelluler (mitochondrial) free radicals.

Lipoic Acid is more to mitochondrial free radical scavenging. Don't forget it powers up the Krebs cycle! (I don't see NAC doing that... in addition NAC will become pro-oxidant if you take too much... say if you're taking more than 600mg) [thumb]

[Steve_86]

Sorry for the bump if this is discussed elsewhere.


What do you guys consider to be the optimum dosage mixture for R-ALA and ALCAR?

Currently I am dosing:
2x100mg K-RALA (Geronova research)
Approximately 700mg ALCAR 30-40 minutes later
Then another 200mg K-RALA 30 mins after

[nowayout]

does one really need ®-alpha-lipoic acid with ALCAR if you're also taking 3gr Vit C and Theanine as an anti-oxidant ?

No, it is probably not necessary to take ALA with ALCAR as long as your ALCAR dosage is not so high as to be less effective than a lower dosage anyway. This paper contains a dose ranging study that found that the kinds of ALCAR doses that would necessitate coadministration of ALA to prevent oxidative damage are less effective than lower ALCAR dosages which do not increase markers of oxidative damage:

Delaying Brain Mitochondrial Decay and Aging with Mitochondrial Antioxidants and Metabolites
JIANKANG LIU, HANI ATAMNA, HIROHIKO KURATSUNE, AND BRUCE N. AMES

This is also discussed at http://cron-web.org/...ts-guide-5.html.

The main reason Ames et al needed to pair ALA with ALCAR in the original study was that the ALCAR dose (1.5% in drinking water, equivalent to about 12g in humans daily) was too high. In the above paper they actually found that both 0.15% (equiv 1.2g human) and 0.5% (equiv 4g human) were more effective than the higher dose, and did not increase markers of oxidative damage. Note that this was for old rats, and it stands to reason that the dosages have to be adjusted downward for middle aged or young rats or humans. This is discussed in the the thread http://www.imminst.o...o...c=26055&hl=

This is important to me as ALA is a big unknown and there are indications that it may cause harm by blocking certain beneficial endogenous adaptive responses (to CR or exercise) long term after stopping supplementation. I therefore think ALA is much too risky at this point.

[medicineman]

will you provide some literature or information regarding the dangers of ALA at the optimum 60mg/day?

[nowayout]

will you provide some literature or information regarding the dangers of ALA at the optimum 60mg/day?

Could I ask where this optimum is taken from? I would be very interested in any dose-ranging study on healthy humans (or rats for that matter) with respect to ALA.

The studies I am referring include the one discussed at http://www.imminst.o...xidative stress, which shows that antioxidants including ALA can block beneficial adaptations due to exercise. I have only seen the abstract, which does not state dosages or whether ALA was tested alone as opposed to in a cocktail. But you can easily find a significant number of studies showing that mega-doses of various antioxidants block beneficial exercise adaptations. It is quite possible that that 60mg of ALA may qualify as a megadose. Quantitative information on the ALA content of food sources is lacking.

What is particularly worrisome about ALA is that whatever it does to block endogenous adaptations may be effectively permanent, even once you have stopped taking it. The following study discusses such a lifelong side effect with respect to CR, but it is quite possible that it might apply to exercise adaptations and who knows what else:

Dietary lipoic acid supplementation can mimic or block the effect of dietary
restriction on life span
Brian J. Merry, Austin J. Kirk, Malcolm H. Goyns

The human-adjusted effective dose used was about 9g of racemic ALA, which contains 4.5g of R-ALA, but in the absence of dose-ranging studies, it is quite possible that the effect is already significant at your suggested dose of 60mg. There is just no way of knowing at this point.

Edited by andre, 08 December 2008 - 10:30 PM.

[Steve_86]

will you provide some literature or information regarding the dangers of ALA at the optimum 60mg/day?

What is particularly worrisome about ALA is that whatever it does to block endogenous adaptations may be effectively permanent, even once you have stopped taking it. The following study discusses such a lifelong side effect with respect to CR, but it is quite possible that it might apply to exercise adaptations and who knows what else:

Dietary lipoic acid supplementation can mimic or block the effect of dietary
restriction on life span
Brian J. Merry, Austin J. Kirk, Malcolm H. Goyns

The human-adjusted effective dose used was about 9g of racemic ALA, which contains 4.5g of R-ALA, but in the absence of dose-ranging studies, it is quite possible that the effect is already significant at your suggested dose of 60mg. There is just no way of knowing at this point.

Now im really scared =/

[medicineman]

the maximum dose which no adverse events noted for ala is 60 mg. thats where i got 60mg from.

yea, im gunna research that and provide feedback. oh well. trial and error and education. thats how i dont take vinpo and hup anymore. maybe add another to the list soon.... but not yet..

Edited by medicineman, 09 December 2008 - 11:27 PM.

[NDM]

the maximum dose which no adverse events noted for ala is 60 mg. thats where i got 60mg from.

yea, im gunna research that and provide feedback. oh well. trial and error and education. thats how i dont take vinpo and hup anymore. maybe add another to the list soon.... but not yet..

could you sum up in a sentence what's the main negative effect of Vinpo? I know only the positives.

[hamishm00]

I think he was referring to vinpo + huperzine at the same time.

[medicineman]

Vinpocetin has similar mode of activity as reserpine on catecholamines, as shown through evidence in increases dopamine metabolites in neural tissue. This means it might promote degrading of catecholamines. Reserpine degrades catecholamines, and hence it achieves its anti-hypertensive effects.

The brain requires a non-changing supply of blood, and this only changes during times of extremity or hallmark bodily changes, otherwise, the brain requires a steady supply of oxygen, hence you never hear of brain claudication, but the thighs or calves for example get achy and painful when oxygen supply is raised but not met, in the case of exercise or vascular disease. So, if your brain is not ischaemic, I see no point in taking vinpo. As a matter of fact, I see it harmful due to its catecholamine degrading effect. Catecholamines are as important in cognition as any other transmitter.

Hup-A directly antagonizes NMDA receptors, and most people hear take piracetam, which is NMDA modulator. So two drugs acting in opposition in a critical mode of memory formation. NMDA receptors are responsible for long term potentiation, and blocking them is not good in normal states, neither is overactivating them. But there is no point in blocking, and priming them. On its own huperzine gives a nice acute, but short lived effect of memory retention, because of acute increases in acetylcholine, but that goes away when receptor numbers change due to excess acetylcholine. Than when you come off it, you become like the candle that glowed so bright, it burned out, and you burn out for a while til you recover normality in you cholinergic system. That is not taking into consideration that by blocking off the NMDA receptors, you are less prone to long term potentiation, and hence all you get is the temporary short term memory. So overall, I would advice taking it possible once or twice a week, with no piracetam, possibly for its BDNF enhancing activity. Otherwise it does more harm than good.