LONGECITY

Pomegranate juice has a lot of documented human studies which are quite impressive (human study showed 30% reduction in artery plaque). I would consider it a must have especially considering the modest price.

Check out dukenukem's quotes in this thread:
http://www.imminst.o...e,and,plaque&s=

Pomegranate juice has a lot of documented human studies which are quite impressive (human study showed 30% reduction in artery plaque).  I would consider it a must have especially considering the modest price. 

Check out dukenukem's quotes in this thread:
http://www.imminst.o...e,and,plaque&s=

I freakin LOVE Pom juice. It's soo good. I get this occasionally at the local store.
http://www.pomwonderful.com ... contains no added sugars, preservatives or colors

It's just so damn expensive for such a small amount. If would be an extra $5 or so a day for a 8-12oz glass. I think its like $4-5'ish for 16oz. That would add up every day. They also have a kickass pure blueberry juice. Someday I wont have to budget.

Let me correct myself: When I said modest price I was referring to the modest price of the pomegranate extract I'm taking (pom40p from BAC) $9.50 for 500 doses. Whatever you decide make sure it's standardized on punicosides and not ellagic acid.

POMEGRANATE, P40p™ is a water soluble extract standardized to a minimum 40% punicosides polyphenols and has the exact ratio of phytochemical markers as in pomegranate juice.

This is an interesting post on resveratrol bioavailablitity:

http://groups.google...e6e0ad8fe958e3e

"Regarding Resveratrol :
http://www.sirtuins....-extension.html

FACT: Almost zero free resveratrol is found in the bloodstream after
oral dosing due to the conjugation of resveratrol with sulfur and
glucuronic acid in the liver. [1,2]

HYPOTHESIS: The evidenced effects of non-oral resveratrol dosing (for
example, in vitro or in vivo by injection) are not available by oral
resveratrol dosing.

Hypothesis Test:

Non-oral Resveratrol Effects
* Blood thinning [3]
* Ischemia protection [4]
* Life extension [5]

Oral Resveratrol Effects
* Blood thinning [6]
* Ischemia protection [7]
* Life extension [8]

ERGO: The hypothesis is falsified since there exists at least three
evidenced effects of non-oral resveratrol that appear to be available
by oral resveratrol. We are thus compelled to adopt the contrary
hypothesis: at least some (if not all) evidenced effects of non-oral
resveratrol are available by oral resveratrol. There are means by
which resveratrol may deliver effect despite hepatic conjugation, but
mechanisms are beyond the scope of this logico-empirical-results
analysis.

(This analysis is expressed in formal logic following its empirical
referents.)
______________________________________________________

[1] http://www.hubmed.or...i?uids=15779070
[2] http://www.hubmed.or...i?uids=12554065

Non-oral Resveratrol Effects:

[3] British Journal of Pharmacology (1999): "trans-Resveratrol
inhibits human platelet aggregation both in vitro and in vivo."
http://www.nature.co...l/0702749a.html

[4] Brain Research (2003): "Resveratrol was injected i.p. (30 mg/kg
body weight) [...] This study demonstrated for the first time that
resveratrol, a polyphenolic antioxidant, can cross the blood-brain
barrier and exert protective effects against cerebral ischemic
injury."
http://www.hubmed.or...i?uids=12470882

[5] Nature (2003): "In yeast, resveratrol mimics calorie restriction
by stimulating Sir2, increasing DNA stability and extending lifespan
by 70%." NOTE: This is an instance of non-oral dosing because yeast
are ahepatic.
http://www.nature.co...ature01960.html

Oral Resveratrol Effects:

[6] Clinica Chimica Acta (1996): "studies were performed on 24 healthy
males aged 26-45 years [...] commercial juice lowered the IC50 for
thrombin (P < 0.001) whereas the resveratrol-enriched juice caused a
dramatic increase (P < 0.001). [...] We conclude that
trans-resveratrol can be absorbed from grape juice in biologically
active quantities and in amounts that are likely to cause reduction in
the risk of atherosclerosis."
http://www.hubmed.or...gi?uids=8814965

[7] Life Sciences (2005): "Male Balb/C mice were treated with
resveratrol for 7 days (50 mg/kg, gavage). [...] elevated levels of
MMP-9 were significantly attenuated in the resveratrol-treated mice as
compared to the vehicle MCAo mice. The study suggests that resveratrol
has protective effects against acute ischemic stroke." NOTE: Feeding
by "gavage" is tube-to-stomach feeding, which does not bypass the
liver.
http://www.hubmed.or...i?uids=16321402

[8] Current Biology (2006): "120 mg/g [ resveratrol / food ] caused an
increase of median and maximum lifespan of 33% and 27%, respectively
(p < 0.001, log rank test), and 600 mg/g food induced 56% and 59%
increase in median and maximum lifespan, respectively (p < 0.001, log
rank test). 600 mg/g food was significantly more effective than 120
mg/g food in prolonging lifespan (p = 0.01, log rank test)."
http://www.hubmed.or...i?uids=16461283

Progress of resveratrol life-extension research:
http://www.longevine...iments_full.jpg

______________________________________________________

Translating the hypothesis into formal logic for evaluation where

N = non-oral resveratrol dosing
O = oral resveratrol dosing

HYPOTHESIS: The evidenced effects of N are not available by O.

HYPOTHESIS-TEST STATEMENT:
If X is an effect of N, then X is not an effect of O.

Fleshing out that statement for clarity of translation:

For any effect X and any studies x and y, if x uses N and x finds X,
then it is NOT the case that if y uses O, y finds X.

Now translating it into second-order predicate logic:

(X)(x)(y)[ (Nx & Xx) -> ~(Oy -> Xy) ]

(I'll avoid stipulating that x =/= y for brevity)
Now instantiating it step-by-step into the first empirical case where

B = found blood-thinning
a = study [3]
b = study [6]

1. (X)(x)(y)[ (Nx & Xx) -> ~(Oy -> Xy) ]
2. (x)(y)[ (Nx & Bx) -> ~(Oy -> By) ]
3. (y)[ (Na & Ba) -> ~(Oy -> By) ]
4. (Na & Ba) -> ~(Ob -> Bb)

And then applying two replacement rules to step 4:

4. (Na & Ba) -> ~(Ob -> Bb)
5. (Na & Ba) -> ~(~Ob v Bb) - conditional exchange
6. (Na & Ba) -> (Ob & ~Bb) - de Morgan's

Now by the semantics of predicate logic we can see that the
hypothesis-test statement is false by observing that its antecedent
(Na & Ba) is true (study [3] has the properties N and B), yet its
consequent is false because in fact b (study [6]) has the properties O
and B. However, according to the hypothesis-test statement, b must
have the property ~B. So it turns out that ~Bb is false since Bb is
true, and thus the consequent (Ob & ~Bb) is false since one of its
conjuncts is false. Therefore, with a true antecedent and false
consequent, the whole statement (Ba & Na) -> (Ob & ~Bb) is false, and
thus the hypothesis is falsified by this single case alone.
Instantiating the hypothesis-test statement into the other two cases
cited above follows same steps to the same result.

Because the hypothesis is falsified we must by logical consequence
adopt the contrary: at least some (if not all) evidenced effects of
non-oral resveratrol are available by oral resveratrol.

http://www.IanGoddard.net "

The quote was for alcar. Here is more info on alcar from LEF. The 1.5g to 3g is pretty consistent across multiple sources, btw.

Most of that was in various disease states, though. While I don't think that doses like this would hurt you, some people might find themselves getting pretty jacked up. ALCAR can modulate glucocorticoid receptor function, resulting in steroid-like immunomodulatory effects. In particular it can cause mood elevation, similar to a steroid like prednisone. It does for me, that's for sure. I see the effect at 1 gram a day, so at 3g, I'd expect to be pretty cranked. Your mileage may vary... I suspect that what a lot of people think is a purely mitochondrial "energy boost" is partially or mostly a GR effect.

ERGO: The hypothesis is falsified since there exists at least three evidenced effects of non-oral resveratrol that appear to be available by oral resveratrol. We are thus compelled to adopt the contrary hypothesis: at least some (if not all) evidenced effects of non-oral resveratrol are available by oral resveratrol. There are means by which resveratrol may deliver effect despite hepatic conjugation, but mechanisms are beyond the scope of this logico-empirical-results analysis.

Sheesh, this guy Goddard has certainly found a long-winded way to say: Yup, oral resveratrol is absorbed. I don't think that's ever been a point of debate.
Edited by niner, 09 March 2007 - 04:21 AM.

Sheesh, this guy Goddard has certainly found a long-winded way to say:  Yup, oral resveratrol is absorbed.  I don't think that's ever been a point of debate.

Human oral resveratrol bioavailability is hugely debated.

Human oral resveratrol bioavailability is hugely debated.

By absorption I just meant that it makes it past the gut. It still has to make it past the liver, and that's the source of most (all?) of the conjugation, resulting in poor ultimate bioavailability.

Yes, bioavailability is a very gray area WRT humans. Yet given the significant effects it has produced in rodent studies when given PO, it seem unlikely to be entirely unabsorbed by humans. Still, the best method of PO dosing to ensure optimizing absorption remains TBD. The rodents in Sinclair's studies had 60% fat diets, but
perhaps absorption is better when consumed with alcohol, other dietary OPCs, etc.,
as well.

Alpine

HIGHLY doubt that some of these companies putting out sustained release products are actually producing the same type of muti-layered, enteric coated time release tablets that pharmas put out (expensive process). If your time release ALA in a cap you can be pretty sure its bullshit.

I saw a patent (and the abstract of a paper) for mixing chitin or chitosan (forget which) with ALA; initially, the ALA on the outside of the mixture was released when the capsule dissolved, resulting in a spike in plasma ALA; some hours later, the chitosan dissolved, releasing more ALA resulting in a second spike. Hardly sustained release, but cheap, low tech, and better than nothing.

The other cheap method I've seen is to just mix it with carnuba wax and hope for the best; as the wax dissolves in the gut, it is supposed to steadily release ALA (or other supplement; time release C is delivered this way, I believe.) Problem, release is inconsistent, especially if the mixture is not made properly. A bolus of wax releasing acidic ALA can lodge in one spot in one's intestine, and I imagine it could do some damage, perhaps resulting in ulceration with chronic use.

I think the evidence for time-release ALA is very thin, based on inferences that may well be unfounded. Unless there are studies demonstrating the necessity, I will continue to use multiple doses throughout the day.

health-nutty:

Human oral resveratrol bioavailability is hugely debated.

IMO, the debate is over: the glucorinated form is carried from the liver through the blood into the cells, which we can infer from the Sinclair rodent studies, where oral resveratrol proved to be highly active. I'd assume it's deglucorinated once in the cell, where it binds to the SIRT genes.

Max, personally I agree with you.

HIGHLY doubt that some of these companies putting out sustained release products are actually producing the same type of muti-layered, enteric coated time release tablets that pharmas put out (expensive process). If your time release ALA in a cap you can be pretty sure its bullshit.

I saw a patent (and the abstract of a paper) for mixing chitin or chitosan (forget which) with ALA; initially, the ALA on the outside of the mixture was released when the capsule dissolved, resulting in a spike in plasma ALA; some hours later, the chitosan dissolved, releasing more ALA resulting in a second spike. Hardly sustained release, but cheap, low tech, and better than nothing.
[...]
I think the evidence for time-release ALA is very thin, based on inferences that may well be unfounded. Unless there are studies demonstrating the necessity, I will continue to use multiple doses throughout the day.

Human oral resveratrol bioavailability is hugely debated.

IMO, the debate is over: the glucorinated form is carried from the liver through the blood into the cells, which we can infer from the Sinclair rodent studies, where oral resveratrol proved to be highly active. I'd assume it's deglucorinated once in the cell, where it binds to the SIRT genes.

And I'm sure that alpine has done the pharmacokinetic studies to prove that bombastic statement.

I know the timed release ALA paper that you're talking about. It's not really two spikes, it's smoother than that. The first wave is ALA leaching out of the chitosan matrix, and the second is from enzymatic degradation of the chitosan in the colon. This sort of biphasic kinetics is also seen in cases of entero-hepatic recycling, where the liver conjugates the drug and secretes it into the bile, then microbial enzymes in the gut cleave off the conjugates and the drug is reabsorbed.

When you say the evidence for time-release ALA is thin, do you mean evidence of clinical benefit, or evidence that the time-release formulations work to maintain blood levels? That these formulations work is unambiguous; the pharmacokinetics has been measured for both plain and time-release ALA, and they do provide elevated ALA concentrations for an extended period. In a study posted upthread, diabetics had a 10% improvement in a parameter related to glucose control from time-release compared to regular ALA. That would be enough to get an endocrinologist's attention, and ensure the time-release version a spot in any formulary. Most people have a hard time taking pills frequently. Once or twice a day is pretty easy, but beyond that, compliance really starts to suffer. Admittedly, a lot of us are more motivated than the average patient. Plain ALA has been shown to work well enough with diabetics, but I don't think anyone has a handle on the function of plain versus time-release as a mitochondrial antioxidant. Since I'm taking ALCAR, I'd rather be safe than sorry.

I don't think there is any debate on resveratrol bioavailability. Absorption is good, but it is highly conjugated in the liver so free resveratrol in the serum is less than 2%. It doesn't get de-conjugated in the cells as far as I know; I think the whole effect is due to the minimal free fraction. If the entire dose made it into the cells, we could probably get by with 10mg/d instead of 500.

.....

When you say the evidence for time-release ALA is thin, do you mean evidence of clinical benefit, or evidence that the time-release formulations work to maintain blood levels?

I mean evidence that serum levels need to be maintained uniformly. not to mention cellular levels. Does it recycle itself like PBN? I doubt it. We need good data on the half life both serum and intra-cellular, no? Or do you have some?

That these formulations work is unambiguous; the pharmacokinetics has been measured for both plain and time-release ALA, and they do provide elevated ALA concentrations for an extended period.  In a study posted upthread, diabetics had a 10% improvement in a parameter related to glucose control from time-release compared to regular ALA.  That would be enough to get an endocrinologist's attention, and ensure the time-release version a spot in any formulary.  Most people have a hard time taking pills frequently.  Once or twice a day is pretty easy, but beyond that, compliance really starts to suffer.  Admittedly, a lot of us are more motivated than the average patient.  Plain ALA has been shown to work well enough with diabetics, but I don't think anyone has a handle on the function of plain versus time-release as a mitochondrial antioxidant.  Since I'm taking ALCAR, I'd rather be safe than sorry.

That was my original concern. PBN or n-tert butyl hydroxylamine might be more effective for this purpose. AFAIK, Ames papers on R-ALA are the only work showing R-ALA protects mitochondria from ROS.

I don't think there is any debate on resveratrol bioavailability.  Absorption is good, but it is highly conjugated in the liver so free resveratrol in the serum is less than 2%.  It doesn't get de-conjugated in the cells as far as I know; I think the whole effect is due to the minimal free fraction.  If the entire dose made it into the cells, we could probably get by with 10mg/d instead of 500.

Hmn. I had assumed it was de-conjugated somehow to get into the cells. The acetylated form hangs around in the cells, releasing resveratrol as it is de-acetylated. Sort of intra-cellular time release. But we know reasonably well that resveratrol works, by whatever mechanism it is absorbed.

Alpine
I saw a patent (and the abstract of a paper) for mixing chitin or chitosan (forget which) with ALA; initially, the ALA on the outside of the mixture was released when the capsule dissolved, resulting in a spike in plasma ALA;  some hours later, the chitosan dissolved, releasing more ALA resulting in a second spike.  Hardly sustained release, but cheap, low tech, and better than nothing.

The other cheap method I've seen is to just mix it with carnuba wax and hope for the best; as the wax dissolves in the gut, it is supposed to steadily release ALA (or other supplement; time release C is delivered this way, I believe.)  Problem, release is inconsistent, especially if the mixture is not made properly.  A bolus of wax releasing acidic ALA can lodge in one spot in one's intestine, and I imagine it could do some damage, perhaps resulting in ulceration with chronic use. 

I think the evidence for time-release ALA is very thin, based on inferences that may well be unfounded.  Unless there are studies demonstrating the necessity, I will continue to use multiple doses throughout the day.

health-nutty:
IMO, the debate is over: the glucorinated form is carried from the liver through the blood into the cells, which we can infer from the Sinclair rodent studies, where oral resveratrol proved to be highly active.  I'd assume it's deglucorinated once in the cell, where it binds to the SIRT genes.

Hugely informative - and also, goes along the lines of what I was saying. Dont place HUGE amounts of faith in legit "time release" ALA coming from a small, unregulated supplement company. This is the kind of questioning and discussion I was trying to foster. Like I said, the only ones looking out for our wallets are ourselves. [thumb] Thanks....

maxwatt, May I ask how you break up/dose/administer your ALA/R-ala dosage? Also how much ALCAR a day do you take? Care to make comments/critique my stack in the first post?
Also, how much Biotin is enough? I believe my multi only has 30mcg. * Update: Responded via PM, thank you.



Niner - trying to validate time release ALA in its current form (cheap, bunk) simply because you use it or backed it openly is pretty weak. It's ok to be wrong. It's not ok to be stubborn. I dont have to PROVE anything buddy. In fact, its those selling time release (and you) that have the burden to prove its worth our extra money. If it was sustained release tablets made by a huge pharma things might be different. We know how this industry works. If you have another motive, let it be known. The facts are before you. I don't know how you can deny them. As I have said, just trying to keep it real here...
Edited by alpine, 14 March 2007 - 05:48 PM.

Niner - trying to validate time release ALA in its current form (cheap, bunk) simply because you use it or backed it openly is pretty weak. It's ok to be wrong. It's not ok to be stubborn. I dont have to PROVE anything buddy. In fact, its those selling time release (and you) that have the burden to prove its worth our extra money. If it was sustained release tablets made by a huge pharma things might be different. We know how this industry works. If you have another motive, let it be known. The facts are before you. I don't know how you can deny them. As I have said, just trying to keep it real here...

Alpine, what exactly is your problem, 'roid rage? You come in here insulting people left and right, and make outlandish claims that you have absolutely no evidence for. You think companies like AOR or Jarrow are selling bunk? The kind of pharmacokinetic studies to prove that a time release formulation works are well within the capabilities of outfits like that. That kind of testing can be contracted out. Hell, when I was a grad student I was one of the subjects in just such a study. I took a pill then got my blood drawn periodically for a day through an indwelling catheter. They paid me $350 bucks, not bad at the time for trying a new formulation of ibuprofen. And alpine, no one is telling you or anyone else to buy anything. The facts are indeed before us, in a place called the scientific literature. The problem is, between you and I, only one of us has the training and experience to read and evaluate those facts. And it ain't you.

I do have a motive here, and I'll be happy to let it be known: It's getting to the truth regarding life extension drugs, and keeping things evidence based and fact based. Sometimes that means slapping down rude yahoos who spew evidence-free crap in this forum.

I mean evidence that serum levels need to be maintained uniformly. not to mention cellular levels. Does it recycle itself like PBN? I doubt it. We need good data on the half life both serum and intra-cellular, no? Or do you have some?

I wish I had data on intra-cellular concentrations. That's really the nub of it. We do have good data on serum concentrations, that's easy enough, but for intracellular data I suppose you'd need to radiolabel the ligand, and get tissue counts. That's a lot of work. There might be easier ways, but that's not something I've ever done. Empirically, you can point to all the diabetes work that's been done with quick release ALA. It gets results, so something good is happening. My concern was that ALCAR is both actively transported into the mitochondria, and is also recycled from the kidney. The ALCAR dose is going to get into the mitochondria and stay for a while. On the other hand, ALA gets in, as far as I'm aware, by passive diffusion. If the serum levels go down, that process has little if any driving force, and it should diffuse right back out. ALA is not recycled that I'm aware of. The modest hydrophobicity of ALA means that it will not be strongly held in either the lipid or aqueous compartments, though it should favor lipid somewhat. There is a transporter called the Na+ dependent multivitamin transporter which biotin and lipoate are both substrates of, but I think it's only in the gut. (This is where the interference with biotin absorption comes from) Lipoic acid does cross the BBB; perhaps there is some accumulation in neural tissue? only speculating. Anyway, the above theoretical concern is what causes me to choose time release ALA for my own use. The mailman and the fedex man both paid me a visit today, and dropped off 4 bottles of time-release ALA. Some R from AOR and a new racemic time release from Source Naturals. It's much cheaper than AOR. When I opened the box from FedEx, the bottles were warm to the touch. It was only in the mid 70s today. Is there such a thing as refrigerated shipping that doesn't cost an arm and a leg?

Jarrow is hand's down the best quality of all. They even make sure all the ingredients in their supplements are non-gmo. Just wish they got a clue on a good multivitamin formulation, so I can save some money from buying Perfect Multi Super Greens.

I use to take many supplements but many just aren't proven enough to make a long term investment on. I stick to the basics nowadays with a good multivitamin, plus 2,000mg additional ascorbic acid with about 2,000mg of bioflavonoids, 20mg NOW Lyc-O-Mato, and 15mg of Carlson Labs FloraGlo Lutein. Perfect Multi Super Greens already has 500mg of vitamin C, vitamin P-350+mg of bioflavonoids, 2,000IU of vitamin D3, 3mg boron, 6mg Lutein, 2mg Lycopene, 10mg silicon, 50mg pomegranate, 50mg magnesium, 5250 ORAC, 200mcg Chromium, 150mcg of clinical selenium (SelenoExcell), and 25mg of Lipoic acid.

Most affordable deal on a stand alone Lipoic acid supplement thats good quality which is 50% S-form and 50% R-form is Natrol 300mg Lipoic acid capsules:

http://www.iherb.com...1&pid=2283&at=0

Time release Lipoic acid is a waste of money. Actually, time release in general is mainly a gimmick. Time release niacin can cause liver damage.
Edited by mirian, 18 June 2007 - 04:11 AM.