ALA (was: Re: Low Carb and Trouble Sleeping)

[Guest guest]

> RE: Re: Low Carb and Trouble Sleeping

>Also, if you take any form of carnitine, you need to take R-alpha-lipoic

>acid. Carnitine boosts mitochondrial energy output and thus

>oxidation, and

>R-ALA is one of the only effective mitochondrial antioxidants out

>there. (Most ALA is NOT the real, orthomolecular R form, though,

>but a mix

>of R-ALA and S-ALA, which is only produced in labs and which appears to

>have numerous undesirable effects.)

>

, Could you please direct me to where you got this info on the

differences between R and S ALA?

Thanky :-)

Suze Fisher

Lapdog Design, Inc.

Web Design & Development

http://members.bellatlantic.net/~vze3shjg

Weston A. Price Foundation Chapter Leader, Mid Coast Maine

http://www.westonaprice.org

----------------------------

" The diet-heart idea (the idea that saturated fats and cholesterol cause

heart disease) is the greatest scientific deception of our times. " --

Mann, MD, former Professor of Medicine and Biochemistry at Vanderbilt

University, Tennessee; heart disease researcher.

The International Network of Cholesterol Skeptics

<http://www.thincs.org>

----------------------------

[Guest guest]

Suze-

>, Could you please direct me to where you got this info on the

>differences between R and S ALA?

>

>Thanky :-)

The most convenient collection of information on the issue I know of is at

http://www.r-lipoic.com. Be aware, though, that it's published by Advanced

Orthomolecular Research, a vitamin company which makes R-ALA

products. That said, it's a good and useful site, and though I haven't

perused the whole thing (I've read about the subject all over the place) it

seems quite solid. You can also just google " R-ALA " and " R-lipoic " and

find a good amount of research.

Basically, R-ALA, the natural form, gets reduced into DHLA, which performs

many important functions, particularly in the mitochondria, and then it

gets recycled back into R-ALA provided certain conditions are met. I'm not

sure how much R-ALA you can keep recycling, but it appears best to

supplement it daily, particularly if you're doing anything to boost

mitochondrial energy output, like working out or supplementing with any

form of carnitine. S-ALA, by contrast, is only turned into DHLA very

ineffectively, and can sometimes actually inhibit proper ALA

activity. I've also read that it can mess up R-ALA receptor sensitivity,

but I don't have any cites for that at the moment.

Here are a couple excerpts from the site. (Unfortunately, HTML formatting

will be lost, so I'm not sure how readable this will be.)

>In another study 42 nerve cells from different parts of the brain were

>exposed to enough buthionine sulfoxamine (BSO) to destroy half of them.

>(BSO is a chemical that makes cells more vulnerable to free radicals by

>depleting the cell of antioxidant defenses). Providing the cells with

>R(+)-Lipoic Acid saved between one half and one third of the brain cells

>that would otherwise have died from necrotic cell death (depending on what

>kind of brain cells were involved). By contrast, neither the S(-)-form,

>nor the racemate (R,S)-lipoic acid found in common supplements, offered

>any significant protection.

>

>The ineffectiveness of S(-)-lipoic acid is not terribly surprising,

>granted that the body converts so little of the artificial enantiomer into

>DHLA as compared with what's achieved using R(+)-lipoic acid. But it's

>surprising to see the impotence displayed by the racemate. After all,

>(R,S)-lipoic acid contains 50% R(+)-Lipoic Acid by weight … and yet the

>presence, in the racemate, of an equal amount of the S(-)-enantiomer not

>only failed to lend a helping hand to the R(+)-Lipoic Acid which is

>present in the racemate, but actually rendered the racemate useless in

>protecting cells from a toxin against which R(+)-Lipoic Acid alone

>provides an effective shield! But we've already seen a couple of reasons

>why this might happen. The S(-)-form could have interfered with the

>supercharging of R(+)-Lipoic Acid to DHLA; it could also have further

>contributed to the imbalance in antioxidant defense created by BSO, by

>interfering with the recycling of glutathione.

>As we've already seen, R(+)-Lipoic Acid has a key place in mitochondrial

>energy production, springing from its role in the pyruvate dehydrogenase

>enzyme complex (PDH) - the same enzyme complex which " charges up " lipoic

>acid into DHLA (see Figure 5).

>

>PDH extracts energy coming into the mitochondria bound up in pyruvic acid

>(which is made in the cell from glucose) and gives that energy to carrier

>molecules. This energy is ultimately used to create the mitochondria's ion

> " reservoir. "

>

>So you'd expect that boosting levels of R(+)-Lipoic Acid might increase

>the mitochondria's ability to make ATP. (And you'd be right - but, as

>we'll see, for the wrong reason). And because the S(-)-form is only poorly

>used as an energy coenzyme by the mitochondria - and, indeed, can actually

>interfere with the mitochondria's ability to use R(+)-Lipoic Acid for this

>purpose! - it also makes sense to look and see if the two lipoic acid

>enantiomers might have different effects on energy production and use.

>

>When researchers have looked into these questions, they've found the same

>sorts of answers we've been seeing with the use of the two enantiomers for

>support of healthy glucose metabolism and as antioxidants. While

>R(+)-Lipoic Acid revs up mitochondria's ability to make cellular fuel, the

>S(-)- form does not - and in some critical situations both S(-)-lipoic

>acid and the racemate may actually deplete the cell's energy supply!

>

>Since PDH needs R(+)-Lipoic Acid as a coenzyme for its function, you might

>expect that giving cells extra R(+)-Lipoic Acid would make PDH extract

>even more energy from pyruvic acid. Not so: when a team of scientists

>provided cultured cells with R(+)-lipoic acid, it was found to have no

>effect on PDH's ability to help process pyruvic acid 67. That might seem

>strange, but it actually does make sense, since the cell normally has all

>the R(+)-Lipoic Acid it needs for PDH activity. It's precisely because it

>has no need for extra lipoic acid that, after " charging up " supplemental

>R(+)-Lipoic Acid into its more potent DHLA form, PDH readily releases the

>extra DHLA into the cell and the rest of the body, where it can lend its

>potent antioxidant assistance.

>

>But when the same scientists provided the cells with R(+)-lipoic acid's

> " evil twin, " they found that S(-)-lipoic acid actually suppresses the

>ability of cells to use pyruvate in energy production, reducing its

>activity by 25 to 30%! The obvious explanation: S(-)-lipoic acid was

>actually getting in the way of the natural R(+)-form of lipoic acid, which

>is needed for PDH to do its job. Looking at their results, the scientists

>concluded that " R(+)-LA [that is, R(+)-lipoic acid], and not a racemic

>mixture of R(+)- and S(-)-LA, should be considered a choice for

>therapeutic applications. " 67

>

>But hold on. If R(+)-Lipoic Acid doesn't increase PDH activity, doesn't

>this mean that R(+)-Lipoic Acid is useless for boosting mitochondrial

>energy production? No - because the effects of R(+)-Lipoic Acid on

>mitochondrial energy production go well beyond PDH, and into the very

>heart of the activity of the mitochondria's ATP turbine.

>

>This was first shown by German scientists, in early experiments using

>mitochondria which had literally been turned inside out to study their

>functioning. 11 These researchers found that providing these special

>mitochondria with R(+)-Lipoic Acid boosts their ATP production. But they

>also found that the two forms of lipoic acid showed " decisive differences "

>in their effects on mitochondrial ATP production. Exposing these

>mitochondria to either the S(-)- form or the racemate actually slows their

>rate of ATP synthesis!

>

>Why would R(+)-Lipoic Acid tubocharge mitochondrial function, while the

>S(-)-enantiomer undermines it? Remember that the " leakiness " of the

>mitochondrial membrane is in large part caused by damage to the proteins

>it contains. One critical kind of damage that these proteins undergo is

>the handcuffing together (crosslinking) of key proteins' sulfur-rich

>cysteine amino acids, which creates disulfide (sulfur-to-sulfur)

>crosslinks between two sulfur atoms. These disulfide handcuffs change the

>structure of the membrane itself and of its functional proteins -

>including the all-important Complex V turbines. It's these structural

>changes that create the " holes " in the " dam " of the mitochondrial inner

>membrane, rendering the mitochondrion an inefficient and " dirty " energy

>producer.

>

>Preventing the crosslinking of sulfur groups is therefore a key part of

>keeping the mitochondrial inner membrane intact, and its proteins

>functional. But in order to maintain the structure and function of this

>system, a molecule must be able to interact with the complex 3-dimensional

>structures of the proteins themselves. So it's easy to see why scientists

>studying the effects of the two forms of lipoic acid have concluded that

>the specific three-dimensional design of R(+)-Lipoic Acid allows it to

>favorably interact with mitochondrial proteins - including the turbines of

>Complex V - while the mirror-opposite architechture of the S(-)-form

>cannot. 11, 68 , 69

>

>In other words, you won't get anywhere trying to install a turbo charger

>in your car if it isn't compatible with your engine. Trying to install the

>wrong unit might even sap your engine's power.

To make a long story short, if you're taking alpha-lipoic acid (AKA ALA,

AKA thiotic acid) which I'm becoming increasingly convinced is a very good

idea, MAKE SURE you're not taking the standard racemic

form. Unfortunately, there are relatively few suppliers of genuine pure

R-ALA, though more and more companies are beginning to offer it. iHerb has

it from Source Naturals, Country Life and Doctor's Best. Regrettably,

though, they're all chock full of nasty fillers. AOR (Advanced

Orthomolecular Research) sells it with only aerosil as a filler, which may

be benign, but it's in a vegicap, which is modestly bad news in my

book. Vitamin Research Products sells it, but I have no idea what fillers

they use.

And then Geronova, which also supplies at least some of the other vendors,

sells it in several different forms. One, used by Doctor's Best and

probably others (unless they have other suppliers, which is quite possible)

is K-R-ALA, or potassium r-lipoate, a salt which stabilizes the R-ALA

against polymerization, which can be a real problem. You can find this in

bulk form for as little as $20 for 25g, though I don't know yet whether

there are any additional fillers or binders or whatnot besides the

potassium, and you can also get it in liquid form from Geronova or their

resellers. They also sell it in a softgel with MCT (and no other fillers)

which is supposed to smooth out the absorption curve, giving you much

steadier blood levels, as opposed to K-R-ALA, which peaks and then

crashes. This is possibly the best form currently available, but it's

quite expensive, and I'm wondering whether bulk K-R-ALA powder could be

taken with a little VCO to get the same effect at much less expense.

Geronova also sells combos of R-ALA and R-DHLA, the reduced form (some

would say, not entirely accurately, the active form), and the LEF sells it

by itself, but it appears likely that it's not a good idea to take DHLA, so

I'd avoid it. (In fact, it seems that it might be counterproductive, just

like S-ALA!)

One final caveat: if you take supplemental ALA in any form, you need to

take some supplemental biotin.

Hope this helps!

-