R-alpha Lipoic Acid - As a Supplement

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The Case for R-alpha Lipoic Acid

R-alpha lipoic acid (RLA - also called R(+) alpha lipoic acid) is the

enantiomer which is produced by the human body in minute quantities.

It has several independent valuable functions in several tissue types,

but perhaps is most important in the mitochondria of cells where it

reduces the generation of reactive oxygen species (ROS) during the ATP

generating respiration cycle, which generation is thought be many to

be a basic mechanism of aging. Since the time when alpha lipoic acid

became synthesized efficiently enough for it to be marketable as a

supplement, the form available to the public has been a racemic

product containing approximately a 50:50 mixture of RLA and its mirror

image S enantiomer (SLA). This is because the usual situation that:

a) non-biological synthetic processes generally produce racemic

products, and

separating out the biologically active isomer is a difficult (and

costly) process,

is fully true for alpha lipoic acid. For most chemicals this is not a

problem since the non-biological forms do no harm or are inactive.

There is now a considerable body of research on the effects of racemic

alpha lipoic acid and RLA (and a much smaller amount on SLA). The many

valuable benefits of alpha lipoic acid have been detailed in many

review papers of which 16 citations are appended. The abstracts of

these papers may be accessed through:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed by

entering their PMID as search string. In addition, much of this

research, particularly as it relates to RLA, is documented at:

http://morelife.org/supplements/RLA.html. A full review of this

research makes the following points clear:

1) Supplementation of alpha lipoic acid in any available form is

highly beneficial for many parameters of health and longevity.

(However, many supplements suppliers of racemic alpha lipoic acid are

fraudulently using the positive results of studies using only RLA to

promote their own racemic product without indicating that the subject

of the study was *not* the racemic chemical.)

2) Although inclusion of SLA within the product still allows it to be

highly valuable, such inclusion has the following effects:

a) it negatively impacts the beneficial effects of RLA on some

important health and longevity parameters,

for other parameters for which RLA is beneficial, SLA has no effect

at all, thus causing a dilution of the overall effectiveness of the

product,

c) with respect to the mitochondrial benefit, SLA may inhibit the

effectiveness of RLA, and

d) in red blood cells SLA is a more effective antioxidant than RLA,

but there is no known systemic benefit of this (unnatural) effect.

3) Thus, supplementation with RLA appears to be more valuable for

promotion of health and longevity than supplementation with the

racemic product. Moreover, gram for gram, RLA is more than twice as

valuable as racemic LA, with the exact relative value dependent on the

particular goal for which the supplement is to be used.

Supply Sources for R-alpha Lipoic Acid

At this time, the following Internet retail sources for procuring RLA

are known to me:

a) http://hfn-usa.com/hfn/r-lipoic-acid.html

http://www.srvitamins.com/sidecatcom.asp?cat=Antioxidants

c) http://www.anabolicfitness.net

d) http://www.globalvitamins.com

e) http://www.smart-publications.com/store/index.html

f) http://research-chems.com/_wsn/page2.html

These sources appear to show that there are currently (at least) four

independent commercial suppliers of R-alpha lipoic acid in North

America.

1) and d) above - A product made by Advanced Orthomolecular

Research (aka Holistic International) The product label states that it

contains 90 caps of 150 mg of RLA plus 100 ug of biotin and retails

for between CDN$45 and CDN$54 depending on where you buy it. It is

available at dozens of health food stores throughout Canada and by

mail order to the US from some.

2) a) and e) above - A product made by Health Freedom Nutrition

stated to contain 60 caps of 50 mg of RLA only, which retails for

US$24.95.

3) c) above - A product stated to contain 100 caps of 100 mg of RLA

only, which retails for US$19.95.

4) f) above - A powdered form of RLA which sells for US$1 per gram for

50 grams or more.

Comparing these in terms of US$ per gram of RLA:

1) costs $2.22 per gram

2) costs $8.31 per gram

3) costs $2.00 per gram

4) costs $1.00 per gram

More about what these prices imply below, but first some information.

I have been delving deeply into the research and manufacturing of R(+)

alpha lipoic acid for some time now (see my webpage on this chemical

at: http://morelife.org/supplements/RLA.html) and from time to time I

have posted much of the information which I have found on the

newsgroup

sci.life-extension. (This can be accessed via a newsreader or through

http://groups.google.com/groups?hl=en & lr= & ie=UTF-8

& group=sci.life-extension) However, I recently visited the

manufacturing facility of my own supplier, LaboChim

(http://www.labochim.com) during a holiday in Northern Italy after

attending the Sixth International Symposium on Neurobiology and

Neuroendocrinology of Aging in Bregenz, Austria.

In the light of the current information which I have acquired and the

growing number of sources of RLA as a supplement product on the North

American market, I decided to update and extend the information which

I have found (besides the peer reviewed studies described on my

website which refer only to the effects of the different pure forms).

1. Manufacturing of Pure Alpha Lipoic Acid Enantiomers

The process of manufacture of RLA is quite time consuming and requires

very careful monitoring of temperatures and times of processing for

each of the 13 steps involved (10 for the racemic and 3 additional for

the RLA). The final steps of separation into pure enantiomers are the

most critical and Labochim has a special patented process which they

would not tell me (it could be that patents are not publicly

accessible in Italy as they are in the US). I do know that (for

reasons detailed below) Labochim takes special measures to do the

final separation of enantiomers and the drying processes (necessary to

remove solvents) at a low temperature. I am not easily " impressed " but

I was certainly pleasantly surprised by the manufacturing methods of

Labochim, particularly with the care, documentation and analysis which

was done at each and every step of the manufacturing process of each

of their products. This is a company which is fully approved to make

pharmaceuticals for the US and European markets and they use the same

careful methods in the manufacture of lipoic acid and pure RLA.

Because of the complexity of the production, I am now convinced that

high purity and quality RLA is unlikely to be available soon in

product forms as inexpensive as are regular vitamins. At Labochim's

required selling price (even in quantity), RLA could likely not be

sold profitably in capsule form for less than $3.00 per gram retail.

Since a reasonable capsule size would be 100 mg (3 or more per day),

this translates to a daily price of just under $1.00 which only the

most serious life extensionists are likely to embrace.

On the other hand, because the Labochim product is so expensive (and

before I understood why) I was, like many others, scouring the world

for other manufacturers. I have so far only found these in Germany

(one only which has provided the RLA used by many of the researchers)

and China (several). The German company wrote to me:

" R(+)-alpha-lipoic acid is currently not available for commercial

purposes. " Some of the Chinese manufacturers tried to sell me racemic

LA as RLA and others did not know the correct name or the CAS number

for RLA. After much searching I did find one or two Chinese companies

which appeared to have the right chemical at a price which is a little

less than half that which Labochim is charging. However, after my

recent visit to Labochim and the analyses that I have seen of product

from other sources, I am no longer looking beyond Labochim for this

chemical.

2. While the racemate does not seem to have this problem, the pure

enantiomer forms (both R(+) and S(-)) have a tendency to polymerize

(attach together forming long chains). This is especially strong at

any temperature above about 25'C. It may still happen that the

polymerized form is absorbed and beneficial after being depolymerized

into its previous chemical form by the digestive system. However, no

one knows whether this depolymerization will, in fact, take place or

whether the polymer will be absorbed, be of any benefit, or even might

be harmful! All that we know is that if the tests for presence of the

molecule are run periodically when it is being stored at a high

temperature, the concentration decreases over time (Labochim provided

me with the data from such tests) because of formation of the polymer.

Labochim strongly suggests that the pure enantiomers should be stored

under refrigeration (or even in a freezer for very long-term storage).

I keep my supply stored in the freezer of my refrigerator.

3. I also purchased a bottle of the Advanced Orthomolecular Research

product, Lot# 040012-0, Exp date 02/2005 and sent 10 of the capsules

to

Labochim for analysis (btw, the bottle said nothing about storage

temperature - although I have been told now that I have informed AOR

of this potential problem they are labeling their bottles with a

warning to keep refrigerated). Labochim takes pains to keep track of

the world supply and has very sophisticated testing facilities (needed

for custom synthesis and high quality manufacturing). They had already

tested some Chinese samples and found them lacking. Here are their

results for the AOR product (bearing in mind some limitations because

they did not have the raw RLA which went into the capsules).

a) The average content of RLA per capsule assayed to 119 mg (instead

of the 150mg stated on the label).

The purity of the ALA in the capsules was: R(+)LA - 91%, S(-)LA -

9% (instead of 100% RLA).

c) The total contents of the capsules weighed from 140-150 mg

(including 100 ug of biotin + microcrystalline cellulose as stated on

the label).

It is possible that some of the missing RLA is due to polymerization

(before I sent them) because none of the suppliers or retail stores

are taking any special measures to keep them at low temperature (and

we had very hot weather in Canada this spring and summer). (Again, I

have been told that AOR has now advised their retailers to keep this

product under refrigeration.) The polymerization could not have

occurred after I purchased the product since I kept it in my

refrigerator and sent the capsules by expedited delivery to Labochim.

Labochim stated that this analysis was similar to what they had seen

in RLA from Chinese sources, but they also said that the purity of

Chinese material appears to vary greatly from one batch to another,

likely because of insufficient process control procedures and

in-process testing.

From all this information, it appears to be almost certain that

the products numbered 1) and 3) above are from Chinese sources and may

be inferior product. Jarrow, which was going to market this RLA

obtained from AOR in the USA, has apparently discontinued their plans

to do so, perhaps because of the variable purity of the product. The

product numbered 2) above, is 4 times the price of the others per gram

of RLA which could reflect either a quality product or a very high

mark-up. Until it is analyzed we cannot really tell which.

Another choice:

After seeing the quality of the facilities at Labochim and considering

the whole situation, I decided to purchase from them 5 kilograms of

RLA powder. A Certificate of Analysis of this product from Labochim

(batch number 123013) shows that it is between 99.4% (by HPLC assay)

and 99.1% (by titrimetric assay) pure RLA with less that 10 ppm heavy

metals, each impurity less than 0.02% and impurity total less than

0.02%. This new purchase is now in my possession, being stored under

refrigeration and available for sale to interested parties. I have

packaged it in 40 gram quantities of powder placed in a polypropylene

zip-lock bag inside another polyethylene protector zip-lock bag. These

will be sent in a padded envelope with a diskette by first class mail

at no extra charge. The diskette serves the dual purpose of keeping

the package stiff and allowing the receiver to determine if the

package has been irradiated (since the disk would then be unreadable).

The product usage instructions are in text and MSWord files on the

diskette.

My price for this product is US$100 for 40 grams of pure powder. (If

you wish other forms of delivery, you will have to pay extra.) If you

wish to take advantage of this offer, email me with your order

(including full name, mailing address, phone number, and any special

shipping requirements) and I will tell you by reply how payment should

be made. The delivery address given should *not* be one in which the

mail will sit at high temperature. For dosage estimating purposes, my

suggestion based on the references at my website is to take from 4-8

mg/kg body weight daily. Therefore 40 grams should last most people 3

to 5 months depending on weight and dosage taken.

Suggestions on usage will be included with the package. Since lipoic

acid competes with biotin, you should certainly take at least an extra

1 mg of biotin daily with the RLA, which you might want to get that

ahead of time. Since biotin is available cheaply from many good

sources, I have no wish to supply it.

Some may think this is pure commericalism and forbidden on this venue,

however in view of the information that I have found and presented, I

think of it more as a service to help others have a quality source of

RLA at a reasonable price. Once there is proven quality product

available in the marketplace at a reasonable price, I will be very

happy to stop providing RLA and spend my time on the many things which

I value more highly such as my website. I am only supplying it to

ensure that I (and my wife) have a source of quality product at a

reasonable price (Labochim will not sell less than 1 kg which is too

much for two people to use in a timely manner).

--Tom s ( Wakfer)

MoreLife for the rational - http://morelife.org

Reality based tools for More Life in quantity & quality

1: Moini H, Packer L, Saris NE.

Antioxidant and prooxidant activities of alpha-lipoic acid and

dihydrolipoic

acid.

Toxicol Appl Pharmacol. 2002 Jul 1;182(1):84-90. Review.

PMID: 12127266

2: Hagen TM, Moreau R, Suh JH, Visioli F.

Mitochondrial decay in the aging rat heart: evidence for improvement

by dietary

supplementation with acetyl-L-carnitine and/or lipoic acid.

Ann N Y Acad Sci. 2002 Apr;959:491-507. Review.

PMID: 11976222

3: Liu J, Atamna H, Kuratsune H, Ames BN.

Delaying brain mitochondrial decay and aging with mitochondrial

antioxidants and

metabolites.

Ann N Y Acad Sci. 2002 Apr;959:133-66. Review.

PMID: 11976193

4: Lynch MA.

Lipoic acid confers protection against oxidative injury in

non-neuronal and

neuronal tissue.

Nutr Neurosci. 2001;4(6):419-38. Review.

PMID: 11843262

5: Packer L, Kraemer K, Rimbach G.

Molecular aspects of lipoic acid in the prevention of diabetes

complications.

Nutrition. 2001 Oct;17(10):888-95. Review.

PMID: 11684397

6: JL, Goldfine ID.

Alpha-lipoic acid: a multifunctional antioxidant that improves insulin

sensitivity in patients with type 2 diabetes.

Diabetes Technol Ther. 2000 Autumn;2(3):401-13. Review.

PMID: 11467343

7: S, Rett K, Henriksen EJ, Haring HU.

Thioctic acid--effects on insulin sensitivity and glucose-metabolism.

Biofactors. 1999;10(2-3):169-74. Review. No abstract available.

PMID: 10609878

8: Ziegler D, Reljanovic M, Mehnert H, Gries FA.

Alpha-lipoic acid in the treatment of diabetic polyneuropathy in

Germany:

current evidence from clinical trials.

Exp Clin Endocrinol Diabetes. 1999;107(7):421-30. Review.

PMID: 10595592

9: Bustamante J, Lodge JK, Marcocci L, Tritschler HJ, Packer L, Rihn

BH.

Alpha-lipoic acid in liver metabolism and disease.

Free Radic Biol Med. 1998 Apr;24(6):1023-39. Review.

PMID: 9607614

10: Packer L.

alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B

signal

transduction and protects against oxidative injury.

Drug Metab Rev. 1998 May;30(2):245-75. Review.

PMID: 9606603

11: Roy S, Packer L.

Redox regulation of cell functions by alpha-lipoate: biochemical and

molecular

aspects.

Biofactors. 1998;7(3):263-7. Review. No abstract available.

PMID: 9568264

12: Biewenga G, Haenen GR, Bast A.

The role of lipoic acid in the treatment of diabetic polyneuropathy.

Drug Metab Rev. 1997 Nov;29(4):1025-54. Review. No abstract available.

PMID: 9421684

13: Biewenga GP, Haenen GR, Bast A.

The pharmacology of the antioxidant lipoic acid.

Gen Pharmacol. 1997 Sep;29(3):315-31. Review.

PMID: 9378235

14: Packer L, Tritschler HJ, Wessel K.

Neuroprotection by the metabolic antioxidant alpha-lipoic acid.

Free Radic Biol Med. 1997;22(1-2):359-78. Review.

PMID: 8958163

15: Packer L, Roy S, Sen CK.

Alpha-lipoic acid: a metabolic antioxidant and potential redox

modulator of

transcription.

Adv Pharmacol. 1997;38:79-101. Review. No abstract available.

PMID: 8895805

16: Packer L, Witt EH, Tritschler HJ.

alpha-Lipoic acid as a biological antioxidant.

Free Radic Biol Med. 1995 Aug;19(2):227-50. Review.

PMID: 7649494