What is R-ALA?
R-lipoic acid is the biologically active form of alpha lipoic acid. It has
been called the mitochondrial antioxidant because it is a key component of
mitochondrial dehydrogenase complexes. R-lipoic acid is directly involved in
cell metabolism and redox states. R-lipoic acid crosses the blood brain
barrier, and helps regulate neuronal calcium homeostasis, scavenges a variety
of reactive oxygen species (ROS) while recycling vitamins C, E and
glutathione. R-lipoic acid has been shown to regulate pro-inflammatory
cytokines, and alter the expression of "toxic genes". R-lipoic acid has been
used to treat diabetes and has been recommended as a "neuroprotective agent"
Why do I need it?
If it is naturally occurring within our bodies, then why do we need to take
lipoic acid as a supplement? There are at least four good reasons. First, as
we age, our bodies lose the ability to synthesize enough Lipoic acid, right
at the time when we most need it. Secondly, you cannot get sufficient
quantities from your foods. Third, the body produces small amounts of
R-Lipoic acid for metabolism that may not be of sufficient quantity to
neutralize rising free radical concentrations. Fourth, a minimum amount is
necessary for normal metabolic processes. Taking larger amounts, can have
pronounced therapeutic effects.
How is R-ALA different from ALA?
I have to get a little technical here in order to make the terminology
meaningful. In chemistry, a compound that has four different groups attached
to carbon has a plane of asymmetry. That carbon is designated “chiral”,
meaning it has “handedness”. That means that the molecule can exist in two
different forms that are non super-imposable mirror images of one another.
Put your right palm on the back of your left hand. What do you see? Both
hands have five fingers, with the same arrangement relative to the thumb and
yet the thumbs point in different directions, so the hands are said to be
mirror images of one another. Chiral molecules, like hands have this
property. One of these isomeric molecules (called stereoisomers or
enantiomers) rotates the plane of light in a machine called a polarimeter to
the right and is designated dextro or +. The other isomer rotates the plane
of light to the left and is called levo or -. There is another consideration
when dealing with chiral molecules that places the four different
substituents in order of priority. The priority is determined by convention
and establishes what is called the ‘Absolute Configuration’ of the molecule.
By starting with the highest priority substituent and moving in a clockwise
direction to the second highest, and on to the third and fourth designates
the molecule R. If you move in the opposite direction, the absolute
configuration is S. Molecules in living systems generally exist in only one
form. When the same molecule is synthesized, it consists of equal amounts of
both forms. Commercially available alpha Lipoic acid is a synthetic product
consisting of two forms, the R+ and S- isomers in equal amounts. As we said,
naturally occurring Lipoic acid, the type your body makes and requires
contains one form, the R-dextro or + form. This gives R-lipoic acid
significantly more potency and efficacy. This is because the body recognizes
R-lipoic acid and knows how to properly metabolize it, since all the key
enzymes are structured to hold only the R-form of lipoic acid.
Does that mean ALA is no good?
Remember, alpha lipoic acid is contains 50% of the natural R-form and 50% of
the unnatural S-form. Most of the therapeutic value lies in the R-form. That
is the reason why people get results when they take an alpha Lipoic acid
supplement.
So if I take half the amount of R-ala compared to ALA, I'll get the same results?
It’s not quite that simple, although until recently researchers thought this
was the case. There is new evidence surfacing that the unnatural S-form may
actually interfere with the beneficial properties of the R-form. In one study
with mice, alpha Lipoic acid at high doses shortened the mean lifespan, but
even at low doses, the R- form increased total life-span. So it is best to
avoid the S-form altogether in order to achieve maximum benefits.
Do you have a list of studies I can reference for R-ALA?
1. Nichols, T.W. Alpha lipoic Acid: Biological Effects and Clinical
Implications,
2. Moini, H., Tirosh, O., R-Alpha Lipoic Acid Action on Cell Redox Status,
the Insulin Receptor, and Glucose Uptake in 3T3-L1 Adipocytes; Archives of
Biochem & BioPhys 397, No2 384-391 (2002)
3. Liu, J. Killilea, D.W. et.al., Age-associated mitochondrial oxidative
decay: Improvement of carnitine acetyltransferase substrate binding affinity
and activity in brain by feeding old rats acetyl-L-carnitine and/or
R-alpha-lipoic acid. Proc Nat Acad Sci 99, 1876-1881 (2002)
4. Liu, J., Atamna, H., et.al. Delaying Brain Mitochondrial Decay and Aging
with Mitochondrial Antioxidants and metabolites. Ann NY Acad Sci 959:133-166
(2002)
5. Liu, J., Head, E., et.al., Memory Loss in old rats is associated with
brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding
acetyl-l-carnitine and/or R-alpha lipoic acid. Proc Natl Acad Sci USA 99,
2356-2361 (2002)
6. Hagen, T.M., Liu, J., et. al.; Feeding acetyl-L-carnitine and lipoic acid
to old rats significantly improves metabolic function while decreasing
oxidative stress, Proc Nat Acad Sci USA vol99, issue 4, 1870-1875 (2002)
7. Hager, K., Marahrens, A.,et.al. Alpha lipoic acid as a new treatment
option for Alzheimer type dementia, Arch Geron Geriatr 32 (3): 275-282 (2001)
8. Hagen, T.M., Shigeno,E.T. et.al. Oxidative Stress in the Aging Rat Heart
is Reversed by Dietary Supplementation with (R)-Lipoic Acid. FASEB J. 15,
700-706. (2001)
9. Hagen, T.M. Increased mitochondrial decay and oxidative stress in the
aging rat heart: improvement by dietary supplementation with (R)-lipoic acid.
In, Free Radicals in Chemistry, Biology and Medicine 27, 262-271. (2000)
10. Hagen, T.M., Vinarsky, V., et.al. (R)-alpha-lipoic acid reverses the
age-associated increase in susceptibility of hepatocytes to
tert-butylhydroperoxide both in vitro and in vivo. Antiox. Redox Signaling 2,
473-483. (2000)
11. Hagen, T.M., Ingersoll, R.T. et.al. (R)-alpha-lipoic acid-supplemented
old rats have improved mitochondrial function, decreased oxidative damage,
and increased metabolic rate. FASEB J. 13, 411-418. (1999)
12. Lykkesfeldt, J. Hagen, T.M., Age-associated decline in ascorbic acid
concentration, recycling and biosynthesis in rat hepatocytes-reversal with
(R)-alpha-lipoic acid supplementation. FASEB J. 12, 1183-1189. (1998)
13. Packer, L; Tritschler, H.J.; Neuroprotection by the Metabolic Antioxidant
Alpha Lipoic Acid; Free Rad Biol Med 22, Nos 1 / 2, 359-378 (1997)
14. Hermann, R.; Niebch, G.; Enantioselective pharmacokinetics and
bioavailability of different racemic alpha lipoic acid formulations in
healthy volunteers. Eur J Pharm Sci 4: 167-174 (1996)
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