R-ALA

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)