Lipoic Acid, Learn about Alpha Lipoic Acid and R-Lipoic Acid

R-Lipoic Acid (RLA) is one of the most important and exciting new nutraceutical compounds to hit the market. It is a powerful antioxidant, a critical co-factor in ATP production, regulates lipid and carbohydrate metabolism, signal transduction and gene transcription. R Lipoic is also neuroprotective, chelates heavy metals, can reverse enzyme and DNA oxidative damage and crosses the blood brain barrier.

R Lipoic Acid from RelentlessImprovement.com has been shown to be more effective by a factor of 8-10 over the commercially available alpha lipoic acid for reducing inflammation, and with its reduced form, R-DihydroLipoic Acid, regulates the pro-inflammatory COX-2 and LOX pathways. This indicates the unnatural SLA is interfering with the body's utilization of the R form. Like natural sugars, (D-form) and amino acids, (L form) the R (+), or dextro (d) form is the natural form of lipoic acid.

GeroNova Research, Inc. has dedicated years of research to producing and processing R-lipoic Acid into stabilized, finished dietary ingredients for the nutritional supplement market. They have stabilized R-lipoic Acid, created highly bio-available dosage forms, introduced R-DihydroLipoic Acid to the market and are constantly researching better ways to build these valuable molecules and make them affordable to the consumer.

Lipoic acid occurs in three different forms:

• R-Lipoic Acid (the R (+) enantiomer) is the pure form found in nature from the simplest organisms up to the humans. Life does not exist without it, and it is found in every cell of the body.
• S-Lipoic acid (The S (-) enantiomer) is a by-product from chemical synthesis and may interfere with some the beneficial properties of the R-form, especially in interactions with proteins and enzymes.
• Alpha-lipoic acid consists of 50/50 racemic mixture of the R and S enantiomers and is the commonly commercially available form of lipoic acid.

R-Lipoic Acid (RLA) is the only naturally-occurring form of alpha-lipoic acid

Think of it this way: you can't fit your right hand into a left-handed glove. If you wore your gloves on the wrong hands, you wouldn't be able to function normallyÑsimply because the gloves wouldn't fit.

In the body enzymes will not accept a Òleft-handedÓ substrate to do the job a right-handed one is designed to do. RLA is the form of lipoic acid that the body recognizes due to the structure and design of the binding sites.

The differences in activity of RLA, SLA and ALA are primarily due to stereospecific binding and competitive inhibition at the active sites of signaling proteins, transcription factors, histone acetylation/deacetylation and flavo-enzymes.

Lipoic Acid Stability, Absorption and Dissolution

RLA, despite all its health benefits, when separated from the S form, is physically unstable. The compound deteriorates relatively rapidly at slightly above room temperature. The heat of friction during encapsulation and the compression of tableting are sufficient to initiate this process. Even a partially polymerized product can pose significant problems in the manufacturing and stability of a dosage form. The polymer reduces dissolution of tablets or capsules, GI absorption and lowers the bioavailability, since it is so poorly absorbed from the GI tract.

Numerous factors affect lipoic acid absorption. Racemic-Alpha Lipoic Acid has poor solubility and absorption from the GI tract, as only 30% reaches the plasma vs. an iv dose. R Lipoic Acid is even less soluble and polymerizes on contact with the low pH environment of the stomach. The insoluble polymer may accumulate in the GI tract over time, since it is essentially insoluble in water or gastric juice.

Lipoic Acid FAQ

What is lipoic acid?

Alpha-lipoic acid, also known as thioctic acid, is a naturally occurring compound that is synthesized by plants and animals, including humans. Alpha-lipoic acid contains two sulfur molecules that can be oxidized or reduced. This feature allows alpha-lipoic acid to function as a cofactor for several important enzymes as well as a potent antioxidant.

How does R-Lipoic acid differ from racemic alpha-lipoic acid?

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 (racemic alpha-lipoic acid) is a synthetic product consisting of two forms, the R+ and S- optical isomers in equal amounts. Naturally occurring lipoic acid, the type the 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 ÒrecognizesÓ R-lipoic acid and ÒknowsÓ how to properly metabolize it, since most key enzymes are structured to hold only the R-form of lipoic acid. There is evidence that the two optical isomers of alpha-lipoic acid have different biological activities.

R-Lipoiic Acid occurs naturally in plants and animals and is the only form that functions as a cofactor for mitochondrial enzymes. Within the mitochondria, RLA is reduced to R-DHLA, the more potent antioxidant, 28 times faster than SLA. One study in humans found RLA to be more bioavailable than SLA when taken orally. RLA was more effective than SLA in enhancing insulin-stimulated glucose transport and metabolism in insulin-resistant rat skeletal muscle, and RLA was more effective than racemic alpha-lipoic acid and SLA in preventing cataracts in rats.

Does that mean alpha lipoic acid is no good?

Alpha lipoic acid contains 50% of the natural R-form and 50% of the unnatural S-form. That is the reason why people get results when they take an alpha lipoic acid supplement. Most of the therapeutic value lies in the R-form, although it must be stabilized and delivered in a dosage from the body can absorb.

Therefore you should be able to take twice as much alpha-lipoic acid and get the same amount of the R-form, and therefore same benefit, right?

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. In another study, SLA was ineffective in treatment of diabetes and inhibited ATP production. Therefore it may be best to avoid the S-form altogether in order to achieve maximum benefits.

What are the best dosage forms of R-lipoic acid?

Unfortunately, the absorption of most commercial RLA powder, capsules and tablets is less than 1%, due to extensive polymerization during manufacturing and in the stomach.

Numerous factors affect GI absorption.

Rac-Alpha-Lipoic Acid has poor solubility in stomach acid, and RLA polymerizes on contact in low pH environments. Therefore, RLA must first be stabilized as a salt, or an aqueous solution of the salt. The newest dosage form is a liquid-filled capsule with RLA and MCT (medium chain triglycerides). The MCT delivery system allows most of the RLA to bypass the harsh environment of the stomach and be delivered into the intestines-liver (entero-hepatic system). MCT's also compete with RLA for entero-hepatic transport systems, allowing higher levels of RLA to reach the plasma and tissues.

Can I take R Lipoic acid with prescription drugs and are there any restrictions?

People undergoing chemotherapy or taking anti-diabetes drugs or who are glucose-intolerant should check with their healthcare professional before taking lipoic acid. Pregnant and lactating women are advised not to take lipoic acid, because of lack of long-term safety data. The PDR reports that no serious side effects have been reported. Side effects are rare, but include allergic skin reactions and possible hypoglycemia in diabetics as a result of improved glucose utilization with high levels of intake. There is also a possibility of biotin depletion. Extremely high doses (over 6 gms/serving) may cause lactic acidosis.

How do you ensure the quality of your R-Lipoic Acid products?

The raw materials used in GeroNova products are received with Certificates of Analysis that certify their composition. The raw materials, as well as the packaging materials, are subjected to strict quality testing before they are accepted into the plant. Throughout the manufacturing process, written Standard Operating Procedures (SOPs) govern every step.

The stability of GeroNova's stabilized R-lipoic acid products has been studied under a variety of conditions of temperature and stability, using methods specified by the USP. Expiration dates, established in accordance with the stability testing results, are stamped on each bottle.

Where do you get the pure R form of Lipoic acid?

Until recently it was extremely difficult and expensive to manufacture R-lipoic acid. This made it cost prohibitive as a nutritional supplement. After three years of ongoing product development, GeroNova Research Inc, working closely with one of their affiliates, perfected the process of manufacturing and stabilizing pure R-lipoic acid as well as R-dihydrolipoic acid, that while still more expensive than r-alpha lipoic acid, is affordable for small and large nutrient companies as well as the general public. Over the next two years we predict that alpha lipoic acid, which has become a 40 metric ton per year nutrient, will be completely replaced by the more powerful and biologically friendly R-form.

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References

• Nutraceuticals in Health and Disease Prevention. Kramer K, Packer L. R-alpha-lipoic acid. In: Kramer K, Hoppe P, Packer L, eds. New York: Marcel Dekker, Inc.; 2001:129-164.
• Enantioselective pharmacokinetics and bioavailability of different racemic a-lipoic acid formulations in healthy volunteers. Hermann R, Niebch G, Borbe HO, et al. Eur J Pharm Sci. 1996;4:167-174.
• Differential effects of lipoic acid stereoisomers on glucose metabolism in insulin-resistant skeletal muscle. Streeper RS, Henriksen EJ, Jacob S, Hokama JY, Fogt DL, Tritschler HJ. Am J Physiol. 1997;273(1 Pt 1):E185-191.
• Stereospecific effects of R-lipoic acid on buthionine sulfoximine-induced cataract formation in newborn rats. Maitra I, Serbinova E, Tritschler HJ, Packer L. Biochem Biophys Res Commun. 1996;221(2):422-429.
• Therapeutic Potential of a-Lipoic Acid: Molecular Aspects. Chandan K. Sen, Sashwati Roy and Lester Packer in Oxidative Stress, Cancer, AIDS and Neurodegenerative Diseases. Eds. L. Montagnier, R. Olivier, C. Pasquier. Marcel Dekker Inc. New York, in press 1996
• Pre-treatment with R-lipoic acid alleviates the effects of GSH depletion in PC12 cells: implications for Parkinson's disease therapy. Bharat S, Cochran BC, et al. Neurotoxicology. 2002 Oct;23(4-5):479-86.
• Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Packer L, Tritschler HJ, Wessel K. Free Radic Biol Med. 1997;22(1-2):359-78.
• Lipoic acid confers protection against oxidative injury in non-neuronal and neuronal tissue. Lynch MA. Nutr Neurosci. 2001;4(6):419-38.
• Chapter 13 in Lipoic Acid in Health and Disease; Wolz, P, Krieglstein J, Neuroprotective Activity of Lipoic and Dihydrolipoic acid. Fuchs J, Schofer, H.; ed. Fuchs J, Packer L, Zimmer G. Marcel Dekker, Inc New York, Basel, Hong Kong (1997) pp205-226.
• Neuroprotective effects of alpha-lipoic acid and its enantiomers demonstrated in rodent models of focal cerebral ischemia. Wolz P, Krieglstein J. Neuropharmacology. 1996 Mar;35 (3):369-75.

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