AOR R(+)-Lipoic Acid SR Time Release. R(+) SR is the natural form of this vital antioxidant. It is the sole form produced in the body for use in the mitochondria. All lipoic acids including conventional “lipoic acid” or “alpha lipoic acid” supplements are only 50% R(+)-lipoic acid; the other half of such supplements is the artificial S(-)-enantiomer. The one feature limiting all lipoic acids is the extremely short plasma half life of around 22 minutes. R(+) SR is specially formulated with a more bioavailable salt form than the conventional “alpha lipoic acid” or R+ Lipoic acid and is more stable to heat and moisture making it more resistant to polymerization. In
addition, R(+)SR is formulated in a special matrix to provide a sustained release guaranteed for 8-10 hours. Two to three capsules of R(+)SR provides a 24 hour coverage of this important and versatile antioxidant.

60 Vegi-Caps 150 mg AOR04112
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SUPPLEMENT FACTS:
Serving Size: 1 Capsule %DRI
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R(+)-lipoic acid..(transamine salt) ........... 150mg *
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*Dietary Reference Intake not established.
Other ingredients: Silicon dioxide, organic sucrose,talc,povidone and shellac gum. Capsule: vegetarian (hydroxypropylmethylcellulose, gellan gum, water and potassium acetate).

AOR guarantees that no ingredients not listed on the label have been added to the product. Contains no wheat, gluten, corn, nuts, dairy, soy, eggs, fish or shellfish.

Suggested Use
Take one capsule twice or three times a day, or as directed by a qualified health practitioner.

Main Applications
* Network antioxidant
* Mitochondrial function
* Cognitive support
* Neurological function
* Anti-aging
* Increases insulin sensitivity

Pregnancy / Nursing
None.

Cautions
• Animal experiments suggest that lipoic acid may alter the body’s response to levothyroxin (eg. Synthroid®). Consult your physician.

Alpha lipoic acid (ALA) is an extraordinary antioxidant. Unfortunately, its effectiveness has been limited on two fronts. Firstly, supplemental lipoic acid has been manufactured with the R+ and S- enantiomers – two molecules with the same chemical formula but with different structures. The R+ form is naturally occurring and the beneficial effects of alpha lipoic acid come from the R+ isomer. The S+ form however is artificial, a byproduct of the manufacturing process and is harmful because it is thought to prevent the utilization of the R+ enantiomer. This is especially detrimental with ALA because the molecule has a

very short half-life in the body, estimated at 22 minutes; the second shortcoming of this molecule. The solution is, in theory, simple. To reap the full benefits of Alpha Lipoic Acid, an R+ sustained release formula would be ideal and would offer continual resistance against free radicals and prolonged insulin sensitivity in diabetics.

Pharmacokinetics

ALA is absorbed in the small intestine, carried to the liver via the portal circulation and distributed throughout the body by the systemic circulation. ALA is a small molecule that is readily assimilated in a non-saturable fashion in doses of 50 to 600 mg. It is naturally present in food although in very small quantities. Supplemental ALA reaches doses that are hundreds of times higher than what is found in food. ALA was thought to be a vitamin in humans and animals but it has since been shown that it is endogenously produced. The R+ form of ALA is more active and more absorbable. ALA can cross the blood brain barrier and, after its absorption, it is found intramitochondrially as well as intra and extra cellularly. It therefore prevents oxidative damage both inside and outside our cells and mitochondria throughout the body. The antioxidant effect associated with Lipoic Acid may confer protection in cases of diabetes, diabetic neuropathy, mytochondrial dysfunction, liver disease, lactic acidosis and could even help control the replication of the human immunodeficiency virus.

Alpha lipoic acid and DHLA form a redox couple capable of recycling antioxidants and are involved in cellular energy production. Incredibly, the antioxidant potential of ALA extends to both the reduced and oxidized form of the molecule. Supplementation with Alpha Lipoic acid decreases plasma protein carbonyls, markers of oxidative stress. The molecule recycles important antioxidants such as vitamin C, vitamin E, glutathione and ubiquinone.

Research

There is evidence that lipoic acid is an anti-aging agent. The key to the antiaging effect of ALA lies in its ability to protect the mitochondria from oxidative stress. It has been demonstrated that as we age, our mitochondria’s slowly become less and less efficient at producing energy. This loss of efficiency results in an increased production and release of free radicals, which injure the cell and the mitochondria, leading to a harmful and destructive cycle. In rats however, supplementation with ALA improves mitochondrial function and reduces the production of ROS halting this vicious cycle.

Lipoic acid is a promising treatment for diabetes and its related complications such as diabetic neuropathy, a treatment for which lipoic acid is approved in Germany. ALA improves insulin sensitivity allowing glucose to enter the cell more easily. For ALA to be considered a viable treatment for diabetes, the molecule must confer protection for longer than the 22-minute half-life currently limiting its effectiveness. Sustained release ALA formulations allow for constant improvements in insulin sensitivity and the results obtained in human trials done with sustained release R(+)-lipoic acid are impressive. Supplementation resulted in sustained decreases in blood glucose that averaged 184mg/dl or just over a 46% decrease. A Meta analysis reviewed all the clinical trials undertaken for the treatment of diabetic neuropathy with alpha lipoic acid. 1258 diabetic patients were included in the analysis, the largest study population ever used to evaluate the effectiveness of a particular treatment for diabetic neuropathy. The conclusions favored the use of lipoic acid in this population. The analysis revealed that the molecule is an effective treatment for neuropathies and that oral supplementation for 4-7 months reduces neuropathic deficits and improves cardiac neuropathy. It was also clear that Alpha lipoic acid is a well-tolerated and safe treatment.

• There is some indication that ALA may be helpful for the treatment and prevention of neurodegenerative disorders. Animal studies indicate that ALA may be of benefit for the management and care of Parkinson’s, Alzheimer’s, Huntington’s, and amyotrophic lateral sclerosis.
• It has been suggested that ALA may have immunostimulating properties and was shown to augment antibody production in animals.
• In Alzheimer’s disease, both oxidative stress and energy depletion are thought to play a significant role in the pathological process leading to inflammation, to the generation of advanced glycation end products and the formation of senile plaques eventually leading to nervous tissue damage. Alpha lipoic acid was used in AD with positive results. The molecule counteracts and prevents both oxidation and energy production malfunction.
• In diabetic rats, alpha lipoic acid reduces growth retardation and congenital anomalies in fetuses, supporting the theory that reactive oxygen species are linked to embryonic malformations.
• Animal studies have shown that in a high fructose diet, lipoic acid helps maintain the function of the antioxidant system and lowers lipid peroxidation and insulin resistance.
• Studies in older rats have shown that glutathione levels drop significantly with age. Glutathione is a powerful free radical scavenger and the major antioxidant species found in cells. Drops in glutathione levels in older rats reached 58% in the heart and 66% in the brain in comparison to younger counterparts. Lipoic acid supplementation increased glutathione levels in the aging brain.
• In another experiment, liver cells isolated from young and older rats were used to see the effectiveness of alpha lipoic acid at preventing liver injury. Total glutathione cellular levels were 37.7% lower in older rats. (R+)-lipoic acid significantly protected the hepatocytes against Butylhydroperoxide (an oxidative stress inducing agent) both in vitro and in vivo. The results suggest that ALA is indicated in liver conditions where oxidative stress confers pathology such as alcoholic liver disease and viral hepatitis. ALA was also shown to protect against cadmium-induced hepatotoxicity in animals.
• In vitro, lipoic acid increased cellular glucose uptake in a manner similar to insulin.

Indications

Alpha lipoic acid is indicated for the treatment of any condition where elevated blood glucose levels and free radicals are involved in the disease process. Both of those mechanisms cause problems in several degenerative processes and are both thought to impact the aging process significantly. Alpha lipoic acid can be used to prevent cataract formation, because it can inhibit the enzyme aldose reductase involved in the formation of lens opacities. Supplementation with this antioxidant also improved biochemical parameters in patients suffering from glaucoma and lead to improvements in visual function.

The area that has been studied most intensely when it comes to the use of lipoic acid is its utilization for diabetic patients. Supplementation improves insulin sensitivity, cellular glucose uptake, prevents diabetic complications, prevents protein glycation, reduces plasma free fatty acids, stimulates glycolysis and inhibits aldose reductase. Incredibly, ALA can treat diabetes once it has developed, prevents the progression of complications related to diabetes and alleviates complications if they are already present.

In healthy people, the benefits are not to be overlooked either. Free radicals, which are quenched by (R+)-lipoic acid, are well known for their injurious effect on health. They damage body structures, oxidize lipids, injure blood vessels, can lead to DNA mutations, contribute to inflammation and are thought to play a key role in degenerative disorders. On a different front, elevations in blood glucose levels damage proteins and lipids. Indeed, sugars and their intermediates will attach to amino acid residues and lipids leading to the formation of advanced glycation end products and advanced lipoxidation end products. As we age, insulin sensitivity decreases which contributes to increases in blood glucose levels, which accelerates the glycation/lipoxidation process. This leads to the loss of function in cellular structures and speeds up the aging process. Alpha lipoic acid offsets this course by increasing insulin sensitivity, which enhances glucose uptake by cells and decreases blood sugar levels.

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