Thread: what is ALA??
08-01-2002, 08:27 PM #1Junior Member
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- Jan 2002
- Bean town
what is ALA??
can some tell me what ala is and what it is used for/?? thanx
08-01-2002, 09:08 PM #2
08-01-2002, 09:18 PM #3
alpha lipoic acid. heard its good for the liver
08-02-2002, 02:23 PM #4
08-03-2002, 11:06 AM #5New Member
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- Sep 2001
ala is the abbreviation for the amino acid alanine
08-04-2002, 02:21 PM #6Registered User
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- Aug 2002
Alpha Lipoic Acid, cant find the article right now...but I know its really good for you
06-30-2004, 04:35 PM #7Originally Posted by karlmone
07-07-2004, 10:47 AM #8VET
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- Nov 2001
ALA is typically used in this context to stand for alpha lipoic acid, though it is also used to stand for alanine and for alpha linoleic acid (omega fatty acid).
the are two isomers of lipoic acid.
regular ALA is a racemate (50/50 mix of the r and s isomers)
a short article regarding the difference between ALA and r-ala (single isomer)
07-07-2004, 10:50 AM #9
Alpha-lipoic acid is available generically from numerous manufacturers. Branded products include Ultra-Lipoic Forte (Westlake Labs).
Alpha-lipoic acid, also known as thioctic acid, is a disulfide compound that is a cofactor in vital energy-producing reactions in the body. It is also a potent biological antioxidant. Alpha-lipoic acid was once thought to be a vitamin for animals and humans. It is made endogenously in humans—the details of its synthesis are still not fully understood—and so it is not an essential nutrient. There are, however, certain situations, for example, diabetic polyneuropathy, where alpha-lipoic acid might have conditional essentiality. And recent research indicates that the antioxidant roles of alpha-lipoic acid may confer several health benefits. Alpha-lipoic acid is found widely in plant and animal sources.
Most of the metabolic reactions in which alpha-lipoic acid participates occur in mitochondria. These include the oxidation of pyruvic acid (as pyruvate) by the pyruvate dehydrogenase enzyme complex and the oxidation of alpha-ketoglutarate by the alpha-ketoglutarate dehydrogenase enzyme complex. It is also a cofactor for the oxidation of branched-chain amino acids (leucine, isoleucine and valine) via the branched-chain alpha-keto acid dehydrogenase enzyme complex.
Alpha-lipoic acid is approved in Germany as a drug for the treatment of polyneuropathies, such as diabetic and alcoholic polyneuropathies, and liver disease.
Alpha-lipoic acid contains a chiral center and consists of two entantiomers, the natural R- or D- entantiomer and the S- or L- entantiomer. Commercial preparations of alpha-lipoic acid consist of the racemic mixture, i.e. a 50/50 mixture of the R- and E-entantiomers. It is represented by the following chemical structure:
Alpha-lipoic acid has a variety of names. In addition to being known as alpha-lipoic acid and thioctic acid, it is also known as lipoic acid, 1,2-dithiolane-3-pentanoic acid; 1,2-ditholane-3-valeric acid; 6,8-thiotic acid; 5-[3-C1,2-dithiolanyl)]-pentanoic acid; delta-[3-(1,2-dithiacyclopentyl)] pentanoic acid; acetate replacing factor and pyruvate oxidation factor. Alpha-lipoic acid is water-insoluble.
Although the details of its synthesis have yet to be worked out, alpha-lipoic acid is synthesized in mitochondria; octanoic acid and L-cysteine (for its sulfur) are precursors in its synthesis.
ACTIONS AND PHARMACOLOGY
Alpha-lipoic acid has biological antioxidant activity, antioxidant recycling activity and activity in enhancing biological energy production.
MECHANISM OF ACTION
Alpha-lipoic acid and its reduced metabolite, dihydrolipoic acid (DHLA), form a redox couple and may scavenge a wide range of reactive oxygen species. Both alpha-lipoic acid and DHLA can scavenge hydroxyl radicals, the nitric oxide radical, peroxynitrite, hydrogen peroxide and hypochlorite. Alpha-lipoic acid, but not DHLA, may scavenge singlet oxygen, and DHLA, but not alpha-lipoic acid, may scavenge superoxide and peroxyl reactive oxygen species.
Alpha-lipoic acid has been found to decrease urinary isoprostanes, O-LDL and plasma protein carbonyls, markers of oxidative stress. Further, alpha-lipoic acid and its redox couple DHLA have been found to have antioxidant activity in aqueous, as well as in lipophilic regions, and in extracellular and intracellular environments. Finally, with regard to alpha-lipoic acid's antioxidant activity, alpha-lipoic acid appears to participate in the recycling of other important biologic antioxidants, such as vitamins E and C, ubiquinone and glutathione.
Exogenous alpha-lipoic acid has been shown to increase ATP production and aortic blood flow during reoxygenation after hypoxia in a working heart model. It is thought that this is due to its role in the oxidation of pyruvate and alpha-ketoglutarate in the mitochondria, ultimately enhancing energy production. This activity, and possibly its antioxidant activity, may account for its possible benefit in diabetic polyneuropathy.
Most pharmacokinetic studies have been performed in animals. Alpha-lipoic acid is absorbed from the small intestine and distributed to the liver via the portal circulation and to various tissues in the body via the systemic circulation. The natural R-entantiomer is more readily absorbed than the L-entantiomer and is the more active form. Alpha-lipoic acid readily crosses the blood-brain barrier. It is found, after its distribution to the various body tissues, intracellularly, intramitochondrialy and extracellularly.
Alpha-lipoic acid is metabolized to its reduced form, dihydrolipoic acid (DHLA), by mitochondrial lipoamide dehydrogenase. DHLA, together with lipoic acid, form a redox couple. It is also metabolized to lipoamide, which functions as the lipoic acid cofactor in the multienzyme complexes that catalyze the oxidative decarboxylations of pyruvate and alpha-ketoglutarate. Alpha-lipoic acid may be metabolized to dithiol octanoic acid, which can undergo catabolism.
INDICATIONS AND USAGE
Lipoic acid shows evidence of being effective in the treatment of diabetic neuropathy and may be useful in treating some other aspects of diabetes. It may help prevent the oxidation of LDL cholesterol and may be protective, generally, against oxidative stress and, specifically, against atherosclerosis, ischemia-reperfusion injury and various radiologic and chemical toxins. It may also be useful in some inborn metabolic disorders. There is less evidence that it might be helpful in some neurodegenerative conditions. There is preliminary evidence that it might have some immune-modulating effects. It has been suggested that lipoic acid may slow aging of the brain and that it may be an anti-aging substance, in general.
Lipoic acid is an approved treatment for diabetic neuropathy in Germany. Numerous studies in both animals and humans have produced promising results with lipoic acid in this neuropathy. In animal models and culture studies, lipoic acid has demonstrated antioxidant properties that help reduce or eliminate a sequence of events that include reduced endoneural blood flow and oxygen tension, which are pre-requisites of neuropathy. In addition, some of these studies have revealed favorable lipoic acid effects that appear to be independent of its antioxidant properties, including increased glucose uptake, promotion of new neurite growth and chelation of transition metals thought to play a role in diabetic neuropathy.
In some animal experiments, lipoic acid, administered for up to three months, significantly reversed the increase in nerve vascular resistance and the decrease in nerve blood flow in diabetic rats. Nerve conduction velocity was entirely restored in some nerve groups after three months of treatment.
Human clinical trials have been similarly encouraging. In one of these studies, subjects received 200 milligrams of intravenous lipoic acid daily. After 21 days, significant pain reduction was achieved in most subjects.
In a larger, multi-center, double-blind, randomized, placebo-controlled study of 328 patients with type 2 diabetes, significant improvements were recorded in several clinical measures of diabetic polyneuropathy, including pain, numbness, paresthesia and burning sensations. These results were evident after three weeks of intravenous lipoic acid given five times weekly in doses of 600 and 1200 milligrams.
Nerve conduction velocity has not been shown to improve in the short-term human studies conducted so far. One group of researchers has suggested that proof of neurophysiological improvement in these neuropathies may emerge from long-term lipoic acid supplementation studies, as has been the case in some animal model studies. "A period of several years," they have observed, "is required to slow progress of diabetic neuropathy due to normalization of blood glucose levels."
There is evidence, too, that lipoic acid may help prevent or slow the development of the atherosclerosis for which diabetics are at higher risk. It may do this, in part, through a gene-regulatory mechanism that helps prevent endothelial cell activity that has been implicated in the progression of atherosclerosis.
With respect to atherosclerosis, in general, lipoic acid's antioxidant and metabolic effects appear to offer some protection, as demonstrated in various animal models. Recently, researchers demonstrated, in a 16-week randomized trial, that lipoic acid, in oral doses of 600 milligrams daily for eight weeks, significantly inhibits the oxidation of LDL-cholesterol in healthy human subjects. The supplements also significantly reduced levels of F-2 isoprostanes, markers of oxidative stress. In this study, lipoic acid proved to be superior to vitamin E in decreasing levels of plasma protein carbonyls. Protein oxidation and LDL-cholesterol oxidation are implicated in heart disease.
Various animal studies have suggested that lipoic acid can prevent or reduce cell and tissue damage in heart attacks and stroke. There is extensive animal work showing that lipoic acid can exert significant protective effects against ischemia-reperfusion injury.
Lipoic acid is believed to work in this context, at least in part, through its antioxidant properties and its reported ability to increase cellular levels of glutathione that are typically depleted by the reactive oxygen species formation that characterizes ischemia-reperfusion. More research is needed to further elucidate these mechanisms and determine whether these results will apply in humans.
Animal work is also suggestive of some modest benefit from lipoic acid in the treatment of various neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and Huntington's disease. Results to date, however, remain inconclusive. Clinical studies are needed.
There is some evidence that children afflicted with inborn errors of pyrurate metabolism may derive some benefit from lipoic acid treatment. Those with Wilson's disease, a genetic disorder characterized by disturbed copper metabolism, may be helped by lipoic acid as well. The supplement has also proved useful in conferring some protection against cadmium poisoning and hexane inhalation. It has also been used in some liver toxicities, such as Amanita phalloides mushroom poisoning.
Lipoic acid's role in immunity is not well understood. There are reports that it can augment antibody response in some animal models of immunosuppression. This research warrants followup.
Claims that lipoic acid slows aging of the brain and is an anti-aging substance generally seem to be related to its potent antioxidant properties. Direct proof of anti-aging is lacking, but there is some animal work suggestive of some possible anti-aging effects.
Rats were fed a lipoic-acid supplemented diet to see whether the substance can reverse age-related declines in metabolism and mitochondrial function. Unsupplemented aged rats (24 to 26 months) exhibited ambulatory activity, said to be a general measure of metabolic activity, that was threefold lower than that of young controls. But this decline was significantly reversed in similarly aged rats supplemented with lipoic acid for two weeks.
Hepatocytes from untreated aged rats, compared with hepatocytes of young controls (three to five months), had significantly lower oxygen consumption and mitochondrial membrane potential. But in supplemented aged rats, hepatocytes, by the same measures, were comparable to those of the young controls.
Lipoic acid supplementation was reported to completely reverse age-related declines in hepatocyte ascorbic acid and glutathione levels. There was additional evidence of decreased oxidative damage in the lipoic-acid supplemented aged rats. The researchers concluded: "Little is known about whether lipoic acid may be an effective anti-aging supplement...in humans. Our present findings using rats would suggest that lipoic acid supplementation may be a safe and effective means to improve general metabolic activity and increase antioxidant status, affording increased protection against external oxidative and xenobiotic insults with age." Again, further study is needed.
CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS
Because of lack of long-term safety data, alpha-lipoic acid should be avoided by pregnant women and nursing mothers.
Those with diabetes and problems with glucose intolerance are cautioned that supplemental alpha-lipoic acid may lower blood glucose levels. Blood glucose should be monitored and antidiabetic drug dose adjusted, if necessary, to avoide possible hypoglycemia.
To date, alpha-lipoic acid in doses up to 600 milligrams daily has been well tolerated.
Supplemental alpha-lipoic acid may lower blood glucose levels. Those with diabetes on antidiabetic medication should have their blood glucose monitored and antidiabetic drug dose appropriately adjusted, if necessary, to avoid possible hypoglycemia.
There are no reports of alpha-lipoic acid overdosage.
DOSAGE AND ADMINISTRATION
Alpha-lipoic acid is available as a racemic mixture of D- and L- entantiomers. Some studies showing significant antioxidant effects have used doses of the racemic mixture of 600 milligrams daily.
Alpha-lipoic acid is available in Germany as a drug to treat polyneuropathy, such as diabetic polyneuropathy, and liver disorders. It is available for oral and parenteral use. Those with diabetic neuropathy use 300 milligrams daily of the oral preparation, taken in divided doses.
Capsules — 100 mg, 330 mg
Tablets — 50 mg
07-07-2004, 01:20 PM #10
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