Te copio un artículo del ALA, con referencias (lo siento que sea largo, pero se lo puedes pegar en la cara al médico que te dijo que no existen protectores hepáticos):
ALPHA LIPOIC ACID
OVERVIEW
Alpha lipoic acid, (also known as lipoic acid, thioctic acid) is a sulfur-containing vitamin-like antioxidant. Alpha lipoic acid is produced naturally in the body and found in the food sources of liver, brewer’s yeast, and potatoes. Alpha lipoic acid has dual role in human health; it is a powerful antioxidant and is a key component for producing cellular energy. As an antioxidant, alpha lipoic acid is unique in that it is both water- and fat-soluble; thus it can be used throughout the body. It also extends and enhances the effect of other antioxidants, which are used to defend the body against free radical damage. In its metabolic role, alpha lipoic acid is a fundamental coenzyme in two vital reactions that lead to the production of cellular energy (ATP). Alpha lipoic acid was first isolated in 1957, and originally, seemed to be a member of the vitamin B–complex. Alpha lipoic acid would have been the first fat-soluble B vitamin isolated. Most human coenzymes are produced from some of the B-complex vitamins or are themselves vitamins (Passwater, 1995). Alpha lipoic acid is not considered a vitamin, but is termed a "conditionally essential" nutrient. This is because presumably the body can produce sufficient levels or it is acquired in sufficient quantities from food (Murray, 1996). The human body can make enough alpha lipoic acid to prevent a recognizable deficiency disease, though not enough to perform all its functions. The optimal level of alpha lipoic acid varies with each person depending on biochemical differences, lifestyle, exercise and how much oxidative stress they experience. Certain diseases, environmental conditions and age can cause a deficiency in lipoic acid, and thus the body often doesn’t make enough to meet all its metabolic and antioxidant needs.
METHOD OF ACTION
Alpha lipoic acid is involved in the metabolic process of converting carbohydrates into energy. When sugar is metabolized in the production of energy, it is converted into pyruvic acid. The pyruvate is broken down by an enzyme complex that contains lipoic acid, niacin and thiamin. Since the human body tends to have only the minimum amount of alpha lipoic acid to prevent recognizable disease, supplementation may help improve energy metabolism. This is particularly applicable in people with lower than normal levels, for example, individuals with diabetes, liver cirrhosis, heart disease and HIV.
As an antioxidant, since alpha lipoic acid is both water- and fat-soluble it is effective against a broader range of free radicals than vitamin C (water soluble) and vitamin E (fat-soluble). Because of it unique size and chemical structure, lipoic acid has access to virtually the entire body, whereas most antioxidants only protect isolated areas of the body. Inside the cell, alpha lipoic acid is quickly broken down to dihydrolipoic acid, and even more potent free-radical scavenger. Supplementation with lipoic acid wards off scurvy (vitamin C deficiency).
THERAPEUTIC APPROACHES
The principal uses of alpha lipoic acid are in the treatment of diabetes and HIV/AIDS. It has also been used in cases of liver cirrhosis, heart disease, cataracts, heavy-metal toxicity and detoxification support.
Alpha lipoic acid is available in supplemental form of tablets and capsules. For use as a general antioxidant, the recommended dose is 20 to 50 mg daily. In the treatment of diabetes, the recommended dose is 300 to 600 mg daily. In the treatment of AIDS, the recommended dose is 150 mg three times daily (Murray, 1996). Although lipoic acid deficiency states have not been demonstrated in human beings, animal studies show that a deficiency of lipoic acid results in reduced muscle mass, brain atrophy, failure to thrive and increased lactic acid accumulation.
DIABETES
Alpha lipoic acid has been used in Europe for over three decades to treat diabetic neuropathy, to help regulate blood sugar, and prevent diabetic retinopathy and cardiopathy. Alpha lipoic acid is an approved drug in Germany for the treatment of diabetic neuropathy. Alpha lipoic acid normalizes blood sugar levels in diabetics and also reduces the secondary effects of diabetes, including retinopathy, cataract formation, nerve and heart damage, as well as increasing energy levels. It is used in the treatment of both insulin-dependent and non-insulin dependent diabetes. Alpha lipoic acid helps control blood sugar by facilitating the conversion of sugar into energy. Alpha lipoic acid reduces glycation (also known as glycosylation), which is the process in which proteins react with excess glucose. This sugar reaction to protein is just as detrimental as oxygen damage (free radical damage). Alpha lipoic acid helps to keep blood sugar levels under control and reduced levels of glucose mean less glycation. This is important in reducing diabetic side effects and slowing aging. In summary, alpha lipoic acid’s effect on diabetes is through its potent antioxidant capabilities, as well improving blood sugar metabolism, reducing glycosylation of proteins, improving blood flow to the peripheral nerves, and actually stimulating regeneration of nerve fibers (Wagh, 1987).
AIDS
Individuals infected with the HIV virus tend to have a compromised antioxidant defense system. During HIV infection, key cells of the immune system called CD lymphocytes lose their ability to make and to transport glutathione. Antioxidants such as glutathione prevent HIV viral replication while reactive oxidants tend to stimulate the virus. Glutathione is a major cellular antioxidant, and thus, the CD lymphocytes are exposed to excess oxidative stress and this contributes to immune system failure. Alpha lipoic acid is a powerful antioxidant and facilitator of glutathione production. A strong antioxidant defense system can help prevent this oxidative damage and help keep the immune system strong.
A study was conducted by Dr. Fuchs and colleagues, to determine the short-term effect of supplemental lipoic acid. Alpha lipoic acid was given as a supplement (150 mg three times daily for a two week period) to HIV-infected patients. Lipoic acid supplementation increased total glutathione in seven of seven patients, plasma ascorbate in nine of ten patients, total plasma sulfur groups in eight of nine patients, and T helper lymphocytes and T helper/suppressor cell ratio in six of ten patients. The conclusion of this study is that lipoic acid supplementation led to significant beneficial changes in the blood of HIV-infected patients (Fuchs, et al., 1993).
Alpha lipoic acid has been beneficial to cancer patients suffering with peripheral neuropathy, a damaging side effect of chemotherapy. Lipoic acid also protects against cancer as a result of its potent antioxidant effects. Lipoic acid protects a complex called Nuclear Factor kappa-B and prevents it from activating oncogenes. Oncogenes are genes that contribute to cancer cell proliferation. When these genes are altered by either NF kappa-B or a carcinogen, they cause the cell to become malignant. Lipoic acid can enter the cytosol of cells and protect NF kappa-B from activation by free radical, radiation, or even sunlight.
Alpha lipoic acid may be helpful in other conditions including Liver cirrhosis, hepatitis, heart disease, cataracts, heavy metal toxicity, and support during detoxification. Its role in detoxification is as a chelator (remover) of heavy metals and toxic minerals from the body.
Alpha lipoic acid protects the nervous system and may be involved in regenerating the nerves. It is being studied in the treatment of Parkinson’s disease and Alzheimer’s disease.
Alpha lipoic acid has been shown to improve antibody response in immunosuppressed animals (Quillin, 1998).
SAFETY ISSUES
Alpha lipoic acid supplementation is very safe. In over 30 years of extensive use and testing in European clinical trials in the treatment of diabetic neuropathy, there have been no reported side effects (Quillin, 1998, Murray, 1996). Studies have not reported any carcinogenic or teratogenic effects. As a precaution, until further information is available, alpha lipoic acid is not recommended for pregnant women. Animal studies show very low toxicity (Murray, 1996).
CURRENT ABSTRACTS
DIABETES
Ziegler D; Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 1997 Sep;46 Suppl 2:S62.
Antioxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes, providing a rationale for a potential therapeutic value in diabetic patients. The effects of the antioxidant alpha-lipoic acid (thioctic acid) were studied in two multicenter, randomized, double-blind placebo-controlled trials. In the Alpha-Lipoic Acid in Diabetic Neuropathy Study, 328 patients with NIDDM and symptomatic peripheral neuropathy were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (ALA 1,200 mg; 600 mg; 100 mg) or placebo (PLAC) over 3 weeks. The total symptom score (TSS) (pain, burning, paresthesia, and numbness) in the feet decreased significantly from baseline to day 19 in ALA 1,200 and ALA 600 vs. PLAC. Each of the four individual symptom scores was significantly lower in ALA 600 than in PLAC after 19 days (all P < 0.05). The total scale of the Hamburg Pain Adjective List (HPAL) was significantly reduced in ALA 1,200 and ALA 600 compared with PLAC after 19 days (both P < 0.05). In the Deutsche Kardiale Autonome Neuropathie Studie, patients with NIDDM and cardiac autonomic neuropathy diagnosed by reduced heart rate variability were randomly assigned to treatment with a daily oral dose of 800 mg alpha-lipoic acid (ALA) (n = 39) or placebo (n = 34) for 4 months. Two out of four parameters of heart rate variability at rest were significantly improved in ALA compared with placebo. A trend toward a favorable effect of ALA was noted for the remaining two indexes. In both studies, no significant adverse events were observed. In conclusion, intravenous treatment with alpha-lipoic acid (600 mg/day) over 3 weeks is safe and effective in reducing symptoms of diabetic peripheral neuropathy, and oral treatment with 800 mg/day for 4 months may improve cardiac autonomic dysfunction in NIDDM.
HIV & AIDS
Suzuki YJ; Aggarwal BB; Packer L. Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun 1992 Dec 30;189(3):1709-15.
Acquired immunodeficiency syndrome (AIDS) results from infection with a human immunodeficiency virus (HIV). The long terminal repeat (LTR) region of HIV proviral DNA contains binding sites for nuclear factor kappa B (NF-kappa B), and this transcriptional activator appears to regulate HIV activation. Recent findings suggest an involvement of reactive oxygen species (ROS) in signal transduction pathways leading to NF-kappa B activation. The present study was based on reports that antioxidants which eliminate ROS should block the activation of NF- kappa B and subsequently HIV transcription, and thus antioxidants can be used as therapeutic agents for AIDS. Incubation of Jurkat T cells (1 x 10(6) cells/ml) with a natural thiol antioxidant, alpha-lipoic acid, prior to the stimulation of cells was found to inhibit NF-kappa B activation induced by tumor necrosis factor-alpha (25 ng/ml) or by phorbol 12-myristate 13-acetate (50 ng/ml). The inhibitory action of alpha-lipoic acid was found to be very potent as only 4 mM was needed for a complete inhibition, whereas 20 mM was required for N- acetylcysteine. These results indicate that alpha-lipoic acid may be effective in AIDS therapeutics.
ANTIOXIDANT
Packer L. Alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal
transduction and protects against oxidative injury. Drug Metab Rev 1998 May;30(2):245-75.
Although the metabolic role of alpha-lipoic acid has been known for over 40 years, it is only recently that its effects when supplied exogenously have become known. Exogenous alpha-lipoic acid is reduced intracellularly by at least two and possibly three enzymes, and through the actions of its reduced form, it influences a number of cell process. These include direct radical scavenging, recycling of other antioxidants, accelerating GSH synthesis, and modulating transcription factor activity, especially that of NF-kappa B. These mechanisms may account for the sometimes dramatic effects of alpha-lipoic acid in oxidative stress conditions (e.g., brain ischemia- reperfusion), and point the way toward its therapeutic use.
Biewenga GP; Haenen GR; Bast A; The pharmacology of the antioxidant lipoic acid Gen Pharmacol 1997 Sep;29(3):315-31.
1. Lipoic acid is an example of an existing drug whose therapeutic effect has been related to its antioxidant activity. 2. Antioxidant activity is a relative concept: it depends on the kind of oxidative stress and the kind of oxidizable substrate (e.g., DNA, lipid, protein). 3. In vitro, the final antioxidant activity of lipoic acid is determined by its concentration and by its antioxidant properties. Four antioxidant properties of lipoic acid have been studied: its metal chelating capacity, its ability to scavenge reactive oxygen species (ROS), its ability to regenerate endogenous antioxidants and its ability to repair oxidative damage.
4. Dihydrolipoic acid (DHLA), formed by reduction of lipoic acid, has more antioxidant properties than does lipoic acid. Both DHLA and lipoic acid have metal-chelating capacity and scavenge ROS, whereas only DHLA is able to regenerate endogenous antioxidants and to repair oxidative damage. 5. As a metal chelator, lipoic acid was shown to provide antioxidant activity by chelating Fe2+ and Cu2+; DHLA can do so by chelating Cd2+. 6. As scavengers of ROS, lipoic acid and DHLA display antioxidant activity in most experiments, whereas, in particular cases, pro-oxidant activity has been observed. However, lipoic acid can act as an antioxidant against the pro-oxidant activity produced by DHLA. 7. DHLA has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C and glutathione. 8. DHLA can provide peptide methionine sulfoxide reductase with reducing
equivalents. This enhances the repair of oxidatively damaged proteins such as alpha-1 antiprotease. 9. Through the lipoamide dehydrogenase-dependent reduction of lipoic acid, the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool, which is usually consumed during oxidative stress. 10. Within drug-related antioxidant pharmacology, lipoic acid is a model compound that enhances understanding of the mode of action of antioxidants in drug therapy.
GLYCATION
Bierhaus A; Chevion S; Chevion M; Hofmann M; Quehenberger P; Illmer T; Luther T; Berentshtein E; Tritschler H; Muller M; Wahl P; Ziegler R; Nawroth PP. Diabetes 1997 Sep;46(9):1481-90.
Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells
Depletion of cellular antioxidant defense mechanisms and the generation of oxygen free radicals by advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic vascular complications. Here we demonstrate that incubation of cultured bovine aortic endothelial cells (BAECs) with AGE albumin (500 nmol/l) resulted in the impairment of reduced glutathione (GSH) and ascorbic acid levels. As a consequence, increased cellular oxidative stress led to the activation of the transcription factor NF-kappaB and thus promoted the upregulation of various NF-kappaB-controlled genes, including endothelial tissue factor. Supplementation of the cellular antioxidative defense with the natural occurring antioxidant alpha- lipoic acid before AGE albumin induction completely prevented the AGE albumin-dependent depletion of reduced glutathione and ascorbic acid. Electrophoretic mobility shift assays (EMSAs) revealed that AGE albumin- mediated NF-kappaB activation was also reduced in a time- and dose- dependent manner as long as alpha-lipoic acid was added at least 30 min before AGE albumin stimulation. Inhibition was not due to physical interactions with protein DNA binding, since alpha-lipoic acid, directly included into the binding reaction, did not prevent binding activity of recombinant NF-kappaB. Western blots further demonstrated that alpha-lipoic acid inhibited the release and translocation of NF- kappaB from the cytoplasm into the nucleus. As a consequence, alpha- lipoic acid reduced AGE albumin-induced NF-kappaB mediated transcription and expression of endothelial genes relevant in diabetes, such as tissue factor and endothelin-1. Thus, supplementation of cellular antioxidative defense mechanisms by extracellularly administered alpha-lipoic acid reduces AGE albumin-induced endothelial dysfunction in vitro.
LIVER DISEASE
Bustamante J; Lodge JK; Marcocci L; Tritschler HJ; Packer L; Rihn BH. Alpha-lipoic acid in liver metabolism and disease. Free Radic Biol Med 1998 Apr;24(6):1023-39.
R-alpha-Lipoic acid is found naturally occurring as a prosthetic group in alpha-keto acid dehydrogenase complexes of the mitochondria, and as such plays a fundamental role in metabolism. Although this has been known for decades, only recently has free
supplemented alpha-lipoic acid been found to affect cellular metabolic processes in vitro, as it has the ability to alter the redox status of cells and interact with thiols and other antioxidants. Therefore, it appears that this compound has important therapeutic potential in conditions where oxidative stress is involved. Early case studies with alpha-lipoic acid were performed with little knowledge of the action of alpha-lipoic acid at a cellular level, but with the rationale that because the naturally occurring protein bound form of alpha-lipoic acid has a pivotal role in metabolism, that supplementation may have some beneficial effect. Such studies sought evaluate the effect of supplemented alpha-lipoic acid, using low doses, on lipid or carbohydrate metabolism, but little or no effect was observed. A common response in these trials was an increase in glucose uptake, but increased plasma levels of pyruvate and lactate were also observed, suggesting that a inhibitory effect on the pyruvate dehydrogenase complex was occurring. During the same period, alpha-lipoic acid was also used as a therapeutic agent in a number of conditions relating to liver disease, including alcohol-induced damage, mushroom poisoning, metal intoxification, and CCl4 poisoning. Alpha-Lipoic acid supplementation was successful in the treatment for these conditions in many cases. Experimental studies and clinical trials in the last 5 years using high doses of alpha-lipoic acid (600 mg in humans) have provided
new and consistent evidence for the therapeutic role of antioxidant alpha-lipoic acid in the treatment of insulin resistance and diabetic polyneuropathy. This new insight should encourage clinicians to use alpha-lipoic acid in diseases affecting liver in which oxidative stress is involved.
NEURODEGENERATIVE DISEASES
Packer L; Tritschler HJ; Wessel K . Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med 1997;22(1-2):359-78.
Reactive oxygen species are thought to be involved in a number of types of acute and chronic pathologic conditions in the brain and neural tissue. The metabolic antioxidant alpha-lipoate (thioctic acid, 1, 2- dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6, 8- dithiooctanoic acid) is a low molecular weight substance that is absorbed from the diet and crosses the blood-brain barrier. alpha- Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which is also exported to the extracellular medium; hence, protection is afforded to both intracellular and extracellular environments. Both alpha-lipoate and especially dihydrolipoate have been shown to be potent antioxidants, to regenerate through redox cycling other antioxidants like vitamin C and vitamin E, and to raise intracellular glutathione levels. Thus, it would seem an ideal substance in the treatment of oxidative brain and neural disorders involving free radical processes. Examination of current research reveals protective effects of these compounds in cerebral ischemia-reperfusion, excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism, and other causes of acute or chronic damage to brain or neural tissue. Very few neuropharmacological intervention strategies are currently available for the treatment of stroke and numerous other brain disorders involving free radical injury. We propose that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas alpha-lipoic acid can. In vitro, animal, and preliminary human studies indicate that alpha- lipoate may be effective in numerous neurodegenerative disorders.
REFERENCES
Bierhaus A; Chevion S; Chevion M; Hofmann M; Quehenberger P; Illmer T; Luther T; Berentshtein E; Tritschler H; Muller M; Wahl P; Ziegler R; Nawroth PP. Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. Diabetes 1997 Sep;46(9):1481-90.
Biewenga GP; Haenen GR; Bast A; The pharmacology of the antioxidant lipoic acid Gen Pharmacol 1997 Sep;29(3):315-31.
Bustamante J; Lodge JK; Marcocci L; Tritschler HJ; Packer L; Rihn BH. Alpha-lipoic acid in liver metabolism and disease. Free Radic Biol Med 1998 Apr;24(6):1023-39.
Fuchs, J. et al., Studies on lipoate effects on blood redox state in human immunodeficiency virus (HIV 1) replication. Arzeim Forsch 43, 1359-1362,1993.
Golan, R.1995. Optimal Wellness. New York: Ballentine books.
Jacob, S. et al., Enhancement of Glucose Disposal in Patients with Type 2 diabetes by Alpha Lipoic Acid. Arzeim Forsch 45,872-874,1995.
Murray, M. 1996. Encyclopedia of Nutritional Supplements. Rocklin, Ca: Prima Publishing.
Packer L. Alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal transduction and protects against oxidative injury. Drug Metab Rev 1998 May;30(2):245-75.
Packer L; Tritschler HJ; Wessel K . Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med 1997;22(1-2):359-78.
Packer, L. Antioxidant Properties of Lipoic Acid and its Therapeutic Effects in Prevention of Diabetes Complications and Cataracts. Annals NY Acad Sci 738, 257-264, 1994.
Packer, L.& Tritschler, H. Alpha Lipoic as a Biological Antioxidant. Free Rad Biol Med 19, 227-250, 1995.
Passwater, R. 1995. Lipoic Acid: The Metabolic Antioxidant.New Canaan, Conneticut: Keats Publishing.
Quillin, P. & N. 1998. Beating Cancer with Nutrition. Tulsa, OK.: Nutrtion Times Press.
Quillin, P. & Reynolds, A. 1988. The La Costa Book of Nutrition. New york: Pharos Books.
Quillin, P. 1989. Healing Nutrients. New York: Random House.
Scott, B. et al., Lipoic and Dihydrolipoic Acids as Antioxidants: A Critical Review. Free Rad Res 20, 119-133, 1994.
Somer, E.1995. The Essential Guide to Vitamins and Minerals.New York: HarperCollins.
Suzuki YJ; Aggarwal BB; Packer L. Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun 1992 Dec 30;189(3):1709-15.
Ziegler D; Gries FA. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes 1997 Sep;46 Suppl 2:S62.
Saludos.
-Animated.gif)
Please Scroll Down to See Forums Below 
.jpg "Research Chemical Sciences")
.png "Research Chemical Sciences")
