Lipoic Acid

Alpha Lipoic Acid – Alpha lipoic acid (ALA) is a vitamin-like antioxidant, sometimes referred to as the “universal antioxidant,” because it is soluble in both fat and water.1 ALA is capable of regenerating several other antioxidants back to their active states, including vitamin C, vitamin E, glutathione and Coenzyme Q10

Alpha lipoic acid has several potential benefits for people with diabetes. It enhances glucose uptake in type 2 (non-insulin-dependent) diabetes, inhibits glycosylation (the abnormal attachment of sugar to protein), and has been used to improve diabetic nerve damage and reduce pain associated with that nerve damage.6 Most studies have used intravenous alpha lipoic acid, but oral supplementation has nonetheless proved partially helpful in treating at least one form of diabetic neuropathy, using 800 mg per day.

Preliminary evidence indicates that 150 mg of alpha lipoic acid, taken daily for one month, improves visual function in people with glaucoma.

Alpha lipoic acid has been shown to inhibit the replication of the HIV virus in the test tube. However, it is not known whether supplementing with alpha lipoic acid would benefit HIV-infected people.9

Intravenous administration of alpha lipoic acid has significantly increased the survival rate of people who have eaten poisonous mushrooms. Such a treatment should be prescribed by a doctor and should not be attempted on one’s own.

The body makes small amounts of alpha lipoic acid. There is only limited knowledge about the food sources of this nutrient. However, foods that contain mitochondria (a specialized component of cells), such as red meats, are believed to provide the most alpha lipoic acid. Supplements are also available.

Clinical Indications:

1. Diabetic neuropathy:

Supplementation with 600 mg, 3 times per day for 3 weeks, resulted in clinical improvement in a double-blind study.

Another study showed little or no benefit. Lower doses, such as 100-200 mg/day, have been used clinically in Europe for diabetic neuropathy.

2. Amanita mushroom poisoning:

Intravenous administration of alpha-lipoic acid has been shown to reduce mortality due to Amanita mushroom poisoning (uncontrolled trials and case reports).

3. Human immunodeficiency virus (HIV):

Alpha-lipoic acid, at a concentration 000 mcg/ml, inhibited HIV replication in vitro; the clinical significance of this finding is not clear. Supplementation with 150 mg, 3 times per day for 14 days, increased the number of helper Tcells in 6 of 10 patients (uncontrolled trial).

4. Burning mouth syndrome:

Supplementation with 200 mg, 3 times per day for 2 months, significantly (p < 0.0001) reduced symptoms, compared with placebo (double-blind trial).

Nutrient Interactions:

Alpha-lipoic acid is a metal chelator and has been shown to increase the excretion of copper in patients with Wilson's disease. Long-term administration might, therefore, promote a deficiency of copper or other minerals in patients without Wilson's disease.

Toxicity:

No serious adverse effects have been reported. However lipoic acid was lethal when administered at a dose of20 mg/kg intraperitoneally to thiamine-deficient rats. This toxic effect was prevented by pre-treatment with thiamine. It would therefore be prudent to administer thiamine or vitamin B-complex to patients receiving lipoic acid who are at risk of being deficient in B-vitamins.

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours.
Br J Cancer 2001 Jun 1;84(11):1544-50 (ISSN: 0007-0920)
Casciari JJ; Riordan NH; Schmidt TL; Meng XL; Jackson JA; Riordan HD Bio-Communications Research Institute, Center for the Improvement of Human Functioning International, 3100 North Hillside Avenue, Wichita, KS 67219, USA.
Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment. Our goal was to determine if ascorbate, in combination with other antioxidants, could kill cells in the SW620 hollow fibre in vitro solid tumour model at clinically achievable concentrations. Ascorbate anti-cancer efficacy, alone or in combination with lipoic acid, vitamin K3, phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC(50)in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally effective against proliferating and non-proliferating cells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma concentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K3. The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing. [Copyright 2001 Cancer Research Campaign.].

References:

1. Kagan V, Khan S, Swanson C, et al. Antioxidant action of thioctic acid and dihydrolipoic acid. Free Radic Biol Med 1990;9S:15.

2. Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN. Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with (R)-alpha-lipoic acid supplementation. FASEB J 1998;12:1183–9.

3. Scholich H, Murphy ME, Sies H. Antioxidant activity of dihydrolipoate against microsomal lipid peroxidation and its dependence on alpha-tocopherol. Biochem Biophys Acta 1989;1001:256–61.

4. Busse E, Zimmer G, Schorpohl B, et al. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittelforschung1992;42:829–31.

5. Kagan V, Serbinova E, Packer L. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Biochem Biophys Res Commun 1990;169:851–7.

6. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19:227–50 [review].

7. Ziegler D, Ulrich H, Schatz H, et al. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. Diabetes Care 1997;20:369–73.

8. Filina AA, Davydova NG, Endrikhovskii SN, et al. Lipoic acid as a means of metabolic therapy of open-angle glaucoma. Vestn Oftalmol 1995;111:6–8.

9. Baur A, Harrer T, Peukert M, et al. Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. Klin Wochenschr 1991;69:722–4.

10. Nichols TW Jr. Alpha-lipoic acid: biological effects and clinical implications. Altern Med Rev 1997;2:177–83 [review].

11. Zempleni J, Trusty TA, Mock DM. Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver. J Nutr 1997;127:1776–81.