Long-term safety of α-lipoic acid (ALA) consumption: A 2-year study

Regulatory Toxicology and Pharmacology

Volumn 46, Issue 3, 2006, Pages 193-201

  Cremer, D R ^a   Rabeler, R ^a   Roberts, A ^b   Lynch, B ^b  

^a EVONIK INDUSTRIES AG   (Germany)

^b Cantox Health Sciences International   (Canada)

Author keywords

Lipoic acid; 2 Year; 24 Months; Anti oxidant; Carcinogenicity; Chronic; Free radical; Safety; Thioctic acid; Toxicity; Tumour

Indexed keywords

THIOCTIC ACID;

ADRENAL GLAND; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANOREXIA; APATHY; ARTICLE; ATAXIA; BEHAVIOR CHANGE; CARCINOGENICITY; CHRONIC TOXICITY; CLINICAL CHEMISTRY; CONTROLLED STUDY; DECREASED APPETITE; DRUG MEGADOSE; DRUG SAFETY; DRUG USE; FEMALE; FOOD INTAKE; HEART WEIGHT; HEMATOLOGICAL PARAMETERS; HISTOPATHOLOGY; LIVER WEIGHT; LONG TERM EXPOSURE; LUNG WEIGHT; MALE; MORTALITY; NONHUMAN; PNEUMONIA; PRIORITY JOURNAL; RAT; THYMUS; TOXICITY TESTING; WEIGHT GAIN;

ADMINISTRATION, ORAL; ANIMALS; ANTIOXIDANTS; BODY WEIGHT; CARCINOGENICITY TESTS; DOSE-RESPONSE RELATIONSHIP, DRUG; EATING; FEMALE; MALE; NO-OBSERVED-ADVERSE-EFFECT LEVEL; ORGAN SIZE; RATS; RATS, SPRAGUE-DAWLEY; THIOCTIC ACID; TIME FACTORS;

ANIMALIA;

EID: 33750607920     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2006.06.003     Document Type: Article

References (42)

1. Betke B., and Savelsberg W. Stage-photometric determination of hemoglobin by means of cyanhemoglobin. Klin. Wochenschr. 28 (1950) 482
2. Biewenga G.P., Haenen G.R., and Bast A. The pharmacology of the antioxidant lipoic acid. Gen. Pharmacol. 29 3 (1997) 315-331
3. Bilska A., and Wlodek L. Lipoic acid-the drug of the future?. Pharmacol. Rep. 57 5 (2005) 570-577
4. Bonnefont-Rousselot D. The role of antioxidant micronutrients in the prevention of diabetic complications. Treat. Endocrinol. 3 1 (2004) 41-52
5. Cremer, D.R., Rabeler, R., Roberts, A., Lynch, B., 2006. Safety evaluation of α-lipoic acid (ALA). Regul. Toxicol. Pharmacol., this issue, doi:10.1016/j.yrtph.2006.06.004.
6. Chidlow G., Schmidt K.G., Wood J.P., Melena J., and Osborne N.N. Alpha-lipoic acid protects the retina against ischemia-reperfusion. Neuropharmacology 43 6 (2002) 1015-1025
7. Denolin-Reubens R., and Durieu H. Presentation by the method of dry smears stained by the Pappenheim method of dry smears stained by the Pappenheim method of cancerous cells in expectorations and extravasations of the pleura and peritoneum; results and limitations of the method. Acta Chir. Belg. 52 5 (1953) 525-534
8. Evans J.L., and Goldfine I.D. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol. Ther. 2 3 (2000) 401-413
9. Flechter H. Unknown. Swiss Med. Wkly. 21 (1956) 259
10. Folin O. On the determination of creatinine and creatine in blood, milk and tissues. J. Biol. Chem. 17 4 (1914) 475-481
11. Freisleben H.J. Lipoate ameliorates ischemia-reperfusion in animal models. Clin. Hemorheol. Microcirc. 23 2-4 (2000) 219-224
12. Fuke H., Koki I., Watanabe N., and Kumada S. Acute, subacute and chronic toxicities of thioctic acid in rats. Nippon Yakurigaku Zasshi 68 (1972) 265 175
13. Gonzalez-Perez O., Gonzalez-Castaneda R.E., Huerta M., Luquin S., Gomez-Pinedo U., Sanchez-Almaraz E., Navarro-Ruiz A., and Garcia-Estrada J. Beneficial effects of alpha-lipoic acid plus vitamin E on neurological deficit, reactive gliosis and neuronal remodelling in the penumbra of the ischemic rat brain. Neurosci. Lett. 321 1-2 (2002) 100-104
14. Habs M., Habs H., and Schmahl D. Influence of thioctic acid (alpha-lipoic acid) on N-nitroso-diethylamine-induced carcinogenesis in male Sprague-Dawley rats. Arzneimittelforschung 30 10 (1980) 1715-1717
15. ® for Nutritional Supplements (1st Ed.). Physicians' Desk Reference (PDR); Demoines, Iowa/Medical Economics Data Production Company; Montvale, New Jersey.
16. Henrisken E.J. Exercise training and the antioxidant α-lipoic acid in the treatment of insulin resistance and type 2 diabetes. Free Radic. Biol. Med. 40 (2006) 3-12
17. Hermann R., Niebch G., Borbe H.O., Fieger-Buschges H., Ruus P., Nowak H., Riethmuller H., Peukert M., and Blume H. Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic formulations in healthy volunteers. Eur. J. Pharm. Sci. 4 (1996) 167-174
18. Hill A.S., Werner J.A., Rogers Q.R., and O'Neill S.L. Lipoic acid is 10 times more toxic in cats than reported in humans, dogs, or rats. J. Anim. Physiol. Anim. Nutr. 88 (2004) 150-156
19. Jendrassik L., and Grof P. Vereinfachte photometrische Methoden zur Bestimmung des Bilirubins. Biochem. Z. 297 (1938) 81-89
20. Kim M.-S., Park J.-Y., Namkoong C., Jang P.-G., Ryu J.-W., Song H.-S., Yun J.-Y., Namgoong I.-S., Ha J., Park I.-S., Lee I.-K., Viollet B., Youn J.H., Lee H.-K., and Lee K.-U. Anti-obesity of α-lipoic acid mediated by suppression of hypothalamic AMP activated protein kinase. Nat. Med. 10 7 (2004) 727-733
21. Lillie R.D., and Ashburn L.L. Supersaturated solutions of fat stains in dilute isopropanol for demonstration of acute fatty degeneration not shown by Herxheimer technic. Arch. Pathol. 36 (1943) 432-435
22. Marangon K., Devaraj S., Tirosh O., Packer L., and Jialal I. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Radic. Biol. Med. 27 9-10 (1999) 1114-1121
23. Marsh W.H., Fingerhut B., and Miller H. Automated and manual direct methods for the determination of blood urea. Clin. Chem. 11 (1965) 624-627
24. Miadokova E., Vlckova V., and Duhova V. Antimutagenic effect of alpha-lipoic acid on three model test systems. Pharmazie 55 11 (2000) 862-863
25. Morgenstern S., Kessler G., Auerbach J., Flor R.V., and Klein B. An automated p-nitrophenylphosphate serum alkaline phosphatase procedure for the AutoAnalyzer. Clin. Chem. 11 9 (1965) 876-888
26. Morgenstern S., Oklander M., Auerbach J., Kaufman J., and Klein B. Automated determination of serum glutamic oxaloacetic transaminase. Clin. Chem. 12 2 (1966) 95-111
27. Packer L., Kraemer K., and Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 17 10 (2001) 888-895
28. Reed L. From lipoic acid to multi-enzyme complexes. Protein Sci. 7 (1998) 220-224
29. Reljanovic M., Reichel G., Rett K., Lobisch M., Schuette K., Möller W., Tritschler H.-J., Mehnert H., and The ALADIN II study group. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (α-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Free Radic. Res. 31 (1999) 171-179
30. Rosenthal S.M., and White E.C. Clinical application of bromosulfphthalein test for hepatic function. JAMA 84 (1925) 1112-1114
31. Ruhnau K.J., Meissner H.P., Finn J.R., Reljanovic M., Lobisch M., Schutte K., Nehrdich D., Tritschler H.J., Mehnert H., and Ziegler D. Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet. Med. 16 12 (1999) 1040-1043
32. Schupke H., Hempel R., Peter G., Hermann R., Wessel K., Engle J., and Kronbach T. New metabolic pathways of α-lipoic acid. Drug Metab. Dispos. 29 6 (2001) 855-862
33. Selvakumar E., Prahalathan C., Sudharsan P.T., and Varalakshmi P. Protective effect of lipoic acid on micronuclei induction by cyclophosphamide. Arch. Toxicol. 9 (2005) 1-5
34. Skeggs Jr. L.T., and Hochstrasser H. Multiple automatic sequential analyses. Clin. Chem. 10 (1964) 918-936
35. Sobrinho-Simoes M. A sensitive method for the measurement of serum uric acid using hydroxylamine. J. Lab. Clin. Med. 65 (1965) 665-668
36. Tankova T., Cherninkova S., and Koev D. Treatment for diabetic mononeuropathy with alpha-lipoic acid. Int. J. Clin. Pract. 59 6 (2005) 645-650
37. Teichert J., Kern J., Tritschler H.J., Ulrich H., and Preiss R. Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Int. J. Clin. Pharmacol. Ther. 36 12 (1998) 625-628
38. Teichert J., Hermann R., Ruus P., and Preiss R. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers. J. Clin. Pharmacol. 43 (2003) 1257-1267
39. van de Mark K., Chen J.S., Steliou K., Perrine S.P., and Faller D.V. Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines. J. Cell Physiol. 194 3 (2003) 325-340
40. Wollin S.D., and Jones P.J. Alpha-lipoic acid and cardiovascular disease. J. Nutr. 133 11 (2003) 3327-3330
41. Wroblewski F., and Ladue J.S. Serum glutamic pyruvic transaminase in cardiac with hepatic disease. Proc. Soc. Exp. Biol. Med. 91 4 (1956) 569-571
42. Ziegler D., Reljanovic M., Mehnert H., and Gries F.A. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp. Clin. Endocrinol. Diabetes 107 7 (1999) 421-430