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LE Magazine September 2003

Alpha Lipoic Acid, Acetyl-L-Carnitine and Carnosine
The Latest Significant Research on This Powerful Life Extension Trio
By Tim Batchelder, B.A.

ALC helps maintain liver function, which is essential for detoxification. One new study found that ALC almost completely restores the age-dependent decline in oxygen consumption, gluconeogenesis, urea synthesis, and ketogenesis found in the liver of old rats to the levels found in young rats.37 ALC also helps prevent hepatoxicity and increases survival during chemotherapy with heptotoxic alkylating agents for cancer.38 ALC and ALA are useful in treating muscle and nerve mitochondrial toxicity caused by nucleoside analog reverse transcriptase inhibitor therapy for HIV-AIDS.39 ALC also enhances detoxification of ethanol in the liver as well as the unpleasant side effects of detoxification. For example, it significantly reduces the onset of tremors in ethanol withdrawal syndrome as well as the level of ethanol intake in alcohol-preferring rats.40 One new study shows that ALA (and its chemical cousin alpha-lipoamide (LM) may work as an antioxidant by chelating iron which is involved in cell death by lysosomal rupture.41 Further, since it has a particular affinity for the liver ALA can also treat liver damage from mushroom poisoning, snake venom, acetaldehyde and viral hepatitis. ALA was studied extensively in the 1950s for radiation protection and was found to be more effective than other common radio-protectants such as cysteamine. It was put to use for victims of Chernobyl, and as a sulfur compound, can bind and eliminate heavy metals. ALA is also shown to decrease smoking-related lipid peroxidation.42 Finally, carnosine is a potent radioprotectant and prevents damage by cold, hyperthermia, and hypoxia.43

Support for Energy, Muscle Recovery and Weight Loss
Exercise creates a heavy load of free radical activity, which makes it a natural target for powerful antioxidants like ALA, ALC and carnosine. Several recent studies have looked at how these compounds work to protect muscle tissue during exercise and maintain energy stores. For example, one study noted that carnosine inhibits lipid peroxidation and oxidative modification of protein in muscle tissue.44 It works as a pH buffer to protect muscle cells from oxidation under the acidic conditions of muscular exertion. Similar, ALA decreases lipid peroxidation and lactic acid accumulation and increases levels of glutathione, vitamins C and E and the activities of mitochondrial enzymes, which prevents tissue damage and improves ATP (energy) synthesis.45 ALA also helps Chronic Fatigue Syndrome.46 Finally, ALA and exercise interact in an additive fashion to improve insulin action in insulin-resistant skeletal muscles in obese rats.47

Conclusion
The surge of recent research on the synergies and anti-aging benefits of ALA, ALC and carnosine is making them an important addition to any supplement plan. What is so exciting is the versatility of these antioxidant compounds, which seem to work in so many body systems, from the nervous system to the cardiovascular, musculoskeletal and immune systems. In doing so they are able to effectively combat the major diseases of our time including diabetes, cognitive decline and Alzheimer’s, heart disease, obesity and immune disorders such as cancer and HIV-AIDS.

References

1. Liu J, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding aceyl-l-carnitine and/or R-alpha- lipoic acid. Proc Natl Acad Sci USA 2002 Feb 19;99(4):2356-61.

2. Hagen TM, et al. Feeding acetyl-l-carntine and lipoic acid to old rats significantly improves the metabolic function while decreasing oxidative stress. Proc Natl Acad Sci USA 2002 Feb 19;99(4):1870-5.

3. Giancaterini A, et al. Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients. Metabolism 2000 Jun;49(6):704-8.

4. Yamano T,et al. Effect of L-carnosine on the hyperglycemia caused by intracranial injection of 2-deoxy-D-glucose in rats. Neurosci Lett 2001 Nov 2;313(1-2):78-82.

5. Packer L, et al. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001 Oct;17(10):888-95.

6. Ford I, et al. The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat. Metabolism 2001 Aug;50(8):868-75.

7. Coppey LJ, et al. Effect of antioxidant treatment of streptozotocin-induced diabetic rats on endoneurial blood flow, motor nerve conduction velocity and vascular reactivity of epineurial arterioles of the sciatic nerve. Diabetes 2001 Aug;50(8):1927-37.

8. Cameron NE, et al. Effect of alpha-lipoic acid on vascular responses and nociception in diabetic rats. Free Radic Biol Med 2001 Jul 1;31(1):125-35.

9. Heitzer T, et al. Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Free Radic Biol Med 2001 Jul 1;31(1):53-61.

10. Ukeda H, et al. Effect of carnosine and related compounds on the inactivation of human Cu,Zn-superoxide dismutase by modification of fructose and glycolaldehyde. Biosci Biotechnol Biochem 2002 Jan;66(1):36-43.

11. Hipkiss AR. On the “struggle between chemistry and biology during aging”--implications for DNA repair, apoptosis and proteolysis, and a novel route of intervention. Biogerontology 2001;2(3):173-8.

12. Packer Let al. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001 Oct;17(10):888-95.

13. Melhem MF, et al. Alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes. J Am Soc Nephrol 2002 Jan;13(1):108-16.

14. Virmani MA, et al. The action of acetyl-L-carnitine on the neurotoxicity evoked by amyloid fragments and peroxide on primary rat cortical neurones. Ann N Y Acad Sci 2001 Jun;939:162-78.

15. Zhang L, et al. Alpha-lipoic acid protects rat cortical neurons against cell death induced by amyloid and hydrogen peroxide through the Akt signalling pathway. Neurosci Lett 2001 Oct 26;312(3):125-8.

16. Dukic-Stefanovic S, et al. AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs? Biogerontology 2001;2(1):19-34.

17. Price DL, et al. Chelating activity of advanced glycation end-product inhibitors. J Biol Chem 2001 Dec 28;276(52):48967-72.

18. Ando S, et al. Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res 2001 Oct 15;66(2):266-71.

19. Pettegrew JW, et al. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer’s disease and geriatric depression. Mol Psychiatry 2000 Nov;5(6):616-32.

20. Sorbi S, et al. Double-blind, crossover, placebo-controlled clinical trial with L-acetylcarnitine in patients with degenerative cerebellar ataxia. Clin Neuropharmacol 2000 Mar-Apr;23(2):114-8.

21. Andreassen OA, et al. Lipoic acid improves survival in transgenic mouse models of Huntington’s disease. Neuroreport 2001 Oct 29;12(15):3371-3.

22. Hager K, et al. Alpha-lipoic acid as a new treatment option for Azheimer type dementia. Arch Gerontol Geriatr 2001 Jun;32(3):275-282.

23. Gonzalez-Perez O, et al. Beneficial effects of alpha-lipoic acid plus vitamin E on neurological deficit, reactive gliosis and neuronal remodeling in the penumbra of the ischemic rat brain. Neurosci Lett 2002 Mar 15;321(1-2):100-4.

24. Piotrowski P, et al. Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants. Folia Neuropathol 2001;39(3):147-54.

25. Liu J, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A 2002 Feb 19;99(4):2356-61.

26. Hagen TM, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A 2002 Feb 19;99(4):1870-5.

27. Zhang WJ, Frei B. Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 2001 Nov;15(13):2423-32.

28. Decker EA, et al. Inhibition of low-density lipoprotein oxidation by carnosine histidine. J Agric Food Chem 2001 Jan;49(1):511-6.

29. El Midaoui A, de Champlain J. Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. Hypertension 2002 Feb;39(2):303-7.

30. Takaoka M, et al. Effects of alpha-lipoic acid on deoxycorticosterone acetate-salt-induced hypertension in rats. Eur J Pharmacol 2001 Jul 20;424(2):121-9.

31. Hipkiss AR, et al. Carnosine, the anti-aging, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev 2001 Sep 15;122(13):1431-45.

32. Roberts PR, Zaloga GP. Cardiovascular effects of carnosine. Biochemistry (Mosc) 2000 Jul;65(7):856-61.

33. Arivazhagan P, et al. Effect of DL-alpha-lipoic acid on glutathione metabolic enzymes in aged rats. Exp Gerontol 2001 Dec;37(1):81-7.

34. Koufaki M, et al. Novel potent inhibitors of lipid peroxidation with protective effects against reperfusion arrhythmias. J Med Chem 2001 Nov 22;44(24):4300-3.

35. Pack RA, et al. Differential effects of the antioxidant alpha-lipoic acid on the proliferation of mitogen-stimulated peripheral blood lymphocytes and leukaemic T cells. Mol Immunol 2002 Feb;38(10):733-45.

36. Casciari JJ, et al.. Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Br J Cancer 2001 Jun 1;84(11):1544-50.

37. Mollica MP, et al. Acetyl-L-carnitine treatment stimulates oxygen consumption and biosynthetic function in perfused liver of young and old rats. Cell Mol Life Sci 2001 Mar;58(3):477-84.

38. Niang M, Melka M. Effect of acetyl-L-carnitine on leukemia L1210 resistant to mitoxantrone. Acta Medica (Hradec Kralove) 2000;43(4):125-8.

39. Patrick L. Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine. : Altern Med Rev 2000 Aug;5(4):290-305.

40. Mangano NG, et al. Effect of acetyl-L-carnitine on ethanol consumption and alcohol abstinence syndrome in rats. Drugs Exp Clin Res 2000;26(1):7-12.

41. Persson HL, et al. Alpha-lipoic acid and alpha-lipoamide prevent oxidant-induced lysosomal rupture and apoptosis. Redox Rep 2001;6(5):327-34.

42. Dietrich M, et al. Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers. Cancer Epidemiol Biomarkers Prev 2002 Jan;11(1):7-13.

43. Akhalaia MIa, et al. Effect of natural radioprotector carnosine on histamine-diamine oxidase system of rat’s myocardium after action of various extreme factors. Radiats Biol Radioecol 2001 Jan-Feb;41(1):56-8.

44. Nagasawa T, et al. In vitro and in vivo inhibition of muscle lipid and protein oxidation by carnosine. Mol Cell Biochem 2001 Sep;225(1-):29-34.

45. Arivazhagan P, et al. Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Chem Biol Interact 2001 Nov 28;138(2):189-98.

46. Logan AC, Wong C. Chronic fatigue syndrome: oxidative stress and dietary modifications. Altern Med Rev 2001 Oct;6(5):450-9.

47. Saengsirisuwan V, et al. Interactions of exercise training and lipoic acid on skeletal muscle glucose transport in obese Zucker rats. J Appl Physiol 2001 Jul;91(1):145-53.

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