Alpha Lipoic Acid in Diabetes:  
As long as we’re discussing ALA, we need to address its importance in diabetes because it is in this disease that the oxidative damage is most dramatic. For a review of the biochemistry of ALA, go to the Alzheimer's section and scroll down to the section on Alpha Lipoic Acid. By the way, for you doctors, patients taking ALA will have lower HbA1C levels and a routine HbA1C level may not be a good index of the patient's dietary compliance. I'll explain why in another chapter.

Any diabetic patient who is NOT on ALA supplementation is, in my opinion, inadequately treated. ALA in high doses can increase the glucose absorption into the muscle cells of non-insulin dependent diabetics (Packer, et.al., Nutrition 2001 Oct;17(10):888-95) . It also decreases insulin resistance in diabetics (Evans and Goldfine, Diabetes Technol Ther 2000 Autumn;2(3):401-13; and Green, et.al., Metabolism 2001 Sep;50(9):1063-9; and Saengsirisuwan, et.al. J Appl Physiol 2001 Jul;91(1):145-53 ).  It can also reduce the damage done by sugar to proteins in the body, a complex process called glycation. It may be partly via this glycation and partly via the increased oxidative, or free radical concentration seen in diabetes that are responsible for many of the destructive effects of the disease. One of the effects of this oxidative stress in diabetes is the decrease in glutathione in the vascular smooth muscle which results in the destruction of the DNA of the smooth muscle cells increasing the probability of strokes and heart attacks in diabetics. Increasing the ALA levels and the cysteine levels reversed this glutathione depletion and therefore the probability of developing vascular disease (Powell et.al, Free Radic Biol Med 2001 Nov 15;31(10):1149-55; Ford et.al. Metabolism 2001 Aug;50(8):868-75 ). All diabetics should be started on ALA as soon as they are diagnosed.

Diabetic kidney disease or nephropathy was studied by measuring thrombomodulin and urinary albumin secretion (Morcos, et.al. Diabetes Res Clin Pract 2001 Jun;52(3):175-83). In diabetics not treated with ALA, these levels progressively increased over the 18 months of the study. In the ALA treated diabetic patients, these levels did not increase, suggesting that ALA protects the endothelial cells of the diabetic kidney from oxidative stress of the disease.  In diabetic rats, Drs. Melhem, et.al. (J Am Soc Nephrol 2001 Jan;12(1):124-33) studied inulin clearance, urinary albumin excretion, fractional albumin clearance, glomerular volume, and glomerular content of immunoreactive transforming growth factor-beta (TGF-beta) and collagen alpha1 (IV) in nondiabetic rats, untreated control diabetic animals, and in 3 other groups of animals treated with ALA, Vitamin E, and Vitamin C. All of these measures of kidney damage were elevated in the diabetic animals compared to nondiabetic rats. ALA prevented elevations in all these variables. ALA was significantly more effective than either vitamin E or C each of which only prevented elevations in some of the variables. All diabetic patients should be started on ALA as soon as they are diagnosed.

In Europe, ALA is used to reduce the effects of oxidative stress in diabetes. And, in fact, it is the drug of first choice in reducing both the destruction of the nerves and the pain of diabetic neuropathies. There are many studies addressing the beneficial effect of ALA on neuropathies and the dysesthesias (pain) associated with this nerve damage (Cameron, et.al. Free Radic Biol Med 2001 Jul 1;31(1):125-35; Some studies demonstrate that ALA increases nitric oxide levels in diabetic patients thereby increasing the blood flow to the microvasculature of the nerves (Strokov, et.al., Bull Exp Biol Med 2000 Oct;130(10):986-90). This is supported by results of studies by Haak, et.al. (Exp Clin Endocrinol Diabetes 2000;108(3):168-74). Whether ALA improves neuropathy by decreasing oxidative stress or increasing perfusion of the nerve or increasing energy availability or osmolyte content or conduction velocity is still unclear. It is probably due to all of the above. In any case, ALA is not only indicated for peripheral neuropathy, but (and I repeat) should be given to all diabetic patients as soon as they are diagnosed.

Not only is ALA a preventive of neuropathy, but it improves symptoms as I’ve already mentioned. Pain rating scales and other measures of subjective symptoms have uniformly demonstrated in all studies reviewed, a dramatic improvement in hyperesthesias and dysesthesias in these patients (Ruhnau, et.al. Diabet Med 1999 Dec;16(12):1040-3; Hilz, et.al. Fortschr Neurol Psychiatr 2000 Jun;68(6):278-88; and quite notably in the ALADIN III Study published in Diabetes Care (1999 Aug;22(8):1296-301) by Zeigler, et.al.). All diabetics should be started on ALA as soon as they are diagnosed.