Alpha Liopic Acid Injection
Alpha lipoic acid (ALA, thioctic acid) is an antioxidant associated with the treatment of glaucoma, alcoholic liver disease, diabetes mellitus, diabetic neuropathy, dementia secondary to Alzheimer's disease or human immunodeficiency virus (HIV) infection, and amanita mushroom poisoning. Most studies supporting the use of ALA for diabetes and diabetic neuropathy took place over a short time (three to five weeks) and involved a small sample of patients, but some studies as long as six months and 24 months have also been completed and are available. In Germany, ALA has been used extensively in the treatment of diabetic neuropathy since 1959. For other purported indications (specifically Alzheimer’s disease, HIV-related dementia, and liver disease), studies of ALA have been lacking or inconclusive. Until stronger studies are available, ALA cannot be recommended for these indications.
Endogenous alpha lipoic acid is available as both an R- and S- enantiomer. Most human clinical trials have used a racemic mixture, though the R-enantiomer is the biologically active component. ALA is rapidly absorbed and distributed into tissues via oral or intraperitoneal administration. Affected tissues and organs include the heart, liver, and skeletal muscle. Within these tissues, ALA is readily reduced to dihydrolipoic acid (DHLA). ALA and DHLA are both water and fat soluble, and ALA is metabolized almost entirely; very little is excreted unchanged. ALA and DHLA are both potent antioxidants that can engage with reactive and chelate metals (iron and copper for ALA and cadmium for DHLA), and ALA is natural cofactor of mitochondrial dehydrogenase complexes. DHLA may also be able to regenerate oxidized vitamins E and C and glutathione.
Diabetes mellitus type 2: Preliminary, short-term studies suggest that ALA may increase insulin sensitivity in patients with type 2 diabetes mellitus; ALA has been shown to increase skeletal muscle glucose uptake and glucose disposal, improving insulin sensitivity and glucose utilization in patients with this condition.
Diabetic neuropathy: Oxidative stress and lipid peroxidation are known causes of neuropathic pain and dysfunction. ALA has been shown to improve the symptoms of neuropathy in patients with diabetes; a meta-analysis of four trials involving intravenous ALA administered daily for three weeks associates ALA with a significant improvement in total symptom scores including pain, burning, and numbness. Improvements have also been noted in neuropathic impairment scores including pin-prick sensation, touch-pressure sensation, and ankle reflexes.
Alpha lipoic acid may improve insulin sensitivity in patients with type 2 diabetes mellitus and may improve symptoms in patients with diabetic neuropathy. Studies regarding other indications are inconclusive or lacking.
Diabetes mellitus: Alpha lipoic acid may decrease blood glucose concentrations; patients with diabetes mellitus should proceed with caution and monitor their blood glucose concentrations as they administer ALA. Patients should also learn to recognize the symptoms of hypoglycemia.
Pregnancy and lactation: Studies are lacking on the use of ALA in pregnancy and lactation. Pregnant or breast-feeding women should avoid ALA until more information is available.
Antidiabetic agents: ALA is known to increase glucose utilization and decrease insulin resistance. This means that patients using antidiabetic agents who begin treatment with ALA may experience increased risk for hypoglycemia and may need to adjust dosages of antidiabetic agents. Patients should be instructed to monitor their blood glucose concentrations. In one study, some patients with type 2 diabetes mellitus receiving both ALA and sulfonylureas required a dose reduction in the sulfonylurea due to mild symptoms of hypoglycemia (Jacob et al, 1999)
Drugs that decrease the effects of antidiabetic agents: Alpha lipoic acid can increase glucose utilization and decrease insulin resistance. Patients receiving other drugs that affect blood glucose or insulin resistance may reduce the beneficial effects of ALA. Examples include anti-retroviral protease inhibitors, atypical antipsychotics, beta-blockers, corticosteroids, cyclosporine, dextrothyroxine, diuretics, glucagon, isoniazid, INH, niacin, phenothiazines, somatropin, rh-GH, sympathomimetics, tacrolimus, triamterene, and thyroid hormones. This list is not inclusive of all drugs that can decrease the effects of antidiabetic agents.
Drugs that increase the effects of antidiabetic agents: ALA can increase glucose utilization and decrease insulin resistance. Other drugs that decrease blood glucose concentrations or insulin resistance may enhance the effects of ALA, possibly causing hypoglycemia. Such drugs include ACE inhibitors, androgens, bortezomib, chromium, disopyramide, fibric acid derivatives, garlic, Allium sativum, green tea, guanethidine, horse chestnut, Aesculus hippocastanum, MAOIs, octreotide, and orlistat. Patients with diabetes taking ALA plus any of these other drugs should be advised to monitor their blood glucose concentrations. This list does not include all drugs that increase the effects of antidiabetic agents.
Drugs that increase or decrease the effects of antidiabetic agents: ALA is known to increase glucose utilization and decrease insulin resistance. Other drugs that may increase or decrease blood glucose concentrations or insulin resistance may counteract the beneficial effects of ALA or enhance its effects and increase the risk of hypoglycemia. Examples include clonidine, cisapride, ethanol, lithium, metoclopramide, pentamidine, and quinolones. Patients with diabetes taking any of these drugs in combination with ALA should monitor their blood glucose concentrations. This list does not include all drugs that may increase or decrease the effects of antidiabetic agents.
Drugs that mask the signs and symptoms of hypoglycemia: ALA can increase glucose utilization and decrease insulin resistance; hypoglycemia may be possible. Patients receiving other drugs that mask the signs and symptoms of hypoglycemia such as beta-blockers, clonidine, reserpine, guanethidine in combination with ALA should be advised to monitor their blood glucose concentrations. This list does not include all drugs that may mask the signs and symptoms of hypoglycemia.
In clinical trials of patients with diabetes, a few patients reported symptoms consistent with mild hypoglycemia, but generally, ALA is well tolerated. Allergic skin conditions have been reported in some patients taking oral ALA. A study in patients with peripheral neuropathy showed a dose-dependent increase in the incidence of nausea, vomiting and vertigo, with the highest incidence in patients taking 1200 mg and 1800 mg/day PO of ALA (Ziegler et al., 2006).