Alpha-lipoic acid (ALA) is an antioxidant formed in the body. Alpha-lipoic acid and its reduced form, dihydrolipoic acid, may quench various reactive oxygen species. (i.e. hydroxyl radicals, hypochlorous acid, peroxynitrite and singlet oxygen).
As a chelator, lipoic acid can trap metals in the blood circulation, thus preventing cellular damage.
Lipoic acid may enter nerve tissue and prevent glucose-related oxidative damage.
Reduced glutathione, a major cellular antioxidant, can be regenerated by alpha lipoic acid in concert with other antioxidants.[~10~]
Dehydroascorbate, reduced vitamin C, can be recycled into ascorbate, vitamin C, by dihydroxylipoic acid. Alpha-lipoic acid may indirectly participate in the regeneration of vitamin E.
Alpha-lipoic acid has a role in enhancing energy production (ATP synthesis).
Alpha-lipoic acid is a cofactor of a-keto-dehydrogenase.
Although it has not been supported by animal studies, ALA increases the antioxidant effects of vitamins C and E, and of glutathione (peptide containing amino acids, functioning as a coenzyme in oxidation-reduction reactions) and supports the detoxifying abilities of the liver.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
Diabetes and Oxidative Stress: In diabetes mellitus, enhanced reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and a decrease in antioxidant capacity occurs and is thought to play a key role in the pathogenesis of late diabetic complications.
A 2002 review reported that hyperglycemia and elevated free fatty acids (FFA) caused by type 2 diabetes and other states of insulin resistance (obesity), results in the generation of ROS and RNS. Enhanced ROS and RNS production activates stress-signaling pathways leading to cellular damage, insulin resistance, and ultimately long-term complications of diabetes. Alpha lipoic acid’s antioxidant properties have been shown to reduce oxidative stress-activated signaling pathways in vitro and in patients with type 2 diabetes. The use of ALA and other antioxidants may be important in preventing activation of these stress-signaling pathways.[~10~]
Diabetes: Nephropathy
In a prospective open and non-randomized study, the effect of ALA on renal endothelial damage and nephropathy was examined in 84 diabetic patients for 18 months. The progression of renal endothelial cell damage and nephropathy were evaluated by thrombomodulation and urinary albumin concentration. Patients received either a placebo or 600 mg of ALA per day. Treatment with ALA decreased thrombomodulation significantly, but did not change urinary albumin concentrations. However, urinary albumin concentration significantly increased in patients without ALA. This result indicates that ALA may inhibit progression of renal endothelial cell damage by oxidative stress in diabetic patients.5
Diabetes: Glucose Uptake: ALA increases glucose uptake through recruitment of the glucose transporter-4 to plasma membranes, a mechanism that is shared with insulin-stimulated glucose uptake. It has been demonstrated that ALA improves glucose disposal in patients with type 2 diabetes.[~15~]
The effect of LA supplementation (600 mg, twice a day) on glucose metabolism was studied in lean and obese patients with type 2 diabetes. Four-week treatment increased glucose effectiveness, which is a dominant factor regulating glucose uptake in diabetic patients. Higher insulin sensitivity and lower fasting blood glucose concentrations were observed only in lean subjects. Supplementation with ALA reduced fasting blood pyruvate and lactate and prevented increases in pyruvate and lactate after glucose loading, indicating that ALA may improve glucose utilization.4
Diabetes: Neuropathy: Past animal data show that ALA
corrects energy metabolism in diabetes neural tissue, possibly by improving
glucose uptake. This suggests that while ALA may not have a direct antioxidant
effect on neural tissue it may be effective by other mechanisms.[~11~]
In a randomized, double-blind, placebo-controlled multicenter trial, 800 mg of ALA was administered to patients with type 2 diabetes to assess the effect of ALA on cardiac autonomic neuropathy. After 4 months of treatment, the authors concluded that oral doses of 800 mg daily slightly improved cardiac autonomic neuropathy.6
Another study on 509 patients with type 2 diabetes, treatment with 600 mg of ALA intravenously for 3 weeks, followed by 600 mg 3 times a day orally for 6 months, did not effect neuropathic symptoms.7
In a 2002 review, van Dam summarized studies on ALA and neuropathy published in the mid-to-late 1990’s. ALADIN, in 1995, reported reductions of neuropathic symptoms (when compared to placebo) following 3 weeks of IV administration with similar effects of oral treatment reported in another study.[~11~] [~12~] In 1999 a 2-year placebo-controlled study administered ALA orally (1200 or 600 mg/day) to patients with diabetes and polyneuropathy. Results showed significant improvements in sural and tibial nerve conduction velocities.[~11~] [~13~] Ziegler and colleagues, in 1999, revealed limited beneficial results of ALA on neuropathic signs and symptoms after IV treatment followed by 6 months oral intake (1800 mg/day.)[~11~] [~14~] Van Dam concludes that the limited number of clinical studies using antioxidants in persons with diabetes and neuropathic symptoms is tempting. He also concludes that substantial evidence for such an approach is lacking, although the current data are promising and results from additional studies will be available soon.[~11~]
Haak and colleagues (2000) administered 1200 mg ALA orally to 8 patients with both type I and type II diabetes and peripheral neuropathy for 6 weeks. The second group of 9 patients with diabetes, both types, and peripheral neuropathy received 600 mg ALA or placebo intravenously. In both groups, results demonstrated that for patients with diabetic polyneuropathy, ALA improved microcirculation. The observed effects are apparently acute effects. A randomized, placebo-controlled study with a larger population of patients is currently under way.[~16~]
Alzheimer's Disease: Excessive lipid peroxidation, protein oxidation, DNA oxidation, and glyco-oxidation have all been documented in the brain in Alzheimer’s disease (AD)[~17~]. A number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations[~17~].
In an open study using nine patients with Alzheimer's disease, 600 mg of ALA was given for almost one year and cognitive functions were measured. Treatment with ALA showed a neuroprotective effect as measured by mini-mental state examination and AD assessment scores.8
Depression: In a review paper, Salazar suggested a possible therapeutic role of ALA for patients with depression.9 Studies showed that insulin plays a role in serotonergic activity by increasing the flow of tryptophan, a precursor of serotonin, into the brain. Synthesis of serotonin appears to be dependent on the concentration of plasma tryptophan and activity of tryptophan hydroxylase, which converts tryptophan to serotonin. Insulin stimulates uptake of glucose and amino acids by muscle cells and promotes influx of tryptophan into the brain, which in turn facilitates serotonin synthesis. Since a large number of people with depression have insulin resistance and ALA plays a key role in insulin metabolism, well-controlled clinical studies are needed to support this hypothesis.
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
Print this page
Contact an Expert
