ALA and Neuropathy
Diabetic neuropathy, which is diagnosed in diabetic patients with peripheral nerve dysfunction when other causes of neuropathy have been excluded, is believed to be due to increased flux through the polyol pathway, leading to accumulation of sorbitol, a reduction in myoinositol, and an associated reduced Na+-K+-ATPase activity, as well as nitric oxide inactivation by increased oxygen free radical activity leading to endoneurial microvascular damage and hypoxia.30 As a potent antioxidant, ALA appears to retard or reverse the progression of peripheral diabetic neuropathy.
In a study designed to assess the efficacy of ALA in the improvement of sural nerve conduction velocity and amplitude in patients with diabetic neuropathy, participants were administered 600 mg ALA per day.31 At the conclusion of the study, ALA failed to improve sural nerve conduction velocity and amplitude; however, researchers noted that their study results should be interpreted with caution due to the study’s uncontrolled nature, researchers’ failure to assess patient compliance, small sample size, and short study duration.
Several studies demonstrate beneficial effects of ALA in the management of peripheral neuropathy. In one study that compared results of patients who were administered 600 mg, 1200 mg, and 1800 mg ALA by mouth, patients reported significant improvements in stabbing and burning pain (subset of total symptom score, or TSS), the Neuropathy Symptoms and Change (NSC) score, and the patients' global assessment of efficacy.32 Benefits were not remarkably different between the three groups, suggesting that an oral dosage of 600 mg provides the most favorable cost-benefit ratio.
In another study that administered ALA orally at a dosage of 600 mg per day for 40 days, ALA administration was found to be associated with reductions in neuropathic symptoms [as demonstrated by reduced Neuropathy Symptom Score (NSS), Subjective Peripheral Neuropathy Screen Questionnaire (SPNSQ), and douleur neuropathique (DN4) questionnaire scores at day 40 versus baseline] and in triglycerides.33
One systematic review of the literature concluded that, when administered intravenously at a dosage of 600 mg per day over a period of 3 weeks, ALA leads to a significant and clinically relevant reduction in neuropathic pain (grade of recommendation A). These researchers also studied orally administered ALA and stated that it was unclear whether or not the improvements seen after 3-5 weeks at an oral dosage of 600 mg were clinically relevant.34
Other systematic reviews maintained that oral and intravenous administration may provide similar benefits. For example, one stated that an oral or intravenous ALA dose of at least 600 mg per day resulted in a 50% reduction in the TSS35 and a more recent (2018) systematic review on ALA in the management of diabetic peripheral neuropathy concluded that current data provides evidence for the benefits of ALA in diabetic peripheral neuropathy treatment at a dose of 600 mg per day, either intravenously or orally, for a duration of at least 3 weeks with minimal side effects. 36
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