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Alpha-lipoic Acid
Background
Alpha-lipoic acid is sulfur-containing free radical scavenger found in the cells of humans and in a variety of foods, such as spinach, broccoli, yeast, liver, kidney, and heart. It has been called a ‘universal’ antioxidant because it is both fat- and water-soluble. Not only is lipoic acid an antioxidant on its own, but it has also been shown to recycle other antioxidants, such as vitamins E and C. It can also chelate with toxic metals, such as mercury, and remove them from the body.
Lipoic acid is approved in Germany for clinical use in the management of diabetic neuropathy. Alpha-lipoic acid has also been used to reduce cell damage associated with mushroom poisoning, radiation, and alcoholic hepatitis. Depletion of lipoic acid has been documented in diabetics, patients with heart disease, and people with liver cirrhosis.
Clinical Studies
Research on lipoic acid supplementation has shown improvements in glucose metabolism, reduced glycosylation of proteins (such as HbA1c), improved blood flow to peripheral nerves, and stimulation of nerve cell regeneration.
Diabetic Neuropathy
Diabetic neuropathy represents a major health problem. A growing body of evidence suggests that oxidative stress resulting from enhanced free-radical formation is one of the causes of diabetic neuropathy. Seven controlled randomized clinical trials of thioctic acid in patients with diabetic neuropathy have been using different study designs, durations of treatment, doses, sample sizes, and patient populations. A comprehensive analysis of these trials confirmed the favorable effects of thioctic acid based on the highest level of evidence (Class Ia). The following conclusions were drawn from this analysis. Short-term treatment for 3 weeks using intravenous lipoic acid 600 mg/day reduces the chief symptoms of diabetic polyneuropathy. This effect on neuropathic symptoms is accompanied by an improvement of neuropathic deficits, suggesting potential for the drug to influence underlying neuropathy favorably. Oral treatment for 4 to 7 months tends to reduce neuropathic deficits and improve cardiac autonomic neuropathy. Clinical and post-marketing surveillance studies have revealed a highly favorable safety profile of lipoic acid.
Another systematic review done in Germany of 15 trials concluded that short-term treatment with alpha-lipoic acid, 600 mg/day, reduced the symptoms of diabetic neuropathy. These conclusions were mainly based on the results of four randomized, double-blind, placebo-controlled studies entitled ALADIN (Alpha Lipoic Acid in Diabetic Neuropathy). In the first ALADIN study, 328 patients with Type II diabetes mellitus and symptomatic peripheral neuropathy were randomly assigned to 100, 600, or 1,200 mg/day of parenteral (IV) alpha-lipoic acid or placebo. After 3 weeks, the patients who completed the study and had received the 600 and 1200 mg/d doses of alpha-lipoic acid had statistically significant improvements in pain, tingling, and numbness compared with placebo.
In the follow-up ALADIN II study, oral alpha-lipoic acid, 600 or 1200 mg/day, was given to 65 patients with Type II and Type II diabetes and symptomatic neuropathy. After 2 years, both doses of alpha-lipoic acid showed an increase in nerve conduction velocity compared with placebo. However, severity of symptoms was not improved, based on a series of physical tests.
ALADIN III examined the effects of short-term treatment with parenteral (IV) alpha-lipoic acid, followed by extended treatment with oral alpha-lipoic acid. In this trial, 503 patients with Type II diabetes and symptomatic peripheral neuropathy were placed in one of three treatment groups: (1) 600 mg/d parenteral alpha-lipoic acid for 3 weeks, then 1800 mg/d of oral alpha-lipoic acid for 6 months; (2) 600 mg/d parenteral alpha-lipoic acid for 3 weeks, then an indistinguishable oral placebo for 6 months; or (3) parenteral placebo for 3 weeks, then oral placebo for 3 months. Neuropathic deficits were significantly reduced in patients receiving parenteral alpha-lipoic acid at 3 weeks. After 6 months of treatment with oral alpha-lipoic acid, a decrease in neuropathy impairment scores was observed.
Finally, the ORPIL study found that oral administration of 1800 mg/d of alpha-lipoic acid reduced neuropathic deficits and symptoms in 22 patients with Type II diabetes and symptomatic polyneuropathy during a 3-week period.
Insulin Resistance
Experimental trials have also provided evidence that lipoic acid might be useful in the treatment of insulin resistance in humans. For example, a 4-week placebo controlled multicenter pilot study was done to determine the effectiveness of oral treatment with lipoic acid on insulin sensitivity in people with Type II diabetes. Seventy-four patients were randomized either to placebo or to treatment consisting of lipoic acid in doses of either 600 mg once daily, twice daily, or three times daily. Prior to treatment, all four groups had comparable degrees of hyperglycemia and insulin sensitivity. Although not every treated subject experienced improvements, a mean increase of 27% in insulin-stimulated glucose disposal was observed among subjects receiving lipoic acid supplementation. In other words, treatment with lipoic acid improved the efficiency with which insulin worked in these patients in only 4 weeks.
Doseage
In clinical trials, significant improvements in nerve conduction velocity with oral doses of 600 to 1200 mg/day for 2 years have been observed. Symptom improvement was also observed using 1800 mg/day orally for 3 weeks. The optimal dose for oral dosing is currently unknown, but a reasonable approach may be a loading dose of 1800mg/day for 3 weeks, followed by a maintenance dose of 600 to 1200 mg/day. Of course, reduction of total body free radical load with other antioxidant nutrients and better glucose control should theoretically work synergistically with lipoic acid supplementation to improve symptoms. The interventions mentioned above using lipoic acid involved no other additional interventions. Alpha-lipoic acid therapy should only be undertaken with the guidance of a healthcare practitioner familiar with its use.
Safety and Side Effects
Clinical studies to date have indicated that alpha-lipoic acid has a favorable safety and side effect profile. Adverse effects tend to be mild and include headache, skin rash, and stomach upset at high doses (>600 mg/day).
Alpha-lipoic acid is sulfur-containing free radical scavenger found in the cells of humans and in a variety of foods, such as spinach, broccoli, yeast, liver, kidney, and heart. It has been called a ‘universal’ antioxidant because it is both fat- and water-soluble. Not only is lipoic acid an antioxidant on its own, but it has also been shown to recycle other antioxidants, such as vitamins E and C. It can also chelate with toxic metals, such as mercury, and remove them from the body.
Lipoic acid is approved in Germany for clinical use in the management of diabetic neuropathy. Alpha-lipoic acid has also been used to reduce cell damage associated with mushroom poisoning, radiation, and alcoholic hepatitis. Depletion of lipoic acid has been documented in diabetics, patients with heart disease, and people with liver cirrhosis.
Clinical Studies
Research on lipoic acid supplementation has shown improvements in glucose metabolism, reduced glycosylation of proteins (such as HbA1c), improved blood flow to peripheral nerves, and stimulation of nerve cell regeneration.
Diabetic Neuropathy
Diabetic neuropathy represents a major health problem. A growing body of evidence suggests that oxidative stress resulting from enhanced free-radical formation is one of the causes of diabetic neuropathy. Seven controlled randomized clinical trials of thioctic acid in patients with diabetic neuropathy have been using different study designs, durations of treatment, doses, sample sizes, and patient populations. A comprehensive analysis of these trials confirmed the favorable effects of thioctic acid based on the highest level of evidence (Class Ia). The following conclusions were drawn from this analysis. Short-term treatment for 3 weeks using intravenous lipoic acid 600 mg/day reduces the chief symptoms of diabetic polyneuropathy. This effect on neuropathic symptoms is accompanied by an improvement of neuropathic deficits, suggesting potential for the drug to influence underlying neuropathy favorably. Oral treatment for 4 to 7 months tends to reduce neuropathic deficits and improve cardiac autonomic neuropathy. Clinical and post-marketing surveillance studies have revealed a highly favorable safety profile of lipoic acid.
Another systematic review done in Germany of 15 trials concluded that short-term treatment with alpha-lipoic acid, 600 mg/day, reduced the symptoms of diabetic neuropathy. These conclusions were mainly based on the results of four randomized, double-blind, placebo-controlled studies entitled ALADIN (Alpha Lipoic Acid in Diabetic Neuropathy). In the first ALADIN study, 328 patients with Type II diabetes mellitus and symptomatic peripheral neuropathy were randomly assigned to 100, 600, or 1,200 mg/day of parenteral (IV) alpha-lipoic acid or placebo. After 3 weeks, the patients who completed the study and had received the 600 and 1200 mg/d doses of alpha-lipoic acid had statistically significant improvements in pain, tingling, and numbness compared with placebo.
In the follow-up ALADIN II study, oral alpha-lipoic acid, 600 or 1200 mg/day, was given to 65 patients with Type II and Type II diabetes and symptomatic neuropathy. After 2 years, both doses of alpha-lipoic acid showed an increase in nerve conduction velocity compared with placebo. However, severity of symptoms was not improved, based on a series of physical tests.
ALADIN III examined the effects of short-term treatment with parenteral (IV) alpha-lipoic acid, followed by extended treatment with oral alpha-lipoic acid. In this trial, 503 patients with Type II diabetes and symptomatic peripheral neuropathy were placed in one of three treatment groups: (1) 600 mg/d parenteral alpha-lipoic acid for 3 weeks, then 1800 mg/d of oral alpha-lipoic acid for 6 months; (2) 600 mg/d parenteral alpha-lipoic acid for 3 weeks, then an indistinguishable oral placebo for 6 months; or (3) parenteral placebo for 3 weeks, then oral placebo for 3 months. Neuropathic deficits were significantly reduced in patients receiving parenteral alpha-lipoic acid at 3 weeks. After 6 months of treatment with oral alpha-lipoic acid, a decrease in neuropathy impairment scores was observed.
Finally, the ORPIL study found that oral administration of 1800 mg/d of alpha-lipoic acid reduced neuropathic deficits and symptoms in 22 patients with Type II diabetes and symptomatic polyneuropathy during a 3-week period.
Insulin Resistance
Experimental trials have also provided evidence that lipoic acid might be useful in the treatment of insulin resistance in humans. For example, a 4-week placebo controlled multicenter pilot study was done to determine the effectiveness of oral treatment with lipoic acid on insulin sensitivity in people with Type II diabetes. Seventy-four patients were randomized either to placebo or to treatment consisting of lipoic acid in doses of either 600 mg once daily, twice daily, or three times daily. Prior to treatment, all four groups had comparable degrees of hyperglycemia and insulin sensitivity. Although not every treated subject experienced improvements, a mean increase of 27% in insulin-stimulated glucose disposal was observed among subjects receiving lipoic acid supplementation. In other words, treatment with lipoic acid improved the efficiency with which insulin worked in these patients in only 4 weeks.
Doseage
In clinical trials, significant improvements in nerve conduction velocity with oral doses of 600 to 1200 mg/day for 2 years have been observed. Symptom improvement was also observed using 1800 mg/day orally for 3 weeks. The optimal dose for oral dosing is currently unknown, but a reasonable approach may be a loading dose of 1800mg/day for 3 weeks, followed by a maintenance dose of 600 to 1200 mg/day. Of course, reduction of total body free radical load with other antioxidant nutrients and better glucose control should theoretically work synergistically with lipoic acid supplementation to improve symptoms. The interventions mentioned above using lipoic acid involved no other additional interventions. Alpha-lipoic acid therapy should only be undertaken with the guidance of a healthcare practitioner familiar with its use.
Safety and Side Effects
Clinical studies to date have indicated that alpha-lipoic acid has a favorable safety and side effect profile. Adverse effects tend to be mild and include headache, skin rash, and stomach upset at high doses (>600 mg/day).