The findings appear in the March 2003 issue of Diabetes Care, http://care.diabetesjournals.org/.
"There appears to be a rather large effect on the pain of diabetic neuropathy with ALA," says Peter Dyck, M.D., Mayo Clinic neurologist and peripheral nerve specialist. "The magnitude of the change is considerable. We also found some improvement in neurologic signs and nerve conduction. We were surprised by the magnitude and the rapidity of the response."
When patients were given ALA, also known as thioctic acid, the researchers found statistically significant improvement in the symptoms of diabetic sensorimotor polyneuropathy (DSPN) damage to multiple nerves caused by diabetes. The researchers measured improvement by a total symptom score, a summation of the presence, severity and duration of burning and sharply cutting pain, prickling sensations and numbness. The patients who took ALA saw a 5.7-point total symptom score improvement from the start of the trial, while those who took placebo, an inactive substance, only improved 1.8 points. ALA produced no unfavorable side effects in the patients taking this substance.
"It’s very safe," says Dr. Dyck. "There have been no known complications."
The alternatives for managing the symptoms of DSPN -- narcotics, analgesics or antiepileptic drugs -- are less than ideal, according to Dr. Dyck.
"Most people can’t work while on narcotics, and there’s the concern about habituation," says Dr. Dyck. "If you take analgesics, you can get kind of dopey."
Dr. Dyck says that the intravenous ALA preparation at the dosage he studied is not available to U.S. physicians. It is available in oral form and in smaller doses in drug stores.
"I think it’s a promising lead for the future, in that antioxidants may be implicated in the cause of diabetic neuropathy, and ALA might conceivably be a preventative or interventative," says Dr. Dyck. "It may well be worthwhile for treatment, but I’d rather patients with diabetic neuropathy not go out swallowing large amounts of this drug yet. It isn’t Food and Drug Administration-approved for this purpose."
Dr. Dyck adds that a large, multi-center trial of oral ALA is under way. "We should see what the further data show before we give this widely to patients with diabetic neuropathy," says Dr. Dyck.
Mayo Clinic physicians Dr. Dyck, Phillip Low, M.D., and William Litchy, M.D., were involved in the design and helped oversee the phase 3 study, which included 120 type 1 or 2 diabetic patients, ages 18-74, with DSPN. The study was conducted at the Russian Medical Academy for Advanced Studies in Moscow. After hospital admission, patients were randomized, or selected by chance, to receive either ALA or a placebo in 14 intravenous doses over three weeks, following one week in which all participants received placebo. The study was double-blinded, thus neither patients nor investigators knew which patients received each substance. The researchers then measured the severity and constancy of each patient’s symptoms of burning and sharply cutting pain, prickling sensations and numbness. Trial participants’ progress was measured by written surveys in addition to testing nerve conduction, function of the autonomic nervous system function and sensation.
If the drug proved effective in this trial, the researchers also wanted to find out why it worked. They found that ALA improves the nerve function damaged by chronic hyperglycemia, or the condition when patients’ blood sugars consistently are not under proper control.
"It is known that ALA is a very strong antioxidant," says Dr. Dyck. "High glucose in diabetes leaves trace chemicals harmful to cells -- that process is called oxidative stress. If you burn something in the oven, it leaves soot. Similarly, in disease, there is ‘soot,’ and there are mechanisms that relieve ‘soot.’ Antioxidants promote getting rid of oxidative stress products.
"Oxidative stress is known to be implicated in many disease processes, including diabetic neuropathy," he adds. "If nerve fibers partially degenerate, you get pain and prickling and other symptoms of diabetic neuropathy."
Since 1959, physicians in Germany have treated diabetic neuropathy with ALA. However, there was insufficient research evidence to warrant its use, Dr. Dyck says. The manufacturer of ALA, a German company called Viatris Inc. (formerly ASTA Medica, Inc.), approached Dr. Dyck and other physicians about conducting clinical trials with this supplement to test its effectiveness in alleviating diabetic neuropathy.
Diabetic neuropathy may compromise a person’s quality of life. Previous studies have shown that patients with this syndrome may become depressed or anxious and may have trouble with work, social obligations, sleep and other daily activities.
Although regulating patients’ blood-sugar levels is the ideal way to prevent diabetic neuropathy, physicians have recognized that not all patients can or will control their blood sugars to the needed degree, according to Dr. Dyck. Some patients do not monitor their glucose levels or use their insulin injections or pumps often enough. For other patients, such as type 1 diabetics, blood sugars may fluctuate wildly and prove difficult to control tightly.
According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 11.1 million people in the United States have been diagnosed with diabetes, while an estimated 5.9 million more remain undiagnosed. NIDDK estimates that of these, 50 percent experience some type of neuropathy.
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Lisa Copeland
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Journal
Diabetes Care