Gamma linolenic acid (GLA)
Also known as evening primrose oil, GLA is an omega-6 fatty acid that’s an important constituent of neuronal cell membranes—and believed to decrease neuropathic pain by having some anti-inflammatory effects.2 This suggests that therapy with GLA has the potential to improve neuronal phospholipid structure and microcirculation.2
Two placebo-controlled trials (N=22,111) showed improvement in pain scores and multiple neurophysiologic assessments in patients with diabetes treated with GLA (360-480 mg/d).20,21 The treatment was well tolerated, but the beneficial effect was more pronounced in those with less severe diabetes.
THE BOTTOM LINE The dose of GLA studied (8 to 12 capsules daily) could lead to problems with patient adherence. In addition, GLA should be used with caution in patients who are taking antiplatelet medication or have seizure disorders.2
Magnesium (Mg)
Mg is highly involved in multiple enzyme systems throughout the body. Although it is very well absorbed from dietary sources,2 patients with diabetes, liver disease, and hormonal imbalances, as well as the elderly, are often deficient in Mg. It is unclear how this affects peripheral neuropathy.13
Mg may have an antinociceptive effect by decreasing intracellular calcium influx and antagonizing N-methyl-D-aspartate receptors and associated nerve signaling.22 A small RCT (N=80) showed Mg to decrease the severity of neuropathic back pain.22 Patients received Mg sulfate 1 g IV, given over 4 hours, every day for 2 weeks. The infusion was then replaced with Mg oxide 400 mg plus Mg gluconate 100 mg, taken orally twice daily for 4 weeks. An improvement in mean pain score was seen as early as 2 weeks, and scores had decreased by 2.8 points (on a 0-10-point scale) at 6 months.
Another small RCT (N=45) gave patients with neuropathy of postherpetic, traumatic, or surgical (but not diabetic) origin Mg chloride 838 mg orally 3 times a day for 4 weeks.23 The supplement was taken with meals. Mean pain scores in the treatment group decreased by 3 points, but this was not significantly different from the improvement seen in those on placebo.
In a similar study, patients (N=110) with type 1 diabetes and a normal serum Mg but an insufficiency as measured by erythrocyte Mg were given Mg gluconate 300 mg or placebo daily for 5 years.8 The supplement slowed the progression of peripheral neuropathy (only 12% of those receiving Mg gluconate experienced a significant worsening of symptoms over the course of the study, compared with 61% of those in the placebo group), but in most cases, it did not lead to an improvement.
No consistent approach to Mg supplementation has been studied, which makes recommending a particular route, dose, or formulation challenging. There is evidence that oral Mg, particularly in the form of Mg oxide, can cause diarrhea, especially in doses >350 mg/d. Mg gluconate and Mg chloride are better tolerated; Mg carbonate should be avoided due to poor oral absorption.2
BOTTOM LINE Mg supplementation appears to slow the progression of diabetic peripheral neuropathy, but is unsafe for patients with renal dysfunction, cardiac conduction abnormalities, or elevated Mg levels.2 Caution is required, too, when considering Mg supplementation for patients taking anticoagulants, bisphosphonates, digoxin, potassium-sparing diuretics, or tetracycline antibiotics.2
CORRESPONDENCE
Mary Onysko, PharmD, BCPS, University of Wyoming, School of Pharmacy Health Sciences Center, Room 292, 1000 E. University Avenue, Laramie, WY 82071; monysko@uwyo.edu