Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy

Abstract

Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus. In addition to the maintenance of a sufficient metabolic control, alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which ALA exerts its effect is unknown. In order to study the effect of ALA on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients (4 female, 4 male, age 60+/-3 years, diabetes duration 19+/-4 years, BMI 24.8+/-1.3 kg/m2) received 1200 mg ALA orally per day over 6 weeks (trial 1). A second group of patients (5 female, 4 male, age 65+/-3 years, diabetes duration 14+/-4 years, BMI 23.6+/-0.7 kg/m2) was studied before and after they had received 600 mg ALA or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation (trial 2). Patients were investigated by nailfold video-capillaroscopy. Capillary blood cell velocity was examined at rest and during postreactive hyperemia (occlusion of the wrist for 2 minutes, 200 mmHg) which is a parameter of the perfusion reserve on demand. The oral therapy with ALA resulted in a significant decrease in the time to peak capillary blood cell velocity (tpCBV) during postocclusive hyperemia (trial 1: 12.6+/-3.1 vs 35.4+/-10.9 s, p<0.05). The infusion of ALA also decreased the tpCBV in patients with diabetic neuropathy (trial 2: before: 20.8+/-4,5, ALA: 11.74+/-4.4, placebo: 21.9-5.0 s, p<0.05 ALA vs both placebo and before infusions) indicating that ALA has an acute effect on microcirculation. Capillary blood cell velocity at rest (rCBV), hemodynamic parameters, hemoglobinA1c and local skin temperature remained unchanged in both studies. These results demonstrate that in patients with diabetic polyneuropathy ALA improves microcirculation as indicated by an increased perfusion reserve on demand. The observed effects are apparently acute effects. With the restriction of the pilot character of this investigation the findings support the assumption that ALA might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum.

THERAPY OF ENDOCRINE DISEASE: A systematic review and meta-analysis of α-lipoic acid in the treatment of diabetic peripheral neuropathy

“…The nerve conduction velocity is gradually diminished in DPN, with estimates of a loss of 0.5 m/s per year (28). However, as an antioxidant, ALA directly terminates free radicals, inhibits peroxidation, increases endoneurial blood flow, and raises the reduced glutathione content of the peripheral nerve (3,29,30,31). Thus, ALA exerts a beneficial effect on the vascular abnormalities of diabetes polyneuropathy and leads to an improvement in peripheral nerve function.…”

Effect of Antioxidant Treatment of Streptozotocin-Induced Diabetic Rats on Endoneurial Blood Flow, Motor Nerve Conduction Velocity, and Vascular Reactivity of Epineurial Arterioles of the Sciatic Nerve

“…In the studies by Cameron and colleagues and in our studies, however, rats were treated with a dietary supplement of ␣-lipoic acid at a dose of ϳ300 -350 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 (15). In addition to the studies conducted with diabetic animal models, treatment of diabetic humans with ␣-lipoic acid reportedly improved microcirculation in patients with peripheral neuropathy as well as autonomic neuropathy and other symptoms of diabetic polyneuropathy (18,48).…”

Hepatic mechanisms of the Walnut antidiabetic effect in mice

“…Walnut leaf and ridge extracts are known to contain high amounts of strong antioxidant components like vitamin C, vitamin E, beta-carotene, lipoic acid, quercetin, naphtoquinones, flavonoids, gallic acid, polyphenols, linoleic and linolenic acids, tannins, and folates that have shown very beneficial anti-diabetic effects in in vitro or in vivo models and in humans [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. Thus, one can speculate that the observed favorable changes in insulin secretion and hepatic gluconeogenesis reported by us are also related to the anti-oxidant effect of walnut, but this hypothesis requires further experimental support.…”