Diabetic Neuropathy - Treatment

Vitamin E - updated: 15 March 2008

Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes

Am J Clin Nutr. 2001 Jun;73(6):1052-7

Manzella D, Barbieri M, Ragno E, Paolisso G.

BACKGROUND: Type 2 diabetes is associated with elevated oxidative stress and declines in antioxidant defense. The disease is also characterized by an imbalance in the ratio of cardiac sympathetic to parasympathetic tone. Antioxidants, vitamin E in particular, may have beneficial effects on the cardiac autonomic nervous system through a decline in oxidative stress. OBJECTIVE: We investigated the possible effects of vitamin E on the cardiac autonomic nervous system, as assessed by analysis of heart rate variability, in patients with type 2 diabetes and cardiac autonomic neuropathy. DESIGN: In a double-blind randomized controlled trial, 50 patients with type 2 diabetes were assigned to treatment with vitamin E (600 mg/d) or placebo for 4 mo. RESULTS: The anthropometric characteristics of the patients remained unchanged throughout the study. Chronic vitamin E administration was associated with decreases in concentrations of glycated hemoglobin (P < 0.05), plasma insulin (P < 0.05), norepinephrine (P < 0.03), and epinephrine (P < 0.02); a lower homeostasis model assessment index (P < 0.05); and improved indexes of oxidative stress. Furthermore, vitamin E administration was associated with increases in the R-R interval (P < 0.05), total power (P < 0.05), and the high-frequency component of heart rate variability (HF; P < 0.05) and decreases in the low-frequency component (LF; P < 0.05) and the ratio of LF to HF (P < 0.05). Finally, change in the plasma vitamin E concentration was correlated with change in the LF-HF ratio (r = -0.43, P < 0.04) independently of changes in the homeostasis model assessment index and plasma catecholamines concentrations. CONCLUSIONS: Chronic vitamin E administration improves the ratio of cardiac sympathetic to parasympathetic tone in patients with type 2 diabetes. Such an effect might be mediated by a decline in oxidative stress.

Publication Types:

• Review

A pilot study on the relation between cisplatin neuropathy and vitamin E

J Exp Clin Cancer Res. 2001 Jun;20(2):277-80

Bove L, Picardo M, Maresca V, Jandolo B, Pace A.

Peripheral sensory neuropathy is the main non-hematological side-effect related to cisplatin chemotherapy. The strong similarity between clinical and neuropathological aspects in peripheral neuropathy induced by cisplatin and neurologic syndromes due to vitamin E deficiency, prompted us to investigate the relationship between cisplatin neuropathy and plasmatic level of vitamin E (alpha-tocopherol). We measured vitamin E in the plasma of 5 patients (Group 1) which developed severe neurotoxicity after cisplatin treatment and in another group of 5 patients (Group 2) we analyzed the plasmatic level of vitamin E before and after 2 or 4 cycles of cisplatin treatment. The results showed that the patients of group 1 presented low plasmatic levels of vitamin E and that the patients of group 2 presented significantly lower levels of vitamin E after 2 or 4 cycles of cisplatin than before treatment. Our preliminary data suggest that an inadequate amount of the antioxidant vitamin E due to cisplatin treatment could be responsible of the peripheral nerve damage induced by free-radicals. Given the lack of toxicity of vitamin E, we need to systematically assess the possible neuroprotective role of vitamin E supplementation in patients treated with cisplatin chemotherapy.

Effect of alpha-tocopherol deficiency on indices of oxidative stress in normal and diabetic peripheral nerve

J Neurol Sci. 1994 Oct;126(1):6-14

Nickander KK, Schmelzer JD, Rohwer DA, Low PA.

We tested the hypothesis that oxidative stress can cause neuropathy by evaluating the effect of alpha-tocopherol depletion in normal and streptozotocin (STZ) diabetic peripheral nerve (known to be subject to oxidative stress). The end points were nerve electrophysiology and indices of oxidative stress. Studies were done on 6 groups of rats at 1 and 3 months: (1) Controls, normal alpha-tocopherol (Con[N]). (2) Controls, alpha-tocopherol-deficient (Con[-]) (3) Controls, alpha-tocopherol supplemented (Con[+]); (4) Diabetic, normal alpha-tocopherol (STZ[N]); (5) Diabetic, alpha-tocopherol-deficient (STZ[-]) (6) Diabetic, alpha-tocopherol supplemented (STZ[+]). An alpha-tocopherol-deficient diet resulted in a rapid depletion of the vitamin in plasma and sympathetic neurones (superior cervical ganglion), and a slower depletion in sensory neurones (dorsal root ganglion) and nerve. The depletion was associated with a reduction in reduced glutathione and an increase in conjugated dienes and hydroperoxides in normal rats, and resulted in similar changes, or accentuated the abnormalities, in diabetic nerves. Changes were more pronounced at 1 than 3 months and alpha-tocopherol supplementation, for the most part, did not prevent the abnormalities. alpha-Tocopherol depletion induced or worsened nerve conduction abnormalities in both sciatic-tibial and caudal nerves. Sensory fibers were more affected than motor fibers and the changes were more pronounced at 3 than 1 month. These findings support the notion that oxidative stress may cause neuropathy and that it might be mechanistically implicated in experimental diabetic neuropathy (STZ-EDN).

Publication Types:

• Animal Study

Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation

J Pain Symptom Manage. 2006 Sep;32(3):237-44

Argyriou AA, Chroni E, Koutras A, Iconomou G, Papapetropoulos S, Polychronopoulos P, Kalofonos HP.

A randomized, controlled trial was performed to assess the efficacy and safety of vitamin E supplementation for prophylaxis against paclitaxel-induced peripheral neuropathy (PIPN). Thirty-two patients undergoing six courses of paclitaxel-based chemotherapy were randomly assigned to receive either chemotherapy with vitamin E (300 mg twice a day, Group I) or chemotherapy without vitamin E supplementation (Group II). A detailed neurological examination and electrophysiological study was performed during and 3 months after chemotherapy. The severity of PIPN was summarized by means of a modified Peripheral Neuropathy (PNP) score. The incidence of neurotoxicity differed significantly between groups, occurring in 3/16 (18.7%) patients assigned to the vitamin E supplementation group and in 10/16 (62.5%) controls (P=0.03). The relative risk (RR) of developing PIPN was significantly higher in controls than in vitamin E group patients (RR=0.3, 95% confidence interval (CI)=0.1-0.9). Mean PNP scores were 2.25+/-5.1 (range 0-15) for patients in Group I and 11+/-11.63 (range 0-32) for those in Group II (P=0.01). Vitamin E supplementation was well tolerated and showed an excellent safety profile. This study shows that vitamin E effectively and safely protects patients with cancer from the occurrence of paclitaxel-induced peripheral nerve damage. A double-blind, placebo-controlled trial is needed to confirm these results.

Publication Types:

• phase II trial

A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results

Support Care Cancer. 2006 Nov;14(11):1134-40. Epub 2006 Apr 19

Argyriou AA, Chroni E, Koutras A, Iconomou G, Papapetropoulos S, Polychronopoulos P, Kalofonos HP.

AIM: A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN). PATIENTS AND METHODS: A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score. RESULTS: The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16-5.47. Mean PNP scores were 4.99+/-1.33 for patients of group I and 10.47+/-10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation. CONCLUSION: Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity.

Publication Types:

• Placebo Controlled

Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study

Diabetes Care. 1998 Nov;21(11):1915-8

Tütüncü NB, Bayraktar M, Varli K.

OBJECTIVE: The present study has examined the effect of vitamin E, the principal modulator of free radical activity, on electrophysiological parameters in patients with diabetic peripheral sensorimotor polyneuropathy, matched for duration of disease and metabolic control. RESEARCH DESIGN AND METHODS: A total of 21 subjects with type 2 diabetes were enrolled in this double-blind randomized placebo-controlled study (vitamin E, 11 patients; placebo, 10 patients). Patients were randomly assigned to receive either 900 mg vitamin E or placebo for 6 months. The average dietary vitamin E consumption of the subjects was similar during the study. The main outcome measure was the electrophysiological tests assessing nerve conduction. Fasting plasma glucose, HbA1, postprandial plasma glucose, and electrophysiological parameters in the basal state and after 6 months of treatment were studied. RESULTS: Glycemic indexes did not show any significant changes during the study, whereas nerve conduction improved significantly in 2 of the 12 studied electrophysiological parameters after 6 months in patients on vitamin E supplementation. The changes in the electrophysiological parameters were obvious in the median motor nerve fibers and tibial motor nerve fibers. Nerve conduction velocity in the median motor nerve fibers (P = 0.0019) and tibial motor nerve distal latency (P = 0.0284) improved significantly after 6 months of vitamin E supplementation. CONCLUSIONS: This study shows that defective nerve conduction in diabetic subjects with mild-to-moderate peripheral neuropathy may be improved by pharmacological doses of vitamin E supplementation. Further studies with a larger number of patients for longer periods of time are needed.

Publication Types:

• double-blind randomized placebo-controlled study

Diabetes mellitus--a free radical-associated disease. Results of adjuvant antioxidant supplementation

Z Gesamte Inn Med. 1993 May;48(5):223-32

Kähler W, Kuklinski B, Rühlmann C, Plötz C.

Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads. The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis. 80 patients affected with a long term diabetic late syndrome were randomised and arranged to 4 groups of n = 20 each. In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium (sodium selenite) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months. In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates. The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner. The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications.

Publication Types:

• Review