R Alpha Lopoic Acid
Alpha-lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo-controlled randomized trial.Full Text Available By: Heinisch, B. B.; Francesconi, M.; Mittermayer, F.; Schaller, G.; Gouya, G.; Wolzt, M.; Pleiner, J.. European Journal of Clinical Investigation, Feb2010, Vol. 40 Issue 2, p148-154, 7p, 2 Charts, 2 Graphs; DOI: 10.1111/j.1365-2362.2009.02236.x
Abstract: Objective The aim of this study was to investigate the effect of alpha-lipoic acid (ALA) treatment on endothelium-dependent and -independent vasodilatation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus. Conclusions Intravenous ALA treatment improves endothelium-dependent vasodilatation in patients with type 2 diabetes, in the absence of effects on forearm vasomotor function.
Effects of Alpha-Lipoic Acid Supplementation in Peripheral Arterial Disease: A Pilot Study.Full Text Available By: Vincent, Heather K.; Bourguignon, Cheryl M.; Vincent, Kevin R.; Taylor, Ann G.. Journal of Alternative & Complementary Medicine, Jun2007, Vol. 13 Issue 5, p577-584, 8p, 4 Charts; DOI: 10.1089/acm.2007.6177
Objective: To examine whether 3 months of lipoic acid (LA) supplementation improved walking tolerance and delayed claudication pain onset in peripheral arterial disease (PAD). Twenty-eight (28) participants (15 men, 13 women) with PAD. Intervention: LA (600 mg/day) or placebo for 3 months. Outcome measures: Walking tolerance was assessed by 6-minute walk test distance, 4-meter walk time, initial claudication pain time (ICT) and distance (ICD), and peak claudication pain. Results: ICT increased 34.4% and 15%, ICD was reduced by 40.5% and 18%, and peak claudication pain ratings were reduced by 93% and 7% in LA and placebo groups, respectively. Conclusions: LA may confer pain relief during exercise. However, longer and larger trials are warranted to determine long-term effects of LA alone or combined with other interventions on PAD symptoms.
Goepp, J. (2010). Reverse Mitochondrial Damage. Life Extension, 16(2), 46-52.
The article discusses the use of lipoic acid to reverse mitochondrial damage. According to the author lipoic acid may play a role in defending against diseases which involve impaired energy utilization such as diabetic neuropathy. R-alpha-lipoic acid enhances mitochondrial function which in turn provides anti-aging benefits such as the prevention of some forms of cardiovascular disease and helping to protect liver cells.
Mijnhout, G., Kollen, B., Alkhalaf, A., Kleefstra, N., & Bilo, H. (2012). Alpha lipoic Acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. International Journal Of Endocrinology, 2012456279.
Objective. We performed a systematic review of the literature to evaluate the effects of alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes mellitus. Research design and methods. Randomised controlled trials using the TSS score as the outcome measure were selected and assessed for their methodological quality. Study selection and quality assessment were performed independently by three observers. Results. Overall, the pooled standardized mean difference estimated from all trials revealed a reduction in TSS scores of -2.26 in favour of alpha lipoic acid administration. Subgroup analyses of oral administration Conclusions. When given intravenously at a dosage of 600 mg/day over a period of 3 weeks, alpha lipoic acid leads to a significant and clinically relevant reduction in neuropathic pain.
Vitamin B1 (Benfotiamine)
Balakumar, P., Rohilla, A., Krishan, P., Solairaj, P., & Thangathirupathi, A. (2010). The multifaceted therapeutic potential of benfotiamine. Pharmacological Research, 61(6), 482-488. doi:10.1016/j.phrs.2010.02.008
Abstract: Thiamine, known as vitamin B1, plays an essential role in energy metabolism. The anti-AGE property of benfotiamine certainly makes it effective for the treatment of diabetic neuropathy, nephropathy and retinopathy.
Vrkonyi, T., & Kempler, P. (2008). Diabetic neuropathy: new strategies for treatment [electronic resource]. Diabetes, Obesity & Metabolism, 10(2), 99-108.
Current therapeutic possibilities can be divided into two groups: the pathogenetically oriented and the symptomatic therapy. One of the most important component of etiology-based treatment is the stabilization of glycemic control. Based on efficacy and safety data benfotiamine and alpha-lipoic acid should be considered as first choices among pathogenetically oriented treatments of diabetic neuropathy.
Schmid, U., Stopper, H., Heidland, A., & Schupp, N. (2008). Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro. Diabetes/Metabolism Research & Reviews, 24(5), 371-377.
Benfotiamine, a lipophilic thiamine diphosphate prodrug, prevented early renal and retinal changes in animal studies, and reduced neuropathic pain in clinical studies. Several mechanisms for these activities have been described. We investigated for the first time direct antioxidant abilities of benfotiamine. Benfotiamine shows a direct antioxidant action. This effect of benfotiamine may be involved in the improvement of diabetic late complications, including peripheral neuropathy.
H., S. (2008). Benfotiamine in Diabetic Polyneuropathy (BENDIP): Results of a Randomised, Double Blind, Placebo-controlled Clinical Study. Experimental & Clinical Endocrinology & Diabetes, 116(10), 600-605.
AIM: Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. METHODS: Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. CONCLUSION: Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.
Winkler, G., Pál, B., Nagybéganyi, E., Ory, I., Porochnavec, M., & Kempler, P. (1999). Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. Arzneimittel-Forschung, 49(3), 220-224.
An overall bneneficial therapeutic effect on the neuropathy status was observed in all three groups during the study, and a significant improvement in most of the parameters studied appeared already at the 3rd week of therapy. The greatest change occurred in the group of patients receiving the high dose of benfotiamine. Metabolic control did not change over the study. It is concluded that benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.
Haupt, E., Ledermann, H., & Köpcke, W. (2005). Benfotiamine in the treatment of diabetic polyneuropathy--a three-week randomized, controlled pilot study (BEDIP study). International Journal Of Clinical Pharmacology And Therapeutics, 43(2), 71-77.
Objective: The aim of the study was to evaluate the efficacy of benfotiamine administered over three weeks Results: A statistically significant improvement in the neuropathy score was observed in the group given active drug when compared to the placebo-treated controls. More patients in the benfotiamine-treated group than in the placebo group considered their clinical condition to have improved. No side effects attributable to benfotiamine were observed.
Wu, S., & Ren, J. (2006). Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-α. Neuroscience Letters, 394(2), 158-162. doi:10.1016/j.neulet.2005.10.022
Abstract: Diabetes mellitus leads to thiamine deficiency and multiple organ damage including diabetic neuropathy. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cerebral oxidative stress. Adult male FVB mice were made diabetic with a single injection of STZ. Fourteen days later, control and diabetic mice received benfotiamine for 14 days. Benfotiamine alleviated diabetes-induced cerebral oxidative stress without affecting levels of AGE, protein carbonyl, tissue factor and TNF-α. Collectively, our results indicated benfotiamine may antagonize diabetes-induced cerebral oxidative stress through a mechanism unrelated to AGE, tissue factor and TNF-α.
Sánchez-Ramírez, G. M., Caram-Salas, N. L., Rocha-González, H. I., Vidal-Cantú, G. C., Medina-Santillán, R., Reyes-García, G., & Granados-Soto, V. (2006). Benfotiamine relieves inflammatory and neuropathic pain in rats. European Journal Of Pharmacology, 530(1/2), 48-53. doi:10.1016/j.ejphar.2005.11.016
Benfotiamine has shown therapeutic efficacy in the treatment of painful diabetic neuropathy in human beings. Results indicate that oral administration of benfotiamine is able to reduce tactile allodynia from different origin in the rat and they suggest the use of this drug to reduce inflammatory and neuropathic pain in humans.
Vitamin B12 (Methylcobalamin)
Vitamin B12 may be more effective than nortriptyline in improving painful diabetic neuropathy. Full Text Available By: TALAEI, AFSANEH; SIAVASH, MANSOUR; MAJIDI, HAMID; CHEHREI, ALI. International Journal of Food Sciences & Nutrition, Nov2009 Supplement 5, Vol. 60, p71-76, 6p, 1 Chart; DOI: 10.1080/09637480802406153
Introduction Despite many therapeutic options, painful diabetic neuropathy is still a common and challenging complication of diabetes mellitus and is often resistant to treatment with current modalities. Methods In this randomized, single-blind clinical trial we compared the efficacy of parenteral vitamin B12 and nortriptyline, for symptomatic improvement of pain, paresthesia, burning, freezing, stabbing and electrical sensation.. Changes in nerve conduction parameters of amplitude, duration and latency were also compared. Conclusion In conclusion, vitamin B12 is more effective than nortriptyline for the treatment of symptomatic painful diabetic neuropathy.
Methylcobalamin effects on diabetic neuropathy and nerve protein kinase C in rats.Detail Only Available By: Mizukami, Hiroki; Ogasawara, Saori; Yamagishi, Shin-Ichiro; Takahashi, Kazunori; Yagihashi, Soroku. European Journal of Clinical Investigation, Apr2011, Vol. 41 Issue 4, p442-450, 9p, 1 Color Photograph, 1 Chart, 3 Graphs; DOI: 10.1111/j.1365-2362.2010.02430.x
(Methycobalamin) (B12) has a special affinity for nerve tissues to promote myelination and transport of axonal cytoskeleton. It is not known, however, how B12 influences on peripheral nerve in experimental diabetic neuropathy. Conclusions This study suggested that correction of impaired neural signalling of oxidative stress-induced damage may be a major attribute to the beneficial effects of B12 on diabetic nerve.
Li, J., Wang, C., Chen, J., Li, X., Feng, Z., & Ma, H. (2010). The preventive efficacy of methylcobalamin on rat peripheral neuropathy influenced by diabetes via neural IGF-1 levels. Nutritional Neuroscience, 13(2), 79-86.
We investigated the preventive efficacy of exogenous methylcobalamin on sciatic nerve IGF-1 expression down-regulation and peripheral nerve deficit under different conditions (hyperglycemia and duration) of experimental diabetes in rats. It is concluded that exogenous methylcobalamin delayed onset of diabetic peripheral neuropathy via up-regulation of neural IGF-1 gene expression, and a better neuroprotective effect could be achieved in the presence of good control of hyperglycemia, especially at early stage of diabetes.
Sun, Y., Lai, M., & Lu, C. (2005). Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurologica Taiwanica, 14(2), 48-54.
Three studies involved the use of vitamin B complex (including B12) as the active drug, and four more studies used methylcobalamin. Both the vitamin B12 combination and pure methylcobalamin had beneficial effects on somatic symptoms, such as pain and paresthesia. In three studies, methylcobalamin therapy improved autonomic symptoms. With both the vitamin B12 combination and pure methylcobalamin, symptomatic relief was greater than changes in electrophysiological results. However, more high-quality, double-blind randomized controlled trials are needed to confirm the effects of vitamin B12 on diabetic neuropathy.
Jacobs, A., & Cheng, D. (2011). Management of diabetic small-fiber neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate. Reviews In Neurological Diseases, 8(1-2), 39-47.
Agents used to treat symptoms of diabetic peripheral neuropathy (DPN) are only palliative, not disease modifying. Although studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that each of these bioavailable B vitamins may reverse the pathophysiology and symptoms of DPN, data on the efficacy of this combination therapy are limited. Therefore, we assessed the efficacy of an oral combination of L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate for improving epidermal nerve fiber density (ENFD) in the lower extremity of patients with DPN. This preliminary study suggests that combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate increases ENFD in patients with DPN.
Mizukami, H., Ogasawara, S., Yamagishi, S., Takahashi, K., & Yagihashi, S. (2011). Methylcobalamin effects on diabetic neuropathy and nerve protein kinase C in rats. European Journal Of Clinical Investigation, 41(4), 442-450. doi:10.1111/j.1365-2362.2010.02430.x
Background: Methyl-base-attached cobalamin (Methycobalamin) (B12) has a special affinity for nerve tissues to promote myelination and transport of axonal cytoskeleton. It is not known, however, how Methycobalamin influences on peripheral nerve in experimental diabetic neuropathy. Materials and Methods: We studied the effects of B12 on expressions and activities of protein kinase C (PKC) in peripheral nerve of streptozotocin-induced diabetic rats. Conclusions: This study suggested that correction of impaired neural signalling of PKC and oxidative stress-induced damage may be a major attribute to the beneficial effects of B12 on diabetic nerve.
Walker, M., Morris, L., & Cheng, D. (2010). Improvement of cutaneous sensitivity in diabetic peripheral neuropathy with combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate. Reviews In Neurological Diseases, 7(4), 132-139.
Studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that these B vitamins may reverse both the symptoms and the pathophysiology of diabetic peripheral neuropathy (DPN). Treatment with oral LMF-MC-PP appears to promote restoration of lost cutaneous sensation in DPN.
Yaqub, B., Siddique, A., & Sulimani, R. (1992). Effects of methylcobalamin on diabetic neuropathy. Clinical Neurology And Neurosurgery, 94(2), 105-111.
We studied the clinical and neurophysiological effects of methylcobalamin on patients with diabetic neuropathy. In a double-blind study, the active group showed statistical improvement in the somatic and autonomic symptoms with regression of signs of diabetic neuropathy. Motor and sensory nerve conduction studies showed no statistical improvement after 4 months. The drug was easily tolerated by the patients and no side effects were encountered.
Ide, H., Fujiya, S., Asanuma, Y., Tsuji, M., Sakai, H., & Agishi, Y. (1987). Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy. Clinical Therapeutics, 9(2), 183-192.
Seven men and four women with symptomatic diabetic neuropathy were treated with methylcobalamin (2,500micrograms in 10 ml of saline) injected intrathecally. Symptoms in the legs, such as paresthesia, burning pains, and heaviness, dramatically improved. The effect appeared within a few hours to one week and lasted from several months to four years. Methylcobalamin caused no side effects with respect to subjective symptoms or characteristics of spinal fluid. These findings suggest that a high concentration of methylcobalamin in spinal fluid is highly effective and safe for treating the symptoms of diabetic neuropathy.
Shehab, D. D., Al-Jarallah, K. K., Mojiminiyi, O. A., Al Mohamedy, H. H., & Abdella, N. A. (2012). Does Vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes?. Diabetic Medicine, 29(1), 43-49. doi:10.1111/j.1464-5491.2011.03510.x
Abstract Aim Despite recent reports linking vitamin D deficiency with increased risk of diabetes mellitus and complications, there is limited data on patients with diabetic peripheral neuropathy. We aimed to evaluate the incidence and associations of vitamin D deficiency in 210 patients with Type 2 diabetes with and without diabetic peripheral neuropathy. Results Eighty-seven patients had diabetic peripheral neuropathy and these patients had significantly longer duration of diabetes and higher HbA1c. Age, gender, incidence of retinopathy and coronary heart disease were not significantly different from those without neuropathy. Mean (SD) vitamin D was significantly lower in those with neuropathy [36.9 (39.9) nmol/l] compared with those without [58.32 (58.9) nmol/l] and 81.5% of patients with neuropathy had vitamin D deficiency compared with 60.4% of those without. Vitamin D showed significant ( P < 0.05) correlations with total cholesterol, LDL-cholesterol and urine microalbumin:creatinine ratio. Binary logistic regression analysis showed that diabetic peripheral neuropathy was significantly associated with vitamin D deficiency Conclusion Vitamin D deficiency is an independent risk factor for diabetic peripheral neuropathy.
Soderstrom, L. H., Johnson, S. P., Diaz, V. A., & Mainous, A. (2012). Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001-2004 NHANES. Diabetic Medicine, 29(1), 50-55. doi:10.1111/j.1464-5491.2011.03379.x
Abstract Aims To evaluate the association between vitamin D insufficiency and peripheral neuropathy in a nationally representative sample of adults with diagnosed diabetes. Results In the weighted population, 81% of adults with diabetes had vitamin D insufficiency. Vitamin D insufficiency was more common among Hispanics (92%) and non-Hispanic black people (98%) than among non-Hispanic white people (76%). Conclusions Vitamin D insufficiency is associated with self-reported peripheral neuropathy symptoms even after adjusting for demographic factors, obesity, co-morbidities, use of medications for neuropathy and diabetes duration and control.
Aalinkeel, R., Hu, Z., Nair, B. B., Sykes, D. E., Reynolds, J. L., Mahajan, S. D., & Schwartz, S. A. (2010). Genomic Analysis Highlights the Role of the JAK-STAT Signaling in the Anti-proliferative Effects of Dietary Flavonoid—‘Ashwagandha’ in Prostate Cancer Cells. Evidence-Based Complementary & Alternative Medicine (Ecam), 7(2), 177-187.
Phytochemicals are dietary phytoestrogens that may play a role in prostate cancer prevention. Forty percent of Americans use complementary and alternative medicines (CAM) for disease prevention and therapy. Ashwagandha (Withania somnifera) contains flavonoids and active ingredients like alkaloids and steroidal lactones which are called ‘Withanolides’. We hypothesize that the immunomodulatory and anti-inflammatory properties of Ashwagandha might contribute to its overall effectiveness as an anti-carcinogenic agent. These studies outline several functionally important classes of genes, which are associated with immune response, signal transduction, cell signaling, transcriptional regulation, apoptosis and cell cycle regulation and provide insight into the molecular signaling mechanisms that are modulated by Ashwagandha, thereby highlighting the use of this bioflavanoid as effective chemopreventive agent relevant to prostate cancer progression.