Effects of alpha-lipoic acid treatment on serum progranulin levels and inflammatory markers in diabetic neuropathy

Objectives Progranulin (PGRN) is a secreted growth factor that helps to regulate neuronal survival by blocking tumor necrosis factor-alpha (TNFα) receptors. The antioxidant alpha-lipoic acid (ALA) is used in diabetic neuropathy to improve nerve conduction and relieve neuropathic pain, but its effects on PGRN levels have not yet been elucidated. Methods In this prospective study, 54 patients with type 2 diabetes and peripheral neuropathy received 600 mg of ALA daily for 6 months. Twenty-four patients with diabetes without neuropathy were also included in the study. Serum PGRN and TNFα levels were determined using enzyme-linked immunosorbent assays. In addition, current perception threshold (CPT) testing was used to assess sensory neuropathy. Results After ALA treatment, serum PGRN levels were significantly increased and CPT values were significantly improved. Furthermore, there were significant positive correlations among TNFα, ICAM-1, and PGRN levels both before and after ALA treatment. A significant negative correlation was observed between the improvements in CPT and the PGRN levels. Furthermore, ICAM-1 levels were an independent predictor of PGRN levels. Conclusions Changes in serum PGRN levels indicate that ALA treatment may have beneficial effects on endothelial function and neuronal inflammation.

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Alpha Lipoic Acid Influence in the Attenuation of Oxidative Stress and of Clinical Manifestations of Neuropathy in Diabetes Mellitus Patients

Internal Medicine ◽

10.2478/inmed-2018-0026 ◽

2018 ◽

Vol 15 (4) ◽

pp. 15-26

Author(s):

Bondar Andrei Cristian ◽

Popa Amorin Remus

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Diabetic Neuropathy ◽

Lipoic Acid ◽

Healthy Subjects ◽

Microvascular Complications ◽

Clinical Manifestations ◽

Clinical Aspects ◽

Alpha Lipoic Acid ◽

Perception Threshold

AbstractAlpha lipoic acid is an antioxidant substance used for the pathogenic treatment of diabetic neuropathy, oxidative stress being a central mechanism in diabetic microvascular complications. Our study included 24 diabetes mellitus patients with diabetic neuropathy and 20 healthy subjects. Diabetes patients were given alpha lipoic acid 600 mg intravenously for 10 days and then per os for 30 days.Significant improvements were observed concerning oxidative stress evaluated by measuring serum malondyaldehide and ceruloplasmin. The clinical characteristic of neuropathy improved, both the level of pain decreased and the vibration perception threshold increased. Our study demonstrated a two times higher level of oxidative stress in patients with diabetes compared to healthy subjects, and that by influencing oxidative stress we could influence the clinical aspects of neuropathy. Further investigations need to be done to explore the pleiotropic effects of alpha lipoic acid on other mechanisms that are implicated in the pathogenies of diabetic neuropathy.

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Efficacy and Safety of the Combination of Superoxide Dismutase, Alpha Lipoic Acid, Vitamin B12, and Carnitine for 12 Months in Patients with Diabetic Neuropathy

Nutrients ◽

10.3390/nu12113254 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3254

Author(s):

Triantafyllos Didangelos ◽

Eleni Karlafti ◽

Evangelia Kotzakioulafi ◽

Zisis Kontoninas ◽

Charalampos Margaritidis ◽

...

Keyword(s):

Quality Of Life ◽

Superoxide Dismutase ◽

Diabetic Neuropathy ◽

Vitamin B12 ◽

Lipoic Acid ◽

Controlled Study ◽

Alpha Lipoic Acid ◽

Double Blind ◽

Perception Threshold

Aim: To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). Patients–methods: In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, n = 43), or placebo (n = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered. Results: At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.027, p = 0.031, and p < 0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated (p < 0.001, p < 0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups (p < 0.001, p < 0.001, p = 0.031, p < 0.001, and p < 0.001 respectively). Conclusions: The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.

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Oral Alpha Lipoic Acid Treatment for Symptomatic Diabetic Peripheral Neuropathy: A Randomized Double-Blinded Placebo-Controlled Study

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200506081407 ◽

2020 ◽

Vol 20 (9) ◽

pp. 1531-1534 ◽

Cited By ~ 1

Author(s):

Mamdouh R. El-Nahas ◽

Ghada Elkannishy ◽

Hala Abdelhafez ◽

Enas T. Elkhamisy ◽

Amr A. El-Sehrawy

Keyword(s):

Peripheral Neuropathy ◽

Lipoic Acid ◽

Diabetic Peripheral Neuropathy ◽

Study Groups ◽

Controlled Study ◽

Alpha Lipoic Acid ◽

Disability Score ◽

Perception Threshold ◽

Outcome Parameters ◽

Double Blinded

Background: Alpha-lipoic acid (ALA) was used in the treatment of diabetic peripheral neuropathy (DPN) using different routes, doses and treatment durations. The aim of this work is to assess the efficacy of oral 600mg ALA twice daily over 6 months in the treatment of patients with DPN. Methods: This is a prospective, single-center, double-blinded, placebo-controlled study conducted at the outpatient clinic of Mansoura Specialized Hospital, Mansoura University. A total of 200 patients with DPN were randomly assigned to add on treatment with either oral 600mg twice daily ALA (n=100) or placebo (n=100) for 6 months. Treatment outcome was assessed using vibration perception threshold (VPT), neurological symptom score (NSS), neurological disability score (NDS), and visual analog scale (VAS) for pain at baseline and at each visit (1, 3 and 6 months) after the start of treatment. Results: Comparison between the study groups regarding the baseline data revealed no statistically significant differences. with respect to the outcome parameters, no significant differences were found between the studied groups at baseline. However, in subsequent visits, ALA-treated patients had significantly better results regarding almost all the outcome parameters (NSS, NDS, VAS, VPT). Mild nausea was reported in 6 patients. None of the studied patients discontinued treatment. Conclusions: Oral 600mg ALA twice-daily treatment for DPN over 6 months is effective, safe and tolerable.

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

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2000-7739 ◽

2000 ◽

Vol 108 (03) ◽

pp. 168-174 ◽

Cited By ~ 54

Author(s):

E. Haak ◽

K. Usadel ◽

K. Kusterer ◽

P. Amini ◽

R. Frommeyer ◽

...

Keyword(s):

Diabetic Neuropathy ◽

Lipoic Acid ◽

Alpha Lipoic Acid ◽

Peripheral Diabetic Neuropathy

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Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis

Life Sciences ◽

10.1016/j.lfs.2018.10.055 ◽

2019 ◽

Vol 216 ◽

pp. 101-110 ◽

Cited By ~ 10

Author(s):

Nasrin Sadeghiyan Galeshkalami ◽

Mohammad Abdollahi ◽

Rezvan Najafi ◽

Maryam Baeeri ◽

Akram Jamshidzade ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Neuropathy ◽

Lipoic Acid ◽

Coenzyme Q10 ◽

Alpha Lipoic Acid ◽

Experimental Diabetic Neuropathy

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The Changes of Nerve Growth Factor Serum Levels After External Muscle Stimulation and The Correlation with Diabetic Neuropathy Symptom in Diabetic Peripheral Neuropathy

Indonesian Journal of Physical Medicine & Rehabilitation ◽

10.36803/ijpmr.v6i01.146 ◽

2017 ◽

Vol 6 (01) ◽

pp. 7

Author(s):

Dian Herdiansyah ◽

Marina Annete Moeliono ◽

Tertianto Prabowo

Keyword(s):

Nerve Growth Factor ◽

Peripheral Neuropathy ◽

Growth Factor ◽

Diabetic Neuropathy ◽

Diabetic Peripheral Neuropathy ◽

Significant Negative Correlation ◽

Muscle Stimulation ◽

Study Objective ◽

Nerve Growth ◽

Before And After

Background: Diabetic Peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Recentstudies have demonstrated the involvement of Nerve growth factor (NGF) in the occurrence of DPN. TheDiabetes Mellitus was caused reduced the number and disruption of the function of the NGF. External MuscleStimulation (EMS) might be induced the NGF synthesis. The study objective has to found the effect of EMSon the NGF.Methods: Study design was before and after treatment without control on subjects with DPN. The bloodsample was taken before and after an intervention, as well as the Diabetic Neuropathy symptom (DNSym) andscore (DNSc). The EMS treated all of the participants within three times a week for four weeks.Results: There were 35 subjects were participated. Paired t-test showed a significant increase in NGF serumlevels and decrease both DNSym and DNSc with the difference value 12.64 ± 16.09 (p=0.000), 1.23 ± 0.82(p=0.000), 1.20 ± 0.85 (p=0.000). There was a significant negative correlation between NGF serum level withthe DNS- INA (r= -0.56; p=0.001) and the DNE-INA (r= -0.48; p=0.007).Conclusion: EMS treatment can increase serum NGF level. EMS has a strong correlation with a decrease inthe value of the DNS-INA and DNE-INA.Keywords: Diabetic Peripheral neuropathy, External Muscle Stimulation, Nerve Growth Factor.

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Evaluating the Efficacy of the Treatment with Benfotiamine and Alpha-lipoic Acid in Distal Symmetric Painful Diabetic Polyneuropathy

Revista de Chimie ◽

10.37358/rc.19.9.7498 ◽

2019 ◽

Vol 70 (9) ◽

pp. 3108-3114 ◽

Cited By ~ 5

Author(s):

Amorin Remus Popa ◽

Simona Bungau ◽

Cosmin Mihai Vesa ◽

Andrei Cristian Bondar ◽

Carmen Pantis ◽

...

Keyword(s):

Diabetic Neuropathy ◽

Lipoic Acid ◽

Combined Therapy ◽

Visual Analogue Pain Scale ◽

Alpha Lipoic Acid ◽

Painful Diabetic Neuropathy ◽

Disability Score ◽

Visual Analogue Pain ◽

Hexosamine Pathway ◽

Lower Limb Pain

Distal symmetric painful diabetic neuropathy is the most frequent clinical form of diabetic neuropathy. The condition appears as a result of alteration of the structure and function of nervous fibres as a consequence of hyperglycaemia. Hyperglycaemia determines the metabolism of glucose on alterative pathways and generates increased oxidative stress, mechanisms that cause an accelerated apoptosis of the neurons and a high intensity of lipid peroxidation. Pathogenic treatment of diabetic neuropathy includes limited options, two of them are: Benfotiamine (inhibits the metabolism of glucose on hexosamine pathway, reducing the formation of advanced glycosylation end products) and alpha-lipoic acid (has a scavenger effect on free radical species). The study included 120 patients with distal symmetric painful diabetic neuropathy randomized in 3 treatment groups. We evaluated the effect of oral administration for 8 weeks of Benfotiamine in a dosage of 300mg/day in monotherapy, of alpha-lipoic acid in a dosage of 600 mg/day in monotherapy, respectively of both -in combined therapy - on the parameters that are used to determine the severity of distal symmetric painful diabetic neuropathy: Diabetic Neuropathy Symptoms score, Neuropathy Disability Score and the intensity of lower limb pain on the visual analogue pain scale. All the three therapies were effective with a statistically significant improvement of these parameters, but the combined therapy with alpha-lipoic acid and Benfotiamine was superior to the monotherapy with alpha-lipoic acid or Benfotiamine.

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Exercise and Nutraceuticals: Eminent approach for Diabetic Neuropathy

Current Molecular Pharmacology ◽

10.2174/1874467214666210629123010 ◽

2021 ◽

Vol 14 ◽

Author(s):

Mayur Bhimrao Kale ◽

Komal Bajaj ◽

Mohit Umare ◽

Nitu L. Wankhede ◽

Brijesh Gulabrao Taksande ◽

...

Keyword(s):

Diabetic Neuropathy ◽

Motor Neurons ◽

Pathological Condition ◽

Weight Lifting ◽

The Public ◽

Beneficial Effects ◽

Current Review ◽

Patients With Diabetes ◽

Anti Oxidant ◽

Oxidant Effect

: Diabetic neuropathy is an incapacitating chronic pathological condition that encompasses a large group of diseases and manifestations of nerve damage. It affects approximately 50% of patients with diabetes mellitus. Autonomic, sensory, and motor neurons are affected. Disabilities are severe, along with poor recovery and diverse pathophysiology. Physical exercise and herbal-based therapies have the potential to decrease the disabilities associated with diabetic neuropathy. Aerobic exercises like walking, weight lifting, the use of nutraceuticals and herbal extracts are found to be effective. Literature from the public domain was studied emphasizing various beneficial effects of different exercises, use of herbal and nutraceuticals for their therapeutic action in diabetic neuropathy. Routine exercises and administration of herbal and nutraceuticals, either the extract of plant material containing the active phytoconstituent or isolated phytoconstituent at safe concentration, have been shown to have promising positive action in the treatment of diabetic neuropathy. Exercise has shown promising effects on vascular and neuronal health and has proven to be well effective in the treatment as well as prevention of diabetic neuropathy by various novel mechanisms, including herbal and nutraceuticals therapy is also beneficial for the condition. They primarily show the anti-oxidant effect, secretagogue, anti-inflammatory, analgesic, and neuroprotective action. Severe adverse events are rare with these therapies. The current review investigates the benefits of exercise and nutraceutical therapies in the treatment of diabetic neuropathy.

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