Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 9/2021

Open Access 01-09-2021 | Diabetic Neuropathy | Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)

Molecular Aspects in the Potential of Vitamins and Supplements for Treating Diabetic Neuropathy

Authors: Tina Okdahl, Christina Brock

Published in: Current Diabetes Reports | Issue 9/2021

Login to get access

Abstract

Purpose of Review

To discuss and provide evidence-based data on dietary supplements as part of treating diabetic neuropathy

Recent Findings

Few randomized controlled trials are available, but some have shown beneficial efficacy of various dietary supplements on objective primary endpoints including nerve conduction velocities and axon potentials as well as subjective patient-reported outcomes.

Summary

No medical cure for diabetic neuropathy exists, and prevention is therefore crucial. Tight glucose control slows the progression of nerve damage in diabetes, but an unmet clinical need for effective interventions is warranted. Consequently, a growing number of patients turn to dietary supplements proposed to possess neuroprotective properties. However, the postulated effects are often not evidence-based as they have not been tested scientifically. Taken together, this review will focus on dietary supplements investigated in clinical trials for their potential capabilities in targeting the molecular mechanisms involved in the underlying pathogenesis of diabetic neuropathy.
Literature
1.
2.
Tesfaye S, Boulton AJM, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. In: Diabetes Care. Diabetes Care. 2010:2285–93.
3.
Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11:521–34.
4.
Jensen TS, Karlsson P, Gylfadottir SS, Andersen ST, Bennett DL, Tankisi H, et al. Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management. Brain. 2021.
5.
Pop-Busui R, Boulton AJM, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136–54.PubMedCrossRef
6.
Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab. 2007;27:1766–91.
7.
Meldgaard T, Olesen SS, Farmer AD, Krogh K, Wendel AA, Brock B, et al. Diabetic enteropathy: from molecule to mechanism-based treatment. J Diabetes Res. 2018.
8.
9.
10.
Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17:24–38.
11.
Román-Pintos LM, Villegas-Rivera G, Rodríguez-Carrizalez AD, Miranda-Díaz AG, Cardona-Muñoz EG. Diabetic polyneuropathy in type 2 diabetes mellitus: inflammation, oxidative stress, and mitochondrial function. J Diabetes Res. 2016:1–16.
12.
Shakeel M. Recent advances in understanding the role of oxidative stress in diabetic neuropathy. Diabetes Metab Syndr Clin Res Rev. 2015;9(4):373–8.CrossRef
13.
Van Dam PS, Cotter MA, Bravenboer B, Cameron NE. Pathogenesis of diabetic neuropathy: focus on neurovascular mechanisms. Eur J Pharmacol. 2013;719(1–3):180–6.PubMed
14.
Athyros VG, Doumas M, Imprialos KP, Stavropoulos K, Georgianou E, Katsimardou A, et al. Diabetes and lipid metabolism. 2000
15.
Perez-Matos MC, Morales-Alvarez MC, Mendivil CO. Lipids: a suitable therapeutic target in diabetic neuropathy? 2017
16.
Yagihashi S, Mizukami H, Sugimoto K. Mechanism of diabetic neuropathy: where are we now and where to go? J Diabetes Investig. 2011;2:18–32.
17.
Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376(9739):419–30.PubMedPubMedCentralCrossRef
18.
19.
Wc K, Eb-C, Se F, Rf H, Jm L, Ea W, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.CrossRef
20.
Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.PubMedCrossRef
21.
Rösen P, Nawroth PP, King G, Möller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a congress series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev. 2001;17:189–212.
22.
Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005;4.
23.
Apfel SC, Apfel SC. Neurotrophic factors and diabetic peripheral neuropathy. Eur Neurol. 1999;41.
24.
Oh YS. Bioactive compounds and their neuroprotective effects in diabetic complications. Nutrients. 2016;8.
25.
Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T, Fawzi Mahomoodally M, Lobine D, et al. Insights on the use of α-lipoic acid for therapeutic purposes. Biomolecules. 2019;9(8).
26.
Attia M, Essa EA, Zaki RM, Elkordy AA. An overview of the antioxidant effects of ascorbic acid and alpha lipoic acid (in liposomal forms) as adjuvant in cancer treatment. Antioxidants. 2020;9.
27.
Eason RC, Archer HE, Akhtar S, Bailey CJ. Lipoic acid increases glucose uptake by skeletal muscles of obese-diabetic ob/ob mice. Diabetes Obes Metab. 2002;4(1):29–35.PubMedCrossRef
28.
Henriksen EJ. Exercise training and the antioxidant α-lipoic acid in the treatment of insulin resistance and type 2 diabetes. Free Radic Biol Med. 2006;40:3–12.
29.
Garcia-Alcala H, Santos Vichido CI, Islas Macedo S, Genestier-Tamborero CN, Minutti-Palacios M, Hirales Tamez O, et al. Treatment with α-lipoic acid over 16 weeks in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose loading. J Diabetes Res. 2015.
30.
Pieralice S, Vari R, Minutolo A, Maurizi AR, Fioriti E, Napoli N, et al. Biomarkers of response to alpha-lipoic acid ± palmitoiletanolamide treatment in patients with diabetes and symptoms of peripheral neuropathy. Endocrine. 2019;66(2):178–84.PubMedCrossRef
31.
Agathos E, Tentolouris A, Eleftheriadou I, Katsaouni P, Nemtzas I, Petrou A, et al. Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res. 2018;46(5):1779–90.PubMedPubMedCentralCrossRef
32.
Mrakic-Sposta S, Vezzoli A, Maderna L, Gregorini F, Montorsi M, Moretti S, et al. R(+)-thioctic acid effects on oxidative stress and peripheral neuropathy in type II diabetic patients: preliminary results by electron paramagnetic resonance and electroneurography. Oxidative Med Cell Longev. 2018.
33.
Ziegler D, Low PA, Litchy WJ, Boulton AJM, Vinik AI, Freeman R, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054–60.PubMedPubMedCentralCrossRef
34.
Zhang DW, Fu M, Gao SH, Liu JL. Curcumin and diabetes: a systematic review. Evidence-based Complementary and Alternative Medicine. Evid Based Complement Alternat Med. 2013.
35.
Memarzia A, Khazdair MR, Behrouz S, Gholamnezhad Z, Jafarnezhad M, Saadat S, et al. Experimental and clinical reports on anti-inflammatory, antioxidant, and immunomodulatory effects of Curcuma longa and curcumin, an updated and comprehensive review. BioFactors. 2021.
36.
Asadi S, Gholami MS, Siassi F, Qorbani M, Khamoshian K, Sotoudeh G. Nano curcumin supplementation reduced the severity of diabetic sensorimotor polyneuropathy in patients with type 2 diabetes mellitus: a randomized double-blind placebo-controlled clinical trial. Complement Ther Med. 2019;43:253–60.PubMedCrossRef
37.
Chen Q, Prior M, Dargusch R, Roberts A, Riek R, Eichmann C, et al. A novel neurotrophic drug for cognitive enhancement and Alzheimer’s disease. PLoS One. 2011;6(12).
38.
Lv J, Cao L, Zhang R, Bai F, Wei P. A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced dpn rat models through negative regulation AMPK on TRPA1. Acta Cir Bras. 2018;33(6):533–41.PubMedCrossRef
39.
Goldberg J, Currais A, Prior M, Fischer W, Chiruta C, Ratliff E, et al. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell. 2018;17(2).
40.
Huang Q, Chen Y, Gong N, Wang YX. Methylglyoxal mediates streptozotocin-induced diabetic neuropathic pain via activation of the peripheral TRPA1 and Nav1.8 channels. Metabolism. 2016;65(4):463–74.PubMedCrossRef
41.
Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Met Syn Obesity Targets Therapy. 2014;7:241–53.
42.
Peh HY, Tan WSD, Liao W, WSF W. Vitamin E therapy beyond cancer: tocopherol versus tocotrienol. Pharmacol Ther. 2016;162:152–69.PubMedCrossRef
43.
Kuhad A, Chopra K. Tocotrienol attenuates oxidative-nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy. Neuropharmacology. 2009;57(4):456–62.PubMedCrossRef
44.
Rajanandh MG, Kosey S, Prathiksha G. Assessment of antioxidant supplementation on the neuropathic pain score and quality of life in diabetic neuropathy patients - a randomized controlled study. Pharmacol Rep. 2014;66(1):44–8.PubMedCrossRef
45.
Ng YT, Phang SCW, Tan GCJ, Ng EY, Henien NPB, Palanisamy UDM, et al. The effects of tocotrienol-rich vitamin E (Tocovid) on diabetic neuropathy: a phase II randomized controlled trial. Nutrients. 2020;12(5).
46.
Hor CP, Fung WY, Ang HA, Lim SC, Kam LY, Sim SW, et al. Efficacy of oral mixed tocotrienols in diabetic peripheral neuropathy: a randomized clinical trial. JAMA Neurol. 2018;75(4):444–52.PubMedPubMedCentralCrossRef
47.
Coste TC, Gerbi A, Vague P, Pieroni G, Raccah D. Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy. Diabetes. 2003;52(10):2578–85.PubMedCrossRef
48.
Rumora AE, LoGrasso G, Hayes JM, Mendelson FE, Tabbey MA, Haidar JA, et al. The divergent roles of dietary saturated and monounsaturated fatty acids on nerve function in murine models of obesity. J Neurosci. 2019;39(19):3770–81.PubMedPubMedCentralCrossRef
49.
Hinder LM, Figueroa-Romero C, Pacut C, Hong Y, Vivekanandan-Giri A, Pennathur S, et al. Long-chain acyl coenzyme A synthetase 1 overexpression in primary cultured Schwann cells prevents long chain fatty acid-induced oxidative stress and mitochondrial dysfunction
50.
Yorek MA. The potential role of fatty acids in treating diabetic neuropathy Current Diabetes Reports. Current Medicine Group LLC. 2018;18.
51.
Redivo DDB, Jesus CHA, Sotomaior BB, Gasparin AT, Cunha JM. Acute antinociceptive effect of fish oil or its major compounds, eicosapentaenoic and docosahexaenoic acids on diabetic neuropathic pain depends on opioid system activation. Behav Brain Res. 2019;372:111992.PubMedCrossRef
52.
Shevalye H, Yorek MS, Coppey LJ, Holmes A, Harper MM, Kardon RH, et al. Effect of enriching the diet with menhaden oil or daily treatment with resolvin D1 on neuropathy in a mouse model of type 2 diabetes. J Neurophysiol. 2015;114(1):199–208.PubMedPubMedCentralCrossRef
53.
Coppey L, Davidson E, Shevalye H, Obrosov A, Yorek M. Effect of early and late interventions with dietary oils on vascular and neural complications in a type 2 diabetic rat model. J Diabetes Res. 2019.
54.
Coppey L, Davidson E, Shevalye H, Obrosov A, Torres M, Yorek MA. Progressive loss of corneal nerve fibers and sensitivity in rats modeling obesity and type 2 diabetes is reversible with omega-3 fatty acid intervention: supporting cornea analyses as a marker for peripheral neuropathy and treatment. Diabetes, Metab Syndr Obes Targets Ther. 2020;13:1367–84.CrossRef
55.
Lewis EJH, Perkins BA, Lovblom LE, Bazinet RP, Wolever TMS, Bril V. Effect of omega-3 supplementation on neuropathy in type 1 diabetes. Neurology. 88(24):2294–301.
56.
Wang D, Zhai JX, Liu DW. Serum folate, vitamin B12 levels and diabetic peripheral neuropathy in type 2 diabetes: a meta-analysis. Mol Cell Endocrinol. 2017;443:72–9.PubMedCrossRef
57.
Iskandar BJ, Nelson A, Resnick D, Skene JHP, Gao P, Johnson C, et al. Folic acid supplementation enhances repair of the adult central nervous system. Ann Neurol. 2004;56(2):221–7.PubMedCrossRef
58.
Sijilmassi O. Folic acid deficiency and vision: a review Graefe’s Archive for Clinical and Experimental Ophthalmology. 2019;257:1573–80.
59.
Yilmaz M, Aktug H, Oltulu F, Erbas O. Neuroprotective effects of folic acid on experimental diabetic peripheral neuropathy. Toxicol Ind Health. 2016;32(5):832–40.PubMedCrossRef
60.
Mottaghi T, Khorvash F, Maracy M, Bellissimo N, Askari G. Effect of folic acid supplementation on nerve conduction velocity in diabetic polyneuropathy patients. Neurol Res. 2019;41(4):364–8.PubMedCrossRef
61.
Niu Y, Li J, Peng R, Zhao X, Wu J, Tang Q. Low vitamin D is associated with diabetes peripheral neuropathy in older but not in young and middle-aged patients. Diabetes Metab Res Rev. 2019;35(6).
62.
Lv WS, Zhao WJ, Gong SL, Fang DD, Wang B, Fu ZJ, et al. Serum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis. J Endocrinol Investig. 2015;38(5):513–8.CrossRef
63.
Wei W, Zhang Y, Chen R, Qiu X, Gao Y, Chen Q. The efficacy of vitamin D supplementation on painful diabetic neuropathy: protocol for a systematic review and meta-analysis. Medicine. 2020;99(31):e20871.PubMedPubMedCentralCrossRef
64.
Zhang B, Zhao W, Tu J, Wang X, Hao Y, Wang H, et al. The relationship between serum 25-hydroxyvitamin D concentration and type 2 diabetic peripheral neuropathy: a systematic review and a meta-analysis. Medicine. 2019;(98).
65.
Tiaka EK, Papanas N, Manolakis AC, Maltezos E. The role of nerve growth factor in the prophylaxis and treatment of diabetic foot ulcers. Int J Burns Trauma. 2011;1(1):68–76.PubMedPubMedCentral
66.
Alam U, Fawwad A, Shaheen F, Tahir B, Basit A, Malik RA. Improvement in neuropathy specific quality of life in patients with diabetes after vitamin D supplementation. J Diabetes Res. 2017.
67.
Ghadiri-Anari A, Mozafari Z, Gholami S, Khodaei SA, Aboutorabi-zarchi M, Sepehri F, et al. Dose vitamin D supplementations improve peripheral diabetic neuropathy? A before-after clinical trial. Diabetes Metab Syndr Clin Res Rev. 2019;13(1):890–3.CrossRef
68.
Allen LH. Vitamin B-12. Adv Nutr. 2012:54–5.
69.
Alvarez M, Sierra OR, Saavedra G, Moreno S. Vitamin B12 deficiency and diabetic neuropathy vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study. 2019
70.
Jayabalan B, Low LL. Vitamin B supplementation for diabetic peripheral neuropathy. Singap Med J. 2016;57:55–9.CrossRef
71.
Didangelos T, Karlafti E, Kotzakioulafi E, Margariti E, Giannoulaki P, Batanis G, et al. Vitamin B12 supplementation in diabetic neuropathy: a 1-year, randomized, double-blind, placebo-controlled trial. Nutrients. 2021;13(2):1–14.CrossRef
72.
Peng HY, Gong YY. Analysis of the effect of probucol-mecobalamin tablets combination on oxidative stress in patients with diabetic peripheral neuropathy. Neurosci Lett. 2021;741:135484.PubMedCrossRef
Metadata
Title
Molecular Aspects in the Potential of Vitamins and Supplements for Treating Diabetic Neuropathy
Authors
Tina Okdahl
Christina Brock
Publication date
01-09-2021
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 9/2021
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-021-01397-1

Other articles of this Issue 9/2021

Current Diabetes Reports 9/2021 Go to the issue

Microvascular Complications—Retinopathy (R Channa, Section Editor)

The Role of Ultra-Widefield Fundus Imaging and Fluorescein Angiography in Diagnosis and Treatment of Diabetic Retinopathy

Microvascular Complications—Retinopathy (R Channa, Section Editor)

Laser Therapy in the Treatment of Diabetic Retinopathy and Diabetic Macular Edema

Microvascular Complications—Retinopathy (R Channa, Section Editor)

Toward a New Staging System for Diabetic Retinopathy Using Wide Field Swept-Source Optical Coherence Tomography Angiography

Hospital Management of Diabetes (A Wallia and J Seley, Section Editors)

Predicting and Preventing Acute Care Re-Utilization by Patients with Diabetes

Microvascular Complications—Retinopathy (R Channa, Section Editor)

Management of Complications and Vision Loss from Proliferative Diabetic Retinopathy

Macrovascular Complications in Diabetes (VS Aroda and L-S Chang, Section Editors)

Cardiovascular Risk Management in Type 1 Diabetes
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits