Research Article
Volume 13 Issue 9 - 2021
Randomized, Placebo-Controlled, Double-Blind Pilot Study of the Antinociceptive Effect of Menaquinone-7 (Vitamin MK-7) in Patients with Peripheral Neuropathy
Dilip S Mehta1, Shashank S Jadhav1, Milind Devale2, Rama Vaidya3, Ashok DB Vaidya3, Sidney J Stohs4 and Vladimir Badmaev5*
1Synergia Life Sciences Pvt. Ltd., Mumbai, India
2Kokan Hospital, Mumbai, India
3Medical and Research Centre, Kasturba Health Society, Mumbai, India
4School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska, USA
5Advisory Board of Synergia Life Sciences Pvt. Ltd, Staten Island, NY, USA
*Corresponding Author:Vladimir Badmaev, Advisory Board of Synergia Life Sciences Pvt. Ltd, Staten Island, NY, USA.
Received: June 29, 2021; Published: August 28, 2021


   A randomized, placebo-controlled double-blind pilot study was conducted to evaluate the efficacy and safety of vitamin MK-7 (menaquinone-7) in comparison to placebo in patients with peripheral neuropathy due to Type 2 diabetes mellitus (DM) or vitamin B12 deficiency (B12D) to facilitate design of a full-size clinical trial. A 100 µg capsule of MK-7 or identical placebo capsule was given twice daily for 8 weeks to 20 ambulatory patients of both genders to evaluate symptoms of peripheral neuropathy in DM and B12D patients. The patients were followed for an additional 4 weeks (total of 12 weeks) and the intensity of the symptoms was self-assessed using a pain Visual Analog Scale (VAS). The serum levels of vitamin MK-7 were determined at the baseline, week 4 and week 8.

   There was a statistically significant decrease in the pain VAS score in DM and B12D patients receiving vitamin MK-7 supplementation vs the corresponding placebo groups. The VAS pain score at baseline was on average approximately 9 out of 10. It was reduced to an average score of about 2 by week 12 in the DM and B12D groups supplemented with vitamin MK-7 vs scores greater than 8 by week 12 in the placebo groups. The VAS score was inversely related to MK-7 levels and peripheral neuropathy symptoms. Vitamin MK-7 was well-tolerated without subjective and objective adverse effects reported during the 8-week therapy and during the additional 4 weeks of follow-up.


Keywords: Vitamin MK-7 Serum Levels; Menaquinone-7 (Vitamin K2-7); Type 2 Diabetes Mellitus; Vitamin B12 Deficiency; Peripheral Neuropathy


  1. Martyn CN and Hughes RA. “Epidemiology of peripheral neuropathy”. Journal of Neurology, Neurosurgery, and Psychiatry4 (1997): 310-318.
  2. Hilton TN., et al. “Excessive adipose tissue infiltration in skeletal muscles in individuals with obesity, diabetes mellitus, and peripheral neuropathy: Association with performance and function”. Physical Therapy11 (2008): 1336-1344.
  3. Trivedi S., et al. “Epidemiology of peripheral neuropathy: An Indian perspective”. Annals of Indian Academy of Neurology3 (2017): 173-184.
  4. Gill HK., et al. “A prospective study of prevalence and association of peripheral neuropathy in Indian patients with newly diagnosed type 2 diabetes mellitus”. Journal of Postgraduate Medicine3 (2014): 270-275.
  5. Bansal D., et al. “Prevalence and risk factors of development of peripheral diabetic neuropathy in Type 2 diabetes mellitus in a tertiary care setting”. Journal of Diabetes Investigation6 (2014): 714-721.
  6. Kumar N. “Neurologic aspects of cobalamin (B12) deficiency”. Handbook of Clinical Neurology 120 (2014): 915-926.
  7. Oosterhuis WP., et al. “Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency”. The Scandinavian Journal of Clinical and Laboratory Investigation 60 (2000): 9-18.
  8. Tanaka H. “Old or new medicine? Vitamin B12 and peripheral nerve neuropathy”. Brain Nerves9 (2013): 1077-1082.
  9. Franques J and Gazzola S. “Metabolic and nutritional neuropathies: update in diabetes, vitamin B12 and copper deficiency”. Revue Neurologique12 (2013): 991-996.
  10. Alvarez M., et al. “Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study”. Endocrine Connections10 (2019): 1324-1329.
  11. Rosenberg CJ and Watson JC. “Treatment of painful diabetic peripheral neuropathy”. Prosthetics and Orthotics International1 (2015): 17-28.
  12. Ong CK., et al. “An evidence-based update on nonsteroidal anti-inflammatory drugs”. Clinical Medicine and Research1 (2007): 19-34.
  13. Lakhan SE., et al. “Botulinum Toxin-A for Painful Diabetic Neuropathy: A Meta-Analysis”. Pain Medicine9 (2015): 1773-1780.
  14. Boyle J., et al. “Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life”. Diabetes Care12 (2012): 2451-2458.
  15. Alleman CJ., et al. “Humanistic and economic burden of painful diabetic peripheral neuropathy in Europe: A review of the literature”. Diabetes Research and Clinical Practice2 (2015): 2015-2025.
  16. Schreiber AK., et al. “Diabetic neuropathic pain: Physiopathology and treatment”. World Journal of Diabetes3 (2015): 432-444.
  17. Kulkarni VK., et al. “The effect of vitamin K2-7 in peripheral neuropathy due to vitamin B12 deficiency and/or diabetes mellitus: A preliminary study”. The Indian Practitioner10 (2013): 625-629.
  18. Mehta DS., et al. “A novel potential role of vitamin K2-7 in relieving peripheral neuropathy”. Journal of Pharmacology and Pharmacotherapeutics4 (2018): 180-185.
  19. Karamzad N., et al. “A systematic review on the mechanisms of vitamin K effects on the complications of diabetes and pre-diabetes”. Biofactors1 (2020): 21-37.
  20. Wewers ME and Lowe NK. “A critical review of visual analogue scales in the measurement of clinical phenomena”. Research in Nursing and Health4 (1990): 227-236.
  21. Davidson KW and Sadowski JA. “Determination of Vitamin K Compounds in Plasma or Serum by High-Performance Liquid Chromatography Using Post-Column Chemical Reduction and Fluorimetric Detection”. In: Methods in Enzymology 282 (1997): 408-409.
  22. International Council for Harmonization of Technical Requirements For Pharmaceuticals For Human Use. Bioanalytical Method Validation M10 (2019).
  23. De Winter JCF. “Using Student’s t-test with extremely small sample sizes”. Practical Assessment, Research and Evaluation 10 (2013).
  24. Dunnigan SK., et al. “Comparison of diabetes patients with "demyelinating" diabetic sensorimotor polyneuropathy to those diagnosed with CIDP”. Brain and Behavior 6 (2013): 656-663.
  25. Sharma KR., et al. “Diabetic demyelinating polyneuropathy responsive to intravenous immunoglobulin therapy”. Archives of Neurology 5 (2002): 751-757.
  26. Sharma KR., et al. “Demyelinating neuropathy in diabetes mellitus”. Archives of Neurology 5 (2002): 758-765.
  27. Guylaine F. “Vitamin K and the Nervous System: An Overview of its Actions”. Advances in Nutrition 3 (2012): 204-212.
  28. Abbott CA., et al. “Explanations for the lower rates of diabetic neuropathy in Indian Asians versus Europeans”. Diabetes Care6 (2010): 1325-1330.
  29. Theuwissen E., et al. “Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status but had no effect on thrombin generation in healthy subjects”. British Journal of Nutrition 108 (2012): 1652-1657.
  30. Choi HJ., et al. “Vitamin K2 Supplementation Improves Insulin Sensitivity via Osteocalcin Metabolism: A Placebo-Controlled Trial”. Diabetes Care9 (2011): e147.
  31. Beulens J., et al. “Dietary Phylloquinone and Menaquinones Intakes and Risk of Type 2 Diabetes”. Diabetes Care8 (2010): 1699-1705.
  32. Dilip S., et al. “Randomized Controlled Trial of the Antinociceptive Effect of Menaquinone-7 (Vitamin MK-7) in Patients with Peripheral Neuropathy”. EC Neurology.
Citation: Vladimir Badmaev, et al. “Randomized, Placebo-Controlled, Double-Blind Pilot Study of the Antinociceptive Effect of Menaquinone-7 (Vitamin MK-7) in Patients with Peripheral Neuropathy”. EC Neurology 13.9 (2021): 112-124.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

November Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the November issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before December 15, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.