Vitamin K2 Supplements for Muscle Recovery

Cachexia Clinical Trial

— Recovery  

Official title:

Effects of Vitamin K2 Supplements on Recovery of Lower Limb Muscle Function After Ankle Injury in Adults

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05161975
• Other study ID #: LithuanianSportsU-7
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 15, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: November 2021
• Source: Lithuanian Sports University
• Contact: Aivaras Ratkevicius, Dr.
• Phone: +37069009974
• Email: aivaras.ratkevicius[@]lsu.lt
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ankle injury is one of the most common injuries which can have long term consequences. Ankle immobilization is often applied for up to six weeks to ensure healing of the soft tissue and fractured bones after such an injury. This causes significant wasting of the lower leg muscles driven by inflammation and oxidative stress. The rate of muscle atrophy and recovery after injury varies significantly by sex and age. These differences might be linked to changes in gene and protein expression associated with regulation of protein synthesis and proteolysis. Interventions that reduce the deleterious effects of ankle injury as well as understanding of the underlying mechanisms could be particularly useful in promotion of healthy ageing. Vitamin K includes a group of structurally related compounds. Phylloquinone (vitamin K1) and menaquinones (vitamin K2s) of which MK-4 and MK-7 are the most important. Vitamin K2 has anti-inflammatory and antioxidant effects and thus may be effective in reducing muscle atrophy during limb immobilization and improving recovery of muscle function after injury. This aim of the current study is to investigate if vitamin K2 supplements can ameliorate muscle atrophy and improve recovery of muscle function after ankle injury. The investigators will study younger (18-39 year old) and older (40-60 year old) men and women to assess effects of sex and age.

Description:

Muscle weakness is associated with impaired quality of life, increased risk of falling, disability and premature mortality. Whilst ageing results in a progressive decline, even short periods of low physical activity can result in significant deterioration of muscle function and metabolic health. One such period of very low activity can occur following illness or injury. This can lead to decrease in lower limb muscle mass and strength. Muscle exercise training promotes recovery of skeletal muscles after injury though improvements vary between individuals and appear to decrease with age. Strategies to retard loss of muscle mass and function during inactivity are, thus, of critical importance in understanding of the mechanisms underlying such effects. Vitamin K includes a group of structurally related compounds named phylloquinone (vitamin K1) and menaquinones (vitamin K2s) of which MK-4 and MK-7 are the most important. Vitamin K is an essential cofactor for gamma carboxylation, required for the effective function of a range of proteins and has been linked to chronic disease and inflammation. Muscle cell studies suggest that vitamin K2 increases expression of myogenic transcription factors such as MyoD and promotes muscle cell proliferation. There are 20 described vitamin K dependent proteins (VKDPs). It is also known that vitamin K2 inhibits the activation of NFkB independently of gamma-carboxylation. This prevents nuclear entry of NFkB and therefore, consequently, vitamin K2 inhibits NFkB to interact with its nuclear receptors. In addition, Vitamin K2 can function as an electron carrier in mitochondria, and therefore play an inhibitory role on oxidative stress and release of ROS. There is, therefore, a strong rationale for investigating the effects of vitamin K2 during ankle immobilisation. The aim of the study is to investigate the effects of vitamin K2 on skeletal muscles after ankle injury and in the recovery process.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 18-60 years of age;
• Lives in Lithuania;
• Able and willing to give informed written consent to participate in the study;
• Recent (24 h before volunteering for the study) ankle injury requiring 6-week ankle immobilization;
• Exercise training program during 6-week recovery is recommended.

Exclusion Criteria:

• Body mass index (BMI) is greater than 30 kg / m2;
• Diabetes complicates cardiovascular diseases,
• Liver disease;
• Blood pressure is greater than 150/90mmHg during the first measurement;
• Incidences of consciousness loss;
• Cancer;
• Dementia;
• Other injuries that affect lower limb muscles;
• Use of anticoagulant drugs;
• Smoking;
• Drug abuse;
• Using drugs that affect muscle function (steroids).

Related Conditions & MeSH terms

• Cachexia
• Muscle Atrophy
• Muscular Atrophy

Intervention

Dietary Supplement:
• Vitamin K2
Volunteers will be randomly assigned to vitamin K2 or placebo group and consume one tablet of the food supplement per day.

Locations

Country	Name	City	State
Lithuania	Lithuanian Sports University	Kaunas
Lithuania	LSMU Kauno ligonine	Kaunas

Sponsors (3)

Lead Sponsor	Collaborator
Lithuanian Sports University	Kappa Bioscience AS, LSMU Kauno ligonine

Country where clinical trial is conducted

Lithuania, 

References & Publications (21)

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Psatha M, Wu Z, Gammie FM, Ratkevicius A, Wackerhage H, Lee JH, Redpath TW, Gilbert FJ, Ashcroft GP, Meakin JR, Aspden RM. A longitudinal MRI study of muscle atrophy during lower leg immobilization following ankle fracture. J Magn Reson Imaging. 2012 Mar;35(3):686-95. doi: 10.1002/jmri.22864. Epub 2011 Nov 1. — View Citation

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Muscle thickness	Transverse images of medial and lateral gastrocnemius, soleus and tibialis anterior muscles will be obtained using B-mode ultrasonography with a 10-15 MHz transducer.	12 weeks.
Primary	Muscle strength	Plantar flexor and extensor strength will be measured using isokinetic dynamometer (Biodex System 3 Biodex Medical Systems, Inc., Shirley, NY, USA).	12 weeks.
Primary	Vitamin K2 status	Blood samples will be taken and plasma levels of vitamin K2 will be assessed.	12 weeks.
Secondary	Cytokine profile	Blood samples will be taken and ELISA assays for insulin, myostatin, TGF-ß2, IGF-1, IL-1b, IL-6 and TNF-alpha will be performed	12 weeks.
Secondary	Gene expression profile	Biopsies of soleus and gastrocnemius muscles will be taken. The mRNA levels of p62, Atrogin 1, MuRF 1, LC3b and Gapdh were assessed using SYBR Green (#4367659, Thermo Fisher Scientific) assay for quantitative PCR.	12 weeks.
Secondary	Protein expression profile	Biopsies of soleus and gastrocnemius muscles will be taken. Western blotting will be carried to examine signalling pathways that control protein synthase (Akt-mTOR-p70s6k).	12 weeks.
Secondary	Metabolic enzyme activity	Biopsies of soleus and gastrocnemius muscles will be taken. Enzyme assays for citrate synthase (CS), succinate dehydrogenase (SDH), ß-hydroxyacyl-coenzyme dehydrogenase (HAD) and other metabolic enzyme will be carried out.	12 weeks.