Dataset Information

Protocol for a randomised controlled trial to investigate the effects of vitamin K2 on recovery from muscle-damaging resistance exercise in young and older adults-the TAKEOVER study.

ABSTRACT:

Background

Regular participation in resistance exercise is known to have broad-ranging health benefits and for this reason is prominent in the current physical activity guidelines. Recovery after such exercise is important for several populations across the age range and nutritional strategies to enhance recovery and modulate post-exercise physiological processes are widely studied, yet effective strategies remain elusive. Vitamin K2 supplementation has emerged as a potential candidate, and the aim of the current study, therefore, is to test the hypothesis that vitamin K2 supplementation can accelerate recovery, via modulation of the underlying physiological processes, following a bout of resistance exercise in young and older adults.

Methods

The current study is a two-arm randomised controlled trial which will be conducted in 80 (40 young (≤40 years) and 40 older (≥65 years)) adults to compare post-exercise recovery in those supplemented with vitamin K2 or placebo for a 12-week period. The primary outcome is muscle strength with secondary outcomes including pain-free range of motion, functional abilities, surface electromyography (sEMG) and markers of inflammation and oxidative stress.

Discussion

Ethical approval has been granted by the College of Medical Veterinary and Life Sciences Ethical Committee at the University of Glasgow (Project No 200190189) and recruitment is ongoing. Study findings will be disseminated through a presentation at scientific conferences and in scientific journals.

Trial registration

ClinicialTrials.gov NCT04676958. Prospectively registered on 21 December 2020.

SUBMITTER: Lithgow H

PROVIDER: S-EPMC9764575 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Protocol for a randomised controlled trial to investigate the effects of vitamin K2 on recovery from muscle-damaging resistance exercise in young and older adults-the TAKEOVER study.

Lithgow Hannah H Johnston Lynsey L Ho Frederick K FK Celis-Morales Carlos C Cobley James J Raastad Truls T Hunter Angus M AM Lees Jennifer S JS Mark Patrick B PB Quinn Terry J TJ Gray Stuart R SR

Trials 20221220 1

<h4>Background</h4>Regular participation in resistance exercise is known to have broad-ranging health benefits and for this reason is prominent in the current physical activity guidelines. Recovery after such exercise is important for several populations across the age range and nutritional strategies to enhance recovery and modulate post-exercise physiological processes are widely studied, yet effective strategies remain elusive. Vitamin K2 supplementation has emerged as a potential candidate, ...[more]

PMID: 36539791

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Project description:BackgroundStudies have investigated the effects of training under hypoxia (HYP) after several weeks in a male population. However, there is still a lack of knowledge on the acute hypoxic effects on physiology and muscle recovery in a female population.MethodsThis randomized-controlled trial aimed to investigate the acute effects of muscle damaging exercise, performed in HYP and normoxia (CON), on physiological responses and recovery characteristics in healthy females. Key inclusion criteria were recreationally active female participants between the age of 18 to 35 years without any previous surgeries and injuries, whilst key exclusion criteria were acute pain situations, pregnancy, and medication intake. The females conducted a muscle-damaging protocol, comprising 5 × 20 drop-jumps, in either HYP (FiO2: 12%) or CON (FiO2: 21%). Physiological responses, including capillary oxygenation (SpO2), muscle oxygenation (SmO2), heart rate (HR), core- (Tcore) and skin- (Tskin) temperature were assessed at the end of each exercise set. Recovery characteristics were quantified by taking venous blood samples (serum creatine-kinase [CK], C-reactive protein [CRP] and blood sedimentation rate [BSR]), assessing muscle swelling of the quadriceps femoris muscle, maximum voluntary isometric contraction (MVIC) of the knee extensor muscles, countermovement jump (CMJ) performance and muscle soreness ratings (DOMS) at 24-, 48- and 72-hrs post-exercise.ResultsSpO2 (HYP: 76.7 ± 3.8%, CON: 95.5 ± 1.7%, p < 0.001) and SmO2 (HYP: 60.0 ± 9.3, CON: 73.4 ± 5.8%, p = 0.03) values were lower (p < 0.05) in HYP compared to CON at the end of the exercise-protocol. No physiological differences between HYP and CON were observed for HR, Tcore, and Tskin (all p > 0.05). There were also no differences detected for any recovery variable (CK, CRP, BSR, MVIC, CMJ, and DOMS) during the 72-hrs follow-up period between HYP and CON (all p > 0.05).ConclusionIn conclusion, our results showed that muscle damaging exercise under HYP leads to reduced capillary and muscle oxygenation levels compared to normoxia with no difference in inflammatory response and muscle recovery during 72 h post-exercise.Trial registrationNCT04902924, May 26th 2021.

Project description:Pre-sleep whey protein intake has been shown to improve overnight muscle protein synthesis, muscle size and strength, and muscle recovery. Despite a growing interest in alternative protein sources, such as plant-based protein, there is no evidence regarding the efficacy of plant-based proteins consumed pre-sleep. Therefore, we aimed to compare whey vs. plant-based pre-sleep protein dietary supplementation on muscle recovery in middle-aged men. Twenty-seven recreationally active, middle-aged men performed 5 sets of 15 repetitions of maximal eccentric voluntary contractions (ECC) for the knee extensors (ext) and flexors (flex), respectively, in the morning. Participants consumed 40 g of either whey hydrolysate (WH, n = 9), whey isolate (WI, n = 6), rice and pea combination (RP, n = 6), or placebo (PL, n = 6) 30 min pre-sleep on the day of ECC and the following two nights. Catered meals (15% PRO, 55% CHO, 30% Fat) were provided to participants for 5 days to standardize nutrition. Plasma creatine kinase (CK), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured at pre, immediately post (+0), +4, +6, +24, +48, and +72 h post-ECC. Isometric (ISOM) and isokinetic (ISOK) maximal voluntary contraction force were measured at pre, immediately post (+0), +24, +48, and +72 h post-ECC. Muscle soreness, thigh circumference, and HOMA-IR were measured at pre, +24, +48, and +72 h post-ECC. CK was increased at +4 h post-ECC, remained elevated at all time points compared to baseline (p < 0.001), and was significantly greater at +72 h compared to all other time points (p < 0.001). IL-6 was increased at +6 h (p = 0.002) with no other time differing from baseline. ISOMext was reduced after ECC (p = 0.001) and remained reduced until returning to baseline at +72 h. ISOMflex, ISOKext, and ISOKflex were reduced after ECC and remained reduced at +72 h (p < 0.001). Muscle soreness increased post-ECC (p < 0.001) and did not return to baseline. Thigh circumference (p = 0.456) and HOMA-IR (p = 0.396) did not change post-ECC. There were no significant differences between groups for any outcome measure. These data suggest that middle-aged men consuming 1.08 ± 0.02 g/kg/day PRO did not recover from damaging eccentric exercise at +72 h and that pre-sleep protein ingestion, regardless of protein source, did not aid in muscle recovery when damaging eccentric exercise was performed in the morning.

Project description:Skeletal muscle function is highly dependent on the ability to regenerate, however, during ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function. We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles, but whether vitamin K has a role in muscle regulation and function is unknown. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells. Cell viability experiments demonstrate that the amount of ATP produced by the cells was unchanged when MK-4 was added, indicating viable cells. Cytotoxicity analysis show that MK-4 reduced the lactate dehydrogenase (LDH) released into the media, suggesting that MK-4 was beneficial to the muscle cells. Cell migration, proliferation and differentiation was characterised after MK-4 incubation using wound scratch analysis, immunocytochemistry and real-time PCR analysis. Adding MK-4 to the cells led to an increased muscle proliferation, increased gene expression of the myogenic transcription factor myod as well as increased cell migration. In addition, we observed a reduction in the fusion index and relative gene expression of muscle differentiation markers, with fewer complex myotubes formed in MK-4 stimulated cells compared to control cells, indicating that the MK-4 plays a significant role during the early phases of muscle proliferation. Likewise, we see the same pattern for the relative gene expression of collagen 1A, showing increased gene expression in proliferating cells, and reduced expression in differentiating cells. Our results also suggest that MK-4 incubation affect low density lipoprotein receptor-related protein 1 (LRP1) and the low-density lipoprotein receptor (LDLR) with a peak in gene expression after 45 min of MK-4 incubation. Altogether, our experiments show that MK-4 has a positive effect on muscle cell migration and proliferation, which are two important steps during early myogenesis.

Project description:New findingsWhat is the central question of this study? Does acute ketone monoester supplementation enhance the recovery of muscle force and modulate circulating cytokine concentrations after muscle-damaging eccentric exercise? What is the main finding and its importance? Ketone monoester supplementation increased plasma β-hydroxybutyrate concentrations but did not attenuate the reduction in muscle force or the increase in plasma inflammatory cytokine concentrations that occurred after eccentric exercise. Notably we report novel data demonstrating a reduction in plasma TRAIL concentrations after eccentric exercise, highlighting TRAIL signalling as a possibly novel regulator of muscle recovery.AbstractMuscle-damaging eccentric exercise is associated with inflammation and impaired muscle force. β-Hydroxybutyrate (β-OHB) reduces muscle protein breakdown during inflammation but whether oral ketone monoester supplementation accelerates recovery of muscle force after eccentric exercise is unknown. Sixteen healthy males and females consumed thrice daily ketone monoester (27 g per dose; n = 8; six females; KES) or isocaloric maltodextrin placebo (n = 8; four females; PLA) drinks (randomized, double-blind, parallel group design) for 3 days beginning immediately after 300 unilateral eccentric quadriceps contractions during complete eucaloric dietary control (1.2 ± 0.1 g/kg BM/day standardized protein). Bilateral muscle force measurements and venous blood sampling were performed before and 3, 6, 24, 48 and 72 h after eccentric exercise. Plasma β-OHB concentrations were greater in KES compared with PLA at 3 h (0.56 ± 0.13 vs. 0.22 ± 0.04 mM, respectively; P = 0.080) and 6 h (0.65 ± 0.41 vs. 0.23 ± 0.02 mM, respectively; P = 0.031) post-eccentric exercise. Relative to the control leg, isokinetic work (by 20 ± 21% in PLA and 21 ± 19% in KES; P = 0.008) and isometric torque (by 23 ± 13% in PLA and 20 ± 18% in KES; P < 0.001) decreased from baseline at 3 h in the eccentrically exercised leg, and remained below baseline at 48 and 72 h, with no significant group differences. Of eight measured plasma cytokines, interleukin-6 (P = 0.008) and monocyte chemoattractant protein-1 (P = 0.024) concentrations increased after 6 h, whereas tumour necrosis factor-related apoptosis-inducing ligand concentrations decreased after 3 h (P = 0.022) and 6 h (P = 0.011) post-exercise with no significant group differences. Oral ketone monoester supplementation elevates plasma β-OHB concentrations but does not prevent the decline in muscle force or alter plasma inflammatory cytokine profiles induced by eccentric exercise.

Project description:Human hepatocellular carcinoma cells, HepG2 , cultured in DMEM containing 10% fetal calf serum. To study gene expression changes induced by Vitamin K2, total RNA was isolated following the Isogen procedure (Nippon-gene, Tokyo, Japan) from HepG2 cells with and without 50 microM of Vitamin K2 treatment for three days. The cDNA microarrays Human Oligo Chip 30K “AceGene” subset A was purchased from Hitachi Software Engineering Co. (Yokohama-City, Japan). This array contains 10368 kinds of gene-specific 50 mer sense oligonucleotides. Subset A contains mainly known function ORF oligo probes. Preparation of fluorescent cDNA targets by an indirect labeling approach was performed using PowerScript reverse transcription kit (Clontech). First-strand cDNAs were synthesized from 30 microg of total RNA from HepG2 cells treated with or without Vitamin K2 using random primer and PoweScript Fluorescent Labelling Kit. Monofunctional, N-hydroxysuccinimide-activated fluorescent dyes (Cy3 and Cy5; Amersham) were coupled to the cDNAs by reaction with the amino functional groups. Untreated cells were labeled with Cy3 as a control and treated cells with Cy5 as a sample. After free dyes were removed using MinElute Purification kit (Qiagen), the targets were mixed together and added to the microarrays, and then incubated overnight (16 hours) at 42?C. The slides were washed at 30?C in each with 2x SSC, 0.1% SDS and 2x SSC for 10 min and 5 min, respectively, and washed in 1x SSC for 5 min. Fluorescent images of the hybridized microarrays were scanned with a fluorescence laser confocal slide scanner (Affymetrix 428 Array Scanner, Affymetrix, Santa Clara, CA). The Cy3 and Cy5 intensities with background subtraction were determined by ImaGene 4.2 software (BioDiscovery, Marina Del Rey, CA). The expression data were then filtered based on their channel intensities, spot size and flag (missing or inaccurate data), and the Cy5/Cy3 ratios were calculated and normalized by median-centering the log-ratio of all genes.

Dataset Information

Protocol for a randomised controlled trial to investigate the effects of vitamin K2 on recovery from muscle-damaging resistance exercise in young and older adults-the TAKEOVER study.

Background

Methods

Discussion

Trial registration

Publications

Protocol for a randomised controlled trial to investigate the effects of vitamin K2 on recovery from muscle-damaging resistance exercise in young and older adults-the TAKEOVER study.

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