As part of the ageing process muscles become weaker. One of the reasons for this is that mitochondria, the 'engines' that provide energy to fuel muscles, age and work less efficiently. Mitochondria are found in almost all cells in the human body. Mitochondria take in nutrients that are provided from food and break these down to create energy-rich compounds to fuel many different processes in the body. Muscles are loaded with mitochondria because they require a lot of energy. Mitochondria naturally produce small compounds called oxidants that can damage muscle cells and can cause inflammation. The cells in the body have a natural defence system to protect against oxidants, but when mitochondria age and become less efficient, the amount of oxidants that they produce can increase. These oxidants can damage muscles and the mitochondria themselves. Antioxidants, such as vitamin C, may help protect muscles from the damage caused by oxidants, and may help mitochondria work more efficiently. In this study, the investigators will explore whether vitamin C can help mitochondria work more efficiently, which may improve muscle strength, and help older people to remain mobile and independent for longer.
The VICS study is a 16-week randomised, double-blind, placebo-controlled two-arm crossover pilot study conducted between the Norfolk and Norwich University Hospital (NNUH) and the Quadram Institute Clinical Research Facility (QI CRF) in Norwich, UK. Investigators are seeking women over the age of 65 years with low habitual fruit and vegetable consumption to determine whether vitamin C supplementation affects mitochondrial function, compared to a matched placebo. Participants will attend 3 clinical visits where investigators will assess skeletal muscle mitochondrial function and membrane turnover using 31-phosphorous magnetic resonance spectroscopy (31P MRS). Investigators will assess muscle strength (hand grip strength and knee extension strength) measured using handheld dynamometers, and physical function measured using the short physical performance battery (SPPB). Investigators will monitor blood levels of vitamin C and inflammatory markers, specifically high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), and the collagen markers procollagen type-1 N-terminal propeptide (P1NP) and collagen type-1 cross-linked C telopeptide (CTX). Participants will consume one oral capsule daily (containing either 500mg vitamin C or a matched placebo) for the first 6-week intervention period, then, after a 4-week washout phase, participants will crossover and consume the other capsule daily for the second 6-week intervention period. Participants will be asked to complete a food frequency (dietary) questionnaire and physical activity questionnaire at each visit to monitor their physical activity levels and fruit and vegetable consumption.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
16
University of East Anglia
Norwich, Norfolk, United Kingdom
Difference in skeletal muscle mitochondrial function between vitamin C and placebo groups.
Comparison of skeletal muscle mitochondrial oxidative capacity (estimated from 31P MRS measured phosphocreatine recovery half-time) following 6 weeks of vitamin C supplementation or 6 weeks of placebo.
Time frame: Week: 6 and 16
Difference in skeletal muscle phosphomonoester to phosphodiester ratio (PME/PDE) between vitamin C and placebo groups.
Skeletal muscle phosphomonoester (PME) and phosphodiester (PDE) concentrations can be measured using 31P MRS, and reflect cell membrane synthesis and breakdown respectively. The signal amplitudes (in arbitrary units) of these two species will be combined to report the (unitless) PME/PDE ratio, which reflects cell membrane turnover and may be related to oxidative stress. Comparison of PME/PDE ratio following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in knee extension strength between vitamin C and placebo groups.
Comparison of knee extension strength following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in hand grip strength between vitamin C and placebo groups.
Comparison of hand grip strength following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in Short Physical Performance Battery (SPPB) score between vitamin C and placebo groups.
The Short Physical Performance Battery (SPPB) assesses three components of physical performance: standing balance, gait speed and chair stands. Each of the three components is scored from 0 (worst possible performance) to 4 (best possible performance). Scores from each of the three components are then summed to provide an overall SPPB score ranging from 0 (worst performance) to 12 (best performance). Comparison of SPPB score following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in plasma vitamin C between vitamin C and placebo groups.
Comparison of plasma vitamin C following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in serum hs-CRP between vitamin C and placebo groups.
Comparison of serum hs-CRP following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in serum IL-6 between vitamin C and placebo groups.
Comparison of serum IL-6 following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in serum TNF-α between vitamin C and placebo groups.
Comparison of serum TNF-α following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in plasma P1NP between vitamin C and placebo groups.
Comparison of plasma P1NP following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
Difference in plasma CTX between vitamin C and placebo groups.
Comparison of plasma CTX following 6 weeks of vitamin C or 6 weeks of placebo.
Time frame: Week: 6 and 16.
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