Effects of Vitamin C on Skeletal Muscle

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.

Eligibility Criteria:
Inclusion Criteria:

* Female, aged 65 years or over
* Non-smoker (or ex-smoker for at least 1 year).
* Engages in less than 20 minutes of structured physical activity per week, including cycling.
* Able to provide informed consent.
* Able to understand basic instructions in English.
* Willing to take daily vitamin C or placebo capsules.

Exclusion Criteria:

* Consumes more than 3 fruits and vegetables per day, including fruit and vegetable juices.
* Consumes vitamin C containing supplements, polyphenols, or other antioxidants (e.g. resveratrol or coenzyme q10).
* Regularly takes anti-inflammatory drugs.
* Alcohol intake \>14 units/week.
* Chronic clinical diseases (e.g., coronary artery/peripheral artery/cerebrovascular diseases, diabetes, chronic kidney disease requiring dialysis, diagnosed low renal function, neurological disorders or diseases that may affect motor/cognitive functions), except hypertension and hyperlipidaemia.
* History of kidney stones within the preceding 12 months.
* Contraindications for undergoing the MRI and exercise study procedures (e.g. major surgery, bilateral hip or knee replacement, non-MRI-compatible pacemaker or metal implants).
* Parallel participation in another research project that involves an intervention.
* Relation to, or co-habitation with, a member of the study team.
* Those who are part of the line manager/supervisory structure of the Chief Investigator.