Muscle Wasting and Rheumatoid Arthritis Flares

People living with Rheumatoid Arthritis (RA) often present with low muscle mass compared to their healthy counterparts. This affects their mobility, overall health and quality of life. Even though low muscle mass in RA has been recognised for decades, it is still highly prevalent and very little is known about its development, progression, and potential management.

The researchers hypothesise that flares of disease activity trigger acute events of muscle wasting due to high inflammation and reduced mobility. This is commonly observed in bed rest studies and people hospitalised for various reasons. If this holds true for RA, it would point towards a stepwise development of RC and potentially allow for time-targeted management of it.

A potential method to manage it is through the use of nutritional supplements. Specifically, amino acid supplementation (commonly used by athletes or people wanting to increase muscle mass) during and shortly after a flare may counteract some of the muscle wasting and allow for better long-term mobility and quality of life for people living with RA.

This study aims to investigate aspects of muscle health changes following a disease flare-up in people with Rheumatoid Arthritis (RA) and test potential interventions to minimise any such changes. The investigators will randomly assign participants to a standard care or a nutritional supplementation group and assess aspects of body composition, muscle health, disease activity and inflammation on five occasions over a 3-month period.

This study aims to investigate aspects of muscle health changes following a disease flare-up in people with Rheumatoid Arthritis (RA) and test potential interventions to minimise any such changes.

RA is the most common inflammatory arthritis manifesting mainly as joint swelling and pain, limiting mobility, and eventually leading to loss of functional capacity. RA also has severe extra-articular manifestations \[1\], affecting several tissues in the body including skeletal muscle \[2\]. People living with RA often present with an adverse body composition profile compared to the general population, characterised by low muscle mass at the presence of unchanged or even increased overall weight \[3\]. This condition, termed Rheumatoid Cachexia, may affect up to 2 out of 3 people with RA and associates with active disease, further reductions in mobility, and low quality of life \[4\].

While rheumatoid cachexia has been studied extensively, the course of its development, as well as potential causes or contributors to it are poorly understood. Inflammation, \[5\] as well as lifestyle factors, such as energy intake and physical activity, may contribute to the observed body composition changes \[6\].

People living with RA often experience flares of disease activity, where high levels of inflammation, cause an acute exaggeration of symptoms, leading to very low levels of mobility. This is commonly treated with corticosteroid injections which will rapidly reduce inflammation and allow the patient to regain mobility. However, that short period of high inflammatory load and low mobility may acutely affect muscle characteristics. Indeed, critically ill patients may lose up to 2% of skeletal muscle per day during the first week of hospitalisation \[7\]. This rapid decline in muscle health has been recently termed Acute sarcopenia (AS) by the European working group in sarcopenia and older persons (EWGSOP) \[8\]. Furthermore, recent work within this research team is currently under review (Aldrich et al., 2023 under review) demonstrating the rapid decline of muscle mass and quality in people suffering with various diseases. Additionally, corticosteroids themselves may further contribute to muscle wasting in RA \[9\]. Yet, the acute effects of flares and their treatment on muscle health in people with RA are not known.

Acute deterioration of muscle health following a flare may point towards a stepwise development of rheumatoid cachexia, i.e., bouts of acute deterioration that accumulate over time in steps rather than a continuous slow loss - which is the current understanding for the development of sarcopenia, the age-related muscle wasting. This would allow for target and potentially short-term interventions that could limit or even reverse muscle deterioration during a flare and help people with RA better maintain their functionality.

Exercise, and particularly resistance exercise, is the most effective way to increase muscle mass, strength, and quality. However, people during and shortly after a flare may not be willing to engage in such an intervention. Additional complexities around gym or home-based delivery, familiarisation, and safe execution render this a complex intervention with potentially limited applicability.

Nutritional supplementation on the other hand, is readily available, relatively cheap, and easy to administer. Specifically, for muscle health, amino acid supplementation, and particularly with leucine, has been shown to improve muscle mass and muscle function in older men and women \[10\]. Moreover, previous research has shown that these amino acid supplements do not suppress appetite, are well tolerated and easy to consume. Finally, recent unpublished data from this laboratory suggest that amino acid concentrations in the blood following consumption alongside a meal remain elevated vs placebo for over 2 hours. This indicates that consuming two supplements per day would provide sufficient amino acids to induce beneficial effects on muscle health.

Therefore, the aims of this investigation are:

1. To understand the effects of acute RA flares on muscle health
2. To assess the efficacy of amino acid supplementation vs. standard care in maintaining muscle health

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of a flare of rheumatoid arthritis

Exclusion Criteria:

* Consultation with RA physician greater than 7 days before
* Allergic to supplement ingredients
* Other health conditions that affect muscle wasting; such as cancer and fibromyalgia
* Previous joint replacement surgery within the last 6 months
* Anyone with underlying kidney conditions
* Currently partaking in other research projects involving treatments, exercise or nutritional interventions for rheumatoid arthritis
* Patients who may be pregnant
* Patients who are unable to provide their own informed consent
* Patients who are unable to speak or understand English
* Participants who have a diagnosis of dementia or Alzheimer's disease
* Disabled participants who require wheelchair access