From the Guidelines
There is no clear evidence that individuals with rheumatoid arthritis (RA) need to avoid citrulline. In fact, citrulline supplementation might potentially be beneficial for some RA patients, though research is still limited. Citrulline is an amino acid that converts to arginine in the body and helps produce nitric oxide, which can support blood flow and reduce inflammation. Some preliminary research suggests that citrulline might help reduce muscle wasting and fatigue, which are common problems in RA. The 2023 American College of Rheumatology guideline for exercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis 1 does not mention citrulline as something to be avoided, instead emphasizing the importance of a "food first" approach and a Mediterranean-style diet for RA management. While some concern exists because citrulline shares a name with anti-citrullinated protein antibodies (ACPAs) involved in RA, dietary citrulline is different and doesn't appear to worsen the autoimmune response in RA. If considering citrulline supplements, RA patients should start with a lower dose and monitor for any changes in symptoms. It's essential to note that citrulline might interact with certain medications, including some used for RA treatment, so patients should consult with their healthcare provider before starting any supplement. Key points to consider:
- Citrulline supplementation may have potential benefits for RA patients, such as reducing muscle wasting and fatigue
- The American College of Rheumatology guideline does not recommend avoiding citrulline
- A "food first" approach and a Mediterranean-style diet are recommended for RA management
- Patients should consult with their healthcare provider before starting any citrulline supplement due to potential interactions with RA medications.
From the Research
Rheumatoid Arthritis and Citrulline Consumption
- There is no direct evidence to suggest that individuals with Rheumatoid Arthritis (RA) should avoid consuming citrulline 2, 3, 4, 5.
- Citrulline is a non-standard amino acid that plays a role in the pathophysiology of RA, and autoantibodies against citrullinated proteins are a hallmark of the disease 2, 3.
- However, the current evidence suggests that citrullination is a normal process in immune and non-immune cells, and dysregulated citrullination is a feature of RA 4.
- Some studies suggest that citrullinated peptides can alter protein structure and trigger an autoimmune response in RA, but they can also promote immune tolerance under certain conditions 5.
- Dietary factors, such as omega-3 fatty acids, may have a protective effect on RA-related autoimmunity, particularly in individuals with a genetic susceptibility to RA 6.
Key Findings
- Anti-citrullinated protein antibodies (ACPAs) are present in up to 80% of patients with RA and are highly specific for the disease 2.
- ACPAs are associated with joint radiographic damage and extra-articular manifestations, and their production is linked to the HLA-DRB1 shared epitope (HLA-DRB1 SE) 3.
- Citrullinated proteins can induce arthritis in transgenic mice carrying HLA-DRB1 SE genes, and ACPAs can induce macrophage TNF-α production, osteoclastogenesis, and complement activation 3.
- The relationship between citrulline consumption and RA is complex, and further research is needed to fully understand the role of citrulline in the disease 2, 3, 4, 5.