Safety and Tolerability of a Combination of Curcumin, Omega-3 and Vitamin D: Results from the PASCOD Study, an RA Prevention Protocol
Bibliographic record
Abstract
Objectives Rheumatoid arthritis (RA) is an inflammatory autoimmune arthritis for which there is currently no cure. Recent research has focused on prevention strategies in individuals at increased risk of RA with the aim of reducing this risk. One such strategy involves dietary interventions. In a secondary analysis of a large prospective clinical trial (VITAL), vitamin D and omega-3 fatty acid supplementation have shown promise in reducing incident RA.[1] In a collagen induced arthritis murine model of RA, we showed that a diet supplemented with Curcumin, omega-3 and vitamin D (COD) reduced arthritis severity and incidence when given during the induction phase.[2] Based on these considerations, we are planning a prospective RA prevention trial using COD in anticitrullinated protein antibody (ACPA) positive individuals. However, there are no clinical trials which have evaluated the combined use of COD in humans. Thus, we conducted PASCOD (Pilot Assessment and Safety of COD) to evaluate the safety and tolerability of COD in healthy human volunteers. Methods Healthy volunteers aged 18-49 years with no history of RA or other autoimmune diseases were recruited (n=50) for a 4-week open-label pre-post design. Baseline visits included overall health and medications survey, anthropometric measures, functional status (RAPID3), a joint symptom questionnaire and a clinical assessment of 44 joints, all of which were repeated at the final visit. Blood specimens were collected for routine hematology and biochemistry. The study was powered to detect the rate of common side effects (>5% frequency), which was the primary outcome. Results Most reported side effects were mild (81.8%), with the most common, being heartburn (32%), fishy taste (30%), and abdominal bloating (24%), which mostly improved over time. Mean adherence was 97% for all 3 supplements. Reflective of this, we observed increases in eicosapentaenoic acid (EPA, p<0.0001), docosahexaenoic acid (DHA, p<0.0001) levels measured in plasma by gas chromatography, and vitamin D levels (p=0.01). Despite the absence of inflammatory arthritis, RAPID3 scores significantly decreased over the trial (p=0.048), driven by a reduction in self-reported joint pain visual analog scale (VAS, p=0.002). Self-reported joint pain score (p=0.008), fatigue VAS (p=0.008) and minutes of AM stiffness (p=0.01) all reduced after COD treatment (Figure). Conclusion Overall, 4 weeks of COD was well-tolerated, with high adherence and mild side effects which mostly improved over time. We observed improvements in self-reported symptoms relevant to individuals at risk for future RA development. This data suggests that COD supplementation is a feasible strategy for consideration in an RA prevention trial. [1.] Hahn J. BMJ 2022:376:e066452. [2.] Hemshekhar M. Arthritis Res Ther 2021;23(1):39.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.004 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".