Vitamin B3 (Nicotinamide) Supplementation in Primary and Scleroderma-Related Raynaud Phenomenon

The aim of this study was to explore if vitamin B3 (nicotinamide) supplementation is a safe and effective adjunctive therapy for patients with primary Raynaud phenomenon (RP) and scleroderma-related RP. The effect of nicotinamide supplementation in human patients with RP has not been studied before.

Primary endpoints were to assess adherence to vitamin B3, vitamin B3-related adverse events, and changes in the following: (1) RP frequency and severity (via the Raynaud Condition Score diary), (2) RP-related quality of life (via the Short-Form Assessment of Systemic Sclerosis-Associated Raynaud's Phenomenon questionnaire), and (3) nailfold videocapillaroscopy (NVC) patterns and parameters. NVC incorporated artificial intelligence using Capillary.io software based on the validated CAPI-Detect algorithm. We conducted a six-week prospective longitudinal, within-participant crossover intervention study using a three-phase study design: A1 (baseline), B (vitamin B3 500 mg twice daily orally), and A2 (vitamin B3 washout); each phase was two weeks long. A total of 38 participants completed the study (20 with primary RP and 18 with scleroderma-related RP).

Vitamin B3 showed excellent adherence (98.7%) with few mild adverse events. NVC patterns improved in 45% postsupplementation (P < 0.001; total cohort), with increased normal and reduced abnormal capillaries. RP-related quality of life and severity improvements were significant only in primary RP, persisting after washout.

Vitamin B3 was well tolerated and improved NVC patterns and parameters in both groups, with benefits persisting postwashout. Participants with primary RP had significant improvements in patient-related outcome measures, which were not found in the scleroderma-related RP group. Scleroderma microvasculature may be more resistant to vasodilation, possibly due to structural remodeling. Improvements during the washout phase suggest that vitamin B3 may induce functional microvascular effects beyond its pharmacological half-life.