Evaluation of the Efficacy of the Addition of a Combination of Pyrimidine Nucleotides and Vitamin B1 and B12 to Standard Treatment in the Management of Painful Radiculopathy and in the Quality of Life of Patients

<b>Background/Objectives</b>: Radiculopathy leads to pain, consequently reducing patient's quality of life (QoL). Research indicates that certain nucleotides, such as cytidine and uridine, along with vitamins B1 and B12, may help alleviate pain and enhance QoL. This study assessed the impact of adding a supplement containing cytidine and uridine nucleotides and vitamins B1 and B12, alongside standard treatment, on radiculopathy-associated pain. <b>Methods</b>: A multicenter, prospective, two-cohort, randomized, open-label study was conducted. The control group received standard treatment, while the experimental group received standard treatment plus the supplement. The primary endpoint was pain reduction measured by a Visual Analog Scale (VAS). Secondary endpoints included functional improvement (Roland Morris questionnaire), clinical improvement (Clinical Global Impression [CGI] scale), and QoL improvement (EQ-5D-5L questionnaire). <b>Results</b>: A total of 122 patients were included from 17 centers across Spain. Both groups showed pain improvement, but the VAS reduction (control: 24.58 vs. experimental: 31.35) was not statistically significant. The Roland Morris score decreased significantly in the experimental group (estimate: -1.70, 95% CI -3.29 to -0.10; <i>p</i> = 0.038), and these patients were 5 times more likely to progress to a better CGI category (OR = 0.20, 95% CI 0.07 to 0.57; <i>p</i> = 0.003). No significant differences were observed in EQ-5D-5L scores or analgesic consumption. <b>Conclusions</b>: The addition of supplemental pyrimidine nucleotides and vitamins B1 and B12 to standard of care treatment improved radiculopathy functional and clinical outcomes. Regarding pain, however, although there was a numerical improvement, it did not reach statistical significance.