The objective for this clinical pilot study was to evaluate changes to chronic pain, vascular health, and inflammatory markers when consuming a dietary supplement blend (DSB, CytoQuel), containing curcumin, resveratrol, tocotrienols, N-Acetylcysteine, and epigallocatechin gallate. An open-label study design was used where 21 study participants were evaluated at baseline and at 2 and 8 weeks after consuming DSB. Participants were randomized to consume 3 capsules once daily versus 2 capsules twice daily. Pain and activities of daily living questionnaires were used to gather subjective data on pain levels and interference with daily living. Blood pressure was measured in both arms and ankles, and the ankle-brachial index (ABI) calculated. Blood samples were used to evaluate markers associated with inflammation and cardiovascular health. Highly significant reduction of chronic pain was seen after 8 weeks (<0.01), both at rest and when physically active. Faster improvement was seen when consuming 3 capsules once daily, compared to 2 capsules twice daily. The pain reduction resulted in improved sleep quality (<0.1), and improved social functioning (<0.01), and less need for support from others (<0.05), Normalization of mildly elevated ABI at study start was seen after 2 weeks. Plasma fibrinogen and von Willebrand Factor and serum matrix metalloproteinase-9 (MMP-9) showed reduction after 2 weeks (not significant), whereas a reduction in serum interleukin-1 receptor antagonist-a (IL-1ra) was statistically significant after 2 weeks (<0.05). Correlation between pain reduction and changes to MMP-9 after 8 weeks was highly significant (<0.01), whereas correlation between pain reduction and changes to IL-1ra reached significance at 2 weeks for the group consuming 3 caps once daily (<0.04). Consuming DSB helped manage pain, increased comfort during daily activities, and improved vascular function. This was associated with selective effects on specific blood biomarkers associated with inflammation and vascular health.