Pain reduction and improved vascular health associated with daily consumption of an anti-inflammatory dietary supplement blend

Abstract

Purpose: 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. Materials and methods: 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. Results: Highly significant reduction of chronic pain was seen after 8 weeks (p<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 (p<0.1), and improved social functioning (p<0.01), and less need for support from others (p<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 (p<0.05). Correlation between pain reduction and changes to MMP-9 after 8 weeks was highly significant (P<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 (p<0.04). Conclusion: 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.

Keywords: ankle-brachial index; cardiovascular disease; fibrinogen; interleukin-1 receptor antagonist; matrix metalloproteinase-9; von Willebrand factor.

Figure 1

Consort flow chart. The chart shows screening and randomization, as well as the number of people completing the 8-week study.

Figure 2

Changes to primary pain complaint during study. Pain scores at rest (A) and when physically active (B) are shown for the subgroup (N=11) that consumed 3 capsules DSB per day (solid lines; Group A), versus the subgroup (N=9) that consumed 2 capsules DSB twice daily (dashed lines; Group B). The average pain scores for baseline, week 2, and week 8 are shown as the group average±SEM. There were no statistically significant differences between the baseline pain levels for the scores. Despite the higher average pain level at rest in Group A than in Group B, the pain reduction was faster and highly significant already at 2 weeks (**p<0.01), and remained significant after 8 weeks (*p<0.05). The average pain when active was similar between the two groups at baseline, but the reduction was most robust in Group A, reaching a high level of statistical significance already at 2 weeks, and remaining highly significant at 8 weeks (**p<0.01). When comparing the two groups, the reduction in pain at rest and when active were significantly lower after 2 weeks of consuming 3 capsules daily when compared to consuming 2 capsules twice daily (pain at rest: ^##p< 0.01, pain when active ^#p<0.05).

Figure 3

Changes to stiffness during study. Stiffness after first awakening (A) and stiffness after sitting, lying, or resting later in the day (B) are shown for the subgroup (N=11) that consumed 3 capsules DSB per day (solid lines; Group A), versus the subgroup (N=9) that consumed 2 capsules DSB twice daily (dashed lines; Group B). The average scores for baseline, week 2, and week 8 are shown as the group average±SEM. There were no statistically significant differences between the baseline pain levels for the scores. Despite the higher baseline average level of stiffness in Group A than in Group B, the reduction in stiffness after first awakening was faster and significant already at 2 weeks (*p<0.05), and reached a high level of significance after 8 weeks (**p<0.01). The average stiffness after sitting, lying, or resting later in the day showed a significant reduction after 8 weeks in both groups, but was faster and more robust in Group A, reaching a high level of statistical significance already at 2 weeks, and remaining highly significant at 8 weeks (**p<0.01). When comparing the two groups, the reduction in stiffness after first awakening and later in the day was significantly lower after 8 weeks of consuming 3 capsules daily when compared to consuming 2 capsules twice daily (^#p<0.05).

Figure 4

Systolic ankle-brachial blood pressure index. The systolic ankle-brachial index (ABI) for the right and left side of the body is shown as the average±standard error of the mean. Both the right (A) and left systolic (B) ABI were mildly elevated above the ideal ratio of 1.0 at study start. Both the right and left systolic ABI showed a similar reduction after 8 weeks of consumption of the test product. This improvement was seen for both Group A consuming 3 capsules daily and Group B consuming 2 capsules twice daily. The improvement from baseline to the 2-week measurement seen in Group A for right systolic ABI was statistically significant already at 2 weeks (*p<0.05), and reached a high level of statistical significance after 8 weeks (**p<0.01). The change did not reach statistical significance for Group B consuming 2 capsules twice daily. For the left systolic ABI, the difference between the two groups at 2 weeks was statistically significant (^#p<0.05).

Figure 5

Changes in blood biomarkers during study. The levels of plasma fibrinogen (A), von Willebrand Factor (vWF, B), serum matrix metalloproteinase-9 (MMP-9, C), and Interleukin-1 receptor antagonist (IL-1ra, D) are shown as the group averages±standard error of the mean. Consumption of DSB was associated with a mild reduction in fibrinogen and vWF, and a gradual reduction in MMP-9 that reached a statistical trend both a 2 and 8 weeks (^(*)p<0.1). A reduction in IL-1ra reached statistical significance at 2 weeks (*p<0.05). Performing multivariate analysis to examine correlations between pain reduction and blood biomarkers confirmed that there was a significant correlation between pain and IL-1ra levels (p<0.04). The correlation between pain reduction and changes to MMP-9 reached a high level of significance at 8 weeks (p<0.01). For the group consuming 3 caps once daily, there was a highly significant correlation between pain reduction and changes to IL-1ra after 2 weeks (p<0.01).