Evaluation of the Effect of Fish Oil Alone and in Combination with a Proprietary Chromium Complex on Endothelial Dysfunction, Systemic Inflammation and Lipid Profile in Type 2 Diabetes Mellitus-A Randomized, Double-Blind, Placebo-Controlled Clinical Study

Purpose: This study was conducted to evaluate the effectiveness of fish oil alone and with an adjunct, a proprietary chromium complex (PCC), on cardiovascular parameters - endothelial dysfunction, lipid profile, systemic inflammation and glycosylated hemoglobin - in a 12-week randomized, double-blind, placebo-controlled clinical study in type 2 diabetes mellitus subjects. Patients and Methods: In this randomized, double-blind, parallel group study, 59 subjects in three groups completed the study: Group A, fish oil 2000 mg; Group B, fish oil 2000 mg + PCC 10 mg (200 mu g of Cr3+); and Group C, fish oil 2000 mg + PCC 20 mg (400 mu g of Cr3+) daily for 12 weeks (2000 mg of fish oil contained 600 mg of eicosapentaenoic acid [EPA] and 400 mg of docosahexaenoic acid [DHA], the omega-3 fatty acids). Endothelial function, by estimating reflection index (RI), biomarkers of oxidative stress (nitric oxide [NO], malondialdehyde [MDA], glutathione [GSH]) and inflammatory biomarkers (highsensitivity C-reactive protein [hsCRP], intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], endothelin-1) were evaluated at baseline, and 4 and 12 weeks. Lipid profile, platelet aggregation and glycosylated hemoglobin [HbA1c) were tested at baseline and 12 weeks. Any reported adverse drug reactions were recorded. Statistical analysis was performed using GraphPad Prism 8. Results: The present study shows that fish oil by itself, at a dose of 2000 mg (600 mg of EPA + 400 mg of DHA) per day, led to significant, but only modest, improvement in cardiovascular parameters (RI from -2.38 +/- 0.75 to -3.92 +/- 0.60, MDA from 3.77 +/- 0.16 to 3.74 +/- 0.16 nM/mL, NO from 30.60 +/- 3.18 to 32.12 +/- 3.40 mu M/L, GSH from 568.93 +/- 5.91 to 583.95 +/- 6.53 mu M/L; p=0.0001), including triglyceride levels. However, when PCC was added to fish oil, especially at the 20 mg dose, there were highly significant improvements in all the parameters tested (RI from -2.04 +/- 0.79 to -8.73 +/- 1.36, MDA from 3.67 +/- 0.39 to 2.89 +/- 0.34 nM/mL, NO from 28.98 +/- 2.93 to 40.01 +/- 2.53 mu M/L, GSH from 553.82 +/- 8.18 to 677.99 +/- 10.19 mu M/L; p=0.0001), including the lipid profile. It is noteworthy that the triglycerides were decreased significantly by addition of 20 mg of PCC although the dose of fish oil was only 2 g/day and the baseline triglyceride levels were only about 200 mg/dL. Fish oil alone did not significantly decrease the HbA1c, whereas the addition of 20 mg of PCC did. Conclusion: Addition of PCC, especially at 20 mg dose, significantly improves the efficacy of fish oil in addressing cardiovascular risk factors compared to fish oil given alone.