Three-month biomarker changes after spirulina with or without nursing-led dietary management in older adults with coronary artery disease: a prospective nonrandomized comparative study.

Background: Spirulina has been studied as a low-cost nutritional supplement, but evidence in older adults with coronary artery disease is limited and nonrandomized comparisons are vulnerable to healthy-adherer and treatment-selection bias. Methods: We conducted a single-center, prospective, nonrandomized interventional comparison of conventional nursing care, spirulina plus routine dietary guidance, and structured nursing-led dietary management plus spirulina (88 participants per group). Group assignment was fixed at enrolment. Ten nutritional, lipid, homocysteine and endothelial biomarkers were assessed at baseline and 3 months; first major adverse cardiovascular events (MACE) were followed for 18 months. Because no single biomarker was prospectively designated as primary, all biomarker analyses were treated as exploratory and false-discovery-rate correction was applied. Reviewer-requested reanalysis used baseline-adjusted regression with measured treatment-selection variables, generalized-overlap weighting as a sensitivity analysis, Kaplan-Meier and Aalen-Johansen estimators, and a parsimonious Cox model. Further sensitivity analyses restricted the cohort to the window during which all three groups were recruiting concurrently and to recipients of a single product batch. Results: Paired biomarker data were available for 259 participants. Compared with control, adjusted 3-month differences for spirulina and diet plus spirulina were, respectively, -0.12 mmol/L (95% CI -0.20 to -0.04) and -0.25 mmol/L (-0.33 to -0.17) for LDL cholesterol; -0.52 μmol/L (-0.74 to -0.31) and -1.05 μmol/L (-1.29 to -0.81) for homocysteine; and +0.89 points (+0.59 to +1.19) and +1.60 points (+1.26 to +1.95) for Mini Nutritional Assessment score. All control-group contrasts remained significant after false-discovery-rate correction, and estimates were essentially unchanged when analysis was restricted to the concurrent recruitment window. First MACE occurred in 24, 18 and 16 participants. Adjusted hazard ratios were 0.74 (0.40-1.37) and 0.62 (0.33-1.17); confidence intervals included no difference. Conclusions: Spirulina-containing strategies were associated with modestly more favorable 3-month biomarker profiles, with larger differences for the combined nursing-led dietary programme. The nonrandomized design, incomplete covariate balance and absence of a dietary-management-only arm preclude causal or synergistic interpretation. The 18-month MACE findings are exploratory and inconclusive.