Dose-dependent effects of squalene on blood pressure and cellular energy biomarkers in patients with stable ischemic heart disease

Περίληψη

Background: Ischemic heart disease (IHD) is associated with mitochondrial dysfunction, oxidative stress, impaired cellular bioenergetics, and persistent vascular injury. These disturbances are reflected by reduced ATP production, altered NAD/NADH redox balance, and lower coenzyme Q10 (CoQ10) levels, together with adverse anthropometric and hemodynamic indicators such as elevated body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Squalene, a natural triterpene with antioxidant properties and relevance to sterol and ubiquinone biosynthesis, may support mitochondrial function and cellular energy metabolism.

Objective: This study evaluated the effects of oral squalene supplementation (300, 600, or 900 mg/day) on BMI, SBP, DBP, and cellular energy biomarkers (ATP, NAD/NADH, and CoQ10) in patients with stable IHD over 84 days.

Methods: A total of 180 participants were allocated into six groups (n = 30 each): healthy controls, healthy volunteers receiving 600 mg/day squalene, cardiac patients without squalene, and cardiac patients receiving 300, 600, or 900 mg/day squalene. Blood samples were collected after overnight fasting on days 1, 14, 28, 56, and 84. ATP and NAD/NADH were measured using colorimetric assays, and CoQ10 was assessed by ELISA. Data was analyzed using repeated-measures ANOVA, one-way ANOVA with Tukey post hoc testing, and independent t-tests, with p < 0.05 considered significant.

Results: At baseline, patients with stable IHD showed significantly elevated BMI, SBP, and DBP compared with healthy controls, together with reduced ATP, NAD/NADH ratio, and CoQ10 levels (p < 0.05). Oral squalene supplementation produced dose-dependent improvements in blood pressure and cellular energy biomarkers over 84 days. ATP increased from baseline values of 3.89–4.54 to 4.62, 5.40, and 6.14 in the 300, 600, and 900 mg/day groups, respectively, by day 84, corresponding to an approximate 19–35% increase across treated groups, while untreated cardiac controls declined from 3.67 to 2.73, corresponding to an approximate 25% decrease. NAD/NADH ratio and CoQ10 also increased progressively across treated groups, with the strongest responses observed at 600 and 900 mg/day, while untreated cardiac controls showed continued declines in these biomarkers. BMI declined modestly in treated groups, while untreated controls remained largely unchanged.

Conclusion: Oral squalene supplementation for 84 days improved blood pressure and enhanced cellular energy biomarkers in patients with stable IHD. The 300 mg/day dose showed beneficial effects on blood pressure, while the 600–900 mg/day doses produced stronger improvements in cellular energy biomarkers, including ATP, NAD/NADH ratio, and CoQ10. These findings suggest that squalene may serve as a promising adjunctive nutritional strategy to support hemodynamic regulation, mitochondrial bioenergetics, and cardiovascular health.

Novelty of Study: This study investigated the dose-dependent effects of oral squalene supplementation on blood pressure, BMI, and key cellular energy biomarkers, including ATP, NAD/NADH ratio, and CoQ10, in patients with stable ischemic heart disease. The findings suggest a dose-related response, with blood pressure improvements observed even at 300 mg/day and stronger cellular energy biomarker responses observed at 600–900 mg/day. This highlights the potential of squalene as an adjunctive nutritional strategy for supporting hemodynamic status and mitochondrial bioenergetics in IHD.

Keywords: Squalene, ischemic heart disease, ATP, NAD/NADH, CoQ10, mitochondrial function, body mass index, systolic blood pressure, diastolic blood pressure, oxidative stress