Cholesterol-Lowering Effects of Heat-Killed Bifidobacterium breve IDCC 4401 (BBR 4401): Integrated Preclinical and Clinical Evidence
Introduction
Hypercholesterolemia is a major risk factor for cardiovascular disease caused by abnormal lipid metabolism. This study evaluated the cholesterol-lowering effects and underlying mechanisms of heat-killed Bifidobacterium breve IDCC 4401 (BBR 4401) in animal and human models.
Objective
This study investigated the cholesterol-lowering effects of heat-killed Bifidobacterium breve IDCC 4401 (BBR 4401), focusing on its mechanisms related to lipid metabolism and bile acid regulation in both preclinical and clinical models.
Method
In the animal study, hypercholesterolemia was induced in rats through a high-cholesterol diet, followed by oral administration of low or high doses of BBR 4401 for 8 weeks. Serum lipid profiles, hepatic lipid accumulation, and fecal bile acid levels were measured.
In a 12-week randomized, double-blind, placebo-controlled trial, 60 adults with moderate hypercholesterolemia (LDL-C 100–150 mg/dL) received either low-dose BBR 4401 (1 × 1010 cells/day), high-dose BBR 4401 (5 × 1011 cells/day), or placebo. Changes in serum lipids, apolipoproteins, and gastrointestinal symptoms were assessed at baseline and post-intervention.
Results
In rats, BBR 4401 significantly reduced total cholesterol by 41.4% (p < 0.05) and LDL-C by 48.3% (p < 0.05), and dose-dependently increased fecal bile acid excretion (p < 0.01) compared with the high cholesterol diet group. Hepatic triglyceride and cholesterol levels decreased by 40.7% and 34.7%, respectively (p < 0.01), indicating improved lipid clearance.
In humans, LDL-C levels significantly decreased in the high-dose group compared to placebo (−1.8% vs. +9.0%; p = 0.008), along with a reduction in apolipoprotein B (−1.0% vs. +5.9%; p = 0.018). Triglyceride levels showed a slight increase in the high-dose group but remained within the normal range (<150 mg/dL) and were not statistically significant (p = 0.084).
No serious adverse events were reported. Participants receiving BBR 4401 also showed significant improvements in gastrointestinal symptoms, including reduced defecation strain (p = 0.033) and distension (p = 0.038).
Conclusion
Heat-killed Bifidobacterium breve 4401 demonstrated significant cholesterol-lowering effects in both animal and human studies. It improved lipid profiles by reducing LDL-C and apolipoprotein B levels and promoted bile acid excretion. Its safety profile and additional gastrointestinal benefits support its potential as a functional ingredient for managing moderate hypercholesterolemia and promoting cardiovascular health.
Patent/Patent Application ID - Novel Bifidobacterium breve IDCC 4401 strain having high resistance ability of acid and bile salt and effect of preventing or treating dyslipidemia, and their killed form ID-BBR 4401/ 1022565070000 (KOR)