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CardiovascularMetabolicProbioticsRCT

L. reuteri NCIMB 30242 Lowered LDL by 11.6%: A Bile Salt Hydrolase RCT

European Journal of Clinical Nutrition, 2012

DOI: 10.1038/ejcn.2012.126

Study Type

Randomized Controlled Trial

Participants

127

Duration

9 weeks

Dosage

2 capsules/day L. reuteri NCIMB 30242 (BSH-active)

Institution

McGill University, Montreal (multicenter)

This 9-week randomized controlled trial tested whether a specific strain of gut bacteria -- Lactobacillus reuteri NCIMB 30242, selected for its bile salt hydrolase activity -- could lower LDL cholesterol in adults with hypercholesterolemia. Published in the European Journal of Clinical Nutrition, the multicenter trial enrolled 127 participants and reported an 11.6% reduction in LDL-C versus placebo, alongside reductions in inflammatory markers and plasma phytosterols. The findings are part of the growing literature on the gut microbiome -- cardiovascular axis, a research area Olivea tracks closely because it underpins the science of olive polyphenols and the broader food-as-medicine hypothesis.

Why This Study Matters

Statins remain the standard pharmacological tool for lowering LDL cholesterol. But a meaningful fraction of patients don't reach their LDL goal on statins alone, and many tolerate them poorly. The search for adjunct therapies -- compounds that work through complementary mechanisms -- has been an active area of cardiovascular research for two decades.

Most prior probiotic studies on cholesterol used mixed strains or strains not selected for any specific mechanism. The results were inconsistent. This trial took a different approach: the researchers pre-selected a single L. reuteri strain (NCIMB 30242) specifically because it expressed high bile salt hydrolase (BSH) activity -- the enzyme that deconjugates bile acids in the gut and forces the liver to synthesize new bile acids from circulating cholesterol. The hypothesis was that a mechanism-targeted strain would produce a measurable LDL reduction where mixed-strain probiotics had not.

The trial is also notable for being conducted in the population that matters most clinically: adults with already-elevated LDL who were not on lipid-lowering medication. That's the group where any incremental tool has the highest potential value.

How It Was Designed

The basics are in the study design bar above: 127 hypercholesterolemic adults, 9 weeks, two capsules per day of L. reuteri NCIMB 30242, randomized double-blind placebo-controlled, multicenter design coordinated through McGill University in Montreal. A few details deserve attention.

The strain itself was characterized in advance. L. reuteri NCIMB 30242 was screened from a panel of candidate strains for high BSH activity, acid tolerance, and bile tolerance -- the three properties required for a probiotic to survive gastric transit and act in the small intestine. This pre-selection step is what separates this trial from earlier probiotic-cholesterol studies that used off-the-shelf strains with unknown mechanism profiles.

The mechanism was also tested directly. The researchers measured plasma deconjugated bile acids and plasma phytosterols (campesterol, sitosterol, stigmasterol) at baseline and study end. If the BSH hypothesis was correct, deconjugated bile acids should rise (because BSH activity strips the glycine or taurine off conjugated bile acids), and absorption of non-cholesterol sterols should fall (because deconjugated bile acids are less efficient at solubilizing dietary sterols in mixed micelles). Measuring these biomarkers turned the trial into a mechanism test, not just an outcome test.

The study was multicenter, which reduces the risk that a single-site result reflects local population or operator effects.

What They Found

Compared to placebo, the L. reuteri NCIMB 30242 group showed statistically significant improvements across cholesterol fractions, inflammatory markers, and bile acid metabolism:

Biomarker Change vs. Placebo p-value What It Measures
LDL cholesterol -11.64% < 0.001 Primary atherogenic lipoprotein
Total cholesterol -9.14% < 0.001 All circulating cholesterol
Non-HDL cholesterol -11.30% < 0.001 All atherogenic particles combined
ApoB-100 -8.41% 0.002 Number of atherogenic particles
LDL-C / HDL-C ratio -13.39% 0.006 Atherogenic vs. protective balance
hs-CRP -1.05 mg/L 0.005 Systemic inflammation
Fibrinogen -14.25% 0.004 Coagulation and inflammation
Deconjugated bile acids +1.00 nmol/L 0.025 Direct BSH mechanism marker
Plasma campesterol -41.5% < 0.05 Phytosterol absorption marker
Plasma sitosterol -34.2% < 0.05 Phytosterol absorption marker

Green indicates a favorable direction vs. placebo. All differences are statistically significant.

Reading the Results

The biomarkers group into four mechanistically linked categories worth unpacking.

Atherogenic lipoproteins (LDL-C, total cholesterol, non-HDL-C, apoB-100). LDL is the standard cardiovascular risk marker, but apoB-100 is arguably the more biologically meaningful number -- it counts the actual number of atherogenic particles in circulation, not just the cholesterol they carry. The trial moved both, and it moved them in tandem. An 11.6% LDL reduction over 9 weeks from a single oral probiotic, with no diet change and no exercise prescription, is in the same range as low-dose statins. The apoB-100 reduction of 8.4% suggests the mechanism is reducing particle number, not just particle size.

Inflammation and coagulation (hs-CRP, fibrinogen). High-sensitivity CRP is the most validated inflammation marker for cardiovascular risk stratification. Fibrinogen is both an inflammatory marker and a direct driver of clot formation. Both fell significantly in the L. reuteri group. This is one of the more interesting signals in the trial because it points to a non-lipid pathway: the gut microbiome may be modulating systemic inflammation independently of the cholesterol effect.

Bile acid metabolism (deconjugated bile acids). The 1.00 nmol/L increase in plasma deconjugated bile acids is the mechanistic smoking gun. It confirms that the BSH enzyme was actually doing what the researchers selected the strain to do. This is the difference between an outcome trial and a mechanism trial -- the data don't just show that cholesterol fell, they show why.

Sterol absorption (campesterol, sitosterol, stigmasterol). These three plant sterols are dietary -- they come from vegetable oils, nuts, and seeds -- and their plasma levels are a clean readout of how efficiently the intestine is absorbing sterols in general. All three dropped by 34 to 41%. The interpretation: BSH-deconjugated bile acids form less effective micelles, so all sterols (cholesterol included) are absorbed less efficiently from the gut. This is the same mechanism that ezetimibe (Zetia) targets pharmacologically, just reached by a different route.

What Didn't Change

Triglycerides and HDL cholesterol were unchanged. This is consistent with the BSH mechanism, which specifically targets cholesterol absorption and bile acid recycling rather than triglyceride metabolism or HDL biology. No serious adverse events were reported, and the strain was well tolerated. The trial was 9 weeks; longer-term durability of the LDL reduction was not assessed in this report.

Broader Context

This trial sits inside a broader research program on the gut microbiome -- cardiovascular axis: the growing understanding that gut bacteria directly influence circulating lipid profiles, blood pressure, inflammation, and atherosclerosis risk through bile acid metabolism, short-chain fatty acid production, and modulation of intestinal permeability. The L. reuteri NCIMB 30242 trial is one of the cleaner mechanistic demonstrations in that literature -- a pre-selected strain, a pre-specified mechanism, and direct measurement of both the mechanism marker (deconjugated bile acids) and the downstream outcome (LDL).

The gut-cardiovascular axis is also where olive-derived compounds become interesting in a new way. Hydroxytyrosol and oleuropein are well-characterized antioxidants and anti-inflammatory polyphenols, with an authorized EFSA health claim for protection of blood lipids from oxidative damage at 5 mg/day of hydroxytyrosol and derivatives. But polyphenols also reach the colon largely intact and are metabolized by gut bacteria into bioactive secondary metabolites. The intersection of olive polyphenols and probiotics is an active frontier in gut-cardiovascular research.

Related Research

Continue exploring the gut-cardiovascular axis and probiotic evidence:

Source: View the original study on PubMed

Olivea's Dosage

This trial tested a specific probiotic strain -- L. reuteri NCIMB 30242 -- not an Olivea product. Olivea's current portfolio focuses on the polyphenol side of the gut-cardiovascular axis: a single tablespoon of Olivea extra virgin olive oil delivers the EFSA-recognized polyphenol dose, and each Olivea capsule delivers over 20 mg of hydroxytyrosol per serving (third-party certificate of analysis confirmed 23.5 mg per capsule).

We share this research for transparency. This is an independent study -- we did not fund it, design it, or conduct it.

Editorial Information

Research note. This article summarizes third-party research published in a peer-reviewed journal. Olivea did not conduct or fund the study. Findings reflect the cited paper only and do not establish efficacy of Olivea products.

Full Citation

Jones ML, Martoni CJ, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial. Eur J Clin Nutr. 2012;66(11):1234-1241. doi:10.1038/ejcn.2012.126

This page summarizes findings from independent, peer-reviewed research. Olivea did not fund, design, or conduct this study. The information presented here is for educational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. These statements have not been evaluated by the Food and Drug Administration. Consult your healthcare provider before starting any supplement.

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