Probiotics for Cardiovascular Disease

Overseen By Michael E Widlansky

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Probiotics, Prebiotics, Antibiotics, Warfarin

Disqualifiers: Unstable angina, LV dysfunction, Hypertension, Renal insufficiency, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how probiotics, such as Goodbelly, might reduce heart attack risk by improving gut bacteria. Researchers are testing whether these probiotics can lower inflammation and enhance blood vessel function in individuals with coronary artery disease (CAD) or Type 2 diabetes without CAD. Participants will take either the probiotic or a placebo to observe any changes in heart health markers. Individuals with a history of CAD or Type 2 diabetes, who haven't recently experienced heart issues or changed specific heart-related medications, might be suitable candidates.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on probiotics and heart health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've had changes in certain heart-related medications in the last 6 weeks or if you're taking specific blood thinners like warfarin.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Lactobacillus plantarum 299v, the probiotic used in the Goodbelly treatment, is generally safe for people. Studies have found that this probiotic can improve blood vessel function and reduce inflammation in individuals with heart disease. Importantly, these benefits occurred without major changes in traditional heart disease risk factors. One study found that this probiotic lowered levels of fibrinogen and LDL cholesterol, both important for heart health. These findings suggest that Lactobacillus plantarum 299v is safe and may benefit those with heart conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the traditional treatments for cardiovascular disease, which often include medications like statins to lower cholesterol or beta-blockers to manage blood pressure, Goodbelly offers a unique approach by using probiotics. This treatment features the active ingredient lactobacillus plantarum 299v, a type of beneficial bacteria that may improve heart health by promoting a balanced gut microbiome. Researchers are excited about this potential because it represents a natural alternative that targets heart health starting from the gut, a mechanism not typically utilized by existing treatments. Additionally, this approach could offer fewer side effects compared to conventional medications, making it an appealing option for patients seeking a more holistic approach.

What evidence suggests that this probiotic might be an effective treatment for cardiovascular disease?

Research shows that Lactobacillus plantarum 299v, a probiotic in Goodbelly, can support heart health by reducing inflammation and improving blood vessel function. In this trial, participants in the "Goodbelly First" arm will consume Lp299v daily. Studies have found that people with coronary artery disease who took Lp299v had lower levels of certain inflammation markers, such as IL-8 and IL-12, which are linked to heart issues. This probiotic also improved the ability of blood vessels to expand and contract, which is crucial for good blood flow. These benefits occurred even without changes in traditional risk factors like cholesterol levels. Overall, Lp299v appears promising for heart health by addressing inflammation and blood vessel function. ^{1 3 6 7 8}

Who Is on the Research Team?

Michael E Widlansky

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for adults aged 40-80 with Type II Diabetes and known coronary artery disease, but not severe heart issues or recent heart attacks. Participants should be able to follow the study plan and not have cognitive impairments, uncontrolled high blood pressure, major organ dysfunction, a history of heavy drinking or drug use, or recent probiotic/antibiotic use.

Inclusion Criteria

I have a history of significant heart artery disease.

I have been diagnosed with Type II Diabetes.

I am between 40 and 80 years old.

Exclusion Criteria

My heart's pumping ability is below normal.

My blood pressure is not higher than 170/100 mmHg.

You use alcohol every day or take illegal drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Lactobacillus plantarum 299v or a placebo daily for 6 weeks

6 weeks

Weekly visits for monitoring and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Goodbelly
• Placebo

Trial Overview The trial tests if a probiotic can reduce inflammation markers in the blood and improve blood vessel function in patients with heart disease. It involves taking either the probiotic Goodbelly or a placebo first, providing stool samples for gut bacteria analysis, and undergoing endothelial function tests.

How Is the Trial Designed?

Group I: Goodbelly First Experimental Treatment 1 Intervention

Subjects in this arm will consume 1 serving of lactobacillus plantarum 299v daily for first 6 weeks.

Group II: Placebo Placebo Group 1 Intervention

Subjects in this arm will consume 1 serving of heat-killed placebo daily for first 6 weeks.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

In a study involving SPF Wistar rats with antibiotic-induced dysbiosis, treatment with the probiotic Lactobacillus reuteri KR2017 significantly reduced myocardial infarct size after ischemia-reperfusion injury, indicating its potential protective effects on heart tissue.

In contrast, treatment with the yeast Saccharomyces boulardii did not show the same beneficial effects, highlighting the importance of specific probiotic strains in managing heart health during ischemic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Antiobiotic-Induced Disbiosis and Its Correction with Probiotics on Myocardial Tolerance to Ischemia-Reperfusion Injury in SPF Rats. Borshchev, YY., Sinitsa, AV., Zakharchenko, MM., et al.[2022]

In a 4-week study involving healthy adults aged 18 to 65, supplementation with Bacillus subtilis strain DE111 significantly reduced total cholesterol levels by 8 mg/dl and non-high-density lipoprotein cholesterol by 11 mg/dl, indicating potential cardiovascular benefits.

While Bifidobacterium animalis subsp. lactis did not show significant changes in cardiovascular health measures, the results suggest that B. subtilis may improve cholesterol levels and endothelial function, warranting further research in older adults or those with existing cardiovascular risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults. Trotter, RE., Vazquez, AR., Grubb, DS., et al.[2022]

Lactiplantibacillus plantarum (Lb. plantarum) has shown potential in reducing the risk of cardiovascular disease (CVD) by regulating metabolism, lowering blood glucose and lipids, and managing blood pressure.

The review emphasizes the importance of incorporating Lb. plantarum through fermented foods into daily diets, which could help alleviate CVD symptoms and improve overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Mechanisms of the Potential Probiotic Lactiplantibacillus plantarum against Cardiovascular Disease and the Recent Developments in its Fermented Foods. Wang, Z., Wu, J., Tian, Z., et al.[2022]

Daily consumption of Lactobacillus plantarum ATCC 14917 significantly inhibited the formation of atherosclerotic lesions in atherosclerosis-prone mice, indicating its potential as a therapeutic intervention.

The probiotic treatment reduced levels of pro-inflammatory cytokines and oxidative stress markers while modulating gut microbiota composition, suggesting a mechanism of action that involves alleviating inflammation and oxidative damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE-/- mice through modulation of proinflammatory cytokines and oxidative stress. Hassan, A., Din, AU., Zhu, Y., et al.[2021]

In a study involving 49 adults with normal to mildly high cholesterol, the probiotic Lactobacillus plantarum ECGC 13110402 significantly reduced LDL cholesterol by 13.9% in those with baseline total cholesterol under 5mM and by 37.6% in those with baseline cholesterol over 6mM, indicating its potential efficacy in lowering cardiovascular risk.

The probiotic also led to a 6.6% reduction in systolic blood pressure and was well-tolerated with no gastrointestinal side effects reported, suggesting it could be a safe alternative or supplement to traditional cholesterol-lowering treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vivo assessment of the cholesterol-lowering efficacy of Lactobacillus plantarum ECGC 13110402 in normal to mildly hypercholesterolaemic adults. Costabile, A., Buttarazzi, I., Kolida, S., et al.[2020]

In a study of 100 overweight volunteers, daily intake of heat-killed Lactobacillus plantarum L-137 (HK L-137) for 12 weeks significantly improved inflammation and lipid metabolism, as indicated by better immune cell proliferation and lower liver enzyme levels.

Participants taking HK L-137 showed greater reductions in total cholesterol and low-density lipoprotein cholesterol, especially those with higher initial inflammation levels, suggesting it may be particularly beneficial for individuals at risk of inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial. Tanaka, Y., Hirose, Y., Yamamoto, Y., et al.[2021]

Lab4 probiotic consortium plus Lactobacillus plantarum CUL66 (Lab4P) significantly reduces atherosclerosis-related parameters in LDL receptor deficient mice fed a high-fat diet for 12 weeks, including lowering LDL/VLDL levels and plaque burden.

Lab4P enhances beneficial HDL levels and alters liver gene expression related to atherosclerosis, suggesting it may stabilize plaques and reduce inflammation, warranting further investigation in human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Lab4P Consortium of Probiotics Attenuates Atherosclerosis in LDL Receptor Deficient Mice Fed a High Fat Diet and Causes Plaque Stabilization by Inhibiting Inflammation and Several Pro-Atherogenic Processes. O'Morain, VL., Chan, YH., Williams, JO., et al.[2022]

In a study involving 16 males with cardiovascular disease, consuming the probiotic Lactobacillus plantarum DSM 9843 for four weeks significantly increased intestinal microbial diversity compared to a placebo group.

While the probiotic did not significantly alter most short-chain fatty acids in feces, it did lead to a decrease in isovaleric and valeric acid concentrations, suggesting specific metabolic changes in the gut.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: a randomized controlled trial. Karlsson, C., Ahrné, S., Molin, G., et al.[2010]

In a 6-month clinical trial with 60 patients, the probiotic Bifidobacterium lactis Probio-M8, when combined with standard treatments, significantly improved symptoms of coronary artery disease (CAD) compared to placebo, as measured by the Seattle Angina Questionnaire.

The probiotic group also showed reductions in depression and anxiety, along with lower levels of inflammatory markers and harmful cholesterol, suggesting that probiotics may enhance both cardiovascular and mental health through gut microbiota modulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bifidobacterium lactis Probio-M8 Adjuvant Treatment Confers Added Benefits to Patients with Coronary Artery Disease via Target Modulation of the Gut-Heart/-Brain Axes. Sun, B., Ma, T., Li, Y., et al.[2022]

Treatment with Lactobacillus reuteri CCFM8631 significantly reduced plasma cholesterol levels and liver damage markers in mice on a high-fat diet, suggesting its potential as a preventive measure against atherosclerosis-related cardiovascular disease.

The probiotic also improved gut health by increasing beneficial short-chain fatty acids and altering gut microbiota composition, which may contribute to its cholesterol-lowering effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus reuteri CCFM8631 Alleviates Hypercholesterolaemia Caused by the Paigen Atherogenic Diet by Regulating the Gut Microbiota. Wang, Q., He, Y., Li, X., et al.[2022]

Two Lactobacillus plantarum strains, S2-5 and S4-1, showed strong probiotic properties, including survival in acidic conditions, tolerance to digestive enzymes, and antimicrobial activity against harmful bacteria.

In an in vivo study, the strain S4-1 significantly reduced serum cholesterol levels in mice when fed fermented milk, highlighting its potential as a beneficial probiotic for cholesterol management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of probiotic properties of Lactobacillus plantarum strains isolated from Chinese sauerkraut. Yu, Z., Zhang, X., Li, S., et al.[2021]

In a rat model of systemic inflammatory response syndrome (SIRS), probiotics Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) significantly reduced myocardial infarction size, suggesting a protective effect against ischemic-reperfusion injury.

The treatment with these probiotics also normalized various inflammatory and immune parameters, indicating their potential to improve cardiovascular health in the context of metabolic and inflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Probiotic Strains on Myocardial Infarction Size, Biochemical and Immunological Parameters in Rats with Systemic Inflammatory Response Syndrome and Polymorbidity. Borshchev, YY., Sonin, DL., Burovenko, IY., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6205737/

Lactobacillus Plantarum 299v Supplementation Improves ... Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and TMAO.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04364074

Acute Probiotic Supplementation and Endothelial Function Our pilot study has demonstrated that supplementation of Lactobacillus plantarum 299v (Lp299v) for 6 weeks to adults with a history of coronary artery disease ...

3. clinicaltrial.be clinicaltrial.be/en/details/260358?per_page=100&only_recruiting=0&only_eligible=0

Pilot Study Lp299v Supplementation in Chronic Heart Failu... The investigators have shown that there are significantly decreased levels of IL-8, IL-12 and Leptin in Lp299v-supplemented patients with CAD.

4. withpower.com withpower.com/trial/phase-cardiovascular-diseases-4-2018-14ef9

Probiotics for Cardiovascular Disease Research shows that Lactobacillus plantarum, a component of Goodbelly, can reduce inflammation and oxidative stress, which are linked to heart disease. In ...

5. ahajournals.org ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.118.313565

Lactobacillus plantarum 299v Supplementation Improves ... The favorable effects of Lp299v occur without favorable changes in traditional cardiovascular risk factors or trimethylamine oxide levels.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0002916523060550

Effect of Lactobacillus plantarum 299v on cardiovascular ... Our results indicate that supplementation of the diet with active cultures of L. plantarum 299v leads to significant reductions in fibrinogen and LDL- ...

7. nature.com nature.com/articles/s41598-021-83252-7

Lactobacillus plantarum 299v probiotic supplementation in ... We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD.

8. ahajournals.org ahajournals.org/doi/abs/10.1161/CIRCRESAHA.118.313565?doi=10.1161/CIRCRESAHA.118.313565

Lactobacillus plantarum 299v Supplementation Improves ... Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and ...