Probiotics for Vascular Aging

Recruiting in Palo Alto (17 mi)

Overseen by Michael E Widlansky

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Medical College of Wisconsin

Must not be taking: Hypertension, Dyslipidemia, Glucose control

Disqualifiers: Hypertension, Diabetes, High cholesterol, others

Trial Summary

What is the purpose of this trial?

Emerging data suggest the gut microbiota regulates multiple mechanisms related to vascular aging, but no intervention targeting the gut microbiota has been tested in older adults without cardiovascular risk factors or cardiovascular disease. Early human data suggest an increase in potentially pathological gut metabolites such as trimethylamine-N-oxide (TMAO) are associated with older age, increased vascular stiffness, increased oxidative stress, and reduced nitric oxide (NO) bioavailability as evidenced by impaired endothelium-dependent vasodilation. Based on this data, the investigators hypothesize that supplementation with Lp299v will reverse human vascular aging in healthy older adults free of known traditional cardiovascular risk factors.

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 are currently taking medications for high blood pressure, cholesterol, or blood sugar control.

What data supports the effectiveness of the treatment Lactobacillus plantarum 299v in fermented oat drink for vascular aging?

Research shows that Lactobacillus plantarum 299v can improve vascular function and reduce inflammation in people with coronary artery disease, which suggests it might help with vascular aging too. ^{1 2 3 4 5}

Is Lactobacillus plantarum 299v safe for human use?

Lactobacillus plantarum 299v has been studied in humans and is generally considered safe, with research showing it can improve vascular function and reduce inflammation without significant adverse effects. ^{6 7 8 9 10}

How does the treatment Lactobacillus Plantarum 299v in fermented oat drink differ from other treatments for vascular aging?

Lactobacillus Plantarum 299v in a fermented oat drink is unique because it uses probiotics to potentially slow down vascular aging by modulating AMPK activity and preventing telomere shortening, which are mechanisms not typically targeted by standard treatments. This approach is novel as it combines the benefits of probiotics with a dietary component, offering a natural alternative to traditional pharmaceutical interventions. ^{1 4 11 12 13}

Research Team

Michael E Widlansky

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for healthy older adults aged 50-99 who have not had a menstrual period in at least 12 months (if female), do not smoke, and are free from diabetes, high cholesterol, cognitive impairments, hypertension treatments, excessive alcohol use, and certain chronic diseases. They should also be inactive (averaging less than 7500 steps per day).

Inclusion Criteria

I have not had a period in the last 12 months or more.

I am between 50 and 99 years old.

Exclusion Criteria

I average more than 7500 steps a day.

Systolic Blood Pressure ≥ 130 mmHg or Diastolic BP ≥ 80mmHg

LDL Cholesterol > 160 mg/dL or Total Cholesterol > 200 mg/dL

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Lp299v supplementation or placebo for 6 weeks

6 weeks

Weekly visits (in-person or virtual) for monitoring and data collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Heat-Killed Placebo control fermented drink (Behavioural Intervention)
• Lactobacillus Plantarum 299v in fermented oat drink (Probiotic)

Trial Overview The study tests if Lactobacillus Plantarum 299v in a fermented oat drink can reverse signs of vascular aging compared to a placebo control drink. It's aimed at older adults without cardiovascular disease or risk factors.

Participant Groups

Group I: Lp299v Experimental Treatment 1 Intervention

Subjects will consume 20 billion colony forming units of Lp299v (1 serving of GoodBelly fermented oat drink) once daily for 6 weeks

Group II: Heat-killed placebo control Placebo Group 1 Intervention

Subjects will consume 1 serving of GoodBelly fermented oat drink that has been treated to heat kill all Lp299v once daily for 6 weeks

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Medical College of Wisconsin Milwaukee, WI

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Dr. Joseph E. Kerschner

Medical College of Wisconsin

Chief Medical Officer since 2011

MD, specific institution not identified

Dr. John R. Raymond, Sr.

Medical College of Wisconsin

Chief Executive Officer since 2010

MD from the Medical University of South Carolina

Findings from Research

In a study involving male Sprague-Dawley rats over 12 weeks, certain strains of lactobacilli probiotics (LP-DR7, LF-DR9, LR-8513d) were found to significantly reduce telomere shortening and enhance AMPK expression, suggesting potential anti-aging effects.

The probiotic LF-DR9 and statin treatment also resulted in lower plasma lipid peroxidation, indicating improved cellular health, while the effects varied depending on the specific strain of lactobacilli used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats. Lew, LC., Hor, YY., Jaafar, MH., et al.[2020]

Lactobacillus plantarum 299v (Lp299v) supplementation in non-daily alcohol users with stable coronary artery disease (CAD) led to improved vascular function, as indicated by enhanced brachial flow-mediated dilation (FMD) and reduced levels of inflammatory markers like IL-8 and IL-12.

The study found significant anti-inflammatory effects from Lp299v, with 997 genes showing changes in expression, including downregulation of pro-inflammatory pathways and an increase in regulatory T-cell activity, suggesting that Lp299v may help reduce cardiovascular risks in CAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation. Hofeld, BC., Puppala, VK., Tyagi, S., et al.[2023]

A genetically modified probiotic (GMP) expressing angiotensin (1-7) combined with exercise training improved gut microbial diversity and altered gene expression related to neuroremodeling and inflammation in aging male rats over a 12-week period.

The study utilized a multi-omics approach, revealing significant changes in microbial composition and gene expression across various tissues, suggesting that this combined intervention may help counteract declines in physical and cognitive function associated with aging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiomics profiling of the impact of an angiotensin (1-7)-expressing probiotic combined with exercise training in aged male rats. Baptista, LC., Zumbro, EL., Graham, ZA., et al.[2023]

In a study involving young and old mice, suppressing gut microbiota with antibiotics for 3-4 weeks reversed age-related arterial dysfunction, improving endothelial function and reducing arterial stiffness in older mice.

The research suggests that age-related changes in the gut microbiome contribute to arterial dysfunction, indicating that targeting gut health could be a promising strategy to preserve arterial function and lower cardiovascular disease risk as we age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice. Brunt, VE., Gioscia-Ryan, RA., Richey, JJ., et al.[2020]

In a study involving 40 spontaneously hypertensive rats, long-term administration of probiotics (Lactobacillus fermentum and a mixture of L. coryniformis and L. gasseri) significantly reduced systolic blood pressure and improved heart and kidney health.

Probiotic treatment improved vascular function by reversing impaired aortic relaxation and reducing oxidative stress markers, indicating their potential as a cardiovascular protective strategy in genetic hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Gómez-Guzmán, M., Toral, M., Romero, M., et al.[2017]

Limosilactobacillus reuteri (L. reuteri) consumption significantly reduced total cholesterol levels by -0.26 mmol/L in a meta-analysis of 6 randomized controlled trials involving 512 participants, indicating its potential to lower cardiovascular disease risk associated with high cholesterol.

However, L. reuteri did not show any significant effects on blood pressure, blood glucose, or other lipid profiles, suggesting that its benefits may be limited to cholesterol management rather than broader metabolic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limosilactobacillus reuteri consumption significantly reduces the total cholesterol concentration without affecting other cardiovascular disease risk factors in adults: A systematic review and meta-analysis. Liu, J., Zhu, R., Song, J., et al.[2023]

In a study involving 20 men with stable coronary artery disease, daily supplementation with Lactobacillus plantarum 299v (Lp299v) for 6 weeks significantly improved vascular endothelial function, as measured by brachial flow-mediated dilation.

Lp299v supplementation also reduced systemic inflammation by decreasing levels of interleukins and leptin, suggesting that gut-derived metabolites may play a role in these cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease. Malik, M., Suboc, TM., Tyagi, S., et al.[2019]

In a 12-week clinical trial with 86 participants, the probiotic Lactobacillus plantarum significantly reduced LDL cholesterol levels by an average of 6.6 mg/dl compared to a placebo group.

The effectiveness of Lactobacillus plantarum in lowering LDL cholesterol may vary based on individual gut microbiota composition, as responders showed specific differences in gut bacteria and body mass index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinct Microbial Taxa Are Associated with LDL-Cholesterol Reduction after 12 Weeks of Lactobacillus plantarum Intake in Mild Hypercholesterolemia: Results of a Randomized Controlled Study. Kerlikowsky, F., Müller, M., Greupner, T., et al.[2023]

The lactic acid bacterial strain Lactobacillus plantarum KSFY02 (LP-KSFY02) effectively prevents oxidative aging in mice, as shown by its ability to improve various organ indices and enhance antioxidant enzyme activity compared to controls.

LP-KSFY02 outperformed traditional antioxidants like Lactobacillus delbrueckii ssp. bulgaricus and vitamin C, indicating its potential as a high-quality probiotic with significant health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive effect of Lactobacillus plantarum KSFY02 isolated from naturally fermented yogurt from Xinjiang, China, on d-galactose-induced oxidative aging in mice. Zhao, X., Yi, R., Zhou, X., et al.[2019]

In a study involving 20 healthy young volunteers, the probiotic Lactobacillus casei LTL1879 significantly improved antioxidant levels and reduced oxidative stress markers after three weeks, indicating potential health benefits.

The probiotic also positively influenced gut microbiota by increasing beneficial bacteria like Bifidobacterium and Lactobacillus while decreasing harmful bacteria, suggesting it may enhance overall gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of the Effect of Lactobacillus casei Obtained from Long-Lived Elderly on Blood Biochemical, Oxidative, and Inflammatory Markers, and on Gut Microbiota in Young Volunteers. Mei, LH., Zheng, WX., Zhao, ZT., et al.[2022]

Probiotics like Lactobacillus and Bifidobacterium, along with their metabolites, have shown significant antioxidative effects that can help reduce oxidative stress in aging mice, particularly when administered in high doses.

The treatment not only improved antioxidative levels in various organs but also positively altered gut microbiota composition, suggesting that a specific combination of probiotics and postbiotics could enhance health in older individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics and their Metabolites Reduce Oxidative Stress in Middle-Aged Mice. Lin, WY., Lin, JH., Kuo, YW., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Multiomics profiling of the impact of an angiotensin (1-7)-expressing probiotic combined with exercise training in aged male rats. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. [2017]

7. Germany pubmed.ncbi.nlm.nih.gov

Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE-/- mice through modulation of proinflammatory cytokines and oxidative stress. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Limosilactobacillus reuteri consumption significantly reduces the total cholesterol concentration without affecting other cardiovascular disease risk factors in adults: A systematic review and meta-analysis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum 299v Supplementation Improves Vascular Endothelial Function and Reduces Inflammatory Biomarkers in Men With Stable Coronary Artery Disease. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Distinct Microbial Taxa Are Associated with LDL-Cholesterol Reduction after 12 Weeks of Lactobacillus plantarum Intake in Mild Hypercholesterolemia: Results of a Randomized Controlled Study. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Preventive effect of Lactobacillus plantarum KSFY02 isolated from naturally fermented yogurt from Xinjiang, China, on d-galactose-induced oxidative aging in mice. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Study of the Effect of Lactobacillus casei Obtained from Long-Lived Elderly on Blood Biochemical, Oxidative, and Inflammatory Markers, and on Gut Microbiota in Young Volunteers. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Probiotics and their Metabolites Reduce Oxidative Stress in Middle-Aged Mice. [2022]