Probiotics for Vascular Aging

Overseen By Ryan Kacala

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Hypertension, Dyslipidemia, Glucose control

Disqualifiers: Hypertension, Diabetes, High cholesterol, 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 tests whether a probiotic drink can help maintain healthy blood vessels in older adults. Researchers believe that improving gut health might reduce signs of vascular aging, such as stiff blood vessels and poor circulation. Participants will consume either a probiotic oat drink containing Lactobacillus Plantarum 299v or a similar placebo drink without active probiotics for six weeks. The study seeks individuals aged 50-99 who are generally healthy and not receiving treatments for heart-related risks or diabetes. As an unphased trial, it offers a unique opportunity to contribute to the scientific understanding of gut health and vascular aging.

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.

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

Research shows that Lactobacillus Plantarum 299v (Lp299v) is generally safe for people. Earlier studies found that Lp299v helps blood vessels function better and reduces swelling in individuals with heart disease. This suggests it might enhance blood vessel function and lower inflammation. Importantly, the FDA considers Lp299v safe for use in food products, indicating no major safety concerns.

Overall, past studies on humans and its FDA safety recognition suggest that Lp299v is well-tolerated. This makes it a promising choice for those interested in using it as a supplement to support heart and blood vessel health. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for vascular aging, which often focus on medications like statins or lifestyle changes to manage risk factors, the probiotic Lactobacillus Plantarum 299v offers a novel approach. This treatment is delivered in a fermented oat drink, making it a natural and potentially more holistic option. Researchers are excited because Lp299v may improve vascular health by directly influencing gut microbiota, which plays a key role in overall inflammation and cardiovascular health. This mechanism of action is distinct from conventional treatments, offering a fresh perspective on managing vascular aging.

What evidence suggests that Lactobacillus Plantarum 299v might be an effective treatment for vascular aging?

Research has shown that Lactobacillus plantarum 299v (Lp299v), which participants in this trial may receive, can improve blood vessel function and reduce inflammation. Studies involving individuals with coronary artery disease (CAD) found that Lp299v enhanced blood vessel function and decreased inflammation without affecting traditional risk factors or TMAO levels. Although some studies did not observe changes in blood pressure, Lp299v still positively impacted blood vessel health. These findings suggest that Lp299v might slow the aging of blood vessels by improving their function and reducing inflammation, even in healthy older adults without heart disease. ^{1 4 5 6 7}

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 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

I have diabetes or my blood sugar levels are high.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Heat-Killed Placebo control fermented drink
• Lactobacillus Plantarum 299v in fermented oat drink

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

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]

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 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]

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]

Atherosclerosis is a major cause of cardiovascular diseases and global mortality, and current treatments primarily targeting dyslipidemia have significant limitations and side effects.

Recent interest in probiotics as nutraceuticals suggests they may help prevent atherosclerosis and could be used alongside existing medications, with ongoing research into their anti-atherogenic effects and mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis. O'Morain, VL., Ramji, DP.[2021]

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 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]

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]

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 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]

Citations

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Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and TMAO.

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Probiotics for Vascular Aging · Info for Participants

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researchgate.net/publication/11018379_Effect_of_Lactobacillus_plantarum_299v_on_cardiovascular_disease_risk_factor_in_smokers

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The investigators and others have established that an orally ingested probiotic (Lactobacillus plantarum 299v, Lp299v) reduces circulating levels of cell ...

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fda.gov

fda.gov/media/178866/download

GRAS Notice (GRN) 1127, Lactiplantibacillus plantarum ...

The genome of L. plantarum ATCC-202195 was compared with that of L. plantarum Lp-. 115, a generally recognized as safe (GRAS) acknowledged ...

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pubmed.ncbi.nlm.nih.gov/12450890/

Effect of Lactobacillus plantarum 299v on cardiovascular ...

L. plantarum administration leads to a reduction in cardiovascular disease risk factors and could be useful as a protective agent in the primary prevention ...