Reference

VS-01™ Vaginal Synbiotic

DS-01® Daily Synbiotic
Overview
Formulation
Directions for Use
Clinical Trials
Strain Selection Process
Testing
Interactions
Reference Library - VS01™
Overview
Formulation
Directions for Use
Clinical Trials
Strain Selection Process
Testing
Interactions

Overview

The vaginal microbiome is the foundation of gynecological, urogenital, and reproductive health. However, day-to-day life including menstruation, sexual activity, exercise, stress, certain prescriptions and cleaners, can easily disrupt the vaginal microbiome, leaving it susceptible to imbalances and unwanted issues. Core discoveries over the past two decades have demonstrated that optimal vaginal health is primarily maintained by the dominance of a single bacterial species: L. crispatus.

Born from 15+ years of leading vaginal microbiome research, VS-01™ is the first vaginal suppository with three proprietary Lactobacillus crispatus strains, clinically validated to restore a healthy vaginal microbiome, sustain optimal vaginal pH, and is demonstrated to be well-tolerated in a clinical setting.

VS-01™ is formulated with three live strains of L. crispatus (LUCA103™, LUCA011™, LUCA009™) selected from a proprietary bank of over 600 microbial strains, based on their strong association with vaginal microbiome stability and resilience.

An innovative nutrient complex was included to create the ideal environment and energy source for the probiotic strains in VS-01™. By providing L. crispatus a growth advantage over other less beneficial species in the vagina, VS-01™’s ingredient complex ensures that these protective bacteria not only survive, but thrive.

Formulation

L. crispatus LUCA103™, L. crispatus LUCA011™, L. crispatus LUCA009™

Probiotic Ecology of three live probiotic strains representative of naturally occurring L. crispatus genomic diversity and associated with vaginal microbiome stability were selected from our proprietary strain bank of over 600 microbial strains.

Maltose, Calcium Lactate, Glutamine, DiBasic Magnesium Citrate, Cystine

A complex of nutrients and molecules was specifically selected to create the ideal environment and energy source for our CST-1™ Probiotic Ecology.  By providing L. crispatus a growth advantage over other less beneficial species in your vagina, our complex ensures that these protective bacteria not only survive, but thrive.

Magnesium Stearate (plant-derived), Hydroxypropyl Methylcellulose (HPMC) (naturally-derived), Cellulose (naturally-derived)

Chemically inactive excipients to support tablet formation, stabilization, or dissolution profiles. HPMC and Cellulose are both naturally derived from wood pulp. 

Directions for Use

How to Use

  • Prepare: Wash your hands and gently press a VS-01™ vaginal tablet out of the aluminum pack.

  • Load: Place the tablet into the applicator. The tablet is in the correct place when it’s protruding halfway out of the applicator.

  • Insert: Insert the applicator into your vagina and push the inner tube towards you to release (just like a tampon). 

  • Dispose: Dispose of the applicator in the trash. Note that each applicator is a Class I Medical Device and cannot be recycled. 

VS-01™ requires your body’s natural lubrication for proper dissolution, and therefore may not be as effective among women experiencing significant vaginal dryness.

Protocol

For Optimal Seeding-Reset

Begin VS-01™ Reset––a clinically-validated protocol to seed an optimal vaginal microbiome and maintain vaginal pH within one month. 

If you menstruate regularly, start Day 1 immediately after your period when bleeding stops (spotting is okay). If you do not menstruate regularly, you may start at any time. 

Continue on Days 4, 7, 14, 21, and 28.

If you miss a day, simply resume as soon as possible. 

For Ongoing Protection-Sustain

Continue VS-01™ monthly to support maintenance of a stable vaginal microbiome and protect against pH disruptors from lifestyle and the environment.  

If you menstruate regularly, start Day 1 immediately after your period when bleeding stops (spotting is okay), and the second vaginal tablet on Day 14. If you do not menstruate regularly, you may start Day 1 at any time. 

If you miss a day, simply resume as soon as possible.

Acclimation

When first starting VS-01™, acclimation can be a common and anticipated experience. Symptoms such as vaginal discharge, mild-to-moderate irritation, or minor cramping may occur shortly after inserting the first vaginal tablet. These effects will normalize as your body adjusts to the protocol. If you are concerned about any potentially unwanted or negative effects, consult with your physician. 

Menses

It is recommended that you do not use VS-01™ while experiencing moderate to heavy bleeding, in order to allow the VS-01™ vaginal tablet to fully dissolve in the vagina and maximize absorption. Generally, Day 1 of each protocol starts as soon as bleeding stops.

Note that it is completely fine to insert VS-01™ while spotting or experiencing light bleeding.

If you experience breakthrough bleeding, <28 day cycles, or irregular periods that may disrupt the VS-01™ protocol, do not worry.  If you are unable to follow the recommended dosing schedule, please take each tablet as close to the dosing schedule as possible.

Clinical Trials

(RCT1) VS-01™ Drives Beneficial Vaginal Microbiome Ecology Shift

A vaginal microbiome dominated by L. crispatus is associated with favorable health outcomes. Synbiotics designed to support or shift vaginal microbiomes into this beneficial ecology from multiple starting ecologies have the potential to deliver health benefits. 

A randomized, double-blind placebo-controlled clinical trial (n=70) in healthy premenopausal women was conducted to compare multiple candidate L. crispatus vaginal synbiotic formulations, versus a leading oral probiotic for vaginal health, and placebo. Participants were randomized to each arm, and received a 30-day dosing regimen with 21-day follow-up. The primary outcome was safety, and the key secondary outcome was vaginal microbiome profiling by high-depth metagenomic sequencing. 

Results revealed a vaginal tablet formulation of VS-01™ demonstrated a significant increase in L. crispatus relative abundance, and the highest rates of conversion to an optimal vaginal microbiome. Participants with a baseline non-optimal vaginal microbiome experienced up to 90% conversion to an  L. crispatus dominant vaginal microbiome during the dosing period, compared to 11% in the placebo arm. VS-01™ significantly outperformed other candidate formulations and a leading oral probiotic for vaginal health. Colonization of VS-01™ strains,  (LUCA103™, LUCA011™, LUCA009™,) was associated with conversion to an optimal vaginal microbiome and a significant increase in strain relative abundance in the vaginal tablet arm. Overall, all formulations were well-tolerated with a favorable safety profile.

This study is the first to demonstrate that a multi-strain vaginal synbiotic (VS-01™) can drive persistent conversion to an optimal vaginal microbiome, coupled with colonization of product strains in different vaginal microbiome ecologies. Oral formulations were not effective in modulating the vaginal microbiome.

Fig. 1 — Change in the average relative abundance of <i>L. crispatus</i> in participants with a non-optimal baseline vaginal microbiome across 21 days of use.
Fig. 1 — Change in the average relative abundance of L. crispatus in participants with a non-optimal baseline vaginal microbiome across 21 days of use.
Fig. 2 — The proportion of participants with a non-optimal baseline vaginal microbiome who converted to an optimal vaginal microbiome.
Fig. 2 — The proportion of participants with a non-optimal baseline vaginal microbiome who converted to an optimal vaginal microbiome.

(RCT-X) VS-01™ Perception Study + QOL assessment

This randomized (2:1) placebo-controlled trial will assess the overall user experience of VS-01™ compared to placebo among 200 premenopausal women (18-55 years) with self-reported vaginal discomforts. Over the course of the study, following the standard VS-01™ protocol, participants will complete questionnaires to evaluate health-related quality of life and self-perceived changes in vaginal discomforts.  

Vaginal health has long been overlooked as an important health outcome. Significant disparities exist among gender in the health and medical community. Specifically, women of color often experience lower-quality health care and have worse health outcomes (Gillispie-Bell, 2021). This study ensures a broad representation of identities and experiences are represented in the sample population. 

This study is part of a broader aim to enrich the biological, ethnocultural, and linguistic diversity of medically studied populations, the applicability of the research findings, and to foster inclusiveness in clinical research and equity in health within the United States. 

Strain Selection Process

We aimed to identify and characterize specific strains of L. crispatus associated with stable, healthy vaginal microbiomes. L. crispatus displays significant diversity in optimal microbiomes, so we built a consortia of three strains that maximize coverage of naturally-occuring genomic diversity. To achieve this, we leveraged V-CLOUD, the field-leading proprietary genomic database containing the largest collection of vaginal genomes and metagenomes, combined with the most extensive gene library and longitudinal dataset on the vaginal microbiome available in the field.

Using V-CLOUD and a deeply sampled longitudinal vaginal microbiome dataset generated by Dr. Ravel, we identified specific genomic elements in some L. crispatus strains associated with vaginal microbiome stability. We screened close to 100 isolates of L. crispatus from healthy women for the presence of these elements, and identified three strains that contain the stability-associated genomic elements and capture nearly three-quarters of genomic diversity found in the human vaginal microbiome. This three strain ecology with broad genetic coverage enhances the formula’s potential to support and maintain an optimal vaginal microbiome.

Additionally, we performed extensive in vitro characterization of these strains for safety (they are free of antibiotic resistance genes and virulence factors, are susceptible to commonly used antibiotics, and are non-inflammatory) and efficacy against harmful microbes.

Testing

Microbiological DataDescriptionUnit of Measure (LOQ)Testing Frequency
Candida albicansAbsent/tabletEvery lot
E. coliAbsent/tabletEvery lot
Pseudomonas aeruginosaAbsent/tabletEvery lot
Staphylococcus aureusAbsent/tabletEvery lot
Yeast and molds≤20 CFU/gEvery lot
Microbiological DataDescriptionUnit of Measure (LOQ)Testing Frequency
Candida albicansAbsent/tabletEvery lot
E. coliAbsent/tabletEvery lot
Pseudomonas aeruginosaAbsent/tabletEvery lot
Staphylococcus aureusAbsent/tabletEvery lot
Yeast and molds≤20 CFU/gEvery lot
Probiotic Identity and PotencyDescriptionUnit of Measure (LOQ)Testing Frequency
PotencyAFU/tablet (active fluorescent units)Every lot
IdentityPositive for L. crispatus LUCA strainsEvery lot
Probiotic Identity and PotencyDescriptionUnit of Measure (LOQ)Testing Frequency
PotencyAFU/tablet (active fluorescent units)Every lot
IdentityPositive for L. crispatus LUCA strainsEvery lot
Chemical Contaminants
Heavy Metals [Inorganic]
DescriptionUnit of Measure (LOQ)Testing Frequency
Arsenic<0.15 ppm (parts per million)Every lot
Lead<0.50 ppmEvery lot
Cadmium<0.05 ppmEvery lot
Mercury<0.30 ppmEvery lot
Chemical Contaminants
Heavy Metals [Inorganic]
DescriptionUnit of Measure (LOQ)Testing Frequency
Arsenic<0.15 ppm (parts per million)Every lot
Lead<0.5 ppmEvery lot
Cadmium<0.05 ppmEvery lot
Mercury<0.30 ppmEvery lot
Chemical Contaminants
Pesticides [Organic]
DescriptionUnit of Measure (LOQ)Testing Frequency
AMPA (breakdown product of glyphosate)< LOQQuarterly
Glyphosate< LOQQuarterly
Pesticides/Biocides [500+ different chemicals]< LOQQuarterly
Chemical Contaminants
Pesticides [Organic]
DescriptionUnit of Measure (LOQ)Testing Frequency
AMPA (breakdown product of glyphosate)< LOQQuarterly
Glyphosate< LOQQuarterly
Pesticides/Biocides [500+ different chemicals]< LOQQuarterly
AllergenUnit of Measure (LOQ)Testing Frequency
Almond<0.1mgQuarterly
Brazil Nut<0.1mgQuarterly
Cashew<0.05mgQuarterly
Celery<0.07mgQuarterly
CornRun and report*Quarterly
Gluten [across barley, rye, oats + wheat] (wheat protein)<20 ppmQuarterly
Crustacean (shrimp protein)<26.2mgQuarterly
Egg<0.2mgQuarterly
Fish<2.6mgQuarterly
Hazelnut<0.1mgQuarterly
Lupin<2.9mgQuarterly
Macadamia Nut<0.1mgQuarterly
Milk<0.2mgQuarterly
MolluscsRun and report*Quarterly
Mustard<0.07mgQuarterly
Peanut<0.2mgQuarterly
Pecan<0.03mgQuarterly
Pine Nut<0.1mgQuarterly
Pistachio<0.05mgQuarterly
Sesame<0.1mgQuarterly
Soy<0.5mgQuarterly
Sulfiting Agents<10 ppmQuarterly
Walnut<0.03mgQuarterly
AllergenUnit of Measure (LOQ)Testing Frequency
Almond<0.1mgQuarterly
Brazil Nut<0.1mgQuarterly
Cashew<0.05mgQuarterly
Celery<0.07mgQuarterly
CornRun and report*Quarterly
Gluten [across barley, rye, oats + wheat] (wheat protein)<20 ppmQuarterly
Crustacean (shrimp protein)<26.2mgQuarterly
Egg<0.2mgQuarterly
Fish<2.6mgQuarterly
Hazelnut<0.1mgQuarterly
Lupin<2.9mgQuarterly
Macadamia Nut<0.1mgQuarterly
Milk<0.2mgQuarterly
MolluscsRun and report*Quarterly
Mustard<0.07mgQuarterly
Peanut<0.2mgQuarterly
Pecan<0.03mgQuarterly
Pine Nut<0.1mgQuarterly
Pistachio<0.05mgQuarterly
Sesame<0.1mgQuarterly
Soy<0.5mgQuarterly
Sulfiting Agents<10 ppmQuarterly
Walnut<0.03mgQuarterly

‡Maximum daily doses are clinically-derived from oral food challenge studies and reflect the most recent advancements in food allergy research.  The reference dose, also termed ED01, is the dose at which 1% of the allergic population would be predicted to experience any objective allergic reaction (i.e., 99% of the allergic population does not experience any objectively measurable reaction).

*Inadequate number of clinical studies using low dose oral challenges with this allergen.

Tablet QualitiesDescriptionUnit of Measure (LOQ)Testing Frequency
pHpH = 3.30 - 5.30Every lot
Disintegration>3 hoursEvery lot
Organoleptic evaluationWhite-to-beige oblong tablets. Neutral aroma.Every lot
Friability<1.00%Every lot
Water activity<0.20Every lot
Loss on drying<5.00%Every lot
Weight variation850mg ± 5%Every lot
Tablet QualitiesDescriptionUnit of Measure (LOQ)Testing Frequency
pHpH = 3.30 - 5.30Every lot
Disintegration>3 hoursEvery lot
Organoleptic evaluationWhite-to-beige oblong tablets. Neutral aroma.Every lot
Friability<1.00%Every lot
Water activity<0.20Every lot
Loss on drying<5.00%Every lot
Weight variation850mg ± 5%Every lot
Endocrine PanelDescriptionUnit of Measure (LOQ)Testing Frequency
Estrogen Panel< LOQQuarterly
Gestagens/Corticosteroids Panel< LOQQuarterly
Paraben Panel< LOQQuarterly
PFAS Panel< LOQQuarterly
Phthalate Panel< LOQQuarterly
Endocrine PanelDescriptionUnit of Measure (LOQ)Testing Frequency
Estrogen Panel< LOQQuarterly
Gestagens/Corticosteroids Panel< LOQQuarterly
Paraben Panel< LOQQuarterly
PFAS Panel< LOQQuarterly
Phthalate Panel< LOQQuarterly

Heavy Metals Testing

Most supplements, fruits, vegetables, milk-derived proteins, and natural products carry some level of heavy metals, which can be very difficult to completely eliminate from the diet due to their uptake by plants from the surrounding air, water, and soil. Food and natural products are regulated in California by CA Prop 65, or "The Safe Drinking Water and Toxic Enforcement Act of 1986", which establishes "safe harbor levels" for a list of chemicals known to the state to potentially cause cancer or reproductive toxicity. Seed abides by these stringent regulations and tests all products for the four main categories of Heavy Metals: Arsenic, Cadmium, Lead, and Mercury. As demonstrated in the table, VS-01™ falls well below the established limits.

EDC Testing

Endocrine-disrupting chemicals (EDCs) are natural or synthetic chemicals that may mimic, block, or interfere with the body’s hormones, which are part of the endocrine system. These chemicals are associated with a wide array of health issues. VS-01™ is tested for a comprehensive panel of over 50 endocrine-disrupting substances including phthalates, per- and polyfluoroalkyl substances (PFAS), parabens, corticosteroids and estrogens.

Pesticide Testing

VS-01™ is tested at third-party accredited laboratories for over 500 pesticide residues using gas chromatography with tandem mass spectrometry.  We [specifically] subject VS-01™ to testing for the ubiquitous pesticide, glyphosate, as well as its breakdown product, aminomethylphosphonic acid (AMPA), using liquid chromatography with tandem mass spectrometry.  This rigorous testing protocol ensures adherence to our strict quality standards.

The full list of pesticides tested may be viewed here.

Allergen Testing

VS-01™ is consistently tested for all 14 allergen classes, including over 20 of the most common allergens as defined by the European Food and Safety Authority (EFSA). This panel extends well beyond the minimum 9 allergens required to test by the FDA.

Toxicology Assessment

We conducted an extensive toxicological review of VS-01™, confirming its non-toxicity and safety for both short-term (<90 days) and long-term (>90 days) use by healthy individuals. Results also demonstrate no reproductive or developmental concerns. 

Osmolality Testing

Osmolality is the number of moles of dissolved particles per kg of water (units mOsm). High osmolality indicates a high concentration of solutes in a solution. Normal vaginal fluid ranges between 300-400 mOsm.

Most vaginal lubricants are hyperosmolar (>2000 mOsm), can cause vaginal epithelial cell death, and loss of barrier integrity in 3-D tissue models. Epithelial damage can increase the risk of infection. Based on third-party laboratory testing with a GLP-compliant quality system, VS-01™ falls under the World Health Organization’s (WHO) established upper limit (1200mOsm) for osmolality.

Vaginal Tissue Model (MatTek) Testing

We subjected VS-01™ to an FDA-recognized tissue culture model derived from healthy, human-derived vaginal epithelial and dendritic cells. Its highly-differentiated structure parallels in vivo vaginal tissue to better understand how products impact the vaginal epithelium. Testing revealed that VS-01™ preserves the integrity of the vaginal epithelial barrier without triggering inflammatory responses. This approach not only reflects our dedication to ethical research practices but also underscores our commitment to developing products that are safe and beneficial for vaginal health.

Interactions

Medications + Pre-existing Conditions

VS-01™ would generally be suitable to take alongside most prescribed or over-the-counter medications as there are no known contraindications between medications and probiotics, prebiotics or postbiotics. That said, if you are currently taking medication for an existing vaginal infection or concern, follow the standard of care prescribed and introduce VS-01™ as directed by your doctor.

Ultimately, we always recommend consulting with a prescribing physician regarding incorporating VS-01™ into your routine alongside any medications or pre-existing conditions.

Pregnancy + Preconception

As with any new product contemplated during pregnancy, or pre-conception, we always recommend a conversation with a physician or obstetrician before trying VS-01™.