Lactobacillus jensenii

Sinopsis

Lactobacillus jensenii: A Comprehensive Reference

1. Identity, Taxonomy, and Classification

Lactobacillus jensenii is a species of Gram-positive, facultative anaerobic, lactic acid-producing, rod-shaped bacterium in the genus Lactobacillus, belonging to the phylum Bacillota. It is classified within the domain Bacteria, phylum Bacillota, class Bacilli, order Lactobacillales, family Lactobacillaceae, and genus Lactobacillus.

Lactobacillus jensenii was discovered by F. Gasser, M. Mandel, and M. Rogosa in 1969. Although sharing many characterization criteria with other species, L. jensenii differed from the similar Lactobacillus leichmannii in a gel electrophoresis analysis of their respective lactic dehydrogenases. The species was named in honour of Sigurd Orla-Jensen, a Danish microbiologist and pioneer of biotechnology.

A key method for differentiating L. jensenii from similar species involved starch gel electrophoresis of lactic dehydrogenases (LDHs) from crude cell extracts. This technique revealed distinct patterns in L. jensenii, including one NAD-dependent D-LDH and two NAD-independent LDHs that exhibited dual specificity for D- and L-lactate substrates.

Phylogenetically, L. jensenii belongs to the emended genus Lactobacillus as defined in the 2020 taxonomic revision of the Lactobacillaceae family, which reorganized the former broad Lactobacillus genus into 25 genera based on core genome phylogeny, average nucleotide identity, and ecological adaptations. The Lactobacillus genus was split up into 25 different genera in April 2020. Many species were reclassified at this time, but L. jensenii remains in the Lactobacillus genus. Its name did not change.

The type strain of L. jensenii is held in multiple international culture collections. Registered type strain designations include ATCC 25258, DSM 20557, JCM 1146, and NRRL B-4550, among others.

Morphological Characteristics

Lactobacillus jensenii is Gram-positive, rod-shaped, negative for catalase and oxidase, and anaerobic. The organism can grow on blood agar. Colonies of L. jensenii are circular, colorless, small, and translucent. Its thick peptidoglycan wall gives this non-spore-forming bacterium its rod-shaped feature.

2. Natural Sources and Ecological Niche

L. jensenii is one of the four main species of Lactobacillus considered to be a major part of the vaginal flora, along with Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus iners.

L. jensenii, along with Lactobacillus crispatus and Lactobacillus gasseri, is a natural vaginal strain of bacteria colonizing biofilms of the vaginal mucosa in healthy females. This particular vaginal lactobacillus contributes to approximately 23% of the vaginal colony population (following Lactobacillus crispatus at ~32%), making it the second most prevalent vaginal lactobacillus in the lower female genital tract.

Lactobacillus forms biofilms in the vaginal and gut microbiota, allowing these species to persist in harsh environmental conditions and maintain ample populations.

L. jensenii is sometimes also found in or used in the production of fermented foods. It is commonly seen as an additive in many yogurts, fermented foods, and probiotic preparations.

Community State Types (CSTs) and the Vaginal Microbiome

Based on high-throughput sequencing studies, five community state types (CSTs) exist in terms of the vaginal microbiome. Research on 396 North American asymptomatic women from four ethnic groups illustrates that the majority of vaginal microbiomes are dominated by single or multiple Lactobacillus species. CSTs I, II, III, and V are dominated by L. crispatus, L. gasseri, L. iners, and L. jensenii, respectively, whereas CST IV refers to a high diversity microbial community characterized by obligate anaerobic bacteria.

Lactobacillus jensenii is defined as a species of vaginal lactobacilli that can be part of Lactobacillus-dominant vaginal microbiotas, typically in combination with other Lactobacillus species. It contributes to maintaining a low vaginal pH and may play a role in the overall health of the vaginal microbiome.

While the association between Lactobacillus dominance and vaginal health generally applies to women of reproductive age, defining a "healthy vaginal microbiome" solely by the abundance of Lactobacillus is considered a generalized and limited description. It excludes considerations for women outside of reproductive age and overlooks variations in vaginal bacterial composition across racialized groups. Not all Lactobacillus species are associated with a healthy vaginal microbiome or the maintenance of favorable gynecological and obstetric outcomes.

3. Historical and Traditional Use

Lactobacillus jensenii is a naturally occurring commensal microorganism rather than an ingredient with a formalized record of deliberate traditional medicinal or culinary preparation. Its historical context is therefore best understood through the broader lens of lactic acid bacteria and fermented foods.

Lactobacilli are ingested through the consumption of traditional fermented products. Representatives of these food products are manufactured in all parts of the world, where they have been a component of human diet throughout millennia. In fermented foods, lactobacilli release organic acids and other substances with antimicrobial properties that allow for the production of microbiologically safe, nutrient-rich fermented matrices of animal and plant origin.

The specific scientific identification of L. jensenii as a distinct species occurred only in 1969–1970 via gel electrophoresis studies on vaginal discharge isolates. Prior to formal taxonomic description, L. jensenii and related vaginal lactobacilli were recognized in a general sense as part of the normal vaginal microflora. In 1892, Albert Döderlein first described the presence of Gram-positive bacilli in the vagina of healthy reproductive-age women with low vaginal pH, and considered the bactericidal action of the vaginal secretions to be due to the lactic acid produced by these bacilli. This early observation laid the conceptual groundwork for understanding the protective role of vaginal lactobacilli, a category that would later encompass L. jensenii.

There is no documented evidence that L. jensenii was specifically isolated, cultivated, or deliberately administered as a remedy in any pre-modern medical tradition. Its contemporary relevance as a dietary supplement or live biotherapeutic product is an entirely modern scientific development.

4. Key Constituents and Active Compounds

Lactobacillus jensenii does not deliver discrete phytochemical or nutritional constituents in the manner of a botanical extract. Rather, its biological activity is attributed to the metabolites it produces, the structural components of the bacterial cell itself, and the ecological interactions it mediates within the vaginal or gut microenvironment. The principal active constituents identified in the scientific literature are as follows:

4.1 Lactic Acid

Lactobacilli produce lactic acid, which contributes to vaginal acidity; this lowered pH is generally accepted to be the main mechanism controlling the composition of the vaginal microbiota. Under current scientific consensus, lactic acid rather than hydrogen peroxide plays the more important role in the antimicrobial properties of protective vaginal Lactobacillus species. L. jensenii produces L-lactic acid isomers, which help maintain pH stability and prevent infection.

4.2 Hydrogen Peroxide (H₂O₂)

L. jensenii is a hydrogen peroxide-producing bacterium; this compound contributes to inhibiting anaerobic growth products such as superoxide anion radicals and hydroxyl radicals. However, the in vivo significance of this mechanism is contested. In the cervicovaginal environment, the production of hydrogen peroxide by vaginal Lactobacillus spp. is often mentioned as a critical factor in antimicrobial properties. However, several lines of evidence support the implausibility of H₂O₂ as an "in vivo" contributor to cervicovaginal antimicrobial properties, and an alternative explanation proposes that lactic acid rather than H₂O₂ plays the more important role.

4.3 Bacteriocin-Like Inhibitory Substances (BLIS)

Under conditions that mimic vaginal fluid, L. jensenii strain 62B produces an extracellular factor (Lj-BLIS) with a molecular weight range of 10–30 kDa and specific bactericidal activity against Gardnerella species. The Lj-BLIS exhibits an unusually narrow spectrum of activity. While L. crispatus and L. gasseri reduced G. piotii growth, L. jensenii strain 62B inhibited its growth completely. Characterization of this inhibitory factor showed it is likely a bacteriocin-like inhibitory substance with narrow-spectrum activity affecting only Gardnerella spp.

4.4 Surface-Associated Proteins

High numbers of lactobacilli in the vaginal tract have been correlated with a decreased risk of infection by the sexually transmitted pathogen Neisseria gonorrhoeae. Lactobacillus jensenii, one of the most prevalent microorganisms in the healthy human vaginal tract, can inhibit gonococcal adherence to epithelial cells in culture. Lactobacilli can inhibit adherence by production of biosurfactants, receptor competition, or coaggregation with the pathogen. Lactobacilli can also inhibit pathogen colonization by causing the host cells to become more resistant to adherence or by suppressing the expression of virulence factors in the pathogen.

4.5 Immunomodulatory Cell Components

Lactobacilli are able to inhibit pathogens in a direct manner by coaggregation or by producing active components such as bacteriocins, lactic acid, and hydrogen peroxide. In addition, they promote the integrity of the epithelium by stimulating mucus secretion and modulating the immune response, which are indirect ways of inhibiting viral and bacterial pathogens.

Research has demonstrated that L. jensenii TL2937 attenuated the expression of proinflammatory cytokines and chemokines by downregulating TLR4-dependent nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activation. Furthermore, L. jensenii TL2937 stimulation upregulated three negative regulators of TLRs: A20, Bcl-3, and MKP-1.

5. Mechanisms of Action

5.1 Acidification of the Vaginal Microenvironment

Lactobacilli utilize several mechanisms to prevent colonization by incoming pathogens, including direct killing of organisms by hydrogen peroxide, bacteriocins, and lowering the pH of the vaginal tract to approximately 4 by production of lactic acid. Vaginal epithelial cells produce glycogen, which lactobacilli ferment, producing D- and L-lactic acid. Some species produce hydrogen peroxide in vitro; however, recent studies suggest that in the hypoxic conditions that exist in the vagina, concentrations may never achieve levels that are inhibitory to other bacteria. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide.

5.2 Biofilm Formation

Vaginal lactobacilli maintain vaginal homeostasis by producing metabolites such as lactate, antimicrobials, hydrogen peroxide, and lactic acid; enhancing mucus viscosity; trapping pathogens; and preventing adhesion, growth, and DNA damage to vaginal epithelial cells.

5.3 Immunomodulation via Toll-Like Receptor Pathways

The immunomodulatory effect of strain TL2937 was not related to a downregulation of TLR4, but was related to an upregulation of the expression of three negative regulators of TLRs: SIGIRR, A20, and IRAK-M. TLR2 has an important role in the anti-inflammatory activity of L. jensenii TL2937, since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M and the production of IL-10 in response to TLR4 activation.

Direct exposure of porcine antigen-presenting cells to L. jensenii in the absence of inflammatory signals increased expression of IL-10 and TGF-β in CD172a+ APCs and caused them to display tolerogenic properties. In addition, pretreatment of CD172a+ APCs with L. jensenii resulted in differential modulation of the production of pro- and anti-inflammatory cytokines in response to TLR4 activation.

5.4 Anti-Inflammatory Cytokine Modulation

Colonization of in vitro cellular multilayers by common vaginal commensals, including L. crispatus and L. jensenii, attenuates pro-inflammatory outcomes, reducing IL-6, IL-8, and TNF-α secretion after TLR stimulation. In particular, vaginal L. crispatus and L. jensenii strains prevent pro-inflammatory activity by decreasing the levels of pro-inflammatory cytokines IL-1α and IL-8.

6. Scientific Evidence by Area of Use

6.1 Vaginal Health and Bacterial Vaginosis (BV)

Overview: Lactobacillus jensenii and other Lactobacillus species that produce lactic acid have been correlated with a decreased rate of bacterial vaginosis, gonorrhea- and HIV-acquisition, and pelvic inflammatory disease.

Community composition evidence: The healthy and diseased state of vaginal microbiota can be classified into five common CSTs according to their respective characteristics. These CSTs are dominated mainly by L. crispatus, L. gasseri, L. iners, bacterial vaginosis-associated bacteria (BVAB), and L. jensenii.

BV and dysbiosis: These vaginal lactobacilli have been recognized to prevent invasion of pathogens by keeping their population in check. However, the disruption of the vaginal ecosystem contributes to the overgrowth of pathogens which causes complicated vaginal infections such as bacterial vaginosis, sexually transmitted infections, and vulvovaginal candidiasis.

Evidence characterization: The association between L. jensenii colonization and reduced BV is primarily epidemiological and observational. Bacterial vaginosis is a genital tract infection in women characterized by a highly diverse vaginal microbiome and few lactobacilli. BV is associated with an elevated risk of adverse reproductive health outcomes such as preterm birth and the acquisition of sexually transmitted infections including HIV. Direct interventional clinical trials using L. jensenii specifically to treat or prevent BV in humans are not established in the published literature as of the available evidence base; most therapeutic lactobacillus trials have focused on other species such as L. crispatus.

6.2 Anti-Gonococcal Activity

In vitro evidence: It has been previously shown that Lactobacillus jensenii, one of the most prevalent microorganisms in the healthy human vaginal tract, can inhibit gonococcal adherence to epithelial cells in culture. Researchers examined the role of epithelial cells and the components of L. jensenii involved in this inhibition of gonococcal adherence. L. jensenii inhibited the adherence of gonococci to glutaraldehyde-fixed epithelial cells like it inhibited the adherence of gonococci to live epithelial cells, suggesting that the epithelial cells do not need to be metabolically active for the inhibition to occur. Furthermore, methanol-fixed L. jensenii also inhibited gonococcal adherence.

Evidence characterization: This evidence is currently limited to cell culture (in vitro) studies. There are no published human clinical trials demonstrating that supplementation with L. jensenii reduces gonorrhea acquisition rates. The in vitro data are mechanistically informative but are not sufficient to draw conclusions about clinical efficacy.

6.3 HIV Prevention

Bioengineered strain research: Vaginal probiotics are being investigated as a dual strategy for prevention of bacterial vaginosis and HIV. Researchers assessed the functional properties of Lactobacillus jensenii, a predominant constituent of the healthy vaginal microbiome, engineered to express the HIV-1 entry inhibitor modified cyanovirin-N (mCV-N).

Wild-type L. jensenii 1153 consistently colonized cervical and vaginal cells in the absence of epithelial damage and apoptosis. The bioengineered derivatives expressing mCV-N or control plasmids showed the same stable colonization pattern, which was reproducible between technologists and bacterial batches.

Vaginal probiotics or live biotherapeutic products as defined by the FDA may reduce the risk of HIV transmission by expressing antiviral factors, restoring the normal microbiota, inhibiting bacterial pathogens, and modulating immuno-inflammatory responses without compromising the homeostatic environment of the host.

Evidence characterization: Research on L. jensenii as an anti-HIV live biotherapeutic is at the preclinical and early-phase experimental stage. The above-cited work used an in vitro epithelial cell colonization model. No published phase 2 or phase 3 clinical trials using L. jensenii (wild type or engineered) for HIV prevention in humans have been identified in the available literature. This area remains investigational.

6.4 Protective Effects Against Sexually Transmitted Viral Infections (HPV, HSV)

The healthy cervicovaginal microbiota is dominated by various Lactobacillus species, which support a condition of eubiosis. Among their many functions, vaginal lactobacilli contribute to the maintenance of an acidic pH, produce antimicrobial compounds, and modulate the host immune response to protect against vaginal bacterial and fungal infections. Increasing evidence suggests that these beneficial bacteria may also confer protection against sexually transmitted infections caused by viruses such as human papillomavirus (HPV), human immunodeficiency virus (HIV), and herpes simplex virus (HSV).

Evidence characterization: The cited evidence linking L. jensenii specifically (as opposed to vaginal lactobacilli generally) to protection against HPV or HSV is derived from observational, epidemiological, and in vitro research. Causal human clinical trial data for L. jensenii against these specific viral pathogens are not established in the current literature.

6.5 Preterm Birth Risk and Pregnancy

Observational and genomic evidence: Each year, 15 million infants are born preterm (before 37 weeks gestation), representing the leading cause of mortality for children under the age of five. Factors such as maternal genetics, environmental interactions, and the vaginal microbiome have been associated with an increased risk of preterm birth. Previous studies show that a vaginal microbiota dominated by Lactobacillus is, in contrast to communities containing a mixture of genera, associated with full-term birth. However, this binary principle does not fully consider more nuanced interactions between bacterial strains and the host. Through a combination of analyses involving genome-sequenced isolates and strain-resolved metagenomics, researchers identified that L. jensenii strains from preterm pregnancies are phylogenetically distinct from strains from full-term pregnancies.

A stable colonization with L. jensenii and related species, as opposed to dominance by L. iners, is associated with better reproductive outcomes.

Evidence characterization: This evidence is observational and genomic. The finding that different L. jensenii strain clades associate with different birth outcomes is a significant and recent scientific development, but does not yet translate into clinical recommendations for supplementation. No interventional trials using L. jensenii to prevent preterm birth have been identified in the available evidence base.

6.6 Intestinal Inflammation and Inflammatory Bowel Disease

Animal and cell-culture evidence (strain TL2937): Researchers studied whether the TL2937 strain was able to protect against the development of colitis in a dextran sodium sulfate (DSS)-induced mouse model. L. jensenii TL2937 was administered to adult BALB/c mice before the induction of colitis by DSS. Colitis and the associated inflammatory response were evaluated for 14 days. Mice fed with L. jensenii TL2937 had lower disease activity index and alterations of colon length when compared to control mice. Reduced myeloperoxidase activity, lower production of pro-inflammatory cytokines (TNF-α, IL-1, CXCL1, MCP-1, IL-15, and IL-17), and higher levels of immunoregulatory cytokines (IL-10 and IL-27) were found in the colon of TL2937-treated mice.

L. jensenii TL2937, a strain with a high capacity to activate TLR2, was also the strain with the highest capacity to down-regulate IL-6 and IL-8 production in porcine intestinal epithelial (PIE) cells in response to ETEC and LPS. The mechanisms behind this anti-inflammatory effect demonstrated that L. jensenii TL2937 inhibits NF-κB and MAPK signaling pathways in ETEC- and LPS-challenged PIE cells.

Evidence characterization: All available evidence for L. jensenii in inflammatory bowel disease is preclinical — derived from in vitro porcine cell models and mouse colitis models. Human clinical data are lacking. This application should be considered highly preliminary and experimental.

6.7 Vulvovaginal Atrophy and Menopausal Changes

Bacterial communities in the vagina cluster into six community state types, of which four are dominated by Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, or Lactobacillus jensenii, and two had low relative abundance of Lactobacillus. There were significant associations between menopause stage and CST (P = 0.004) and between vulvovaginal atrophy and CST (P = 0.002). Perimenopausal women were more likely to be classified as CST IV-A or the L. gasseri CST, whereas postmenopausal women were often classified as CST IV-A. CSTs dominated by L. crispatus and L. iners were more prevalent in premenopausal women.

Evidence characterization: These findings are from observational cross-sectional and longitudinal cohort studies. They characterize shifts in vaginal CST across the reproductive lifespan without establishing that L. jensenii supplementation alters vulvovaginal atrophy outcomes. No interventional trials for this indication have been identified for L. jensenii specifically.

7. Dosage Forms and Preparations

Lactobacillus jensenii is commonly seen as an additive in many yogurts, fermented foods, and probiotic supplements. In the context of current scientific investigation, it appears in several preparation formats:

Oral probiotic supplements: L. jensenii is incorporated into multi-strain oral probiotic capsules and powders. No standardized dosage for oral supplementation has been established in the published clinical literature.
Vaginal probiotic/live biotherapeutic formulations: Experimental vaginal formulations are under investigation for bacterial vaginosis and sexually transmitted infection prevention. These are not yet approved mainstream therapeutics.
Bioengineered strains: Investigational preparations, such as L. jensenii engineered to secrete cyanovirin-N (mCV-N), have been developed and tested in preclinical in vitro models as potential vaginal microbicides. These remain experimental.
Fermented foods: L. jensenii may be present naturally or as an added culture in fermented dairy and other products.

Dosage: There is not enough reliable information to know what an appropriate dose of L. jensenii might be. No published human clinical trials have established a specific efficacious dose or colony-forming unit (CFU) count for L. jensenii supplementation across any indication. The research literature on this organism, where dosing is mentioned at all, pertains to experimental in vitro and animal models rather than standardized human clinical protocols.

8. Body Systems and Health Areas of Association

Female reproductive/urogenital system: Primary ecological niche; associated with reduced BV, protection against STIs (gonorrhea, HIV, HPV, HSV), maintenance of vaginal pH, and reproductive outcomes including preterm birth.
Immune system: Documented immunomodulatory activity via TLR2/TLR4 signaling modulation, upregulation of negative regulators of inflammation, and promotion of tolerogenic antigen-presenting cell phenotypes (primarily in preclinical models).
Gastrointestinal system: Preclinical evidence from the TL2937 strain in mouse colitis and porcine intestinal epithelial cell models suggests potential for intestinal anti-inflammatory effects; no human data available.
Urinary tract: By virtue of its colonization of the urogenital mucosa, L. jensenii has been posited to limit uropathogen ascension, though clinical evidence for this specific species is not established.

9. Safety Considerations and Known Interactions

9.1 General Safety Profile

Lactobacilli constitute the dominant microbiota in many fermented foods and comprise widely used probiotics. However, these bacteria can cause rare infections, mostly in diabetic and immunocompromised subjects in the presence of risk factors such as prosthetic heart valves, and dental procedures or caries.

Lactobacilli are normally safe for vaginal use, as there are few reports of infections by lactobacilli. However, more studies are needed to elucidate which strain could be more effective and the appropriate protocol of use, including duration and dosage.

9.2 Documented L. jensenii Infections

Lactobacillus jensenii is a commensal species normally found in the female genitourinary tract, with known protective activity against harmful pathogens including Candida and Gardnerella vaginalis. Although classically a benign member of the normal microflora, opportunistic infections due to Lactobacillus have been observed. The most common manifestation is endocarditis, although bacteremia, liver/pelvic/splenic abscesses, pyelonephritis, meningitis, pneumonia, and even septic arthritis secondary to Lactobacillus have been documented.

In 2019, 2020, and 2021, a total of 17, 15, and 16 cases, respectively, including endocarditis, bacteremia, and other infections, were reported among lactobacilli as a whole. These annual numbers are higher than those observed previously. Among the species implicated in that three-year surveillance period, L. jensenii was associated with 5 cases.

Bloodstream infection by lactobacilli is rare but often fatal, with 30% of endocarditis cases caused by the genus resulting in patient mortality. While L. jensenii takes advantage of nonimmunocompetence in patients, immunocompetent cases have also been observed.

A published case report describes polymicrobial bacteremia due to Lactobacillus jensenii occurring in a pregnant patient, and separate case literature documents penicillin-sensitive L. jensenii bacteremia and mitral valve endocarditis attributed to this species. These cases are rare but clinically notable.

A case report published in PMC (2020) describes renal and perinephric abscesses involving Lactobacillus jensenii and Prevotella bivia in a young woman following a ureteral stent procedure.

9.3 Risk Factors for Infection

The species implicated in infections are the same that are widely used in fermented foods and probiotic applications. These episodes of infections occurred primarily in patients with medical conditions such as preterm birth, diabetes, and immunodeficiency — conditions in which probiotic lactobacilli are also potentially beneficial as a treatment aid.

Increasing reports on Lactobacillus bacteremia-associated morbidity and mortality in immunocompromised patients have raised safety concerns about the use of probiotic lactobacilli in this group.

9.4 Antibiotic Sensitivity

Published case reports indicate that clinical isolates of L. jensenii in the context of bacteremia have demonstrated penicillin sensitivity, which is relevant to treatment selection in the rare event of infection. Resistance profiles may vary by strain, and susceptibility testing is recommended in clinical infection contexts.

9.5 Interactions

No formal drug–interaction studies for L. jensenii supplementation have been identified in the peer-reviewed literature. Empirically, as with all probiotic lactobacilli, concurrent antibiotic therapy would be expected to reduce viable counts of any administered L. jensenii strain, as lactobacilli are susceptible to many antibiotics including penicillins, macrolides, and chloramphenicol, though resistance profiles are strain-specific.

10. Summary of Evidence Strength

Vaginal microbiome health marker (observational): Robust cross-sectional and longitudinal epidemiological evidence that L. jensenii-dominant CST (CST V) is associated with a generally healthy vaginal microbiome; the strength of protection may be less than that of L. crispatus-dominant CST I.
BV-associated protection: Observational evidence is consistent; interventional human trial data using L. jensenii specifically are lacking.
Anti-gonococcal activity: In vitro evidence only; clinical significance unestablished.
HIV prevention (bioengineered): Preclinical/experimental; no human trials published.
STI viral protection (HPV, HSV): Indirect observational evidence; no specific L. jensenii interventional data.
Preterm birth: Observational and genomic; strain-level differences identified but no therapeutic evidence.
IBD/intestinal inflammation (TL2937): Animal and in vitro preclinical data only; no human evidence.
Overall supplement evidence: People use L. jensenii for many different purposes, but there is no good scientific evidence to support its use as a deliberate oral or vaginal supplement across any specific clinical indication at the time of current evidence review.