The lactic acid bacterium Lactobacillus plantarum TENSIA® can be used in foodstuff or in dietary supplements.
Lactobacillus plantarum TENSIA® (DSM 21380)
Origin, identification, deposition, ownership
Lactobacillus plantarum TENSIA® is of healthy human origin. It has been discovered and investigated by BioCC LLC researchers in collaboration with researchers from the University of Tartu.
Strain Lactobacillus plantarum TENSIA® was identified on the basis of biochemical activity with the API 50CHL System (bioMérieux, France) kit as Lactobacillus plantarum (coincidence with the type strain: excellent, ID %-99.9, T index -0.86).
The molecular identification of the strain TENSIA® as Lactobacillus plantarum was confirmed by ITS-PCR (Internal-Transcribed Spacer Polymerase Chain Reaction) and 16S rRNA sequencing.
L. plantarum TENSIA® was deposited in Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ; Germany), under the number DSM 21380, in accordance with the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure, by BioCC LLC on 16.04.2008.
L. plantarum TENSIA® is the property and trademark of BioCC LLC.
Mechanisms of action
Lactobacillus plantarum strain TENSIA® is a multipotent microbe of healthy child origin, the most prominent feature of which is the ability to produce several compounds possessing direct or indirect blood pressure-reducing effects and moderate antioxidative activity.
Blood pressure regulation in the human body is quite complicated. At least three mechanisms have been described. The blood pressure-lowering mechanism of Lactobacillus plantarum TENSIA® is complex, connected with the absorption of several blood pressure-lowering properties, having metabolites produced by the probiotic additive.
- Our in vitro studies indicate that TENSIA® expresses proteolytic properties and can produce ACE inhibitory activity due to production of bioactive di-peptides (Ile-Leu and Phe-Leu).
ACE-inhibitory peptides inhibit the activity of the Angiotensin I-converting enzyme (ACE), thus inhibiting the renin–angiotensin system with consequent vasodilatation.
- TENSIA® can produce NO and to use nitrates as a substrate for NO production.
One cardiovascular disease risk factor is elevated blood pressure combined with arterial stiffness and endothelial dysfunction (which is characterized by impairment of nitric oxide [NO] bioavailability).
- The moderate antioxidative activity of the strain contributes to the improvement of other cardio-vascular risk factors (e.g. excessive oxidative stress) and through this contributes to cardiovascular health.
Reactive oxygen species (ROS) are products of normal cellular metabolism and derive from various sources in different cellular compartments. Oxidative stress resultant from an imbalance between ROS generation and antioxidant defense mechanisms is important in the pathogenesis of cardiovascular diseases, including hypertension.
Additionally, consumption of Lactobacillus plantarum TENSIA®
- helps to maintain and restore the balance of intestinal microflora.
- increases the number of useful lactobacilli in the gut, which ensures the breakdown of absorbable nutrient compounds.
- enhances the human body’s natural resistance to several enteropathogens due to strong antimicrobial activity through production of variety of antimicrobial compounds (organic acids and hydrogen peroxide, plantaricins)
- In food products plantarum TENSIA® reduces the risk of foodborne infections by suppressing potentially pathogenic bacteria due to antimicrobial activity against enteric pathogens like listeria, salmonella and shigella, and psychrophilic microbes.
Biosafety and tolerability
Lactobacilli, incl. the species Lactobacillus plantarum, have been consumed for centuries in the form of fermented foods and are generally recognised as safe (FAO/WHO, 2002). The species L. plantarum is considered by EFSA to be suitable for the Qualified Presumption of Safety (QPS) approach (EFSA, 2007 and 2012).
At the same time, Lactobacillus plantarum as a species is a normal component of the intestinal microbiota in humans. The human (healthy child) origin of the strain Lactobacillus plantarum TENSIA® is a prerequisite for its harmless status and suitability for oral application.
Science-based safety testing of L. plantarum TENSIA® has been carried out in test-tube and on laboratory animals.
The antibiotic susceptibility profile of L. plantarum TENSIA® was determined according to ISO 10932:2010 with VetMIC Lact-1 and VetMIC Lact-2 plates (SVA National Veterinary Institute, Uppsala, Sweden). The minimum inhibitory concentrations for L. plantarum TENSIA® did not exceed the MIC cut-off values proposed for the species Lactobacillus plantarum proposed by EFSA (EFSA 2012).
The biosafety of L. plantarum TENSIA® has been tested in a mouse toxicity model of 30 days of feeding. No translocation of bacteria into blood and no pathological shifts were found by the morphological and histological evaluation of the liver, spleen and gut (Songisepp et al., 2012).
The safety and tolerability of L. plantarum TENSIA® has been proved in two age groups of a general healthy population: adults (age 20…60 y) and the elderly (> 65 y). In human intervention trials with healthy adult and elderly volunteers, no adverse gastro-intestinal effects (abdominal pain, flatulence, bloating) were reported and no increased inflammatory indices (hs-CRP, WBC count; IgG, IgM and IgE levels) or kidney and liver markers (serum creatinine, albumin, alanine transaminase [ALAT], aspartate transaminase [ASAT]) were found after 3-week daily consumption of L. plantarum TENSIA® in doses of 1.5 x 108 to as high as 2 x 1010 viable microbial cells (Songisepp et al., 2012).
The strain L. plantarum TENSIA® was elaborated as a probiotic by BioCC LLC in cooperation with the University of Tartu Departments of Microbiology and Biochemistry according to FAO /WHO guidelines (2002).
Faecal recovery/survival in GIT
One of the selection criterions for probiotics is the ability to survive in the GI tract in order to be effective in therapeutic actions and carry on normal metabolic activity after consumption. The high faecal recovery of a probiotic strain after consumption reflects the viability and good survival of a particular strain in the GI tract.
L. plantarum TENSIA® is able to survive in the human gastrointestinal passage. RT–PCR analysis with strain-specific primers confirmed the appearance of L. plantarum TENSIA® in the faeces of over 80% of adult and elderly volunteers after 3-week daily consumption of L. plantarum TENSIA® with functional food in a daily dose of at least 1.5 x 108 CFU.
Results of clinical trials
Cardiovascular diseases incl. high blood pressure are major causes of mortality in Europe and throughout the world, and a substantial burden on the health care system and society as a whole. Increased blood pressure is the main confounding factor for impaired functioning of the cardio-vascular system. Preventive measures (including lifestyle changes and eating habits) are some of the possible solutions.
The health effects of L. plantarum TENSIA® have been tested on over 700 people.
Several clinical trials (mainly in Estonia as well as an independent trial in Russia) with volunteers consuming the Harmony® cheese or yoghurt comprising L. plantarum TENSIAâ have shown the positive effects of increasing the level of L. plantarum TENSIA® in the human body, stabilizing the intestinal lactobiota and most importantly, helping to reduce blood pressure.
In the randomized double blinded placebo controlled (DBPC) cross-over study (ISRCTN15061552) with 3-week treatment periods with 83 reasonably healthy adults of both sexes aged 18-65 years showed that continuous consumption of L. plantarum TENSIA® with the Harmony® cheese resulted in significantly different reduction (p = 0.007) in SBP accompanied by the significantly different reduction (p = 0.026) in DBP in the verum group (Harmony® group) as compared to the control (regular Edam-type cheese) (Mikelsaar et al., 2012).
The average reduction of SBP over 8 weeks of administration of the Harmony® cheese comprising L. plantarum TENSIA® was 6.66 mmHg and 4.34 mmHg for DBP. The corresponding figures for placebo were, respectively, 2.56 mmHg and 1.21 mmHg.
Figure 1. Average change (with standard errors) in systolic blood pressure and in diastolic blood pressure in the verum group after administration of 50 g of the Harmony™ cheese containing L. plantarum TENSIA® and the placebo group after 4 and 8 weeks
The reduction of blood pressure for 5mm/Hg reduces the prevalence of cardiovascular diseases and stroke for 20-40% and even a 2-3mmHg lower usual SBP would involve about an 8-10% lower stroke mortality and about a 5-7% lower mortality from other vascular causes (Appel et al., 2006; Chobanian et al., 2003, Vasan et al., 2001).
Administration of L. plantarum TENSIA® also improved some atherosclerosis markers. A significant reduction in LDL/HDL ratio occurred within the verum group both during a short-term, i.e. 4-week (p = 0.0397), as well as a long-term, i.e. 8-week (p = 0.0155), consumption period.
More importantly, continuous consumption of L. plantarum TENSIA® resulted in significantly different reduction (p = 0.0028) in oxidized-LDL (ox-LDL), the oxidative stress index (OSI) (p = 0.0004) and total peroxide count (TPX) (p = 0.0039) in the verum group as compared to the control.
The scientific research of the BioCC LLC proves that regular, at least for 8 week consumption of 50g/day probiotic Harmony® cheese comprising L. plantarum TENSIA® helps to maintain the cardio-vascular system / heart health through reduction of blood pressure, and also by improvement of the antioxidant defence of human body.
Ongoing clinical trials:
Effect of a dietary supplement containing L. plantarum TENSIA® DSM21380 on subjects with high-normal blood pressure up to grade-1 hypertension.
An 8-week randomised blinded placebo-controlled parallel designed two-armed study incl. 2-week follow-up period.
Clinical trial is conducted in Estonia, EU from October 2017 – December 2020.
Independent human trial in Russia
A DBPC study carried out between E-piim Production Ltd (Estonia) and the Institute of Nutrition under the Russian Academy of Medical Sciences in Moscow (Russia) evaluated the clinical efficacy of a hypocaloric diet supplemented with Harmony® cheese comprising L. plantarum TENSIA® in Russian adult patients with obesity and hypertension with accompanying diseases with standard treatment.
Summary of the trial:
- More efficient reduction of body mass index in the L. plantarum TENSIA® group compared with control
- Significant decrease of water content after probiotic cheese consumption.
- Significant association between plantarum TENSIA® colonization and blood pressure reduction
- Significant reduction of the plasma triglyceride level in the probiotic group.
According to research results with subjects with metabolic syndrome from the Russian Food Institute (Russian Academy of Science) the Harmony® cheese comprising L. plantarum TENSIA® is a functional product with a special marking and E-Piim production Ltd has entered the Russian market.
The effect of 3 weeks of consumption of L. plantarum TENSIA® with yoghurt has been assessed in cross-over double-blinded intervention (ISRCTN79645828) with healthy adults (n = 43) in daily dose of 6 × 109 CFU.
For details see: Hütt, P, Songisepp, E, Rätsep, M, Mahlapuu, R, Kilk, K, Mikelsaar, M “Impact of probiotic L. plantarum TENSIA® in different dairy products on anthropometric and blood biochemical indices of healthy adults” Beneficial Microbes 2015 1;6(3):233-43.
L. plantarum TENSIA® tolerates technological processing well and copes well with different stressors. The strain withstands the manufacturing process of food, is able to multiply at relatively low (+12oC) and high (+45oC) temperatures and in a carbohydrate-scarce medium. TENSIA® is able to survive at 55oC. The lyophilised strain tolerates 80oC for 4 hours without loss in viability in an environment with aw < 0.95
BioCC has developed concepts for the creation of TENSIA® containing food products and dietary supplements.
Used in products
Hütt, P, Songisepp, E, Rätsep, M, Mahlapuu, R, Kilk, K, Mikelsaar, M
„Impact of probiotic plantarum TENSIA in different dairy products on anthropometric and blood biochemical indices of healthy adults” Beneficial Microbes 2015 1;6(3):233-43.
Hütt P, Rätsep M, Vallas M, Songisepp
E. Lactobacillus plantarum TENSIA DSM 21380 helps to maintain heart health through lowering (high-normal) blood pressure. Bulletin of the IDF 2014; 472: 1-10
Sharafedtinov K K, Plotnikova O A, Alexeeva R I, Sentsova T B, Songisepp E, Stsepetova J, Smidt I, Mikelsaar M.
Hypocaloric diet supplemented with probiotic cheese improves body mass index and blood pressure indices of obese hypertensive patients – a randomized double-blind placebo-controlled pilot study. Nutrition Journal 2013, 12:138
Mikelsaar M., Hutt P., Stsepetova J., Smidt I., Shkut E., Ratsep M., Zilmer M., Songisepp E.
Probiotic Heart cheese «Harmony» comprising plantarum TENSIA, influences blood pressure and metabolic health indices. Voprosy pitania 2012, 81(3), 74-81 In Russian
Sharafetdinov Kh.Kh., Plotnikova O.A., Alekseeva R.I., Sentsova T.B., Kaganov B.S.
Influence of a low-calorie diet with inclusion of probiotic product containing bacterias Lactobacillus plantarum TENSIA®. ™ DSM 21380 on clinical and metabolic characteristics in patients with obesity and arterial hypertension. Voprosy pitania 2012, 81(1), 80-85 In Russian