Lactobacillus frementum ME-3: A Probiotic with Antioxidant Activities


Lactobacillus fermentum is a Gram-positive species of bacterium in the genus Lactobacillus. IT is a normal inhabitant of the human intestinal tract.

There are two known commercialized strains of Lactobacillus fermentum:

Lactobacillus fermentum

  • Lactobacillus fermentum VRI-003 PCC®
  • Lactobacillus fermentum strain ME-3 DSM-14241

Lactobacillus fermentus ME-3 was discovered in 1994 when joint research between The University of Linkoping initiated a scientific cooperative agreement between the Department of Pediatrics and the Department of Microbiology of the University of Tartu. The agreement aimed to find associations between allergies and intestinal microbiota.

Professor Marika Mikelsaar of the The University of Tartu led the joint research project since her and her team had long-lasting experience in research into microbial ecology and the lactobacilli of the human organism.

Their discovery of L. fermentum showed that it had double functional properties:

  • Antimicrobial activity against intestinal pathogens
  • High total antioxidative activity (TAA) and total antioxidative status (TAS) characterized by a complete glutathione system of synthesis, uptake and redox turnover.

In April 2009, Marika Mikelsaar, published in Microbial Ecology in Health and Disease an article entitled, Lactobacillus fermentum ME-3 – an antimicrobial and antioxidative probiotic.

They demonstrated that Lactobacillus fermentum ME-3 was able to lower the level of oxidized LDL cholesterol and thus improve cardiovascular disease.

Figure 7 from the article illustrates the balance of oxidative stressor (pro-oxidants) and antioxidant defense systems. The verbiage underneath the diagram is reproduced below:

“A net of prooxidants and the potency of antioxidant defence system normally balanced in the human body. (a) A summary effect of oxidative stressors and potency of antioxidant defence system of the human body are normally balanced. An imbalance leads to oxidative stress. PUFA, polyunsaturated fatty acids; SOD, superoxide dismutase; GSHPx, glutathione peroxidase; CAT, catalase; HO1, haem oxygenase; GSH, reduced glutathione. (b) Oxidative stress causes the production of oxidized LDL (oxLDL), which is a potent atherogenic and inflammatory agent. Strain ME-3 lowers the level of oxLDL. LDL, low-density lipoprotein; CVD, cardiovascular diseases.” (Source)



The authors started to check the antioxidant charecteristics of Lactobacillus fermentum ME-3. Table IV (from the article) lists the antioxidative properties of L. fermentum ME-3:

Table IV

Antioxidativity-related properties and effects of strain ME-3.

Property/effect Experimental (ES), animal (AS), human (HS) study (reference nos)
Expression of Mn-SOD, prolonged survival time in presence of high H2O2, scavenging of superoxide and hydroxyl radicals ES (156)
Characterized by high TAA and TAS values ES (156,157)
Containing of GSH and related antioxidative enzymes ES (157,158)
Working as natural antioxidant in soft cheese spreads with different fats ES (159)
Maintaining its high TAA during production of probiotic cheese ES (136)
Removal effect of metals (prooxidants) from environment ES (160)
Elevation of blood TAS or TAA and TAA in the gut mucosa HS, AS (100,102,157,161,162)
Elevation of oxyresistance of LDL HS (100,157,162)
Lowering level of oxLDL HS (100,102,162)
Lowering level of isoprostanes HS (100,162,163)
Lowering the glutathione redox ratio in blood, in the gut mucosa, in skin HS, AS (100,102,157,161,164)
Lowering lipid peroxidation in the gut mucosa AS (161,164)
Lowering level of BCD-LDL HS (100,162,167)
Positive effects on post-prandial status of OxS, blood lipoprotein status and urine isoprostanes HS (162,163)

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“BCD-LDL, baseline diene conjugates in low-density lipoprotein; GSH, reduced glutathione; H2O2, hydrogen peroxide; LDL, low-density lipoprotein; Mn-SOD, manganese superoxide dismutase; oxLDL, oxidized low-density lipoprotein; OxS, oxidative stress; TAA, total antioxidative activity; TAS, total antioxidative status. (Source)

In 2010 an article in Prikladnaja biohimija i mikrobiologija apperaed by the authors Kullisaar T, Songisepp E, Aunapuu M, Kilk K, Arend A, Mikelsaar M, Rehema A, Zilmer M. The title of the article is Complete glutathione system in probiotic Lactobacillus fermentum ME-3.

The abstract of the article demonstrates a complete glutathione system with Lactobacillus fermentum ME-3:

“Results of this study show that probiotic L. fermentum ME-3 contains both glutathione peroxidase and glutathione reductase. We also present that L. fermentum ME-3 can transport GSH from environment and synthesize GSH. This means that it is characterized by a complete glutathione system: synthesis, uptake and redox turnover ability that makes L. fermentum ME-3 a perfect protector against oxidative stress.” (Source)

On August 4, 2004, U.S. Patent US20040151708 A1 was published with the U.S. Patent and Trademark Office. The inventors were Marika Mikelsaar, Mikhel Zilmer, Tiiu Kullisaaar, Heidi Annuk, Epp Songisepp and was entitled Strain of micro-organism lactobacillus fermentum me-3 as novel anti-microbial and anti-oxidative probiotic.

On July 3, 2014, inventors Marika Mikelsaar, Mikhel Zilmer, Tiiu Kullisaaar, Heidi Annuk, Epp Songisepp through the applicant University of Tartu, U.S. Patent WO2014102692 A1 was published. It is entitled Method of treatment using lactobacillus fermentum me-3.

In the U.S., Lactobacillus fermentum ME-3 is marketed by Essential Formulas Incorporated under the trademark name Reg’Activ.

Lactobacillus fermentum ME-3 can also be found in the Hellus product line of foods. Hellus is a Estonian food manufacturer an their products are sold mainly in Europe.

Another product called Reg’Activ Cholesterol exists primarily in Europe.

“The product Reg’Activ Cholesterol has been specially formulated for cardiovascular health. This innovative formulation combines L. fermentum ME-3 with functional ingredients, exerting a triple effect on cholesterol levels, protection against oxidative stress, and metabolism of homocysteine.” (Source)


Reg’Activ – Essential Formulas

Hellus products (Estonia)

Reg’Activ Cholesterol (Europe)

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