Benefits
Oxidized LDL and other oxidative stress markers
In an 8 week randomized double-blind trial in adults with borderline-high blood lipids, 200 ml a day of kefir with ME-3 lowered oxidized LDL by 6%, a larger change than with the same kefir without the strain, an outcome listed as primary in a registry entry made after the trial began; only the 76 of 164 people who finished were analyzed. A 100 person trial of the kefir reported lower oxidation markers after a meal without a placebo comparison.
Blood antioxidant activity in healthy adults
In a 3 week double-blind trial in 24 healthy adults, ME-3 capsules raised blood total antioxidative activity and status from baseline, only 4% and 2.5% more than placebo, with no between-group test reported, and the glutathione redox ratio did not change. In a 21 person open study, goat milk fermented with ME-3 and plain goat milk both raised these markers.
LDL cholesterol and triglycerides, blood lipid markers
In the 8 week kefir trial, LDL cholesterol, a stated main outcome along with triglycerides, fell 5% and triglycerides 17% with ME-3, and both changes differed from plain kefir (P = 0.037 and 0.044) among the 76 people who finished out of 164 randomized. These are lipid markers, not heart outcomes. An open study of a Reg'Activ product with red yeast rice had no control group.
Triglyceride response after a meal
In a randomized, double-blind, placebo-controlled trial in 100 healthy adults, kefir enriched with ME-3 was reported to lower blood triglycerides and oxidized LDL after a meal and to raise HDL cholesterol and paraoxonase activity. The published abstract does not give the dose, the trial length or the size of the differences from placebo kefir.
Gut lactobacilli and passage of the strain through the gut
In 3 week studies, total stool lactobacilli rose with ME-3 capsules and with fermented goat milk, and the strain was recovered from the stool of all 16 goat milk drinkers but not after capsules. In the 8 week kefir trial, ME-3 was found in stool in 8% of the probiotic group at the start, 62% at 4 weeks and 56% at 8 weeks. This shows passage, not lasting colonization.
Skin and blood oxidation markers in adults using emollients
In 16 adults with mild to moderate atopic dermatitis who all used emollients, the 10 who drank goat milk fermented with ME-3 for 3 months had larger falls in skin iron, skin diene conjugates and the skin glutathione redox ratio than 6 unsupplemented controls. There was no placebo, and the clinical severity score fell in both groups.
Mechanism of action
Glutathione made and recycled by the bacterium
In laboratory work, ME-3 contains glutathione peroxidase and glutathione reductase and can both take up and make glutathione, which its developers propose as the basis of its antioxidant effects. Whether this raises glutathione in people is not established: in the 3 week capsule trial the blood glutathione redox ratio did not change.
Bile salt breakdown and blood lipids
In a plate test, ME-3 showed bile salt hydrolase activity equal to one comparison strain and higher than two others. The kefir trial authors propose this, together with the strain's sugar-splitting enzymes, as a route to lower blood lipids. These are laboratory findings and were not measured in the people studied.
Gut barrier and glycation in cell and animal models
In human gut cell cultures, ME-3 limited the rise in permeability caused by the cancer drug irinotecan or by bacterial endotoxin and reduced inflammatory cytokine release. In diabetic mice given 10^10 CFU daily for 12 weeks, it reduced some glycation products in the kidneys; two authors of the mouse study were from VF Bioscience. Neither effect has been tested in people.
Clinical trials
Randomized, double-blind, placebo-controlled parallel trial; 200 ml a day of kefir containing ME-3 (8 x 10^9 CFU/day) versus the same kefir made without the strain, for 8 weeks; primary outcomes named in the paper LDL cholesterol and triglycerides; registered ISRCTN49744186 in 2014, after the trial began, with oxidized LDL and urinary isoprostanes also listed as primary outcomes; analysis of completers only; funded by the European Regional Development Fund, the Estonian Ministry of Education and Research and the University of Tartu; all authors from the University of Tartu, which holds a US patent on the strain, and three of them (Mikelsaar, Kullisaar and Zilmer) are named on that patent; not PubMed-indexed (Mikelsaar et al. 2015, BMC Nutr)
164 clinically healthy Estonian adults aged 35 to 65 with borderline-high LDL cholesterol or high triglycerides were randomized (83 kefir with ME-3, 81 plain kefir); 137 were measured at 4 weeks and 76 (43 and 33) at 8 weeks.
At 4 weeks, lipid profiles were mostly similar between groups, though triglycerides and oxidized LDL fell within the ME-3 group. At 8 weeks, among completers, LDL cholesterol fell 5%, triglycerides 17% and oxidized LDL 6% in the ME-3 group, and these changes differed from plain kefir (P = 0.037, 0.044 and 0.0002); total cholesterol rose in the plain kefir group. More than half of those randomized did not finish, only completers were analyzed, and diet was not recorded. Urinary isoprostanes, a registered primary outcome, were not reported. Body mass index, blood pressure and glucose did not change.
Randomized, double-blind, placebo-controlled trial of kefir enriched with ME-3; outcomes measured after a meal; the abstract gives no dose, duration or primary outcome; University of Tartu group that developed the strain, including patent inventors Kullisaar, Songisepp, Mikelsaar and Zilmer; not PubMed-indexed (Kullisaar et al. 2011, Cent Eur J Biol)
100 clinically healthy adults.
The abstract reports that the ME-3 kefir significantly reduced oxidized LDL, baseline diene conjugates in LDL, oxidized LDL bound to beta-2 glycoprotein, urinary 8-isoprostanes and triglycerides after the meal, and raised HDL cholesterol and paraoxonase activity. It does not say whether these were comparisons with placebo kefir or within-group changes, and gives no effect sizes; the full text is not openly available.
Randomized, double-blind, placebo-controlled trial; three capsules twice daily (8.4 log CFU per capsule, stated daily dose 9.2 log CFU) versus identical capsules of saccharose and microcellulose for 3 weeks; registered ISRCTN53164826, with no primary outcome listed in the registry or paper; funded by Estonian Science Foundation, Estonian Technology Agency and EU grants; four authors (Songisepp, Kullisaar, Zilmer and Mikelsaar) share the strain's patent application (Songisepp et al. 2005, Nutr J)
24 healthy adults aged 40 to 60 in Estonia (12 per group); one member of the probiotic group was withdrawn with a respiratory infection.
Total stool lactobacilli rose from baseline with ME-3 and not with placebo, but ME-3 itself was not detected in stool. Blood total antioxidative activity and status rose from baseline; the extra rise over placebo was 4% and 2.5%, with no between-group test reported. The glutathione redox ratio did not change. No adverse effects on general welfare or gut function were recorded. Lab markers, not health outcomes.
Open study, randomization not described in the abstract: 150 g/day of goat milk fermented with ME-3 versus plain goat milk for 21 days; a 2005 report from the same group describes an open goat milk study of the same size, group split, dose and length, in which the fermented milk also contained two supporting strains (L. plantarum LB-4 and L. buchneri); University of Tartu group that developed the strain (Kullisaar et al. 2003, Br J Nutr)
21 healthy adults in Estonia (16 fermented goat milk, 5 plain goat milk; mean age 50 in the 2005 report).
The abstract reports that the fermented milk prolonged the resistance of lipoproteins to oxidation, lowered peroxidized lipoproteins, oxidized LDL, urinary 8-isoprostanes and the glutathione redox ratio, and raised total antioxidative activity. The 2005 report found that plain goat milk also raised antioxidant activity and lowered the glutathione redox ratio. Because the comparator was unfermented milk, the study tests the fermented product, not the strain alone.
Controlled study without placebo: goat milk fermented with ME-3 daily for 3 months (amount printed in the abstract as 200 mg/day) versus no supplement, with regular emollient use in both groups; University of Tartu group including strain inventors Kullisaar, Mikelsaar and Zilmer; not PubMed-indexed (Kaur et al. 2008, Cent Eur J Med)
16 adults with mild to moderate atopic dermatitis (10 fermented goat milk, 6 controls).
Skin iron, skin diene conjugates and the skin glutathione redox ratio fell more in the fermented milk group than in controls (P < 0.05 for each), and in that group blood oxidized LDL fell and reduced glutathione rose. A review by the developers reports that the clinical severity score (SCORAD) fell in both groups, from 4.8 to 1.9 with fermented milk and from 4.8 to 2.3 in controls. Markers, not a test of skin symptoms.
Randomized, double-blind, placebo-controlled pilot; ME-3 capsules of about 10^9 CFU, three twice a day, or saccharose and microcellulose placebo capsules for 3 weeks alongside standard rehabilitation; described in a review by the strain's developers, with the primary report in congress proceedings (Mikelsaar and Zilmer 2009, Microb Ecol Health Dis)
21 patients, mean age about 80, about 12 days after a stroke (10 ME-3, 11 placebo).
Oxidized glutathione, oxidized LDL, diene conjugates and total antioxidant activity improved from baseline in the ME-3 group, and end values of oxidized LDL, oxidized glutathione and antioxidant activity differed from placebo, a comparison of end values rather than of changes. Functional independence scores improved more on placebo, which the authors attribute to a lower starting level in the ME-3 group. No functional benefit was shown.