Lactobacillus fermentum ME-3 A New Frontier in Glutathione Therapy

Glutathione is essential to the functioning of each and every cell in the human body, but modern times have made it increasingly challenging for our stores to be maintained at optimal levels. Could a 'good bacteria' called Lactobacillus fermentum help support this increasingly prevalent deficiency? 

Lactobacillus fermentum ME-3 (often referred to as ME-3) is a strain of probiotic bacteria that was discovered and isolated at the University of Tartu, Estonia in 1995. At the time, scientists were surveying a wide range of Lactobacillus bacteria, looking for strains that might exhibit antioxidant activity. When ME-3 was tested, it was found to express extremely high antioxidant activity.[1] Subsequent studies revealed that Lactobacillus fermentum ME-3 synthesizes glutathione.

Glutathione, which is made in all cells throughout the body, is referred to as the Master Antioxidant.[2] It is also important for functioning of the immune system[3] and a critical regulator of detoxification in all cells.[4] Because glutathione levels are so important to these major body systems, it has become recognized as a key biomarker of aging.[5]

The purpose of this article is to explain Lactobacillus fermentum ME-3’s remarkable benefits and to summarize the overall importance of glutathione to human health.

Structure of Glutathione

Glutathione is composed of three amino acids: glutamate, cysteine and glycine. Glutathione’s power as an antioxidant is due to its sulfhydryl (-SH) group on the cysteine portion of the structure shown above. Glutathione can “donate” the hydrogen proton from the sulfhydryl group, which neutralizes free radicals.[6]

A substantial body of research links glutathione depletion with a greater incidence of many diseases and accelerated aging. For example, it has been reported that low plasma glutathione levels represent an increased risk for cardiovascular disease,[7] diabetes,[8] rheumatoid arthritis,[9] and Alzheimer’s disease.[10]

In addition to synthesizing glutathione, Lactobacillus fermentum ME-3 is also able to recycle oxidized glutathione (GSSG), which is inactive, back to its active state (GSH), which is reduced glutathione.[11]

Glutathione levels have also been shown to parallel telomere length and telomerase activity, which is an important indicator of lifespan.[12] Telomeres have been compared to the little protective plastic tips on the ends of shoelaces. Telomers are repetitive sections of DNA at the end of a strand of DNA that protect chromosomes. Each time a cell divides, the telomers shorten. Low levels of glutathione are associated with an accelerated rate of telomere shortening.[13] Both telomers and glutathione are now recognized as biomarkers of aging.

Glutathione depletion is also associated with progressive loss of mitochondrial function due to mitochondrial DNA (mDNA) damage.[14] In animal studies, protecting mitochondrial DNA from damage is directly proportional to longevity.[15] In a human clinical trial with elderly adults, it was reported that higher glutathione levels are associated with a lower incidence of illnesses and higher levels of self-perceived health. These studies suggest that glutathione levels may be a potential marker of physiological and functional aging.[16]

Glutathione’s antioxidant activity is especially important for systems in the body that have a high rate of metabolic activity such as the immune system[17], nervous system[18], gastrointestinal system[19], and the liver[20].

Lactobacillus fermentum ME-3 also produces the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD).[21] Mitochondria consume over 90 percent of the oxygen used by cells, which makes them especially vulnerable to oxidative free radical damage.[22] In fact, it is estimated that from 1-3% of the oxygen entering the mitochondrial electron transport chain is converted into the singlet oxygen free radical (O₂⁻), which makes it the most abundant free radical occurring in the human body.[23] Manganese superoxide dismutase (MnSOD) is critically important because it is the primary antioxidant that neutralizes the highly reactive superoxide free radical. Because MnSOD constitutes the first line of defense in cells against oxidative stress in mitochondria,[24] it is sometimes referred to as the Guardian of the Powerhouse.[25]

Lactobacillus fermentum ME-3 provides additional antioxidant power because it helps regenerate or recycle other oxidized antioxidants such as vitamin C, vitamin E, lipoic acid and coenzyme back to their active forms. Because Lactobacillus fermentum ME-3 produces two of the body’s most powerful antioxidants, glutathione and MnSOD, it has been shown to have the highest Total Antioxidant Activity (TAA) and the highest Total Antioxidant Status (TAS) of any probiotic tested to date.^[26]

Lactobacillus fermentum ME-3 has also been shown to have a positive effect on important cardiovascular risk factors as evidenced by the results from the following 2-week double-blind, placebo-controlled human clinical trial. Subjects taking ME-3 had reductions in oxidized LDL-cholesterol and triglycerides along with an increase in both HDL-cholesterol and paraoxonase. In addition to having antioxidant activity, paraoxonase enzymes are important because they detoxify some key agricultural pesticides.[27] During this clinical trial, the values of these markers all got slightly worse for the placebo control subjects.

Glutathione is also a key regulator of detoxification in all cells, but especially in the liver. Although detoxification clinical trials have not been conducted with ME-3 specifically, scientists conclude that ME-3’s ability to increase glutathione levels will result in improved detoxification.

Glutathione regulates many important detoxification processes including toxic metals such as mercury[28] and cadmium[29], reactive oxygen species (ROS)[30] and a wide range of xenobiotics[31]. Glutathione also gets depleted during the process of detoxifying substances that many people are commonly exposed to such as alcohol[32], artificial sweeteners such as aspartame[33], tobacco smoke[34], and the commonly used analgesic acetaminophen[35].

Lactobacillus fermentum ME-3 produces short-chain fatty acids (SCFAs), hydrogen peroxide, and nitric oxide.[36] These postbiotic metabolites help promote healthy bacterial balance in the gastrointestinal tract.

Lactobacillus fermentum ME-3 also helps lower several key inflammatory markers such as high sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6). Studies show that ME-3 also stimulates production of the peptide adiponectin and reduces levels of glycated hemoglobin.[37] These functions each play a role in managing inflammatory activity.

Organophosphates are one of the most commonly used pesticides worldwide. They are sprayed on commercial food crops and are a primary ingredient in many pesticide and insecticide products used in residential homes and gardens. They are also used commercially in plasticizers, as antifoaming agents in lubricants and hydraulic fluids and flame-retardants.

Lactobacillus fermentum ME-3 upregulates the activity of a paraoxonase enzyme called PON1, which helps detoxify organophosphates.[38] A 2004 report stated the following, “Almost every person is, or has been, exposed to organophosphate insecticides in their home, work or environment.”[39] In a study titled Forth National Report on Human Exposure to Environmental Chemicals, it was reported that 93% of children tested had measurable metabolites of organophosphates.[40] Studies have linked childhood organophosphate exposure a to higher incidence of ADHD[41] and autism[42].

In order to be effective, a probiotic must be able to withstand and survive exposure to the extremely acidic condition in the stomach. Studies with Lactobacillus fermentum ME-3 reveal that it survives at pH values ranging from 4.0 to 2.5 without a loss in viable cell count. Even at pH 2.0, the ME-3 strain survived for up to 6 hours. When exposed to bile acids, ME-3 survived for 24 hours without significant loss of live bacteria.[43] Thus, while testing in the human body has not been conducted, in vitro testing suggests that Lactobacillus fermentum ME-3 can tolerate exposure to harsh acidity in the stomach as well as exposure to bile acids in the small intestine. Hence, Lactobacillus fermentum ME-3 thrives and survives in conditions that simulate the harsh environments of the human gastrointestinal tract.

Lactobacillus fermentum ME-3: Summary of Human Clinical Trials

1. Reduction in Oxidized LDL-Cholesterol: The first column shows that individuals taking ME-3 had a 16% reduction in the levels of oxidized LDL-cholesterol compared to placebo controls.[44]
2. Reduced 8-Isoprostanes: The second column reports that people taking ME-3 had a 20% reduction in levels of 8-isoprostanes, which indicates reduced amounts of free radical damage due to ME-3’s antioxidant activity.[45]
3. Elevated Glutathione: The study reported in the third column shows that people taking ME-3 had a remarkable 49% increase in the ratio of reduced to oxidized glutathione.[46]
4. Probiotics, Oxidative Stress, Inflammation and Diseases: [47] The fourth column reports the increase in Total Antioxidant Activity (TAA) gained by the individuals taking Lactobacillus fermentum ME-3. (data for this comes from the following 2 studies; individual results are not shown on graph)

In the late 1980s, Drs. Calvin Lang and John Richie began studying glutathione’s effect on aging. In their initial study, they administered a glutathione precursor to the drinking water of mosquitoes which resulted increased glutathione levels 50-100%. Boosting glutathione resulted in a 30-38% increase in lifespan over controls.[48] To date, in all other animal models that have been tested, boosting glutathione has resulted in better health and increased longevity.[49]

Glutathione deficiency is associated with increased risks to chronic degenerative diseases and increased glutathione levels are associated with better health and increased longevity. An increasing body of scientific research supports the ‘Glutathione Deficiency Hypothesis’, which suggests that glutathione deficiency is a primary biochemical mechanism of aging that can be effectively modified by boosting glutathione levels. Consequently, it has been suggested that glutathione levels are effective and reliable biomarker of aging.[50] Thus, increasing glutathione levels by taking Lactobacillus fermentum ME-3 is an effective proactive step people can take to improve their health and increase their longevity.

AVAILABILITY OF LACTOBACILLUS FERMENTUM ME-3:

The patent for Lactobacillus fermentum ME-3 is held by the University of Tartu in Estonia. World-wide distribution rights have been signed to VF Bioscience/Belgium. To locate products containing ME-3, type Lactobacillus fermentum ME-3 in the search field of your internet browser.