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ME-3 Stability in Humans
To be effective, a probiotic must be able to survive exposure to the highly acidic conditions in the stomach and digestive enzymes and bile acids present in the small intestine.
The results of in vitro studies report that Lactobacillus fermentum ME-3 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 six hours. When exposed to bile acids, ME-3 survived for 24 hours without significant loss of live bacteria.44 Although testing in the human body has not been conducted, in vitro testing suggests that Lactobacillus fermentum ME-3 may be able to tolerate exposure to harsh acidity in the stomach and 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.
Human Clinical Trials
Figure 2 summarizes ME-3's antioxidant effects in human clinical trials, listed as follows:
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.45
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.46
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.47
4. Probiotics, Oxidative Stress, Inflammation and Diseases:48 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 two studies; individual results are not shown on graph.
Study 1 – Improved Atopic Dermatitis: Many patients with atopic dermatitis have genetic polymorphisms in glutathione-dependent enzymes, which results in increased oxidative stress, inflammation, and impaired skin membrane barrier function.49 Individuals receiving ME-3 experienced significant reduction in inflammation with accompanying improvements in skin condition, blood markers, and in self-assessment rating scores.50
Study 2 – Improved Stroke Recovery: Stroke patients consuming ME-3 exhibited significant improvements in both the Scandinavian Stroke Scale (from 33 up to 42) and the Functional Independence Measure Inventory (from 21 up to 40). Stroke patients also experienced impressive improvements in the following blood markers: oxidized LDL-cholesterol, glutathione levels, ratio of reduced to oxidized glutathione, total antioxidant capacity, paraoxonase enzyme activity as well as reductions in markers of inflammation and free radical damage.51
In conclusion, new understanding that has emerged from the Human Microbiome Project is the concept of keystone strains of probiotic bacteria. Keystone strains are defined as sub-dominant strains of probiotic bacteria that are capable of exerting large biological effects. Lactobacillus fermentum ME-3, which produces glutathione, is a keystone strain of probiotic bacteria. When ingested by humans in doses ranging from 4 to 6 billion bacteria per daily dose, ME-3 has been shown to provide substantial reduction in inflammatory markers as well as improvements in antioxidant protection and detoxification. These biological changes are known to contribute to improvements in a wide range of health conditions. Consequently, glutathione-induced improvements in health correlate with the concept that glutathione levels are a biomarker of aging.
Figure 3: Glutathione: A Reliable Biomarker of Aging
Glutathione and Aging
In the late 1980s and 1990s, Drs. Calvin Lang and John Richie started studying glutathione's effect on aging. Their previous studies in mosquitoes, mice, and humans had shown that a deficiency of glutathione in many tissues and organisms is a general phenomenon of aging. They hypothesized that if glutathione deficiency could be corrected it would result in an increase in life span. In their initial study, they administered a glutathione precursor to the drinking water of mosquitoes, which resulted in a 50-100% increase in their glutathione levels. This resulted in a 30-38% increase in life span over control values.52
In a related study, Canadian researcher Dr. G. Buonous studied the effects of a glutathione-rich diet (whey protein) on glutathione levels and survival of 21-month-old mice (equivalent to 55-60 years old in humans) over six months, which was the equivalent of 80 years old in humans. Both tissue glutathione levels and longevity increased significantly over controls.53 Also, paralleling the decline in glutathione levels with aging in animals, other studies reported that glutathione levels gradually decline with aging in healthy men and women ranging in age from 20 to 94.54,55
Glutathione reductase is an enzyme that increases levels of reduced/active glutathione. Researchers in Denmark measured levels of glutathione reductase in 41 centenarians who were 100 to 105 years old and compared them with a similar group of average individuals between the ages of 60-79. The results showed that glutathione reductase levels in centenarians were higher than those in the younger elderly subjects. Also, glutathione reductase activity was highest in the centenarians who had the highest functional capabilities. Consequently, higher glutathione reductase activity, which increases reduced glutathione levels, seems to be associated with better health and increased life span.56
Paralleling the fact that higher glutathione levels are associated with better health and increased longevity are studies reporting that lower glutathione levels are associated with chronic diseases and that glutathione levels are a biomarker that can be used to monitor the severity and progress of diseases.57 In fact, lower glutathione levels are associated with a wide range of chronic degenerative diseases such as arthritis, HIV/AIDS, various cancers, cataracts, diabetes, heart disease, leukemia, kidney failure, hearing loss, macular degeneration, and urinary, GI, and musculoskeletal diseases.58,59,60,61
The evidence linking glutathione levels with greater health and increased longevity are causing some researchers to proclaim that glutathione is a reliable biomarker of aging. For example, a 2016 study published in Oxidative Medicine and Cellular Longevity is titled "Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity."62
Glutathione and Mitochondrial DNA
Low levels of glutathione have been shown to be associated with progressive loss of mitochondrial function, which results from accumulated damage to mitochondrial DNA (mtDNA).63 In animal studies, the ability to protect mitochondrial DNA from damage is directly proportional to longevity.64
Glutathione, Telomeres, and Telomerase
Telomeres are repeat sections of DNA located on the ends of each chromosome. The purpose of telomeres is to protect the ends of chromosomes, which allows cells to divide without damaging our genes. However, telomere shortening is a biomarker of aging. With each cellular division, telomeres shorten slightly and telomere shortening is the main cause of age-related breakdown of cells.65,66 In 2009, the Nobel Prize in Physiology or Medicine was awarded to three scientists for the discovery of how our chromosomes and DNA are protected by telomeres and the enzyme telomerase.67
Telomerase is an enzyme that can place additional DNA repeat sections on the ends of telomeres. Preliminary results from animal studies and human cell culture studies suggest that therapies which increase telomerase activity and lengthen telomeres hold the key to life extension and reducing the rate of aging.68
Glutathione levels have been shown to parallel telomerase activity, which is an important indicator of life span. The results of this study reveal that glutathione is a key regulator of telomerase activity. Furthermore, the authors of this study state that telomerase activity was found to be maximal when the ratio of reduced/oxidized glutathione was high.69 A study with elderly humans revealed that higher glutathione levels are associated with a lower incidence of illnesses and higher levels of self-rated health, which is what would be expected if elevated glutathione levels are increasing telomerase activity and lengthening telomeres.70
Because glutathione deficiency is associated with increased risks to chronic degenerative diseases and increased glutathione levels are associated with better health and increased longevity, it has been suggested that glutathione blood levels may be an effective and reliable marker of physiological/functional aging.70
The body of research that has been reviewed in this article shows clearly that higher glutathione levels are associated with better health and life extension. Thus, one of the most effective proactive steps people can take to improve their health and their longevity is to boost their glutathione levels. Lactobacillus fermentum ME-3 boosts glutathione levels. In human clinical trials, individuals taking ME-3 achieved a 49% increase in the ratio of reduced to oxidized glutathione.
Although Lactobacillus fermentum ME-3 is a stain of probiotic bacteria, products containing ME-3 should not be categorized as probiotics. Glutathione is so critically important to health that products containing ME-3 should be categorized as anti-aging and life extension products. Having a safe, effective way to boost glutathione levels daily has the potential to be a revolution is health and medicine.
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Ross Pelton is the Natural Pharmacist. He received his BS degree in pharmacy from the University of Wisconsin. He also has a PhD in psychology and is a certified clinical nutritionist (CCN). In October 1999, Ross was named as one of the Top 50 Most Influential Pharmacists in America by American Druggist magazine for his work in natural medicine. He is the author of ten books and numerous online health seminars. Ross is currently the scientific director for Essential Formulas. The link to his blog and personal website is http://naturalpharmacist.net.