It’s hard to imagine that our gut could play such a big role in detoxification but it does. We are learning more about the gut microbiome and all the probiotic strains that help support good health. Sometimes I get frustrated when people just focus on one little bitty thing, like one supplement (say vitamin C for example, or zinc) as if it were the cure for all diseases. I think big picture, like antioxidants that are made in every cell, trillions of them, every day, every second for that matter. God-given antioxidants and today my focus is glutathione. I focus a lot on glutathione because both me and Sam (and 4 of our closest friends) are all deficient. It’s one of those antioxidants that has wide-spread effects from head to toe, and it’s important to protecting our DNA, and we all know that DNA damage can increase our risk for all sorts of diseases including cancer. The longer we live, the more depleted our glutathione stores are, and the higher our risk for cancer is. There’s a new probiotic strain that naturally boosts glutathione, but before I give you details on how to buy it and where it’s sold I want to make the case for glutathione.
First the Facts
Fact: We make glutathione in our body, all of us do.
Fact: Glutathione is depleted very quickly because we really challenge our bodies and cellular trash needs to be taken out. Antioxidant production is key to reducing free radicals. Several trillion mitochondria depend on glutathione for their sheer survival. See my image above to see what a cell looks like. The green and orange organelles are your mitochondria. In total, you have several pounds of these mitochondria energy-generators and they need glutathione to protect them.
Fact: Hundreds of medications (I call them “drug muggers”) deplete your natural warehouse of glutathione; so does drinking beer, a glass of wine or any alcohol use. This might surprise you but acetaminophen (paracetamol) is a strong drug mugger of glutathione in case you use that for pain relief.
Fact: Almost all supplements of glutathione are big and bulky and appear to degrade in the gut when taken orally. Most supplements do not easily penetrate your cells and get into the mitochondria to help you which is why ‘cooking it up’ inside your cells is critical to producing healthy amounts of it. Fact: Intracellular production of glutathione is challenged by the availability of the three amino acids necessary for glutathione production namely cysteine, glutamine and glycine.
Fact: Glutathione regenerates other powerful antioxidants like vitamin C and vitamin E just when you think they are used up. It basically gives them a second shot at snatching up harmful compounds all over your body, think of it as giving these antioxidants a “buy one get one free” deal! Without glutathione, these antioxidants only get to clean you up one time around. Cellular trash needs to be taken out and glutathione is just one powerful antioxidant that is essential to our body. By the very nature of their physiological tasks, your liver, heart and immune system all require adequate amounts of glutathione to keep you healthy. If you’d like to know more about glutathione, please refer to this article, Chronic Illness Responds to Glutathione.
Today I’d like to share big news about a probiotic strain that is newly available on the market. The full name is Lactobacillus Fermentum ME-3. Let me break that down for you:
In the scientific literature you will likely see it abbreviated as “L. Fermentum ME-3.”
ME-3 refers to the strain and again, this is a relatively newly discovered probiotic strain that is now patented for it’s special ability to boost glutathione levels. It is a multi-tasking probiotic strain unlike some strains which are just good for traveler’s diarrhea for example.
Here’s the story
L. fermentum ME-3 was first isolated in 1995 by Marika Mikelsaar, MD, PhD and her team at the University of Tartu, in Estonia. This is one smart woman who ultimately won an award for her work as a microbiologist in 2007. Professor and Doctor Marika Mikelsaar received the European Union award for the discovery of L. fermentum ME-3. Prior to her discovery of ME-3, she had been working with the Russian Space Program and studying the intestinal microflora of Russian astronauts. She didn’t get to go fly in a rocket ship or go into space, she just studied their gut microbiome day in day out, and as I think about it, that task alone deserves some kind of award LOL! Anyway, bless her heart, in 1995 she isolated L. fermentum ME-3 and since that time a lot of research has gone into finding out the health benefits of the lactobacillus-related probiotic.
An extensive amount of research on ME-3 has been conducted by Mihkel Zilmer, MD, PhD who also works at the University of Tartu in Estonia and his focus is on how this probiotic surprisingly boosts glutathione, a powerful antioxidant. This glutathione-boosting aspect came as a bit of a surprise. You see, this is not typical of probiotics which are most often associated with gut health and immunity.
Since I study Functional Medicine and its clinical applications I know that glutathione plays a crucial role in our antioxidant defenses and detoxification pathways. It is virtually impossible to take a truly effective supplement of it. They work but only to a certain point. You can absolutely take supplements of glutathione, however my point is it’s really hard to get a high enough level of glutathione with supplements because you don’t know what portion is oxidizing (back-firing on you) and what portion is actually getting into the cell to do its house-keeping duties.
Taking glutathione supplements by mouth may also trigger problems for people with a SNP in their transsulfuration pathway that causes them to feel poorly with sulfur-based foods, medications or dietary supplements. So to have a natural probiotic like L. fermentum ME-3 that raises glutathione naturally -and intracellulary- is really awesome and much anticipated.
L. fermentum ME-3 supplements do just that. They are sold under the brand name of Reg’Activ™ and there are 3 different formulas which you will learn more about below. One is for heart health, another for immune function and another for liver and detoxification. The company that distributes the Reg’Activ™ formulas is Essential Formula’s Inc, and I proudly represent them, even more proudly now for they have brought something very special to the world and I’m excited to share the news.
L. fermentum ME-3 Improves Glutathione via 3 Different Mechanisms
1) ME-3 synthesizes glutathione itself*
2) ME-3 regenerates reduced glutathione (GSSG) back into its active state (GSH)*
3) ME-3 takes any available glutathione molecules from it’s surrounding environment like a sponge.
Want more good stuff? Let’s go…
More glutathione, BAM!
ME-3 substantially increases glutathione levels.* We can safely deduce it will increase glutathione’s capability for detoxifying. Glutathione is known to support the body’s normal detoxification systems particularly in regard to heavy metals like mercury, arsenic and lead. Glutathione is known to help neutralize air pollutants and agricultural pesticides. Speaking of…
Organophosphates are one of the most widely used pesticides in the entire world sprayed on commercial food crops. These compounds are also used in plasticizers, flame retardants and hydraulic fluids. Some of us (like me) make an enzyme in our body naturally called PON1 or paraoxonase 1 which helps a little in terms of detoxifying organophosphates but if you have a SNP in the PON1 gene like my husband Sam and a couple of my friends, well then you have a really hard time detoxifying these poisons. You need to be incredibly careful about eating them, and buy organic whenever possible. Almost every person is exposed to organophosphates which are dangerously “sticky” to our cells, even if you have a fully functional PON1 gene and enzyme system. It’s just super exciting to me to have a natural probiotic that helps the body respond to typical exposure to organophosphates. The L. fermentum ME3 probiotic may be especially useful for people with a PON1 gene because it helps detoxify organophosphates.*
To learn more about PON1 and other genes, later on go read my article, Genes, Methylation & Your Health.
Love your liver.
It’s not the most glamorous organ I know. But liver health is crucial to detoxification, after all that is where your enzyme systems are born. Most people ignore their liver altogether unless you are told it’s “fatty” or “compromised” and then your liver gets your attention. Herbs that support liver include milk thistle and artichoke but what about glutathione? Do you realize that’s where most of your glutathione is made? The glutathione pathway is one of the mechanisms for neutralizing and removing a wide range of toxins in the body. L. fermentum ME-3 has the ability to increase total antioxidant activity and may help support a healthy liver.*
Reduce pro-inflammatory cytokines.
Systemic inflammation plays a role in pain and cardiovascular disease. L. fermentum ME-3 has been shown to help maintain healthy levels of several key markers such as high-sensitivity C-reactive protein (if you’re looking on your lab it is hs-CRP), and interleukin 6 (or IL-6) that are already within the normal range.* There are probably others but they have not been teased out, after all ME-3 is kind of like a new kid on the block.
Lower sticky fats, without a statin?
Hmm…yes I think so! L. fermentum ME-3 has been shown to help maintain triglyceride levels already in the normal range and increase levels of the “good” HDL cholesterol* It even helps maintain healthy levels of oxidized LDL-cholesterol already within the normal range.*
Who here wants lower blood sugar?! ME-3 is capable of stimulating production of adiponectin* which you read about in my book Diabetes Without Drugs. Adiponectin is a hormone that when deficient plays a role in atherosclerosis and insulin resistance. Since we are on this tangent of diabetes, I may as well tell you L. fermentum ME- was shown to reduce levels of glycated hemoglobin* or hemoglobin A1c, shown on your lab as HbA1c. This is a biomarker for blood sugar often measured in people with diabetes or metabolic syndrome.
ME-3 is a survivor!
Probiotics have to be able to survive your stomach acid and L. fermentum ME-3 easily withstands highly acidic conditions in the stomach as well as exposure to the digestive bile acids present in your small intestine. At a pH of 2.0 which is really acidic, the ME-3 strain survived up to 6 hours.* When exposed to bile acids, it survived for 24 hours without significant loss of bacteria.*
Where can you buy it?
There are hundreds of stores now carrying the special Reg’Activ™ formulas and you can find a list here, and also put in your zip code to find the closest location. Reg’Activ™ formulas are sold online as well.
You may buy here online and I have arranged Free First Class Shipping for all of you…
Summary of Human Clinical Trials With Lactobacillus fermentum ME-3
Title: An antioxidant probiotic reduces postprandial lipemia and oxidative stress.
Journal: Central European Journal of Biology. 2011;Vol. 6(1): pp. 32-40.
Authors: Tiiu Kullisaar, Jelena Shepetova, Kersti Zilmer, Epp Songisepp,
Aune Rehema, Marika Mikelsaar, Mihkel Zilmer
Subjects: One hundred clinically healthy volunteers (75 females, 25 males, age 40-65 years) were recruited into a double-blind placebo-controlled randomized study.
For various reasons, 25 people in the control group and 2 in the treated group dropped out. Hence, the results are based on 48 treated subjects and 25 controls.
Study Design: This study utilized kefir with ME-3 added as the test agent and kefir without any probiotic as the control agent. Both kefir solutions were identical nutrient composition, color, taste, and caloric value. Volunteers all consumed an identical standard meal.
Testing: After a 2-week introductory period, baseline blood and urine samples were obtained 2.5 hours after ingestion of the standard meal. Then volunteers also ingested 200 ml of kefir with ME-3 or control kefir daily for two weeks and were then re-tested.
Results: Volunteers ingesting kefir containing ME-3 exhibited the following:
a) -16% in oxidized LDL-cholesterol (reduces cardiovascular disease risks)
b) -20% in 8-isoprostanes (reduction in free radical damage)
c) 10% increase in HDL-cholesterol
d) 18% increase in paraoxonase enzyme activity (PON1) which regulates
detoxification of pesticides and provides antioxidant activity
e) 10% decline in triglycerides
Title: Antioxidative probiotic fermented goats’ milk decreases oxidative stress-mediated atherogenicity in human subjects.
Journal: British Journal of Nutrition. 2003; Vol. 90; pp.449-456.
Authors: Tiiu Kullisaar, Epp Songisepp, Marika Mikelsaar, Kersti Zilmer,
Tiiu Vihalemm, and Mihkel Zilmer
Subjects: Twenty-one healthy subjects (aged 35-65) divided into 2 groups.
Study Design: during the 3-week study, 16 participants consumed 150 grams of goats’ milk fermented with Lactobacillus fermentum ME-3 (test group) while 5 participants ingested 150 g fresh goats’ milk without probiotics (control group).
Testing: Blood and urine samples were initially tested and then again at the end of the 3-week trial. Blood was analyzed for total antioxidant activity (TAA), total antioxidant status (TAS), ratio of oxidized to reduced glutathione, oxidized LDL-cholesterol and 8-isoprostanes (measure of free radical damage to unsaturated fatty acids). Also, fecal samples were collected at the beginning (day 0) and again at the end of the trial (day 21).
Survivability & Gastrointestinal Persistence: Initial testing reported that Lactobacillus fermentum was present in the intestinal tract of only 4 of the 16 test subjects. At the end of the trial, fecal samples revealed that the GI tract of all 16 test subjects were colonized with ME-3. Furthermore, testing also revealed that ingesting goats’ milk fermented with Lactobacillus fermentum ME-3 resulted in a doubling of live ME-3 bacteria in the intestinal tract.
These results provide two important pieces of data:
When taken orally, ME-3 survives transit through stomach, which means it does not get killed when exposed to strong stomach acids.
When orally ingested ME-3 arrives in the intestinal tract, the bacteria are able to adhere to the mucosal lining and grow/multiply as evidenced by doubling the concentration of live ME-3 bacteria after 21 days.
Reduction of Cardiovascular Risks: Free radical damage to lipoproteins (oxidized LDL-cholesterol) can ultimately damage cells that line the arteries, resulting in plaque build-up and atherosclerosis, which is one of the primary causes of cardiovascular disease. ME-3’s antioxidant activity resulted in a substantial decrease in oxidized LDL-cholesterol.
Increased Antioxidant Protection:
The ME-3 test subjects exhibited a substantial reduction in urinary levels of 8-isoprostanes (8-EPI) which is recognized as one of the most reliable ways of measuring oxidative stress.
One of the most significant findings was that oral ingestion of ME-3 resulted in a substantial improvement in the systemic ratio of reduced (active) glutathione to oxidized (inactive) glutathione, which indicates a significant improvement in antioxidant protection throughout the entire body.
Significant increase in Total Antioxidant Activity (TAA), which also indicates an improvement in both cellular and whole body antioxidant activity.
Title: Probiotics, Oxidative Stress, Inflammation and Diseases
Publication: 4th Central European Congress on Food. May 15-17, Caveat, Croatia.
Authors: Tiiu Kullisaar, Marika Mikelsaar, Sirje Kaur, Epp Songisepp, Kersti Zilmer,
Pirje Jutt, Aet Lukmann, Jaak Maaroos, Jaak Kals, and Mihkel Zilmer
Part 1: Atopic Dermatitis: 11 patients with atopic dermatitis, ages 20-42 years old, randomized into 2 groups. During the 3-month trial, 5 patients consumed goats’ milk with ME-3 while 6 people acted as placebo controls.
Results: Patients with atopic dermatitis generally have abnormalities of their glutathione-system along with increased oxidative stress, inflammation and often impaired skin membrane barrier function. Individuals receiving ME-3 experienced significant improvements in skin condition, blood markers and in self-assessment rating scores.
Part 2: Brain Stroke: 21 patients (ages 71-89) who had experienced a brain stroke sometime between 8 to 22 days earlier were randomly divided into 2 groups. Subjects consumed either 3 capsules of ME-3 twice daily or 3 placebo capsules twice daily for time that ranged from 10 days to 3 weeks. Patients were evaluated on the Functional Independence Measure inventory (FIM) and on the Scandinavian Stroke Scale (SSS).
Results: Stroke patients consuming ME-3 exhibited significant improvements in both the Scandinavian Stroke Scale and the Functional Independence Measure inventory. 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 [PON] enzyme activity as well as reductions in markers of inflammation and free radical damage.
Part 3: Assay of Blood & Urine Markers: 15 healthy volunteers, ages (40-65). After a 2-week introductory period, the volunteers were randomized into a double-blind, placebo-controlled, crossover trial. Individuals ingested kefir with ME-3 or placebo kefir for two weeks. After a 3-week wash-out period, new blood & urine samples were taken and then subjects crossed over to take the alternate regime for an additional 2 weeks.
Results: Volunteers taking ME-3 experienced improvements in all blood and urine markers evaluated compared to controls.
Doses of Lactobacillus fermentum ME-3 Used in the Human Clinical Trials
Capsules: In most of the studies where the test subjects were taking capsules containing Lactobacillus fermentum ME-3, the dose was one billion bacteria per day. In the brain stroke study, the dose was 6 billion per day.
Kefir: The probiotic doses in kefir are substantially higher, providing approximately 20-30 billion bacteria per day.
NOTE: Even though the daily dose of ME-3 is much higher in the kefir delivery method compared to the dose of ME-3 in capsules, it is interesting to note that the magnitude of the beneficial changes (oxidized LDL-cholesterol, PON enzyme activity and total antioxidant status) are quite similar in the kefir trials compared to the capsule trials. This indicates large doses (20-30 billion) do not provide additional benefit beyond moderate doses containing several billion bacteria. The Reg’Activ formulas contain from 4 to 6 billion CFU of ME-3 per day.
1. Konstantinidis KT, Tiedje JM, Towards a Genome-Based Taxonomy for Prokaryotes. J Bacteriol. Sep 2005; 187(18):6258-6264
2. Mikelsaar M, Zilmar M., Lactobacillus fermentum ME-3… Microb Ecol Health Dis. Apr 2009;21(1):1-27.
3. Sepp E., et al., Intestinal microflora of Estonian and Swedish infants. Acta Paediatr. 1997 Sept;86(9):956-61
4. Mikelsaar M., Probiotic lactobacilli in antioxidative defence.
5. UT Professor Marika Mikelsaar Receives Prestigious EU Award:
6. Kullisaar T., et al., Complete glutathione system in probiotic Lactobacillus fermentum ME-3. Applied Biochemistry & Microbiology; Sep 2010,46(5):481.
7. US Patent, 20040151708 A1: https://www.google.com/patents/US20040151708
8. Fariss MW. et al., Role of Mitochondria in Toxic Oxidative Stress. Molecular Interventions. April 20015;5(2):94-111.
9. Hutt P, et al… Journal of Applied Microbiology. 2006; Vol.100:1324-1332.
10. Central European Journal of Biology 2011, vol. 6(1).
11. Holvoet P. Acta Cardiol. 2004 Oct;59(5):479-84.
12. Pastore A., et al., Analysis of glutathione:Implication in redox and detoxification. Clin Chim Acta. 2003 Jul 1:333(1);19-39.
13. Wu G., et al., Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92.
14. US Patent WO 2014102692 A1: Method of treatment using Lactobacillus fermentum ME-3.
15. Casida J, Quistad G., (2004). Organophosphate Toxicology: Safety Aspects of Nonacetylcholinesterase Secondary Targets. Chemical Research in Toxicology, Vol. 17, No.8, pp. 983-992.
16. Songisepp E. Evaluation of technilogical and functional properties of the new probiotic Lactobacillus fermentum ME-3. Diss Med Univ Tartuensis; 2005.