Healthy Aging Tip #4 - Glutathione - The Master Defender against disease, toxins and aging

Healthy Aging Tip - # 4 Glutathione - The Master Defender against disease, toxins and aging.

Preface and reminder that the focus of Healthy Aging Tips (HATs) centers on what we can do to help minimize or (preferably) prevent accelerated or inappropriate aging which, of course, must begin by recognizing the causes of accelerated aging. These tips, at least initially, discuss some of the less commonly recommended methods to slow senescence.

At the top of the “Causes” list are Oxidation and Inflammation -- just two of many contributors to accelerated aging, yet highly significant. Excessive and inappropriate oxidation results in inflammation. Excessive, inappropriate inflammation leads to many medical problems at any age. We are all in various stages of the aging process, but there are numerous methods to help prevent accelerated aging.

The conclusion of first HAT report indicated, “Glutamine increases production of the main antioxidant in the body identified as Glutathione which is considered the “master antioxidant” which then boosts immune function, protects tissues from damage and detoxifies harmful substances. Glutathione helps repair damage caused by stress, pollution, radiation, infection, drugs, poor diet, aging, injury, trauma and burns.”_[7]

First published in 1986, Dr. Eric R. Braverman’s, classic and highly-informative reference on amino acids, The Healing Nutrients Within, details the “use of amino acids to achieve optimal health.” In this book, Dr. Braverman addresses the complexity of maintaining glutathione levels and covers the biochemical aspects in the chapter on L-Cysteine – a nonessential amino acid which is a precursor in the production of glutathione. However, various fairly recent studies assessing conversion efficacy of N-acetyl L-cysteine to glutathione indicate that is difficult and using NAC is not a reliably-effective method of increasing GSH.

When discussing maintenance of glutathione levels or repleting low levels, until quite recently, the best method was by IV infusions—often not easily accessible and can be costly. Previously, various oral GSH supplements had mixed reviews about efficacy. Now with the availability of GSH in the superior liposomal oral delivery form in both gel and capsules, reports and studies are showing good results. The unique liposomal structure by-passes digestive interferences which allows liposomal GSH to enter the blood stream directly and results in faster nutrient absorption and utilization. Reports and studies reference this liposomal form as “lipGSH.”

Critical points for this report are gleaned from books by Board Certified Cardiologist, Thomas E. Levy, MD, JD titled: GSH, Master Defender and Board Certified Functional Neurologist, David Perlmutter, MD, FACN, ABIHM and Fellow of the American College of Nutrition, Power Up Your Brain, along with several instructional reports by Dr. Levy in conjunction with LivOn Labs, source of supplemental Lipo-Spheric™ GSH; plus technical data from ProThera, Designs for Health and other GSH reports. There is also an abundance of YouTube clips with Dr. Levy.[References] While this report seems lengthy, it barely scratches the surface of this extensive topic. Following are just some of the key highlights:

INTRODUCTION

GLUTATHIONE LEVELS – PREDICTOR OF LONGEVITY
Glutathione (GSH) is a sulphuric tri-peptide molecule produced inside nearly every cell in the human body from three amino acids - glutamic acid, cysteine and glycine. Our glutathione level is a predictor of how long we’ll live. People living to 100 years old have GSH levels similar to that of 30 to 50 year olds. Typically, GSH begins to decline around age 45.

Healthy cells produce Glutathione. When cells run out of GSH, they die!

Chronic disease sufferers face even more of a repletion challenge since one-third of this population are missing the genes to create and manage glutathione levels._[1]

GSH is found in the highest levels in the liver, lining of lungs, kidney, heart, brain, eyes, spleen and pancreas. As a donator of electrons, GSH functions intracellularly and is the single-most important non-enzymatic antioxidant. GSH is considered the most powerful, “master antioxidant” in the body and is the main protector of normal cellular function. Vitamin C is the most important antioxidant everywhere else in the body. _[2,3,4]

Market research suggests fewer than 6% of consumers are familiar with the importance of glutathione; yet, a PubMed search reveals over 86,000 references for published clinical studies showing glutathione plays a central role in good health. Currently, there is significant interest in connections between health, longevity and GSH levels……obviously important and welcome news.

Thousands of clinical studies published in the last few years provide convincing proof that depleted cellular and blood levels of GSH precede disease and death; high levels improve health and extend life! Research conclusively shows that boosting GSH levels can improve immune system function and defend the body against free radicals, toxins, poisons, ionizing radiation, microorganisms (including bacteria, viruses, fungi, and parasites), emotional stress, physical stress, and premature aging._[2]

When intracellular GSH levels drop, oxidative stress increases and diseases of cells and then, eventually, tissue follow until a clinically-recognizable disease affecting the body is apparent. If a cell is diseased and has increased oxidative stress, then its glutathione levels will always be depressed. Chronic illness as well as long-term toxic exposure not only depletes stores of glutathione but also inhibits its production._[2]

FUNCTIONS OF GSH
• Helps protect cells from the damage caused by harmful free radicals
• Promotes detoxification and optimal cellular health
• Supports a healthy liver and immune system _[2]

Glutathione assists with detoxifying xenobiotics and heavy metals, neutralizes hydrogen peroxide, maintains the integrity of blood cells and helps transport amino acids across cell membranes. GSH aids in the breakdown of oxidized fats, is necessary for carbohydrate metabolism and is also involved in metabolizing insulin and regulating blood glucose levels._[5]

GSH supports neurotransmitter levels that affect mood and helps keep the brain functional and healthy. Toxic insults to the brain include its own natural production of reactive oxygen species (ROS) that produce oxidative stress and neuronal cell damage along with exposure to toxic metals, mycotoxins and pesticides. All can deplete GSH. Lyme patients with high levels of brain inflammation are frequently found to be low in GSH._[7]

GSH balances brain chemistry and makes brain receptors more sensitive to dopamine and serotonin, the neuro-transmitters critical for healthy brain function.
Catch 22: Antidepressants are found to deplete glutathione which may also help contribute to depression._[6]

GSH is a major protector of our detoxifying organ, the liver. Those who routinely take the pain medication acetaminophen (Tylenol) also called paracetamol or any of the other 600 medications on the market containing acetaminophen need to supplement to restore glutathione levels. In 2001, Registered Pharmacist, Suzy Cohen, was recommending the use of N-Acetyl Cysteine (NAC) to help helps protect the liver and restore glutathione levels; now we can go directly to the benefits of GSH by using the liposomal form._[8]

Since GSH production naturally declines with age, supplementation provides countless benefits. Note the list of conditions potentially improved by GSH on the last page.

What Causes Glutathione Deficiency?

Answer: Life, in general. The list is long.

Glutathione changes gene expression for aging and disease. Functional Medicine pioneer, Mark Hyman, MD, found he has gene missing called GSTM1 crucial to making and recycling glutathione. He reports that roughly half of Americans are missing one or more of the genes necessary to produce enough GSH. The percentage climbs even higher among his critically ill patients; the vast majority of whom have rock-bottom glutathione levels. “Keeping a high level of glutathione is critical to preventing disease,” he says._[1]

Glutathione levels can be reduced by metabolism, itself, mental and emotional stress, physical stress (exercise), infection, injury, chemicals, drugs of all types including acetaminophen (Tylenol, Panadol, Tylenol Arthritis Pain, Aspirin-Free Anacin and any cold medicine containing acetaminophen) and/or codeine. Alcohol depletes the liver of GSH and cigarette-smoke, second hand smoke and any drugs that must be neutralized (detoxed) by the liver will also deplete glutathione. Rx drugs also negatively affect GSH levels in kidneys, heart and other tissues. X-rays and ultraviolet rays from sunlight, marijuana drugs, and bacterial or viral infections including HIV are also culprits. Xenoestrogens such as BPA and toxic halocarbons used in plastics, dry cleaning solvents, pesticides, herbicides, refrigerants, environmental toxins and electropollution from computers, cell phones, TV, power lines, microwaves and toxins in air, food and water that we know about…and many that we don’t, all affect liver function from overuse which depletes GSH._[2]

Even without the extra toxic demands exerted by 21st century living, the requirement for GSH production is high. Immune system cells such as mast cells and white blood cells, as well as organ tissues – most notably the brain, heart, lungs, liver, and eyes – depend on GSH for survival. Healthy, unchallenged cells can produce a sufficient amount of GSH for a host of protective and metabolic functions; but add in those additional factors— cellular levels of GSH can be quickly depleted._[2]

Dr. Perlmutter says: “We are in a situation where our manufacturing and our recycling of glutathione is maxed out. We just can’t detoxify fast enough.”_[4]

Why is oxidative stress a concern?
A major cause of ill health and premature aging is excessive oxidative stress which is the constant attack against the body’s structures by electron-stealing pro-oxidants._[2]

To appreciate the value of glutathione, one must be aware of the detrimental effects of free-radical damage or oxidative stress -- often described or visualized as the body “rusting” or the process of “electron-stealing activity.” That occurs when the critical balance between free-radical generation and antioxidant defense is unfavorable. This damaging, electron-stealing occurrence is present in virtually all disease processes and conditions associated with aging. Oxidative stress is associated with damage to a wide range of molecular species including lipids, proteins and nucleic acids (DNA and RNA). Short-term oxidative stress may also occur in tissues injured by trauma, infection, heat injury, toxins, hyperoxia and excessive exercise._[2]

Oxidative stress is known to contribute significantly to all inflammatory diseases (arthritis, vasculitis, glomerulonephritis, lupus, diabetes, adult respiratory diseases syndrome), ischemic diseases (heart diseases, stroke, intestinal ischema), hemochromatosis, AIDS, emphysema, organ transplantation, gastric ulcers, hypertension and preeclampsia, neurological disorders (Alzheimer's, Parkinson's, muscular dystrophy, alcoholism, smoking-related diseases and many others including that of interest to Afibbers; ie, structural remodeling and formation of cardiac fibrosis. An excess of oxidative stress can lead to the oxidation of lipids and proteins which is associated with changes in their structure and functions._[2]

The power of electrons (Recall all the posts about “Healing is Voltage?)
Dr. Levy points out the continuous intracellular defense by GSH as a result of its power to promote healthy flow and supply of electrons within every cell in the body and summarizes:

….. “Without proper flow of electrons, your body will die. In fact, the health status for all living organisms is determined by overall electron flow. In the same way gasoline runs a car, electrons run the cell. Anything that impedes the flow of electrons in the body or robs them from the cells and tissues will adversely affect health. Anything that improves flow by donating electrons improves health. Electrons are the fuel of all life.”

Example of the dynamics of life and health:
Good electron flow = health, energetic, long life.
Poor electron flow = low energy and disease
No electron flow = death .... End quote …Ref._[2]


Repleting GSH is not typically easy… until now
While there are food sources of GSH, because of the rapid depletion of GSH from environmental pollution/toxins, the binding up of heavy metals, poor diet, oxidative stress, medications, stress and age, supplementation offers the best chance for optimal repletion and correction of a wide variety of chronic ailments. It is difficult to assimilate and accumulate enough glutathione from diet alone. Producing GSH in the body requires adequate amounts of cysteine, glutamic acid, glycine and two important enzymes; and if the body is already depleted of GSH, supplementation is necessary. “The average American consumes only 35 milligrams of glutathione per day,” says Lise Alschuler, ND, FABNO._[10]

Dr. Perlmutter explains: “One reason that glutathione wallows in relative obscurity is that, unlike vitamin C or E, it isn’t easily shoehorned into a supplement you can swallow. “With glutathione it’s not that easy. That’s because to succeed as an oral supplement, a nutrient must be able to wiggle through the intestinal wall and into the bloodstream, he explains. Otherwise it’s doomed to be destroyed in the gut. Here is where glutathione’s size works against it. A large molecule, called a tripeptide, glutathione cannot sneak through the intestinal wall intact. Instead, its three amino acids are broken apart during digestion and reassembled in the blood. (To get around this problem, many practitioners give therapeutic doses of glutathione intravenously.)_[4]

Now, we have access to the liposomal form of GSH.

There are mixed success reviews on various encapsulated oral forms of GSH including Reduced Glutathione, but now that liposomal delivery of GSH (and other nutrients) is available, it’s definitely proving to be very useful and effective. And also good news is the liposomal form does not cause any expenditure of energy or use electrons in the process.

A May 2014 study by Ritchie et. al. published in the European Journal of Medicine indicates, that daily supplementation of Setria® Glutathione is effective at increasing body stores of GSH by 30-35% over a 6-month period. This was a randomized, controlled trial of glutathione on humans using both high and low-doses for 6 months. Levels of increased GSH were found in blood, erythrocytes, plasma, lymphocytes and buccal mucosa and a number of immune markers increased significantly as well._[9]

This successful Setria form is produced by Kyowa Hakko, USA and uses a patented fermentation technology to manufacture a pure form of Setria® for liposomal delivery of Glutathione. It’s sold in the US by various suppliers including LivOn Labs, Healthy Origins, Pure Encapsulations, Jarrow, Life Extension, Nutricology and many more.
The key to finding the effective brand is the “Setria ®” designation on the label.
[setriaglutathione.com]

Supplementing with GSH
Caveat: While typically a small minority, those with extreme sulfur sensitivity may not tolerate supplemental GSH. Also, those with methylation defects are also found less tolerant of GSH. Note also: Glutathione use during chemotherapy is not recommended, unless otherwise directed by a physician.

The Lypo-Spheric GSH (Liv-On Labs) is an oral gel packet containing highly purified phospholipids that are made from Identity-preserved, non-GMO soy lecithin, but it does not contain the whole form of soy lecithin. This product is available online [www.livonlabs.com] and iHerb sells under the name LypriCel GSH… and it is the same Liv-On product - slightly discounted.

Dosing: The LypoSpheric gel packet contains 450 mg – 1 packet daily
Encapsulated versions typically are 500 mg/capsule - also 1 daily unless treating for specific conditions; then higher dosing is prescribed. Morning dosing is best.

Vitamin B6 in the Pyridoxal 5-Phosphate form is an essential enxyme reaction element in the production of GSH. Add 10 mg a day to your GSH supplement.[5]

Food sources of glutathione include avocado, asparagus, broccoli, garlic, grapefruit, eggs, spinach, tomatoes, turmeric, and un-denatured whey protein (ideally from grass fed cows). [www.immunehealthscience.com]

The LivOn Labs website at this link also has a list of GSH-containing foods, [blog.livonlabs.com]; however, the experts say if degenerative conditions exist, supplementation offers the most effective way for higher repletion dosing.

A Highly-reliable GSH food source is Un-denatured Whey Protein… meaning it is minimally processed by a special limited-heat process… is known to remarkably up-regulate the natural production of glutathione via the natural glycine and cysteine content. It’s also from clean sources. There are numerous studies showing increase stats; one was quoted as being near 67% increase… (sorry, I missed the reference title). There are many imposters of this special whey protein so it’s important to use a reliable source. Look for the name Proserum® whey on the label where the protein content is listed. Proserum® is made by Wisdom Proteins. [www.wellwisdom.com]

Be aware that Glutathione is at its lowest level in the morning and should be replenished daily through a healthy diet or supplementation with Setria® Glutathione.

Many supplement brands using the Setria GSH in both gel form and encapsulated are listed at this web link and include familiar names such as the Liv-On Laboratories, Healthy Origins, Life Extension, Pure Encapsulations, NOW and more. [setriaglutathione.com] See more links below for Setria Information.

The Results RNA’s product recommended by Garry F. Gordon, MD, DO MD(H) is now available online through Amazon.com as one source. It’s a spray version… their comments:

The Leading Glutathione – Extensive research confirms that supplementation of GSH is a crucial requirement for superior health, effective treatment and prevention of disease. Advanced Cellular Glutathione now makes oral supplementing possible.

Remarkable Efficacy – A major Advancement in Glutathione supplementation, Results RNA has developed Advanced Cellular Glutathione (ACG). ACG Glutathione Extra Strength is an intra-oral spray GSH that tastes great and has been proven by an independent clinical research firm to effectively increase intracellular levels of GSH by over 10% in only 7 hours.

GOOD MORNING, GLUTATHIONE!
Here’s a surprise: If you eat a breakfast of a whole orange, steak and eggs, you are on
your way to a healthy day by helping your body replenish its glutathione reserve; but if
you have cereal with blueberries and 2% milk and a glass of apple juice for breakfast,
you may be sabotaging your antioxidant protection. This seems to contradict what
mainstream nutrition teaches about a healthy diet, but it’s true for glutathione because
the ways of optimizing one’s status of this valuable antioxidant do not always conform to
common maxims. [setriaglutathione.com]

More informative links on Setria®
[setriaglutathione.com] Setria ® glutathione – the one that gets in.

Setria = Set (Balance) + Tria (tripeptide). A unique tripeptide form of glutathione that has been clinically shown to raise blood glutathione levels.
Infographic: [setriaglutathione.com]
[setriaglutathione.com]
Interactive Brand page [setriaglutathione.com]

Examples of Recent Studies showing positive results using liposomal GSH (a few of many)

Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Richie JP Jr, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE Eur J Nutr. 2014 May 5. PubMed PMID: 24791752
CONCLUSIONS: These findings show, for the first time, that daily consumption of GSH supplements was effective at increasing body compartment stores of GSH. [www.ncbi.nlm.nih.gov]

Milestone Study Shows Oral Supplement Setria® Glutathione Effectively Enhances Body’s Most Important Protective Antioxidant [setriaglutathione.com]

Liposomal Antioxidants for Protection against Oxidant-Induced Damage. Suntres ZE. Journal of Toxicology 2011 May 24. Article ID 152474. [www.hindawi.com]

Natural killer cell cytotoxicity: how do they pull the trigger? Immunology. Topham NJ, Hewitt, EW 2009 Sep. PubMed PMCID: 2747134. [www.ncbi.nlm.nih.gov]

The systemic availability of oral glutathione. Witschi A, Reddy S, Stofer B, Lauterburg BH. J Altern Complement Med. 2011 Sep;17(9):827-33. doi: 10.1089/acm.2010.0716. [www.ncbi.nlm.nih.gov]

Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Bernard Schmitta, , Morgane Vicenzib, , Catherine Garrel, Frédéric M. Denisb,, Redox Biol. 2015 Dec; 6: 198–205. Published online 2015 Jul 29. doi: 10.1016/j.redox.2015.07.012 PMCID: PMC4536296

Summary
Overall, the ultimate organ we should strive to nourish and protect is the brain since without a functional brain, we have no quality of life. This HAT report on lipGSH is highly relevant for brain protection and, as noted, so many other manifestations of oxidation and inflammation that occur with aging.

Read Dr. Perlmutter’s book…. Power Up Your Brain. It offers an abundance of useful and relevant information supporting the importance of glutathione.

This review of GSH will segue nicely into a future post on a related topic: the importance of nitric oxide production to help keep arteries open and blood flowing.

N.B. Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis. McKinley-Barnard S, Andre T, Morita M2, Willoughby DS. J Int Soc Sports Nutr.2015 Jun 10;12:27. doi: 10.1186/s12970-015-0086-7. eCollection 2015. [www.ncbi.nlm.nih.gov]

Healthy regards,

Jackie


Healthy Aging Tip #1 – Amino Acid L-Glutamine [www.afibbers.org]
Healthy Aging Tip #2 – GABA, cortisol, stress and Afib [www.afibbers.org]
Healthy Aging Tip #3 – Fibrinogen and Vitamin C[www.afibbers.org]


References
[1] Townsend Letter, January 1016, p 89
[2] GSH – The Master Defender ( 2009) Thomas E. Levy, MD, JD
[3] LivOn Laboratories Liposome-Encapsulated Glutathione June 22, 2013
by Dr. Thomas Levy [blog.livonlabs.com]
Dr. Levy on YouTube: [www.google.com]
The Most Important Antioxidant in Your Cells –Thomas Levy MD [www.ihealthtube.com]
[4] David Perlmutter, MD, FACN, ABIHM, Power Up Your Brain: The Neuroscience of Enlightenment (Hay House, 2011).
[5] Product Data – Glutathione – Designs for Health; Suffield, CT
[6] The Mood Cure, Julia Ross, MA. © 2003
[7] Townsend Letter, October 2015, “Lyme Brain” Causes and Solutions, Nichole McFadzean Ducharme, ND.
[8] Suzy Cohen, R Ph [suzycohen.com]
[9] Richie JP Jr, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2014 May 5. PubMed PMID: 24791752 [www.ncbi.nlm.nih.gov]
[10] [experiencelife.com]

Suntres ZE. Liposomal Antioxidants for Protection against Oxidant-Induced Damage. Journal of Toxicology 2011 May 24. Article ID 152474.

Topham NJ, Hewitt, EW. Natural killer cell cytotoxicity: how do they pull the trigger? Immunology. 2009 Sep. PubMed PMCID: 2747134.

Setria ® glutathione – the one that gets in
Setria = Set (Balance) + Tria (tripeptide). A unique tripeptide form of glutathione that has been clinically shown to raise blood glutathione levels.
[setriaglutathione.com]

Results RNA [www.resultsrna.com]
Smart Publications [www.smart-publications.com]
YouTube presentation plus dozens of other links [www.youtube.com]

Conditions potentially benefited by GSH supplementation
(Source: GSH – The Master Defender)
AIDS
Alzheimer’s disease
Cancer
Crohn’s disease
Chronic fatigue
Dermatitis diabetes
Down syndrome
Heart disease
Glaucoma
Hair loss
Hearing loss
Huntington’s
Hepatitis
High cholesterol
Inflammatory bowel disease
Kidney failure
Lung diseases…bronchitis, emphysema, COPD and asthma
Macular degeneration
Male infertility
MS
Pancreatitis
Parkinson’s
Prostate – including cancer and obstructive prostatic disease
Psoriasis
Schizophrenia
Stroke ….and many others.

I did get and try the lip GSH and boy did I get palpitations. I will try a smaller dose earlier in the morning. It sounds so good.

Dee