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HYDROGEN SUPPLEMENTS – MAKE HYDROGEN DRINKS

Fred Liers PhD hydrogen supplements drinks H2I love hydrogen supplements. So should you. Since starting my morning—and often afternoon—routine of making hydrogen drinks in the kitchen, I have come to appreciate the surge of energy lasting many hours, as well as a host of other benefits.

Most of all, I am amazed how easy hydrogen supplements are to use considering how much they do for you, and how well they complement the supplements I already take—seeming to make them all more effective.

I typically use one or two effervescing Active H2 Ultra tablets or Vital Reaction tablets in 8–16 ounces of water. Then I like to open one Megahydrate capsule directly in the effervescing water. I wait about 90 seconds to let the tablets stop “fizzing” and then I drink immediately. Allowing the drink to sit for a few minutes is okay, but the sooner you drink it, the higher the concentration of hydrogen.

HYDROGEN SUPPLEMENTS ARE EFFECTIVE

Hydrogen supplements are among the newer, cutting-edge nutritional formulas available to support optimal health. More than 500 scientific articles now support the therapeutic potential hydrogen for essentially every organ system and in 150 human disease models, according to the non-profit Molecular Hydrogen Foundation. In fact, hydrogen is rapidly incorporated into medicine, sports medicine, peak performance, elite fitness, and more.

Hydrogen is an antioxidant. It is also an extremely small molecule that can penetrate even the tiniest cellular compartments. This helps explain how hydrogen works to offer free-radical defense throughout the entire body.

The medical and scientific literature is clear. Hydrogen’s modes of action:

  • H2 reduces oxidative stress as a selective antioxidant and by maintaining homeostatic levels of glutathione, superoxide dismutase, catalase, etc.
  • H2, like other gaseous signaling molecules (i.e. NO, CO, H2S), appears to have cell signal-modulating activity affording it with anti-inflammatory, anti-obesity, and anti-allergy benefits.

We include hydrogen supplements in HPDI’s system of Foundational Supplements. In fact, hydrogen formulas as just one of six foundational supplements. We consider hydrogen a “secondary” foundational supplement usually to be added to a supplement regimen after the four primary ones: multivitamins, antioxidant & vitamin C formulas, essential fatty acids, and superfoods high in dietary nucleic acids (i.e., Rejuvenate! superfoods).

HYDROGEN MEDICINE

The scientific literature discusses the use of molecular hydrogen for many clinical applications, including:

• Metabolic Syndrome including diabetes, hyperlipidemia, arteriosclerosis, hypertension, and obesity

• Ischemia/reperfusion injuries, including cerebral and myocardial infarctions, organ transplants, post-cardiac arrest

• Neuroprotection, including applications for dementia, Parkinson’s disease, depression, and anesthesia

• Inflammation, including applications for polymicrobial sepsis, rheumatoid arthritis, wound healing, and bowel diseases

• Mitochondrial diseases

• Hemodialysis and ventilation

• Aging, including cognitive decline

• Exercise, including applications for fatigue, lactic acid, recovery, and oxidative stress related to heavy exercise

Side effects of cancer therapies, including radiotherapy and chemotherapy

• Many other benefits

(Source: Molecular Hydrogen Foundation)

HOW HYDROGEN WORKS

According to the Molecular Hydrogen Foundation, there are three ways molecular hydrogen exerts positive health effects.

1. Molecular hydrogen easily diffuses into subcellular compartments where it scavenges cytotoxic oxygen radicals, thereby protecting DNA, RNA, and proteins against oxidative stress.

2. Molecular hydrogen triggers activation or upregulation of additional antioxidant enzymes (e.g., glutathione, superoxide dismutase, catalase, and others) and/or cytoprotective proteins of the body.

3. Molecular hydrogen may be a novel signaling molecule that alters cell signaling, cell metabolism, and gene expression. This may explain its apparent anti-inflammatory, anti-allergic, and anti-apoptotic (or anti-cell death) effects.

hydrogen supplements Active H2 Ultra tablets

Active H2 Ultra hydrogen supplement (60 tablets).

HYDROGEN IS SAFE

Molecular hydrogen exhibits great safety, and it is regarded as safe for use in the body. It is shown no toxicity even in high concentrations.

Safety standards have long been established for high concentrations of hydrogen for inhalation largely because of the history of high-pressure H2 gas used in deep-water diving gas mixtures for preventing decompression sickness.

Notably, H2 gas combusts only at temperatures higher than 527 °C, and it explodes by chain reaction with oxygen (O2) only in the range of H2 concentration (4–75%, vol/vol).

Molecular hydrogen is used for medical applications safely by several ingestion methods including inhalation of 1–4% hydrogen gas, for example, which exhibits great effectiveness. All these factors mean that hydrogen is safe, easy-to-use, and effective for therapeutic purposes.

vital reaction hydrogen supplements

Vital Reaction hydrogen supplement (60 tablets).

DRINKING HYDROGEN-INFUSED WATER

According to the Molecular Hydrogen Foundation, drinking H2-rich water is the easiest, and often the most effective, method for obtaining hydrogen.

Drinking hydrogen-infused water is easy to do, and convenient as you can drink it at home or while traveling. Effective hydrogen products HPDI carries include Vital Reaction tablets, Active H2 tablets, and Megahydrate capsules.

As noted, I make one or two hydrogen drinks daily, first in the morning and then often again in the afternoon. I drink them on an empty stomach. I enjoy a significant energy boost, which helps power me through my day. I gain other benefits, including improved athletic performance, noticeably faster recovery from exercise, and an overall greater sense of well-being.

I highly recommend you try hydrogen supplements for yourself, and then consider them for your clients or patients. Our experience is that most people are pleasantly surprised by the results they get from hydrogen supplements, especially if they have a need for exceptional free-radical defense, or stand to benefit from the proven effects hydrogen uniquely provides (see list above).

Once you try hydrogen, you will want to continue taking it because the benefits are so significant. Let the power of hydrogen starting working for you on a daily basis!

hydrogen supplements Megahydrate

Dr. G. Patrick Flanagan’s Megahydrate (60 capsules).

HYDROGEN RESOURCES

Hydrogen Articles

Hydrogen for Optimal Health

Wonders of Molecular Hydrogen

Molecular Hydrogen (H2) at the Forefront of Health Research

The Science Behind MegaHydrate by Hank Liers, PhD

Hydrogen Products

Active H2 Ultra tablets

Vital Reaction tablets

Megahydrate capsules

Other Hydrogen Resources

Molecular Hydrogen Foundation

hydrogen supplements megahydrate active H2

Hydrogen supplements like Megahydrate and Active H2 are foundational in the HPDI supplement system.

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WONDERS OF MOLECULAR HYDROGEN

Fred Liers PhD molecular hydrogen H2I drink hydrogen-infused water. You should, too. Why? Because the age of hydrogen is here. Molecular hydrogen, that is. We now know that molecular hydrogen has therapeutic potential for nearly every organ in the human body, as well as for 150 different human disease models! And it’s extremely safe.

MOLECULAR HYDROGEN: BACKGROUND

Molecular hydrogen, also known as “diatomic hydrogen,” is a colorless, tasteless, and odorless gas.

Elemental hydrogen (H) is the most abundant element in the universe constituting 75% of its mass. Yet, it is absent on earth in its monoatomic form, being present in water, and inorganic and organic compounds. Molecular hydrogen is found in the earth’s atmosphere at less than one part per million.

molecular hydrogen H2 water

Hydrogen-infused water is a simple means to consume molecular hydrogen.

The science regarding benefits to health of molecular hydrogen (H2) has advanced rapidly in recent years thanks to the pioneering efforts of research scientists around the globe.

Now hydrogen science is moving quickly beyond theory to practical applications. Moreover, new products exist allowing medical professionals and consumers to leverage the health benefits of hydrogen.

For decades, diatomic molecular hydrogen was generally considered an “inert” gas. That is perhaps the primary reason that molecular hydrogen has been recognized as a therapeutic molecule only recently.

Indeed, science has known about the health benefits of molecular hydrogen as early as 1798. Yet, as noted, for most of modern history the belief persisted that hydrogen was inert in the body. It was only in the late 20th century (ca. 1975) that it gained the attention of medical researchers, and only in the past 10 years has evidence for the health effects of molecular hydrogen gained critical mass in the scientific literature.

There are now more than 500 peer-reviewed articles demonstrating the therapeutic potential of hydrogen for nearly every organ in the human body, as well as in 150 different human disease models, according to the Molecular Hydrogen Foundation.

HEALTH BENEFITS OF MOLECULAR HYDROGEN (H2)

• Molecular hydrogen reduces oxidative stress as a selective antioxidant and by maintaining homeostatic levels of glutathione, superoxide dismutase, catalase,  and other free-radical scavenging nutrients.

• The antioxidant capacities of molecular hydrogen are such that it is beneficial for persistent and acute oxidative stress.

• Acute oxidative stress arises from a multitude of causes, including inflammation, cardiac or cerebral infarction, organ transplantation, heavy exercise, cessation of operative bleeding, and many other causes.

• Persistent oxidative stress relates to reactive oxygen species (ROS) generated in the body throughout life. For example, during exercise, exposure to pollutants and toxins or UV light, as well as physical and psychological stresses, and the aging process itself. As aerobic organisms, we generate ROS when breathing consumes oxygen.

• Molecular hydrogen is effective against hydroxyl radicals (OH). The hydroxyl radical is the radical species that causes much of the oxidative damage in the body. While vitamin C, glutathione, and certain plant-based antioxidants are somewhat effective against this radical, there is no Nrf2-induced enzyme that effectively quenches the hydroxl radical.

• This positions molecular hydrogen as a uniquely effective antioxidant against the hydroxyl radical. Notably, when molecular hydrogen quenches the hydroxyl radical, it produces water, which is non-toxic in the body.

• Beyond this, molecular hydrogen, like other gaseous signaling molecules such as NO, CO, H2S, appears to exhibit cell signal-modulating activity that confers it with anti-inflammatory, anti-obesity, anti-allergy, and many other benefits.

MOLECULAR HYDROGEN MEDICINE

The scientific literature discusses the use of molecular hydrogen for many clinical applications, including the following:

• METABOLIC SYNDROME including diabetes, hyperlipidemia, arteriosclerosis, hypertension, and obesity

• ISCHEMIA / REPERFUSION injuries including cerebral and myocardial infarctions, organ transplants, post-cardiac arrest

• NEUROPROTECTION including applications for dementia, Parkinson’s disease, depression, and anesthesia

• INFLAMMATION including applications for polymicrobial sepsis, rheumatoid arthritis, wound healing, and bowel diseases

• MITOCHONDRIAL DISEASES

• HEMODIALYSIS / VENTILATION

• AGING including cognitive decline

• EXERCISE including applications for fatigue, lactic acid, recovery, and oxidative stress related to heavy exercise

SIDE EFFECTS OF CANCER THERAPIES including radiotherapy and chemotherapy

• MANY OTHER BENEFITS

athlete molecular hydrogen performance race

Athletes benefit from molecular hydrogen. You can, too.

HOW MOLECULAR HYDROGEN WORKS

According to the Molecular Hydrogen Foundation, there are three ways molecular hydrogen exerts positive health effects.

1.  Molecular hydrogen easily diffuses into subcellular compartments where it scavenges cytotoxic oxygen radicals, thereby protecting DNA, RNA, and proteins against oxidative stress.

2.  Molecular hydrogen triggers activation or upregulation of additional antioxidant enzymes (e.g., glutathione, superoxide dismutase, catalase, and others) and/or cytoprotective proteins of the body.

3.  Molecular hydrogen may be a novel signaling molecule that alters cell signaling, cell metabolism, and gene expression. This may explain its apparent anti-inflammatory, anti-allergic, and anti-apoptotic (or anti-cell death) effects.

MOLECULAR HYDROGEN IS SAFE

Molecular hydrogen exhibits great safety, and it is regarded as safe for use in the body. It is shown no toxicity even in high concentrations.

Safety standards are already established for high concentrations of molecular hydrogen for inhalation because high-pressure H2 gas is used in deep-water diving gas mixtures to prevent decompression sickness.

Notably, H2 gas combusts only at temperatures higher than 527 °C, and it explodes by chain reaction with oxygen (O2) only in the range of Hconcentration (4–75%, vol/vol).

Molecular hydrogen can be used for medical applications safely by several ingestion methods including inhalation of 1–4% hydrogen gas, which exhibits great effectiveness.

All these factors mean that molecular hydrogen is safe, easy-to-use, and effective for therapeutic purposes.

molecular hydrogen H2 water

Hydrogen-infused water is safe, easy-to-consume, and cost effective.

USING MOLECULAR HYDROGEN

Methods for consuming molecular hydrogen include inhalation, oral ingestion of hydrogen-infused water, injection of hydrogen saline, and direct diffusion (eye drops, baths, cosmetics, etc.).

An advantage of inhaled H2 gas is that is acts rapidly. In this respect, may be suitable for defense against acute oxidative stress.

It has been shown that inhalation of 3–4% hydrogen (H2) gas reaches a plateau at approximately 10–20 μM in the arterial and venous blood in about 20 minutes. This is shown not to affect any physiological parameters (e.g., blood pressure), suggesting no adverse effects.

According to the Molecular Hydrogen Foundation, the consensus is that drinking H2-rich water is the easiest, and often the most effective, method for obtaining molecular hydrogen although it does not provide as many hydrogen molecules to the body as other methods.

Some studies show consuming H2-infused water to be more effective than inhalation or increasing intestinal H2 production via lactulose administration.

Another advantage of drinking hydrogen infused water is that it allows gastric induction of ghrelin, which is mediated via activation of beta 1 adrenergic receptors.

Above all, drinking hydrogen-infused water is easy to do, and convenient as you can drink it at home or while traveling.

HYDROGEN-INFUSED WATER

Inhalation of molecular hydrogen gas may be impractical for continuous H2 consumption in daily life. In contrast, solubilized H2 (hydrogen-infused water) is a portable, easily administered, and safe means to ingest H2.

H2 can be dissolved in water up to 0.8 mM (1.6 mg/L) under atmospheric pressure at room temperature without changing pH.

Hwater can be made by several methods: infusing H2 gas into water under pressure, electrolyzing water to producing H2, and reacting magnesium metal or its hydride with water.

Notably, H2 penetrates glass or plastic walls of vessels in a short time, yet aluminum containers retain hydrogen gas for a long time.

Water ionizers produce hydrogen gas via electrolysis. This method produces hydrogen concentrations from less than 0.05 ppm to more than 2.5 ppm. Typically 0.1 to 0.7 ppm hydrogen is produced, yet most companies manufacturing water ionizers neither know the concentration produced nor understand the significance of hydrogen for health.

In this regard, depending upon the production method much of the water containing molecular hydrogen exhibits a negative oxygen reduction potential (ORP). Yet, ORP is only a general indication of hydrogen production and is not a measurement of its concentration.

A second method of producing hydrogen-rich water by electrolysis is by infusion. In this method, hydrogen is directly infused into filtered water within a machine.

Another convenient method to generate molecular hydrogen is to add alkali-earth metals to water. Magnesium metal in commonly used for this purpose. This method allows for the production of high concentrations of molecular hydrogen that are generally near saturation (1.6 ppm), and therefore less water needs to be consumed by individuals drinking it.

Magnesium sticks and tablets/capsules are available (some of which are placed in water and others that can be consumed directly) that rapidly produce 2–4 ppm molecular hydrogen concentration. Like electrolysis, adding metals to water also increased the pH of water because they reduce the concentration of H+ ions.

Other methods exist that can produce supersaturated concentrations of molecular hydrogen with or without alteration of water pH. Advantages of these methods include having to drink a fraction of the amount of water in order to obtain an equal amount of molecular hydrogen.

Drinking water containing molecular hydrogen is probably the easiest and most cost-effective means for most persons to obtain hydrogen.

man drinks water infused with molecular hydrogen

Hydrogen-infused water can be consumed using tablets, prepared H2 beverages, or ionized water.

MOLECULAR HYDROGEN FROM YOUR MICROBIOME

Certain types bacteria in the intestinal tract produce hydrogen gas from non-digestible fibers, which may explain how fiber-rich diets reduce inflammation, and exert cardiovascular and other health benefits.

Diets low in dietary fiber from fruits and vegetables, or a decrease in microbiome diversity could potentially reduce production of molecular hydrogen. This could exert adverse effects on health.

The presence (or absence) of a diverse and robust microbiome may be one of the most significant factors in terms of how much hydrogen can be generated in the body. Most people today do not create the levels of molecular hydrogen in their digestive tracts that humans in earlier time periods generated largely because due to modern diets and less than optimal microbiome health.

Factors that influence or reduce microbiome health and diversity include antibiotic use, imbalanced diet, lack of certain fiber-rich vegetables in the diet, and consumption of herbicides, pesticides, and GMOs (that include glyphosate) that harm microbial populations and cause “leaky gut”.

As knowledge increases regarding ways we can support a healthy microbiome, the biological significance of hydrogen historically produced in our digestive tracts will be better understood.

BENEFIT TODAY FROM MOLECULAR HYDROGEN

The clinical applications of molecular hydrogen are impressive. One of the great advantages of molecular hydrogen infused water is that  it is easy to consume it, or make it in your own home or wherever you happen to be.

HPDI now sells a tablet hydrogen product from Purative known as Active H2.

Active H2 is a unique, patent-pending combination of all-natural minerals used to generate molecular hydrogen and electron-rich potential (-ORP). This distinguishes it from existing hydrogen formulas and electrolysis (water ionizers).

Active H2 is easy to use.  Simply place one tablet of in a 1/2 liter (16 oz) container of pure water (filled to the top) and close tightly. Wait at least 5–10 minutes for it to completely disintegrate (fizz), and then drink.

A one pint glass mason jar works well as a container for this purpose. However, you can use up to one liter (about 32 ounces) of water in a container, so a quart mason jar also works well. Consume the hydrogen-infused water ideally at least 30 minutes before food.

Active H2 formula consists of a proprietary blend of pure magnesium, malic acid, fumaric acid, and maltose that synergistically act to generate molecular hydrogen and electron-rich potential (-ORP).

Active H2 is the only all-natural add-in tablet providing molecular hydrogen in the amount of greater than 1.8 ppm, That is, one tablet typically generates molecular hydrogen in the concentration of about 2 ppm.

There are other molecular hydrogen products, including tablets, sticks, and pre-infused bottled products like H2Bev. H2Bev provides about 1.2–1.5 ppm of molecular hydrogen and comes in a 12 oz coated aluminum container for excellent H2 retention.

MOLECULAR HYDROGEN SUMMARY

Molecular hydrogen sits in the unique position of providing significant, wide-ranging benefits for health with an unmatched ease-of-use, and at relatively low cost for what it delivers.

We highly recommend the use of molecular hydrogen for its health benefits and for therapeutic applications. This includes the consumption of hydrogen-infused water whether from prepared H2 beverages, water ionizers, or highly effective Active H2 tablets.

Below we include important scientific abstracts you may find helpful in understanding the benefits and applications of molecular hydrogen.

 

SCIENTIFIC STUDIES ON MOLECULAR HYDROGEN

Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles

From: http://www.ncbi.nlm.nih.gov/pubmed/26483953

Abstract
Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum. Hydrogen gas of less than 4% is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.

Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine

From: http://www.ncbi.nlm.nih.gov/pubmed/24769081

Abstract
Molecular hydrogen (H2) has been accepted to be an inert and nonfunctional molecule in our body. We have turned this concept by demonstrating that H2 reacts with strong oxidants such as hydroxyl radical in cells, and proposed its potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signaling reactive oxygen species; therefore, there should be no or little adverse effects of H2. There are several methods to ingest or consume H2; inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline into the eyes. The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.

Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.

From: http://www.ncbi.nlm.nih.gov/pubmed/25251220

Abstract
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.

The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance

From: http://www.ncbi.nlm.nih.gov/pubmed/23680032

Abstract
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums. There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.

Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases

From: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377272/

Abstract
Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson’s disease and three models of Alzheimer’s disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson’s disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease.

Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases

From: http://www.ncbi.nlm.nih.gov/pubmed/21621588

Abstract

BACKGROUND:
Mitochondria are the major source of oxidative stress. Acute oxidative stress causes serious damage to tissues, and persistent oxidative stress is one of the causes of many common diseases, cancer and the aging process; however, there has been little success in developing an effective antioxidant with no side effect. We have reported that molecular hydrogen has potential as an effective antioxidant for medical applications [Ohsawa et al., Nat. Med. 13 (2007) 688-694].

SCOPE OF REVIEW:
We review the recent progress toward therapeutic and preventive applications of hydrogen. Since we published the first paper in Nature Medicine, effects of hydrogen have been reported in more than 38 diseases, physiological states and clinical tests in leading biological/medical journals. Based on this cumulative knowledge, the beneficial biological effects of hydrogen have been confirmed. There are several ways to intake or consume hydrogen, including inhaling hydrogen gas, drinking hydrogen-dissolved water, taking a hydrogen bath, injecting hydrogen-dissolved saline, dropping hydrogen-dissolved saline into the eyes, and increasing the production of intestinal hydrogen by bacteria. Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.

MAJOR CONCLUSIONS:
Hydrogen has biological benefits toward preventive and therapeutic applications; however, the molecular mechanisms underlying the marked effects of small amounts of hydrogen remain elusive.

GENERAL SIGNIFICANCE:
Hydrogen is a novel antioxidant with great potential for actual medical applications. This article is part of a Special Issue entitled Biochemistry of Mitochondria.

Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications

From: http://www.ncbi.nlm.nih.gov/pubmed/21736547

Abstract
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H(2)) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H(2) has a number of advantages as a potential antioxidant: H(2) rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H(2). There are several methods to ingest or consume H(2), including inhaling hydrogen gas, drinking H(2)-dissolved water (hydrogen water), taking a hydrogen bath, injecting H(2)- dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H(2) by bacteria. Since the publication of the first H(2) paper in Nature Medicine in 2007, the biological effects of H(2) have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H(2) shows not only effects against oxidative stress, but also various anti-inflammatory and antiallergic effects. H(2) regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H(2) remain elusive.

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

From: http://www.ncbi.nlm.nih.gov/pubmed/17486089

Abstract
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.

ADDITIONAL RESOURCES

MOLECULAR HYDROGEN (H2) AT FOREFRONT OF HEALTH RESEARCH
by Hank Liers, PhD (from the HPDI blog)

ACTIVE H2 (tablet product)

Molecular Hydrogen Foundation (MHF)

Contact Us:

You can reach HPDI by calling 1-800-228-4265, email support(at)IntegratedHealth.com, or visit the retail website: www.IntegratedHealth.com

Health care professionals and retailers can apply for wholesale account, which includes access to the HPDI reseller website: www.HealthProductsDistributors.com

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THE AMAZING HEALING POTENTIAL OF NATURAL NRF2 ACTIVATORS

Dr. Hank Liers, PhD natural nrf2 activators healing potential

When I first learned about Nrf2 activators in early 2012, I became quite enthusiastic about new knowledge that natural substances called polyphenolic compounds had the ability to activate this transcription factor. Once released in the cell Nrf2 can migrate to the nucleus and cause the body to endogenously produce high levels of key protective/antioxidant enzymes.

I soon published several blog articles on this subject including a June 2012 article entitled New Directions For Preventing Free-Radical Damage and a July 2012 article entitled Natural Phytochemical Nrf2 Activators for Chemoprevention.

Also, I actively began the development of a new product called Ultimate Protector™ that contains many concentrates and extracts from fruits and vegetables. This product functions as 1) an excellent source of many Nrf2 activators contained in 29 different fruits and vegetables, 2) a source of powerful antioxidants exhibiting an ORAC5.0 value of 486,000 units in six small capsules, and 3) a source of non-GMO Vitamin C.

NRF2 Activators in Ultimate Protector

Ultimate Protector™ Nrf2 Activator Formula

In October 2012, I published a blog article titled Ultimate Protector™ Brunswick Labs ORAC5.0™ Test Results summarizing the laboratory test results that showed Ultimate Protector’s extremely high antioxidant values for the top five free-radical types found in the body.

It is interesting to note that over 16 years ago I formulated a wonderful antioxidant formula called PRO-C™. PRO-C™ contains Buffered Vitamin C (in the form of powdered calcium, magnesium, and zinc ascorbates), high-potency Grape Extract (from grape pulp, skins, and seeds), Green Tea Extract, reduced Glutathione, N-Acetyl-L-Cysteine (NAC), R-Lipoic Acid, coenzyme forms of Vitamin B2 and Vitamin B6, and Selenium.

PRO-C™ has been one of the most effective products at supporting health I have ever formulated. Our current knowledge shows that PRO-C™ contains four effective Nrf2 activators, selenium needed for glutathione peroxidase functioning, Vitamin B2 and Vitamin B6 that support the effectiveness of glutathione, and antioxidants including Vitamin C and glutathione. I recently wrote a blog article titled PRO-C™ SUPER ANTIOXIDANT FORMULA that provides details concerning this formula.

My current personal list of supplements that I (and my wife) take every day includes both Ultimate Protector™ and PRO-C™. We feel gifted to have these products available to us!!

In this article, I will provide greater insight into the natural sources of Nrf2 activators and how they perform in the body.

SOME KEY ENZYMES MODULATED BY Nrf2 ACTIVATORS

Activation of Nrf2 results in the induction of many cytoprotective proteins. We have seen articles that claim over 200 different enzymes can be produced in the body by Nrf2 activators, but have also seen reference that over 4,000 enzymes may be produced!  Examples of some of the key enzymes are shown below:

  • NAD(P)H quinone oxidoreductase 1 – a prototypical Nrf2 target gene that catalyzes the reduction and detoxification of highly reactive quinones that can cause redox cycling and oxidative stress.
  • Superoxide dismutases (SOD) – enzymes that catalyze the dismutation of superoxide (O2) into oxygen and hydrogen peroxide. Thus, they are an important antioxidant defense in nearly all cells exposed to oxygen where superoxide is one of the main reactive oxygen species. SOD is known to provide powerful antinflammatory activity.
  • Glutamate-cysteine ligase which is the rate-limiting step in the synthesis of glutathione (GSH), a very powerful endogenous antioxidant. Glutamate-cysteine ligaseis a characteristic Nrf2 target gene, which establish Nrf2 as a regulator of glutathione, one of the most important antioxidants in the body.
  • Heme oxygenase-1 (HO-1) is an enzyme that catalyzes the breakdown of heme into the antioxidant biliverdin, the anti-inflammatory agent carbon monoxide, and iron. HO-1 is a Nrf2 target gene that has been shown to protect from a variety of pathologies, including sepsis, hypertension, atherosclerosis, acute lung injury, kidney injury, and pain.
  • The glutathione S-transferase (GST) family includes cytosolic, mitochondrial, and microsomal enzymes that catalyze the conjugation of GSH with endogenous and xenobiotic electrophiles. After detoxification by GSH conjugation catalyzed by GSTs, the body can eliminate potentially harmful and toxic compounds. GSTs are induced by Nrf2 activation and represent an important route of detoxification.
  • The UDP-glucuronosyltransferas (UGT) family catalyze the conjugation of a glucuronic acid moiety to a variety of endogenous and exogenous substances, making them more water soluble and readily excreted. Important substrates for glucuronidation include bilirubin, and acetaminophen. Nrf2 has been shown to induce UGT1A1 and UGT1A6.
  • Multidrug resistance-associated proteins  (Mrps) are important membrane transporters that efflux various compounds from various organs and into bile or plasma, with subsequent excretion in the feces or urine, respectively. Mrps have been shown to be upregulated by Nrf2 and alteration in their expression can dramatically alter the pharmacokinetics and toxicity of compounds.

NATURAL FOODS AND FOOD EXTRACTS PROMOTE THE EXPRESSION OF Nrf2

The March 2011 Epub Biochemical Basis for Functional Ingredient Design from Fruits reports: “Functional food ingredients (nutraceuticals) in fruits range from small molecular components, such as the secondary plant products, to macromolecular entities, e.g., pectin and cellulose, that provide several health benefits.  In fruits, the most visible functional ingredients are the color components anthocyanins and carotenoids.

“In addition, several other secondary plant products, including terpenes, show health beneficial activities.  A common feature of several functional ingredients is their antioxidant function. For example, reactive oxygen species (ROS) can be oxidized and stabilized by flavonoid components, and the flavonoid radical can undergo electron rearrangement stabilizing the flavonoid radical.  Compounds that possess an orthodihydroxy or quinone structure can interact with cellular proteins in the Keap1/Nrf2/ARE pathway to activate the transcription of antioxidant enzymes.

“Carotenoids and flavonoids can also exert their action by modulating the signal transduction and gene expression within the cell. Recent results suggest that these activities are primarily responsible for the health benefits associated with the consumption of fruits and vegetables.”

One of the interesting aspects of the extensive research that has been conducted is the fact that many of the polyphenols that have been shown to activate Nrf2 have been used in natural healing formulas for many years. For example, an article in a November 2010 production titled Nutraceutical antioxidants as novel neuroprotective agent expands on the classes of “antioxidant” compounds that are neuroprotective and operate either via direct antioxidant action or via the keap1-Nrf2 pathway:

“A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic.

“All of these compounds are generally considered to be antioxidants.  They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.”

Ultimate Protector NRF2 Activator ORAC

DIETARY FLAVONOIDS AS NRF2 ACTIVATORS

One of the ways dietary flavonoids work to confer their multiple health effects is via the keap1-Nrf2 pathway.  That is substances which are both themselves antioxidants and activators of the keap1-Nrf2 pathway produce significant results through keap1-Nrf2 and activating the body’s own antioxidant and defensive systems.

Flavonoids are a large family of polyphenolic compounds synthesized by plants. Many of the common dietary flavonoids are shown in Table 1 below along with their common food sources.

Table 1: Common Dietary Flavonoids

Flavonoid Subclass Dietary Flavonoids Some Common Food Sources
Anthocyanidins  Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin Red, blue, and purple berries; red and purple grapes; red wine
Flavonols  Monomers (Catechins) Catechin, Epicatechin, Epigallocatechin, Epicatechin gallate, Epigallocatecin gallate Dimers and Polymers: Theaflavins, Thearubigins, Proanthocyanidins Catechins: Teas (particularly green and white), chocolate, grapes, berries, apples Theaflavins, Thearubigins: Teas (particularly black and oolong) Proanthocyanidins: Chocolate, apples, berries, red grapes, red wine.
Flavanones Hesperetin, Naringenin, Eriodictyol Citrus fruits and juices, e.g., oranges, grapefruits, lemons.
Flavonols Quercetin, Kaempferol, Myricetin, Isorhamnetin Widely distributed: yellow onions, scallions, kale, broccoli, apples, berries, teas.
Flavones Apigenin, Luteolin Parsley, thyme, celery, hot peppers.
Isoflavones Daidzein, Genistein, Glycitein Soybeans, soy foods, legumes.

In addition to flavonoids many other plant based substances appear to produce health benefits through hormetic effects mediated by Nrf2.  The December 2011 publication Nutritional antioxidants and adaptive cell responses: an update reports: “Many plant antioxidants, intaken through the daily diet or plant-derived dietary supplements, have been shown able to prevent free radical-related diseases by counteracting cell oxidative stress. However, it is now considered that the in vivo beneficial effects of these phytochemicals are unlikely to be explained just by their antioxidant capability.

“Several plant antioxidants exhibit hormetic properties, by acting as ‘low-dose stressors’ that may prepare cells to resist more severe stress. In fact, low doses of these phytochemicals activate cell signaling pathways (being the most prominent examples the modulation of the Nrf2/Keap1 pathway, the NF-κB pathway and the Sirtuin-FOXO pathway) but high doses are cytotoxic.

“Herein we review the adaptive responses induced by the most known plant hormetic antioxidants, which are sulforaphane, resveratrol, curcumin, flavonoids, green tea catechins and diallylsulphides [in garlic], as well as the molecular mechanisms involved in such responses. Furthermore, this review outlines that the hormetic properties of these bioactive plant antioxidants might be successfully employed for realizing health-promoting dietary interventions especially in the field of neurodegenerative diseases and cancer.”

Ultimate Protector Nrf2 activator

INTERESTING FACTS REGARDING NRF2 ACTIVATORS

1) An interesting fact is that Nrf2 is ubiquitously expressed with the highest concentrations (in descending order) in the kidney, muscle, lung, heart, liver, and brain. 

2) Another important fact is that the well-known nutrition supplement lipoic acid is a potent activator of Nrf2 and thus increases Gluthatione levels, which may explain its protective effect against diabetic co-morbidities. Additionally, the nutritional supplements tocotrienols (active forms of Vitamin E) and N-Acetyl-L-Cysteine (NAC) are also effective Nrf2 activators!

3) We have observed that the natural plant substances with the highest ORAC5.0 values appear to be among the most effective Nrf2 activators. For example, see the table below. In particular, note that Curcumin (98%), Grape Seed Extract, Green Tea Extract, and Reservatrol which are commonly used for their excellent Nrf2 activator effects are the most powerful in-vitro antioxidants . Please note that Ultimate Protector is over 50% more powerful as an antioxidant than the best single plant ingredient.

TABLE 2: ORAC5.0™ COMPARATIVE RESULTS

Ingredient Peroxyl Radical Hydroxyl Radical Peroxy-nitrite Radical Super-
oxide Radical
Singlet O2 Radical Total ORAC5.0
Curcumin 98% 5,750 8,920 906 597 66,290 82,500
Bilberry 25% 7,000 25,000 1,000 16,000 5,000 54,000
Cocoa 10,000 28,000 1,000 11,000 2,000 52,000
Grape Seed Extract 17,000 47,000 1,000 25,000 4,000 94,000
Green Tea Extract 11,000 41,000 2,000 56,000 3,000 113,000
Coffee Berry Extract 5,000 29,000 1,000 1,000 2,000 38,000
Mangosteen 4,000 8,000 1,000 18,000 4,000 35,000
Pine Bark 7,000 23,000 1,000 17,000 2,000 50,000
Resveratrol 12,000 50,000 1,000 8,000 22,000 93,000
ULTIMATE PROTECTOR 6,300 5,900 2,500 106,000 52,000 173,000
Results are expressed in micro mole TE/g
4) Here is a list of the ingredients in ULTIMATE PROTECTOR™:  USP-grade non-GMO Buffered Vitamin C, AnthoComplete™ (high-ORAC powder from Wild Blueberry, Wild Bilberry, Acai, Black Currant Extract, Sweet Cherry, Raspberry, Elderberry, Blackberry, Aronia, Black Soybean Hull Extract, and Blue Corn), CoffeeBerry®Forte (high-ORAC powder from Coffee Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), VitaBerry®Plus (high-ORAC powder: from freeze-dried Grape Seed, Wild Blueberry, Wild Bilberry, Cranberry, Tart Cherry, Prune, Raspberry Seed, Strawberry, Trans-Resveratrol, and Quercetin), VitaVeggie® (high-ORAC powder from Broccoli, Broccoli Sprouts, Tomato, Kale, Carrot, Brussels Sprouts, Onion and Spinach), and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients).

NEUROPROTECTION BY POLYPHENOL STIMULATION OF THE NRF2 / ARE PATHWAY 

Below are two abstracts that discuss how modulation of the Nrf2/ARE pathway by food polyphenols can provide neuroprotection through the activation of the heme-oxygenase enzyme.

Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. (Oct. 2011)

ABSTRACT

In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes.

Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation of Nrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders.

Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.

The major green tea polyphenol, (-)-epigallocatechin-3-gallate, induces heme oxygenase in rat neurons and acts as an effective neuroprotective agent against oxidative stress. (Aug. 2009)

ABSTRACT

Oxidative stress induced by hyperglycemia is a key factor in the pathogenesis of diabetic complications, such as neuropathy. Recently, green tea catechins have received much attention, as they can facilitate a number of antioxidative mechanisms and improve glycemic control. The aim of this study was to investigate the cytoprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against oxidative stress damage in a cell line of rat neurons. The role of heme oxygenase 1 (HO-1) induction by EGCG and the transcriptional mechanisms involved were also evaluated.

Immortalized rat neurons (H 19-7) were exposed to various concentrations of EGCG (10-200 microM). After treatments (6 or 24 hours), cells were harvested for the determination of heme oxygenase activity, mRNA levels, and protein expression. Nuclear levels of Nrf2, a transcriptional factor involved in HO-1 activation, were also measured. Neurons were pretreated for 12 hours with EGCG 50 microM or EGCG 50 microM + zinc protoporphyrin IX 10 microM and then exposed for 2 hours to 50 mmicro/mL glucose-oxidase before cell viability was determined.

In cultured neurons, elevated expression of HO-1 mRNA and protein were detected after 6 hours of incubation with 25-100 microM EGCG, and its induction relates with the activation of Nrf2. Interestingly, pre-incubation (12 hours) with EGCG 50 microM resulted in an enhanced cellular resistance to glucose oxidase-mediated oxidative damage; this cytoprotective effect was considerably attenuated by zinc protoporphyrin IX, an inhibitor of heme oxygenase activity.

In this study, we demonstrated that EGCG, the major green tea catechin, induced HO-1 expression in cultured neurons, possibly by activation of the transcription factor Nrf2, and by this mechanism was able to protect against oxidative stress-induced cell death.

 

The following review article abstract shows how natural products containing Nrf2 activator/antioxidant ingredients might be used to support health and anti-aging.

Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS (July 2012)

REVIEW ARTICLE

Abstract: Nrf2 (nuclear erythroid 2-related factor 2) is a basic region leucine-zipper transcription factor which binds to the antioxidant response element (ARE) and thereby regulates the expression of a large battery of genes involved in the cellular antioxidant and anti-inflammatory defence as well as mitochondrial protection. As oxidative stress, inflammation and mitochondrial dysfunctions have been identified as important pathomechanisms in amyotrophic lateral sclerosis (ALS), this signaling cascade has gained interest both with respect to ALS pathogenesis and therapy. Nrf2 and Keap1 expressions are reduced in motor neurons in postmortem ALS tissue.

Nrf2-activating compounds have shown therapeutic efficacy in the ALS mouse model and other neurodegenerative disease models. Alterations in Nrf2 and Keap1 expression and dysregulation of the Nrf2/ARE signalling program could contribute to the chronic motor neuron degeneration in ALS and other neurodegenerative diseases. Therefore, Nrf2 emerges as a key neuroprotective molecule in neurodegenerative diseases.

Our recent studies strongly support that the Nrf2/ARE signalling pathway is an important mediator of neuroprotection and therefore represents a promising target for development of novel therapies against ALS, Parkinson’s disease (PD), Huntington’s disease (HD), and Alzheimer’s disease (AD). Simultaneous blockage of disease-specific broad toxic signaling cascades in motor neurons and glia may ultimately lead to more efficient neuroprotection in ALS. Stimulation of defense mechanisms that modulate neuroprotective genes which affect both neuronal and glial functions is a novel therapeutic approach and holds great promise. A key molecule to affect a variety of defense mechanisms is the transcription factor Nrf2 which activates the Nrf2/ARE signaling program. Nrf2 acts as master regulator of the cellular antioxidant response by stimulation of over 250 phase II genes that should be referred to as “prolife genes” since they save cells from death.

Nrf2 activation can at once regulate the expression of multiple cytoprotective enzymes that are capable of simultaneous inhibition of major pathogenic pathways described in ALS such as oxidative stress, neuroinflammation, and mitochondrial dysfunction. Decreased Nrf2 expression was found in motor neurons in ALS postmortem brain and spinal cord. We have established the proof-of-concept that the Nrf2/ARE program is a viable target with excellent therapeutic potential for ALS. While there are still multiple gaps of knowledge on the path from Nrf2 dissociation to nuclear localization and its action as transcription factor, activation of the Nrf2 signaling cascade represents a novel and unique attempt to find a cure for ALS and other neurodegenerative diseases by fortifying the intrinsic defense mechanisms of neurons.

CONCLUSION

In this article I have shown how foods such as fruits, vegetables, herbs, and their extracts can stimulate extremely powerful protective enzymes in the body that work to keep us healthy. I strongly suggest that our readers eat an organic diet that emphasizes these foods and highly recommend the use of nutritional supplements such as Ultimate Protector™ and PRO-C™ that can further support the activation of the Nrf2 pathways in the body!

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