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ULTIMATE PROTECTOR+ BRUNSWICK LABS ORAC6.0 TEST REPORT

Dr. Hank Liers, PhDHPDI’s new product ULTIMATE PROTECTOR+ is a next generation cell protection formula that simultaneously meets the needs for high levels of Vitamin C, full spectrum antioxidants* (high ORAC values), and protective enzyme activators (Nrf2 activators from plant-based polyphenols) in a single product. This potent combination of characteristics distinguishes the formula because no other single product available today offers such complete protection.

All three of ULTIMATE PROTECTOR+‘s components provide significant protection against the various types of free radicals that cause cellular damage in the body. In particular, the full spectrum of antioxidants derived from high ORAC fruits, vegetables, and herbs (as well as Vitamin C) provide extremely powerful exogenous sources of protection against oxidative stress. To obtain a quantitative measure of just how powerful these external sources are we have elected to conduct ORAC testing.

ORAC TESTS

ORAC (standing for “Oxygen Radical Absorption Capacity”) was developed by Brunswick Labs as an analytical tool for estimating the antioxidant capacity of substances. It is an in vitro test that was an important advancement in commercially available analysis of the peroxyl free-radical’s trapping ability of foods and ingredients. It has become a de facto standard in the natural products industry. However, the original ORAC method was considered to be just a starting point for comprehensive antioxidant analysis.

The fact is that there are a variety of “free radicals” that operate in humans — the most important of which are the primary radicals hydroxyl, peroxyl, peroxynitrite, singlet oxygen, and superoxide anion. Brunswick Labs has reported that even though the peroxyl is the major free radical in the body, it represents no more than 27% of the total antioxidant potential of selected fruits and vegetables. In addition, the original ORAC method favors certain antioxidant substances over others (e.g., anthocyanins over carotenoids) due to the use of a single free radical source (peroxyl radical).

These radicals are formed, behave, and are defended against differently. They all contribute to: 1) a general condition called “oxidative stress,” or cellular damage, and 2) broad human health concerns caused, for example, by inflammation, and DNA and protein damage. They are each implicated in different health problems – from cardiovascular disease to macular degeneration and Alzheimer’s disease and to skin damage and aging. Below we provide a brief summary of these free radicals.

The Peroxyl Radical is very important in many biological systems, including lipid peroxidation, DNA cleavage, and protein backbone modification. Hydroxyl is highly reactive and cannot be eliminated by our endogenous enzymes (such as SOD and glutathione). It can damage virtually all types of macromolecules: carbohydrates, nucleic acids, lipids, and amino acids. In the skin, hydroxyl radicals are created by UV exposure. Peroxynitrite is a reactive nitrogen species that is particularly harmful to proteins. It has been implicated in the development of certain cancers, hepatitis, and chronic inflammation. In the skin, peroxynitrite contributes to the breakdown of vital proteins, such as collagen.

Singlet Oxygen is generated in the skin by by UV. In vivo, it is linked to the oxidation of LDL cholesterol and cardiovascular disease. Singlet oxygen is highly unstable and durable. Carotenoids are very effective at scavenging singlet oxygen. Superoxide Anion is a precursor of all other reactive oxygen species and sometimes is referred to as “the mother of free radicals.” It is highly toxic and contributes to lipid and DNA damage. Antioxidants that scavenge superoxide anion also help prevent the formation of radicals such as hydrogen peroxide and hydroxyl. Superoxide anion has been linked to hypertension and cardiovascular damage.

Recently, Brunswick Labs has introduced a new test called ORAC6.0. This test expands the ORAC platform to measure the antioxidant capacity against each of the five primary reactive oxygen species mentioned above as well as Hypochlorite (HOCl) which is another important free radical that is commonly found in the body as a by-product of the metabolism of other free radicals. Direct reaction of HOCl with plasmid DNA gives rise to single- and double-strand breaks via chloramine-mediated reactions. ORAC6.0 substantially improves broad-spectrum antioxidant analysis and gives evidence of the diverse antioxidant potential of natural products against radicals other than just peroxyl.  Brunswick Labs’ research shows that the antioxidants found in a wide range of natural products are effective against these primary radicals, and that in many cases a preponderance of a product’s antioxidant capacity is described by performance against the six free radicals included to the ORAC6.0 panel.

RESULTS OF ULTIMATE PROTECTOR+ ORAC6.0 TEST

Recently [August/2019] Brunswick Labs has tested ULTIMATE PROTECTOR+™ using the new ORAC6.0 tests. The results reveal an incredible overall ORAC6.0 value of 272,743 µmole TE/gram (i.e., 272,743 per gram!). In addition, the results show that the formula offers excellent protection against all of the six types of free radicals. Specifically, the results show values of 3,376 µmole TE/gram for peroxyl radicals, 5,569 µmole TE/gram for hydroxyl radicals, 2,758 µmole TE/gram for peroxynitrite radicals, 221,866 µmole TE/gram for superoxide anion radicals, 34,169 µmole TE/gram for singlet oxygen radicals, and 5,005 µmole TE/gram for hypochlorite radicals. The table (below) shows for each free radical type the ORAC6.0 daily values for six capsules of ULTIMATE PROTECTOR+™ containing 3.55 grams of the formula.

The overall daily ORAC6.0™ value for six capsules  obtained by adding the values for each free radical type is 968,237 units (272,743 units x 3.55 g)! To the best of our knowledge there is no other product that even comes close to providing such complete protection both in terms of breadth of coverage and overall strength. The Brunswick Labs ORAC6.0™ test results for ULTIMATE PROTECTOR+™ are posted on our blog.


Ultimate Protector+ nrf2 activator formula

 

The bottom line is that you (or anyone) can stand to benefit dramatically from an advanced antioxidant formula that provides exceedingly high ORAC6.0 values and hence amazingly high cell protection…with just a modest daily dose of six small capsules. If you are at all interested to see how well this formula can protect your heath, then we suggest you try a bottle. See for yourself how ULTIMATE PROTECTOR+™ acts to provide you with the ultimate level of protection against free radicals. It’s 100% guaranteed.

ULTIMATE PROTECTOR+™ ORAC6.0 Units Per Serving (six capsules)

ORAC6.0 Units
Per Serving*

Free Radical Type
11,985 Peroxyl Radical is very important in many biological systems, including lipid peroxidation, DNA cleavage, and protein backbone modification.
19,770 Hydroxyl is highly reactive and cannot be eliminated by our endogenous enzymes. It damages virtually all types of macromolecules: carbohydrates, nucleic acids, lipids, and amino acids. In the skin, hydroxyl radicals are created by UV exposure.
9,791 Peroxynitrite is a reactive nitrogen species that is particularly harmful to proteins. It has been implicated in the development of certain cancers, hepatitis, and chronic inflammation. In the skin, peroxynitrite contributes to the breakdown of vital proteins, such as collagen.
121,300 Singlet Oxygen is generated in the skin by UV exposure. It is linked to the oxidation of LDL cholesterol and cardiovascular disease.
787,624 Superoxide Anion is a precursor of all other reactive oxygen species – sometimes referred to as “the mother of free radicals.” It is highly toxic and contributes to lipid and DNA damage.

17,768

Hypochlorite HOCl – direct reaction of HOCl with plasmid DNA gives rise to single- and double-strand breaks via chloramine-mediated reactions.

968,237

Total ORAC6.0 Per Daily Serving of Six Capsules (3.55 g)

View the Brunswick Labs Ultimate Protector™ ORAC6.0 Test Report Here

 

ULTIMATE PROTECTOR+™ contains USP-grade non-GMO Vitamin C, SFB® standardized fruit blend (~50% polyphenols, high-ORAC powder: 9,000 µmole TE/g) from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), Green Tea Extract (93% polyphenols, 50% EGCG), VinCare® Whole Grape Extract (>80% polyphenols, ORAC>19,000 µmole TE/g), Calcium Malate, Magnesium Malate, and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients and is a known Nrf2 activator).

* Full-spectrum antioxidants in Ultimate Protector+ include polyphenols, flavonoids, anthocyanidins, oligomeric proanthocyanidins, catechins, curcuminoids, ellagic acid, pterostilbene, resveratrol, chlorogenic acid, xanthines, punicalagins, quercetin, zeaxanthin, carotenoids, polysaccharides, quinic acid, and others.

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ULTIMATE PROTECTOR+ NRF2 ACTIVATOR FORMULA – NEW DESIGN!

Dr. Hank Liers, PhD ultimate protector+ antioxidant Nrf2 activator formulaToday I discuss HPDI’s newly updated ULTIMATE PROTECTOR+ antioxidant, cell protection, and Nrf2 activator formula. I first formulated Ultimate Protector in 2012 after I learning about plant-based Nrf2 activators.

My original idea behind developing Ultimate Protector was to unite three design elements in a single formula preventing and ameliorating free-radical damage in the body. I recently updated Ultimate Protector (now Ultimate Protector+) based on availability of improved ingredients and additional research studies on Nrf2 activators.

ULTIMATE PROTECTOR+ ADVANCED CELL PROTECTION & NRF2 ACTIVATOR FORMULA

The three design elements include: 1) non-GMO Vitamin C, 2) high ORAC5.0 antioxidants, and 3) multiple plant-based Nrf2 activators. Nrf2 activators cause release of Nrf2 proteins that are bound in every call of the body. Once released they migrate to the cell nucleus where they cause genetic transcription of antioxidant enzymes that can neutralize excess free-radicals in the body.

THREE ELEMENTS OF ULTIMATE PROTECTOR+ FORMULA

1 – NON-GMO VITAMIN C

The new Ultimate Protector+ includes the same amount of Vitamin C as before—owing to its ability to rapidly reduce superoxide and nitroxide radicals, and scavenge hydroxyl, alkoxyl, and peroxyl radicals. Vitamin C also reacts with non-radical species like singlet oxygen and hypochlorous acid. Vitamin C ‘recycles’ other antioxidants (in its role as electron donor) and allows them to quench more free radicals. Vitamin C itself was recently shown to be a Nrf2 activator.

ultimate protector+ nrf2 activator formula uses three modes of action

Ultimate Protector+ uses three modes of action

2 – HIGH-ORAC6.0 VALUE INGREDIENTS

By means of carefully choosing plant ingredients with the highest ORAC 6.0 values, the product can neutralize all five major types of free radicals commonly found in the body, including: 1) peroxyl, 2) hydroxyl, 3) peroxynitrite, 4) singlet oxygen, and 5) superoxide anion. Ultimate Protector+ includes many plant-based ingredients with high ORAC6.0 values. These include green tea extract, whole grape extract, curcumin, resveratrol, bilberry, and mangosteen.

Brunswick Labs tested Ultimate Protector+™using the ORAC6.0™ test. The results reveal an extremely high overall ORAC6.0 value of 272,743 µmole TE/gram (i.e., 272,743 per gram!). In addition, the results show that the formula offers excellent protection against all six types of free radicals measured. Specifically, the results show values of 3,376 µmole TE/gram for peroxyl radicals, 5,569 µmole TE/gram for hydroxyl radicals, 2,758 µmole TE/gram for peroxynitrite radicals, 221,866 µmole TE/gram for superoxide anion radicals, 34,169 µmole TE/gram for singlet oxygen radicals, and 5,005 µmole TE/gram for hypochlorite radicals. The table (below) shows for each free radical type the ORAC6.0 daily values for six capsules of Ultimate Protector+™ containing 3.55 grams of the formula.ORAC6.0 test results

The overall daily ORAC6.0™ value for six capsules obtained by adding the values for each free radical type is 968,237 units (272,743 units multiplied by 3.55 gram (serving size)! To my knowledge, no other product comes close to providing such complete protection both in terms of breadth of coverage and overall strength. For a fuller explanation of Brunswick Labs ORAC6.0™ test results for Ultimate Protector+™ please read my article “Ultimate Protector+ Brunswick Labs ORAC6.0 Test Report.”

3 – POTENT NRF2 ACTIVATORS

The science on Nrf2 activators clearly shows a wide variety of plant polyphenols act endogenously to cause genetic transcription of many protective enzymes, like superoxide dismutase, glutathione transferase, and heme oxygenase. Many well-known, well-researched Nrf2 activators are high ORAC5.0 antioxidants. These first act as antioxidants giving up an electron, and then act as weak pro-oxidants needed to stimulate Nrf2 activity. In Ultimate Protector+ these ingredients include green tea extract, whole grape extract, curcumin, resveratrol, bilberry, and mangosteen. In addition, ingredients such as extracts of apple, blueberry, cranberry, pomegranate, blueberry, apple, chokeberry, and goji berry are shown in studies to be important Nrf2 activators.

ULTIMATE PROTECTOR+ SUMMARY

Ultimate Protector+ is a powerful antioxidant and Nrf2 activator formula. Both ORAC6.0™ test results and user experience confirm its effectiveness for quenching free radicals and preventing or reducing oxidative damage from all major types of free radicals. There is currently no other antioxidant and/or Nrf2 activator formula available that provides the level of cell protection afforded by Ultimate Protector+.

Ultimate Protector+ is available from HPDI: ULTIMATE PROTECTOR+
(http://www.integratedhealth.com/ultimate-protector.html)

12 plant-based Nrf2 activators

ULTIMATE PROTECTOR+ RESOURCES

ULTIMATE PROTECTOR+: http://www.integratedhealth.com/ultimate-protector.html

ULTIMATE PROTECTOR ORAC6.0™ TEST RESULTS
(http://www.integratedhealthblog.com/wp-content/uploads/2019/08/up-orac6.pdf)

BLOG ARTICLES

Ultimate Protector+ Brunswick Labs ORAC6.0™ Test Report
http://www.integratedhealthblog.com/ultimate-protector-brunswick-labs-orac6-0-test-report/

Amazing Healing Potential of Natural Nrf2 Activators:
http://www.integratedhealthblog.com/amazing-healing-potential-natural-nrf2-activators/

Preventing Free Radical Damage with Ultimate Protector+:
http://www.integratedhealthblog.com/amazing-healing-potential-natural-nrf2-activators/

Ultimate Protector+ Design Considerations: http://www.integratedhealthblog.com/scientific-basis-ultimate-protector/

Natural Phytochemical Nrf2 Activators for Chemoprevention:
http://www.integratedhealthblog.com/natural-phytochemical-nrf2-activators-for-chemoprevention/

New Directions For Preventing Free Radical Damage:
http://www.integratedhealthblog.com/new-directions-for-preventing-free-radical-damage/

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Rejuvenation Program: Part Four

FOUNDATIONAL ELEMENTS IN THE HPDI MASTER REJUVENATION PROGRAM

Fred Liers PhD rejuvenation programThe HPDI Rejuvenation Program provides practices, protocols, and recommendations proven over 31 years. It is a complete program to rejuvenate, regenerate, and boost vitality to body, mind, and spirit. It is especially helpful for those who want to restore health.

The program emphasizes establishing basic nutrition, foundational nutritional formulas, and high-RNA Rejuvenate!™ superfoods and other sources of dietary nucleic acids. The program rests on six elements: 1) Attitude/Commitment, 2) Detoxification, 3) Preventing Toxicity, 4) Health Building Nutrition, 5) Building Powerful Immunity, and 6) Supporting Protocols.

The six foundational elements remain powerful individually, but act synergistically when combined to support optimal health. The results are greatly improved capabilities for your body to heal, regenerate, rejuvenate, and restore its vitality.

As I stated in Part Three of the Rejuvenation Program series, health building nutrition plays a major role in the process of rejuvenation. We recommend emphasizing organic and/or wildcrafted foods, consuming more plant-based foods, raw foods, and generally consuming natural, whole foods (e.g., avoiding refined/processed foods).

I also discussed foods recommended in our Rejuvenation Program. Our recommendations include consuming foods high in nucleic acids (RNA and DNA). RNA-rich foods include chlorella and  Rejuvenate!™ superfoods. Rejuvenate! superfoods provide therapeutic levels of nucleic acids to support optimal rejuvenation, revitalization, and health. They also provide supporting nutrients (e.g., d-ribose, coenzyme B vitamins) that maximize utilization and healing effects of dietary nucleic acids in the body.

HPDI offers three versions of Rejuvenate!, including Rejuvenate! (original greens)Rejuvenate PLUS, and Rejuvenate! Berries & Herbs. Rejuvenate! PLUS and Rejuvenate Berries & Herbs are the most complete. Both provide delicious taste, therapeutic levels of dietary RNA, nutrients that support the body’s use of nucleic acids (e.g., d-ribose), a complete multivitamin, essential fats, and high levels of protein.

THE NEED FOR NUTRITIONAL SUPPLEMENTATION

Last month, I discussed dietary/food aspects of nutrition. Today, I present key roles played by what we call “foundational” (or sometimes “core”) nutritional supplements. Foundational nutritional supplements are one of the critical means to success in creating powerful health by establishing optimal nutrient status in the body. Foundational supplements include: 1) multivitamins, 2) An antioxidant / Vitamin C formula, 3) essential fats, and 4) high-RNA superfoods.

We have found that proper nutritional supplementation provides important nutrients not always easily available in the diet. This partly relates to the fact that our needs for nutrients have never been greater. In addition, there are various reasons that most foods are deficient in nutrients, and therefore cannot or do not provide levels of nutrients required to sustain optimal health.

Some reasons dietary supplements are necessary include the fact that most crops are grown in nutrient-deficient or depleted soils; increased demands by the body due to greater needs for nutrients (relating to detoxification, stress, pollution, etc.); biochemical individuality resulting in greater needs for certain nutrients depending on the biochemistry unique to individuals. Biochemical individuality means that a person may require many times the US Daily Value of specific nutrients. In fact, one person may need hundreds of times the amount of a nutrient compared to a different person.

In addition, needs change during the year due to environmental circumstances. Changing seasons, environments, air/water supply, etc. mean that an individual’s need for nutrients typically changes during the year (e.g., more vitamin D needed in the winter, more nutrients needed to deal with pollution associated with urban environments or stress, etc.). Nutrient density of foods also varies by location, season, etc. The availability of nutrients in foods (even organically grown foods) can vary substantially due to season, geography, growing methods, etc.

All these factors add up to the fact that it is difficult to ensure optimal nutrient status without supplementation. Because the need for nutrients is greater than ever for most people, the need for nutritional supplementation is also greater than ever. Nutritional supplements provide an effective (and cost effective) means to ensure the high levels of nutrients required to build, sustain, and maintain optimal health.

NUTRITIONAL SUPPLEMENTS IN THE HPDI REJUVENATION PROGRAM

ESTABLISHING FOUNDATIONAL NUTRITION

Foundational formulas are the primary supplements we recommend for success not only in our Rejuvenation Program, but also for helping create better health generally. In fact, foundational supplement formulas are the basic building blocks for establishing and maintaining high nutritional status at all times in any program. (While foods are your primary source of nutrients, nutritional supplements are the best way to ensure intake of nutrients needed for good health.)

As noted above, the four foundational nutritional supplements we recommend are: 1) a high-potency multivitamin, 2) an essential fats formula (omega-3 and omega-6), and 3) Vitamin C (preferably buffered) with antioxidants (especially bioflavonoids), and 4) Rejuvenate!™ superfoods (and/or other high-RNA superfoods).

These four types of foundational formulas are the most important supplements and superfoods. Even if you take no other dietary supplements, these are the formulas that ensure you get basic nutrients required for good health. In fact, no diet or nutritional supplementation program is complete without them.

I will now consider the four types of foundational formulas, explain how they function, and reasons why they essential for good health.

FOUNDATIONAL #1: A HIGH-QUALITY MULTIVITAMIN

A high-quality, high-potency multivitamin is the single most important supplement you can take. A good multivitamin ensures you receive important nutrients not always available in optimal amounts in foods. Taking a multivitamin helps guarantee uptake of nutrients that ar e not readily available because modern diets have strayed far from traditional diets. In addition, modern lifestyles create far greater demands for critical nutrients even as many nutrients are increasingly less available from foods. Multivitamins help break the cycle of deficiency and degeneration.

Critical nutrients provided by a good therapeutic multivitamin formula include a wide range of essential vitamins, minerals, and cofactors. Such a formula will usually include trace minerals, fat-soluble vitamins (A, E, D, & K), coenzyme B vitamins, magnesium, or other nutrients known to be deficient in the diets of most individuals.

Important factors to consider when looking for a good multivitamin, include high-potency, forms, completeness, balance, assimilability (e.g., ease of uptake and rapid assimilation), ease of use (convenience), etc.

High-potency is important because for most nutrients, the so-called “daily value” is simply inadequate for most people. Most individuals need many times the daily value of vitamins for good health. This is because daily values are established based on minimum amounts required for sustain life (e.g., survival) rather than the optimal amounts needed for good health.

As noted, studies of biochemical individuality show that individuals may require many times greater amounts of specific nutrients than are needed by the average person. Because most vitamins (especially water soluble ones) are essentially non-toxic even in relatively large doses (i.e., hundreds or sometimes thousands of times the daily value), it pays to provide your body with larger amounts of critical nutrients that it may require because you may not be an ‘average’ person.

Complicating this picture is the fact that individuals needs for specific nutrients vary widely. Thus, for example, one person’s need for vitamin C may be somewhat higher than average, yet the same person’s need for vitamin D may be significantly higher than average.

The proper forms of the nutrients are another critical factor. While forms have not always been a prime consideration (either of consumers or formulators), they are critically important. Forms are worthy of attention because we know that the form of a vitamin or mineral can make a major difference in terms of how it assimilated and used in the body.

For example, Krebs cycle bionutrients (i.e., mineral carriers, such as citrates, malates, alpha-ketoglutarates, succinates, or fumarates) are known to be superior precisely because they are the forms naturally recognized and utilized in the body. This is because these forms are used in the Krebs cycle (or citric acid cycle) that is part of the metabolic pathway used to generate energy (ATP) from nutrients in foods. In contrast, elemental forms of minerals and/or forms that are not part of the Krebs cycle may be more difficult to assimilate because they must be converted into forms the body can use. The biological cost is reduced bioavailability, as well as cellular energy expense and time required for metabolic conversion. As you can see, forms matter for health!

Other important factors include completeness and balance. Completeness is important in a multivitamin because the body requires a wide range of nutrients working together to create and sustain health. Many multivitamins are neither complete nor balanced. This relates partly to the fact that multivitamins are often not designed with an understanding of nutrients, forms, or amounts needed for health. Consequently, many commonly available multivitamins incorporate less effective forms, inadequate amounts, and improper ratios of nutrients. This reflects a general lack of understanding by formulators about how nutrients work together to build and sustain health. In contrast, supplements are available that provide completeness and balance.

HPDI offers several high-quality, balanced, and complete multivitamins providing easily assimilated forms of nutrients in optimal amounts. These include Hank & Brian’s Mighty Multi-Vite!, Multi Two caps or tabs, and Chewable Kids Mighty-Multi! (which is also designed for adults to enjoy, too). We recommend our capsule formulas because they are the easier to assimilate. However, our tablet formulas are both effective and cost-effective. Children benefit greatly from a multivitamin, and for them we offer our chewable Kids Mighty-Multi! multivitamin formula.

FOUNDATIONAL #2: AN ANTIOXIDANT / VITAMIN C FORMULA

Vitamin C is legendary for its healing capacities. Yet, it is notable that despite numerous studies and accolades by nutritionists, it remains underutilized by mainstream medicine and is completely under-appreciated for the healing powerhouse it represents for human health.

We include Vitamin C as a foundational formula because we understand its role in creating and sustaining optimal health. Vitamin C not only is a potent antioxidant, but also a powerful immune builder/anti-viral, cholesterol controller, and connective tissue strengthener. In fact, no other vitamin or nutrient can take its place in terms of what it can contribute to human health, longevity, and well-being.

Ever since Linus Pauling wrote Vitamin C and the Common Cold, Vitamin C has held a place of esteem among nutritional scientists and consumers of Vitamin C products. Pauling went on to present further studies and to write his best-seller How to Live Longer and Feel Better (rev. 2006). Vitamin C plays a major role both in his discussion of vitamins and in the supplement regimens he recommends.

In nature, Vitamin C is always combined with bioflavanoids. Bioflavanoids (such as rutin, quercetin, catechins, anthocyandins, and oligomeric proanthocyanidins (OPCs)), work synergistically with Vitamin C to create powerful antioxidant effects, counteract inflammation, and strengthen connective tissues. In addition, Vitamin C and bioflavanoids combine with other antioxidants (including glutathione, lipoic acid, and selenium) in a process called “redox cycling.” In this process, antioxidants protect and “spare” each other, thereby allowing for significantly increased antioxidant protection in the body.

We offer a variety of Vitamin C products, including formulas with bioflavonoids. Our Vitamin C formulas include Ultimate Protector+™, PRO-C™, Buffered Vitamin C tabs, and Buffered Vitamin C powder. We typically recommend taking a buffered Vitamin C product to prevent acidosis and help maintain proper pH levels in the body.

We consistently find that one of greatest means for success in creating health using dietary supplements is to ensure you take all four types of foundational formulas. For example, many people take one or two foundational formulas: a multivitamin, essential fats, Vitamin C plus bioflavonoids, and/or high-RNA superfoods. But how many people take all four daily? Do you take all four daily? You might be surprised at the results if you took them all daily. This is because foundational formulas work together synergistically and leverage each other in ways that exceed the health-building effects that can be expected when foundational formulas are taken individually.

FOUNDATIONAL #3: AN ESSENTIAL FATS FORMULA

Many people understand the need to take supplemental multivitamins. The need for essential fatty acids (EFAs) has gained increased attention recently, and it is no less important. More people are consuming fish, fish oils, and vegetarian sources of essential fats, including chia seeds. However, the need for supplementing diet with essential fats to ensure adequate daily intake has never been greater than today.

There are two basic essential fats: alpha-linoleic acid (omega-3) and linolenic acid (omega-6). Other fats are sometimes included as being essential fats, including gamma-linolenic acid (GLA), an important omega-6 fatty acid, and eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), important omega-3 fatty acids.

Essential fats are considered ‘essential’ because they are needed for biological processes (i.e., they are required to sustain life) rather than acting only as a food-based source of energy (as do many other non-essential fatty acids). Humans, therefore, must ingest essential fatty acids both for survival and for good health.

Essential fats play multiple roles in the body and serve many different functions. These functions include being modified to make eicosanoids (affecting pain and inflammatory processes); regulating steroid production and hormone synthesis; regulating pressure in the eyes, joints and blood vessels; mediating the immune response; regulating smooth muscle and autonomic reflexes; are needed for oxygen transport from red blood cells to tissues; are necessary for kidney function and fluid balance; preventing clumping of red blood cells; regulating mood and depression, and regulating nerve transmission.

Every cell and organelle within the cells are encased and protected by membrane made of phospholipids. A major component of these phospholipids are essential fatty acids that control membrane fluidity and the ability to pass important nutrients into the cells and toxins out of the cells. Without adequate essential fats the cell membranes can become rigid and dysfunctional.

We offer an essential fats product, called Hank & Brian’s Essential Fats Plus E. This product contains EPA and DHA from highly purified fish oils, GLA from cold-processed borage oil, and full spectrum Vitamin E consisting of all eight natural forms of tocotrienols and tocopherols. These mixed forms of Vitamin E perform many beneficial functions in the body (such as lowering cholesterol and clearing plague out of blood vessels) and also protect the essential fats from oxidizing in the capsule and in your body. The ratio of EPA to GLA in this products is 4:1, which is considered the ideal ratio for optimal effects in the body.

FOUNDATIONAL #4: HIGH-RNA SUPERFOODS, INCLUDING REJUVENATE! FORMULAS

Our recommendations for foundational formulas now include high-RNA superfoods. We first recommend a multivitamin, an antioxidant / Vitamin C formula, and essential fatty acids. After these three foundational formulas are established in a daily regimen, the addition of a high-RNA superfood further contributes to excellent health.

We include high-RNA superfoods (and especially recommend Rejuvenate!™ superfoods) in our foundational supplements program after having studied the remarkable healing powers of chlorella and other high-RNA nutrients for six years. When taken in sufficient amounts, superfoods high in ribonucleic acid (RNA) show remarkable effects in the body. These effects include higher energy levels, greater endurance, better muscle strength, easier breathing, lower cholesterol levels, reductions in angina pains (and other positive cardiovascular effects), more stable blood sugar, better vision, and a more youthful appearance (smoother skin, fewer wrinkles, etc.), and many other benefits.

Our assessment of dietary nucleic acids being essential nutrients is shared by scientists on the cutting-edge of nutrition. In Nucleic Acid Nutrition and Therapy, Dr. Benjamin S. Frank asserts that dietary nucleic acids (RNA, DNA) are “essential nutrients of human beings” as distinct from non-essential, accessory nutrients. He considers nucleic acids and nucleotides an essential dietary category, i.e., as being nutrients “just as essential for humans as vitamins, minerals, proteins, carbohydrates, and lipids” (Frank).

After having studied the positive health effects of dietary RNA in the clinic for more than 20 years, Dr. Frank asserted:

“[N]ucleic acids are an essential nutrient in our daily diets, and […] optimal health and reduced aging are clearly related to their intake, more than to any other nutrient. Nucleic acids in our diets are of paramount importance for the repairing of molecular and gross tissue degeneration, and for combating the process of aging by simple, effective and essentially non-toxic, natural means.”

Dr. Frank’s conclusion that RNA is more essential to health than any other single nutrient underscores the central role of nucleic acids for human health.

We share Dr. Frank’s conclusions regarding the “essential” nature of nucleic acids and nucleotides, and their central role in human health. In fact, it is our direct experience with the health-building effects of dietary nucleic acids (e.g., in chlorella and other foods) that led to further our knowledge of nucleic acid nutrition and therapy, and develop our line of high-RNA Rejuvenate!™ superfoods. Rejuvenate!™ superfoods both provide optimal levels of nucleic acids and include supporting nutrients (e.g., d-ribose, coenzyme B vitamins), which maximize the beneficial effects of dietary RNA for health.

The nucleic acids in Rejuvenate!™ superfoods work directly with HPDI’s other foundational nutritional supplements to create, sustain, and support optimal nutrition for health and healing. We recommend Rejuvenate!™ and/or other high-RNA superfoods as part of program of foundational nutritional supplements that work together to provide full spectrum nutrition. It is because foundational formulas provides a full spectrum of essential nutrients that it is critical to success in our Rejuvenation Program, and to create, maintain, and/or rebuild health.

FOUR FOUNDATIONAL SUPPLEMENTS  =  POWERFUL SYNERGY FOR HEALTH

The best news with respect to dietary nucleic acids is that while they are essential nutrients, their inclusion in our foundational supplement program powerfully leverages their effects by facilitating greater synergy among all nutrients available to the body via foundational supplements. This synergy means the total package of nutrients delivered by all four types of foundational supplements combined delivers far more health-building nutrition than any single foundational formula delivers individually. That’s synergy in action.

The means by which all four foundational supplements succeed in creating and contributing to powerful health relates less to the fact that each singly provides an ‘essential’ piece of the nutrition puzzle. Success relates instead to the fact that when all foundational formulas are taken together, their healthy benefits multiply and greatly exceed the sum of benefits provided by individual foundational formulas. This is a primary reason we emphasize establishing foundational nutrition both within our Rejuvenation Program, and more generally as a starting point for the creation of powerful health.

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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.

Also, I actively began the development of a product called Ultimate Protector that contains many concentrates and extracts from fruits, vegetables, and herbs. This product functions as 1) an excellent source of many Nrf2 activators, 2) a source of powerful antioxidants exhibiting an extremely high ORAC5.0 value per serving, and 3) a source of non-GMO Vitamin C.

More recently (July 2019) I have updated the product to Ultimate Protector+ that contains some exciting new ingredients that are now available on the market including SFB® (Standardized Fruit Blend) that contains among others mangosteen, goji berry, pomegranate, and apple extracts (click on the ingredient name to see detailed blog articles concerning these). In addition, I have added significant amounts of ingredients that are well known as potent Nrf2 activators and antioxidants including Green Tea extract and VinCare® whole grape extract.

 

Ultimate Protector+

New Ultimate Protector+

 

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 ligase is a characteristic Nrf2 target gene, which establishes 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 giant knotweed and 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.”

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+

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 100% 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+    3,376    5,569 2,758 221,866 34,169 267,738
Results are expressed in micro mole TE/g

The total Ultimate Protector+ ORAC5.0 value per serving of 6 small vegetarian capsules (containing 3.55 g) is over 950,00 Micro mole TE.

4) Here is a list of the ingredients in ULTIMATE PROTECTOR+: USP-grade non-GMO Vitamin C, SFB® standardized fruit blend (~50% polyphenols, high-ORAC powder: 9,000 µmole TE/g) from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), Green Tea Extract (93% polyphenols, 50% EGCG), VinCare® Whole Grape Extract (>80% polyphenols, ORAC>19,000 µmole TE/g), Calcium Malate, Magnesium Malate, and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients and is a known Nrf2 activator).

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!

SOURCES

BLOG ARTICLES

 SCIENTIFIC ARTICLES

 

8

Natural Phytochemical Nrf2 Activators for Chemoprevention

Dr. Hank Liers here considers mechanisms involved in the activation of transcription factor Nrf2. Nrf2 is encoded by the NFE2L2 gene. Nrf2 can induce expression of genes encoding for antioxidant enzymes. Thus, it contributes to regulation of oxidative stress. Dr. Liers’ interest regards use of natural phytochemical Nrf2 activators for improving health. Also, see his post, “New Directions for Preventing Free-Radical Damage”(06.27.19).

INTRODUCTION
Nrf2 SIGNALING, FOODS, AND HEALTH

Dr. Hank Liers, PhD nrf2 activatorsDespite progress in the early detection and treatment of cancer, overall mortality rates for most cancers of epithelial origin have not declined during the past three decades. Consequently, in recent years attention has been directed to cancer prevention.

Carcinogenesis can be viewed as a multistep process in which the genes controlling proliferation, differentiation, and apoptosis are transformed and altered under selective environmental pressures.

Tumor development involves three distinct, yet closely linked, phases: initiation, promotion, and progression. The initiation phase is a rapid and irreversible event that occurs when a normal cell is exposed to a carcinogenic event. Frequently, unrepairable or misrepaired DNA damage happens in the initiation phase.

Promotion and progression processes are relatively longer processes than the initiation stage, and are considered reversible. Using various animal cancer models, scientists found that all three cancer development stages can be intervened by treatment with natural (or synthetic) chemicals.

Epidemiological and population studies also establish a close relationship between incidence of cancer and consumption of certain types of food.

The term “chemoprevention” was first coined in 1976 by Michael Sporn, when he referred to prevention of malignancy development by vitamin A and its synthetic analogs. Since then, chemoprevention has been adopted as one of the major tactics to modulate the process of carcinogenesis. Many research studies have proven this strategy is effective in reducing the incidence of cancer in well-defined high-risk groups.

Chemoprevention is by definition the use of natural (or pharmacologic) agents to inhibit the development of invasive cancer. The chemicals with a cancer preventive activity are referred to as chemopreventive agents. A chemopreventive agent can inhibit carcinogenesis either by blocking the DNA damage at initiation stage or by arresting or reversing the processes at promotion and progression stages. Most of the chemical substances used in cancer chemoprevention studies are natural phytochemicals found in food.

On the basis of the inhibition stages, chemopreventive agents have been classified into two categories, namely blocking agents and suppressing agents. Blocking agents act by preventing carcinogens from reaching the target sites, from undergoing metabolic activation, or from subsequently interacting with crucial cellular macromolecules such as DNA, RNA, and proteins at initiation stages.

Suppressing agents, on the other hand, inhibit the malignant transformation of initiated cells at either the promotion or the progression stage. Some agents may work on all three stages of carcinogenesis, and are hence classified into both categories.

DIETARY PHYTOCHEMICALS ARE NATURE’S CHEMOPREVENTIVE AGENTS

Many different animal models and cancer cell lines have been used to evaluate the chemopreventive values of phytochemicals, and have led to the discovery of new classes of chemopreventive agents. These agents include isothiocyanates (such as sulforaphane) from cruciferous vegetables, polyphenols from green and black tea, curcuminoids (from turmeric root), stilbenes such as resveratrol (from giant knotweed plant), flavonoids such as quercetin, and anthocyanidins (from many fruits and soybeans).

Progress also has been made in understanding the mode of action of newly identified chemopreventive agents. Exposure to the chemopreventive agents produces certain level of reactive oxygen species (ROS) or electrophiles, and causes mild oxidative/electrophilic stresses in cells.

Ultimate Protector+

Such mild oxidative stresses are sufficient to initiate the signaling pathways that, in turn, can activate a variety of cellular events, such as induction of phase II detoxification enzymes and antioxidant enzymes, expression of tumor-suppressor genes, and inhibition of cell proliferation and angiogenesis.

In order to survive under a variety of environmental or intracellular stresses, our cells have developed highly efficient protective mechanisms to protect themselves from oxidative or electrophilic challenges. Proteins that comprise phase II detoxification and antioxidant enzymes provide an enzymatic line of defense against reactive oxygen species. These enzymes include superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione S-transferase (GST), and glutamate cysteine ligase.

Induction of phase II and antioxidant enzymes are regulated at the DNA/gene level by antioxidant responsive element (ARE). ARE-mediated gene expression plays a central role in the cellular defense against cellular oxidative damage.

Experimental evidence supports the view that induction of ARE-mediated cytoprotective enzymes is a critical and sufficient mechanism to enable protection against carcinogenesis provoked by environmental and endogenous insults.

One of the key ARE-binding transcription factors is Nrf2. Induction of cytoprotective enzymes in response to ROS, electrophiles, and chemopreventive agents is a cellular event that is highly dependent on Nrf2 protein.

Nrf2 BOOSTS CELL DETOXIFICATION AND ANTIOXIDANT ENZYMES

By activating Nrf2 signaling, chemopreventive agents can increase cellular detoxification and antioxidant enzymes, thereby enhancing removal of reactive carcinogens and blocking carcinogenesis. This hypothesis has been tested in many studies.

For example, a study with sulforaphane (an isothiocyanate present abundantly in cruciferous vegetables) has shown that oral administration of this phytochemical could effectively block benzo[a]pyrene-induced forestomach tumors in mice. This protective effect was abrogated in mice that could not produce Nrf2, supporting a critical role of phase II detoxification and antioxidant enzymes in the prevention of carcinogenesis by chemopreventive agents.

Nrf2 is normally bound in the cytoplasm of cells to a protein called KEAP1. However, when an appropriate phytochemical agent attaches to a kinase receptor on the cell wall a phosphate group is released that causes the Nrf2 to be released. The Nrf2 then migrates into the cell nucleus and causes an antioxidant enzyme, such as SOD, to be released. This endogenously produced enzyme then can protect against ROS, electrophiles, and chemopreventive agents.

In practice, it has been found that a combination of multiple polyphenols works significantly better than single ingredients at activating Nrf2. In fact, in one experiment it was found that a combination of five ingredients all known to be Nrf2 activators was 18 times more effective than any single ingredient. Furthermore, it was found that this combination of five ingredients  increased levels of SOD by 30% and catalase by 56% after 120 days.

ULTIMATE PROTECTOR+
A POWERFUL, NATURAL Nrf2 ACTIVATION FORMULA FOR GREATER HEALTH

In view of the above information and the fact that new and more effective ingredients are available, we have updated our exceptional formula designed to maximize activation of Nrf2 in the body. This new product is ULTIMATE PROTECTOR+. It is among the most advanced, natural Nrf2 activator formula on the market today.

We include a broad range of Nrf2 activators in ULTIMATE PROTECTOR+. These activators source from a wide variety of freeze-dried and concentrated fruits, vegetables, and herbs. These include USP-grade non-GMO Vitamin C , SFB® standardized fruit blend (~50% polyphenols, high-ORAC powder: 9,000 µmole TE/g) from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry), Curcumin(standardized extract with 95% curcuminoids), Trans-Resveratrol(98% from Giant Knotweed), Green Tea Extract(90% polyphenols, 50% EGCG),  and VinCare® Whole Grape Extract (>80% polyphenols, ORAC>19,000 µmole TE/g). In addition the product contains Calcium Malate and Magnesium Malate, that support ATP and enzyme product and Bioperine® (a patented black pepper extract that significantly enhances absorption of all ingredients and is a known Nrf2 activator).

Phytochemicals provided by the array of freeze-dried and concentrated fruits, vegetables, and herbs in the formula include: Polyphenols, Phenolic acids, Proanthocyanidins (OPCs), Anthocyandins, Catechins, Glucosinolates, Zeaxanthin, Lutein, Lycopene, Beta Carotene, Chlorogenic acid, Ellagic acid, Quercetin, Quinic acid, Trans-Resveratrol, Ferulic acid, Punicalagins, Phloridzin, Polysaccharides, Xanthones and more.

In addition to these Nrf2 activators (above), ULTIMATE PROTECTOR+ contains an extremely broad array of plant based antioxidants from the same sources described above, as well as from non-GMO USP grade Vitamin C. All ingredients in this product have been used in chemoprevention protocols, as well as in protocols aimed at preventing free-radical damage in the body.

Ultimate Protector is now available on the HPDI website!

 

Ultimate Protector+Ultimate Protector+ is new and improved

 

REFERENCES

“Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells.”  Am J Physiol Lung Cell Mol Physiol 294: L478–L488, 2008.

“Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals.” Planta Med. 2008 Oct; 74(13): 1526–39. Epub 2008 Oct 20.

“Nrf2: a potential molecular target for cancer chemoprevention by natural compounds.” Antioxid Redox Signal. 2006 Jan–Feb; 8(1–2):99–106.

“Cancer chemoprevention by phytochemicals: potential molecular targets, biomarkers and animal models.” Acta Pharmacol Sin. 2007 Sep; 28(9): 1409–21.

“Natural dietary anti-cancer chemopreventive compounds: redox-mediated differential signaling mechanisms in cytoprotection of normal cells versus cytotoxicity in tumor cells.” Acta Pharmacol Sin. 2007 Apr; 28(4): 459–72.

“Anticarcinogenesis by dietary phytochemicals: cytoprotection by Nrf2 in normal cells and cytotoxicity by modulation of transcription factors NF-kappa B and AP-1 in abnormal cancer cells.” Food Chem Toxicol. 2008 Apr; 46(4): 1257–70. Epub 2007 Sep 15.

“Signal transduction events elicited by cancer prevention compounds.” Mutat Res. 2001 Sep 1; 480–481: 231–41.

“Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention.” Toxicology. 2010 Dec 5; 278(2): 229–41. Epub 2009 Oct 20.

“NF-kappa B and Nrf2 as potential chemopreventive targets of some anti-inflammatory and antioxidative phytonutrients with anti-inflammatory and antioxidative activities.” Asia Pac J Clin Nutr. 2008; 17 Suppl 1:269–72.

“Regulation of NF-E2-Related Factor 2 Signaling for Cancer Chemoprevention: Antioxidant Coupled with Antiinflammatory.” Antioxid Redox Signal. 2010 Dec 1; 13(11): 1679–98. Epub 2010 Aug 17.

“Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention.” AAPS J. 2010 Mar; 12(1): 87–97. Epub 2009 Dec 15.

“Dietary chemopreventive compounds and ARE/EpRE signaling.” Free Radic Biol Med. 2004 Jun 15; 36(12): 1505–16.

 “Multiple molecular targets in cancer chemoprevention by curcumin.” AAPS J. 2006 Jul 7; 8(3): E443–9.

ADDITIONAL RESOURCES

Ultimate Protector™

The Amazing Healing Potential of Natural Nrf2 Activators – by Dr. Hank Liers

Preventing Free-Radical Damage Using Ultimate Protector™ – by Dr. Hank Liers

New Directions for Preventing Free-Radical Damage  – by Dr. Hank Liers

Ultimate Protector and the Role of Foundational Supplements for Health – by Fred Liers, PhD