Dr. Hank Liers, PhD ultimate protector+ nrf2 antioxidantFred Liers PhD ultimate protector+ Nrf2 antioxidant formula

There’s a new kind of super-antioxidant formula in town. It will quench your free radicals in ways you never conceived. It’s called Ultimate Protector+. Its benefits are many due to a triple-action design that includes instructing cells to make their own antioxidants, a process known as Nrf2 activation. The benefits range from anti-aging and anti-inflammatory effects to support for immunity, brain function, and cardiovascular health. Your body depends on antioxidants to defend it from oxidative stressors. And Ultimate Protector+ defends you like nothing else can.

Ultimate Protector+ is among the world’s premier Nrf2 antioxidant supplements. It started when Dr. Hank realized that a triple-mode formula could best leverage the antioxidant powers available via Nrf2 activators in supplement form. That is, he could develop an ultra-effective Nrf2 activator-antioxidant formula by combining 1) non-GMO vitamin C, 2) potent exogenous (external) antioxidants from plant substances, and 3) plant-based Nrf2 transcription factor activators for endogenous (internal) antioxidant production within cells.

Dr. Hank designed Ultimate Protector+ to provide the most comprehensive antioxidant protection going beyond any supplement. The proof of his design methodology is the fact that one serving (six small capsules) of Ultimate Protector+ provides nearly 1,000,000 ORAC6.0 units. The ORAC6.0 test from Brunswick Labs measures how effectively an antioxidant can perform against six different free radicals: hydroxyl, peroxyl, peroxynitrite, singlet oxygen, superoxide anion, and hypochlorite (hypchlorous acid).

Ultimate Protector+ nrf2 activator formula

Most antioxidant supplements may effectively quench one or two types of free radicals. What makes Ultimate Protector+ different is its unique capacity to quench all six major free radicals. Ultimate Protector+ provides a significant edge in defending your body against the full spectrum of oxidants encountered in daily life.

The distinctive advantage of balanced free radical defense against a broad spectrum of oxidants distinguishes Ultimate Protector+ as a premier antioxidant and anti-aging supplement. This also makes it a “go-to” formula for supporting strong immunity, mitigating the effects of inflammation, enhancing brain function, boosting cardiovascular health, etc., as well as generally maintaining high antioxidant status in cells.

plant-based antioxidants nrf2 activators ultimate protector+


Looking at the Brunswick Labs’ ORAC6.0 test results (from August 2019) for Ultimate Protector+, you see various oxidants (hydroxyl radical, peroxyl radical, singlet oxygen, etc.) are quenched at somewhat different levels. What is most important is that all six types are quenched, and that the total level of antioxidant protection—968,237 µmole TE/gram—is extremely high. To get an idea of how high that level of protection is, consider that a typical “good” antioxidant supplement might provide about 7,000–10,000 µmole TE/gram.

Specifically, the test results for Ultimate Protector+ 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 (3.55 g) is obtained by adding the values for each free radical type. The total of 968,237 units is calculated by multiplying 272,743 units x 3.55 gram serving). To our knowledge there is no other Nrf2 or antioxidant formula that comes close to providing the complete protection of Ultimate Protector+ in terms of breadth of coverage and overall strength.


Ultimate Protector+ is a next generation cell protection formula that simultaneously meets the body’s needs for 1) high levels of Vitamin C, 2) full spectrum antioxidants (including polyphenols, flavonoids, anthocyanidins, oligomeric proanthocyanidins, catechins, curcuminoids, ellagic acid, pterostilbene, resveratrol, chlorogenic acid, xanthines, punicalagins, quercetin, zeaxanthin, carotenoids, polysaccharides, quinic acid, and more), and 3) many of the most protective enzyme activators (Nrf2 activators) — in a single product! This potent combination of characteristics distinguishes the formula because no other single formula available today offers such complete protection.

Ultimate Protector+ supplies nutrients that provide anti-aging, anti-inflammatory, and pain relieving effects, as well as ultra-high levels of antioxidant protection. Damage to cells caused by free-radicals contributes to many degenerative health conditions and to the aging process. This formula effectively supports the body in combating adverse effects of free-radicals.

ultimate protector+ triple action antioxidant nrf2 supplement


• Anti-aging

• Anti-inflammatory

• Pain relief

• Acts to support the body regarding brain function, cardiovascular conditions, hypertension, and supports strong immunity

• Ultra powerful free radical defense. Helps prevent and mitigate free radical damage that contributes to conditions of poor health.

• Facilitates the body’s internal production of antioxidant enzymes within cells by supplying many powerful natural Nrf2 transcription factor activators

• Ultra effective, high potency, best-in-class antioxidant protection


• Plant Based Nrf2 Activators Potentiate the Body’s Internal Antioxidant Systems

• Ultra-High Antioxidant Potency as measured by ORAC6.0 testing to be over 968,000 micro moles TE per serving!

• Complete Formula Defends Body Against All Six Major Classes of Free Radicals including: 1) peroxyl, 2) hydroxyl, 3) peroxynitrite, 4) singlet oxygen, 5) superoxide anion, and 6) hypochlorite

• Provides 12+ Fruit- and Vegetable-Based Antioxidants and Nrf2 Activators to Offer Full Spectrum Protection

• Synergistic Formula Combines Effects of Endogenous (Internally Produced) Antioxidants, Exogenous (externally supplied) Antioxidants, and Vitamin C

• 100% non-GMO Ingredients (includes non-GMO Vitamin C)

• Contains calcium and magnesium malates supporting ATP & enzyme production

• Includes BioPerine ® a black pepper extract that significantly enhances the absorption of all of the nutrients in the formula

• Veggie Capsules (suitable for vegetarians and vegans)

• Easy to Take. Just six small capsules daily provides optimal antioxidant protection.

• Best in Class Cell Protection

Ultimate Protector+ provides high levels of antioxidants


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).

Ultimate Protector+ is contained in a capsule suitable for vegetarians (i.e., a veggie cap) and contains no magnesium stearate.


Ultimate Protector+ satisfies three distinct needs: 1) The need for a non-GMO Vitamin C product. That is, a Vitamin C formula that avoids genetically modified sources, 2) The need for a single powerful antioxidant formula. That is, a single, easy-to-take antioxidant formula offering a broad range of extremely high ORAC6.0 plant source #antioxidants, and 3) The need for a supplement providing a full spectrum of many of the most powerful Nrf2 activators. That is, a supplement providing a wide range of natural #Nrf2 transcription factor activators that allow the body to make its own antioxidant enzymes (e.g., superoxide dismutase (SOD), catalase, heme oxygenase, and glutathione peroxidase).

Ultimate Protector+ is an invaluable supplement for individuals requiring a high-quality, high-potency, and highly effective antioxidant supplement providing exceptionally well-rounded antioxidant protection against a broad range of free radicals. It has a unique triple action capacity to provide the nutrients required by the body for maximum free-radical defense, including plant-based Nrf2 activators that allow cells to produce their own antioxidants.

Providing nearly one million ORAC6.0 units is just one of the ways Ultimate Protector+ supports optimal health. Combining super antioxidant power with non-GMO vitamin C and Nrf2 activators makes Ultimate Protector+ an ideal choice for anyone seeking the highest levels of antioxidant protection.


Ultimate Protector+

Ultimate Protector+
(detailed product information)


Amazing Healing Potential of Natural Nrf2 Activators

Ultimate Protector+ Design Considerations

New Directions For Preventing Free-Radical Damage

Natural Phytochemical Nrf2 Activators for Chemoprevention

Ultimate Protector+ Brunswick Labs ORAC6.0 Test Report

Rejuvenation Program Part 4: Foundational Elements in the Master Rejuvenation Program


Ultimate Protector+ Phenomenal Test Results! 986,000 ORAC6.0 units Versus Six Types of Free Radicals (https://www.youtube.com/watch?v=klx1YSjCStk)

Dr. Hank Liers Deep Dive: Ultimate Protector+ (https://www.youtube.com/watch?v=TVLQlr_0SyU)





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.


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.



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


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.”


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+ 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+

12 plant-based Nrf2 activators


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



Ultimate Protector+ Brunswick Labs ORAC6.0™ Test Report

Amazing Healing Potential of Natural Nrf2 Activators:

Preventing Free Radical Damage with Ultimate Protector+:

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

Natural Phytochemical Nrf2 Activators for Chemoprevention:

New Directions For Preventing Free Radical Damage:


Rejuvenation Program: Part Four


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.


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.



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.


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.


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.


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.


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.


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.



Dr. Hank Liers, PhD ultimate protector plus Nrf2In early 2012 a friend of mine told me about a new product he was taking from a company called LifeVantage. He informed me all he needed to take on a daily basis was one small tablet in order to be protected against free-radical damage of any sort. And that he didn’t even need to take Vitamin C!

I have formulated nutritional supplements for a long time (>25 years), so I knew there was something not quite right about what I was hearing. When I learned he was buying from a multi-level marketing company his story became understandable, but not believable.

I decided I would investigate the product in order to better understand the logic behind it. I watched videos regarding the science underpinning this product, and I read the scientific literature for months.

What I learned was intriguing, so I decided I would formulate a product dealing with free-radical protection that would take the science and the art of formulation to new levels. I would name the product “Ultimate Protector”!!

More recently in early 2019, I decided to upgrade the product because of significant advances in materials and research findings. It is clearer now that most plant polyphenols have Nrf2 activity and often there are many phytochemical (as many as 50 or more) in any specific plant that are both antioxidants and Nrf2 activators. Even well known ingredients such as n-acetyl-l- cysteine, lipoic acid, vitamin C, and black pepper extract exhibit Nrf2 activity. Our upgraded product has been named Ultimate Protector+.


Ultimate Protector +


According to Dr. Joe McCord, in the last 10 years or so there have been over 80,000 papers in peer reviewed publications that relate to Nrf2 activators. Many of these have clearly demonstrated that plant polyphenols are perhaps the best way to intake substances that will stimulate the endogenous production of protective enzymes. In fact, many reputable scientists believe the best way to prevent cancer is via the use of plant polyphenols.

There are also many papers in the scientific literature that have shown the consumption of fruits and vegetables (including herbs) that are inherently high in polyphenols to be one of the best ways to improve health and prevent conditions of poor health. Please see my blog article on this subject: “The Amazing Healing Potential of Natural Nrf2 Activators” (http://www.integratedhealthblog.com/amazing-healing-potential-natural-nrf2-activators/).

In the world of nutritional supplements it is not often that significant scientific/clinical studies are conducted on specific products. The reason for this is primarily economic. However, just as in the case of Nrf2 activators, hundreds of thousands of studies have been conducted by organizations around the world that show the benefits of specific ingredients or groups of ingredients, and these ingredients are used in the development of healthful nutritional supplements.

It is laudable that LifeVantage has had a few scientific/clinical studies done on their product containing five specific Nrf2 activators. This positively supports the huge amount of scientific papers on the subject. However, these few studies do not imply it is a better product than products developed using additional carefully selected ingredients highlighted in the scientific literature. Progress is made continuously in the area of nutritional supplements allowing us to improve on existing products.

As an example of how being aware of the scientific literature on Nrf2 activators, as well as being experienced in the design of groundbreaking new nutritional products, I was recently delighted to observe that high ORAC5.0 values are associated with many of the best Nrf2 activators identified in the scientific literature. This is discussed in my blog article referenced above.

Indeed, this observation is in contrast to the statements by many (even the scientists) that taking antioxidants is unnecessary and perhaps harmful. It appears that these antioxidants may perform double duty by first operating as antioxidants in the body (including the gastrointestinal tract) and in the process become weak pro-oxidants that function as powerful Nrf2 activators. Of course, if you are not aware of ORAC5.0 testing, then it would not be possible to make such an observation.


My goal when I formulated Ultimate Protector™ was to create a product with three basic functions. That is, 1) a source of non-GMO Vitamin C (1.5 gm/daily serving), 2) provide powerful antioxidant protection via proven high ORAC sources, and 3) a multiple ingredient source of many Nrf2 activators, thereby providing the body with means to produce a wide variety of protective enzymes endogenously.


It is important to realize Vitamin C is a vitamin that is a cofactor in at least eight enzymatic reactions, including several collagen syntheses reactions that when dysfunctional (usually because of lack of Vitamin C) cause the most severe symptoms of scurvy. In animals, these reactions are especially important in wound healing and in preventing bleeding from capillaries. It is important to understand that no other substance can provide these functions.

Vitamin C acts as an electron donor and/or hydrogen donor, and this ability makes it a potent antioxidant. It rapidly reduces superoxide and nitroxide radicals and scavenges hydroxyl, alkoxyl, and peroxyl radicals. It also reacts with non-radical species such as singlet oxygen and hypochlorous acid. It has been observed in in vitro experiments that Vitamin C acts as the first line of defense in the plasma. In order to learn more about the important role of Vitamin C, please see my blog article: “Vitamin C – An Amazing Nutrient” (www.integratedhealthblog.com/vitamin-c-an-amazing-nutrient/).


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 elected to conduct ORAC testing.

The fact is that there are a variety of “free radicals” that operate in humans. The most important are the primary radicals hydroxyl, peroxyl, peroxynitrite, singlet oxygen, superoxide anion, and hypochlorite. Brunswick Labs has developed a test called ORAC6.0. This test expands the ORAC platform to measure the antioxidant capacity against each of the six primary reactive oxygen species mentioned above (not just against the peroxyl radical as ORAC does). ORAC6.0 substantially improves broad-spectrum antioxidant analysis and gives evidence of the diverse antioxidant potential of natural products against radicals.

Recently [8/2019] Brunswick Labs has tested ULTIMATE PROTECTOR+™ using the new ORAC6.0 test. The results reveal an incredible overall ORAC6.0 value of 272,743 µmole TE/gram (i.e., 272,743 per gram!). This corresponds to a total ORAC6.0 value per serving of over 968,000 μmole TE per serving. In addition, the ORAC5.0 value was measured to be over 950,000 μmole TE per serving. The results have shown that the formula offers excellent protection against all of the six major types of free radicals found in the body.


Ultimate Protector +

Ultimate Protector+ is new and improved!


In the development of Ultimate Protector+™, I have been able to find an extremely strong ingredient called SFB® (Standardized Fruit Blend) that contains 9 different fruit extracts that have been shown to be very powerful antioxidants and Nrf2 activators. These are details below.

1. SFB® – (Standardized Fruit Blend)

SFB® is a nutritious, non-GMO blend that provides a broad spectrum of polyphenols, anthocyanins, and other antioxidants derived from water and/or ethanol extracts of whole red grape (Vitis vinifera), cranberry (Vaccinium macrocarpon), pomegranate (Punica granatum) with >75% polyphenols, blueberry (Vaccinium uliginosum), apple (Malus pumilla Mill), mangosteen (Garcinia mangostana), bilberry (Vaccinium myrtillis), chokeberry (Aronia arbutifolia), and goji berry (Lycium barbarum). This powder has an ORAC value in excess of 9,000 µmole TE/g and contains >50% polyphenols.

Polyphenols and anthocyanins are not all created equal. Every fruit, vegetable and herb provides its own set of unique polyphenols and anthocyanins that reside in the body for different lengths of time and in different locations, providing a range of benefits. SFB® has been designed to provide a wide range of plant polyphenols, flavonoids, anthocyanins, catechins, OPCs, zeaxanthin and other carotinoids, etc. Published research associates these plant ingredients with healthy aging, inflammation management, improved blood sugar metabolism, and cardiovascular disease management.

SFB® provides the following benefits: Superior source of natural antioxidants and Nrf2 activators, helps ameliorate the effects of premature aging, promotes cardiovascular health, promotes healthy brain function and mental acuity, promotes healthy vision, promotes healthy blood sugar levels, and is an excellent source of flavonoids and organic acids.

I have prepared detailed blog articles for the ingredients in SFB®. Below these are summarized and links to the articles are provided.

a) Cranberry Extract

Ultimate Protector + Includes Cranberry

Ultimate Protector+ Includes Cranberry Extract

Cranberry extract is an especially good source of antioxidant polyphenols. In animal studies, the polyphenols in cranberries have been found to decrease levels of total cholesterol and so-called “bad” cholesterol. Cranberries may also inhibit the growth of tumors in human breast tissue and lower the risk of both stomach ulcers and gum disease.

Here is a list of the antioxidant and anti-inflammatory phytonutrients in found in cranberry extract.

Type of Phytonutrient Specific Molecules
Phenolic Acids hydroxybenzoic acids including vanillic acids;
—Phenolic Acids (cont.) hydroxycinnamic acids inculding caffeic,
—Phenolic Acids (cont.) coumaric, cinnamic, and ferulic acid
Proanthocyanidins epicatechin oligomers
Anthocyanins cyanidins, malvidins, and peonidins
Flavonoids quercetin, myricetin, kaempferol
Triterpenoids ursolic acid


    • Cranberries hold significantly high amounts of phenolic flavonoid phytochemicals called oligomeric proanthocyanidins (OPC’s). Scientific studies have shown that consumption of the berries have potential health benefits regarding cancer, aging and neurological diseases, inflammation, diabetes, and bacterial infections.
    • Antioxidant compounds in cranberry extract including OPC’s, anthocyanidin flavonoids, cyanidin, peonidin and quercetin may support cardiovascular health by counteracting against cholesterol plaque formation in the heart and blood vessels. Further, these compounds help the human body lower LDL cholesterol levels and increase HDL-good cholesterol levels in the blood.
    • Scientific studies show that cranberry juice consumption offers protection against gram-negative bacterial infections such as E.coli in the urinary system by inhibiting bacterial-attachment to the bladder and urethra.
    • It is known that cranberries turns urine acidic. This, together with the inhibition of bacterial adhesion helps prevent the formation of alkaline (calcium ammonium phosphate) stones in the urinary tract by working against proteus bacterial-infections.
    • In addition, the berries prevent plaque formation on the tooth enamel by interfering with the ability of the gram-negative bacterium, Streptococcus mutans, to stick to the surface. In this way cranberries helps prevent the development of cavities.
    • The berries are also good source of many vitamins like vitamin C, vitamin A, ß-carotene, lutein, zeaxanthin, and folate and minerals like potassium, and manganese.
  • Oxygen Radical Absorbance Capacity (ORAC) demonstrates cranberry at an ORAC score of 9584 µmol TE units per 100 g, one of the highest in the category of edible berries.

b) Pomegranate Extract

Ultimate Protector+ Includes Pomegranate

Ultimate Protector+ Includes Pomegranate Extract

For thousands of years, the pomegranate has been extensively used as a source of food and medicine. Full of antioxidants, vitamin C and potassium, pomegranate has been used to control body weight, reduce cholesterol, fight against cell damage, and inhibit viral infections. Pomegranate extracts have anti-bacterial effects.

Pomegranates are rich in ellagic acid, gallic acid, lignans, polyphenols and other bioactive compounds, and have been shown to lower blood pressure and enhance vascular function. Furthermore, it can offset some of the negative effects of medications and chemicals. These compounds occur naturally in its peel, seeds, leaf and juice. The seeds are high in p-coumaric acid, plant sterols, tannins and fatty acids. In addition to their antihypertensive effects, they may help reduce blood sugar levels.

Pomegranate fruit is a rounded berry with a thick reddish skin covering approximately 200–1400 white to deep red or purple seeds. Pomegranate seeds are edible and hold strong antioxidant and anti-inflammatory properties due to their high content of hydrolysable tannins and anthocyanins. As compared to the antioxidant activity of vitamin E, β-carotene, and ascorbic acid, the pomegranate antioxidants appear unique due to combinations of a wide array of polyphenols, having a broader range of action against several types of free radicals. As compared to the recognized antioxidants in red wine and green tea, anthocyanins from pomegranate fruit possess significantly higher antioxidant activity.

Pomegranate has been used in various medicinal systems of medicine for the treatment and therapy of a multitude of diseases and ailments. In the ancient Indian medicinal system, i.e., in Ayurvedic medicine, the pomegranate was considered to be a whole pharmacy unto itself. It was recommended to be used as an antiparasitic agent and to treat diarrhea and ulcers. The medicinal properties of pomegranate have sparked significant interest in today’s scientific community as evidenced by the scientific research relating to health benefits of pomegranate that have been published in last few decades.

Studies have shown that pomegranate and its constituents can efficiently affect multiple signaling pathways involved in inflammation, cellular transformation, hyperproliferation, angiogenesis, initiation of tumorigenesis, and eventually suppressing the final steps of tumorigenesis and metastasis. The pomegranate constituents are shown to modulate transcription factors, pro-apoptotic proteins, anti-apoptotic proteins, cell cycle regulator molecules, protein kinases, cell adhesion molecules, pro-inflammatory mediators, and growth factors.

c) Chokeberry (Aronia)

Ultimate Protector+ Includes Chokeberry

Ultimate Protector+ Includes Chokeberry Extract


Aronia melanocarpa (black chokeberry) has attracted scientific interest due to its deep purple, almost black pigmentation that arises from dense contents of polyphenols, especially anthocyanins. Total polyphenol content is 1752 mg per 100 g in fresh berries, anthocyanin content is 1480 mg per 100 g, and proanthocyanidin concentration is 664 mg per 100 g. These values are among the highest measured in plants to date.

The plant produces these pigments mainly in the leaves and skin of the berries to protect the pulp and seeds from constant exposure to ultraviolet radiation and production of free radicals. By absorbing UV rays in the blue-purple spectrum, leaf and skin pigments filter intense sunlight, serve antioxidant functions and thereby have a role assuring regeneration of the species.

Analysis of polyphenols in chokeberries has identified the following individual chemicals (among hundreds known to exist in the plant kingdom): cyanidin-3-galactoside, cyanidin-3-arabinoside, quercetin-3-glycoside, epicatechin, caffeic acid, delphinidin, petunidin, pelargonidin, peonidin, and malvidin. All these except caffeic acid are members of the flavonoid category of phenolics.

In a standard measurement of antioxidant strength, the oxygen radical absorbance capacity or ORAC, demonstrates aronia to have one of the highest values yet recorded for a fruit — 16,062 micro moles of Trolox Eq. per 100 g. The components contributing to this high measurement were both anthocyanins and proanthocyanidins, with the proanthocyanidin level “among the highest in foods”, which may explain their potent astringent taste.

d) Goji Berry

Ultimate Protector+ Includes Goji Berry

Ultimate Protector+ Includes Goji Berry Extract

Goji Berries contain abundant polysaccharides (LBPs, comprising 5%–8% of the dried fruits), scopoletin (6-methoxy-7-hydroxycoumarin, also named chrysatropic acid, ecopoletin, gelseminic acid, and scopoletol), the glucosylated precursor, and stable vitamin C analog 2-O-β-D-glucopyranosyl-L-ascorbic acid, carotenoids (zeaxanthin and β-carotene), betaine, cerebroside, β-sitosterol, flavonoids, amino acids, minerals, and vitamins (in particular, riboflavin, thiamin, and ascorbic acid).

The predominant carotenoid is zeaxanthin, which exists mainly as dipalmitate (also called physalien or physalin). The content of vitamin C (up to 42 mg/100 g) in goji berry (also known as wolfberry) is comparable to that of fresh lemon fruits. As to the seeds, they contain zeaxanthin (83%), β-cryptoxanthin (7%), β-carotene (0.9%), and mutatoxanthin (1.4%), as well as some minor carotenoids.

In fact, increasing lines of experimental studies have revealed that L. barbarum berries have a wide array of pharmacological activities, which is thought to be mainly due to its high LBPs content. Water-soluble LBPs are obtained using an extraction process that removes the lipid soluble components such as zeaxanthin and other carotenoids with alcohol. LBPs are estimated to comprise 5%–8% of LBFs and have a molecular weight ranging from 24 kDa to 241 kDa. LBPs consist of a complex mixture of highly branched and only partly characterized polysaccharides and proteoglycans.

The glycosidic part accounts, in most cases, for about 90%–95% of the mass and consists of arabinose, glucose, galactose, mannose, rhamnose, xylose, and galacturonic acid. LBPs are considered the most important functional constituents in LBFs. Different fractions of LBPs have different activities and the galacturonic acid content is an imperative factor for activities of LBP. The bioactivities of polysaccharides are often in reverse proportion with their molecular weights. Increasing lines of evidence from both preclinical and clinical studies support the medicinal, therapeutic, and health-promoting effects of LBPs.

e) Mangosteen

Ultimate Protector+ Includes Mangosteen

Ultimate Protector+ Includes Mangosteen Extract

The Mangosteen extract in Ultimate Protector+ has been extracted with non-GMO food grade ethanol and distilled water. Testing has indicated the product contains over 10% polyphenols.

Mangosteen extract in obtained from the skin and whole fruit for which numerous biological activities have been reported including: antimutagenic, antibacterial, hypocholesterolemic, antioxidant, and protective against tumorigenesis.

Mangosteen contains nutrients with antioxidant capacity, such as vitamin C and folate. Plus, it provides xanthones — a unique type of plant compound known to have strong antioxidant properties. In several test-tube and animal studies, the antioxidant activity of xanthones has resulted in anti-inflammatory, anticancer, anti-aging, heart protective, and antidiabetic effects.

Additionally, some research suggests that certain plant compounds in mangosteen may have antibacterial properties — which could benefit your immune health by combating potentially harmful bacteria. In a 30-day study in 59 people, those taking a mangosteen-containing supplement experienced reduced markers of inflammation and significantly greater increases in healthy immune cell numbers compared to those taking a placebo.

f) Apple Extract

Ultimate Protector+ Includes Apple

Apples contain a large concentration of flavonoids, as well as a variety of other phytochemicals, and the concentration of these phytochemicals may depend on many factors, such as cultivar of the apple, harvest and storage of the apples, and processing of the apples. The concentration of phytochemicals also varies greatly between the apple peels and the apple flesh.

Some of the most well studied antioxidant compounds in apples include quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-rhamnoside, catechin, epicatechin, procyanidin, cyanidin-3-galactoside, coumaric acid, chlorogenic acid, gallic acid, and phloridzin. Recently researchers have examined the average concentrations of the major phenolic compounds in six cultivars of apples. They found that the average phenolic concentrations among the six cultivars were: quercetin glycosides, 13.2 mg/100 g fruit; vitamin C, 12.8 mg/100 g fruit; procyanidin B, 9.35 mg/100 g fruit; chlorogenic acid, 9.02 mg/100 g fruit; epicatechin, 8.65 mg/100 g fruit; and phloretin glycosides, 5.59 mg/100 g fruit.

The compounds most commonly found in apple peels consist of the procyanidins, catechin, epicatechin, chlorogenic acid, phloridzin, and the quercetin conjugates. In the apple flesh, there is some catechin, procyanidin, epicatechin, and phloridzin, but these compounds are found in much lower concentrations than in the peels. Quercetin conjugates are found exclusively in the peel of the apples. Chlorogenic acid tends to be higher in the flesh than in the peel.

Because the apple peels contain more antioxidant compounds, especially quercetin, apple peels may have higher antioxidant activity and higher bioactivity than the apple flesh. Research showed that apples without the peels had less antioxidant activity than apples with the peels. Apples with the peels were also better able to inhibit cancer cell proliferation when compared to apples without the peels. More recent work has shown that apple peels contain anywhere from two to six times (depending on the variety) more phenolic compounds than in the flesh, and two to three times more flavonoids in the peels when compared to the flesh. The antioxidant activity of these peels was also much greater, ranging from two to six times greater in the peels when compared to the flesh, depending on the variety of the apple. This work is supported a study which found that rats consuming apple peels showed greater inhibition of lipid peroxidation and greater plasma antioxidant capacity when compared to rats fed apple flesh.

Many of these phytochemicals from apples have been widely studied, and many potential health benefits have been attributed to these specific phytochemicals. The procyanidins, epicatechin and catechin, have strong antioxidant activity and have been found to inhibit low density lipoprotein (LDL) oxidation in vitro. In mice, catechin inhibits intestinal tumor formation and delays tumors onset. One study found that chlorogenic acid has very high alkyl peroxyl radical (ROO•) scavenging activity. Compared to about 18 other antioxidant compounds (including quercetin, gallic acid, α-tocopherol), chlorogenic was second only to rutin. Since ROO• may enhance tumor promotion and carcinogenesis, chlorogenic acid may add to the protective effect of apples against cancer. Chlorogenic acid has been found to inhibit 8-dehydroxy-deoxyguanosine formation in cellular DNA in a rat model following treatment with 4-nitroquinoline-1-oxide.

Quercetin is also a strong antioxidant, and is thought to have potential protective effects against both cancer and heart disease. Briefly, quercetin has been found to down regulate expression of mutant p53 in breast cancer cells, arrest human leukemic T-cells in G1, inhibit tyrosine kinase, and inhibit heat shock proteins. Quercetin has protected Caco-2 cells from lipid peroxidation induced by hydrogen peroxide and Fe2+. In mice liver treated with ethanol, quercetin decreased lipid oxidation and increased glutathione, protecting the liver from oxidative damage. Recently, it has been found that high doses of quercetin inhibit cell proliferation in colon carcinoma cell lines and in mammary adenocarcinoma cell lines, but at low doses quercetin increased cell proliferation (20% in colon cancer cells and 100% in breast cancer cells). However, low doses of quercetin (10 uM) inhibited cell proliferation in Mol-4 Human Leukemia cells and also induced apoptosis. Quercetin inhibited intestinal tumor growth in mice, but not in rats. Low levels of quercetin inhibited platelet aggregation, calcium mobilization, and tyrosine protein phosphorylation in platelets. Modulation of platelet activity may help prevent cardiovascular disease.

g) Blueberry and Bilberry Extract

wild bilberry and wild blueberry
Wild bilberry and wild blueberry provide Nrf2 activators.

The key compounds in bilberry fruit are called anthocyanins and anthocyanosides. These compounds help build strong blood vessels and improve circulation to all areas of the body. They also prevent blood platelets from clumping together (helping to reduce the risk of blood clots), and they have antioxidant properties (preventing or reducing damage to cells from free radicals). Anthocyanins boost the production of rhodopsin, a pigment that improves night vision and helps the eye adapt to light changes.

Bilberry fruit is also rich in tannins, a substance that acts as an astringent. The tannins have anti-inflammatory properties and may help control diarrhea.

Bilberries have been shown to have the highest Oxygen Radical Absorbance Capacity (ORAC) rating of more than 20 fresh fruits and berries. The antioxidant properties of bilberries were shown to be even stronger than those of cranberries, raspberries, strawberries, plums, or cultivated blueberries.

The antioxidant powers and health benefits of bilberries and blueberries can be attributed to a number of remarkable compounds contained in them, including the following:

  • Anthocyanins
    • malvidins
    • delphinidins
    • pelargonidins
    • cyanidins
    • peonidins
  • Hydroxycinnamic acids
    • caffeic acids
    • ferulic acids
    • coumaric acids
  • Hydroxybenzoic acids
    • gallic acids
    • procatchuic acids
  • Flavonols
    • kaempferol
    • quercetin
    • myricetin
  • Other phenol-related phytonutrients
    • pterostilbene
    • resveratrol
  • Other nutrients
    • lutein
    • zeaxanthin
    • Vitamin K
    • Vitamin C
    • manganese

Other Ingredients

As with the original Ultimate Protector formula, we have included Curcumin (95% min. curcuminoids) and Trans-resveratrol (greater than 98%) because they are important in the Nrf2 and antioxidant literature. In addition, we have included Green Tea extract (high in EGCG) and VinCare® Whole Grape Extract (also present in SFB® and is very high in oligomeric proanthocyanidins – OPCs). 

These additional ingredients are detailed below:

1) Curcumin

Ultimate Protector+ Includes Curcumin

Ultimate Protector+ Includes Curcumin

We have included Curcumin (95% curcuminoids in ULTIMATE PROTECTOR™. This ingredient contains three main chemical compounds – Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin – collectively known as Curcuminoids and all derived from Turmeric. Curcumin has been shown to be one of the most potent Nrf2 transcription factor activators. Studies have reported that curcumin and turmeric protect the liver against several toxicants both in vitro and in vivo. A number of reports showed the curative action of turmeric and curcuminoids. Curcumin is a potent scavenger of free radicals such as superoxide anion radicals, hydroxyl radicals, and nitrogen dioxide radicals. It exerts powerful antioxidant and anti-inflammatory properties.

2) Trans-Resveratrol (98% from Polygonum cuspidatum – giant knotweed)

Knotweed (Polygonum cuspidatum) is a major source for resveratrol.

Trans-resveratrol provides antioxidant protection, boosts cellular energy, and balances the immune system. It has been proven in studies to activate the SIRT1 longevity gene and enhance cellular productivity. Several research studies have shown that trans-resveratrol activates Nrf2 transcription factor, significantly modulates biomarkers of bone metabolism, inhibits pro-inflammatory enzymes such as COX-1 and COX-2, and exhibits cardioprotective effects, neuroprotective properties, and caloric restrictive behavior. Trans-resveratrol has shown the ability to increase the number of mitochondria thereby increasing total daily energy. Studies have shown that trans-resveratrol promotes an increase in mitochondrial function. Increased mitochondrial function translates into an increase in energy availability, improved aerobic capacity, and enhanced sensorimotor function. Trans-resveratrol has an ORAC value of 31,000 µmole TE/g.

3) Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

Green Tea Extract contains highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. Green tea extract is obtained from the unfermented leaves of Camellia sinensis for which numerous biological activities have been reported including: cell protective, antimicrobial, and antioxidant. The green tea extract in Ultimate Protector is extracted is extracted by non-GMO ethanol and distilled water and contains ~ 90% polyphenols and 50% epigallocatechingallate (EGCG).

Epigallocatechin gallate (EGCG) is the most abundant catechin compound in green tea. It is well established that EGCG is a potent antioxidant and anti-inflammatory agent. Epidemiological studies show that consumption of 100 or more mg of EGCG per day is beneficial, as it is the most potent Nrf2 activator among all green tea catechins. EGCG exhibits robust diffusion through bodily tissues, including the endothelium of the blood brain barrier.

EGCG has the capacity to activate Nrf2/ARE and induce Heme oxygenase-1 (HO-1) expression. Several studies have shown that EGCG can also interact with kinases, causing the disassociation of Nrf2/Keap1 complex.

Protective effects of EGCG have been reported against ischemia/reperfusion injury. Administration of EGCG showed improved neurologic scores, reduced infarct volume, and ameliorated neuronal apoptosis due to increased GSH biosynthesis (via Nrf2 activation) and decreased ROS content. By inducing the expression of Nrf2 and HO-1, EGCG increases important endogenous antioxidants in microglial cells.

4) VinCare® whole grape extract (seed, pulp, and skin)

Ultimate Protector+ Includes Whole Grape Extract

Ultimate Protector+ Includes Whole Grape Extract

Whole Grape Extract contains highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. The Oligomeric Proanthocyanidins (OPCs) in grape extract are able to strengthen collagen fibers in aging or damaged connective tissue and can act as a preventative against connective tissue degradation. Some research indicates that anthocyanidins, which are found in extracts of grape seed, skin, and stems (but not in grape seed extract), can reduce oxidized glutathione while at the same time become reduced themselves. In addition, extracts of grape skin and pulp (but not those of grape seed extract) contain trans-resveratrol that has been shown to have cell protective effects.

Grape seed extract has been reported to demonstrate a remarkable spectrum of biological, pharmacological and therapeutic properties against oxidative stress. The antioxidative activities of grape seed extract have been found to be much stronger than those of vitamins C and E. Studies have indicated that grape seed extract showed a protective effect on cardiovascular disease, nephropathy, atherosclerosis, and neuropathy, among other conditions.

Vincare® contains ~80% polypnenols and has an ORAC value of about 19,000 µmole TE/g. ORAC 5.0 testing of grape seed extract exhibits one of the highest values of any tested material at about 100,000 µmole TE/g.

It has been shown that grape seed OPCs activate nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). Click here to view an excellent article entitled Proanthocyanidins [OPCs] against Oxidative Stress: From Molecular Mechanisms to Clinical Applications.

Partial List of Phytochemicals in Ultimate Protector+

The total combination of freeze-dried and concentrated fruits, vegetables, and herbs in Ultimate Protector+ provides a wide range of choices to the body in terms of specific substances, including the following Phytochemicals: Anthocyandins, Beta-Carotene, Chlorogenic acid, Catechins, Curcuminoids, Ellagic acid, Ferulic acid, Lutein, Lycopene, Mangostins, Phenolic acids, Phloridzins, Polyphenols, Polysaccharides, Oligomeric Proanthocyanidins (OPCs), PteroStilbenes, Punicalagins, Quercetin, Trans-Resveratrol, Xanthones, and Zeaxanthins.

Additional Ingredients

Also included in Ultimate Protector+ are calcium and magnesium malate that support ATP and enzyme production in the body. In addition, the product contains Bioperine® a black pepper extract that has been shown to enhance the absorption of nutrients by 30–60 percent, enhances the absorption of curcuminoids by up to a factor of 20,  and is itself an Nrf2 activator!


Six veggie capsules provides the following percentages of the Daily Value:

Serving Size: 6 Veggie Capsules Servings per Container: 30
Amount Per Serving Amounts % Daily Value
Vitamin C (as 100% USP-grade, non-GMO ascorbic acid) 1,500 mg 1667%
Calcium (from calcium malate) 60 mg 6
Magnesium (from magnesium malate) 60 mg 15
SFB®† (50% polyphenols, Orac: 9,000 units/gm) 180 mg *
Curcumin (95% min. curcuminoids from Curcuma longa) (root) 135 mg *
Green Tea extract (92% polyphenols, 50% EGCG) 135 mg *
Trans-Resveratrol 98% 135 mg *
Vincare®† whole grape extract (80% polyphenols, Orac: 19,000 units/gm) 135 mg *
Bioperine®†† 7.5 mg *
* Daily Value not established

Other ingredients: vegetarian capsule (veggie cap), microcrystalline cellulose, silica, and ascorbyl palmitate.

Directions for Use: As a dietary supplement take two capsules three times daily with food, or as directed by a health care professional.

ULTIMATE PROTECTOR+ Does Not Contain: wheat, rye, oats, barley, corn, gluten, soy, egg, dairy, yeast, sugar, shellfish, GMOs, wax, preservatives, colorings, or artificial flavorings.

ULTIMATE PROTECTOR+ will be most effective when used in conjunction with other foundational nutritional supplements that support the body’s metabolism, including Multi Two or Mighty Multi-Vite!™ (therapeutic multivitamin formulas), Essential Fats plus E (essential fatty acids with Vitamin E), PRO-C™ (antioxidant formula), and one of our high-RNA Rejuvenate!™ superfoods.

†SFB® and VinCare® are registered trademark of Ethical Naturals, Inc.

†† Bioperine® is a registered trademark of Sabinsa Corporation.


New Directions for Preventing Free-Radical Damage

Natural Phytochemical Nrf2 Activators for Chemoprevention

Hank Liers, PhD


Dr. Hank Liers is the CEO and chief product formulator for Health Products Distributors, Inc. He has been studying and using natural means of achieving health since 1984. Dr. Liers received his PhD in physics in 1969 from the University of Minnesota and has applied his analytical abilities to learning and applying a scientific approach to nutrition.


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  • Description and Comparison of ORAC Tests for Well Known Plant Ingredients and Ultimate Protector™
  • Questions & Answers about Ultimate Protector


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.


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.


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.”


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+


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.


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).


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)


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)


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)


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.


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!