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ULTIMATE PROTECTOR+ TRIPLE ACTION NRF2 ANTIOXIDANT SUPPLEMENT – UPDATE

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+

ULTIMATE PROTECTOR+ TEST RESULTS

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+
PRODUCT INFORMATION

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

ULTIMATE PROTECTOR+ BENEFITS

• 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

ULTIMATE PROTECTOR+ FEATURES

• 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+ INGREDIENTS

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+ RECAP

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+ RESOURCES

Ultimate Protector+

Ultimate Protector+
(detailed product information)

HPDI BLOG ARTICLES

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

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

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

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

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

Rejuvenation Program Part 4: Foundational Elements in the Master Rejuvenation Program
http://www.integratedhealthblog.com/the-master-rejuvenation-program-part-4/

VIDEOS

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)

 

 

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ULTIMATE PROTECTOR+ BRUNSWICK LABS ORAC6.0 TEST REPORT

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

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

ORAC TESTS

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

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

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

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

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

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

RESULTS OF ULTIMATE PROTECTOR+ ORAC6.0 TEST

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

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


Ultimate Protector+ nrf2 activator formula

 

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

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

ORAC6.0 Units
Per Serving*

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

17,768

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

968,237

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

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

 

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

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

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THE AMAZING HEALING POTENTIAL OF NATURAL NRF2 ACTIVATORS

Dr. Hank Liers, PhD natural nrf2 activators healing potential

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

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

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

 

Ultimate Protector+

New Ultimate Protector+

 

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

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

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

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

SOME KEY ENZYMES MODULATED BY Nrf2 ACTIVATORS

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

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

NATURAL FOODS AND FOOD EXTRACTS PROMOTE THE EXPRESSION OF Nrf2

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

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

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

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

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

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

DIETARY FLAVONOIDS AS NRF2 ACTIVATORS

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

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

Table 1: Common Dietary Flavonoids

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

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

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

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

 

Ultimate Protector+

INTERESTING FACTS REGARDING NRF2 ACTIVATORS

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

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

3) We have observed that the natural plant substances with the highest ORAC5.0 values appear to be among the most effective Nrf2 activators. For example, see the table below. In particular, note that Curcumin (98%), Grape Seed Extract, Green Tea Extract, and Reservatrol which are commonly used for their excellent Nrf2 activator effects are the most powerful in-vitro antioxidants . Please note that Ultimate Protector+ is over 100% more powerful as an antioxidant than the best single plant ingredient.

TABLE 2: ORAC5.0™ COMPARATIVE RESULTS

Ingredient Peroxyl Radical Hydroxyl Radical Peroxy-nitrite Radical Super-
oxide Radical
Singlet O2 Radical Total ORAC5.0
Curcumin 98% 5,750 8,920 906 597 66,290 82,500
Bilberry 25% 7,000 25,000 1,000 16,000 5,000 54,000
Cocoa 10,000 28,000 1,000 11,000 2,000 52,000
Grape Seed Extract 17,000 47,000 1,000 25,000 4,000 94,000
Green Tea Extract 11,000 41,000 2,000 56,000 3,000 113,000
Coffee Berry Extract 5,000 29,000 1,000 1,000 2,000 38,000
Mangosteen 4,000 8,000 1,000 18,000 4,000 35,000
Pine Bark 7,000 23,000 1,000 17,000 2,000 50,000
Resveratrol 12,000 50,000 1,000 8,000 22,000 93,000
ULTIMATE PROTECTOR+    3,376    5,569 2,758 221,866 34,169 267,738
Results are expressed in micro mole TE/g

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

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

NEUROPROTECTION BY POLYPHENOL STIMULATION OF THE NRF2 / ARE PATHWAY 

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

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

ABSTRACT

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

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

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

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

ABSTRACT

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

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

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

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

 

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

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

REVIEW ARTICLE

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

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

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

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

CONCLUSION

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

SOURCES

BLOG ARTICLES

 SCIENTIFIC ARTICLES

 

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ULTIMATE PROTECTOR+ INGREDIENTS – CRANBERRY

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberryUltimate Protector+ contains cranberry extract, as well as components from 12 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I will explore the ingredient cranberry, which is a component of SFB® – Standardized Fruit Blend from Ethical Naturals, Inc.

Ultimate Protector+ Includes Cranberry

Ultimate Protector+ Includes Cranberry Extract

SFB® – Standardized Fruit Blend

SFB® is a proprietary formula that combines extracts from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry. It is high in fruit polyphenols, flavonoids, anthocyanins, catechins, proanthocyanins, ellagic acid, xanthines, chlorogenic acid, pterostilbenes, resveratrol, phloridzin, quercetin, zeaxanthin, carotenoids, polysaccharides, quinic acid, and more. With its diverse blend, SFB® offers over 40-50% polyphenols as well as >9,000 ORAC units in a single gram.

Polyphenols, anthocyanins and other plant elements are powerful ingredients associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

HEALTH BENEFITS OF CRANBERRIES

Cranberries (Vaccinium macrocarpon) are native to the boggy regions of temperate and subalpine North America and Europe. Although Native Americans used them extensively, they were first cultivated in the U.S. in the early 19th century. Cranberries grow on viney plants belonging to the heath family Ericaceae that also includes blueberries, bilberries, huckleberries, and bearberries (Arctostaphylos uva ursi). Cranberries contain tannins, fiber, anthocyanins (and other flavonoids), and Vitamin C. Their tannins prevent bacteria from attaching to cells. Consequently, cranberries have been used against infections, including urinary tract infections. In addition, cranberries may be helpful in protecting against heart disease and stroke.

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                     epicatechins
Anthocyanins                              cyanidins, malvidins, and peonidins
Flavonoids                                   quercetin, myricetin, kaempferol
Triterpenoids                              ursolic acid

OTHER CRANBERRY INFORMATION

    • 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 against 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 prevent cardiovascular disease 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, zea-xanthin, 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.

For more information on cranberries visit: http://www.whfoods.com/genpage.php?tname=foodspice&dbid=145

SCIENTIFIC STUDIES ON THE ANTIOXIDANT EFFECTS OF CRANBERRIES

Below, I provide relevant scientific studies on the antioxidant effects and potential health benefits of cranberries.

PREVENTION OF OXIDATIVE STRESS, INFLAMMATION AND MITOCHONDRIAL DYSFUNCTION IN THE INTESTINE BY DIFFERENT CRANBERRY PHENOLIC FRACTIONS.

ABSTRACT

Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-α and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor κB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor γ co-activator-1-α, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.

 CHEMICAL CHARACTERIZATION AND CHEMO-PROTECTIVE ACTIVITY OF CRANBERRY PHENOLIC POWDERS IN A MODEL CELL CULTURE. RESPONSE OF THE ANTIOXIDANT DEFENSES AND REGULATION OF SIGNALING PATHWAYS

ABSTRACT

Oxidative stress and reactive oxygen species (ROS)-mediated cell damage are implicated in various chronic pathologies. Emerging studies show that polyphenols may act by increasing endogenous antioxidant defense potential. Cranberry has one of the highest polyphenol content among commonly consumed fruits. In this study, the hepato-protective activity of a cranberry juice (CJ) and cranberry extract (CE) powders against oxidative stress was screened using HepG2 cells, looking at ROS production, intracellular non-enzymatic and enzymatic antioxidant defenses by reduced glutathione concentration (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity and lipid peroxidation biomarker malondialdehyde (MDA). Involvement of major protein kinase signaling pathways was also evaluated. Both powders in basal conditions did not affect cell viability but decreased ROS production and increased GPx activity, conditions that may place the cells in favorable conditions against oxidative stress. Powder pre-treatment of HepG2 cells for 20 h significantly reduced cell damage induced by 400 μM tert-butylhydroperoxide (t-BOOH) for 2 h. Both powders (5–50 μg/ml) reduced t-BOOH-induced increase of MDA by 20% (CJ) and 25% (CE), and significantly reduced over-activated GPx and GR. CE, with a significantly higher amount of polyphenols than CJ, prevented a reduction in GSH and significantly reduced ROS production. CJ reversed the t-BOOH-induced increase in phospho-c-Jun N-terminal kinase. This study demonstrates that cranberry polyphenols may help protect liver cells against oxidative insult by modulating GSH concentration, ROS and MDA generation, antioxidant enzyme activity and cell signaling pathways.

CRANBERRY EXTRACT SUPPRESSES INTERLEUKIN-8 SECRETION FROM STOMACH CELLS STIMULATED BY HELICOBACTER PYLORI IN EVERY CLINICALLY SEPARATED STRAIN BUT INHIBITS GROWTH IN PART OF THE STRAINS

From: http://www.sciencedirect.com/science/article/pii/S1756464613000364

ABSTRACT

It is known that cranberry inhibits the growth of Helicobacter pylori (HP). In human stomach, HP basically induces chronic inflammation by stimulating stomach cells to secrete interleukin (IL)-8 and other inflammatory cytokines, and causes stomach cancer, etc. The aim of this study was to investigate the inhibiting effects of cranberry on HP growth and IL-8 secretion from stomach cells induced by HP, using clinically separated HP strains. HP growth in liquid culture and on-plate culture was evaluated by titration after 2-day incubation and by agar dilution technique, respectively. For IL-8 experiments, MKN-45, a stomach cancer cell line, was incubated with HP for 24 h and IL-8 in the medium was assayed by ELISA. Cranberry suppressed growth of the bacteria only in six of the 27 strains. Meanwhile, it suppressed IL-8 secretion in all the strains. The results may suggest a possible role of cranberry in prevention of stomach cancer by reducing gastric inflammation.

EFFECTS OF CRANBERRY POWDER ON BIOMARKERS OF OXIDATIVE STRESS AND GLUCOSE CONTROL IN DB/DB MICE

From: http://www.ncbi.nlm.nih.gov/pubmed/24353827

ABSTRACT

Increased oxidative stress in obese diabetes may have causal effects on diabetic complications, including dyslipidemia. Lipopolysccharides (LPS) along with an atherogenic diet have been found to increase oxidative stress and insulin resistance. Cranberry has been recognized as having beneficial effects on diseases related to oxidative stress. Therefore, we employed obese diabetic animals treated with an atherogenic diet and LPS, with the aim of examining the effects of cranberry powder (CP) on diabetic related metabolic conditions, including lipid profiles, serum insulin and glucose, and biomarkers of oxidative stress. Forty C57BL/KsJ-db/db mice were divided into the following five groups: normal diet + saline, atherogenic diet + saline, atherogenic diet + LPS, atherogenic diet + 5% CP + LPS, and atherogenic diet + 10% CP + LPS. Consumption of an atherogenic diet resulted in elevation of serum total cholesterol and atherogenic index (AI) and reduction of high density lipoprotein (HDL)-cholesterol. However, with 10% CP, the increase in mean HDL-cholesterol level was close to that of the group with a normal diet, whereas AI was maintained at a higher level than that of the group with a normal diet. LPS induced elevated serum insulin level was lowered by greater than 60% with CP (P < 0.05), and mean serum glucose level was reduced by approximately 19% with 5% CP (P > 0.05). Mean activity of liver cytosolic glutathione peroxidase was significantly increased by LPS injection, however it was reduced back to the value without LPS when the diet was fortified with 10% CP (P < 0.05). In groups with CP, a reduction in mean levels of serum protein carbonyl tended to occur in a dose dependent manner. Particularly with 10% CP, a reduction of approximately 89% was observed (P > 0.05). Overall results suggest that fortification of the atherogenic diet with CP may have potential health benefits for obese diabetes with high oxidative stress, by modulation of physical conditions, including some biomarkers of oxidative stress.

SUMMARY

Cranberry extract is full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector+ such an outstanding nutritional supplement.

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ULTIMATE PROTECTOR+ INGREDIENTS – APPLE

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberry Ultimate Protector+ includes apple extract, as well as extracts from 12 different fruits, vegetables, and herbs. Each of these ingredients contain substances considered to be polyphenols, antioxidants, and Nrf2 activators. In this article, I explore the ingredient apple (Malus pumila mill.) extract, which is a component of SFB® – Standardized Fruit Blend from Ethical Naturals, Inc.

apple extract

Ultimate Protector+ Includes Apple

SFB® is a proprietary formula that combines extracts from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry. It is high in fruit polyphenols, flavonoids, anthocyanins, catechins, proanthocyanins, ellagic acid, xanthines, chlorogenic acid, pterostilbenes, resveratrol, phloridzin, quercetin, zeaxanthin, and quinic acid. With its diverse blend, SFB® offers over 40-50% polyphenols as well as >9,000 ORAC units in a single gram.

Polyphenols, anthocyanins and other plant elements are powerful ingredients associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

HEALTH BENEFITS OF APPLE

The Apple extract in Ultimate Protector+ has been extracted with non-GMO food grade ethanol and distilled water. Testing has indicated the product contains over 40% polyphenols. In numerous epidemiological studies, apples have been associated with a decreased risk of chronic diseases such as cardiovascular disease, cancer, and asthma.

When compared to many other commonly consumed fruits in the United States, apples had the second highest level of antioxidant activity. Apples also ranked the second for total concentration of phenolic compounds, and perhaps more importantly, apples had the highest portion of free phenolics when compared to other fruits.

APPLE PHYTOCHEMICALS

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.

SCIENTIFIC STUDIES ON THE ANTIOXIDANT EFFECTS OF APPLE

Below, I provide relevant scientific studies on the antioxidant effects and potential health benefits of apple.

Apple phytochemicals and their health benefits

Jeanelle Boyer1 and Rui Hai Liu1

Abstract

Evidence suggests that a diet high in fruits and vegetables may decrease the risk of chronic diseases, such as cardiovascular disease and cancer, and phytochemicals including phenolics, flavonoids and carotenoids from fruits and vegetables may play a key role in reducing chronic disease risk. Apples are a widely consumed, rich source of phytochemicals, and epidemiological studies have linked the consumption of apples with reduced risk of some cancers, cardiovascular disease, asthma, and diabetes. In the laboratory, apples have been found to have very strong antioxidant activity, inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol. Apples contain a variety of phytochemicals, including quercetin, catechin, phloridzin and chlorogenic acid, all of which are strong antioxidants. The phytochemical composition of apples varies greatly between different varieties of apples, and there are also small changes in phytochemicals during the maturation and ripening of the fruit. Storage has little to no effect on apple phytochemicals, but processing can greatly affect apple phytochemicals. While extensive research exists, a literature review of the health benefits of apples and their phytochemicals has not been compiled to summarize this work. The purpose of this paper is to review the most recent literature regarding the health benefits of apples and their phytochemicals, phytochemical bioavailability and antioxidant behavior, and the effects of variety, ripening, storage and processing on apple phytochemicals..

Cancer chemopreventive potential of apples, apple juice, and apple components.

 Gerhauser C1.

From: https://www.ncbi.nlm.nih.gov/pubmed/18855307

Abstract

Apples ( MALUS sp., Rosaceae) are a rich source of nutrient as well as non-nutrient components and contain high levels of polyphenols and other phytochemicals. Main structural classes of apple constituents include hydroxycinnamic acids, dihydrochalcones, flavonols (quercetin glycosides), catechins and oligomeric procyanidins, as well as triterpenoids in apple peel and anthocyanins in red apples. Several lines of evidence suggest that apples and apple products possess a wide range of biological activities which may contribute to health beneficial effects against cardiovascular disease, asthma and pulmonary dysfunction, diabetes, obesity, and cancer (reviewed by Boyer and Liu, Nutr J 2004). The present review will summarize the current knowledge on potential cancer preventive effects of apples, apple juice and apple extracts (jointly designated as apple products). In brief, apple extracts and components, especially oligomeric procyanidins, have been shown to influence multiple mechanisms relevant for cancer prevention in IN VITRO studies. These include antimutagenic activity, modulation of carcinogen metabolism, antioxidant activity, anti-inflammatory mechanisms, modulation of signal transduction pathways, antiproliferative and apoptosis-inducing activity, as well as novel mechanisms on epigenetic events and innate immunity. Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.

Apple Peel Polyphenols and Their Beneficial Actions on Oxidative Stress and Inflammation

. 2013; 8(1): e53725.
Marie Claude Denis, Alexandra Furtos, Stéphanie Dudonné, Alain Montoudis, Carole Garofalo, Yves Desjardins, Edgard Delvin, and Emile Levy
From: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553108/#

Abstract

Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidants may contribute to the body’s natural defenses against inflammatory diseases.

Hypothesis

To define the polyphenols extracted from dried apple peels (DAPP) and determine their antioxidant and anti-inflammatory potential in the intestine. Caco-2/15 cells were used to study the role of DAPP preventive actions against oxidative stress (OxS) and inflammation induced by iron-ascorbate (Fe/Asc) and lipopolysaccharide (LPS), respectively.

Results

The combination of HPLC with fluorescence detection, HPLC-ESI-MS TOF and UPLC-ESI-MS/MS QQQ allowed us to characterize the phenolic compounds present in the DAPP (phenolic acids, flavonol glycosides, flavan-3-ols, procyanidins). The addition of Fe/Asc to Caco-2/15 cells induced OxS as demonstrated by the rise in malondialdehyde, depletion of n-3 polyunsaturated fatty acids, and alterations in the activity of endogenous antioxidants (SOD, GPx, G-Red). However, preincubation with DAPP prevented Fe/Asc-mediated lipid peroxidation and counteracted LPS-mediated inflammation as evidenced by the down-regulation of cytokines (TNF-α and IL-6), and prostaglandin E2. The mechanisms of action triggered by DAPP induced also a down-regulation of cyclooxygenase-2 and nuclear factor-κB, respectively. These actions were accompanied by the induction of Nrf2 (orchestrating cellular antioxidant defenses and maintaining redox homeostasis), and PGC-1α (the “master controller” of mitochondrial biogenesis).

Conclusion

Our findings provide evidence of the capacity of DAPP to reduce OxS and inflammation, two pivotal processes involved in inflammatory bowel diseases.

APPLE SUMMARY

Apple is an important fruit full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector+ such an outstanding nutritional supplement.