0

MIGHTY MULTI-VITE! MULTIVITAMIN – UPDATE

Dr. Hank Liers, PhD mighty multi vite multivitamin supplementFred Liers PhD Hank Brian mighty multi vite multivitamin

Think you take a complete multivitamin? Well, maybe not. Typical multivitamins simply do not provide enough nutrients for optimal health. Or for that matter, the proper forms and carriers of nutrients to do the job right—the all important task of providing you with essential nutrients for health. Not so easy these days? Well, Hank & Brian’s Mighty Multi-Vite! can help—a lot!

MIGHTY MULTI-VITE! DEFINES A COMPLETE MULTIVITAMIN

The task of providing you with a complete set of nutrients—as easily absorbed forms—is where Hank & Brian’s Mighty Multi-Vite! shines brightly in the world of #multivitamins. Quite simply, Dr. Hank Liers carefully formulated Mighty Multi-Vite! as the most advanced, complete multivitamin available. It uniquely includes a wide range of vitamins, minerals, cofactors, herbs, antioxidants, and Nrf2 activators (nutrients that allow your body to make its own antioxidants). This wide range of nutrients alone puts Mighty Multi-Vite! in a class by itself.

Calling HPDI’s Mighty Multi-Vite! “complete” is an understatement. While other multivitamins may contain more ingredients, Dr. Hank’s goal is not to “stuff” as many ingredients (or amounts) into Mighty Multi-Vite! as possible. That is a “shotgun” approach—Dr. Hank avoids it—that often results in too large capsules, huge tablets (“horse pills”), or eight-per-day dosages that are hard to consume—and even harder to stick with over time. You get the idea.

Instead, Dr. Hank carefully designed Mighty Multi-Vite! to include both a broad range of essential nutrients and abundant amounts of the most important nutrients for health in easily to assimilate forms using multiple carriers that give the body choices. For example, the body requires far smaller amounts of coenzyme B vitamins (which are the  natural forms best utilized by cells) than conventional forms of B vitamins. This allows for more efficient dosing and does not “waste” space in the capsule allowing more room for other nutrients, like antioxidants and Nrf2 activators. In a nutshell, few multivitamins are so well balanced and designed carefully to give the body what it needs for optimal health. You get it all in just four (4) regular size capsules, daily. How easy is that?

As I mentioned, Mighty Multi-Vite! includes highly absorbable forms of nutrients. These include mineral carriers like Krebs Cycle bionutrients—carriers that feed the energy producing system in the body—including malates, ascorbates, aspartates, sebacates, citrates, and glycinates. Thus, we use magnesium malate, and calcium ascorbate and citrate. The whole point is that the body immediately recognizes and utilizes these forms.

In practice, Dr. Hank’s inclusion of the most absorbable forms and carriers means you actually absorb and assimilate more of the ingredients—whether vitamins, minerals, cofactors, antioxidants, herbs, or Nrf2 activators—than you would from the same old conventional forms and carriers (oxides, for example) found in many multivitamins, especially “off-the-shelf” or “one-a-day” type formulas. Many so-called “boutique” formulas use conventional forms and carriers. Who knew!?

To top it off, many advanced ingredients in Mighty Multi-Vite! (like Nrf2 activators) are nowhere to be found in the vast majority of multivitamins. You might not even know to look for them!

However, the biggest benefit of the science behind Mighty Multi-Vite! is how you feel when taking it. I really feel the difference. Your multivitamin should work for you and support your best health. If your multivitamin is not giving you what you need—or you can’t feel the difference it makes in your life—then why take it? Maybe it is better than nothing, but why settle for less when better options are available?

The single biggest reason I am a huge fan of Mighty Multi-Vite! is because I have taken it for more than 20 years. I have gained all the benefits it offers—for thousands of days—year after year. I am more than confident in its superior benefits not just for me, but because I have seen many other people gain benefits, and heard countless positive testimonies from happy customers. I know you can gain major benefits from it, too.

But wait, there’s more! Read the overview (below) for some nitty, gritty details distinguishing Dr. Hank’s design of Mighty Multi-Vite!. These not-so-little details can make all the difference for your good health.Mighty Multi-Vite multivitamin supplement

MIGHTY MULTI-VITE! OVERVIEW

COMPLETE, BALANCED ESSENTIAL NUTRITION – Provides a full spectrum of nutrients exceptionally well balanced for creating and maintaining optimal heatlh. Mighty Multi-Vite! offers all of the most important vitamins along with minerals, cofactors, antioxidants, herbs, and Nrf2 activators.

RAPID, EASY ASSIMILATION – Incorporates the most bioavailable vitamin and mineral carriers most easily recognized and rapidly assimilated by your body. In addition, the formula uses multiple forms of mineral carriers to ensure assimilation. In addition, the capsule form (compared to tablets) speeds uptake because it does not require time for the body to break it down.

ENERGIZING – Includes coenzyme form vitamins and Krebs Cycle bionutrients that work with your body to create super high energy levels. Provides significantly higher levels of B vitamins than most multivitamins (especially coenzyme B vitamins). These vitamins are known for boosting energy, supporting the body during times of stress, and supporting nerve, heart, brain and immune system function.

FEATURES & BENEFITS OF MIGHTY MULTI-VITE! MULTIVITAMIN

• A full-spectrum of B-complex vitamins, most in coenzyme forms, as well as more conventional forms. Includes Vitamin B1 as thiamin HCl, Vitamin B2 as riboflavin and riboflavin-5’-phosphate, Vitamin B3 as niacinamide and niacin, Vitamin B5 as pantothenic acid, Vitamin B6 as pyridoxine HCl and pyridoxal-5’-phosphate, folate as L-5-methyltetrahydrofolate calcium (L-5-MTHF), Vitamin B12 as methylcobalamin, and biotin

• All of the most absorbable and usable forms of the fat-soluble vitamin group, including Vitamin A (as alpha & beta-carotene), Vitamin E (as d-alpha tocopherol succinate), Vitamin D3 (as cholecalciferol), and Vitamin K (as phytonadione (K1) and MK-7 (menaquinone-7) (K2))

• A complete and balanced supply of the most abundant carotenoids found in the body, including beta-carotene, alpha-carotene, lycopene and lutein

• A variety of the best-known herbal preparations, including whole grape extract (seeds, pulp, skin), turmeric (95% curcuminoids), broccoli sprouts powder, and octacosanol (from rice bran)

• All of the known essential minerals in forms readily absorbed and recognized by the body including calcium, magnesium, potassium, zinc, manganese, boron, copper, chromium, molybdenum, vanadium, and selenium

• Mineral carriers such as ascorbates, Krebs cycle bionutrients, and amino acids providing the body with important metabolic substrates and vitamins, including citrate, succinate, malate, glycinate, aspartate, sebacate, and Vitamin C

• Contains a wide range of antioxidants and Nrf2 activators including Buffered Vitamin C, Vitamin A, Vitamin E, Carotenoids, NAC, whole grape extract, curcuminoids, and broccoli sprouts

• Includes N-Acetyl-L-Cysteine (NAC), an important sulfur-containing amino acid supporting the body’s antioxidant and detoxification systems, and betaine HCl to support digestive processes

• Includes Choline and inositol which play a crucial role in all the cell membranes of the body, in brain function, and in liver function

• Includes Nrf2 transcription factor activators (i.e., Nrf2 activators), which are nutrients that direct cells to produce their own antioxidants, making your body an antioxidant production machine. Most multivitamins contain few, if any Nrf2 activators. Mighty Multi-Vite! is one of the few multivitamins whose design intentionally provides Nrf2 activators.

• Exclusion of the prooxidant minerals of iron and iodine which can lead to excessive free-radical production and PABA that sometimes adversely affects brain function in some individuals. (Note: we sell iodine formulas separately.)

• Capsule form ensures maximum absorption of ingredients

• Four-per-day full dosage allows for partial dosing for children, seniors, and pets

• Vegetarian formula (including capsule) suitable for vegetarians and vegans

• Exclusion of ingredients such as wheat, dairy, corn, soy, gluten, and egg having well-known antigenic properties and that may be associated with allergy or delayed hypersensitivity reactions

• A minimum of excipients, fillers, lubricants, etc. having deleterious effects in some individuals

• NON-GMO (no genetically modified organisms)

CONSIDER MIGHTY MULTI-VITE!

Most people don’t think too hard about their multivitamins. They focus on taking the supplement de jour (whatever supplements make headlines) or continue taking the same one-a-day multivitamin.

That is too bad because a multivitamin truly is the single most important nutritional supplement. We at HPDI place the multivitamin first—above all other supplements—in importance. Our Foundational Supplements system starts with a multivitamin because it is the only formula designed to provide the basic nutrients essential for health. That is, you can add other essential nutrients (like vitamin C or essential fats) to complete your regimen. But the multivitamin remains king (or queen) because it establishes your baseline nutrient intake. That is something is to consider when selecting the multivitamin you will take daily for the rest of your life.

Ask yourself: Is my multivitamin complete, providing all the most important nutrients I need for health? Is it easily absorbed using multiple, readily assimilated forms and usable carriers of those nutrients? Is it proven to work? Is it easy to take? Do I notice the effects?

If you answer “no” to any of these questions, or if you simply never think about it, then consider Hank & Brian’s Mighty Multi-Vite!. You should love your multivitamin because of how it supports your health. We think you will love Mighty Multi-Vite!.

MIGHTY MULTI-VITE! RESOURCES

Hank & Brian’s Mighty Multi-Vite!

HPDI Multivitamins

Foundational Supplements

VIDEOS

HPDI YouTube Channel

Foundational Supplements video

1

THE AMAZING HEALING POTENTIAL OF NATURAL NRF2 ACTIVATORS

Dr. Hank Liers, PhD natural nrf2 activators healing potential

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

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

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

 

Ultimate Protector+

New Ultimate Protector+

 

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

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

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

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

SOME KEY ENZYMES MODULATED BY Nrf2 ACTIVATORS

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

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

NATURAL FOODS AND FOOD EXTRACTS PROMOTE THE EXPRESSION OF Nrf2

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

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

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

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

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

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

DIETARY FLAVONOIDS AS NRF2 ACTIVATORS

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

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

Table 1: Common Dietary Flavonoids

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

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

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

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

 

Ultimate Protector+

INTERESTING FACTS REGARDING NRF2 ACTIVATORS

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

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

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

TABLE 2: ORAC5.0™ COMPARATIVE RESULTS

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

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

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

NEUROPROTECTION BY POLYPHENOL STIMULATION OF THE NRF2 / ARE PATHWAY 

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

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

ABSTRACT

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

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

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

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

ABSTRACT

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

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

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

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

 

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

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

REVIEW ARTICLE

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

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

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

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

CONCLUSION

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

SOURCES

BLOG ARTICLES

 SCIENTIFIC ARTICLES

 

8

Natural Phytochemical Nrf2 Activators for Chemoprevention

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

INTRODUCTION
Nrf2 SIGNALING, FOODS, AND HEALTH

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

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

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

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

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

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

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

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

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

DIETARY PHYTOCHEMICALS ARE NATURE’S CHEMOPREVENTIVE AGENTS

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

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

Ultimate Protector+

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

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

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

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

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

Nrf2 BOOSTS CELL DETOXIFICATION AND ANTIOXIDANT ENZYMES

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

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

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

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

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

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

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

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

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

Ultimate Protector is now available on the HPDI website!

 

Ultimate Protector+Ultimate Protector+ is new and improved

 

REFERENCES

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

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

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

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

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

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

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

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

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

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

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

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

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

ADDITIONAL RESOURCES

Ultimate Protector™

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

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

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

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

2

PRO-C AND ULTIMATE PROTECTOR – COMPARISON OF ANTIOXIDANT FORMULAS

Dr. Hank Liers, PhD antioxidant formulasI have written extensively regarding the benefits HPDI’s PRO-C™ and Ultimate Protector™ antioxidant formulas. Based upon my experience with these formulas they are among the most effective antioxidant formulas available.

Both antioxidant formulas are included in HPDI’s system of foundational supplements and work most effectively when used with multivitamins, essential fats, and superfoods.

Yet, both formulas also are excellent standalone products that can rapidly provide the body with extremely high protection against free radicals.
Ultimate Protector antioxidant formulas

We are often asked “which of these two antioxidant formulas should I take?” My answer usually is to take both formulas. I personally take both of them on a daily basis.

Below I will briefly show the reason my answer is to take both formulas. I include information showing the relationship, in terms of ingredients of the two formulas (per serving of three (3) capsules daily of PRO-C and six (6) capsules daily of Ultimate Protector).

Ultimate Protector

INGREDIENTS OF ANTIOXIDANT FORMULAS

PRO-C™ (per serving of three “00” veggie caps)

• Buffered non-GMO Vitamin C (1,500 mg)  buffered with Ca/Mg/Zn
• Grape Extract (seed, skin, and pulp) (90 mg)
• Green Tea Extract 95% polyphenols 40% min. EGCG (90 mg)
• Glutathione – reduced (60 mg)
• N-Acetyl-l-Cysteine (NAC) (45 mg)
• R-Lipoic Acid (15 mg)
• Coenzyme B2/R5P (3 mg)
• Coenzyme B6/P5P (3 mg)
• Selenium from l-selenomethionine (30 mcg)
• Calcium (70 mg)
• Magnesium (70 mg)
• Zinc (6 mg)

ULTIMATE PROTECTOR™ (per serving of six “0” veggie caps)

• Vitamin C as non-GMO Ascorbic acid (1500 mg)
• Anthocomplete™ (135 mg)  Wild Blueberry, Wild Bilberry, Acai, Black Currant Extract, Sweet Cherry, Raspberry, Elderberry, Blackberry, Aronia, Black Soybean Hull Extract, and Blue Corn
• CoffeeBerry®Forte (135 mg)
• Vitaberry® Plus (90 mg) freeze-dried Grape Seed, Wild Blueberry, Wild Bilberry, Cranberry, Tart Cherry, Prune, Raspberry Seed, Strawberry, Trans-Resveratrol, and Quercetin
• VitaVeggie® (90 mg)  Broccoli, Broccoli Sprouts, Tomato, Kale, Carrot, Brussels Sprouts, Onion, and Spinach
• Curcumin 95%  (90 mg)
• Trans-Resveratrol 98% (90 mg)
• Malic Acid (500 mg)
• Calcium (60 mg)
• Magnesium (60 mg)
• BioPerine® (7.5 mg)

The products together contain nine (9) unique PRO-C™ ingredients, eight (8) unique Ultimate Protector™ ingredients, and three (3) overlapping ingredients.

DISCUSSION OF ANTIOXIDANT FORMULAS

PRO-C™

When PRO-C™ was first released in 1997 there were few publications available regarding Nrf2 ingredients and their benefits. The product design was based on the work of Dr. Lester Packer and his work done on the “Antioxidant Network” showing how nutrients such as Vitamin E, Vitamin C, Glutathione, and Lipoic acid work in a redox network to regenerate key nutrients in the body (see Figure 1. below)

doctor lester packer antioxidant formulas

                                                Figure 1. – Dr. Packer’s Antioxidant Network

At that time the powerful antioxidant formulas of Grape Seed Extract and Green Tea Extract were well known, but their powerful Nrf2 effects were not discovered until later. These ingredients are able to trap free radicals and conserve the body’s store of network antioxidants.

Also, the Nrf2 effects of NAC and Lipoic acid were not known at the time, but their powerful effects on the body were known to support the production of glutathione. Additionally, the super powerful glutathione (reduced) was included with supporting coenzymes B2 (from riboflavin 5′-phosphate) and B6 (from pyridoxal 5′-phosphate) that allow the enzymes glutathione reductase and transferase to function at a higher level.

ULTIMATE PROTECTOR™

From the beginning of the design process, Ultimate Protector™ (UP) was focused on creating a highly effective Nrf2 activator formula with outstanding antioxidant effects. Our understanding was that a very broad spectrum of plant polyphenols including flavonoids, anthocyandins, oligoproanthocyanidins (OPCs), etc. would deliver the best results.

We selected Futureceuticals Anthocomplete™, CoffeeBerry® Forte, Vitaberry® Plus, and VitaVeggie® in order to accomplish this and added Curcumin 95%, and Trans-Resveratrol 98% because of the powerful scientific findings regarding Nrf2 activation for these two ingredients. We found out later in testing that this combination of ingredients produces very high ORAC5.0 values (486,000 units/serving of six capsules) and works effectively against all of the primary types of free radicals in the body.

WHY TAKE BOTH PRO-C™ AND
ULTIMATE PROTECTOR™ ANTIOXIDANT FORMULAS?

Ultimate Protector versus PRO-C antioxidant formulas

Venn diagram showing unique and overlapping ingredients in PRO-C and Ultimate Protector.

There are 29 unique Nrf2 activator ingredients in Ultimate Protector (UP) and four (4) non-overlapping Nrf2 activator ingredients in PRO-C. Thus by taking both formulas you are able to receive 33 identifiable Nrf2 activator ingredients (870 mg). The amount of unique Nrf2 ingredients is probably significantly more than this because most of the identifiable ingredients contain a range of plant polyphenols.

Other unique ingredients of each formula include glutathione – reduced (60 mg), malic acid (500 mcg), zinc (6 mg), selenium (30 mcg), B2 (3 mg) and B6 (3 mg) from coenzyme forms, and Bioperine (7.5 mg) (for enhanced absorption of nutrients). These are important ingredients to have the formulas work more effectively together.

The overlapping ingredients in the formula include Vitamin C (3 gm – 1.5 gm from each formula), calcium (130 mg – 70 mg from PRO-C & 60 mg from UP), magnesium (130 mg – 70 mg from PRO-C & 60 mg from UP), and a little grape seed extract (~10 mg). We view this to be very positive especially because we believe that most people should take in at least 3 grams daily of Vitamin C. Equal amounts of calcium and magnesium balance each other in the body and have many important functions such as being part of critical enzymes.

SOURCES & RESOURCES

The Antioxidant Miracle. Lester Packer, PhD, and Carol Coleman. New York: John Wiley and Sons, 1999.

“Antioxidant Cocktail Update: Part 1: The Take Home Message is to Use Antioxidant Supplements”
(Interview of Dr. Lester Packer by Richard A. Passwater, PhD, Whole Foods Magazine, 1999)

HPDI BLOG ARTICLES

CONTACT US:

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

Health care professionals and resellers can apply for wholesale account, which includes access to the HPDI reseller website: HealthProductsDistributors.com. Email: Support(at)HealthProductsDistributors.com.

0

ULTIMATE PROTECTOR INGREDIENTS – CRANBERRY

Hank Liers cranberries cranberry ultimate protector Nrf2Ultimate Protector™ contains freeze dried cranberry, as well as components from 29 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 explore the ingredient strawberries, which is a component of VitaBerry Plus® from Futureceuticals.

VITABERRY PLUS®

VitaBerry® (N1023) is the trade name for a line of high ORAC blends of fruit powders and fruit extracts, exclusively available through FutureCeuticals.

VitaBerry® is a proprietary formula that combines wild bilberry and wild blueberry, cranberry, raspberry, strawberry, prune, cherry, and grape whole powders and extracts into lines of custom blends. High in fruit polyphenols, anthocyanins, proanthocyanins, ellagic acid, chlorogenic acid, resveratrol, and quinic acid, VitaBerry offers 6,000 ORAC units in a single gram.

VitaBerry® Plus (N81.3) combines the standard blend of VitaBerry® with resveratrol and quercetin to deliver a minimum of 12,000 ORAC units per gram.

Cranberry

Cranberries

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.

Cranberries are 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 cranberries.

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 cranberries 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.
  • In 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 the sites given below:
https://www.healthambition.com/health-benefits-of-cranberry-juice/
or
http://www.whfoods.com/genpage.php?tname=foodspice&dbid=145

Scientific Studies on the Antioxidant Effects of Cranberry

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.

Ultimate Protector cranberry cranberries

SUMMARY

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

ADDITIONAL RESOURCES

 

Contact Us:

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

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