Fred Liers PhD foundational supplements nutritionHPDI foundational supplements are designed to provide a complete range of essential nutrients that complement a healthy diet and lifestyle. They help ensure sufficient levels of nutrients required for good health.

We define foundational supplements as basic or “core” supplements that should be part of everyone’s daily regimen. They are the foundation of a complete nutritional supplement program.

HPDI has a three-tiered system of nutritional supplements: 1) Foundational Supplements, 2) Enhancement Formulas, and 3) Specific-Condition Formulas. All three tiers comprise a complete nutritional supplement program.

When properly combined, these three tiers of nutritional supplements help create optimal health. This month, I explain how to use HPDI foundational supplements, the base or bottom tier of the system (see cone diagram below).

The HPDI supplement system can be visualized as a cone having a base of Foundational Supplements ascending toward an apex of Enhancement Formulas and Specific Condition Formulas.

foundational supplements HPDI system

The HPDI Supplement System includes six types of Foundational Supplements forming its base.


My intent is to guide consumers and health care professionals to decide the foundational supplements that are best for their purposes, and that provide the most effective results.

For anyone new to HPDI’s Foundational Supplements system, we recommend six basic types of supplements. The six categories are: 1) multivitamin formulas, 2) vitamin C / antioxidant formulas, 3) essential fats, 4) high-RNA foods (Rejuvenate! superfoods), 5) gut health formulas, and 6) hydrogen formulas.

We established the original three types of foundational supplements about 1988. We have always suggested that clients and health professionals take and/or recommend multivitamins, vitamin C and antioxidants, and essential fats.

About 10 years ago, we added high-RNA foods (like Rejuvenate! superfoods) as a fourth type of foundational supplement because research indicates dietary nucleic acids are essential nutrients—see our blog articles on nucleic acids, Benjamin S. Frank, MD, PhD, and about Rejuvenate! superfoods (Original, Plus, and Berries & Herbs).

Two categories of foundational supplements are new: gut health formulas and hydrogen formulas. Hank wrote an article (Amending the HPDI Foundational Program) about these changes in April. We added these two categories after much consideration regarding their benefits, and have written extensively about them in this blog (see resources section below).

The entire HPDI supplement system is depicted (above) as a cone. The six types of foundational supplements form the base of the cone. Enhancement Formulas and Specific-Condition formulas sit above toward the apex.

ultimate protector foundational supplements

Ultimate Protector Nrf2 formula is a foundational supplement in the vitamin C / antioxidant category.


I use all six types of HPDI foundational supplements. I take the following supplements (below) and present them here as an example of how they can be integrated into a complete supplement regimen. Foundational Supplements I take:

1. Multivitamin: Hank & Brian’s Mighty Multi-Vite! (4 per day in divided doses)

2. Vitamin C / antioxidants: PRO-C (6-8 per day) and Ultimate Protector Nrf2 activator (8-12 per day)

3. Essential Fats: Essential Fats Plus E (4 per day)

4. Rejuvenate!™ superfood: All three Rejuvenate! superfoods (2-8 scoops per day)

5. Gut Health: RESTORE For Gut Health (1-2 ounces per day) and Prescript-Assist™ probiotic (soil-based organisms) (1-3 per week)

6. Hydrogen: Megahydrate (2-6 per day)

Taking one supplement from each of the six foundational supplement categories builds, supports, and maintains optimal health.

We at HPDI recommend everyone take one of each type of foundational supplement. That is, we suggest an individual select for personal use a multivitamin, vitamin C/antioxidant formula, essential fats formula, Rejuvenate!™ superfood (or other high-RNA superfood), hydrogen product, and at least one gut health product (depending on their gut-health needs).

Similarly we suggest health care professionals recommend for their clients one of each of the six types of foundational supplements.

The other two categories in the HPDI nutritional supplement system are Enhancement Formulas and Specific-Condition Formulas (see cone diagram). These are not foundational supplements. However, I include the supplements I take in these categories for the sake of completeness, as well as to show how Enhancement and Specific-Condition Formulas integrate with Foundational Supplements to form a complete supplement program providing a wide-range of essential nutrients required for health.

Enhancement Formulas I take include: B-Complex-50 (B complex), Myo-Mag (magnesium/malic acid), Ubiquinol-50, Bone Guardian, and Vitamin D3 Plus.

Specific Condition Formulas I take include: Joint Health Formula, Allergy Support Formula, Eye & Vision Formula, Intestinal Rejuvenation Formula, and Warrior Mist (pain topical), and Warrior Sleep (sleep topical).

While I take supplements from all three categories (Foundationals, Enhancements, and Specific-Condition) in the HPDI supplement system, I always prioritize foundational supplements—I take them first—because they are base on which my personal supplement program rests.

Foundational supplements should be the base on which your supplement program—or those of your clients—rests, as well.

We have seen the results of taking a complete set of foundational supplements. They work because the nutrients they provide are needed by everyone.

HPDI foundational supplements multivitamin

Muti Two Caps is a high-potency multi with coenzyme forms for optimal utilization in the body.


Individuals who take all types of foundational supplements do best in terms of optimizing health. The reason is that all six types provide nutrients required for good health.

I can attest that HPDI Foundational Supplements are effective for improving or maintaining good health. In addition, I have witnessed numerous instances where individuals benefit most greatly when taking all four–and now all six–types of foundational supplements.

Each of the six categories of foundational supplement provide unique benefits. Yet, each performs functions required by the human body for good health. That is one reason when they are combined they exert synergistic effects for health going far beyond the benefits of using, one, two, or three of the types of foundational supplements.


I talk to people who may or may not take a multivitamin. And they may or may not take vitamin C. Yet, they may take calcium for their bones, glucosamine for their joints, and lutein for their eyes. Or they may take a low-potency, off-the-shelf multivitamin providing merely the RDA for all nutrients.

There is nothing wrong with individuals taking supplements they regard as important or useful. But that cannot guarantee that a wide range—and sufficient levels—of nutrients necessary for health are available to the body on a regular basis.

In fact, I regard the supplement intake programs of most persons to be “hit-or-miss.” They may consume nutrients important for a few functions in the body, yet fail to obtain other essential nutrients required for the nutrients they take to work most effectively. We have written extensively on this topic on our website and in blog articles (see below).

Not taking regularly a complete set of foundational supplements likely means key nutrients (and key levels of nutrients) go missing. Over time, this means fewer and lower levels of nutrients available to support the body’s needs for them at levels known to sustain the good health.

The best way to ensure a sufficient range of nutrients at plentiful levels is to take foundational supplements. After a baseline of nutrients is established by taking foundational supplements, additional supplements can be added, as necessary.

rejuvenate superfood foundational supplements

High-RNA foods like Rejuvenate! PLUS superfood provide dietary nucleic acids important for health.


After obtaining sufficient levels of basic nutrients required for health, then a person can add (or you can recommend) specific nutrients or formulas that target certain problems or issues. This is the basis for HPDI development of Enhancement Formulas and Specific-Condition Formulas.

Nutritional supplements in the categories of Enhancement Formulas and Specific-Condition Formulas therefore “stack” on top of HPDI’s Foundational Supplements (see cone diagram above). In this way, a complete nutritional supplement program begins with the most essential nutrients and continues with customizations based on the unique needs of an individual.


Enhancement Formulas in the HPDI system are supplements we regard as falling into the next tier in terms of importance, at least for most people. They do not necessarily provide essential nutrients, and yet many people (including myself) benefit significantly from them.

Enhancement Formulas include: magnesium formulas (topical and capsule), Vitamin D3 Plus, Nascent Iodine, Vitamin B12 (methylcobalamin), mushroom-based products (like Immune-Assist™), Prolyt (proteolytic enzymes), Digase (plant-based enzymes), and Warrior Mist (topical pain reliever), and many other formulas.


In the HPDI system, individuals can add (in a modular way) various formulas and single nutrients designed to support a particular set of needs or a target a specific condition.

We offer a complete range of supplements (almost 100) including a range of supplements formulated to address specific conditions. These include Joint Health Formula, Eye & Vision Formula, Blood Sugar Support, Allergy Support Plus, Prosta Plus, and many other formulas.


HPDI Foundational Supplements collectively form the base tier of a complete nutritional supplement system comprised of three tiers: 1) Foundational Supplements (six types), 2) Enhancement Formulas (or simply “Enhancements”), and 3) Specific-Condition Formulas.

Foundational Supplements are necessary because they provide nutrients foundational to health. Taking them daily or recommending your clients take them daily can help mean big differences in health, nutrition, and quality of life.

We at HPDI design our nutritional supplements to be the most effective dietary supplements available. HPDI products are known for: 1) Advanced Formulation (including use of superior forms of nutrients), 2) Ultra-High Purity, 3) Avoidance of Harmful Ingredients, and 4) being made with Good Manufacturing Practices (GMP). For more details, please see The HPDI Difference and our Statement on Additives (Excipients).

At least 40 of HPDI’s products are formulated by Dr. Hank Liers. They fall in all categories in HPDI’s supplement system. They can be found under “Dr. Hank Liers original formulas.”

omega plus foundational supplement

Omega Plus provides exceptionally well-balanced omega-3 and omega-6 fatty acids.


We frequently get questions from HPDI clients and resellers regarding foundational supplements. These questions include:

“Why did you add gut health and hydrogen products to your foundational supplements program?”
We found it necessary to add categories for gut health and hydrogen because they provide nutrients that are support the body and help ensure the foundational supplement system supports health most effectively. You can read more in previous blog articles (see below).

“Which is the better multivitamin: Multi Two or Mighty Multi-Vite!™?”
It depends on whether you need more B vitamins or antioxidants. Multi Two provides more B vitamins and Mighty Multi-Vite™ provides more antioxidants and cofactors. I take a separate HPDI B-Complex-50 formula, so I take Mighty Multi-Vite!™ as my primary multivitamin.

“What are the differences between Rejuvenate!™ Original, PLUS, and Berries & Herbs superfoods?”
They each provide about 340 mg of dietary nucleic acids. Original is the “greenest” with a large percentage of dietary nucleic acids coming from chlorella and spirunlina. PLUS is our most popular and 30% is identical to Original with more protein and a built-in multivitamin complex. Berries & Herbs contains no greens, yet more nucleic acids (390 mg), protein, and a built-in multivitamin. See our Rejuvenate! comparison page for more information.

“Should I take a vitamin C formula with antioxidants like PRO-C or one with Nrf2 activators like Ultimate Protector?”
Both provide vitamin C and Nrf2 activators, but Ultimate Protector provides more types of Nrf2 activators. Ultimate Protector capsules are smaller than PRO-C capsules, so a daily dose may require taking more capsules.

“How important are hydrogen supplements?”
Very important for energy production, recovery, antioxidant functions, and gut health. Hydrogen supplements like Active H2 and Megahydrate ensure high levels of hydrogen are available in the body.

What are your best products for supporting gut health?
It depends on your needs: cleansing (Intestinal Rejuvenation Formula), probiotic/microbiome support (Prescript-Assist™), or tightening tight junctions in the gut (RESTORE)? We offer products for all these purposes.

These are just a few questions frequently asked about HPDI foundational supplements. If you need more information about products, please contact the HPDI office (800-228-4265) or email support@healthproductsdistributors.com.

You can also contact Fred Liers, PhD (520-400-0155) or Hank Liers, PhD (formulator) with questions you may have regarding products, ingredients, or formulation.


Foundational Supplements

HPDI Full Product Overview

The Need for Foundational Supplements (.pdf)

The HPDI Difference (4 Pillars of Formulation)


Amending the HPDI Foundational Supplements Program

Foundational Supplements Remain Fundamental

Vitamin C / Antioxidants

PRO-C and Ultimate Protector Comparison

Questions and Answers about Ultimate Protector

The Amazing Healing Potential of Natural Nrf2 Activators

Ultimate Protector™: First Impressions

Ultimate Protector™ Brunswick Labs ORAC5.0™ Test Results

Preventing Free-Radical Damage Using Ultimate Protector™

Description and Comparison of ORAC Tests for Well Known Plant Ingredients and Ultimate Protector™

Ultimate Protector and the Role of Foundational Supplements for Health

Natural Phytochemical Nrf2 Activators for Chemoprevention

New Directions for Preventing Free Radical Damage

Review of Scientific Research on Oligomeric Proanthocyanidins (OPC)” by Dr. Hank Liers

“Vitamin C – An Amazing Nutrient” by Dr. Hank Liers

Rejuvenate! Superfoods

Rejuvenate! Berries & Herbs: Ingredients for Optimal Nutrition

9 Things to Know About Rejuvenate!™ Superfoods

High-RNA Rejuvenate!™ Superfood

Get Results with Rejuvenate! Superfoods

Dietary RNA for Athletic Performance



Super-Tasty Morning Nutritional Drinks


The Science Behind Megahydrate

Hydrogen for Optimal Health

Wonders of Molecular Hydrogen

Gut Health

Gut Health – Effects of Glyphosate and Antibiotics

Gut Health – Intestinal Rejuvenation Formula


Vitamin formulas, including multivitamins

Mighty Multi-Vite!

Multi Two Caps

Rejuvenate!™ Berries & Herbs

Rejuvenate!™ PLUS

Rejuvenate!™ (Original)

Rejuvenate! Superfoods: Product Comparison

Ultimate Protector™ Nrf2 Activator (vitamin C/antioxidant)

PRO-C (Vitamin C/Antioxidant formula)

Intestinal Rejuvenation Formula (gut health)

Restore For Gut Health (lignite formula)

Active H2 (hydrogen)

Megahydrate (hydrogen)

Prescript-Assist™ (probiotic/prebiotic)




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® (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.




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:

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.


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


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


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


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


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



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



Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist strawberriesUltimate Protector™ contains freeze dried strawberries, 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® (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.

Strawberry strawberries


Strawberries long have grown wild in the world’s temperate regions. They have been cultivated for several thousand years and were prized among the ancient Romans. Most of the common varieties of strawberry derive from a hybrid (Frangaria x ananassa). Strawberries have an ORAC value of 1,540, which is very high among the fruits and vegetables tested by the USDA. They are a good source of vitamins C, K, B2, B5, B6, and folate. They also contain appreciable amounts of the minerals manganese, iodine, and potassium, as well as dietary fiber.

Like other berries, the antioxidants contained in strawberries may be useful against diseases of the heart and arteries by preventing the oxidation of lipids. The phytonutrient phenols most abundant in strawberries are anthocyanins and ellagitannins. The anthocyanins help to prevent oxidative damage from free radicals in body. The unique phenol profile of the strawberry enables it not only to protect the heart, but also to fight inflammation. Studies have shown that strawberries also protect the brain from oxidative stress and may therefore reduce age-related cognitive decline in brain function. Strawberries have been shown to be Nrf2 activators that can stimulate the endogenous production of protective enzymes in the body.

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

  • Anthocyanins
    • cyanidins
    • pelargonidins
  • Flavonols
    • procyanidins
    • catechins
    • gallocatechins
    • epicatechins
    • kaempferol
    • quercetin
  • Hydroxy-benzoic acids
    • ellagic acid
    • gallic acid
    • vanillic acid*
    • salicylic acid
  • Hydroxy-cinnamic acids
    • cinnamic acid
    • coumaric acid
    • caffeic acid
    • ferulic acid
  • Tannins
    • ellagitannins
    • gallotannins
  • Stilbenes
    • resveratrol

For more information on strawberries visit: http://www.whfoods.com/genpage.php?tname=foodspice&dbid=32

Scientific Studies on the Antioxidant Effects of Strawberries

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

Strawberry as a functional food: an evidence-based review

From: http://www.ncbi.nlm.nih.gov/pubmed/24345049


Emerging research provides substantial evidence to classify strawberries as a functional food with several preventive and therapeutic health benefits. Strawberries, a rich source of phytochemicals (ellagic acid, anthocyanins, quercetin, and catechin) and vitamins (ascorbic acid and folic acid), have been highly ranked among dietary sources of polyphenols and antioxidant capacity. It should however be noted that these bioactive factors can be significantly affected by differences in strawberry cultivars, agricultural practices, storage, and processing methods: freezing versus dry heat has been associated with maximum retention of strawberry bioactives in several studies. Nutritional epidemiology shows inverse association between strawberry consumption and incidence of hypertension or serum C-reactive protein; controlled feeding studies have identified the ability of strawberries to attenuate high-fat diet induced postprandial oxidative stress and inflammation, or postprandial hyperglycemia, or hyperlipidemia in subjects with cardiovascular risk factors. Mechanistic studies have elucidated specific biochemical pathways that might confer these protective effects of strawberries: upregulation of endothelial nitric oxide synthase (eNOS) activity, downregulation of NF-kB activity and subsequent inflammation, or inhibitions of carbohydrate digestive enzymes. These health effects may be attributed to the synergistic effects of nutrients and phytochemicals in strawberries. Further studies are needed to define the optimal dose and duration of strawberry intake in affecting levels of biomarkers or pathways related to chronic diseases.

Bioactive Compounds and Antioxidant Activity in Different Types of Berries


Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.

Dietary intakes of berries and flavonoids in relation to cognitive decline

From: http://www.ncbi.nlm.nih.gov/pubmed/22535616


Objective: Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women.

Methods: Beginning in 1980, a semiquantitative food frequency questionnaire was administered every 4 years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at 2-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariate-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes.

Results: Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (eg, for a global score averaging all 6 cognitive tests, for blueberries: p-trend = 0.014 and mean difference = 0.04, 95% confidence interval [CI] = 0.01–0.07, comparing extreme categories of intake; for strawberries: p-trend = 0.022 and mean difference = 0.03, 95% CI = 0.00–0.06, comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we found for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends = 0.015 and 0.053, respectively, for the global score).

Interpretation: Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.

Addition of strawberries to the usual diet decreases resting chemiluminescence of fasting blood in healthy subjects-possible health-promoting effect of these fruits consumption

From: http://www.ncbi.nlm.nih.gov/pubmed/24912053


OBJECTIVE: Regular strawberry consumption augmented plasma antioxidant activity and decreased lipid peroxidation suggests preventive potential of these fruits against oxidative stress-dependent disorders. Blood phagocytes are important source of oxidants that may contribute to systemic oxidative stress. We examined the effect of strawberry consumption on the luminol enhanced whole blood chemiluminescence (LBCL) reflecting oxidants generation by circulating phagocytes in healthy subjects.

METHODS: Thirty-one healthy subjects (being on their usual diet) consumed 500 g of strawberry pulp daily (between 11.00-14.00) for 30 days (1st strawberry course) and after 10 day wash-out the cycle was repeated (2nd strawberry course). Fasting blood and spot morning urine samples were collected before and after each strawberry course for measuring resting and agonist (fMLP)-induced LBCL, various phenolics and plasma antioxidant activity. Twenty subjects served as a control in respect to LBCL changes over the study period.

RESULTS: Strawberry consumption decreased median resting LBCL and this effect was more evident after the 1st course (by 38.2%, p < 0.05) than after the the 2nd one (18.7%), while fMLP-induced LBCL was constant. No changes in LBCL were noted in controls. Strawberries increased fasting plasma levels of caffeic acid and homovanillic acid as well as urolithin A and 4-hydroxyhippuric acid in spot urine. Plasma antioxidant activity and the number of circulating phagocytes did not change over the study period. Resting LBCL correlated positively with the number of circulating polymorphonuclear leukocytes at all occasions and negative correlation with plasma 4-hydroxyhippuric acid was noted especially after the first strawberry course (r = -0.46, p < 0.05).

CONCLUSIONS: The decrease in resting LBCL suggests that regular strawberry consumption may suppress baseline formation of oxidants by circulating phagocytes. This may decrease the risk of systemic imbalance between oxidants and anti-oxidants and be one of mechanisms of health-promoting effect of these fruits consumption.

Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy subjects

From: http://www.ncbi.nlm.nih.gov/pubmed/25120279


Strawberries contain anthocyanins and ellagitanins which have antioxidant properties. We determined whether the consumption of strawberries increase the plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10 volunteers (age 41 ± 6 years, body weight 74.4 ± 12.7 kg) that consumed 500 g of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot morning urine samples were collected at baseline, during fruit consumption and after a 6 day wash-out period. DPPH decomposition was measured in both deproteinized native plasma specimens and pretreated with uricase (non-urate plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect on the antioxidant activity of native plasma and circulating phenolics. Non-urate plasma DPPH decomposition increased from 5.7 ± 0.6% to 6.6 ± 0.6%, 6.5 ± 1.0% and 6.3 ± 1.4% after 3, 6 and 9 days of supplementation, respectively. The wash-out period reversed this activity back to 5.7 ± 0.8% (p<0.01). Control subjects did not reveal any changes of plasma antioxidant activity. Significant increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times after 6 days of supplementation with fruits) was noted. Strawberry consumption can increase the non-urate plasma antioxidant activity which, in turn, may decrease the risk of systemic oxidants overactivity.

One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans

From: http://www.ncbi.nlm.nih.gov/pubmed/24406274


Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk.

Impact of strawberries on human health: insight into marginally discussed bioactive compounds for the Mediterranean diet


OBJECTIVE: To review and update the current knowledge on the potential impact of strawberry on human health, with particular attention on compounds and indirect mechanisms of action not exhaustively considered.

DESIGN: Personal perspectives and recent data.

SETTING: International.

RESULTS: Our research group was among the few groups that have recently investigated the folate content in fresh, stored and processed strawberries, and the data look very promising. As well, some in vivo evidence of the impact of strawberry intake on the folate status in humans have already been reported, but a new increasing interest on this field is strongly hoped. Furthermore, the hypouricaemic effects previously ascribed to cherry consumption need to be evaluated in respect to strawberry intake. At the moment, inconsistent results come from the few investigations designed at this proposal. In our studies, a great interindividual variability was observed on plasma urate levels in response to strawberry intake, suggesting a putative effect.

CONCLUSIONS: The mechanisms responsible for the potential health-promoting effects of strawberry may not be necessarily searched in the activity of phytochemicals. Particularly, a greater interest should be addressed to show whether a prolonged strawberry consumption may effectively improve the folate status and reduce the incidence of folate-related pathological conditions. Furthermore, the hypouricaemic effects of cherries need to be evaluated also in respect to strawberry intake, and the mechanisms of actions and anti-gout potentialities need to be studied in detail. Future investigations involving human trials should be aimed at following these underestimated scientific tracks.

strawberry strawberries fruit


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


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



Dr. Hank Liers, PhD biography HPDI integratedhealth formulator scientist physicist black currant extractUltimate Protector contains black currant extract, 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 will explore the ingredient black currant extract, which is a component of Anthocomplete™ from Futureceuticals.


AnthoComplete™ (N669) is a specially designed blend of anthocyanins derived from wild bilberry and wild blueberry, açaí, black currant extract, sweet cherry, raspberry, elderberry, blackberry, aronia, black soybean hull extract, and blue corn. Anthocyanins are powerful plant polyphenols associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

Carefully designed to maximize the amount of beneficial anthocyanins that can be available in a single source, AnthoComplete™ is a proprietary formula suitable for a wide range of applications.

With its diverse blend, AnthoComplete™ contains a minimum level of 10% anthocyanins, 3,000 ORAC μmole TE/g (typical), and 15% total phenolics (typical).

Owing to the high levels of anthocyanins and vitamin C, two types of important antioxidants, black currants have been shown by scientific research to have many benefits in promoting health and wellness. Vitamin C is an essential nutrient required for the body’s normal functions and the antioxidant polyphenols in black currants (particularly anthocyanins) may help in maintaining cardiovascular health, aging and brain health, urinary tract health, and healthy vision.

Black Currant

Black Currant Berries


Black currants (Ribes nigrum) have been used in a wide variety of foods for many years. They contain a relatively large vitamin C content, more than almost any other commonly consumed fruit. Ongoing research is further showing the benefits of black currants based largely on the polyphenolic content of the fruit and its related products.

Black currants have antioxidant value (oxygen radical absorbance capacity – ORAC) of 7950 Trolex Equivalents per 100 g, which is one of the highest value for fruits after chokeberries, elderberry, and cranberries.

The intensely dark color of blackcurrants is due to its high content of anthocyanin — primarily 3-glucosides and 3-rutinosides of cyanidin and delphinidin. It has been found that these components exhibit powerful hydroxyl radical scavenging abilities and protect endothelial cells in model systems.

In addition, the anthocyanins have been shown to positively influence the α-glucosidase phase of starch digestion providing a reduction of sugar release during starch food digestion.

Also, black currants are a good source of glycosylated flavonols such as quercetin, myrecetin and kaempferol. Scientific studies at the fundamental cellular level have indicated that these compounds can interact with the bodies own innate Antioxidant Response Elements (ARE), such as the transcription factor Nrf2, and more specifically stimulate expression of the detoxification enzymes such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes.


Below, we provide a few relevant scientific studies on the antioxidant effects and potential health benefits of black currant extracts.

Biological activity of blackcurrant extracts (Ribes nigrum L.) in relation to erythrocyte membranes.
From: http://www.ncbi.nlm.nih.gov/pubmed/24527456


Compounds contained in fruits and leaves of blackcurrant (Ribes nigrum L.) are known as agents acting preventively and therapeutically on the organism. The HPLC analysis showed they are rich in polyphenol anthocyanins in fruits and flavonoids in leaves, that have antioxidant activity and are beneficial for health. The aim of the research was to determine the effect of blackcurrant fruit and leaf extracts on the physical properties of the erythrocyte membranes and assess their antioxidant properties. The effect of the extracts on osmotic resistance, shape of erythrocytes and hemolytic and antioxidant activity of the extracts were examined with spectrophotometric methods. The FTIR investigation showed that extracts modify the erythrocyte membrane and protect it against free radicals induced by UV radiation. The results show that the extracts do not induce hemolysis and even protect erythrocytes against the harmful action of UVC radiation, while slightly strengthening the membrane and inducing echinocytes. The compounds contained in the extracts do not penetrate into the hydrophobic region, but bind to the membrane surface inducing small changes in the packing arrangement of the polar head groups of membrane lipids. The extracts have a high antioxidant activity. Their presence on the surface of the erythrocyte membrane entails protection against free radicals.


Anthocyanin-rich black currant extract suppresses the growth of human hepatocellular carcinoma cells.


Dietary antioxidants, such as anthocyanins, are helpful in the prevention and control of various diseases by counteracting the imbalance of oxidative and antioxidative factors in the living systems. Black currant (Ribes nigrum L., Grossulariaceae) is known to contain high amounts of anthocyanins (250 mg/100 g fresh fruit). Black currant fruits have been used in Asian and European traditional medicine for the treatment of a variety of diseases. Black currant extract has recently been found to be the second most effective amongst nine different berry extracts studied for their free radical scavenging activity. Constituents present in black currant juice have been found to exert a number of health-promoting effects, including immunomodulatory, antimicrobial and antiinflammatory actions, inhibition of low-density lipoprotein, and reduction of cardiovascular diseases. Although antioxidant and antiinflammatory effects of black currant juice could be of value in preventing and treating oxidative stress- and inflammation-driven cancers, no experimental evidence is available to now. The objective of the present study was to evaluate the potential antiproliferative effects of black currant fruit skin extract against HepG2 human liver cancer cells. The aqueous extract yielded an anthocyanin-rich fraction with cyanidin-3-O-rutinoside as one of the major anthocyanins. This fraction exhibited a potent cytotoxic effect on HepG2 cells and this effect was more pronounced than that of delphinidin and cyanidin, two major aglycones of anthocyanins present in black currant. Our results indicate, for the first time, that black currant skin containing an anthocyanin-rich fraction inhibits the proliferation of liver cancer cells, possibly due to additive as well as synergistic effects. This product could be useful in the prevention and treatment of human hepatocellular carcinoma.


Black currant anthocyanins abrogate oxidative stress through Nrf2-mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma.


Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost > 1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off potential cancer risks and mortality. A major predisposing condition, pertinent to the development and progression of HCC is oxidative stress. We previously reported a striking chemopreventive effect of anthocyanin-rich black currant skin extract (BCSE) against diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats. The current study aims to elucidate the underlying antioxidant mechanisms of black currant anthocyanins implicated in the previously observed chemopreventive effects against experimental hepatocarcinogenesis. Dietary BCSE (100 and 500 mg/kg) administered four weeks before and 18 weeks after DENA challenge decreased abnormal lipid peroxidation, protein oxidation, and expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in a dose-responsive fashion. Mechanistic studies revealed that BCSE upregulated the gene expression of a number of hepatic antioxidant and carcinogen detoxifying enzymes, such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes, in DENA-initiated animals. Protein and mRNA expressions of nuclear factor E2-related factor 2 (Nrf2) were substantially elevated with BCSE treatment, providing a direct evidence of a coordinated activation of the Nrf2-regulated antioxidant pathway, which led to the upregulation of a variety of housekeeping genes. The results of our study provide substantial evidence that black currant bioactive anthocyanins exert chemopreventive actions against DENA-inflicted hepatocarcinogenesis by attenuating oxidative stress through activation of Nrf2 signaling pathway.


Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response.

From: http://www.ncbi.nlm.nih.gov/pubmed/22213170


Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti-inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis. Dietary BCSE (100 or 500 mg/kg) treatment for 22 wk afforded a striking inhibition of DENA-induced hepatic gamma-glutamyl transpeptidase-positive preneoplastic foci in a dose-responsive fashion. There was a significant increase in hepatic expression of heat shock proteins (HSP70 and HSP90), cyclooxygenase-2, and nuclear factor-κB (NF-κB) in DENA-exposed rat livers. Dietary BCSE dose-dependently abrogated all these elevated inflammatory markers. The possible cardiotoxicity of BCSE was assessed by monitoring cardiac functions using transthoracic echocardiography. BCSE-mediated anti-inflammatory effects during rat liver carcinogenesis have been achieved without any cardiotoxicity. Our results provide convincing evidence, for the very first time, that suppression of the inflammatory cascade through modulation of the NF-κB signaling pathway could be implicated, at least in part, in the chemopreventive effects of black currant bioactive phytoconstituents against experimental hepatocarcinogenesis. These results coupled with an excellent safety profile of BCSE support the development of black currant phytochemicals for the chemoprevention of inflammation-driven hepatocellular cancer.


Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats.


Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) fruits have a high anthocyanin content. This “superfruit” is known to possess various pharmacological effects including alleviation of chronic oxidative stress and inflammation. In contrast to a large volume of literature on the health benefits of black currant, limited evidence on antitumor effects of black currant exists with virtually no data on the prevention of experimental carcinogenesis. In the current study, we have investigated the chemopreventive effects of an anthocyanin-rich black currant skin extract (BCSE) utilizing our well-characterized model of rat liver carcinogenesis. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary BCSE for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. BCSE dose-dependently decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was confirmed by histopathological examination of liver sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in DENA-induced rat liver tumorigenesis respectively. Mechanistic studies revealed that BCSE-mediated proapototic signal during experimental hepatocarcinogenesis may be propagated via the up-regulation of Bax and down-regulation of Bcl-2 expression at the translational level. These results along with a safety profile of BCSE encourage the development of black currant bioactive constituents as chemopreventive agents for human liver cancer.


Purified Anthocyanins from Bilberry and Black Currant Attenuate Hepatic Mitochondrial Dysfunction and Steatohepatitis in Mice with Methionine and Choline Deficiency


Abstract Image

The berries of bilberry and black currant are a rich source of anthocyanins, which are thought to have favorable effects on nonalcoholic steatohepatitis (NASH). This study was designed to examine whether purified anthocyanins from bilberry and black currant are able to limit the disorders related to NASH induced by a methionine-choline-deficient (MCD) diet in mice. The results showed that treatment with anthocyanins not only alleviated inflammation, oxidative stress, steatosis, and even fibrosis but also improved depletion of mitochondrial content and damage of mitochondrial biogenesis and electron transfer chain developed concomitantly in the liver of mice fed the MCD diet. Furthermore, anthocyanins treatment promoted activation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α). These data provide evidence that anthocyanins possess significant protective effects against NASH and mitochondrial defects in response to a MCD diet, with a mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.


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



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



Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberry

Ultimate Protector contains resveratrol, 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 will explore the ingredient resveratrol, which is added as a separate ingredient in addition to being a component in VitaBerry Plus® from Futureceuticals.

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants in response to injury or when the plant is under attack by pathogens such as bacteria and fungi. Natural sources of resveratrol include giant knotweed (Polygonum cuspidatum) and the skin of grapes, blueberries, raspberries, and mulberries. Resveratrol has two isomers: cis and trans, with the latter being the most abundant.  Piceid, also known as polydatin, is a glucoside form of resveratrol found in Japanese knotweed. HPDI includes the very pure 99% resveratrol form from giant knotweed in Ultimate Protector. This material contains greater than 96% of the trans form.

giant knotweed resveratrol

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



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.


Resveratrol provides anti-oxidant protection, boosts cellular energy, and balances the immune system. It has been proven in studies to activate the SIRT1 longevity gene and enhance cellular productivity. Several research studies have shown that trans-resveratrol significantly modulates biomarkers of bone metabolism, inhibits pro-inflammatory enzymes such as COX-1 and COX-2, and exhibits chemopreventive properties, cardioprotective effects, neuroprotective properties, and caloric restrictive behavior. Trans-resveratrol has shown the ability to increase the number of mitochondria thereby increasing total daily energy. Studies have shown that trans-resveratrol promotes an increase in mitochondrial function, that translates into an increase in energy availability, improved aerobic capacity, and enhanced sensorimotor function. Resveratrol has been shown to be a powerful Nrf2 activator that can support the body’s endogenous production of protective enzymes.

Scientific Studies on the Antioxidant Effects of Resveratrol

Databases of scientific studies (like the National Institutes of Health (NIH) PubMed database) contain thousands of up-to-date studies and abstracts about resveratrol

Below, we provide a few relevant scientific studies on the antioxidant effects and potential health benefits of resveratrol.

Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2.


Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. Resveratrol was also shown to confer vasoprotection in animal models of type 2 diabetes and aging. However, the mechanisms by which resveratrol exerts its antioxidative vasculoprotective effects are not completely understood. Using a nuclear factor-E(2)-related factor-2 (Nrf2)/antioxidant response element-driven luciferase reporter gene assay, we found that in cultured coronary arterial endothelial cells, resveratrol, in a dose-dependent manner, significantly increases transcriptional activity of Nrf2. Accordingly, resveratrol significantly upregulates the expression of the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1, gamma-glutamylcysteine synthetase, and heme oxygenase-1. Resveratrol treatment also significantly attenuated high glucose (30 mM)-induced mitochondrial and cellular oxidative stress (assessed by flow cytometry using MitoSox and dihydroethidine staining). The aforementioned effects of resveratrol were significantly attenuated by the small interfering RNA downregulation of Nrf2 or the overexpression of Kelch-like erythroid cell-derived protein 1, which inactivates Nrf2. To test the effects of resveratrol in vivo, we used mice fed a high-fat diet (HFD), which exhibit increased vascular oxidative stress associated with an impaired endothelial function. In HFD-fed Nrf2(+/+) mice, resveratrol treatment attenuates oxidative stress (assessed by the Amplex red assay), improves acetylcholine-induced vasodilation, and inhibits apoptosis (assessed by measuring caspase-3 activity and DNA fragmentation) in branches of the femoral artery. In contrast, the aforementioned endothelial protective effects of resveratrol were diminished in HFD-fed Nrf2(-/-) mice. Taken together, our results indicate that resveratrol both in vitro and in vivo confers endothelial protective effects which are mediated by the activation of Nrf2.


Mitochondrial Protection by Resveratrol

From: http://www.medscape.com/viewarticle/745451


Mitochondrial dysfunction and oxidative stress are thought to play important roles in mammalian aging. Resveratrol is a plant-derived polyphenol that exerts diverse antiaging activities, mimicking some of the molecular and functional effects of dietary restriction. This review focuses on the molecular mechanisms underlying the mitochondrial protective effects of resveratrol, which could be exploited for the prevention or amelioration of age-related diseases in the elderly.


Age-specific mortality rates from heart disease, stroke, complications of diabetes, Alzheimer disease, and cancer increase exponentially with age, which imposes a huge financial burden on the health care systems in the Western world. There is an urgent need for effective therapeutic strategies that have the potential to promote health in the elderly, simultaneously preventing or delaying the development of various diseases of aging. During the past decade, dietary supplementation with resveratrol (3,5,4′-trihydroxystilbene) has emerged as a promising approach to counteract age-related diseases. Resveratrol is a naturally occurring polyphenol found in more than 70 species of plants, including grapes (Vitis vinifera), cranberries (Vaccinium macrocarpon), and peanuts (Arachis hypogaea), which was shown to confer diverse physiological effects in laboratory animals including cancer protection, microvascular protection, neuroprotection, cardioprotection, and antidiabetic effects. In this review, we consider the evidence in support of the hypothesis that mitochondrial protective effects of resveratrol underlie its antiaging action that can prevent/delay the development of age-related diseases in the cardiovascular system and other organs. The use of resveratrol as a dietary supplement to promote mitochondrial health in the elderly and diabetic patients is discussed.


Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells

From: http://ajplung.physiology.org/content/294/3/L478 


Nuclear erythroid-related factor 2 (Nrf2), a redox-sensitive transcription factor, is involved in transcriptional regulation of many antioxidant genes, including glutamate-cysteine ligase (GCL). Cigarette smoke (CS) is known to cause oxidative stress and deplete glutathione (GSH) levels in alveolar epithelial cells. We hypothesized that resveratrol, a polyphenolic phytoalexin, has antioxidant signaling properties by inducing GSH biosynthesis via the activation of Nrf2 and protects lung epithelial cells against CS-mediated oxidative stress. Treatment of human primary small airway epithelial and human alveolar epithelial (A549) cells with CS extract (CSE) dose dependently decreased GSH levels and GCL activity, effects that were associated with enhanced production of reactive oxygen species. Resveratrol restored CSE-depleted GSH levels by upregulation of GCL via activation of Nrf2 and also quenched CSE-induced release of reactive oxygen species. Interestingly, CSE failed to induce nuclear translocation of Nrf2 in A549 and small airway epithelial cells. On the contrary, Nrf2 was localized in the cytosol of alveolar and airway epithelial cells due to CSE-mediated posttranslational modifications such as aldehyde/carbonyl adduct formation and nitration. On the other hand, resveratrol attenuated CSE-mediated Nrf2 modifications, thereby inducing its nuclear translocation associated with GCL gene transcription, as demonstrated by GCL-promoter reporter and Nrf2 small interfering RNA approaches. Thus resveratrol attenuates CSE-mediated GSH depletion by inducing GSH synthesis and protects epithelial cells by reversing CSE-induced posttranslational modifications of Nrf2. These data may have implications in dietary modulation of antioxidants in treatment of chronic obstructive pulmonary disease.


Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells

From: http://www.sciencedirect.com/science/article/pii/S2213231713000645


Neurons rely on the release and subsequent cleavage of GSH to cysteinylglycine (CysGly) by astrocytes in order to maintain optimal intracellular GSH levels. In neurodegenerative diseases characterised by oxidative stress, neurons need an optimal GSH supply to defend themselves against free radicals released from activated microglia and astroglia. The rate of GSH synthesis is controlled largely by the activity of γ-glutamyl cysteine ligase. Expression of γ-glutamyl cysteine ligase and of the Xc- system, which facilitates cystine uptake, is regulated by the redox-sensitive transcription factor, nuclear factor erythroid-2-related factor 2 (Nrf2). Compounds that can activate the Nrf2-ARE pathway, referred to as ‘Nrf2 activators’ are receiving growing attention due to their potential as GSH-boosting drugs.

This study compares four known Nrf2 activators, R-α-Lipoic acid (LA), tert-butylhydroquinone (TBHQ), sulforaphane (SFN) and Polygonum cuspidatum extract containing 50% resveratrol (PC-Res) for their effects on astroglial release of GSH and CysGly. GSH levels increased dose-dependently in response to all four drugs. Sulforaphane produced the most potent effect, increasing GSH by up to 2.4-fold. PC-Res increased GSH up to 1.6-fold, followed by TBHQ (1.5-fold) and LA (1.4-fold). GSH is processed by the ectoenzyme, γ-glutamyl transpeptidase, to form CysGly. Once again, SFN produced the most potent effect, increasing CysGly by up to 1.7-fold, compared to control cells. TBHQ and PC-Res both induced fold increases of 1.3, followed by LA with a fold increase of 1.2. The results from the present study showed that sulforaphane, followed by lipoic acid, resveratrol and Polygonum multiflorum were all identified as potent “GSH and Cys-Gly boosters”.

Resveratrol Upregulates Nrf2 Expression To Attenuate Methylglyoxal-Induced Insulin Resistance in Hep G2 Cells

From: http://pubs.acs.org/doi/abs/10.1021/jf302831d


Oxidative stress can result in insulin resistance, a primary cause of type-2 diabetes. Methylglyoxal (MG), a highly reactive dicarbonyl metabolite generated during glucose metabolism, has also been confirmed to cause pancreatic injury and induce inflammation, thereby resulting in insulin resistance. Recently, resveratrol has been reported to exert antioxidant properties, protecting cells from the generation of reactive oxygen species (ROS). The aim of this study was to evaluate resveratrol activation of nuclear factor erythroid 2-related factor 2 (Nrf2) to attenuate MG-induced insulin resistance in Hep G2 cells. Therefore, the molecular signaling events affecting resveratrol-mediated heme oxygenase-1 (HO-1) and glyoxalase expression levels were further investigated in this study. Our findings indicated that resveratrol activated the extracellular signal-regulated kinase (ERK) pathway but not the p38 or c-Jun N-terminal kinase (JNK) pathways, subsequently leading to Nrf2 nuclear translocation and elevation of HO-1 and glyoxalase expression levels. Moreover, resveratrol significantly elevated glucose uptake and protected against MG-induced insulin resistance in Hep G2 cells. In contrast, depletion of Nrf2 by small interfering RNA (si-RNA) resulted in the abrogation of HO-1 and glyoxalase expression in the MG-treated resveratrol group in Hep G2 cells. Administration of an appropriate chemopreventive agent, such as resveratrol, may be an alternative strategy for protecting against MG-induced diabetes.


Resveratrol restores sirtuin 1 (SIRT1) activity and pyruvate dehydrogenase kinase 1 (PDK1) expression after hemorrhagic injury in a rat model.

From: http://www.ncbi.nlm.nih.gov/pubmed/24395567


Severe hemorrhage leads to decreased blood flow to tissues resulting in decreased oxygen and nutrient availability affecting mitochondrial function. A mitoscriptome profiling study demonstrated alteration in several genes related to mitochondria, consistent with the mitochondrial functional decline observed after trauma hemorrhage (T-H). Our experiments led to the identification of sirtuin 1 (SIRT1) as a potential target in T-H. Administration of resveratrol (a naturally occurring polyphenol and activator of SIRT1) after T-H improved left ventricular function and tissue ATP levels. Our hypothesis was that mitochondrial function after T-H depends on SIRT1 activity. In this study, we evaluated the activity of SIRT1, a mitochondrial functional modulator, and the mitochondrial-glycolytic balance after T-H. We determined the changes in protein levels of pyruvate dehydrogenase kinase (PDK)-1 and nuclear c-Myc, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and NF-E2-related factor (NRF)2 after T-H and after treatment with resveratrol or a combination of sirtinol (a SIRT1 inhibitor) and resveratrol. We have also tested the activity of mitochondrial complex 1. SIRT1 enzyme activity was significantly decreased after T-H, whereas resveratrol treatment restored the activity. We found elevated PDK1 and c-Myc levels and decreased PGC-1α, NRF2 and mitochondrial complex I activity after T-H. The reduced SIRT1 activity after T-H may be related to declining mitochondrial function, since resveratrol was able to reinstate SIRT1 activity and mitochondrial function. The elevated level of PDK1 (an inhibitor of pyruvate dehydrogenase complex) after T-H indicates a possible shift in cellular energetics from mitochondria to glycolysis. In conclusion, SIRT1 modulation alters left ventricular function after T-H through regulation of cellular energetics.


Resveratrol suppresses PAI-1 gene expression in a human in vitro model of inflamed adipose tissue.

From: http://www.ncbi.nlm.nih.gov/pubmed/23819014


Increased plasminogen activator inhibitor-1 (PAI-1) levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NF κ B pathway. Together, resveratrol can act as NF κ B inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.


Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease.

From: http://www.ncbi.nlm.nih.gov/pubmed/24799987


The prevalence of obesity and related conditions like non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and therapeutic options are limited. Alternative treatment options are therefore intensively sought after. An interesting candidate is the natural polyphenol resveratrol (RSV) that activates adenosinmonophosphate-activated protein kinase (AMPK) and silent information regulation-2 homolog 1 (SIRT1). In addition, RSV has known anti-oxidant and anti-inflammatory effects. Here, we review the current evidence for RSV-mediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis (NASH) pathogenesis with respect to free fatty acid (FFA) flux from adipose tissue, hepatic de novo lipogenesis, inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits. We review the in vivo evidence from animal studies and clinical trials. The abundance of animal studies reports a decrease in hepatic triglyceride accumulation, liver weight and a general improvement in histological fatty liver changes, along with a reduction in circulating insulin, glucose and lipid levels. Some studies document AMPK or SIRT1 activation, and modulation of relevant markers of hepatic lipogenesis, inflammation and oxidation status. However, AMPK/SIRT1-independent actions are also likely. Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes. Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.


Modulatory role of resveratrol on cytotoxic activity of cisplatin, sensitization and modification of cisplatin resistance in colorectal cancer cells.

From: http://www.ncbi.nlm.nih.gov/pubmed/25815689


Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Cisplatin (CIS) is one of the most active cytotoxic agents in current use and it has proven efficacy against various human malignancies. However, its clinical usefulness has been restricted by detrimental side effects, including nephrotoxicity and myelosuppression. The aim of the present study was to attempt to decrease the required dose of CIS, in order to minimize its side effects, and increase its capability to arrest, delay or reverse carcinogenesis. In addition, the present study aimed to ameliorate CIS‑resistance in CRC cells, using the natural compound resveratrol (RSVL). RSVL (3,4′, 5‑trihydroxy‑trans‑stilbene) is a naturally occurring polyphenol present in the roots of white hellebore (Veratrum grandiflorum O. Loes) and extracted from >70 other plant species. RSVL can exert antioxidant and anti‑inflammatory activities, and it has been shown to be active in the regulation of numerous cellular events associated with carcinogenesis. The present study evaluated the effects of RSVL on sensitization of both parent and CIS‑resistant HCT‑116 CRC cells to the action of cisplatin. The CIS was administered at a dose of 5 and 20 µg/ml, and CIS cytotoxicity, apoptosis, cell cycle and cisplatin cellular uptake were examined in the presence and absence of RSVL (15 µg/ml). RSVL treatment showed anti‑proliferative effects and enhanced the cytotoxic effects of cis against the growth of both parent and CIS‑resistant HCT‑116 CRC cells, with a half maximal inhibitory concentration of 4.20 µg/ml and 4.72 µg/ml respectively. RSVL also induced a significant increase in the early apoptosis fraction and enhanced the subsequent apoptotic effects of CIS. The cellular uptake of CIS was significantly increased in the presence of RSVL, as compared with CIS treatment alone, and RSVL treatment sensitized the CIS‑resistant HCT‑116 cells. In conclusion, RSVL treatment increased the cytotoxic activity of CIS against the growth of both parent and CIS‑resistant HCT-116 CRC cells.


Resveratrol treatment rescues hyperleptinemia and improves hypothalamic leptin signaling programmed by maternal high-fat diet in rats.

From: http://www.ncbi.nlm.nih.gov/pubmed/25801629


PURPOSE: Perinatal high-fat diet is associated with obesity and metabolic diseases in adult offspring. Resveratrol has been shown to exert antioxidant and anti-obesity actions. However, the effects of resveratrol on leptinemia and leptin signaling are still unknown as well as whether resveratrol treatment can improve metabolic outcomes programmed by maternal high-fat diet. We hypothesize that resveratrol treatment in male rats programmed by high-fat diet would decrease body weight and food intake, and leptinemia with changes in central leptin signaling.

METHODS: Female Wistar rats were divided into two groups: control group (C), which received a standard diet containing 9 % of the calories as fat, and high-fat group (HF), which received a diet containing 28 % of the calories as fat. Dams were fed in C or HF diet during 8 weeks before mating and throughout gestation and lactation. C and HF male offspring received standard diet throughout life. From 150 until 180 days of age, offspring received resveratrol (30 mg/Kg body weight/day) or vehicle (carboxymethylcellulose).

RESULTS: HF offspring had increased body weight, hyperphagia and increased subcutaneous and visceral fat mass compared to controls, and resveratrol treatment decreased adiposity. HF offspring had increased leptinemia as well as increased SOCS3 in the arcuate nucleus of the hypothalamus, which suggest central leptin resistance. Resveratrol treatment rescued leptinemia and increased p-STAT3 content in the hypothalamus with no changes in SOCS3, suggesting improvement in leptin signaling.

CONCLUSIONS: Collectively, our data suggest that resveratrol could reverse hyperleptinemia and improve central leptin action in adult offspring from HF mothers attenuating obesity.



Resveratrol is an important polyphenol, antioxidant, and Nrf2 activator that helps to make Ultimate Protector such an outstanding nutritional supplement.