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ULTIMATE PROTECTOR DESIGN CONSIDERATIONS

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

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

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

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

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

 

Ultimate Protector+

BACKGROUND

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

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

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

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

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

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

ULTIMATE PROTECTOR GOALS

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

VITAMIN C IN ULTIMATE PROTECTOR

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

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

ORAC5.0 VALUES OF ULTIMATE PROTECTOR

The full spectrum of antioxidants derived from high ORAC fruits, vegetables, and herbs (as well as Vitamin C) provide extremely powerful exogenous sources of protection against oxidative stress. To obtain a quantitative measure of just how powerful these external sources are we elected to conduct ORAC testing.

The fact is that there are a variety of “free radicals” that operate in humans. The most important are the primary radicals hydroxyl, peroxyl, peroxynitrite, singlet oxygen, and superoxide anion. Brunswick Labs has test called ORAC5.0™. This test expands the ORAC platform to measure the antioxidant capacity against each of the five primary reactive oxygen species mentioned above (not just against the peroxyl radical as ORAC does). ORAC5.0™ substantially improves broad-spectrum antioxidant analysis and gives evidence of the diverse antioxidant potential of natural products against radicals.

Brunswick Labs has previously tested Ultimate Protector™ using the ORAC5.0™ tests. The results revealed an incredible overall ORAC5.0 value of 173,000 µmole TE/gram, an exceptionally high value. In addition, the results show that the formula offers excellent protection against all of the five major types of free radicals. Specifically, the results show values of 6,300 (µmole TE/gram) for peroxyl radicals, 5,900 (µmole TE/gram) for hydroxyl radicals, 2,500 (µmole TE/gram) for peroxynitrite, 106,000 (µmole TE/gram) for superoxide anion, and 52,000 (µmole TE/gram) for singlet oxygen.

Currently we are testing Ultimate Protector+ using the ORAC5.0™ (or the new ORAC6.0 test that adds hypochlorite).We will publish the new test results when they available.

 

Ultimate Protector+

Ultimate Protector+ is new and improved!

Nrf2 CONSIDERATIONS REGARDING ULTIMATE PROTECTOR

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

1. SFB® – (Standardized Fruit Blend)

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

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

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

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

a) Cranberry Extract

Ultimate Protector+ Includes Cranberry

Ultimate Protector+ Includes Cranberry Extract

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

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

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

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

b) Pomegranate Extract

Ultimate Protector+ Includes Pomegranate

Ultimate Protector+ Includes Pomegranate Extract

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

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

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

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

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

c) Chokeberry (Aronia)

Ultimate Protector+ Includes Chokeberry

Ultimate Protector+ Includes Chokeberry Extract

HEALTH BENEFITS OF CHOKEBERRY (ARONIA)

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

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

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

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

d) Goji Berry

Ultimate Protector+ Includes Goji Berry

Ultimate Protector+ Includes Goji Berry Extract

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

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

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

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

e) Mangosteen

Ultimate Protector+ Includes Mangosteen

Ultimate Protector+ Includes Mangosteen Extract

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

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

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

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

f) Apple Extract

Ultimate Protector+ Includes Apple

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

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

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

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

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

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

g) Blueberry and Bilberry Extract

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

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

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

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

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

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

Other Ingredients

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

These additional ingredients are detailed below:

1) Curcumin

Ultimate Protector+ Includes Curcumin

Ultimate Protector+ Includes Curcumin

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


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

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

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


3) Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

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

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

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

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

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

Ultimate Protector+ Includes Whole Grape Extract

Ultimate Protector+ Includes Whole Grape Extract

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

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

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

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

Partial List of Phytochemicals in Ultimate Protector+

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

Additional Ingredients

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

COMPOSITION

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

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

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

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

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

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

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

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

ADDITIONAL RESOURCES

New Directions for Preventing Free-Radical Damage

Natural Phytochemical Nrf2 Activators for Chemoprevention

Hank Liers, PhD

HANK LIERS, PHD

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

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ADDITIONAL RESOURCES

  • Ultimate Protector™ Brunswick Labs ORAC5.0™ Test Results
  • Description and Comparison of ORAC Tests for Well Known Plant Ingredients and Ultimate Protector™
  • Ultimate Protector™: First Impressions
  • Questions & Answers about Ultimate Protector

OTHER RESOURCES

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PREVENTING FREE RADICAL DAMAGE WITH ULTIMATE PROTECTOR+

Back in 2012, I learned about Nrf2 activators and was excited about pursuing the development of a supplement that would incorporate the new knowledge we were learning into a effective product for preventing free radical damage. At that time, I published two articles: New Directions for Preventing Free Fadical Damage and Natural Phytochemical Nrf2 Activators for Chemoprevention. I started working on a new Nrf2-activator formula I called Ultimate Protector that incorporated many of the ideas contained in these articles. The product was introduced November 2012.

More recently, in early 2019, I decided to upgrade the product using new information and ingredients. The upgraded product is called Ultimate Protector+. In this article, I provide new details of our design logic and product ingredients. I expect the new formula to be released in July 2019.

Ultimate Protector+

Ultimate Protector+ is new and improved!

PREVENTING FREE RADICAL DAMAGE WITH ULTIMATE PROTECTOR+

Ultimate Protector+™ is a unique cell protection formula that simultaneously meets the needs for high levels of non-GMO Vitamin C, full spectrum antioxidants (high ORAC values), and protective enzyme activators (Nrf2 activators) in a single product. This potent combination of characteristics distinguishes the formula because no other single product available today offers such complete protection. This is the single best formula for preventing free radical damage that is available.

Ultimate Protector+™ provides extremely high levels of natural antioxidants, including high levels of ingredients such as polyphenols, flavonoids, anthocyanidins, oligomeric proanthocyanidins, catechins, curcuminoids, pterostilbene, resveratrol, chlorogenic acid, punicalagins, zeaxanthin and other carotenoids that act powerfully as antioxidants. These antioxidants come from more than 12 plant-based ingredients with demonstrated free-radical quenching capacity. These “exogenous” food-based antioxidants (supplied from outside the body) provide you with immense oxidative defenses that can be used to defend against free-radical assault.

Ultimate Protector+™ contains USP-grade non-GMO Vitamin C , SFB® standardized fruit blend (~50% polyphenols, high-ORAC powder: 9,000 µmole TE/g) from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), Green Tea Extract (90% polyphenols, 50% EGCG), VinCare® Whole Grape Extract (>80% polyphenols, ORAC>19,000 µmole TE/g), Calcium Malate, Magnesium Malate, and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients and is a known Nrf2 activator).

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

NUTRITIONAL CONSIDERATIONS AND APPLICATIONS

Ultimate Protector+™ satisfies three distinct needs:

1) The need for a non-GMO Vitamin C product. That is, a Vitamin C formula that avoids protein from genetically modified sources such as corn, potatoes, or beets.

2) The need for a single, powerful antioxidant formula for preventing free radical damage. That is, a single, easy-to-take antioxidant formula offering a broad range of extremely high-ORAC plant source antioxidants. These antioxidants should protect against the full range of free radicals found in the human body including: superoxide anion (O2·-), peroxyl radicals (ROO·), hydroxyl radicals (HO·), singlet oxygen (1O2), and peroxynitrite (ONOO-).

3) The need for a supplement providing a full spectrum of Nrf2 activators. That is, a supplement providing a wide range of natural Nrf2 transcription factor activators that allow the body to make its own antioxidant enzymes (e.g., superoxide dismutase (SOD), catalase, hemeoxygenase, and glutathione peroxidase). Scientific research has shown that these are found naturally in many fruits, vegetable, and herbs. These ingredients provide a wide range of Nrf2 activators that result in significantly high levels of the endogenously produced antioxidant enzymes.

The ways Ultimate Protector+™ satisfies these three needs are discussed below:

1) NON-GMO VITAMIN C / ASCORBIC ACID

High-quality, USP grade Vitamin C has been obtained historically from corn, potatoes, and/or beets. Unfortunately, many of these sources have to a large extent gone to genetically modified (GMO) variants. However, with highly refined production methods and the use of PCR testing, we have been able to obtain final products that are free from GMOs.

In nature, Vitamin C is found generally in plant sources containing polyphenols. Vitamin C and polyphenols work together to provide a high level of antioxidant protection and they support the function of each other in the process. For example, Vitamin C is needed by the body to produce collagen and certain polyphenols (especially oligomeric proanthocyanidins) (OPCs) crosslink the collagen and make it stronger.

2) EXTREMELY HIGH ORAC SOURCES

Free radicals are reactive species that can have adverse effects on normal physiological functions. Studies associate the five major types of free radicals (i.e., hydroxyl, peroxyl, peroxynitrite, singlet oxygen, and superoxide anion) with health conditions such as cardiovascular disease, hypertension, breakdown of vital proteins, chronic inflammation, Alzheimer’s disease, and certain cancers. Avoiding free radical damage is the goal.

Antioxidants function as a vital line of defense against free radicals by blocking their attack on DNA, vital proteins, lipids, and amino acids. Until now, efforts to identify the effect of antioxidants on all five types of free radicals were constrained by limited testing procedures. However, new technological developments have resulted in a comprehensive testing method called the Total ORAC5.0™ assay. Because of the development of the Total ORAC5.0™ test, it is now possible to target and measure the effects of antioxidants on the five major types of free radicals found in the body.

We are currently in the process of testing Ultimate Protector+™ using this new ORAC5.0™ assay. We are confident that our formula offers protection against these five major types of free-radicals because we combine a wide range of extremely high-ORAC fruit, vegetable, and herbal blends. As soon as the results are available (in July 2019), we will update this article with the findings.

3) NRF2 TRANSCRIPTION FACTOR ACTIVATORS

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 (ROS). 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 an 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 disease 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 phytochemicals is a cellular event that is highly dependent on Nrf2 protein. By activating Nrf2 signaling, phytochemicals can increase cellular detoxification and antioxidant enzymes, thereby enhancing removal of ROS and toxic chemicals and preventing disease. Numerous research studies carried out over the last 15 years have demonstrated the effectiveness of a very wide range of Nrf2 activators extracted from fruits, vegetables, and herbs.

For example, a study with sulforaphane (an isothiocyanate present abundantly in cruciferous vegetables) shows that oral administration of this phytochemical can effectively block benzo[a]pyrene-induced forestomach tumors in mice. This protective effect was abrogated in mice that could not produce Nrf2. This supports the 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. Also, there are other mechanisms that allow Nrf2 to be released from KEAP1. The released Nrf2 then migrates into the cell nucleus and causes an antioxidant enzyme (e.g., superoxide dismutase (SOD)) to be fabricated and released. This endogenously produced enzyme then can protect against ROS, electrophiles, and other toxic agents.

In practical experience, it has been found that a combination of multiple polyphenols works significantly better than single ingredients. 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 was able to increase levels of SOD by 30% and catalase by 56% after 120 days of taking the combination.

In view of the considerations above, we include a wide range of Nrf2 activators in Ultimate Protector+™. These include a large variety of freeze-dried and concentrated fruits, vegetables, and herbs. These include Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, 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)

Ultimate Protector+™ includes the following phytonutrients in its array of freeze-dried and concentrated fruits, vegetables, and herbs: polyphenols, flavonoids, anthocyanins, catechins, proanthocyanins, ellagic acid, xanthines, chlorogenic acid, pterostilbenes, resveratrol, phloridzin, quercetin, zeaxanthin, carotinoids, polysaccharides, quinic acid, and more.

The phytochemical ingredients in Ultimate Protector+™ are discussed below:

1. SFB® – (Standardized Fruit Blend)

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

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

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

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

a) Cranberry Extract

Ultimate Protector+ Includes Cranberry

Ultimate Protector+ Includes Cranberry Extract

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

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

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

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 regarding cancer, aging and neurological diseases, inflammation, diabetes, and bacterial infections.
    • Antioxidant compounds in cranberry extract including OPC’s, anthocyanidin flavonoids, cyanidin, peonidin and quercetin may support cardiovascular health by counteracting against cholesterol plaque formation in the heart and blood vessels. Further, these compounds help the human body lower LDL cholesterol levels and increase HDL-good cholesterol levels in the blood.
    • Scientific studies show that cranberry juice consumption offers protection against gram-negative bacterial infections such as E.coli in the urinary system by inhibiting bacterial-attachment to the bladder and urethra.
    • It is known that cranberries turns urine acidic. This, together with the inhibition of bacterial adhesion helps prevent the formation of alkaline (calcium ammonium phosphate) stones in the urinary tract by working against proteus bacterial-infections.
    • In addition, the berries prevent plaque formation on the tooth enamel by interfering with the ability of the gram-negative bacterium, Streptococcus mutans, to stick to the surface. In this way cranberries helps prevent the development of cavities.
    • The berries are also good source of many vitamins like vitamin C, vitamin A, ß-carotene, lutein, 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.

b) Pomegranate Extract

Ultimate Protector+ Includes Pomegranate

Ultimate Protector+ Includes Pomegranate

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

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

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

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

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

c) Chokeberry (Aronia)

Ultimate Protector+ Includes Chokeberry

Ultimate Protector+ Includes Chokeberry

HEALTH BENEFITS OF CHOKEBERRY (ARONIA)

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

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

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

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

d) Goji Berry

Ultimate Protector+ Includes Goji Berry

Ultimate Protector+ Includes Goji Berry

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

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

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

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

e) Mangosteen

Ultimate Protector+ Includes Mangosteen

Ultimate Protector+ Includes Mangosteen

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

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

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

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

f) Apple Extract

Ultimate Protector+ Includes Apple

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

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

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

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

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

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

g) Blueberry and Bilberry Extract

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

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

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

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

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

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

2) Curcumin

Ultimate Protector+ Includes Curcumin

Ultimate Protector+ Includes Curcumin

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


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

giant knotweed resveratrol

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

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


4) Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

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

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

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

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

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

Ultimate Protector+ Includes Whole Grape Extract

Ultimate Protector+ Includes Whole Grape Extract

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

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

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

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

7) Bioperine®:

Bioperine® is a black pepper extract that has been shown to enhance the absorption of nutrients by 30–60 percent and makes all of the nutrients in this product more effective.

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

COMPOSITION: six veggie capsules provides the following percentages of the Daily Value:

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

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

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

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

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

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

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

ADDITIONAL RESOURCES

New Directions for Preventing Free-Radical Damage

Natural Phytochemical Nrf2 Activators for Chemoprevention

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ULTIMATE PROTECTOR+ INGREDIENTS – BLUEBERRY AND BILBERRY

Dr. Hank Liers, PhDUltimate Protector+ contains blueberry and bilberry extracts, as well as components from 12 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article, I will explore the ingredients blueberry and bilberry, which are components of SFB® – Standardized Fruit Blend from Ethical Naturals, Inc.

Ultimate Protector+ Includes Blueberry and Bilberry

Ultimate Protector+ Includes Bilberry and Blueberry

SFB® – Standardized Fruit Blend

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

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

HEALTH BENEFITS OF
BILBERRY AND BLUEBERRY

Bilberry is any of several Eurasian  species of low-growing shrubs in the genus Vaccinium, bearing edible, nearly black berries. The species most often referred to is Vaccinium myrtillus L., but there are several other closely related species. Bilberries are distinct from blueberries but closely related. Whereas the bilberry is native to Europe, the blueberry is native to North America.

The bilberry fruit is smaller than that of the blueberry, but with a fuller taste. Bilberries are darker in color, and usually appear near black with a slight shade of purple. While blueberry fruit pulp is light green in color, bilberry is red or purple, heavily staining the fingers, lips, and tongue of consumers eating the raw fruit. The color comes from diverse anthocyanins.

So-called wild (lowbush) blueberries, smaller than cultivated highbush ones, are prized for their intense color. “Wild” has been adopted as a marketing term for harvests of managed native stands of lowbush blueberries. The bushes are not planted or genetically manipulated, but they are pruned or burned every two years, and pests are “managed.” The content of polyphenols and anthocyanins in lowbush (wild) blueberries (V. angustifolium) exceeds values found in highbush cultivars.

wild bilberry and wild blueberry

Wild bilberry and wild blueberry provide Nrf2 activators.

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

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

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

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

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

Scientific Studies on the Antioxidant Effects of Bilberry and Blueberry

Databases of scientific studies (like the National Institutes of Health (NIH) PubMed database) contain thousands of up-to-date studies and abstracts about various Vaccinium species, including wild bilberry and wild blueberry (V. myrtillis and V. angustfolium, respectively).

We provide a few relevant scientific studies on the antioxidant effects of wild bilberry and wild blueberry.

In vitro anticancer activity of fruit extracts from Vaccinium species.

From: http://www.ncbi.nlm.nih.gov/pubmed/8693031

Abstract

Fruit extracts of four Vaccinium species (lowbush blueberry, bilberry, cranberry, and lingonberry) were screened for anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA). The crude extracts, anthocyanin and proanthocyanidin fractions were not highly active in QR induction whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of lowbush blueberry, cranberry, lingonberry, and bilberry were 4.2, 3.7, 1.3, and 1.0 microgram tannic acid equivalents (TAE), respectively, Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07 microgram TAE). In contrast to their effects on QR, crude extracts of lowbush blueberry, cranberry, and lingonberry were active inhibitors of ODC activity. The concentrations of these crude extracts needed to inhibit ODC activity by 50% (designated IC50) were 8.0, 7.0, and 9.0 micrograms TAE, respectively. The greatest activity in these extracts appeared to be contained in the polymeric proanthocyanidin fractions of the lowbush blueberry, cranberry, and lingonberry fruits (IC50 = 3.0, 6.0, and 5.0 micrograms TAE, respectively). The anthocyanidin and ethyl acetate extracts of the four Vaccinium species were either inactive or relatively weak inhibitors of ODC activity. Thus, components of the hexane/chloroform fraction of bilberry and of the proanthocyanidin fraction of lowbush blueberry, cranberry, and lingonberry exhibit potential anticarcinogenic activity as evaluated by in vitro screening tests.

Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells.

From: http://www.ncbi.nlm.nih.gov/pubmed/17460300

Abstract

PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre- or posttranslational levels of oxidative stress defense enzymes heme-oxygenase (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal pigment epithelial (RPE) cells.

METHODS: Confluent ARPE-19 cells were preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25% enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal, cells were oxidatively challenged with H(2)O(2). The concentration of intracellular glutathione was measured by HPLC and free radical production determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and mRNA levels were determined by Western blot and RT-PCR, respectively.

RESULTS: Preincubation with bilberry extract ameliorated the intracellular increase of H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8- and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions contributed similarly to mRNA upregulation.

CONCLUSIONS: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and GST-pi in RPE, suggesting that they stimulate signal transduction pathways influencing genes controlled by the antioxidant response element.

Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism.

From: http://www.ncbi.nlm.nih.gov/pubmed/24565673

Abstract

The objectives of this study were to compare the anti-inflammatory effects of anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and to determine the relationship between their antioxidant capacity and anti-inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 μg/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1β (IL-1β) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 μg/ml or higher. Tumor necrosis factor α (TNFα) mRNA levels and secretion were also significantly decreased in LPS-treated macrophages. The levels of the repression were comparable for all berry anthocyanins. LPS-induced nuclear factor κB (NF-κB) p65 translocation to the nucleus was markedly attenuated by all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA significantly decreased cellular reactive oxygen species (ROS) levels with a concomitant decrease in IL-1β mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1β mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-κB independent of the NRF2-mediated pathways.

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

From: http://pubs.acs.org/doi/abs/10.1021/jf504926n

Abstract

The berries of bilberry and black currant are rich source of anthocyanins, which are thought to have favorable effects on non-alcoholic 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 the 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 mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.

Effect of blueberry on hepatic and immunological functions in mice.

From: http://www.ncbi.nlm.nih.gov/pubmed/20382588

Abstract

Background: Conventional drugs used in the treatment and prevention of liver diseases often have side effects, therefore research into natural substances are of significance. This study examined the effects of blueberry on liver protection and cellular immune functions.

METHODS: To determine the effects of blueberry on liver protective function, male mice were orally administered blueberry (0.6 g/10 g) or normal saline for 21 days. Hepatic RNA was extracted by Trizol reagent, and the expression of Nrf2, HO-1, and Nqo1 was determined by real-time RT-PCR. Superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenate were determined, and liver index was measured. To assess the effects of blueberry on cellular immune function, male mice received blueberry (0.4, 0.6, or 0.8 g/10 g) for 35 days, and the percentages of CD3+, CD4+, and CD8+ T lymphocyte subgroups in peripheral blood were detected by flow cytometry, the index of the thymus and spleen was measured, and lymphocyte proliferation in the spleen was determined by MTT assay.

RESULTS: Blueberry treatment significantly increased the expression of Nrf2, HO-1, and Nqo1, the important antioxidant components in the liver. Hepatic SOD in the blueberry group was higher and MDA was lower than that in the control group (P<0.05). Blueberry also increased the index of the spleen and enhanced the proliferation of lymphocytes of the spleen (P<0.05). The percentages of the CD3+ and CD4+ T lymphocyte subsets and the CD4+/CD8+ ratio were also increased by blueberry (P<0.05).

CONCLUSIONS: Blueberry induces expression of Nrf2, HO-1, and Nqo1, which can protect hepatocytes from oxidative stress. In addition, blueberry can modulate T-cell function in mice.

Anthocyanins: Janus Nutraceuticals Displaying Chemotherapeutic and Neuroprotective Properties

From: http://link.springer.com/chapter/10.1007/978-94-007-4575-9_21

Abstract

Anthocyanins are natural polyphenolic compounds widely distributed as pigments in many fruits and vegetables. In addition to displaying antioxidant properties, these nutraceuticals exhibit anti-inflammatory, anti-proliferative, and pro-apoptotic activities suggesting their potential as novel chemotherapeutic agents. Through cell cycle down-regulation, and context-specific pro-oxidant activity, anthocyanins induce cytotoxicity in cancer cells in vitro and in vivo. Specifically, via regulation of the Bcl-2 protein family and induction of caspase-dependent or caspase-independent apoptotic pathways, anthocyanins inhibit the growth of cancers by inducing cell death. Moreover, by modulating the activities of specific kinases and proteases, including (but not limited to) cyclin-dependent kinases, mitogen-activated protein kinases, matrix metalloproteases, and urokinase-type plasminogen activators, anthocyanins induce apoptosis, inhibit motility, and suppress invasion of cancer cells. In marked contrast to their effects in cancer cells, we have found that anthocyanins display significant anti-apoptotic activity in neurons. Antioxidant properties of these nutraceuticals, particularly at the level of the mitochondria, appear to underlie their neuroprotective effects. The opposing effects of anthocyanins on cancer cells and neurons suggest that these nutraceuticals are promising candidates for development as either chemotherapeutic agents or novel neuroprotective compounds for the treatment of cancers or neurodegenerative diseases, respectively.

Recent Research on Polyphenolics in Vision and Eye Health

From: http://pubs.acs.org/doi/abs/10.1021/jf903038r#end-1

Abstract

A long-standing yet controversial bioactivity attributed to polyphenols is their beneficial effects in vision. Although anecdotal case reports and in vitro research studies provide evidence for the visual benefits of anthocyanin-rich berries, rigorous clinical evidence of their benefits is still lacking. Recent in vitro studies demonstrate that anthocyanins and other flavonoids interact directly with rhodopsin and modulate visual pigment function. Additional in vitro studies show flavonoids protect a variety of retinal cell types from oxidative stress-induced cell death, a neuroprotective property of significance because the retina has the highest metabolic rate of any tissue and is particularly vulnerable to oxidative injury. However, more information is needed on the bioactivity of in vivo conjugates and the accumulation of flavonoids in ocular tissues. The direct and indirect costs of age-related vision impairment provide a powerful incentive to explore the potential for improved vision health through the intake of dietary polyphenolics.

Bilberry Extracts Induce Gene Expression Through the Electrophile Response Element

From: http://www.tandfonline.com/doi/abs/10.1207/s15327914nc5401_11#.VLK6LVqBO24

Abstract

A number of genes important for detoxification and antioxidant defense induced by mild stress generated by, for example, physical activity/exercise, caloric restriction, or alcohol may provide health benefits by causing the organism to mount such a defense response. More recently, induction of these defenses has also been attributed to phytochemicals or secondary metabolites from dietary plants. Many polyphenols, which constitute a large fraction of these phytochemicals, increase cellular levels of antioxidants, such as glutathione and other components of the detoxification systems, via the transactivation of genes containing electrophile response elements (EpREs) within their promoters. One such gene, γ-glutamylcysteine synthetase, has previously been shown to be positively regulated by quercetin, a flavonoid found in high concentrations in onions, apples, and bilberries through EpRE transactivation. As a further step, we have investigated whether bilberries and quercetin have the ability to induce transcription of Fos-related antigen 1 (Fra-1), which contains two EpREs in its promoter. Fra-1 is a member of the activator protein 1 (AP-1) family of transcription factors and, due to the lack of transactivation domain Fra-1, can suppress activation of AP-1. We present results demonstrating that extracts from bilberries, and the flavonoid quercetin, abundant in bilberries, induce the fra-1 promoter and the cellular content of Fra-1 mRNA. We further provide evidence that this induction is mediated through EpREs.

Bilberry (Vaccinium myrtillus)

From: http://www.sigmaaldrich.com/life-science/nutrition-research/learning-center/plant-profiler/vaccinium-myrtillus.html

Synonyms / Common Names / Related Terms
Airelle, anthocyanins, Bickbeere (German), bilberry leaf, black whortle, Blaubeere (Dutch), blaubessen, bleaberry, blueberry, blueberry leaf, bogberry, bog bilberry, burren myrtle, cranberry, dwarf bilberry, dyeberry, Ericaceae (family), European blueberry, Heidelbeere (Dutch), Heidelbeereblatter, heidelberry, huckleberry, hurtleberry, lingonberry, lowbush blueberry, Mirtillo nero (Italian), Myrtilli folium, Myrtilli fructus, Myrtilus niger Gilib., Optiberry, resveratrol, sambubiosides, trackleberry, Vaccinium angulosum Dulac, Vaccinium montanum Salibs., Vaccinium myrtillus anthocyanoside extract, VMA extract, VME, whortleberry, wineberry
Mechanism of Action

Pharmacology:

  • Constituents: Bilberry contains several compounds that have demonstrated biological activity. The main chemicals contained in bilberry extract have been shown to be: anthocyanins30,31, flavonoids, hydroquinone, oleanolic acid, neomyrtillin, sodium, tannins, and ursolic acid17,20,32,33,34. Bilberry also contains resveratrol.28,29 The anthocyanosides, tannins, and flavonoids have been of particular scientific interest. Flavonoids have been shown in vitro to possess a number of biological properties, including inhibition of prostacyclin synthesis, reduction of capillary permeability and fragility, free radical scavenging, inhibition of a wide range of enzymes, impairment of coagulation and platelet aggregation, and anticarcinogenicity.33,5
  • Mechanism of action: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes heme-oxygenase-1 and glutathione S-transferase-pin cultured human retinal pigment epithelial cells, suggesting that they stimulate signal transduction pathways, influencing genes controlled by the antioxidant response element.30
  • Antibacterial effects: In an in vitro study using Staphylococcus aureus, Staphylococcus aureus Oxford, Enterococcus faecalisBacillus subtilis, and Escherichia coli, an aqueous extract of bilberry leaves had a MIC of 12.7-17.8mg/mL and an aqueous extract of bilberry fruit had a MIC of 15.4-30.7mg/mL.24
  • Anticarcinogenic effects: In an in vitro study, anthocyanin-rich extracts from bilberry (Vaccinium myrtillus L.) inhibited the growth of a colon cancer cell line.6
  • Bomser et al. screened fruit extracts of bilberry for potential anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA).5 The crude extracts, anthocyanin, and proanthocyanidin fractions were not found to be highly active in Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) induction, whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of bilberry were 1.0mcg tannic acid equivalents (TAE). Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07mcg TAE). The anthocyanidin and ethyl acetate extracts of bilberry were either inactive or relatively weak inhibitors of ornithine decarboxylase (ODC) activity. The authors concluded that components of the hexane/chloroform fraction of bilberry exhibit potential anticarcinogenic activity, as evaluated by in vitro screening tests.
  • Antihyperglycemic effects: In normal and depancreatized dogs, oral administration of bilberry leaves reduced hyperglycemia, even when the glucose was injected intravenously concurrently.15,16
  • Antioxidant effects: Bilberry contains anthocyanosides that are flavonoid derivatives of anthocyanins (the blue, red, or violet pigments found in many berry varieties), which are closely related in structure and activity to flavonoids17 and possess free radical scavenging/antioxidant properties. Antioxidant properties have been attributed to bilberry based on in vitro studies.1,2,34
  • Antiplatelet activity: In a clinical study of 30 subjects with normal platelet aggregation, 480mg of Myrtocyan® (Vaccinium myrtillus anthocyanins) daily, 3g of ascorbic acid daily, or both treatments all reduced platelet aggregation after 30 and 60 days.11 Bilberry anthocyanins reduced platelet aggregation more than ascorbic acid alone, but bilberry anthocyanins and ascorbic acid together were the most effective. Also, in in vitro studies, anthocyanins extracted from bilberry have inhibited platelet aggregation.13,14,10,12
  • Flavonoids have been shown in vitro to inhibit prostacyclin synthesis. In one animal model, Vaccinium myrtillus anthocyanosides were studied for their effects on prostacyclin-like activity in rat arterial issue.7
  • Antiproliferative effects: According to one laboratory study, anthocyanins were the predominant phenolic compounds in bilberry extracts.31 Compared to other plants with anthocyanins, such as black currant or lingonberry, cell growth inhibition was greater for bilberry than other plants studied. The pro-apoptosis marker, Bax, was increased 1.3-fold in bilberry-treated cells, whereas the pro-survival marker, Bcl-2, was detected only in control cells. The results demonstrated that bilberry and other berry extracts containing anthocyanins inhibited cancer cell proliferation, mainly via the p21WAF1 pathway.
  • Antiulcer effects: In an animal study, large doses of cyanidin chloride from bilberry significantly increased gastric mucosal release of prostaglandin E2.19 In animal models of gastric ulcers, cyanidin chloride showed antiulcer activity.26,8
  • Astringent effects: Bilberry contains tannins that have been used medicinally as astringents and to treat diarrhea.
  • Connective tissue stabilizing effects: An in vitro study has suggested that anthocyanosides appear to stabilize connective tissue by enhancing collagen synthesis, inhibiting collagen degradation, and enhancing collagen cross linking.35 In contrast, Boniface et al. found a significant decrease in connective tissue synthesis (collagen and glycoproteins) in gingival tissue samples of 12 adult diabetics treated with 600mg of anthocyanosides daily for two months.36
  • Hepatoprotective activity: In an animal study, anthocyans exerted a protective effect on liver cells.27
  • Hyperglycemic effects: In an oral glucose tolerance test in healthy rats, an alcoholic extract of Vaccinium myrtillus leaves increased serum glucose levels compared to controls.25
  • Hypotensive effects: Bilberry has been theorized to potentially drop blood pressure, based on pre-clinical evidence of vascular smooth muscle-relaxing properties.21,22,23
  • Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Intracellular signaling effects: Anthocyanosides have been shown to inhibit cAMP phosphodiesterase, which is involved in intracellular signal transduction pathways.8
  • Ocular effects: Anthocyanosides have been shown to exert direct effects on the retina, including the alteration of local enzymatic reactions and enhancement of the recovery of rhodopsin.9 The multi-ingredient product Mirtogenol (Pycnogenol® – French maritime pine bark extract and Mirtoselect® – standardized bilberry extract) has been reported to lower intraocular pressure and improve ocular blood flow.37
  • Smooth muscle relaxant effects: Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Vasoprotective effects: Flavonoids have been shown in vitro to reduce capillary permeability and fragility. Anthocyanosides have been studied for their potential protective effect in disorders due to abnormal capillary fragility.33

Pharmacodynamics/Kinetics:

  • There are limited data regarding the pharmacodynamics and kinetics of Vaccinium myrtillus (bilberry) anthocyanosides (VMA). In one animal study, bilberry anthocyanosides were rapidly distributed after intra-peritoneal injection and intravenous administration.38 In another animal study, bilberry anthocyanosides were found to be eliminated via the bile and urine with a modest level of liver extraction.32
  • Bioavailability in animals is low. Following oral doses in rats, plasma levels of VMA reached a peak at 15 minutes and declined rapidly within two hours, and the absolute bioavailability was 1.2% of the administered dose.38 The gastrointestinal absorption of VMA was 5% of the administered dose. Another study found a differential affinity of VMA for certain tissues (especially skin and kidney).20 This suggests that different tissues may have more persistent local concentrations.
References:

  1. Martin-Aragon S, Basabe B, Benedi JM, and et all. In vitro and in vivo antioxidant properties of Vaccinium myrtillus. Pharmaceutical Biology 1999;37(2):109-113.
  2. Prior R, Cao G, Martin A, and et all. Antioxidant capacity as influence by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agricult Food Chem 1998;46:2686-2693.
  3. Martin-Aragon S, Basabe B, Benedi J, and et all. Antioxidant action of Vaccinium myrtillus L. Phytotherapy 1998;46:S104-S106.
  4. Laplaud, P. M., Lelubre, A., and Chapman, M. J. Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations. Fundam Clin Pharmacol 1997;11(1):35-40. 9182074
  5. Bomser, J., Madhavi, D. L., Singletary, K., and Smith, M. A. In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 1996;62(3):212-216.
  6. Zhao, C., Giusti, M. M., Malik, M., Moyer, M. P., and Magnuson, B. A. Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth. J Agric Food Chem  10-6-2004;52(20):6122-6128. 15453676
  7. Morazzoni P and Magistretti MJ. Effects of Vaccinium myrtillus anthocyanosides on prostacyclin-like activity in rat arterial issue. Fitoterapia 1986;57:11-14.
  8. Magistretti, M. J., Conti, M., and Cristoni, A. Antiulcer activity of an anthocyanidin from Vaccinium myrtillus. Arzneimittelforschung  1988;38(5):686-690. 3415709
  9. Cluzel, C., Bastide, P., Wegman, R., and Tronche, P. [Enzymatic activities of retina and anthocyanoside extracts of Vaccinium myrtillus (lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, alpha-glycerophosphate dehydrogenase, 5-nucleotidase, phosphoglucose isomerase)]. Biochem Pharmacol 1970;19(7):2295-2302. 4329039
  10. Morazzoni P and Bombardelli E. Vaccinium myrtillus L. Fitoterapia 1996;66:3-29.
  11. Pulliero G, Montin S, Bettini V, and et al. Ex vivo study of the inhibitory effects of Vaccinium myrtillus anthocyanosides on human platelet aggregation. Fitoterapia 1989;60:69-75.
  12. Bottecchia D. Preliminary report on the inhibitory effect of vaccinium myrtillus anthocyanosides on platelet aggregation and clot retraction. Fitoterapia 1987;48:3-8.
  13. Zaragoza, F., Iglesias, I., and Benedi, J. [Comparative study of the anti-aggregation effects of anthocyanosides and other agents]. Arch Farmacol Toxicol 1985;11(3):183-188. 4096552
  14. Fdez, M., Zaragoza, F., and Alvarez, P. In vitro platelet aggregation effects of anthocyanosides of vaccinium myrtilus L. Anales de la Real Academia de Farmacia 1983;49:79-90.
  15. Bever B. Plants with oral hypoglycemic action. Q J Crude Drugs Res 1979;17:139-196.
  16. Allen, F. M. Blueberry leaf extract: Physiologic and clinical properties in relation to carbohydrate metabolism. 89:1577-81, 1927. JAMA 1927;89:1577-1581.
  17. Havsteen, B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 4-1-1983;32(7):1141-1148. 6342623
  18. Colombo D and Vescovini R. Controlled clinical trial of anthocyanosides from Vaccinium myrtillus in primary dysmenorrhea. G Ital Obstet Ginecol 1985;7:1033-1038.
  19. Mertz-Nielsen, A., Munck, L. K., Bukhave, K., and Rask-Madsen, J. A natural flavonoid, IdB 1027, increases gastric luminal release of prostaglandin E2 in healthy subjects. Ital J Gastroenterol  1990;22(5):288-290. 2134327
  20. Lietti, A., Cristoni, A., and Picci, M. Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity. Arzneimittelforschung 1976;26(5):829-832. 9100
  21. Colantuoni, A., Bertuglia, S., Magistretti, M. J., and Donato, L. Effects of Vaccinium Myrtillus anthocyanosides on arterial vasomotion. Arzneimittelforschung  1991;41(9):905-909. 1796918
  22. Bettini V. Effects of Vaccinium myrtillus anthocyanosides on vascular smooth muscle. Fitoterapia 1984;55(5):265-272.
  23. Bettini V, Mayellaro F, Ton P, and et al. Interactions between Vaccinium myrtillusanthocyanosides and serotonin on splenic artery smooth muscle. Fitoterapia 1984;55(4):201-208.
  24. Brantner, A. and Grein, E. Antibacterial activity of plant extracts used externally in traditional medicine. J Ethnopharmacol 1994;44(1):35-40. 7990502
  25. Neef H, Declercq P, and Laekeman G. Hypoglycaemic activity of selected European plants. Phytotherapy Research 1995;9:45-48.
  26. Cristoni, A. and Magistretti, M. J. Antiulcer and healing activity of Vaccinium myrtillus anthocyanosides. Farmaco [Prat] 1987;42(2):29-43. 3582621
  27. Mitcheva, M., Astroug, H., Drenska, D., Popov, A., and Kassarova, M. Biochemical and morphological studies on the effects of anthocyans and vitamin E on carbon tetrachloride induced liver injury. Cell Microbiol 1993;39(4):443-448. 8329983
  28. Lyons, M. M., Yu, C., Toma, R. B., Cho, S. Y., Reiboldt, W., Lee, J., and van Breemen, R. B. Resveratrol in raw and baked blueberries and bilberries. J Agric Food Chem  9-24-2003;51(20):5867-5870. 13129286
  29. Rimando, A. M., Kalt, W., Magee, J. B., Dewey, J., and Ballington, J. R. Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem 7-28-2004;52(15):4713-4719. 15264904
  30. Milbury, P. E., Graf, B., Curran-Celentano, J. M., and Blumberg, J. B. Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells. Invest Ophthalmol Vis Sci 2007;48(5):2343-2349. 17460300
  31. Wu, Q. K., Koponen, J. M., Mykkanen, H. M., and Torronen, A. R. Berry phenolic extracts modulate the expression of p21(WAF1) and Bax but not Bcl-2 in HT-29 colon cancer cells. J Agric Food Chem 2-21-2007;55(4):1156-1163. 17243699
  32. Lietti, A. and Forni, G. Studies on Vaccinium myrtillus anthocyanosides. II. Aspects of anthocyanins pharmacokinetics in the rat. Arzneimittelforschung  1976;26(5):832-835. 989354
  33. Mian E. Anthocyanosides and microvessel walls: new findings on the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Med 1977;68(52):3565-3581.
  34. Marcollet M, Bastide P, and Tronche P. Effet angio-protecteur des anthocyanosides de Vaccinium myrtillus odjective vis a vis de la liberation de la lactate deshydrogenase (LDH) et de ses isoenzymes cardiaques chez le rat soumis a une epreuve de nage. C R Soc Biol  1970;163:1786.
  35. Jonadet, M., Meunier, M. T., Bastide, J., and Bastide, P. [Anthocyanosides extracted from Vitis vinifera, Vaccinium myrtillus and Pinus maritimus. I. Elastase-inhibiting activities in vitro. II. Compared angioprotective activities in vivo]. J Pharm Belg 1983;38(1):41-46. 6553084
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  38. Morazzoni, P., Livio, S., Scilingo, A., and Malandrino, S. Vaccinium myrtillus anthocyanosides pharmacokinetics in rats. Arzneimittelforschung  1991;41(2):128-131. 2043174

BLUEBERRY & BILBERRY SUMMARY

Wild bilberries and wild blueberries are important fruits full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector+ such an outstanding nutritional supplement.

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REJUVENATE! BERRIES & HERBS – INGREDIENTS FOR OPTIMAL NUTRITION

Fred Liers PhD rejuvenate! berries & herbs superfoodI write a lot about superfood ingredients, and especially those in HPDI’s Rejuvenate! superfoods. One superfood I write about less often is Rejuvenate! Berries & Herbs.

This may relate to the fact that Rejuvenate! Original and Rejuvenate! PLUS provide plenty of greens like chlorella and spirulina. Greens make these superfoods popular, and it is easy educating health care professionals and consumers alike on their benefits.

Rejuvenate! Berries & Herbs is different. It provides ultra-high ORAC value (14,200+) per serving. It also provides more dietary nucleic acids (390 mg) per serving than other Rejuvenate! superfoods. It tastes so good it may the HPDI’s best-tasting superfood. Even Health Ranger Mike Adams loves it, and stocks it in his online store.

Rejuvenate! Berries & Herbs superfood

Rejuvenate! Berries & Herbs is one of three HPDI superfoods providing dietary nucleic acids.

REJUVENATE! BERRIES & HERBS IS DIFFERENT: IT LACKS GREENS

But it lacks greens. And greens are what almost everyone wants. As noted, Rejuvenate! Original and PLUS formulas provide high levels of greens like chlorella and spirulina. Berries & Herbs provides none.

For some people, no greens is just great. We developed Berries & Herbs because we want to offer one superfood with high levels of dietary nucleic acids that does NOT contain greens.

Formulating a high-RNA superfood without greens is an admirable goal. Most of the dietary nucleic acids in Rejuvenate! superfoods (and dietary RNA is what makes HPDI superfoods unique) come from greens. For example, chlorella contains amazingly high levels of nucleic acids, more than any other ingredient.

THE VERSATILE, NON-GREEN SUPERFOOD WITH NUCLEIC ACIDS

Rejuvenate! Berries & Herbs was created as superfood lacking greens. It suits its purpose because: 1) certain individuals cannot stomach greens like chlorella; 2) many people enjoy greens, but also desire variety; 3) many prefer a fruity, berry-flavored superfood for reasons of taste–and Berries & Herbs tastes delicious.

While the lack of greens could be perceived as a liability, it is one of the greatest benefits of Rejuvenate! Berries & Herbs.

rejuvenate! berries & herbs superfood greens continuum

Rejuvenate! Berries & Herbs is the HPDI superfood without greens.

In this article, I want to recap the benefits of Berries & Herbs and present some new information on ingredients, characteristics, and qualities of this unique, non-green superfood.

GREENS ARE GREAT, BUT SO ARE “BERRIES & HERBS”

First, I haven’t written an article about Berries & Herbs since February 2014 when I published “Be Healthy with Rejuvenate! Berries & Herbs.” That was an in-depth piece. And the information is still 100% true: I favor greens, as in greens provided by Rejuvenate! Original (greens) and Rejuvenate! PLUS (sweet greens).

One major difference: while I consume plenty of greens those green Rejuvenate! superfoods, there is now more room in my diet for non-green superfoods. That means Berries & Herbs.

I already take 5–10 servings per day of Rejuvenate! Original. That may sound like a lot, but I reduce my food intake to accommodate higher levels of superfoods. I feel satisfied with reduced food intake when consuming higher levels of superfoods.

As a result, my dietary nucleic acid intake is quite high. High levels of dietary nucleic acids are part of what make Rejuvenate! superfoods unique. High-purity and nutrient density are other major benefits.

I probably do not require more dietary nucleic acids (unlike athletes like pro cyclist Irena Ossola whose training and performance benefit from higher levels of dietary RNA). I already get sufficient RNA.

However, there are many reasons I consume Rejuvenate! Berries & Herbs:

 Berries & Herbs can be more filling than Rejuvenate! Original. Therefore it makes a nutritious breakfast drink, or after breakfast power booster.

• Contains a full-spectrum multivitamin. It doesn’t replace my daily multivitamin (Hank & Brian’s Mighty Multi-Vite!), but it does give me an extra boost of vitamins/minerals in liquid form (smoothie, blender drink, or plain in almond milk, juice, or water).

• Tastes amazingly good. That means it makes a delicious and healthy “refresher”  or “snack” between meals. It also makes a great after dinner “dessert” drink.

• Makes yummy shakes of whatever consistency you like. You can use less liquid (or more Berries & Herbs) for a thicker shake. Add a drop or two of stevia if you desire a sweeter taste.

• Tasty replacement for drinks like hot cocoa, tea, or coffee.

• Blends well with milks, yogurt/kefir, nut milks, and herbal teas.

• Great addition to foods, including fruit, berries, granola, and grains.

• Nutritious when used as an ingredient in homemade bars (see bar recipes).

• Delicious in plain water and without added sweeteners.

• Kids love Berries & Herbs. It can be added to drinks and foods as a healthy booster. Since my son loves Berries & Herbs, I use it in his drinks and foods.

These are just a few of the advantages of Berries & Herbs that I know from personal experience, and from talking to many people who use it regularly.

rejuvenate! berries & herbs superfood

MORE THAN MEETS THE EYE: EIGHT BENEFITS OF BERRIES & HERBS

There’s a lot more to Rejuvenate! Berries and Herbs that you might guess. I identified eight key benefits of Berries & Herbs in my previous post. A few of these benefits overlap with those I mention (above) as reasons I consume Berries & Herbs. But most of the eight benefits are unique:

1) TASTES GREAT

2) HIGHER RNA LEVELS THAN OTHER REJUVENATE!™ SUPERFOODS

3) CELL-SUPPORTING HERBS FOR OPTIMAL HEALTH

4) SLOWER DETOXIFICATION FOR A GENTLER DETOX EXPERIENCE

5) HIGH PROTEIN (ALL VEGETARIAN)

6) MULTIVITAMIN WITH COENZYME B COMPLEX FOR ADDITIONAL NUTRIENTS

7) HIGH ANTIOXIDANT VALUE (14,200+ ORAC) FOR REJUVENATING POWER

8) NRF2 ACTIVATORS SUPPORT ANTIOXIDANT PRODUCTION IN CELLS

These eight benefits create a profile of advantages specific to Berries & Herbs. I will discuss most of these benefits below.

HIGH LEVELS OF DIETARY NUCLEIC ACIDS (RNA, DNA)

Before I talk about how good Berries & Herbs tastes (and did I mention it tastes really good?), I want to present information about dietary nucleic acids.

Dietary nucleic acids are so important for health that Dr. Benjamin S. Frank devoted his entire life to studying them. He declared them to be “essential nutrients” for health like vitamins and minerals.

One way dietary nucleic acids (RNA, DNA) support health is by boosting production of energy (ATP) in the body. When ATP production is high, the body has sufficient energy to support many of the biological functions required for keeping you healthy.

Read more about health benefits of dietary nucleic acids in my article, “9 Things to Know About Rejuvenate! Superfoods” and other blog articles.

Inspired by Dr. Frank’s scientific writings, my father Dr. Hank Liers formulated the series of Rejuvenate! superfoods specifically with the idea of providing high levels of dietary nucleic acids (RNA, DNA) to support optimal health. All three Rejuvenate! superfoods provide at least 340 mg of dietary nucleic acids.

To be exact, Rejuvenate! (Original) and Rejuvenate! PLUS both provide 340 mg of dietary nucleic acids per serving. Rejuvenate! Berries & Herbs provides a whopping 390 mg of dietary nucleic acids!

That’s 50 mg more dietary nucleic acids per serving. As I noted, an extra 50 mg of dietary nucleic acids (Rejuvenate Berries & Herbs compared to other Rejuvenate! superfoods) may not seem like much, yet those servings add up.

At one serving daily, in a single week you will consume an “extra” 350 mg of dietary RNA (at 50 mg more per day). That is a full extra serving weekly. If you take two servings daily, that’s 700 mg additional dietary nucleic acids.

Dr. Frank tells us that a small amount dietary RNA goes a long way in terms of health benefits. He states that relatively small amounts of RNA (e.g., 100 mg daily) can provide noticeable health benefits.

Yet, larger amounts provide more benefits and create a stronger foundation for health (Frank 117). For example, individuals who benefit from larger amounts of RNA include athletes, individuals experiencing stress, and those seeking to recover from injuries.

An extra 350–700 mg dietary nucleic acids weekly can make a difference for health. It also means that a container Berries & Herbs can last longer than a container of Rejuvenate! PLUS in terms of providing more RNA per serving.

How much RNA do you need? That depends. 1,000 mg is a solid goal. That’s just two and one half (2.5) servings of Berries & Herbs or approximately five scoops.

HOW MUCH RNA DO WE NEED?

Dr. Benjamin S. Frank and other experts suggest an “optimal” intake in the range of 1,000–1,500 mg. This means 2.5 to 4 servings per day, or five to eight small scoops of Berries & Herbs. This amount can reasonably be attained by consuming, for example, a morning smoothie and an afternoon shake with three scoops of Berries & Herbs each.

After reaching a daily intake of about 1,500 mg, the benefits obtained by increased RNA consumption begin leveling. Greater intake of nucleic acids beyond this amount seems to provide fewer benefits.

An Olympic athlete in training might benefit from a daily RNA intake of 2,500 or 3,000 mg. Yet, most of us don’t have these high requirements because we aren’t pushing our bodies to such a level of activity and intensity.

That doesn’t mean you can’t gain similar benefits as those that might be conferred to an Olympian by optimizing your daily intake at a level that gives you sufficient dietary nucleic acids for rejuvenation, energy, and vitality.

Begin with a serving or two per day of Berries & Herbs (or another Rejuvenate! superfood), and work up to 1,000–1,500 mg daily.

GIVE IT TIME

It takes the body a few weeks to become saturated with nucleic acids. For me, it seems to be about 12 days.

Thus it can initially take two to four weeks after starting a high-RNA diet to see the benefits of nucleic acids. You may immediately notice greater energy or body warmth. (Likewise, when you stop taking nucleic acids, the benefits will still last several weeks.)

By consuming Berries & Herbs regularly after the body is saturated with RNA, you easily maintain your body’s supply of dietary nucleic acids. Maintaining your daily intake of dietary RNA helps sustain health.

INCLUDES HIGH-POTENCY MULTIVITAMIN WITH COENZYME B COMPLEX

A major benefit of Rejuvenate! Berries & Herbs is that it contains a high-potency multivitamin. Why is this important? While many people take a multivitamin, most multivitamins provide inadequate amounts of essential nutrients required for health.

In fact, many multivitamins provide the “Daily Value” established by the US government for critical nutrients. Daily values have replaced what was formerly known as “recommended daily allowances,” yet typically remain at or barely above levels required to prevent diseases of deficiency. These are not levels optimal for human health.

That is, daily values are not designed to create optimal health. They are minimum values based upon levels required for to avoid deficiencies. There is a huge difference between minimum levels needed for survival or prevent deficiencies. Indeed, the body assimilates and utilizes far higher levels to build and maintain robust health.

Still, the majority of multivitamins are formulated to provide minimum daily values. Thus, the majority of persons taking multivitamins obtain minimal values that do not create optimal health.

We at HPDI know the importance of a high-potency multivitamin for providing nutrients at levels that fall into ranges necessary for creating, supporting, and maintaining excellent health. After all, HPDI’s founder-formulator Dr. Hank Liers specializes in designing effective, high-potency multivitamins. He has done this for more than 25 years.

HPDI offer several excellent standalone multivitamins. But until the advent of Rejuvenate! Berries & Herbs, only HPDI’s Rejuvenate! PLUS superfood included a built-in multivitamin.

Dr. Liers wanted to confer the same nutritional advantages to consumers of Berries & Herbs. The vitamins added to HPDI’s superfoods like Berries & Herbs may not in every case completely replace the need for a standalone multivitamin. However, they do make the formula far more nutritious and more effective, partly helping the body better utilize dietary nucleic acids.

When it came to formulating Rejuvenate! Berries & Herbs, Dr. Liers not only incorporated a high-potency multivitamin, but also made sure the forms of these vitamins would be only the ones best used by the body.

Many of the vitamins (including the B complex vitamins) in Berries & Herbs are coenyzme-form vitamins or other forms best-recognized and/or utilized in the body. Best recognized almost always means natural. For example, Berries & Herbs does not include folic acid, which is a synthetic form of folate, but instead use calcium folinate (folinic acid), the natural co-enzyme form of folate.

Here are the vitamins in one serving that make up the multivitamin complex in Rejuvenate! Berries & Herbs:

• VITAMIN C (250 MG) (417% OF DAILY VALUE)

• VITAMIN E AS D-ALPHA TOCOPHERYL SUCCINATE (90 IU) AND HIGH GAMMA MIXED TOCOPHEROLS (25 MG) (300% OF DAILY VALUE)

• VITAMIN D3 (1,000 IU) (250% OF DAILY VALUE)

• VITAMIN K1 (0.5 MG) (625% OF DAILY VALUE)

• VITAMIN (100 MG)

• CHOLINE (50 MG)

• VITAMIN B1 FROM THIAMIN DIPHOSPHATE (7.5 MG) (500% OF DAILY VALUE)

• VITAMIN B2 FROM RIBOFLAVIN-5′-PHOSPHATE (6.8 MG) (400% OF DAILY VALUE)

• VITAMIN B3 AS NIACINAMIDE (60 MG) (300% OF DAILY VALUE)

• VITAMIN B5 AS PANTOTHENIC ACID (30 MG) (300% OF DAILY VALUE)

• VITAMIN B5 FROM COENZYME PANTETHINE (13 MG) (130% OF DAILY VALUE)

• VITAMIN B6 FROM PYRIDOXAL-5′-PHOSPHATE (10 MG) (500% OF DAILY VALUE)

• FOLATE AS FOLINIC ACID (1 MG) (250% OF DAILY VALUE)

• BIOTIN (0.9 MG) (300% OF DAILY VALUE)

• VITAMIN B12 AS METHYLCOBALAMIN (0.2 MG) (3,333% OF DAILY VALUE)

This list of course does not include other vitamins in Rejuvenate! Berries & Herbs ingredients, such as nutrients found in vegetable sprout powders, vegetable protein powders, stabilized rice bran, or in many of the herbal ingredients like burdock, ginger, or turmeric.

Another advantage of coenzyme vitamins is the body needs less of any given coenzyme vitamin because it does not need to convert non-coenzyme vitamins into usable forms. Therefore, the body requires less of a coenzyme-form vitamin.

That is a good thing because it does not cause the body to waste energy using enzymes to convert synthetic vitamins into their coenzyme forms. While coenzyme vitamins are relatively expensive to source, they are often very affordable to consumers because the body only needs tiny amounts of them.

Unlike many conventional B vitamins typically used in multivitamins, there are no losses of coenzyme B vitamins in vivo (in the body) due to conversion processes because they are immediately recognized by the body. This represents a powerful boost in effectiveness for minimal rise in cost.

HPDI uses coenzyme vitamins in many of their products because of their high value in terms of health and well being. The future of vitamin supplements lies in coenzyme-form vitamins because they are the most natural and most effective, and the most easily assimilated by the body.

In fact, HPDI was among the first companies to incorporate coenzyme form vitamins into its formulas. Dr. Hank Liers understands their value for human health. We will continue formulating products with coenzyme vitamins like Rejuvenate! Berries & Herbs.

VITAMINS INCREASE EFFECTIVENESS OF DIETARY NUCLEIC ACIDS

The vitamins (including coenzyme-form vitamins) in Rejuvenate! Berries & Herbs provide a significant benefit. They boost the effectiveness of the dietary nucleic acids.

Dr. Benjamin S. Frank certainly was clear about the effects of vitamins on the human body, including its capacity for using dietary RNA for therapeutic purposes. In his regimen for using nucleic acids for health as documented in Dr. Frank’s No-Aging Diet, he recommends taking a “therapeutic-strength” multivitamin daily (76).

Dr. Frank performed many human and animal studies using dietary nucleic acids. He nearly always included vitamins in his regimens. Very often he placed subjects on separate B-complex supplements.

Dr. Frank specifically states that the addition vitamin B-complex to the RNA regimen enhances the effects of dietary RNA. For example, he mentions how the B-complex support the rejuvenating effects of RNA on facial skin (Nucleic Acid Nutrition and Therapy 27).

Dr. Frank often specifies additional vitamins for dealing with certain conditions. For example, in his chapter on how his no-aging diet can help with osteoarthritis, he recommends patients take an additional 250 mg of pantothenic acid (vitamin B5) and 500 mg of vitamin C.

In his writings on dietary recommendations, Dr. Frank not only recommends B-complex vitamins, but also vitamin A, vitamin C, and vitamin D. He also incorporates a wide range of minerals in his formulas for patients.

Minerals he recommends include magnesium, zinc, and potassium. He also mentions other nutrients, such as coenzyme Q (ubiquinone/ubiquinol), enzymes, amino acids (e.g., carnosine, glutathione), and natural sugars (e.g., ribose and deoxyribose).

The inclusion of a complete multivitamin complex in Rejuvenate! Berries & Herbs helps make dietary nucleic acids more effective.

Learn more about our complete line of foundational supplements, including multivitamins.

HIGH-ORAC NUTRITION & ANTIOXIDANT PROTECTION

Rejuvenate! Berries & Herbs is an excellent, well-balanced superfood. Few superfoods stack up against it when you consider all the nutrition it provides.

Which brings us to another benefit: High antioxidant values. Berries & Herbs is in a class by itself when it comes to providing antioxidant power. That is, the power to quench free radicals.

One measure of the antioxidant values of foods and nutrients is ORAC value. ORAC stands for “oxygen radical absorbance capacity.” An ORAC test measures antioxidant capacities in vitro (test tube).

ORAC by itself is not the only or necessarily the best measure of antioxidant value because the oxygen radicals are not the only oxidants. A more comprehensive test would be the ORAC5.0 test, which measures the free-radical quenching powers of a sample against five different types of oxidants.

Nevertheless, ORAC remains a useful guide to the oxidant quenching powers of a superfood. Berries & Herbs provides an ORAC value of greater than 14,270 units per 38.9 gram serving.

There exist few individual foods, for example, that exhibit an ORAC value anywhere close to this figure. Even the highest-ORAC foods (like prunes or blueberries) fall short, being at most one-third as effective.

Most individual berries provide ORAC values in the range of 5,000–7,000 units per 100 gram serving (usually one cup or eight ounces), which translates into about 50–70 ORAC units per gram. Berries & Herbs tops such figures by providing 367 ORAC units per gram.

This means the ORAC value provided by Rejuvenate! Berries & Herbs in a single two-scoop serving (about 5 tablespoons) equals the ORAC the average high-ORAC berry (about 60 ORAC units/gram) provides in about six one-cup servings (48 tablespoons).

Serving-for-serving, Berries & Herbs is greater than six times more potent as an antioxidant substance than most foods considered high-ORAC. It also means you’ll need to consume far less Berries & Herbs to gain the antioxidant benefits you would from a much larger quantity of high-ORAC foods.

Berries & Herbs offers 367 ORAC units per gram! One serving is about 39 grams, so there is a huge amount of free-radical quenching power in just a single serving.

How huge is that? Since Berries & Herbs provides 14,276 ORAC units per serving (38.9 grams), then for a typical 100 gram ORAC equivalency, it provides an ORAC value of 36,684. Most ORAC food charts stop at about 14,500 units per 100 g (and average high-ORAC foods hover at 5,000 units per 100 g) to put those values in perspective.

Gram for gram, Berries & Herbs offers more than twice the ORAC value of the highest ORAC foods. And at least five to seven times more ORAC value than “average” high-ORAC foods (strawberries, raspberries, and blackberries) providing 5,000–7,000 ORAC units per 100 grams).

Antioxidant power is a unique benefit for Rejuvenate! Berries & Herbs, and one that is hard to be matched by any superfood, anywhere.

HIGH-ORAC BERRIES & POLYPHENOLS

I will talk more about about antioxidant nutrients in Rejuvenate! Berries & Herbs when discussing its cell-protecting herb and nutrient blend.

The major free-radical quenching power Berries & Herbs actually lies in its berry and polyphenol content. The extraordinary free radical-quenching capacities of Rejuvenate! Berries & Herbs relate directly to the fact that berries, as well as plant-based polyphenols (like those found in grapes and grape extract) contain relatively large quantities of antioxidants.

Also, the berries and polyphenols in in the formula come in highly concentrated forms. For example, we include potent berry blends like VitaBerry® Plus® and a carefully selected organic freeze-dried berry complex. The blends provide many types of berries, polyphenols, and other antioxidant nutrients acting synergistically to create higher ORAC values than a formula with fewer types of these berries or polyphenols.

NRF2 ACTIVATORS

Many plant-based antioxidants also act as Nrf2 activators. Nrf2 is a transcription factor encoded in human genes and whose antioxidant response pathway is our primary cellular defense against oxidative stresses. Nrf2 increases expression of important antioxidant enzymes in cells.

What this means is that Nrf2 activators are substances that activate the cells’ own production of antioxidant defenses. Because there is significant overlap between the food-based (i.e., exogenous) antioxidants and Nrf2 activators stimulating the body’s production of its own antioxidant enzymes, the berry complexes and polyphenols in Rejuvenate! Berries & Herbs serve double-duty as externally supplied antioxidants and stimulators of the body’s own antioxidant production.

The study of Nrf2 activator nutrients is an exciting area of research due to the potential for Nrf2 activators to significantly boost human health by enabling the body to unlock its potential for creating antioxidants.

The body already produces its own antioxidant defenses, but Nrf2 activators significantly enhance this process, thereby allowing far greater production of antioxidants for cell protection.

Rejuvenate! Berries & Herbs was not formulated as a Nrf2 activator formula. Yet, research shows there is significant overlap among the antioxidant substances in Berries & Herbs and nutrients known for activating Nrf2 transcription factor.

Known Nrf2 activators in Rejuvenate! Berries & Herbs include vegetable sprouts powder, blueberry powder, cranberry powder, strawberry powder, raspberry powder, vitaberry plus, burdock root, astragalus, turmeric, ginger root, rhodiola rosea (root), rutin, n-acetyl-l-cysteine, milk thistle extract, licorice (root), green tea extract, dandelion root, vitamin E (d-alpha tocopherol), lipoic acid, grape extract, and transresveratrol.

To learn more about Nrf2 activators, please see “The Amazing Healing Potential of Natural Nrf2 Activators,” “Natural Phytochemical Nrf2 Activators for Chemoprevention,” and other Nrf2-related articles on HPDI blog.

HPDI also offers Ultimate Protector, which is an antioxidant, vitamin C, and Nrf2 activator formula in a capsule. Ultimate Protector is not a high-RNA superfood, but a standalone HPDI foundational supplement. The two formulas can be combined, and in fact are formulated so they can be taken together in the HPDI system. Six small capsules of Ultimate Protector provide 486,000 ORAC5.0 units per serving. When taken together, the two formulas product more than 500,000 ORAC5.0 units per serving.

As noted, Berries & Herbs is not formulated as an antioxidant or Nrf2 activator formula per se. Yet, it provides significant antioxidant and Nrf2 activation.

When any Rejuvenate! superfood (including Berries & Herbs) is combined with Ultimate Protector (or another vitamin C and antioxidant formula), a multivitamin (like Multi Two), and essential fats (like Essential Fats Plus E), all four types of foundational formulas work together to support optimal health. Read more about how HPDI’s foundational supplements system works to support optimal health.

CELL-SUPPORTING HERBAL COMPLEX (“SUBFORMULA”)

One of the top features provided by Rejuvenate! Berries & Herbs is a blend of foods, herbs, and nutrients that collectively constitute a “subformula” created to support cell function and optimal cellular health.

Because this cell-protecting subformula contains many proven ingredients, it may appear to be more nutrient-dense substances heaped on top of an already densely packed Rejuvenate! Berries & Herbs superfood.

But the cell-protecting blend is something totally different. It’s not related to nucleic acid content, or to the built-in coenzyme B vitamin complex, or the high-quality protein content. It is a groundbreaking, game-changing set of ingredients that sets Berries & Herbs apart from nearly every superfood, including other Rejuvenate! superfoods.

The truth is that today our cells are under constant attack by thousands of different stresses. They are bombarded by toxic chemicals in the air, water, and soil. These chemicals include everything from pesticides and herbicides to household cleaning chemicals and industrial contaminants.

Our cells are also attacked by radiation. For example, elevated levels due to nuclear accidents like Fukushima and high background levels remaining from nuclear tests. Not to mention exposures from medical and dental x-rays. All these exposures lead to cumulative damage.

Other cellular toxins include daily exposures to chlorine, fluoride, bromine, and other halogens. And of course, exposures to heavy metals like lead, mercury, and cadmium from numerous other sources like dental amalgams, old paint, contaminated fish, and many other sources.

There are many other toxins our cells must deal with daily. Rejuvenate! Berries & Herbs is formulated to help cells deal with this assault by providing nutrients that support optimal function. This includes supporting your antioxidant defenses, immune system, energy production system, detoxification, and other important functions.

Dr. Hank Liers initially created this subformula of ingredients at the request of veterinarian Randy Aronson, VMD, who is Dr. Liers partner in the development of the 2Docs line of pet wellness formulas (www.IntegratedHealth.com/2docs-pet-supplements.html).

Dr. Randy was looking for a potent combination of ingredients that could optimally support the health and vigor, as well as recovery from illness of many of his pet patients suffering from degenerative diseases. Dr. Hank’s formula worked for Dr. Randy’s animal patients.

Dr. Hank saw its potential benefits for people. He began thinking about what a human version of the formula might look like, and how it could be incorporated into a product. At the time, HPDI was developing it’s latest Rejuvenate!™ superfood. While formulating the superfood, Dr. Hank realized that these “herbs” and other nutrients could perfectly complement the “berries” he put in the formula. “Berries & Herbs” was born.

Rejuvenate! Berries & Herbs thus contains a cell-protecting blend of organic and/or wildcrafted herbs and antioxidants. The cell-protecting subformula includes the following ingredients:

Organic astragalus, organic burdock root, organic turmeric root, organic ginger root, n-acetyl-l-cysteine (NAC), k-rutin™, standardized milk-thistle extract (>82% silymarin), standardized green tea extract (>95% polyphenols, >55% EGCG), organic licorice root, organic dandelion root, organic dulse, organic kelp, standardized Rhodiola rosea root (>3% rosavins), alpha-lipoic acid, BioVin™ grape seed, skin, and pulp extract, Immune-Assist™ (synergistic blend of organic mushroom extracts including Agaricus blazei, Cordyceps sinensis hybrid, Lentinula edodes, Grifola frondosa, Ganoderma lucidum, and Coriolus versicolor), transresveratrol (from Polygonum cuspidatum), germanium sesquioxide, and l-selenomethionine.

This subformula of ingredients makes a Berries & Herbs almost a “stealth” superfood. That is, many of the other benefits are more directly evident. Like high level of vegetarian-friendly protein or a built-in multivitamin.

The inclusion of dietary nucleic acids may be more obviously beneficial than cell-protective nutrients. But the subformula of cell-protective nutrients and herbs offers major benefits.

A nutritionist might read the label and realize the immune-building power of the cell-protective subformula. An acupuncturist might see its capacity for increasing energy or “chi.” A naturopath may identify potential for detoxification. In fact, most health professionals recognize value in the subformula’s ingredients.

The cell-supporting subformula is effective for supporting immunity, energy production, and detoxification, and other healthy benefits. The herbs and nutrients in the cell-supporting subformula make Rejuvenate! Berries & Herbs unique, and distinguishes it from other superfoods.

BERRIES & HERBS IS A HIGH-PROTEIN SUPERFOOD

Beyond the advantages of Rejuvenate! Berries & Herbs discussed, you might think the benefits stop there. But here is another one: Berries & Herbs is a high-protein powerhouse.

Dr. Hank Liers designed Berries & Herbs not only as a great-tasting, well-rounded superfood with dietary nucleic acids, multivitamins and minerals, but also as a high protein formula.

Higher protein (12 g per serving) means more complete nutritional support for people using Rejuvenate! Berries & Herbs as a food, snack, or nutritious drink.

The 12 grams of protein in a single two-scoop serving of Rejuvenate! Berries & Herbs is about six rounded tablespoons of it.

It’s easy to consume two scoops at a time because it tastes so good. Whether you choose to mix it in a smoothie, shake it up in jar, drink it plain in water, or add to fresh juice, you can count on its protein to help sustain you.

Adult females require about 46 grams of protein per day. Two servings of Rejuvenate! Berries & Herbs provides a woman with more than half (52%) of her daily recommended intake of protein.

Adult males require more protein (about 56 grams daily) than females. But even for men, two servings of Berries & Herbs provide almost 43% of their recommended daily protein intake.

PROTEIN SUITABLE FOR VEGETARIANS

The high-quality protein in Rejuvenate! Berries & Herbs comes from non-GMO brown rice, organic sprouted flaxseed (powder), organic hemp protein (powder), and a blend of garden sprouts. Here is the breakdown of the major protein sources in Rejuvenate! Berries & Herbs:

• High Protein Organic Garden Sprout Blend (3,000 mg/serving). Included in this blend are pea protein, quinoa sprouts, broccoli sprouts, alfalfa sprouts, daikon radish sprouts, red clover sprouts, and natural vanilla favor. Greater than 65% protein.

• Brown Rice Protein (Non-GMO) (9,000 mg/serving)

• Flaxseed Powder (3,000 mg/serving) (15–30% protein)

• Organic Hemp Protein Powder with Fiber (3,000 mg/serving)

I will present more information (below) regarding specific nutritional information for each of these superior vegetable-based protein sources. Selenium (from l-Selenomethionine), and Vitamin D3 (cholecalciferol).

FINAL WORDS: TASTE, TASTE & TASTE!!

I rarely save best things for last. But while delicious taste may not be a health benefit, it qualifies as one of the outstanding features of Rejuvenate! Berries & Herbs.

Berries & Herbs has a beautiful aroma and flavor that tickles taste buds with intense berry flavors and lingering fruity notes. Its taste is like a blast of berries in the mouth probably because that’s exactly what it is.

Most people like it. I myself was astonished that a superfood could taste so good.  If you haven’t tried it before, you’re likely to be pleasantly surprised.

Below I include detailed information about Rejuvenate! Berries & Herbs. Here is a superfood you can rely on for solid nutrition, great taste, and high levels of dietary nucleic acids supporting optimal health. ~

rejuvenate! berries & herbs high-RNA superfood

Rejuvenate! Berries & Herbs is a Dr. Hank Liers “original” formula.

DETAILED INFORMATION ABOUT REJUVENATE!™ BERRIES & HERBS

REJUVENATE!™ BERRIES & HERBS CONTAINS THE FOLLOWING UNIQUE INGREDIENTS

VitaBerry® Plus® (400 mg/serving)

VitaBerry® Plus® is a nutritious ingredient having extremely high ORAC value and is derived from freeze-dried Grape Seed, Wild Blueberry, Wild Bilberry, Cranberry, Tart Cherry, Prune, Raspberry Seed, Strawberry, Resveratrol, and Quercetin. In fact, this powder has an ORAC value in excess of 1.2 million units per 100 grams. Therefore at the 400 mg level that this material is found in Rejuvenate! Berries & Herbs it provides a minimum of 4,800 ORAC units. Because excessive exposure to free radicals may cause severe pain and inflammation, high-ORAC VitaBerry® Plus® significantly can contribute to preventing oxidative damage in the body.

VitaBerry® Plus® provides the following benefits:

• Superior source of natural antioxidants

• Helps prevent the effects of premature aging

• Promotes cardiovascular health

• Promotes healthy brain function and mental acuity

• Promotes healthy vision

• Promotes healthy blood sugar levels

• Excellent source of flavonoids and organic acids

• Promotes urinary tract health

• Promotes healthy skin

ORGANIC FREEZE-DRIED BERRY COMPLEX (6,000 mg)

The freeze-dried berry complex in Rejuvenate! Berries & Herbs is a proprietary blend of organic strawberries, raspberries, blueberries, and cranberries. Berries contain many powerful phytochemicals that can improve health. They are high in fiber and relatively low in sugar, and will not lead to surges to insulin when eaten in moderation.

BLUEBERRIES

The berries of the blueberry plant (Vaccinium angustfolium) exhibit among the highest levels of antioxidant activity of all fruits and vegetables. In particular, they contain the polyphenol anthocyanin (a pigment that gives fruits their red, purple and dark blue colors).

Anthocyanins are powerful flavonoid antioxidants that help protect the body from free radical damage and diseases associated with aging. Blueberries contain not only 25-30 different types of anthocyanins, but also chlorogenic acid (believed to be a tumor inhibitor), and the pigment cyanidin (an anti-inflammatory).

Blueberries contain silicon (an element believed to be helpful for the pancreas) and are considered to be helpful for diabetes.

Blueberries also have been effective for many health conditions, and may protect the body against age related declines in neural and cognitive functions, short-term memory loss, macular degeneration of the retina, and urinary tract infections (due to compounds that inhibit the adherence of bacteria to uroepithelial walls).

There is evidence that blueberries may improve glucose metabolism via the action of chlorogenic acid, serve as a powerful anti-inflammatory agents (useful against arthritis and other inflammatory conditions), and reduce the risk of tumorigenesis.

The antioxidant power of foods is measured in ORAC units (Oxygen Radical Absorbance Capacity), which indicate the total amount of a food’s antioxidant capacity. High ORAC values indicate greater antioxidant capacity. High-ORAC foods may therefore protect cells from oxidative damage.

Two studies have shown that eating high-ORAC fruits and vegetables (or doubling the intake of fruits and vegetables) elevates the antioxidant capacity of the blood 13-25% (see Jrnl of Clinical Nutrition 68: 1081-87).

When ORAC values for 40 fruits and vegetables were measured by the USDA’s Agricultural Research Service at its Human Nutrition Research Center on Aging (HNRCA) at Tufts University, fresh blueberries scored the near the top, having 2,400 ORAC units per 100 grams (3.5 ounces).

Serum levels of anthocyanins found in blueberries have been shown to rise significantly after ingestion of freeze-dried blueberry powder and correlate with an increase in serum antioxidant capacity as measured in ORAC units (Mazza et al., Jrnl of Agricultural and Food Chemistry 50 (26): 7731-37; 2002)

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.

RASPBERRIES

Raspberries (and blackberries) belong to the rose family (Rosaceae). The red raspberry was first cultivated in Europe about 400 years ago. There are several varieties native to North America, including a black raspberry native to southern states (that has been crossed with European varieties) and a red raspberry (Rubus idaeus) from which originate most commercially grown varieties.

Raspberries contain anthocyanins, fiber (including the cholesterol lowering soluble form pectin), phytochemicals (ellagic acid, coumaric acid, ferulic acid), calcium, and vitamins A, C, and E. Ellagic acid is known to be antiviral, antibacterial, anticarcinogenic, and antimutagenic. It has been shown to inhibit the mutation of cells and to prevent the binding of carcinogens to DNA.

Raspberries have 1,220 ORAC units per 100 grams (3.5 ounces), among the highest of the forty fruits and vegetables tested by the USDA.

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 strawberries protect the brain from oxidative stress and may therefore reduce age-related cognitive decline in brain function.

CELL PROTECTIVE ORGANIC & WILDCRAFTED HERBS AND ANTIOXIDANTS

ORGANIC ASTRAGALUS POWDER (200 mg)

Astragalus is derived from the root of a plant (Astragalus membranaceus) in the pea family. It is an adaptogen, meaning it has a balancing effect on bodily functions. Astragalus is often used to strengthen or tone the body’s overall vitality, improve digestion, and support the spleen. Studies confirm it contains biologically active compounds, including a polysaccharide that stimulates the immune system.

ORGANIC BURDOCK ROOT (200 mg per serving)

Burdock root is one of the foremost cleansing herbs, providing nourishing support for the blood, the liver, and the natural defense system. It is rich in Vitamins B1, B6, B12, and E, as well as manganese, copper, iron, zinc, sulfur, and more. Burdock root is often found in tonic formulas and special blends designed for internal cleansing.

In traditional herbal texts, Burdock root is described as a “blood purifier” or “alterative” and was believed to clear the bloodstream of toxins. During the industrial revolution, Burdock was used as a medicine to help people cope with the increasing environmental pollution.

Burdock root has been used both internally and externally for eczema and psoriasis, as well as to treat painful joints and as a diuretic. In traditional Chinese medicine, burdock root, in combination with other herbs, is used to treat sore throats, tonsillitis, colds, and even measles. It is eaten as a vegetable in Japan and elsewhere. Burdock is a mild laxative. It also aids in the elimination of uric acid. The herb contains polyacetylenes that have both anti-bacterial and anti-fungal properties.

ORGANIC TURMERIC ROOT POWDER (150 mg per serving)

Turmeric, a polyphenol, contains substances called curcuminoids that are powerful antioxidants, pain relievers, and anti-inflammatories. Curcuminoids have been shown to exhibit antibacterial activity.

ORGANIC GINGER ROOT (150 mg per serving)

Ginger rhizome (Zingiber officinale) is an incredibly active and effective gastrointestinal aid with the following properties: 1) Contains a digestive enzyme whose effectiveness even exceeds that of papain; 2) Stimulates the flow of saliva and increases the concentration of the digestive enzyme amylase in the saliva; and 3) Activates peristalsis and increases intestinal muscle tone. Ginger is also known to be helpful in cases of nausea.

N-ACETYL-L-CYSTEINE (NAC) (100 mg per serving)

NAC is a powerful free radical scavenger. A majority of orally ingested NAC rapidly undergoes deacetylation to form L-cysteine, which is necessary for glutathione production. NAC, therefore, has powerful implications for immune function and increasing the body’s free-radical trapping capacity.

NAC’s effectiveness in treating patients with acetaminophen overdose is well documented. NAC has been used with good results in treatment of respiratory illness and diseases such as chronic bronchitis and chronic obstructive pulmonary disease. Additionally, NAC has well-known antimucolytic properties, and has been shown to increase mucociliary transport in lungs.

k-RUTIN™ (100 mg per serving)

Rutin (quercetin-3-rutinoside) is a glycoside of the flavonoid quercetin. The chemical structure of rutin and quercetin consequently are very similar. Indeed, both rutin and quercetin are used in many countries as medications for blood vessel protection, and both are found as ingredients in numerous nutritional supplement preparations and herbal remedies.

k-Rutin™ is an alkalinized form of rutin having greater solubility than the rutin included in traditional nutritional supplements. That is, based on laboratory studies, it is a more soluble anthocyanin moiety (functional group) than rutin.

RECOGNIZED HEALTH BENEFITS OF RUTIN

• Rutin inhibits platelet aggregation and decreases capillary permeability, which thins blood and improves circulation

• Rutin exerts anti-inflammatory activity

• Rutin inhibits aldose reductase activity. Aldose reductase is an enzyme normally present in the eye and elsewhere in the body. It helps change glucose into a sugar alcohol called sorbitol that is associated with cataract formation

• Rutin strengthens capillaries. It therefore can reduce symptoms of capillary- and circulatory-related health conditions, including hemophilia. It also may help prevent common venous edemas of legs and feet.

• Rutin can reduce cytotoxicity of oxidized LDL cholesterol and reduce the risk of heart disease

• Evidence indicates rutin can be used to treat hemorrhoids, varicosis, and microangiopathy

• Rutin acts as an antioxidant. A study of the superoxide anion scavenging activity of rutin and six other flavonoids (including quercetin, morin, acacetin, hispidulin, hesperidin, and naringin) showed rutin had the strongest scavenging activity.

• Rutin provides essential support molecules for Vitamin C absorption and helps prevent breakdown of Vitamin C in the body before it is metabolized

• Rutin is believed to stabilize the collagen matrix by preventing free-radical damage, thereby helping to maintain the health of the body’s collagen

Rutin is a flavonoid (or bioflavonoid) within a class of flavonoids that includes hesperidin, quercetin, eriodictyl, and citron. Rutin is essential for the absorption of Vitamin C.

While rutin in nature is found in many nutritious foods (e.g., citrus, red apples, teas, broccoli, onions), it is easily taken in supplement form. This is especially important because the body cannot produce flavonoids. They must be supplied through diet (and it is prudent to take them in supplemental form in order to maximize health).

Flavonoids boost the effectiveness of Vitamin C, improve eye health, strengthen capillaries, reduce cholesterol, improve blood circulation, and act as antioxidants. Recent studies indicate flavonoids may be a significant factor in guarding the body against infections and major illnesses.

MILK THISTLE EXTRACT (STANDARDIZED TO GREATER THAN 82% SILYMARIN) (100 mg per serving)

Extensive research has shown that silymarin – the major component of milk thistle extract – exerts both a protective and restorative effect on the liver and is able to stimulate the growth of new liver cells to replace old damaged cells.

GREEN TEA EXTRACT (STANDARDIZED TO GREATER THAN 95% POLYPHENOLS & GREATER THAN 55% EGCG) (100 mg per serving)

Green tea extract is used primarily for its free radical fighting capabilities. Its key ingredient, epigallocatechin gallate (EGCG), protects against digestive and respiratory infections. It helps block the tumor-promoting actions of carcinogens, ultraviolet light, and metastasis from an original site in the skin, stomach, small intestine, liver or lung. EGCG also reduces platelet aggregation about as much as aspirin.

Green tea is very effective in inhibiting pathogenic bacteria that cause food poisoning and increases levels of friendly intestinal bacteria. It also blocks the attachment of the bacteria associated with dental caries to the teeth.

ORGANIC LICORICE ROOT (100 mg per serving)

Licorice is a moist, soothing herb that is anti-inflammatory and expectorant, controls coughing and has hormonal and laxative effects. It is further used to prevent liver toxicity and to treat tuberculosis and adreno-corticoid insufficiency.

Licorice contains flavonoids, isoflavonoids, chalcones, and triterpene saponins, with the main being glycyrrhetinic acid with 24-hydroxyglycyrrhetinic acid (which is 100 times sweeter than sugar).

Licorice is used internally for asthma, bronchitis, coughs, peptic ulcer, arthritis, allergic complaints and after steroid therapy. It is said to accelerate the healing of peptic ulcers and is used in cases of adreno-corticoid insufficiency. It is also used in Chinese medicine to revitalize the heart and treat palpitations, boosting the spleen, for coughing and wheezing, as well as detoxifying the body and digestive system.

ORGANIC DANDELION ROOT POWDER (100 mg per serving)

Dandelion root enhances the flow of bile, improving such conditions as liver congestion, bile duct inflammation, hepatitis, gallstones, and jaundice.

ORGANIC NOVA SCOTIA DULSE (100 mg per serving)

The dulse in Rejuvenate! Berries & Herbs is hand-harvested, low-temperature sun-dried, and immediately milled into a fine powder. The entire harvesting and handling process follows strict organic standards to eliminate possible processing contamination. Analytical testing shows that our dulse contains approximately 30% minerals including over 30 minerals (includes many trace minerals).

ORGANIC ICELANDIC KELP (100 mg per serving)

The milled kelp (Laminaria digitata) in Rejuvenate! Berries & Herbs grows deep in the cold subtidal waters of northwestern Iceland. This kelp is the only commercially available kelp that is sustainably harvested, dried, milled and bagged following the organic standards of Quality Assurance International. It is also an excellent source of organic iodine.

RHODIOLA ROSEA ROOT (STANDARDIZED TO GREATER THAN 3% ROSAVINS) (100 mg per serving)

Rhodiola rosea (aka “Arctic root”) is categorized as an adaptogen due to its observed ability to increase resistance to a variety of chemical, biological, and physical stressors. It has a reputation for stimulating the nervous system, improving depression, enhancing work performance, improving sleep, eliminating fatigue, and preventing high altitude sickness.

Rhodiola species contain a range of antioxidant compounds, including p-tyrosol, organic acids (gallic acid, caffeic acid, and chlorogenic acid), and flavonoids (catechins and proanthocyanidins).

The adaptogenic properties, cardiopulmonary protective effects, and central nervous system activities of Rhodiola rosea have been attributed primarily to its ability to influence levels and activity of biogenic monoamines such as serotonin, dopamine, and norepinephrine in the cerebral cortex, brain stem, and hypothalamus.

ALPHA-LIPOIC ACID (75 mg per serving)

Alpha lipoic acid is normally made in the human body, where it functions primarily as an important metabolic nutrient. As such, it plays a crucial role in the metabolism of both fats and carbohydrates into energy. In addition, lipoic acid functions as an extremely powerful antioxidant capable of trapping many different types of free radicals in the body.

Because it is both water and fat soluble, lipoic acid can operate in a broader range of body tissues than most other antioxidants. Its small size allows lipoic acid to enter areas of the body not easily accessible to many other substances; this allows lipoic acid, for example, to enter the cell nucleus and prevent free-radical damage to DNA.

Because it is such a powerful antioxidant and can easily function and exist in both a reduced and oxidized state, lipoic acid can protect other important antioxidants such as glutathione, Vitamin E, and Vitamin C. Lipoic acid is also able to chelate heavy metals such as lead, cadmium, mercury, free iron, and free copper out of the body.

BIOVIN™ HIGH OPC GRAPE EXTRACT (PULP, SKIN, AND SEED) (50 mg per serving)

The BioVin™ grape extract in Rejuvenate! Berries & Herbs is extracted by ethanol and water and contains the highest percentage of OPCs of any product on the market. OPCs, a class of bioflavonoids, are one of nature’s most powerful free-radical scavengers.

As bioflavonoids, OPCs help to increase the effectiveness of Vitamin C. OPCs cross the blood-brain barrier to provide antioxidant protection to central nervous system tissue.

Studies have clearly demonstrated that OPCs improve and normalize capillary activity, strengthening capillary walls. OPCs bind to collagen fibers, realigning them in the process to a more youthful, undamaged structure. Elasticity, flexibility, and strength are thereby restored to connective tissue.

IMMUNE-ASSIST™ (40 mg per serving)

A combination of more than 200 different polysaccharides, derived from the enzymatic breakdown of complex organic plant material from six different species of medicinal mushrooms.

These mushrooms include Agaricus blazei, Cordyceps sinensis hybrid, Lentinula edodes, Grifola frondosa, Ganoderma lucidum, andCoriolus versicolor. Immune-Assist™ is made in the US using only USDA Certified Organic materials.

Immune-Assist is similar to other mushroom based polysaccharides in that it is formulated through an enzymatically activated process whereby complex cross-linked polysaccharides from vegetable sources are converted to biologically active immunomodulators composed of simpler sugars such as arabinose and xylose.

Immune-Assist™ does contain simple polysaccharides, but it also contains much more complex polysaccharides, including cross-linked beta mannans and beta-glucans, and hetero-polysaccharides which combine both alpha- and beta-bound monosaccharides in the same molecule. These complex polysaccharide compounds are not found in earlier-generation bran-based supplements like AHCC. This is the reason that Immune-Assist™shows such a greater range of immuno-modulation bioactivity than any other bran-based supplements.

Immune-Assist™ not only contains arabinoxylane, but also lentinan, grifolan (Dr. Nanba’s original Maitake D-Fraction), PSK and PSP, and active hemicellulose correlated compound (AHCC).

TRANS-RESVERATROL (FROM POLYGONUM CUSPIDATUM) (10 mg per serving)

Trans-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 agents, anticarcinogenic 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.

GERMANIUM SESQUIOXIDE (15 mg per serving)

Germanium sesquioxide shows considerable promise in immune support by boosting levels of gamma interferon in a dose dependant fashion. Studies indicate that germanium sesquioxide may be effective in combating certain viral and malignant conditions. Other studies suggest benefits toward free radical damage, cataracts, hypertension, and osteoporosis.

SELENIUM (from L-SELENOMETHIONINE) (25 mcg per serving)

Selenium is a trace mineral required in the body. Its primary function is carried out in the form of selenomethionine, which is incorporated into four active sites of the enzyme glutathione peroxidase. This enzyme protects the body against free-radical damage (especially when it occurs in cell membranes) caused by the oxidation of unsaturated fatty acids.

Selenium historically has been linked to Vitamin E because Vitamin E blocks the production of oxidized fatty acids in cell membranes. Selenium also appears to exert antioxidant activity by itself. Selenium is involved in the production and utilization of thyroid hormone, and it is antagonistic to heavy metals, including lead, mercury, aluminum, and cadmium.

According to a publication of the National Research Council (NRC), “One could reasonably suppose that selenium is involved [e.g., exerts a protective function] in such human medical problems as cataracts, diseases of the liver, cardiovascular or muscular diseases, and the aging process.” Selenium in its vital role in glutathione peroxidase affects all components of the immune system, including the development and function of all white blood cells.

HIGH PROTEIN GARDEN SPROUT BLEND (3,000 MG PER SERVING)

For thousands of years individuals have been using the healing power of vegetable sprouts. When a dormant seed begins to sprout, it enters a stage of tremendous vitality. Antioxidants and enzymes are produced that protect the developing plant and enable rapid growth.

Exciting new research has identified the role of glucosinolates and iosthiocyanates (classes of phytochemicals inherent in sprouts) that appear to positively influence metabolism in the human body.

Studies have suggested that sprout phytonutrients can promote the maintenance of healthy organs, healthy anti-inflammatory conditions, reduce the effects of toxins, and help to fight the effects of age-related free-radical activity.

The specific blend of sprouts used in Rejuvenate! Berries & Herbs was chosen to provide all of the above benefits while also yielding a blend with greater than 65% protein. Included in this blend are pea protein, quinoa sprouts, broccoli sprouts, alfalfa sprouts, daikon radish sprouts, red clover sprouts, and natural vanilla favor.

BROWN RICE PROTEIN (NON-GMO) (9,000 MG PER SERVING)

The rice protein in Rejuvenate! Berries & Herbs is extracted using a proprietary enzyme process starting from non-genetically modified rice. Our rice protein is processed without the use of acids, bases or other chemicals. In addition, the protein content of the extracted product is over 70%. That is substantially higher than other extraction methods (less than 53%) that leave a much higher percentage of carbohydrate in the end product. The protein of brown rice contains all of the essential amino acids, but it is somewhat low in the amino acid lysine. For this reason we have added supplemental lysine (400 mg/serving) to the formula.

FLAXSEED POWDER (3,000 MG PER SERVING)

Flax seeds (Linum usitatissimum L.) contain essential fatty acids (an excellent vegetarian source of omega-3 alpha-linolenic acid), protein, soluble fiber, insoluble fiber, antioxidant lignans, minerals, and vitamins. Lignans are a phytoestrogens considered to be antioxidants. Flax seeds contain among the highest levels of lignans among all plant foods.

Whole flax seeds are an excellent nutritional food. However, whole flax seeds can be difficult to digest and its nutrients typically are poorly absorbed. Flax seeds contain natural enzyme inhibitors that prevent digestion. This natural protective mechanism means that a seed may be eaten, pass through the body, and still grow into a plant (i.e., completely surviving the digestive process!).

Milling or grinding the seeds does not decrease natural enzyme inhibitors that reduce the bioavailability of flax. Only sprouting decreases natural inhibitors that otherwise will prevent complete digestion, absorption, and assimilation of flax seeds.

Flaxseed Powder provides an ideal solution to maximize health benefits of flax seeds. The process of germination fundamentally changes nutrient composition of the seed.

Nutrients including enzymes, amino acids, and vitamins substantially increase and become more bioavailable. This allows for better availability and absorption of these nutrients in the body. For example, sprouting flaxseed doubles antioxidant (ORAC) value. In addition, “anti-nutrients” such as phytic acid, enzyme inhibitors, and insoluble fibers all decrease. This further increases bioavailability and nutrient absorption of flax, and thereby boosting the health benefits attainable from consuming it.

The flaxseed powder in Rejuvenate! Berries & Herbs contain oil amounts varying between 38–45%, with the oil offering a high percentage (47–53%) of the omega-3 alpha-linolenic acid (ALA) and 15–18% omega-6 linoleic acid.

Alpha-linolenic acid (ALA) is an essential fatty acid acting in the human body as a substratum for the transformation into EPA and DHA through the action of desaturation and elongation enzymes. The seeds also contain some omega-6 essential fatty acids and exhibit a favorable omega-3 to omega-6 ratio of 3:1. Modern diets contain too few omega-3 fatty acids.

Flaxseed powder possess 15–30% protein (typically 20%) and the amino acids of flax protein have no limiting factors in the adult diet (i.e., they are a complete protein source having all of the essential amino acids in an appropriate balance). Flax seeds are also a source of magnesium, calcium, potassium, phosphorus, zinc, and copper. They also have demonstrated antioxidant activity. The most important antioxidants they provide are phytoestrogens known as lignans.

The human body easily digests flax seeds. The seed’s outer layer is rich in mucilloid soluble fiber (flax seed possesses 10–15% soluble fiber) and absorbs at least four times its weight in water. When mixed with water or stomach juices, the seeds form a gel that creates a physical barrier between the carbohydrates and the digestive enzymes that break them down. The carbohydrates thereby are digested and converted into glucose (blood sugar) at a slow, uniform rate. There is no insulin surge or spike needed to lower the blood sugar level. The water-retaining capacity of the gel also maintains bodily hydration (i.e., helping level out water intake) and electrolyte balance.

ORGANIC HEMP PROTEIN POWDER WITH FIBER (3,000 MG PER SERVING)

We have chosen to include certified organic hemp protein with fiber in Rejuvenate! Berries & Herbs. This raw whole food protein powder is rich in complete protein, branch chain amino acids, omega 3 and 6 essential fatty acids and healthy dietary fiber. Our certified organic hemp protein powder is cold milled from certified organic hemp seed and contains contains 37% protein, 43% fiber and 10% fat. The product contains no genetically modified organisms, no additives or preservatives, no THC, and is kosher certified.

A MULTIVITAMIN WITH COENZYME B-COMPLEX

We have added the following vitamins to the formula: Vitamin C (250 mg), Vitamin E as d-alpha tocopheryl succinate (90 IU) and high gamma mixed tocopherols (25 mg), Vitamin D3 (1,000 IU), Vitamin K1 (0.5 mg), inositol (100 mg), choline (50 mg), calcium pantothenate (30 mg), niacinamide (60 mg), pantethine (13 mg), pyridoxal-5′-phosphate (10 mg), thiamin diphosphate (7.5 mg), riboflavin-5′-phosphate (6.8 mg), calcium folinate (1 mg), biotin (0.9 mg), and methylcobalamin (0.2 mg).

While coenzyme vitamins usually cost significantly more than the synthesized vitamins (up to 50 times more), they remain quite affordable because they are only required by the body in very small amounts. That is, the body only needs small amounts because there are no in vivo losses related to any conversion processes. We therefore include coenzyme form vitamins in Rejuvenate! Berries & Herbs in quantities helpful to the body.

The inclusion of coenyzme forms of vitamins significantly contributes to making our supplement formulas more effective than if we used conventional (i.e., non-coenzyme form) vitamins. Moreover, it increases effectiveness without substantially raising our costs. Thus, the benefits considerably outweigh the costs, especially for individuals who consume our formulas, thereby reaping the benefits coenzyme vitamins offer for human health and well being.

ENZYMES TO ENHANCE NUTRIENT UTILIZATION

The complexity and significant amounts of proteins and peptides found in Rejuvenate! Berries & Herbs requires the combination of multiple proteases to optimize digestion. Proteins are made up of over twenty different amino acids, with each combination presenting different characteristics. Each of the proteolytic enzymes in Rejuvenate! Berries & Herbs offers different abilities to break the chemical bonds found in the proteins. However, the combination of enyzmes shows the greatest rate of hydrolysis.

Peptidase breaks amino acids off the ends of the peptide chain. Our proprietary enzyme complex contains both amino-peptidase and carboxy-peptidase activities, and therefore it can remove amino acids from both ends of the peptide chain. Protease 4.5 breaks bonds at points within the peptide chain dependent upon their bond specificities. Significant action of this enzyme has been seen both in the laboratory and in digestive product usage. Protease 4.5 has an optimal pH of 4.5 (pH range 2.0 to 6.0). Protease 6.0 has an optimal pH of 6.0 (pH range 4.0 to 11.0). Together these proteases provide proteolytic action throughout the human digestive system.

Because Rejuvenate! Berries & Herbs contains a large amount of plant-based ingredients, we have added the enzyme cellulase to the formula. Cellulase offers distinct advantages for individuals consuming large amounts of vegetable matter. This enzyme hydrolyzes the bonds in various fibers. Cellulase hydrolyzes glucose-glucose bonds in cellulose. By disrupting the structure of the fiber matrices that envelop most of the nutrients in plants, cellulase increases the nutritional value of fruits and vegetables.

PREBIOTICS AND TASTE ENHANCERS

Rejuvenate! Berries & Herbs includes inulin (from chicory root), xylitol (from organic hardwoods), mannitol (a powerful superoxide free-radical trapper), malic acid (a Krebs cycle intermediate), organic mixed berry flavoring, organic vanilla flavoring, and stevia leaf extract. We include these ingredients in order to provide prebiotics, enhanced taste, and various health benefits.

ORGANIC ALOE VERA EXTRACT

We demand high-quality source materials containing the most biologically active and effective ingredients available. The aloe vera selected for Rejuvenate! Berries & Herbs meets our high standards. This aloe vera extract combines ground breaking research and state-of-the-art manufacturing to preserve and enhance aloe vera’s natural benefits in the form of ACTIValoe™, a standardized certified organic Aloe vera with 10% total polysaccharides by weight.

The purity and quality of ACTIValoe™ is verified by scientific analysis (i.e., Proton NMR Analysis, HPLC, SEC, etc.) and is certified by the International Aloe Science Council for its content and purity. Furthermore, ACTIValoe™ is guaranteed to retain biological activity to help deliver the healing properties of Aloe vera.

Biologically active aloe is believed to reduce severe joint and muscle pain associated with arthritis, as well as pain related to tendinitis and injuries. When applied directly to the area of pain, aloe vera penetrates the skin to soothe the pain. Studies have also found that ingestion of biologically active aloe on a daily basis can help prevent and cause a regression of adjutant arthritis.

Aloe vera extract can relieve gastrointestinal problems and may be one of the plant’s most ancient uses. Even today, people consume aloe vera to help relieve ulcerous, gastrointestinal and kidney problems. People have described improved regularity, greater intestinal comfort and enhanced energy levels after ingesting biologically active aloe vera. In addition, many who have suffered from indigestion, irritable bowel syndrome, increased stomach acid, peptic and duodenal ulcers, and colitis report relief from these conditions following ingestion of aloe vera.

Coronary heart disease is one of the major causes of death in the US. However, studies suggest that the ingestion of aloe vera may have a beneficial effect on the accumulation of blood fat lipids associated with the disease.

Test groups given aloe vera showed a decrease in total cholesterol, triglyceride, phospholipid, and nonesterified fatty acid levels, each of which, when elevated, seem to accelerate the accumulation of fatty material in large and medium-sized arteries, including the coronary arteries of the heart.

REJUVENATE!™ BERRIES & HERBS CONTAINS THESE INGREDIENTS FOUND IN HPDI’S REJUVENATE! (ORIGINAL) FORMULA

CHLORELLA GROWTH FACTOR (CGF) (200 MG PER SERVING)

In the early 1950s, the Japanese researcher Fujimaki separated a previously undiscovered substance from a hot-water extract of chlorella that is now known as “Chlorella Growth Factor” (CGF). CGF is a nucleotide-peptide complex comprised mostly of nucleic acid derivatives.

The sugars identified in the nucleotide include glucose, mannose, rhamnose, arabinose, galactose, and xylose. Amino acids found in the peptide include glutamine, alanine, serine, glycine, proline, asparagine, threonine, lysine, cysteine, tyrosine, and leucine.

It is known that CGF is produced during intense photosynthesis and enables chlorella to grow extremely rapidly. During this process, a single cell may multiply into four daughter cells as rapidly as every 20 hours. CGF not only promotes this rate of reproduction, but also is itself rapidly increased.

In Japan, Dr. Yoshiro Takechi showed that CGF stimulates lactobaccilus (the “good” bacteria) to grow at four times the usual rate. Experiments with microorganisms, young animals, and children have demonstrated that CGF promotes faster than normal growth. In adults and mature organisms, CGF appears to enhance the functions of nucleic acids at the cellular level that relate to the production of proteins, enzymes, and energy, as well as to stimulate tissue repair and offer protection against toxic substances at the cellular level.

D-RIBOSE (2,000 MG PER SERVING)

D-Ribose (ribose) is a sweet, crystalline, water-soluble powder. It is a naturally occurring 5-carbon sugar found in all living cells. Ribose is a component of RNA and therefore essential for living creatures. It is also a component of ATP, NADH, and other metabolism-related substances.

The biological importance of ribose relates to the fact that it is the rate-limiting compound that regulates the activity of the purine nucleotide pathway of adenine nucleotide metabolism. As such, ribose plays a central role in the synthesis of ATP, coenzyme-A, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), DNA, RNA, and other important cellular constituents.

Ribose is the only known compound the body can use for performing this critical metabolic function. Specifically, ribose administration bypasses the slow and rate-limited pentose phosphate pathway to stimulate adenine nucleotide synthesis and salvage in vivo. In addition, it has been shown that de novo adenine nucleotide synthesis in skeletal muscle is rate limited by the availability of ribose.

D-ribose is commonly found in foods, especially foods high in RNA (ribonucleic acid), such as brewer’s yeast. D-ribose is essential for life and can be made by the body (e.g., from glucose). However, d-ribose from food sources can significantly boost the amount of ribose available to the body, thereby enhancing processes that utilize it.

Ribose derivatives play a significant role in the body. Important ribose derivatives encompass those having phosphate groups attached at the 5 position, including mono-, di-, and triphosphate forms, and 3-5 cyclic monophosphates. Diphosphate dimers, known as coenzymes, form an essential class of compounds with ribose. When such purine and pyrimidine derivatives are coupled with ribose, they are known as nucleosides(bases attached to ribose). Phosphorylated nucleosides are known as nucleotides. When adenine (a purine derivative) is coupled to ribose it is known as adenosine. ATP is the 5′-triphosphate derivative of adenosine. (The adenine portion of ATP consists of ribose and adenine. The triphosphate portion of ATP consists of three phosphate molecules.)

Ribose therefore is found in many important biological molecules, including adenosine triphosphate (ATP), nucleotides and nucleotide enzymes, and in RNA. D-ribose (as ribonucleoside diphosphates) notably converts to deoxyribonucleoside diphosphates, precursor molecules for DNA.

Ribose generates adenosine triphosphate (ATP) in the body. Supplemental ribose increases the rate at which ATP is generated, thereby improving exercise performance and enabling faster muscle growth. This is possible because supplemental ribose enables the body to bypass the conversion steps needed to create or re-create the adenosine nucleotide. Replacing adenine nucleotides normally takes time for the body to accomplish, and this process can reduce the rate of healing and repair (e.g., of muscle fibers). Supplemental ribose essentially increases the speed at which adenosine nucleotides can be replaced by providing raw material for the creation of more ATP.

Ribose similarly has been shown to boost synthesis and salvage of other nucleotides in the body, including those found in heart and skeletal muscle. Supplemental ribose again bypasses the rate-limiting conversion processes (i.e., of the pentose phosphate pathway), thereby speeding syntheses of nucleotides that provide energy to these tissues.

RIBOSE AS A SIGNIFICANT COMPONENT OF NUCLEIC ACIDS

Nucleotides are the molecular building blocks of DNA and RNA. They are chemical compounds consisting of a heterocyclic base, a 5-carbon sugar (ribose or deoxyribose) and at least one phosphate group. They are the monomers of nucleic acids, and 3 or more can bond together to form a nucleic acid.

Nucleosides are glycosylamines consisting of a base (or nucleobase) to a ribose (or deoxyribose) ring. Some nucleosides are cytidine, adenosine, guanosine, and inosine. When nucleosides are phosphorylated in cells, they produce nucleotides (see above).

Given the importance of ribose as an essential part of nucleic acids, nucleotides, nucleosides, its role in the production of energy (as ATP), and its ability to increase synthesis and salvage of nucleotides in the body, the inclusion of ribose in a formula designed to provide high levels of nucleic acids appears especially appropriate.

NUTRITIONAL YEAST (1,500 MG PER SERVING)

Nutritional yeast belongs to the same family of organisms as edible mushrooms. It may be considered man’s oldest industrial micro-organism. For more than 50 years, our supplier has been manufacturing primary grown nutritional yeast (Saccharomyces cerevisiae), grown specifically for its nutritional value. After the fermentation process is completed the yeast is harvested, thoroughly washed, pasteurized, and dried on roller drum dryers. The special growth medium and unique drying process are the secrets to the exceptional performance of the nutritional yeast in our product.

The result is a high-quality non-GMO product containing protein (approximately 48%) composed of essential and non-essential amino acids, dietary fiber, B-complex vitamins, and minerals such as selenium, chromium, potassium, magnesium, sodium, copper, manganese, iron, and zinc.

Nutritional yeast is extraordinarily rich in nucleic acids. In fact, nutritional yeast contains approximately 6% RNA among the highest of known foods.

In Dr. Frank’s protocols described in his book Nucleic Acid Nutrition and Therapy he used both nutritional yeast and high RNA extracts of nutritional yeast to obtain healing and regeneration.

Furthermore, nutritional yeast contains additional functional and beneficial components such as beta-1,3 glucan, trehalose, mannan and glutathione. Studies have show that these components have potential health benefits such as, improved immune response, normalization of cholesterol, and cellular normalization properties.

RICE BRAN SOLUBLES (2,000 MG PER SERVING)

Rice bran solubles are one of the most nutrient-dense superfoods available today. They derive entirely from rice. Specifically, they are a highly concentrated soluble carbohydrate and lipid-rich component of stabilized rice bran (i.e., a non-chemically modified water-soluble fraction). They are also a complete, great-tasting, natural source of B-complex vitamins (i.e., thiamin, niacin, vitamin B6) and contain many other nutrients, including amino acids, antioxidants, essential fatty acids, and phytonutrients, rice bran solubles are one of the world’s perfect whole foods, lacking only a few trace minerals.

In fact, our non-GMO rice bran solubles product offers at least 29 vitamins and minerals, and more than 90 antioxidants. Among these are lipoic acid (useful in blood glucose control), tocopherols, and tocotrienols (which may have a positive effect on cholesterol levels).

Alpha tocotrienol has been shown to provide up to fifty times more antioxidant power than alpha tocopherol. Rice bran solubles also contain essential fatty acids, including phospholipids, gamma oryzanol, ferulic acid, and phytosterols.

Certain antioxidants in rice bran solubles are documented as supportive in retarding the aging process and combating fee radicals. They strengthen the body’s ability to regenerate and increase energy and stamina.

Our producer of the stabilized brown rice bran in Rejuvenate! Berries & Herbs utilizes a process that reliably inactivates the lipase in rice bran while retaining the rest of the food’s chemistry. This is done with a mechanical extrusion process that forces the grain to deform as it squeezes through small openings in a metal die. The high rate of deformation during extrusion causes just the right amount of internal heating for the precise amount of time needed to inactivate the lipase. The result is a stabilized rice bran product that retains most of the vital nutrients of fresh rice bran, but has a shelf life measured in years rather than hours.

KEY NUTRITIONAL ELEMENTS IN RICE BRAN SOLUBLES

• Gamma oryzanol, beta sitosteryl ferulate, and five other related compounds. These are potent antioxidants and trace nutrients that play a vital role in many aspects of human physiology. Gamma oryzanol is found only in rice bran and has been used successfully in dealing with female hormone imbalances.
 Tocopherols and Tocotrienols – These include all of the eight known forms of Vitamin E including d-alpha tocopherol. The importance of the other forms is probably at least equal to the alpha form.

• Polyphenols, including ferulic acid, alpha-lipoic acid, and four other polyphenols. Lipoic acid plays an important role in sugar metabolism at the cellular level and is a powerful antioxidant. Ferulic acid also is a powerful antioxidant.

• Important minerals magnesium, calcium, and phosphorous, as well as manganese and other trace minerals. Minerals are involved in all of the enzyme functions of the body including those involved in energy production.

• Phytosterols, including beta sitosterol, campesterol, stigmasterol, and at least eleven more. Phytosterols have been shown to prevent the absorption of cholesterol, support healthy prostate function, and help to build immune function.

• Carotenoids, including beta-carotene, alpha carotene, lycopene, lutein, zeaxanthin, and more. Although beta-carotene is commonly sold as a single-ingredient supplement, alpha-carotene may in fact be more important. Lycopene is responsible for some of the recent health claims relating to tomatoes, and lutein and zeaxanthin play key roles in retinal function.

• Essential amino acids including tryptophan, histidine, methionine, cysteine, cystine, and arginine. Amino acids are the body’s basic materials for building all of its enzymes, DNA, RNA, and connective tissue.

• Nine B vitamins supporting the body’s metabolic machinery, polysaccharides (known among other functions to support immunity), and phospholipids. Phospholipids are vital to maintaining healthy cell membranes.

• Lecithin, which provides the important phospholipids phosphatidyl choline and phosphatidyl serine.

• Seven identified enzymes, including coenzyme Q10 and superoxide dismutase (an important antioxidant).

HIGH PHOSPHATIDE LECITHIN (98%OIL FREE, NON-GMO, FROM SUNFLOWER SEEDS) (1,500 MG PER SERVING)

In recent years, there is renewed interest in the health benefits and dietary requirements of lecithin. Growing evidence now suggests that dietary lecithin is important preventing many pathologic conditions. Lecithin is used as a dietary supplement for purpose of treating or preventing several human diseases, including cirrhosis of the liver, arteriosclerosis, and certain deficiencies of brain function and memory. In fact, the most recent research has shown that lecithin is an essential dietary component for ensuring optimal nutrition.

Lecithin and its component phosphatidyl choline are known to be essential for liver function. In fact, even a few weeks on a choline-deficient diet has been shown to cause abnormalities in liver function. Studies in primate models of alcohol-induced cirrhosis have shown that lecithin protects the body from alcohol liver damage. This is a particularly important finding because liver cirrhosis caused by excessive intake of alcohol is the fourth leading cause of death in people 25–64 years of age in the US.

Lecithin has also been shown to be essential for proper brain development in infants and children. Supplementing animal diets with lecithin at during specific times of brain development has been shown permanently to increase cognitive function.

MAGNESIUM

Magnesium is one of the most abundant, available metals on earth, and plays crucial roles in the sustenance of life and its chemical processes. The divalent nature of the magnesium cation makes it an ideal activator for enzyme systems. Estimates for its usage in human body systems include over fifty different biochemical reactions and its necessary presence for the operation of over 300 enzymes.

Magnesium is essential for energy production, maintenance of electrolyte balance, and neuromuscular function. Investigations into rates of magnesium deficiency show that individuals in developed countries are at remarkably high risk for magnesium deficiency.

The suspected primary cause of this risk for deficiency are inadequate, depleted diets that are high in processed foods (from which magnesium is removed but not replaced).

There are several nutritional requirements in the body in order for mitochondria to manufacture ATP. These essential nutrients include oxygen, magnesium, food substrate, ADP, and inorganic phosphate, as well as Vitamin B1, Vitamin B2, and Vitamin B6 in their phosphorylated coenzyme forms.

The body also needs adequate stores of malate (an important Krebs cycle intermediate) in order for most of these nutrients to function effectively in the process of ATP production. When any of these nutrients are not present in adequate amounts within the mitochondria, a vicious cycle can occur in which ATP is not created in amounts sufficient for proper cellular functioning.

Insufficient amounts of ATP mean that the B vitamins may not be adequately phosphorylated leading to improper metabolism and further reductions in ATP production. The much less efficient anaerobic production of ATP will be utilized to a greater extent in such cases.

A balance point may be reached in which the body produces only a fraction of the optimal amount of ATP. Under these conditions muscle weakness and fatigue may occur.

Abraham and Flechas report that supplementing the diet with magnesium may reverse such conditions of low energy (Jrnl of Nutritional Medicine 3: 49-59).

For the above reasons, we have included magnesium in Rejuvenate! Berries & Herbs from magnesium malate (providing both magnesium and malate) and magnesium ascorbate (providing additional magnesium as well as Vitamin C).

DULSE

Dulse is a sea vegetable (i.e., seaweed) that is a rich source of iron, potassium, iodine, Vitamin B6, riboflavin, and dietary fiber. It provides a wide range of minerals, trace elements, enzymes and phytochemicals, as well as some high-quality vegetable protein. Our certified organic raw dulse is sustainably harvested from well-protected coastal passages and low temperature dried.

FOLINIC ACID

Folinic acid, also known as 5-formyl tetrahydrofolate, is one active form in a group of vitamins known as folates. In contrast to folic acid, a synthetic form of folate, folinic acid is one of the forms of folate found naturally in foods. Folate deficiency is believed to be the most common vitamin deficiency in the world due to food processing, food selection, and intestinal disorders. In the body folinic acid may be converted into any of the other active forms of folate.

Folate coenzymes are responsible for the following important metabolic functions: 1) Formation of purines and pyrimidines which, in turn, are needed for synthesis of the nucleic acids DNA and RNA. 2) Formation of heme, the iron-containing protein in hemoglobin, 3) Interconversion of the 3-carbon amino acid serine from the 2-carbon amino acid glycine, 4) Formation of the amino acids tyrosine from phenylalanine and glutamic acid from histidine, 5) Formation of the amino acid methionine from homocysteine (Vitamin B12 as methylcobalamin also is needed for this conversion). Elevated levels of homocysteine have been implicated in a wide range of health disorders. In the reconversion of homocysteine to methionine the body uses the methionine to make the important amino acid s-adenosylmethionine (SAMe) which is known to be helpful in cases of depression, 6) Synthesis of choline from ethanolamine, 7) Formation and maturation of red and white blood cells, and 8) Conversion of nicotinamide to N’-methylnicotinamide.

METHYLCOBALAMIN (COENZYME FORM OF VITAMIN B12)

Methylcobalamin is one of two coenzyme forms of B12 (along with adenosylcobalamin) and can be used directly by the body without metabolic conversion.

Vitamin B12 is involved in numerous important body functions, including: 1) Red blood cell formation and control of pernicious anemia, 2) The synthesis and function of nerve tissue, such as myelin, 3) The metabolism of carbohydrates, fats, and proteins (Vitamin B12 is necessary for the conversion of methylmalonate to succinic acid, an important Krebs cycle intermediate in energy production), 4) The synthesis or transfer of single carbon units (e.g., allowing the interconversion of serine and glycine and the conversion of homocysteine to methionine), 5) Serving as a coenzyme in the biosynthesis of methyl groups, and 6) Involvement in reactions that convert disulfides (S-S) to the important sulfhydryl group (S-H).

COMPOSITION

REJUVENATE!™ BERRIES & HERBS CONTAINS:

Rice Protein, Vegetable Sprouts Protein (65% protein – organic), Hemp Protein with fiber (37% protein – organic), Flaxseed Powder, Rice Bran Solubles, D-Ribose, Blueberry powder (organic freeze dried), Cranberry powder (freeze dried), Strawberry powder (organic freeze dried), Raspberry powder (organic freeze dried), Nutritional Yeast (brewers yeast), Lecithin (98% oil free, high phosphatide, non-GMO, from sunflower seeds), Xylitol (from organic hardwood), Mannitol, Inulin/fructooligosaccharides (chicory root), VitaBerry Plus, L-Lysine (USP grade), Vanilla Flavoring (organic), Mixed Berry Flavoring (organic), RNA from yeast, Vitamin C (from Mg ascorbate), Chlorella Growth Factor (CGF), Burdock Root (organic), Astragalus Root (organic), Turmeric (organic), Proprietary Enzyme Blend (Protease, Peptidase, Cellulase), Ginger Root (organic), L-Malic Acid, Rhodiola rosea (root) (3% rosavins), k-Rutin™, N-Acetyl-L-Cysteine, Milk Thistle Standardized Extract (82% silymarin), Licorice (root) (organic), Kelp (organic), Dulse (organic), Inositol, Green Tea Extract (95% polyphenols), Dandelion Root (organic), Aloe vera (ActivAloe 200:1 – organic), Vitamin E (d-alpha tocopheryl succinate), Magnesium (from Mg malate), Stevia Leaf Extract, Lipoic Acid, Vitamin B3 (niacinamide), BioVin® Grape Extract, Choline (from bitartrate), Immune-Assist (organic medicinal mushrooms), Pantothenic Acid, Vitamin E (high-gamma mixed tocopherols), Vitamin B5 Pantethine, Germanium Sesquioxide, Resveratrol (from polygonum cuspidatum), Vitamin B6 (Pyridoxal-5′-phosphate), Vitamin B2 (riboflavin-5′-phosphate), Vitamin B1 (thiamin diphosphate), Magnesium (from Mg ascorbate), Biotin, Folinic Acid (from calcium folinate), Vitamin K1 (as phylloquinone), Vitamin B12 (as methylcobalamin), Selenium (from l-Selenomethionine), and Vitamin D3 (cholecalciferol).

BERRIES & HERBS IS ONE OF THREE REJUVENATE! SUPERFOODS

There are three unique superfoods in the Rejuvenate! line. They are Rejuvenate! (Original), Rejuvenate! PLUS, and Rejuvenate! Berries & Herbs. A complete side-by-side comparison of these superfoods is available.

SOURCES & RESOURCES

REVIEWS

“Rejuvenate! Berries & Herbs is Rich in RNA, Plant Proteins” (by Mike Adams, the Health Ranger)

“Rejuvenate!™ PLUS Superfood is High in DNA and RA with Sprouts, Chlorella and More” (by Mike Adams)

“Superfood for Cellular Survival” (by Dr. Mark Sircus)

HPDI BLOG ARTICLES

“9 Things to Know About Rejuvenate!™ Superfoods”

“High-RNA Rejuvenate!™ Superfood”

“Rejuvenate! – The Original, High-RNA Superfood”

“The Amazing Healing Potential of Natural Nrf2 Activators”

Review of Scientific Research on Oligomeric Proanthocyanidins (OPC)

DIETARY NUCLEIC ACIDS – DR. BENJAMIN S. FRANK, PART 1

DIETARY NUCLEIC ACIDS – DR. BENJAMIN S. FRANK, PART 2

Super-Tasty Morning Nutritional Drinks

Superfood Bars with Rejuvenate! Berries & Herbs

BOOKS & JOURNAL ARTICLES

Dr. Frank’s No-Aging Diet: Eat and Grow Younger. Dial Press, 1976.

Nucleic Acid Nutrition and Therapy. Rainstone Publishing, 1977

Nucleic Acid and Anti Oxidant Therapy of Aging and Degeneration. Royal Health Books, 1977.

Nucleic Acid Therapy in Aging and Degenerative Disease–A Metabolic Approach with DNA, RNA, and Related Metabolites. Psychological Library, 1968.

The Problem of Age, Growth and Death. C.S. Minot. Putnam’s Sons, 1908.

“On the influence of nucleic acids of various origin upon the growth and longevity of the white mouse. ” T. Brailsford Robertson. Australian J. Exp Biol Med Sci, 1928, 5: 47–67.

“The effect of yeast nucleic acid on the survival time of 600 day old albino mice.” Thomas Gardner. J Gerontol, 1946, 1: 445–456

“Prolongation of the life span in rats.” Max Odens. J. American Geriatrics Soc., 1973, XXI: 450–451.

INTERVIEWS

Interview with Dr. Hank Liers, Part 1: Nutritional supplements and cellular energy

Interview with Dr. Hank Liers Part 2: High-RNA superfoods

Interview with Dr. Hank Liers Part 3: Chemical sensitivities and chlorella detoxification

Interview with Dr. Hank Liers Part 4: Reversing mass chemical contamination

Interview with Dr. Hank Liers Part 5: Superior nutrition for pet health

PRODUCTS

Rejuvenate! Berries & Herbs

Rejuvenate!™ PLUS

Rejuvenate!™ (Original)

Rejuvenate! Superfoods: Side-by-Side Comparison

Ultimate Protector™ Nrf2 Activator

HPDI FOUNDATIONAL SUPPLEMENTS

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

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ULTIMATE PROTECTOR INGREDIENTS – WILD BILBERRY AND WILD BLUEBERRY

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

Ultimate Protector contains wild bilberry and wild blueberry, 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 ingredients wild bilberry and wild blueberry, which are components of Anthocomplete™ and VitaBerry Plus® from Futureceuticals.

ANTHOCOMPLETE™

AnthoComplete™ (N669) is a specially designed blend of anthocyanins derived from wild bilberry and wild blueberry, acai, 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).

Bilberry / Blueberry wild bilberry and wild bluebery

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.

HEALTH BENEFITS OF WILD BILBERRY AND WILD BLUEBERRY

Bilberry is any of several Eurasian  species of low-growing shrubs in the genus Vaccinium, bearing edible, nearly black berries. The species most often referred to is Vaccinium myrtillus L., but there are several other closely related species. Bilberries are distinct from blueberries but closely related. Whereas the bilberry is native to Europe, the blueberry is native to North America.

The bilberry fruit is smaller than that of the blueberry, but with a fuller taste. Bilberries are darker in color, and usually appear near black with a slight shade of purple. While blueberry fruit pulp is light green in color, bilberry is red or purple, heavily staining the fingers, lips, and tongue of consumers eating the raw fruit. The color comes from diverse anthocyanins.

So-called wild (lowbush) blueberries, smaller than cultivated highbush ones, are prized for their intense color. “Wild” has been adopted as a marketing term for harvests of managed native stands of lowbush blueberries. The bushes are not planted or genetically manipulated, but they are pruned or burned every two years, and pests are “managed”. The content of polyphenols and anthocyanins in lowbush (wild) blueberries (V. angustifolium) exceeds values found in highbush cultivars.

wild bilberry and wild blueberry

Wild bilberry and wild blueberry (above) provide Nrf2 activators.

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

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

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

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

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

Scientific Studies on the Antioxidant Effects of Wild Bilberry and Wild Blueberry

Databases of scientific studies (like the National Institutes of Health (NIH) PubMed database) contain thousands of up-to-date studies and abstracts about various Vaccinium species, including wild bilberry and wild blueberry (V. myrtillis and V. angustfolium, respectively).

We provide a few relevant scientific studies on the antioxidant effects of wild bilberry and wild blueberry.

In vitro anticancer activity of fruit extracts from Vaccinium species.

From: http://www.ncbi.nlm.nih.gov/pubmed/8693031

Abstract

Fruit extracts of four Vaccinium species (lowbush blueberry, bilberry, cranberry, and lingonberry) were screened for anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA). The crude extracts, anthocyanin and proanthocyanidin fractions were not highly active in QR induction whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of lowbush blueberry, cranberry, lingonberry, and bilberry were 4.2, 3.7, 1.3, and 1.0 microgram tannic acid equivalents (TAE), respectively, Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07 microgram TAE). In contrast to their effects on QR, crude extracts of lowbush blueberry, cranberry, and lingonberry were active inhibitors of ODC activity. The concentrations of these crude extracts needed to inhibit ODC activity by 50% (designated IC50) were 8.0, 7.0, and 9.0 micrograms TAE, respectively. The greatest activity in these extracts appeared to be contained in the polymeric proanthocyanidin fractions of the lowbush blueberry, cranberry, and lingonberry fruits (IC50 = 3.0, 6.0, and 5.0 micrograms TAE, respectively). The anthocyanidin and ethyl acetate extracts of the four Vaccinium species were either inactive or relatively weak inhibitors of ODC activity. Thus, components of the hexane/chloroform fraction of bilberry and of the proanthocyanidin fraction of lowbush blueberry, cranberry, and lingonberry exhibit potential anticarcinogenic activity as evaluated by in vitro screening tests.

 

Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells.

From: http://www.ncbi.nlm.nih.gov/pubmed/17460300

Abstract

PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre- or posttranslational levels of oxidative stress defense enzymes heme-oxygenase (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal pigment epithelial (RPE) cells.

METHODS: Confluent ARPE-19 cells were preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25% enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal, cells were oxidatively challenged with H(2)O(2). The concentration of intracellular glutathione was measured by HPLC and free radical production determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and mRNA levels were determined by Western blot and RT-PCR, respectively.

RESULTS: Preincubation with bilberry extract ameliorated the intracellular increase of H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8- and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions contributed similarly to mRNA upregulation.

CONCLUSIONS: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and GST-pi in RPE, suggesting that they stimulate signal transduction pathways influencing genes controlled by the antioxidant response element.

 

Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism.

From: http://www.ncbi.nlm.nih.gov/pubmed/24565673

Abstract

The objectives of this study were to compare the anti-inflammatory effects of anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and to determine the relationship between their antioxidant capacity and anti-inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 μg/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1β (IL-1β) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 μg/ml or higher. Tumor necrosis factor α (TNFα) mRNA levels and secretion were also significantly decreased in LPS-treated macrophages. The levels of the repression were comparable for all berry anthocyanins. LPS-induced nuclear factor κB (NF-κB) p65 translocation to the nucleus was markedly attenuated by all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA significantly decreased cellular reactive oxygen species (ROS) levels with a concomitant decrease in IL-1β mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1β mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-κB independent of the NRF2-mediated pathways.

 

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

From: http://pubs.acs.org/doi/abs/10.1021/jf504926n

Abstract

The berries of bilberry and black currant are rich source of anthocyanins, which are thought to have favorable effects on non-alcoholic 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 the 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 mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.

 

Effect of blueberry on hepatic and immunological functions in mice.

From: http://www.ncbi.nlm.nih.gov/pubmed/20382588

Abstract

Background: Conventional drugs used in the treatment and prevention of liver diseases often have side effects, therefore research into natural substances are of significance. This study examined the effects of blueberry on liver protection and cellular immune functions.

METHODS: To determine the effects of blueberry on liver protective function, male mice were orally administered blueberry (0.6 g/10 g) or normal saline for 21 days. Hepatic RNA was extracted by Trizol reagent, and the expression of Nrf2, HO-1, and Nqo1 was determined by real-time RT-PCR. Superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenate were determined, and liver index was measured. To assess the effects of blueberry on cellular immune function, male mice received blueberry (0.4, 0.6, or 0.8 g/10 g) for 35 days, and the percentages of CD3+, CD4+, and CD8+ T lymphocyte subgroups in peripheral blood were detected by flow cytometry, the index of the thymus and spleen was measured, and lymphocyte proliferation in the spleen was determined by MTT assay.

RESULTS: Blueberry treatment significantly increased the expression of Nrf2, HO-1, and Nqo1, the important antioxidant components in the liver. Hepatic SOD in the blueberry group was higher and MDA was lower than that in the control group (P<0.05). Blueberry also increased the index of the spleen and enhanced the proliferation of lymphocytes of the spleen (P<0.05). The percentages of the CD3+ and CD4+ T lymphocyte subsets and the CD4+/CD8+ ratio were also increased by blueberry (P<0.05).

CONCLUSIONS: Blueberry induces expression of Nrf2, HO-1, and Nqo1, which can protect hepatocytes from oxidative stress. In addition, blueberry can modulate T-cell function in mice.

 

Anthocyanins: Janus Nutraceuticals Displaying Chemotherapeutic and Neuroprotective Properties

From: http://link.springer.com/chapter/10.1007/978-94-007-4575-9_21

Abstract

Anthocyanins are natural polyphenolic compounds widely distributed as pigments in many fruits and vegetables. In addition to displaying antioxidant properties, these nutraceuticals exhibit anti-inflammatory, anti-proliferative, and pro-apoptotic activities suggesting their potential as novel chemotherapeutic agents. Through cell cycle down-regulation, and context-specific pro-oxidant activity, anthocyanins induce cytotoxicity in cancer cells in vitro and in vivo. Specifically, via regulation of the Bcl-2 protein family and induction of caspase-dependent or caspase-independent apoptotic pathways, anthocyanins inhibit the growth of cancers by inducing cell death. Moreover, by modulating the activities of specific kinases and proteases, including (but not limited to) cyclin-dependent kinases, mitogen-activated protein kinases, matrix metalloproteases, and urokinase-type plasminogen activators, anthocyanins induce apoptosis, inhibit motility, and suppress invasion of cancer cells. In marked contrast to their effects in cancer cells, we have found that anthocyanins display significant anti-apoptotic activity in neurons. Antioxidant properties of these nutraceuticals, particularly at the level of the mitochondria, appear to underlie their neuroprotective effects. The opposing effects of anthocyanins on cancer cells and neurons suggest that these nutraceuticals are promising candidates for development as either chemotherapeutic agents or novel neuroprotective compounds for the treatment of cancers or neurodegenerative diseases, respectively.

Recent Research on Polyphenolics in Vision and Eye Health

From: http://pubs.acs.org/doi/abs/10.1021/jf903038r#end-1

Abstract

A long-standing yet controversial bioactivity attributed to polyphenols is their beneficial effects in vision. Although anecdotal case reports and in vitro research studies provide evidence for the visual benefits of anthocyanin-rich berries, rigorous clinical evidence of their benefits is still lacking. Recent in vitro studies demonstrate that anthocyanins and other flavonoids interact directly with rhodopsin and modulate visual pigment function. Additional in vitro studies show flavonoids protect a variety of retinal cell types from oxidative stress-induced cell death, a neuroprotective property of significance because the retina has the highest metabolic rate of any tissue and is particularly vulnerable to oxidative injury. However, more information is needed on the bioactivity of in vivo conjugates and the accumulation of flavonoids in ocular tissues. The direct and indirect costs of age-related vision impairment provide a powerful incentive to explore the potential for improved vision health through the intake of dietary polyphenolics.

 

Bilberry Extracts Induce Gene Expression Through the Electrophile Response Element

From: http://www.tandfonline.com/doi/abs/10.1207/s15327914nc5401_11#.VLK6LVqBO24

Abstract

A number of genes important for detoxification and antioxidant defense induced by mild stress generated by, for example, physical activity/exercise, caloric restriction, or alcohol may provide health benefits by causing the organism to mount such a defense response. More recently, induction of these defenses has also been attributed to phytochemicals or secondary metabolites from dietary plants. Many polyphenols, which constitute a large fraction of these phytochemicals, increase cellular levels of antioxidants, such as glutathione and other components of the detoxification systems, via the transactivation of genes containing electrophile response elements (EpREs) within their promoters. One such gene, γ-glutamylcysteine synthetase, has previously been shown to be positively regulated by quercetin, a flavonoid found in high concentrations in onions, apples, and bilberries through EpRE transactivation. As a further step, we have investigated whether bilberries and quercetin have the ability to induce transcription of Fos-related antigen 1 (Fra-1), which contains two EpREs in its promoter. Fra-1 is a member of the activator protein 1 (AP-1) family of transcription factors and, due to the lack of transactivation domain Fra-1, can suppress activation of AP-1. We present results demonstrating that extracts from bilberries, and the flavonoid quercetin, abundant in bilberries, induce the fra-1 promoter and the cellular content of Fra-1 mRNA. We further provide evidence that this induction is mediated through EpREs.

 

Bilberry (Vaccinium myrtillus)

From: http://www.sigmaaldrich.com/life-science/nutrition-research/learning-center/plant-profiler/vaccinium-myrtillus.html

Synonyms / Common Names / Related Terms
Airelle, anthocyanins, Bickbeere (German), bilberry leaf, black whortle, Blaubeere (Dutch), blaubessen, bleaberry, blueberry, blueberry leaf, bogberry, bog bilberry, burren myrtle, cranberry, dwarf bilberry, dyeberry, Ericaceae (family), European blueberry, Heidelbeere (Dutch), Heidelbeereblatter, heidelberry, huckleberry, hurtleberry, lingonberry, lowbush blueberry, Mirtillo nero (Italian), Myrtilli folium, Myrtilli fructus, Myrtilus niger Gilib., Optiberry, resveratrol, sambubiosides, trackleberry, Vaccinium angulosum Dulac, Vaccinium montanum Salibs., Vaccinium myrtillus anthocyanoside extract, VMA extract, VME, whortleberry, wineberry
Mechanism of Action

Pharmacology:

  • Constituents: Bilberry contains several compounds that have demonstrated biological activity. The main chemicals contained in bilberry extract have been shown to be: anthocyanins30,31, flavonoids, hydroquinone, oleanolic acid, neomyrtillin, sodium, tannins, and ursolic acid17,20,32,33,34. Bilberry also contains resveratrol.28,29 The anthocyanosides, tannins, and flavonoids have been of particular scientific interest. Flavonoids have been shown in vitro to possess a number of biological properties, including inhibition of prostacyclin synthesis, reduction of capillary permeability and fragility, free radical scavenging, inhibition of a wide range of enzymes, impairment of coagulation and platelet aggregation, and anticarcinogenicity.33,5
  • Mechanism of action: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes heme-oxygenase-1 and glutathione S-transferase-pin cultured human retinal pigment epithelial cells, suggesting that they stimulate signal transduction pathways, influencing genes controlled by the antioxidant response element.30
  • Antibacterial effects: In an in vitro study using Staphylococcus aureus, Staphylococcus aureus Oxford, Enterococcus faecalisBacillus subtilis, and Escherichia coli, an aqueous extract of bilberry leaves had a MIC of 12.7-17.8mg/mL and an aqueous extract of bilberry fruit had a MIC of 15.4-30.7mg/mL.24
  • Anticarcinogenic effects: In an in vitro study, anthocyanin-rich extracts from bilberry (Vaccinium myrtillus L.) inhibited the growth of a colon cancer cell line.6
  • Bomser et al. screened fruit extracts of bilberry for potential anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA).5 The crude extracts, anthocyanin, and proanthocyanidin fractions were not found to be highly active in Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) induction, whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of bilberry were 1.0mcg tannic acid equivalents (TAE). Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07mcg TAE). The anthocyanidin and ethyl acetate extracts of bilberry were either inactive or relatively weak inhibitors of ornithine decarboxylase (ODC) activity. The authors concluded that components of the hexane/chloroform fraction of bilberry exhibit potential anticarcinogenic activity, as evaluated by in vitro screening tests.
  • Antihyperglycemic effects: In normal and depancreatized dogs, oral administration of bilberry leaves reduced hyperglycemia, even when the glucose was injected intravenously concurrently.15,16
  • Antioxidant effects: Bilberry contains anthocyanosides that are flavonoid derivatives of anthocyanins (the blue, red, or violet pigments found in many berry varieties), which are closely related in structure and activity to flavonoids17 and possess free radical scavenging/antioxidant properties. Antioxidant properties have been attributed to bilberry based on in vitro studies.1,2,34
  • Antiplatelet activity: In a clinical study of 30 subjects with normal platelet aggregation, 480mg of Myrtocyan® (Vaccinium myrtillus anthocyanins) daily, 3g of ascorbic acid daily, or both treatments all reduced platelet aggregation after 30 and 60 days.11 Bilberry anthocyanins reduced platelet aggregation more than ascorbic acid alone, but bilberry anthocyanins and ascorbic acid together were the most effective. Also, in in vitro studies, anthocyanins extracted from bilberry have inhibited platelet aggregation.13,14,10,12
  • Flavonoids have been shown in vitro to inhibit prostacyclin synthesis. In one animal model, Vaccinium myrtillus anthocyanosides were studied for their effects on prostacyclin-like activity in rat arterial issue.7
  • Antiproliferative effects: According to one laboratory study, anthocyanins were the predominant phenolic compounds in bilberry extracts.31 Compared to other plants with anthocyanins, such as black currant or lingonberry, cell growth inhibition was greater for bilberry than other plants studied. The pro-apoptosis marker, Bax, was increased 1.3-fold in bilberry-treated cells, whereas the pro-survival marker, Bcl-2, was detected only in control cells. The results demonstrated that bilberry and other berry extracts containing anthocyanins inhibited cancer cell proliferation, mainly via the p21WAF1 pathway.
  • Antiulcer effects: In an animal study, large doses of cyanidin chloride from bilberry significantly increased gastric mucosal release of prostaglandin E2.19 In animal models of gastric ulcers, cyanidin chloride showed antiulcer activity.26,8
  • Astringent effects: Bilberry contains tannins that have been used medicinally as astringents and to treat diarrhea.
  • Connective tissue stabilizing effects: An in vitro study has suggested that anthocyanosides appear to stabilize connective tissue by enhancing collagen synthesis, inhibiting collagen degradation, and enhancing collagen cross linking.35 In contrast, Boniface et al. found a significant decrease in connective tissue synthesis (collagen and glycoproteins) in gingival tissue samples of 12 adult diabetics treated with 600mg of anthocyanosides daily for two months.36
  • Hepatoprotective activity: In an animal study, anthocyans exerted a protective effect on liver cells.27
  • Hyperglycemic effects: In an oral glucose tolerance test in healthy rats, an alcoholic extract of Vaccinium myrtillus leaves increased serum glucose levels compared to controls.25
  • Hypotensive effects: Bilberry has been theorized to potentially drop blood pressure, based on pre-clinical evidence of vascular smooth muscle-relaxing properties.21,22,23
  • Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Intracellular signaling effects: Anthocyanosides have been shown to inhibit cAMP phosphodiesterase, which is involved in intracellular signal transduction pathways.8
  • Ocular effects: Anthocyanosides have been shown to exert direct effects on the retina, including the alteration of local enzymatic reactions and enhancement of the recovery of rhodopsin.9 The multi-ingredient product Mirtogenol (Pycnogenol® – French maritime pine bark extract and Mirtoselect® – standardized bilberry extract) has been reported to lower intraocular pressure and improve ocular blood flow.37
  • Smooth muscle relaxant effects: Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Vasoprotective effects: Flavonoids have been shown in vitro to reduce capillary permeability and fragility. Anthocyanosides have been studied for their potential protective effect in disorders due to abnormal capillary fragility.33

Pharmacodynamics/Kinetics:

  • There are limited data regarding the pharmacodynamics and kinetics of Vaccinium myrtillus (bilberry) anthocyanosides (VMA). In one animal study, bilberry anthocyanosides were rapidly distributed after intra-peritoneal injection and intravenous administration.38 In another animal study, bilberry anthocyanosides were found to be eliminated via the bile and urine with a modest level of liver extraction.32
  • Bioavailability in animals is low. Following oral doses in rats, plasma levels of VMA reached a peak at 15 minutes and declined rapidly within two hours, and the absolute bioavailability was 1.2% of the administered dose.38 The gastrointestinal absorption of VMA was 5% of the administered dose. Another study found a differential affinity of VMA for certain tissues (especially skin and kidney).20 This suggests that different tissues may have more persistent local concentrations.
References:

  1. Martin-Aragon S, Basabe B, Benedi JM, and et all. In vitro and in vivo antioxidant properties of Vaccinium myrtillus. Pharmaceutical Biology 1999;37(2):109-113.
  2. Prior R, Cao G, Martin A, and et all. Antioxidant capacity as influence by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agricult Food Chem 1998;46:2686-2693.
  3. Martin-Aragon S, Basabe B, Benedi J, and et all. Antioxidant action of Vaccinium myrtillus L. Phytotherapy 1998;46:S104-S106.
  4. Laplaud, P. M., Lelubre, A., and Chapman, M. J. Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations. Fundam Clin Pharmacol 1997;11(1):35-40. 9182074
  5. Bomser, J., Madhavi, D. L., Singletary, K., and Smith, M. A. In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 1996;62(3):212-216.
  6. Zhao, C., Giusti, M. M., Malik, M., Moyer, M. P., and Magnuson, B. A. Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth. J Agric Food Chem  10-6-2004;52(20):6122-6128. 15453676
  7. Morazzoni P and Magistretti MJ. Effects of Vaccinium myrtillus anthocyanosides on prostacyclin-like activity in rat arterial issue. Fitoterapia 1986;57:11-14.
  8. Magistretti, M. J., Conti, M., and Cristoni, A. Antiulcer activity of an anthocyanidin from Vaccinium myrtillus. Arzneimittelforschung  1988;38(5):686-690. 3415709
  9. Cluzel, C., Bastide, P., Wegman, R., and Tronche, P. [Enzymatic activities of retina and anthocyanoside extracts of Vaccinium myrtillus (lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, alpha-glycerophosphate dehydrogenase, 5-nucleotidase, phosphoglucose isomerase)]. Biochem Pharmacol 1970;19(7):2295-2302. 4329039
  10. Morazzoni P and Bombardelli E. Vaccinium myrtillus L. Fitoterapia 1996;66:3-29.
  11. Pulliero G, Montin S, Bettini V, and et al. Ex vivo study of the inhibitory effects of Vaccinium myrtillus anthocyanosides on human platelet aggregation. Fitoterapia 1989;60:69-75.
  12. Bottecchia D. Preliminary report on the inhibitory effect of vaccinium myrtillus anthocyanosides on platelet aggregation and clot retraction. Fitoterapia 1987;48:3-8.
  13. Zaragoza, F., Iglesias, I., and Benedi, J. [Comparative study of the anti-aggregation effects of anthocyanosides and other agents]. Arch Farmacol Toxicol 1985;11(3):183-188. 4096552
  14. Fdez, M., Zaragoza, F., and Alvarez, P. In vitro platelet aggregation effects of anthocyanosides of vaccinium myrtilus L. Anales de la Real Academia de Farmacia 1983;49:79-90.
  15. Bever B. Plants with oral hypoglycemic action. Q J Crude Drugs Res 1979;17:139-196.
  16. Allen, F. M. Blueberry leaf extract: Physiologic and clinical properties in relation to carbohydrate metabolism. 89:1577-81, 1927. JAMA 1927;89:1577-1581.
  17. Havsteen, B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 4-1-1983;32(7):1141-1148. 6342623
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SUMMARY

Wild bilberries and wild blueberries are important fruits full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.

 

up-4 elderberry wild bilberry and wild blueberry

Ultimate Protector provides wild bilberry and wild blueberry, and 27 other Nrf2 activator-containing plant-based ingredients.

ADDITIONAL RESOURCES