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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 – RESVERATROL

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

Ultimate Protector+ includes resveratrol, as well as extracts from 12 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I will explore the ingredient resveratrol, which is added as a separate ingredient in addition to being a component in the ingredients of SFB® Standardized Fruit Blend and VinCare® Whole Grape Extract from Ethical Naturals, Inc.

Ultimate Protector+ Includes Resveratrol

Ultimate Protector+ Includes Resveratrol

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants in response to injury or when the plant is under attack by pathogens such as bacteria and fungi. Natural sources of resveratrol include giant knotweed (Polygonum cuspidatum) and the skin of grapes, blueberries, raspberries, and mulberries. Resveratrol has two isomers: cis and trans, with the latter being the most abundant.  Piceid, also known as polydatin, is a glucoside form of resveratrol found in Japanese knotweed. HPDI includes the very pure 98% resveratrol form from giant knotweed in Ultimate Protector+. This material contains greater than 96% of the trans form.

Knotweed (Polygonum cuspidatum) is a major source for resveratrol

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

SFB® Standardized Fruit Blend

SFB® Standardized Fruit Blend 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. SFB® has been designed to provide a wide range of plant polyphenols, flavonoids, anthocyanins, resveratrol, catechins, OPCs, zeaxanthin and other carotinoids, etc.

VinCare® Whole Grape Extract

VinCare® Whole Grape Extract (seed, pulp, & skin) 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.

Vincare® contains >80% polyphenols 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.

HEALTH BENEFITS OF RESVERATROL

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

Scientific Studies on the Antioxidant Effects of Resveratrol

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

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

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

Abstract

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

Mitochondrial Protection by Resveratrol

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

Abstract

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

Introduction

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

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

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

Abstract

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

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

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

Abstract

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

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

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

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

Abstract

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

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

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

 Abstract

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

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

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

 Abstract

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

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

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

 Abstract

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

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

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

 Abstract

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

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

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

 Abstract

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

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

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

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

SUMMARY

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

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PRO-C ANTIOXIDANT FORMULA UPDATE + VIDEO

Dr. Hank Liers, PhD pro-c™ pro-c super antioxidant formulaFred Liers PhD pro-c antioxidant vitamin c nrf2 formulaLooking for an advanced antioxidant formula? Already using or recommending vitamin C? Curious about cellular Nrf2 activation? Look no further than PRO-C™.

PRO-C™ is among the most effective antioxidant formulas available. It is an HPDI foundational supplement that works most effectively when used with multivitamins, essential fats, and superfoods. However, it is also an excellent standalone formula that can rapidly provide the body with extremely high protection from free radicals.

We ourselves have taken PRO-C daily for many years with excellent results. Our personal experience together with detailed feedback from health professionals and end-users affirms the effectiveness of PRO-C as a super-antioxidant–vitamin C-Nrf2 activator formula.

PRO-C provides 500 mg of buffered vitamin C per capsule (buffered with calcium, magnesium, and zinc) along with grape extract (seed, skin, pulp) and green tea extract (95% polyphenols). In addition, we include a special combination of the “network antioxidants” l-glutathione (reduced), n-acetyl-l-cysteine (NAC), r-lipoic acid, and selenium. Vitamin B2 and Vitamin B6 in coenzyme forms support the enzymatic effectiveness of the “network antioxidants”. The formula works so well because this combination of ingredients leverages the antioxidant power of vitamin C, grape extract, green tea extract, and the other nutrients to act synergistically in order to maximize effectiveness.

FORMULATION HISTORY AND THE SCIENCE BEHIND PRO-C™

What you may not know is the history of the development PRO-C and the scientific knowledge on which Dr. Hank Liers based his formulation of it.

Dr. Hank formulated his first product in 1989. It was a potent antioxidant formula he called PYC-C™ (sounds like “pixie”). PYC-C consisted of a combination of buffered Vitamin C (including magnesium, calcium, and zinc ascorbates) and pycnogenols from pine bark.

Much of the scientific research data Dr. Hank collected during the development of PYC-C regarding oligomeric proanthocyanidins (OPC) he later incorporated into an article (currently published on this blog) titled “Review of Scientific Research on Oligomeric Proanthocyanidins (OPC)” (rev. 2017)

By 1997 Dr. Hank had gathered a great deal of new scientific information regarding green tea catechins and the nutrients termed “network antioxidants” by Dr. Lester Packer, director of Packer Lab at University of California, Berkeley. Beyond this information, Dr. Hank studied additional research regarding how various nutrients worked together synergistically. At that point, he was ready to formulate the new, improved PRO-C™ super antioxidant formula.

PRO-C combines the ingredients of PYC-C (now known as OPC-C™) and uses grape pulp, skin, and seed extract with green tea extract (with high polyphenols >95% and EpiGalloCatechinGalate (EGCG) >45%), n-acetyl-l-cysteine (NAC), reduced glutathione (GSH), R-lipoic acid, selenium, and coenzyme Vitamins B2 and B6.

PRO-C super antioxidant formula 180 cap 90 cap

HPDI launched PRO-C™ in late 1997. It rapidly became one of our best-selling products. Our customers raved about how effective it was for them if they felt like they were “coming down with something” (like a cold, flu, virus, infection, etc.). Greater skin elasticity greatly helped pregnant women avoid stretch marks and episiotomies. Today, we highly recommend its use together with our other Foundational Supplements to ensure optimal health and anti-aging effects.

THE PRO-C™ SUPER ANTIOXIDANT FORMULA

PRO-C™ super antioxidant formula is extremely synergistic, especially in so far as it increases the body’s ability to quench free radicals in its aqueous (i.e., water-based) compartments. Because antioxidants may become free radicals themselves after they have done their job, the body has developed an elaborate system for recovery of oxidized antioxidants.

 

Dr. Lester Packer was the primary researcher investigating the synergistic character of antioxidants. He made this statement in his interview with Dr. Richard Passwater after publication of Packer’s The Antioxidant Miracle (1999):

[The major theme of] The Antioxidant Miracle is that antioxidants work in a coordinated manner. They interact with one another, and this interaction, which we like to call the antioxidant network, is very important to the overall antioxidant defense that we possess. The key members of the antioxidant network are vitamin E and vitamin C, but there are other participants in this network. These are thiol antioxidants, antioxidants that contain sulfur groups in the body. Glutathione perhaps is the best known of these, but there are other sulfur-containing antioxidants that also are very important.”

Dr. Packer continues:

“This whole antioxidant network works like an orchestra depending on individuals who have, of course, different complements of antioxidants depending upon their nutritional regimens and the individuality of their own body metabolisms. The idea behind having a network of antioxidants is that if one antioxidant happens to be deficient the others can compensate and still keep the antioxidant defense system strong.”

The following diagram shows some of the relationships in the antioxidant network and how they support each other.

Lester Packer antioxidant network diagram Figure 1 – Dr. Packer’s Antioxidant Network

We see, for example, reduced glutathione (GSH) has the ability to reduce oxidized Vitamin C back to its unoxidized state. Vitamin C reduces oxidized Vitamin E back to its unoxidized state, and both reduces glutathione and spares it for other important functions, including detoxification and immune enhancement.

Many polyphenols (e.g., oligomeric proanthocyanidins (OPCs), anthocyanidins and catechins) found in red grape and green tea extracts spare Vitamin C and glutathione in the body, as well as operate as powerful antioxidants, anti-inflammatories, and connective tissue strengtheners.

grapes grape extract antioxidant

Grapes provide antioxidant nutrients such as polyphenols, OPCs, anthocyans, and resveratrol.

R-Lipoic Acid (see abstracts below) operates as an antioxidant both in its oxidized and reduced states, reduces the oxidized forms of both Vitamin E and Vitamin C, and and has been shown to enhance glutathione levels. Because several of these substances are able to protect Vitamin E contained in cell membranes, this combination also has a significant beneficial effect on the fat soluble antioxidant status of the body!

The nutrients in PRO-C have been carefully selected and balanced to provide optimal effects, especially as related to free radical protection, detoxification, immune system enhancement, connective tissue strengthening, and reduction of inflammation. PRO-C therefore provides outstanding nutritional support in a wide variety of conditions of poor health, as well as acts to support and maintain a state of health and well-being.

It the last several years the research results on Nrf2 activators have become well known and products developed that take advantage of these nutrients. For details see our blog article Natural Phytochemical Nrf2 Activators for Chemoprevention. Researchers have been studying specifically how enzyme-activating substances such as OPCs and anthocyans activate a transcription factor known as Nrf2 that causes the body to endogenously produce higher levels of a wide variety of protective enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase.

Although we did not know about Nrf2 activators in 1997 when we formulated PRO-C, we have subsequently learned that four of the ingredients in the formula have powerful Nrf2 activity. These include grape seed extract, green tea extract, NAC, and r-lipoic acid. With this knowledge, we now understand that PRO-C provides both powerful external antioxidants (with extremely high ORAC5.0 values) that support redox cycles within the body, but also provides ingredients that allow the body to endogenously produce powerful protective enzymes for even greater free-radical protection and health.

PRO-C™ ANTIOXIDANT FORMULA INGREDIENTS

PRO-C contains buffered vitamin C (in the form of powdered calcium, magnesium, and zinc ascorbates), high-potency grape extract (from grape pulp, skins, and seeds), green tea extract (with>95% polyphenols and >45% EGCG), reduced glutathione, N-Acetyl-L-Cysteine (NAC), R-lipoic acid, coenzyme forms of vitamin B2 (R5P) and vitamin B6 (P5P), and selenium.

Below we will discuss each ingredient and show some of the research that confirms its effectiveness.

VITAMIN C

Vitamin C typically is called l-ascorbic acid or ascorbate and is an essential nutrient for humans and other animal species. The term “vitamin C” refers to a number of vitamins that have vitamin C activity in animals, including ascorbic acid and its salts (e.g., magnesium ascorbate, calcium ascorbate, sodium ascorbate, etc.), and some oxidized forms such as dehydroascorbate and semidehydroascorbate.

Vitamin C is known to perform many critical functions within the body involving detoxification, tissue building, immune enhancement, pain control, and controlling or killing pathogenic organisms. It is also known to be helpful for wound and bone healing, healthy skin and eyes, fighting infections, stress control, toxic exposure, and repairing damaged tissue of all types. For much more information on the many benefits of Vitamin C see our blog article Vitamin C – An Amazing Nutrient.

Below are two abstracts that show some of the beneficial effects of Vitamin C when used with other network antioxidants:

ABSTRACT 1:
Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.
Sastre J, Asensi M, Gasco E, Pallardo FV, Ferrero JA, Furukawa T, Vina J
In: Am J Physiol (1992 Nov) 263(5 Pt 2):R992-5

We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L- cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.

ABSTRACT 2:
The effect of glutathione and vitamins A, C, and E on acute skin flap survival.

Hayden RE, Paniello RC, Yeung CS, Bello SL, Dawson SM
In: Laryngoscope (1987 Oct) 97(10):1176-9

Vitamins A, C, and E act as antioxidants and as free radical scavengers in biological systems. Glutathione is involved in several reactions in vitamin metabolism and also plays an important role in cell membrane protection against lipid peroxidation by free radicals. We sought to use these natural defense mechanisms against oxygen free radicals formed during reperfusion of ischemic skin flaps. An acute axial random skin flap model was utilized in the rat. Vitamins or glutathione were administered by oral gastric tube or intravenously in the perioperative period, and survival of the flap was measured at 1 week. Glutathione, beta-carotene, ascorbic acid and alpha-D- tocopherol showed mean flap survival of 84% to 89%, each of which was significantly improved over saline controls (67% p less than .0005). The mechanisms and biochemistry of these vitamins, and their interactions with other vitamins and with glutathione, are discussed, along with clinical implications of free radical scavenging and skin flap survival.

GRAPE EXTRACT

Grape extract (seeds, skin, pulp) contain highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. The Oligomeric Proanthocyanidins (OPCs) in grape seed 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 anthocyans, which are found in extracts of grape 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 stems (but not those of grape seed extract) contain a material called trans-resveratrol that has been shown to have chemopreventive effects.

Below we have provided some of the abstracts that are included in our broad list of relevant abstracts for PRO-C.

ABSTRACT 3:
Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice.
Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ
In: Gen Pharmacol (1998 May) 30(5):771-6

1. The comparative protective abilities of a grape seed proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragmentation in the hepatic and brain tissues, as well as production of reactive oxygen species by peritoneal macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evidenced by decreases in the chemiluminescence response in peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain tissues, at the doses that were used. Similar results were observed with respect to lipid peroxidation in hepatic mitochondria and microsomes and in brain homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA- induced lipid peroxidation and DNA fragmentation in liver and brain, as well as a dose-dependent inhibition of TPA-induced reactive oxygen species production in peritoneal macrophages. 5. GSPE and other antioxidants provided significant protection against TPA-induced oxidative damage, with GSPE providing better protection than did other antioxidants at the doses that were employed.

ABSTRACT 4:
Clinical and capillaroscopic evaluation of chronic uncomplicated venous insufficiency with procyanidins extracted from vitis vinifera
Costantini A, De Bernardi T, Gotti A
In: Minerva Cardioangiol (1999 Jan-Feb) 47(1-2):39-46

BACKGROUND: The pharmacological treatment of non-complicated chronic venous insufficiency is a current and well-debated topic. The introduction of new products with action on the venous system, improved knowledge on the physiopathology of venous insufficiency and the possibility provided by new analytical instruments, have given new impulse to the consolidation of the clinical value of phlebotonics in this indication. METHODS: In light of this, 24 patients with non-complicated chronic venous insufficiency were treated with oral administration of Oligomeric Proanthocyanidins (Pycnogenols-OPC) 100 mg/day. To evaluate the therapeutic efficacy of the treatment, an instrumental evaluation by optical probe capillaroscope was employed in addition to the traditional subjective clinical parameters: swelling, itching, heaviness and pain. The videocapillaroscope examination was performed at the lower third of the leg and the first toe. Edema in the capillaroscopic field, the number of observable capillaries and the capillary dilatation were the parameter chosen to evaluate the efficacy of treatment. All patients completed the study with no reports of adverse events during the period of observation. RESULTS: The results obtained show a positive clinical response (improved or absent symptoms) in over 80% of patients, with significant improvement of symptoms already evident after the first 10 days of treatment. The mechanism of action of the OPCs explains the rapid reduction of the swelling of the lower limbs and correlated with this are the other evaluable symptoms: heaviness and itching. Particularly striking results were observed for itching and pain which completely disappeared during the course of therapy in 80% and 53% of the patients respectively. Noteworthy is the good correlation between the clinical and instrumental data, with improvement in a total of 70% of patients. CONCLUSIONS: The results obtained in the course of this clinical experience, with evident improvement already during the first weeks of treatment, the absence of adverse events added to the benefit of a once-a-day administration, justify the use of OPC in the treatment of non-complicated chronic venous insufficiency.

ABSTRACT 5:
Polymeric procyanidin fraction from defatted grape seeds protects HepG2 cells against oxidative stress by inducing phase II enzymes via Nrf2 activation.
Younghwa Kim, Youngmin Choi, Hyeonmi Ham, Heon-Sang Jeong, Junsoo Lee
Kim, Y., Choi, Y., Ham, H. et al. Food Sci Biotechnol (2013) 22: 485. https://doi.org/10.1007/s10068-013-0105-x

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that regulates antioxidant response element (ARE)-driven phase II detoxification enzymes. In this study, induction of phase II enzymes via Nrf2/ARE activation in the cytoprotective effect of crude polyphenol extract (CPE), oligomeric procyanidin fraction (OPF), and polymeric procyanidin fraction (PPF) from defatted grape seeds in HepG2 cells was evaluated. Among these treatments, the treatment with PPF significantly increased Nrf2 protein expression in the nuclear fraction. Treating the samples increased heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) protein expression in a dose-dependent manner, and PPF significantly increased the levels of phase II enzymes. Cellular generation of reactive oxygen species (ROS) were effectively reduced by PPF. These results suggest that pretreatment with PPF shows a cytoprotective effect by inhibiting ROS production and inducing HO-1 and NQO1 expression via Nrf2 activation in HepG2 cells.

GREEN TEA EXTRACT

Green tea extract is obtained from the unfermented leaves of Camellia sinensis for which numerous biological activities have been reported including: antimutagenic, antibacterial, hypocholesterolemic, antioxidant, and protective against tumorigenesis. Below we have selected a few of the many abstracts we have on file showing the benefit of green tea extract.

Green tea antioxidant polyphenols catechins

Green tea leaves are high in antioxidant polyphenols and catechins.

ABSTRACT 6:
Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention.
Khan SG, Katiyar SK, Agarwal R, Mukhtar H
In: Cancer Res (1992 Jul 15) 52(14):4050-2

Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.

ABSTRACT 7:
INHIBITORY EFFECT OF SIX GREEN TEA CATECHINS AND CAFFEINE ON THE GROWTH OF FOUR SELECTED HUMAN TUMOR CELL LINES.
In: Anticancer Drugs (1996 Jun) 7(4):461-8
Institutional address: Department of Pharmacology and Toxicology College of Pharmacy University of Arizona Tucson 85721 USA.

Green tea is an aqueous infusion of dried unfermented leaves of Camellia sinensis (family Theaceae) from which numerous biological activities have been reported including antimutagenic, antibacterial, hypocholesterolemic, antioxidant, antitumor and cancer preventive activities. From the aqueous-alcoholic extract of green tea leaves, six compounds (+)-gallocatechin (GC), (-)-epicatechin (EC), (-)- epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)- epigallocatechin gallate (EGCG) and caffeine, were isolated and purified. Together with (+)-catechin, these compounds were tested against each of four human tumor cells lines (MCF-7 breast carcinoma, HT-29 colon carcinoma, A-427 lung carcinoma and UACC-375 melanoma). The three most potent green tea components against all four tumor cell lines were EGCG, GC and EGC. EGCG was the most potent of the seven green tea components against three out of the four cell lines (i.e. MCF-7 breast cancer, HT-29 colon cancer and UACC-375 melanoma). On the basis of these extensive in vitro studies, it would be of considerable interest to evaluate all three of these components in comparative preclinical in vivo animal tumor model systems before final decisions are made concerning which of these potential chemopreventive drugs should be taken into broad clinical trials.

GLUTATHIONE AND N-ACETYL-L-CYSTEINE (NAC)

Glutathione and NAC (a major precursor of glutathione) both provide important protection against toxins and free radicals, and can strengthen the immune system. Glutathione is considered to be one of the most important protective substances in the human body with almost 60% of liver detoxification accounted for by this key substance. In addition, glutathione is one of the most potent anti-viral substances known.

Some research has indicated that glutathione may not be able to enter easily into certain types of cells, but NAC is able to enter these cells and be converted into glutathione once inside the cell. Thus, the combination of glutathione and NAC appear to be more potent than either alone.

Below we provide some of the key abstracts we have on file regarding NAC and glutathione.

ABSTRACT 8
GSH rescue by N-acetylcysteine.
Ruffmann R Wendel A
In: Klin Wochenschr (1991 Nov 15) 69(18):857-62

Reduced glutathione (GSH) is the main intracellular low molecular weight thiol. GSH acts as a nucleophilic scavenger and as an enzyme-catalyzed antioxidant in the event of electrophilic/oxidative tissue injury. Therefore, GSH has a major role as a protector of biological structures and functions. GSH depletion has been recognized as a hazardous condition during paracetamol intoxication. Conversely, GSH rescue, meaning recovery of the protective potential of GSH by early administration of N-acetylcysteine (NAC), has been found to be life-saving. Lack of GSH and electrophilic/oxidative injury have been identified among the causes of the adult respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and the acquired immunodeficiency syndrome (AIDS). Experimental and early clinical data (in ARDS) point to the role of NAC in the treatment of these conditions. Recently, orally given NAC has been shown to enhance the levels of GSH in the liver, in plasma, and notably in the bronchoalveolar lavage fluid. Rescue of GSH through NAC needs to be appreciated as an independent treatment modality for an array of different disease, all of which have one feature in common: pathogenetically relevant loss of GSH.

ABSTRACT 9
Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.
Bridgeman MM Marsden M MacNee W Flenley DC Ryle AP
In: Thorax (1991 Jan) 46(1):39-42

N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-Acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung.

R-LIPOIC ACID / ALPHA-LIPOIC ACID

R-Lipoic Acid is normally made at low levels in the human body, where it functions primarily as an important metabolic nutrient in the conversion of pyruvic acid into acetyl coenzyme A. As such, it plays a crucial role in the metabolism of both fats and carbohydrates into energy. In addition, r-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 is able to 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 as such in both a reduced and oxidized state, lipoic acid is able to protect other important antioxidants such as glutathione, Vitamin E, and Vitamin C. R-lipoic acid is also able to chelate heavy metals such as lead, cadmium, mercury, free iron, and free copper out of the body.

Below we provide relevant scientific abstracts from our database regarding R-Lipoic acid.

ABSTRACT 10:
Alpha-Lipoic acid as a biological antioxidant.
Packer L Witt EH Tritschler HJ
In: Free Radic Biol Med (1995 Aug) 19(2):227-50

alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.

ABSTRACT 11:
Regeneration of glutathione by α-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity.
Zhang J, Zhou X, Wu W, Wang J, Xie H, Wu Z.
In: Environ Toxicol Pharmacol. 2017 Apr;51:30-37. doi: 10.1016/j.etap.2017.02.022. Epub 2017 Feb 27.

Alpha-lipoic acid (α-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). However, the underlying molecular mechanism by which α-LA regenerates GSH remains poorly understood. The current study aimed to investigate whether α-LA regenerates GSH by activation of Nrf2 to alleviate cadmium-induced cytotoxicity in HepG2 cells. In the present study, we found that cadmium induced cell death by depletion of GSH through inactivation of Nrf2. Addition of α-LA to cadmium-treated cells reactivated Nrf2 and regenerated GSH through elevating the Nrf2-downstream genes γ-glutamate-cysteine ligase (γ-GCL) and GR, both of which are key enzymes for GSH synthesis. However, blocking Nrf2 with brusatol in the cells co-treated with α-LA and cadmium reduced the mRNA and the protein levels of γ-GCL and GR, thus suppressed GSH regeneration by α-LA. Our results indicated that α-LA activated Nrf2 signaling pathway, which upregulated the transcription of the enzymes for GSH synthesis and therefore GSH contents to alleviate cadmium-induced cytotoxicity in HepG2 cells.

SELENIUM

Selenium has been shown by clinical research to be a key mineral in the body’s defenses against free radicals and has been shown to be a major factor in reducing the symptoms of HIV infections and in the prevention of tumors. Selenium is used in conjunction with glutathione to form the powerful enzyme glutathione peroxidase that is responsible for detoxification of peroxides formed during the process of aerobic metabolism in humans and other animals.

ABSTRACT 12
Serum selenium concentrations in rheumatoid arthritis.
In: Ann Rheum Dis (1991 Jun) 50(6):376-8

O’Dell JR, Lemley-Gillespie S, Palmer WR, Weaver AL, Moore GF, Klassen LW

Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis.

ABSTRACT 13
Studies on selenium in top athletes.
Dragan I, Ploesteanu E, Cristea E, Mohora M, Dinu V, Troescu VS
In: Physiologie (1988 Oct-Dec) 25(4):187-90

The authors performed a controlled trial in 18 top athletes (9 weight lifters and 9 rowers, girls) in order to make evident some chronic and acute effects (antioxidant) of selenium. Nonprotein–SH (essential glutathione), lipid peroxides (MDA-malondialdehyde), glucose-6-phosphate dehydrogenases (G-6-PDH) and fructose-1,6- diphosphate aldolase in serum, have been recorded initially on basal conditions, after 3 weeks of treatment (100 micrograms/day selenium or placebo) and again after 3 weeks of treatment, also on basal conditions, when crossing over the groups (between a free interval of 10 days). In another trial we registered these parameters on basal conditions and after two hours of hard training accompanied by a per oral administration of 150 micrograms selenium (respectively placebo). The results show significant changes under selenium treatment of the peroxides, G-6-PDH and light changes, not significant of the nonprotein–SH, changes which could suggest an antioxidant effect of this element.

VITAMINS B2 and B6 IN COENZYME FORMS

Vitamin B2 as coenzyme riboflavin-5-phosphate is a key vitamin that supports the regeneration of glutathione (via glutathione reductase). Vitamin B6 as coenzyme pyridoxal-5-phosphate is a key vitamin that supports the ability of glutathione to combine with toxic substances (via glutathione transferase) in the process of eliminating them from the body. They are especially effective in their coenzyme forms which allows them to be directly utilized by the body starting in the intestinal tract.

MAGNESIUM, CALCIUM, AND ZINC

Magnesium, zinc, and calcium synergistically work with (and enhance the effects of) the other ingredients in PRO-C. Minerals are especially needed as active components of enzymes that drive metabolic activity. For example, magnesium is required in the functioning of more than 325 types of enzymes.

PRO-C™ SUPER ANTIOXIDANT FORMULA BENEFITS

HIGHLY EFFECTIVE VITAMIN C FORMULA PLUS ANTIOXIDANTS. A complete vitamin C formula, a powerful antioxidant Formula, and Nrf2 activator combined in a single advanced supplement!

POWERFUL, SYNERGISTIC FREE-RADICAL QUENCHING FORMULA. PRO-C™ components work together to quench free radicals in your body. Vitamin C enables grape seed extract to function more effectively, and conversely grape seed extract potentiates vitamin C. Green tea extract boosts ORAC (Oxygen Radical Absorbance Capacity) value.

PROVIDES SIGNIFICANT AMOUNTS OF POWERFUL NRF2 ACTIVATORS (from Grape Extract, Green Tea Extract, NAC, and R-Lipoic Acid) that stimulate the production of the body’s own protective antioxidants including superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase.

SUPERIOR, BUFFERED (NON-ACIDIC) FORM OF VITAMIN C. Mineral Ascorbates never acidify your body, keeping you pH balanced. Staying alkaline is an important element in maintaining a healthy body.

RAPID ASSIMILATION. Capsule form ensures rapid uptake and assimilation in the body. You may also empty capsule contents into water, food, or directly Into mouth, if desired. Good, mildly tart taste!

COMPOSITION OF PRO-C™ SUPER ANTIOXIDANT FORMULA

One (1) vegetarian capsule of PRO-C provides the following percentages of the Daily Value:

NUTRIENT AMOUNT % Daily Value
Vitamin C (from mineral ascorbates) 500 mg 833%
BioVin® Grape Extract 30 mg *
Green Tea Extract 30 mg *
Calcium (from calcium ascorbate) 23 mg 2.3%
Magnesium (from magnesium ascorbate) 23 mg 5.7%
L-Glutathione (reduced) 20 mg *
N-Acetyl-L-Cysteine (NAC) 15 mg *
R-Lipoic Acid 5 mg *
Zinc (from zinc ascorbate) 2 mg 13%
Vitamin B2 (from riboflavin-5′-phosphate) 1 mg 118%
Vitamin B6 (from pyridoxal-5′-phosphate) 1 mg 50%
Selenium (from l-selenomethionine) 10 mcg *

* No established Daily Value

DIRECTIONS: As a dietary supplement take 1–3 capsules or more daily in divided doses (i.e., spread out over the day), or as recommended by a health care professional. It initially may be useful to take up to 6 capsules per day in divided doses for one week. The contents of the capsule may be emptied into juice or food, as needed.

INGREDIENTS: PRO-C™ SUPER ANTIOXIDANT FORMULA contains only the highest-quality USP grade magnesium ascorbate, USP grade calcium ascorbate, BioVin® grape extract (greater than 75% polyphenols, 93% OPC, greater than 3.5% anthocyanidins from grape pulp, skins, and seeds, and a small amount of trans resveratrol), green tea extract (95% min. polyphenols and 45% min. EGCG), l-glutathione (reduced), USP grade n-acetyl-l-cysteine, USP grade zinc ascorbate, r-(+)-lipoic acid, riboflavin-5′-phosphate, pyridoxal-5′-phosphate, l-selenomethionine, the smallest amounts of microcrystalline cellulose and silica in a vegetarian capsule.

PRO-C™ does not contain wheat, rye, oats, corn antigen, barley, gluten, soy, egg, dairy, yeast, sugar, sulfates, phosphates (other than coenzyme forms), fats, chlorides, GMOs, wax, preservatives, colorings, or artificial flavorings.

Click here to order PRO-C™.

SOURCES & RESOURCES

BOOKS

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

How to Live Longer and Feel Better. Dr. Linus Pauling. Corvallis, OR: Oregon State University Press, 2006.

ARTICLES

Review of Scientific Research on Oligomeric Proanthocyanidins (OPC)” (rev. 2017) by Hank Liers, PhD

“Vitamin C – An Amazing Nutrient” by Hank Liers, PhD

PRO-C™ and Ultimate Protector™ – Comparison by Hank Liers, PhD

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

ABSTRACTS

PRO-C™ / Vitamin C Abstracts

Catechin Abstracts

N-Acetyl-L-Cysteine (NAC) Abstracts

Lipoic Acid Abstracts

WEBSITES

Orthomolecular.org
(Therapeutic Nutrition Based Upon Biochemical Individuality)

PRODUCTS

PRO-C™Super Antioxidant Formula

Ultimate Protector™Nrf2 Activator Formula

OPC-C™

HPDI Vitamin C Products

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PRO-C AND ULTIMATE PROTECTOR – COMPARISON OF ANTIOXIDANT FORMULAS

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

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

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

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

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

Ultimate Protector

INGREDIENTS OF ANTIOXIDANT FORMULAS

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

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

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

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

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

DISCUSSION OF ANTIOXIDANT FORMULAS

PRO-C™

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

doctor lester packer antioxidant formulas

                                                Figure 1. – Dr. Packer’s Antioxidant Network

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

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

ULTIMATE PROTECTOR™

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

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

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

Ultimate Protector versus PRO-C antioxidant formulas

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

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

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

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

SOURCES & RESOURCES

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

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

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