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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, 55% 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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D-RIBOSE: ENERGIZING SMART SUGAR

Fred Liers PhD riboseAvoiding excess dietary sugars is one of the healthiest things. But there is one sugar that really is good for you. That sugar is D-ribose.

In fact, D-ribose is so healthy for you, it may be the one sugar you won’t want to live without. A little background to this amazing sugar.

D-ribose is a 5-carbon monosaccharide occurring naturally in living cells. D-ribose importantly forms the carbohydrate parts of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). That means d-ribose is the sugar essential for the biological function of all living creatures, including humans.

Supplemental D-ribose is associated with many benefits. These benefits include greater energy, less fatigue, and faster muscle recovery. These benefits relate to the capacities of D-ribose as a total body energizer because it boosts energy production (as ATP) in the body.

For individuals suffering low energy levels associated with chronic fatigue syndrome (CFS), low energy levels, and other problems related to low energy (ATP) production, D-ribose can mean a significantly higher level of energy. In cases of extremely low energy, it can mean the capacity to function more normally.

ribose energy woman power health

D-ribose energizes every cell in our bodies.

Athletes and bodybuilders were among the earliest to recognize D-ribose for purposes of improving performance and recovery times. D-Ribose also exerts anti-anxiety, stress reduction, and potential anti-depressant properties. There is additional evidence suggesting that supraphysiological amounts of ribose may have cardioprotective effects, especially for the ischemic heart.

Supplemental D-ribose usually comes in the form of a sweet, crystalline, water-soluble powder. It is also available in capsules or tablets, including chewable tablets.

Humans synthesize d-ribose from foods, including glucose and various dietary sugars. But there are benefits to supplemental D-ribose. One of the major reasons is the important role of D-ribose in the production of energy (ATP) in human cells.

D-RIBOSE BENEFITS

• GREATER ENERGY (ATP) PRODUCTION

• FASTER RECOVERY

• REDUCED FATIGUE

• IMPROVES ATHLETIC PERFORMANCE

• SUPPORTS MITOCHONDRIAL FUNCTION

• AIDS CHRONIC FATIGUE AND FIBROMYALGIA

• SUSTAINS CARDIAC AND SKELETAL MUSCLE

• BETTERS PHYSIOLOGICAL FUNCTION UNDER ANAEROBIC CONDITIONS

• SUPPORTS LONGEVITY OF BLOOD CELLS

• ANTI-ANXIETY EFFECTS

• STRESS REDUCTION

ribose sugar natural heart energy ATP RNA

D-ribose is heart healthy unlike most dietary sugars (e.g., sucrose).

RIBOSE FOR ENERGY (ATP) PRODUCTION

The body uses D-ribose to generate adenosine triphosphate (ATP).  ATP provides energy for all bodily movements and every chemical reaction in cells. ATP is the source of all energy in the body and it’s constantly broken down and recreated due to the processes of life.

The adenine portion of ATP consists of one molecule of adenine and ribose (i.e., five-carbon sugar). The triphosphate portion of ATP consists of three phosphate molecules. When a phosphate breaks off from ATP, then energy is released. The compound then becomes adenosine diphosphate (ADP), which consists of adenosine and two phosphate molecules. When another phosphate molecule breaks off, it becomes adenosine monophosphate (AMP).

It is well established that ratios of ATP, ADP, and AMP are essential for regulating energy in cells. Under extreme physiological stress (e.g., high-intensity exercise), our cells cannot recreate ATP rapidly enough to supply cells with required energy. Concentrations of ADP and AMP rise causing a reduction in cellular energy. When the body’s rate of ATP use continues exceeding the rate at which it can be generated, cells “lose” nucleotides in order to restore the ratio between ATP, ADP, and AMP.

During anaerobic metabolism, AMP levels can rise within cells, thereby disturbing the ratios of ATP to ADP and AMP. The body can reduce AMP concentrations by degrading AMP to simpler end products resulting in a significant decrease in the adenine nucleotide pool. Under extreme conditions (e.g., prolonged high-intensity exercise or the diminished blood flow to tissues witnessed in ischemia), the adenine nucleotide pool may decrease by 30–50%. These effects can significantly compromise physical performance.

Here is where D-ribose supplementation works to support energy production. Supplemental D-ribose allows the body to bypass relatively slow conversion steps required for recreating the adenosine nucleotide providing critical material for ATP production. That is, D-ribose can increase the speed of nucleotide replacement. This has implications not only for sports performance, but also for general health. D-ribose is especially useful in situations where greater energy may be required, as in low energy, chronic fatigue, fibromyalgia, or combating the effects of aging.

D-RIBOSE RATE-LIMITING SUGAR FOR NUCLEOTIDE SYNTHESIS

One of the most important aspects of D-ribose for health relates to the fact that it is the rate-limiting compound that regulates the activity of the purine nucleotide pathway of adenine nucleotide metabolism. As such, ribose plays a central role not only in the synthesis of ATP, but also of coenzyme-A, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), DNA, RNA, and other important cellular constituents.

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

Specifically, human muscle cells (e.g., heart and skeletal muscle cells) do not rapidly replace lost nucleotides because of the lack of two rate-limiting enzymes in the pentose phosphate pathway metabolizing glucose to ribose-5-phosphate. Ribose itself forms 5-phosphoribosyl-1-pyrophosphate, a rate-limiting compound in nucleotide synthesis. As noted, supplemental D-ribose allow the body to bypass the rate-limited steps of the pentose phosphate pathway, thereby accelerating nucleotide synthesis (and salvage).

STOPPING THE VICIOUS CYCLE OF ENERGY DEPLETION

It should not take a genius to figure out that when energy production is optimized, overall health will improve. Yet, the same principle also applies in reverse. That is, there are many instances in which low energy levels can fuel lower energy levels. For example, when illness, stressors, or other factors deplete large amounts of the body’s supply of energy, they can gradually (or not so gradually) lessen the body’s capacity to produce more by overtaxing the energy production system.

This cascade of reduced energy production can become a vicious cycle in which there are few reserves left to support the body’s need for greater energy. D-Ribose is one of the only nutrients that can reverse the downward spiral in ATP production when demands exceed supply. By feeding the body’s own system for producing energy, and thereby supplying the raw material required to produce it, supplemental D-ribose can helps break the cycle of low energy levels.

fatigue ribose natural sugar energy atp cells

Chronic low energy? D-ribose is required for creating energy for all biological functions.

A ROLE FOR SUPPLEMENTAL D-RIBOSE

To recap the importance of supplemental D-ribose: D-ribose increases the rate at which ATP is generated. This improves exercise performance and allows for faster muscle growth. All this is possible because supplemental ribose helps the body bypass the conversion steps needed to create or re-create adenosine nucleotides.

Because replacing adenine nucleotides normally requires a certain amount of time, providing the body with D-ribose supplementally via diet can reduce rates of healing and repair in muscle cells. That is, supplemental D-ribose can increase the speed at which adenosine nucleotides are replaced by providing raw material for the creation of more ATP. That is how D-ribose improves athletic performance and supports optimal energy production, as well as optimal muscle health.

The significance of the science behind ATP production is that almost everyone can benefit from supplemental D-ribose. Whether you are an athlete requiring rapid repletion of energy, a person suffering from low energy levels or chronic fatigue, or anyone who wishes to improve energy production supporting optimal health.

ribose energizes beautiful athletic girl with colorful balloons jumping on the beach

Fatigued to fantastic: a plentiful supply of D-ribose helps ensure an abundance of energy.

REJUVENATE! SUPERFOODS INCLUDE D-RIBOSE

We at HPDI have focused our efforts on formulating the most effective nutritional supplements and superfoods. When Dr. Hank Liers formulated our original high-RNA Rejuvenate! superfood, he put D-ribose into it. In fact, all of our Rejuvenate! superfoods provide significant amounts of D-ribose.

Rejuvenate! (original greens) provides 1,500 mg D-ribose per serving (one small scoop). Rejuvenate! PLUS provides 1,800 mg per serving (two scoops). Rejuvenate! Berries & Herbs provides 2,000 mg per serving (two scoops).

ribose energy dietary nucleic acids rejuvenate superfoods

All Rejuvenate! superfoods provide high levels of D-Ribose.

A major reason HPDI includes D-ribose in its superfoods–and perhaps the most obvious one–is simply that we formulate unique, high-RNA superfoods to support optimal energy production in the body. D-ribose supports that goal by various means.

D-ribose is the rate-limiting sugar for the uptake and assimilation of dietary nucleic acids (RNA, DNA, nucleotides, and nucleosides). This is because D-ribose is actually the sugar backbone of these nutrients. As such, the body requires D-ribose in order to utilize and create (or recreate) dietary nucleic acids.

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

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

Thus, D-ribose plays important roles as an essential part of nucleic acids, nucleotides, and nucleosides; in the production of energy (as ATP); and the synthesis and salvage of nucleotides in the body.

Rejuvenate! superfoods are formulated to provide high levels of nucleic acids. D-ribose helps the body optimize its use of nucleic acids and their constituent components. Having D-ribose in our superfoods not only supports energy production directly, but also allows maximum use of the dietary RNA they are formulated to provide.

Rejuvenate! superfoods provide nutrients that boost energy levels significantly and consistently for optimal health, healing, and wellness. The inclusion of D-ribose importantly supports the powerful nucleic acid nutrition these superfoods offer, as well as supplements the body’s intake and synthesis of D-ribose.

ribose energy rejuvenate plus (500g) RNA nucleic acids doctor hank liers original

REJUVENATE! PLUS provides 1,800 mg of D-ribose per serving.

SUMMARY

D-Ribose of one of the most important natural sugars for life and health. It is one of the few nutrients that can boost energy levels naturally. When taken with other important biological nutrients, including dietary RNA, DNA, nucleotides, and nucleosides, D-ribose is truly a nutritional powerhouse that can support good health and the energy levels required to live life to its fullest. We believe the best way to obtain supplemental D-ribose is to consume Rejuvenate! superfoods.

SOURCES & RESOURCES

REJUVENATE! SUPERFOODS

REJUVENATE! PLUS

REJUVENATE! BERRIES & HERBS

REJUVENATE! ORIGINAL (GREENS)

REJUVENATE! COMPARISON GUIDE

HPDI BLOG ARTICLES

GET RESULTS WITH REJUVENATE SUPERFOODS

9 THINGS TO KNOW ABOUT REJUVENATE! SUPERFOODS

DIETARY RNA FOR ATHLETIC PERFORMANCE

TECHNICAL INFORMATION

Pentose-Phosphate Pathway: Elsevier’s Review of Biochemistry

From Fatigued to Fantastic (excerpt) by Jacob Teitelbaum, MD

D-Ribose technical information (Vista Chemicals)

Enhancing Cardiac Energy with Ribose (LEF)

SCIENTIFIC STUDIES

The Use of D-Ribose in Chronic fatigue syndrome and fibromyalgia (J Altern Complement Med.)

D-Ribose Aids Advanced Ischemic Heart Failure Patients (Int J Cardiol.)

D-Ribose, a Metabolic Substrate for Congestive Heart Failure (Prog Cardiovasc Nurs.)

D-Ribose as a Supplement for Cardiac Energy Metabolism (J Cardiovasc Pharmacol Ther.)

Ribose Accelerates the Repletion of the ATP Pool During Recovery from Reversible Ischemia of the Rat Myocardium (J Mol Cell Cardiol.)

Significance of the 5-phosphoribosyl-1-pyrophosphate pool for cardiac purine and pyrimidine nucleotide synthesis: studies with ribose, adenine, inosine, and orotic acid in rats (Cardiovasc Drugs Ther.)

Stimulation of Myocardial Adenine Nucleotide Biosynthesis by Pentoses and Pentitols (Pflugers Arch.)

The Role of Ribose on Oxidative Stress During Hypoxic Exercise (J. Med. Food)

D-Ribose Benefits Restless Legs Syndrome (J Altern Complement Med.)