Dr. Hank Liers, PhD myo-mag magnesium malic acid energizing formulaFred Liers PhD myo-mag magnesium malic acid energizing supplement

Got energy? That’s a big question. Many people are low on energy. A major cause of low energy is magnesium deficiency. In fact, studies show 50%–90% of people are deficient, often highly deficient. Magnesium boosts energy levels by feeding the body’s energy production system or Krebs cycle.

Myo-Mag— HPDI’s magnesium and malic acid formula — is designed to supercharge your energy production system to support a high energy lifestyle. Are you ready for what Myo-Mag can do for your energy? Well, it boosts energy, but does a lot more, too!

Getting enough magnesium is critical, of course. But it is equally important to get readily assimilable forms of magnesium and the synergistic nutrients required for its uptake and utilization. Myo-Mag provides optimal forms of magnesium and synergistic nutrients required to create energy (as ATP) for higher energy living. Myo-Mag feeds the body’s energy production system (Krebs cycle), which maximizes cellular energy. That is why users of Myo-Mag report far greater energy levels.


Myo-Mag supplies critical nutrients for energy production (as ATP) in the body. But it offers benefits far beyond boosting energy levels. Being a super magnesium formula, Myo-Mag optimizes all other beneficial effects of magnesium. In addition to energy production, magnesium is essential for muscle health, cardiovascular health, balancing calcium levels (and ensuring proper calcium uptake), as well as for proper function of more than 800 enzyme systems in the body.


ENERGYMyo-Mag supplies your cellular energy system with raw materials it can use immediately to produce energy for high vitality living. Myo-Mag can help you create energy fast—and naturally!

• MENTAL ENERGY – Just as Myo-Mag boosts physical energy, it can also boost mental energy. The energizing forms of magnesium and synergistic nutrients it provides create cellular energy the body can use for all purposes requiring energy.

MUSCLE RECOVERYMyo-Mag supports muscle health, muscle use, and muscle recovery. You might call Myo-Mag a muscle formula, and indeed “Myo” means “muscle” in Greek. Muscles that are properly nourished function well and are loose, not contracted, overly tight, or cramped. Muscles can benefit from Myo-Mag!

RELAXATION AND CALMING – In addition to being an “energy” production formula, Myo-Mag provides forms of magnesium and other nutrients that allow the body to relax. Muscle relaxation is a well known effect of magnesium. Also, the counterbalancing effect of magnesium on calcium in cells contributes to a relaxation effect. Too much calcium by itself (without being balanced) by magnesium can lead to muscle contraction and tension.

• GREATER SENSE OF WELL-BEINGMyo-Mag can provide an overall sense of well being. This is likely due both to the wide range of benefits and effects of magnesium (see list below) combined with the benefits of the synergistic nutrients it provides. For example, a combination of the known benefits of muscle relaxation, improved mood, and increased vitality can together contribute to an overall increased sense of well-being.

• CARDIOVASCULAR HEALTH – The heart is a muscle and gain major benefits from the right forms of magnesium, like other muscles

• HEADACHES – The ingredients in Myo-Mag are known to help headaches, including migraine headaches

• MANY OTHER BENEFITS – Due to its status as an exceptional magnesium & malic acid formula, Myo-Mag provides all benefits associated with magnesium (see list below), but also supercharges these benefits due to the malic acid (malate), B vitamins, and other synergistic nutrients.

myo-mag magnesium malic acid energizing formula


Myo-Mag is an advanced magnesium formula that supports metabolism, energy production (ATP), and optimal cellular function. It allows for rapid uptake and absorption of easily assimilated forms of magnesium. It also provides critical nutrients supporting energy production in the body. Because Myo-Mag rapidly boosts magnesium levels, individuals usually notice greater physical and mental energy, reduced fatigue, and often a greater sense of overall well being.


Myo-Mag contains ingredients participating in the production of ATP. One vegetarian capsule contains 100 mg of magnesium and over 300 mg of malic acid. Vitamin B1 is included as Thiamin HCl and vitamin B2 is included as both Riboflavin and Riboflavin 5′-phosphate. Also included are vitamin B6 in its pyridoxal 5′-phosphated coenzyme form, manganese (because high levels of magnesium can deplete the body of it), magnesium carbonate (a malic acid buffer), and glycine as the carrier for a portion of the magnesium and for the manganese.

Supplementing the diet with magnesium and malic acid may reverse conditions of low energy. Suggested daily amounts include 300–600 mg of magnesium and 1200–2400 mg of malic acid.


There are several key nutrients needed by mitochondria to manufacture ATP in the body. These include oxygen, magnesium, food substrate, ADP, and inorganic phosphate, as well as Vitamin B1, Vitamin B2, and Vitamin B6 in their phosphorylated (coenzyme) forms.

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

Insufficient amounts of ATP means that some B vitamins may not be adequately phosphorylated leading to improper metabolism and further reductions in ATP production. The much less efficient anaerobic production of ATP may be utilized to a greater extent. A balance point may be reached wherein the body produces only a fraction of the optimal amount of ATP. Under these conditions muscle weakness and fatigue may occur.

Vitamin B6 in its coenzyme form (pyridoxal-5’-phosphate) and magnesium are required for normal activity of malate dehydrogenase enzymes  involved in ATP production in the Krebs Cycle. In addition, the respiratory chain involved in ATP synthesis requires adequate amounts of the coenzyme  forms of B vitamins B1 and B2, which are the precursors of NAD and FAD. These two B vitamins, like B6, require a magnesium-dependent phosphate transfer reaction to become biologically active. Magnesium deficiency would therefore create a sluggish respiratory chain and a decreased efficiency in the transfer of reducing equivalents from the cytosol to the mitochondria. Supplementing the diet with magnesium and malic acid boosts energy production and thereby can reverse conditions of low energy.

In “Management of Fibromyalgia: Rationale for the Use of Magnesium and Malic Acid,” Abraham and Flechas reported that supplementing the diet with magnesium and malic acid may reverse such conditions of low energy (Jrnl of Nutritional Medicine 1992 3: 49–59). The recommended daily amounts include 300–600 mg of magnesium and 1200–2400 mg of malic acid.


Magnesium is a key ingredient in Myo-Mag which provides 100 mg per capsule in the form of magnesium malate. Magnesium plays a major role in energy production in the body. In particular, magnesium plays a critical role in key enzymatic reactions  for both aerobic and anaerobic glycolysis, which is the oxygen-dependent metabolic pathway that coverts glucose in to energy at ATP and NADH.

In order to appreciate the many benefits Myo-Mag offers, it helps to understand the effects and benefits of magnesium. Magnesium levels influence many physiological processes and functions. These include:

• Increases energy by greater production of ATP (adenosine triphosphate) in cells
• Supports production and function of over 800 enzyme systems in the body
• Relaxes muscles / reduces muscle tension
• Boosts vitality, endurance, and strength
• Improves cardiovascular / heart health (relaxes cardiac muscle)
• Relieves pain, including chronic pain
• Ideal for arthritis / fibromyalgia / joint pain
• Improves health of skin and mucous membranes
• Eases headaches and migraine headaches
• In sports medicine — replenishes Mg levels for energy (combats fatigue, and
soothes pain and sore muscles)
• Improves mood and reduces stress
• Increases memory and cognitive functions
• Boosts immune system
• Improves assimilation of calcium / builds stronger bones
• Balances calcium and magnesium levels in cells
• Proven antimicrobial and antiseptic
• Raises DHEA (dehydroepiandrosterone) levels naturally
• Eases menopause and premenstrual syndrome (pms)
• Supports healthy libido (and endocrine system)
• Anti-aging, rejuvenating, revitalizing
• Keeps cell membranes flexible
• Controls cholesterol production in the body
• Regulates blood sugar levels / needed for insulin production, transport, and
function in cells
• Supports antioxidant systems
Given the wide range of benefits conferred by magnesium on the human body, it becomes apparent that no level of deficiency is acceptable. Magnesium is simply critical for life and for health. It is far better to have more magnesium than less.
MYO-MAG contains three types of magnesium: magnesium malate, magnesium carbonate, and magnesium diglycinate. As noted, the malate form of magnesium offers the unique benefit of feeding the energy production system in the body. The magnesium carbonate in the formula acts as a buffering agent while magnesium glycinate is absorbed into the bloodstream thereby increasing absorption beyond the gastrointestinal tract.


Myo-Mag provides malic acid via magnesium malate, which breaks down in the body into about 80% malic acid and 15% magnesium. Malic acid is a compound (molecular formula C4H6O5made by all living organisms. Malic acid contributes to the sour taste of fruits, and its name derives from the Latin word for apple. Esters and salts of malic acid are known as malates. The malate anion is an intermediate in the citric acid cycle, or Krebs cycle, which produced energy (ATP) in the body.
According to Abraham and Flechas (1992): “Malate is the only metabolite of the citric acid cycle which correlates positively with physical activity.” They add: “Following endurance training of athletes, muscles were characterized by a 50% increase in the malate-aspartate redox shuttle enzymes, where malate plays a key role…When there is increased demand for ATP, there is also an increased demand and utilization of malate.”


Myo-Mag includes manganese because high levels of magnesium can deplete manganese. The classes of enzymes that have manganese cofactors is large and includes oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, lectins, and integrins. The reverse transcriptases of many retroviruses (though not lentiviruses such as HIV) contain manganese. The best-known manganese-containing polypeptides may be arginase and Mn-containing superoxide dismutase (Mn-SOD)

Manganese is an essential human dietary element. It is present as a coenzyme in several biological processes, which include macronutrient metabolism, bone formation, and free radical defense systems. It is a critical component in dozens of proteins and enzymes. The human body contains about 12 mg of manganese, mostly in the bones. The soft tissue remainder is concentrated in the liver and kidneys. In the human brain, the manganese is bound to manganese metalloproteins, most notably glutamine synthetase in astrocytes.


Taking 1–3+ Myo-Mag provide nutrients that help the body create energy. However, taking 3–6 (or more) Myo-Mag daily would meet the need for supplementing with 300–600 mg of magnesium and 1200–2400 mg of malic acid that is known to reverse conditions of low energy. We recommend starting low (1-2 capsules) and then gradually increasing the dosage. Myo-Mag is contained in a vegetarian capsule to ensure rapid assimilation.

COMPOSITION: One (1) vegetarian capsule of Myo-Mag provides the following percentages of the Daily Value:

Magnesium (Mg malate, diglycinate, carbonate) 100 mg 24%
Malic Acid (Mg malate)
300 mg *
Manganese (Mn diglycinate) 5 mg 217%
Vitamin B1 (Thiamin HCl) 10 mg 633%
Vitamin B2 (Riboflavin) 8 mg 615%
Vitamin B2 (Riboflavin-5′-phosphate) 2 mg 154%
Vitamin B6 (Pyridoxal-5′-phosphate) 5 mg 294%
Glycine (Mg and Mn diglycinate) 160 mg *

* No established Daily Value

DIRECTIONS: As a dietary supplement take 1–3+ capsules daily, or as directed by a health care professional.

INGREDIENTS: MYO-MAG only contains the highest-quality USP grade magnesium malate, magnesium diglycinate, magnesium carbonate, manganese diglycinate, thiamin HCl, riboflavin, pyridoxal-5′-phosphate, riboflavin-5′-phosphate, vegetable cellulose (capsule), microcrystalline cellulose, and silica.

MYO-MAG does not contain wheat, rye, oats, corn, barley, gluten, soy, egg, dairy, yeast, sugar, GMOs, sulfates, chlorides, wax, preservatives, colorings, or artificial flavorings.


Energy is important for life and health. And whether you realize it or not, large numbers of factors—some of which are beyond your control—conspire daily to rob you of energy. These factors may include low magnesium levels, stress to EMF exposure (like Wi-Fi or cell phone radiation), adverse dietary influences (like glyphosate/RoundUp), other chemical and/or environmental exposures, and even just lack of exercise. One of the easiest things to do is to take Myo-Mag to get the magnesium, malic acid, and synergistic nutrients you need to build greater energy levels. Get ready to blast off! ⚡



Myo-Mag Magnesium & Malic Acid Formula

HPDI Mineral Formulas

Myo-Mag on Amazon

HPDI Blog Articles

The Health Benefits of Oral Magnesium Using Myo-Mag by Dr. Hank Liers


Uses and Benefits of Magnesium Glycinate

Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection
(J Parenter Enteral Nutr Sep-Oct 1994;18(5):430-5.)


Natural Phytochemical Nrf2 Activators for Chemoprevention

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


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

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

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

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

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

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

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

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

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


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

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

Ultimate Protector+

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

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

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

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

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


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

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

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

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


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

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

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

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

Ultimate Protector is now available on the HPDI website!


Ultimate Protector+Ultimate Protector+ is new and improved



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

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

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

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

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

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

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

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

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

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

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

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

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


Ultimate Protector™

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

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

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

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


New Directions For Preventing Free Radical Damage

Dr. Hank Liers, PhD free radical damage

As you may know, free radical damage is associated with virtually every major health condition. For many years we have recommended taking antioxidants to protect against free radicals and for preventing free radical damage to the body.

Antioxidants we recommend include Vitamin C, Vitamin E, plant polyphenols (e.g., grape seed extract), green tea extract, rutin and other bioflavonoids, and amino acids and peptides (e.g., n-acetyl-l-cysteine and glutathione) to deal with free radicals. Using this approach, individuals often achieve excellent results.

In the last ten years, a new approach has become a major topic of scientific interest and research. This approach utilizes substances that induce strong activation of the body’s own enzyme systems. Some natural substances under study include turmeric (curcumin), sulforaphane (found in broccoli sprouts), transresveratrol (found in red wine and giant knotweed), and green tea extracts.

Nrf2 Activators Produce Antioxidant Enzymes Combating Free Radicals

Researchers specifically are studying how enzyme-activating substances activate a transcription factor known as Nrf2 that causes the body to produce higher levels of enzymes including superoxide dismutase (SOD), catalase, heme oxygenase, and glutathione peroxidase.

A human clinical trial of a nutritional supplement containing turmeric, milk thistle extract, green tea extract, bacopa, and ashwaganda showed this combination of phytochemicals can reduce lipid peroxides in the body by significant amounts after only one month. Further research on this same supplement has shown these enzyme inducers affect the function of up to 4,000 genes in the body related to internal protection systems.

Currently there are several supplements on the market that are classified as Nrf2 activators. My own approach to this includes a combination approach using very powerful antioxidants (for example, those with extremely high ORAC5.0 values such as whole grape extract) in combination with Nrf2 activators derived from plant extracts (such as transresveratrol and curcumoids).

My updated product (Ultimate Protector+) using this approach will be available in July 2019 so be on the look out for it!

Ultimate Protector+


Ultimate Protector+ is a next-generation cell protection formula providing high levels of non-GMO Vitamin C, calcium and magnesium malate (supports ATP and enzyme production), a full spectrum of exceptionally high potency antioxidants (in accordance with ORAC6.0 testing), many of the most powerful natural Nrf2 protective enzyme activators, and Bioperine® to facilitate absorption of all ingredients – all in a single product! This potent combination of characteristics distinguishes our formula so that no other single product available today offers such complete protection. This is the best formula available for countering free radical damage. 100% non-GMO. 180 veggie caps per bottle.

ULTIMATE PROTECTOR+ contains USP-grade non-GMO Ascorbic Acid, 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+provides completecoverage for free-radical protection by satisfying three distinct needs in single cell protection formula:

Mode 1) A non-GMO Vitamin C product. Ultimate Protector+contains a Vitamin C formula without genetically modified sources of corn, potatoes, or beets. 100% Non-GMO Vitamin C!

Mode 2) A single, powerful antioxidant formula. Ultimate Protector+ provides a powerful 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), peroxynitrite (ONOO-), and hypochlorite (HOCl).

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 six types of free radicals were constrained by limited testing procedures. However, new technological developments have resulted in a comprehensive testing method called the Total ORAC6.0 assay. Because of the development of the Total ORAC6.0™ test, it is now possible to target and measure the effects of antioxidants on the six major types of free radicals found in the body. Recently [8/2019] Brunswick Labs has tested ULTIMATE PROTECTOR+™ using the new ORAC6.0 test. The results reveal an incredible overall ORAC6.0 value of 272,743 µmole TE/gram (i.e., 272,743 per gram!). This corresponds to a total ORAC6.0 value per of over 968,000 μmole TE per serving of six small capsules. In addition, the ORAC5.0 value was measured to be over 950,000 μmole TE per serving. The results have shown that the formula offers excellent protection against all of the six major types of free radicals found in the body.

Mode 3) A full spectrum of Nrf2 activators. Ultimate Protector+ is a supplement providing a broad range of the most powerful natural Nrf2 transcription factor activators that allow the body to make its own antioxidant enzymes (e.g., superoxide dismutase (SOD), catalase, heme oxygenase, and glutathione peroxidase). Scientific research has shown that these are found in a wide range of fruits, vegetable, and herbs and that products which provide a wide range of Nrf2 activators give significantly higher levels of the endogenously produced antioxidant enzymes.





Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberry Ultimate Protector+ includes goji berry extract (also known as wild fresh goji berry fruit powder extract and wolfberry extract), 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 goji berry (Lycium barbarum) extract which is a component of SFB® – Standardized Fruit Blend from Ethical Naturals, Inc.

Ultimate Protector+ Includes Goji Berry

Ultimate Protector+ Includes Goji Berry

SFB® is a proprietary formula that combines extracts from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry. It is high in fruit polyphenols, flavonoids, anthocyanins, catechins, proanthocyanins, ellagic acid, xanthines, chlorogenic acid, pterostilbenes, resveratrol, phloridzin, quercetin, zeaxanthin, carotinoids, polysaccharides, quinic acid, and more. With its diverse blend, SFB® offers over 40-50% polyphenols as well as >9,000 ORAC units in a single gram.

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


The Goji Berry extract in Ultimate Protector+ is non-GMO and has been extracted with  water. Testing has indicated the product contains over 1.5% polyphenols. In numerous epidemiological studies, goji berries have been associated with a decreased risk of chronic diseases such as cardiovascular disease, cancer, and asthma.


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.

Scientific Studies on the Antioxidant Effects of GOJI BERRIES

Databases of scientific studies (like the National Institutes of Health (NIH) PubMed database) contain numerous of up-to-date studies and abstracts about goji berries.

Below we provide a few relevant scientific studies on the health benefits of goji berries.

Goji Berries as a Potential Natural Antioxidant Medicine: An Insight into Their Molecular Mechanisms of Action.

Oxid Med Cell Longev. 2019 Jan 9;2019:2437397. doi: 10.1155/2019/2437397. eCollection 2019.
Authors: Ma ZF, Zhang H, Teh SS, Wang CW, Zhang Y, Hayford F, Wang L, Ma T, Dong Z, Zhang Y, Zhu Y1
From: https://www.ncbi.nlm.nih.gov/pubmed/30728882


Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.

An evidence-based update on the pharmacological activities and possible molecular targets of Lycium barbarum polysaccharides

Drug Des Devel Ther. 2015; 9: 33–78.
Authors: Jiang Cheng, Zhi-Wei Zhou, Hui-Ping Sheng, Lan-Jie He, Xue-Wen Fan, Zhi-Xu He, Tao Sun, Xueji Zhang, Ruan Jin Zhao, Ling Gu, Chuanhai Cao,  and Shu-Feng Zhou
From: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277126/


Lycium barbarum berries, also named wolfberry, Fructus lycii, and Goji berries, have been used in China and other Asian countries for more than 2,000 years as a traditional medicinal herb and food supplement. L. barbarum polysaccharides (LBPs) are the primary active components of L. barbarum berries and have been reported to possess a wide array of pharmacological activities. Herein, we update our knowledge on the main pharmacological activities and possible molecular targets of LBPs. Several clinical studies in healthy subjects show that consumption of wolfberry juice improves general wellbeing and immune functions. LBPs are reported to have antioxidative and antiaging properties in different models. LBPs show antitumor activities against various types of cancer cells and inhibit tumor growth in nude mice through induction of apoptosis and cell cycle arrest. LBPs may potentiate the efficacy of lymphokine activated killer/interleukin-2 combination therapy in cancer patients. LBPs exhibit significant hypoglycemic effects and insulin-sensitizing activity by increasing glucose metabolism and insulin secretion and promoting pancreatic β-cell proliferation. They protect retinal ganglion cells in experimental models of glaucoma. LBPs protect the liver from injuries due to exposure to toxic chemicals or other insults. They also show potent immunoenhancing activities in vitro and in vivo. Furthermore, LBPs protect against neuronal injury and loss induced by β-amyloid peptide, glutamate excitotoxicity, ischemic/reperfusion, and other neurotoxic insults. LBPs ameliorate the symptoms of mice with Alzheimer’s disease and enhance neurogenesis in the hippocampus and subventricular zone, improving learning and memory abilities. They reduce irradiation- or chemotherapy-induced organ toxicities. LBPs are beneficial to male reproduction by increasing the quality, quantity, and motility of sperm, improving sexual performance, and protecting the testis against toxic insults. Moreover, LBPs exhibit hypolipidemic, cardioprotective, antiviral, and antiinflammatory activities. There is increasing evidence from preclinical and clinical studies supporting the therapeutic and health-promoting effects of LBPs, but further mechanistic and clinical studies are warranted to establish the dose–response relationships and safety profiles of LBPs.

Biological activities and potential health benefit effects of polysaccharides isolated from Lycium barbarum L.

2013 Mar;54:16-23. doi: 10.1016/j.ijbiomac.2012.11.023. Epub 2012 Nov 28.
Jin M1, Huang Q, Zhao K, Shang P.
From: https://www.ncbi.nlm.nih.gov/pubmed/23200976


Recently, isolation and investigation of novel ingredients with biological activities and health benefit effects from natural resources have attracted a great deal of attention. The fruit of Lycium barbarum L., a well-known Chinese herbal medicine as well as valuable nourishing tonic, has been used historically as antipyretic, anti-inflammation and anti-senile agent for thousands of years. Modern pharmacological experiments have proved that polysaccharide is one of the major ingredients responsible for those biological activities in L. barbarum. It has been demonstrated that L. barbarum polysaccharides had various important biological activities, such as antioxidant, immunomodulation, antitumor, neuroprotection, radioprotection, anti-diabetes, hepatoprotection, anti-osteoporosis and antifatigue. The purpose of the present review is to summarize previous and current references regarding biological activities as well as potential health benefits of L. barbarum polysaccharides.

Goji (Lycium barbarum and L. chinense): Phytochemistry, Pharmacology and Safety in the Perspective of Traditional Uses and Recent Popularity

Planta Med 2010; 76(1): 7-19
Author: Olivier Potterat
From: https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0029-1186218#AT0541-1


Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinensewith consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as “Lycium barbarum polysaccharides”, which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products.


Goji Berries are an important fruit full of polyphenols, antioxidants, polysaccharides (LBPs), carotenoids, and Nrf2 activators that help to make Ultimate Protector+ such an outstanding nutritional supplement.



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

Ultimate Protector+ contains curcuminoids (greater than 95% from turmeric), 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 curcuminoids. Curcuminoids are added as a separate ingredient in Ultimate Protector+.

Ultimate Protector+ Includes Curcumin

Ultimate Protector+ Includes Curcumin

Curcuminoids are the major active component of turmeric, a yellow compound isolated from the plant Curcuma longa (a member of the ginger family) and has been used for centuries in traditional medicines. Curcuminoids in turmeric include curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin (these are standardized in the Sabinsa Curcumin C3 Complex® ingredient).

turmeric plant curcuminoids

The turmeric plant produces beautiful flowers

Extensive research over the past 30 years indicates that these molecules can provide positive benefits against a wide range of health issues related to cell function, lungs, liver, nervous system, joint function, metabolism, and cardiovascular system. Numerous lines of evidence indicate that curcuminoids are highly pleiotropic with anti-inflammatory, hypoglycemic, antioxidant, wound healing, and antimicrobial activities.

Curcuminoids exert both direct and indirect antioxidant effects by scavenging reactive oxygen species (ROS) and inducing the expression of cytoprotective proteins in an Nrf2-dependent way. It is considered a bifunctional antioxidant. The nuclear-factor-erythroid-2-related factor 2 (Nrf2), is a ubiquitous master transcription factor which induces the endogenous production of cytoprotective proteins/enzymes through binding to antioxidant response elements (AREs) at the DNA/gene level.

An excellent and extensive online source of information on curcuminoids (curcumin) can be found at: http://examine.com/supplements/Curcumin/

Scientific Studies on the Health Protective Effects of Curcuminoids

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

Curcumin curcuminoids

Turmeric root is the source of curcuminoids

Below we provide a few relevant scientific studies on the antioxidant effects and potential health benefits of curcumin/curcuminoids.

Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets


Curcumin (diferuloylmethane), a yellow pigment in the spice turmeric (also called curry powder), has been used for centuries as a treatment for inflammatory diseases. Extensive research within the past two decades has shown that curcumin mediates its anti-inflammatory effects through the downregulation of inflammatory transcription factors (such as nuclear factor kappaB), enzymes (such as cyclooxygenase 2 and 5 lipoxygenase) and cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6). Because of the crucial role of inflammation in most chronic diseases, the potential of curcumin has been examined in neoplastic, neurological, cardiovascular, pulmonary and metabolic diseases. The pharmacodynamics and pharmacokinetics of curcumin have been examined in animals and in humans. Various pharmacological aspects of curcumin in vitro and in vivo are discussed in detail here.

Antioxidant and anti-inflammatory properties of curcumin


Curcumin, a yellow pigment from Curcuma longa, is a major component of turmeric and is commonly used as a spice and food-coloring agent. It is also used as a cosmetic and in some medical preparations. The desirable preventive or putative therapeutic properties of curcumin have also been considered to be associated with its antioxidant and anti-inflammatory properties. Because free-radical-mediated peroxidation of membrane lipids and oxidative damage of DNA and proteins are believed to be associated with a variety of chronic pathological complications such as cancer, atherosclerosis, and neurodegenerative diseases, curcumin is thought to play a vital role against these pathological conditions. The anti-inflammatory effect of curcumin is most likely mediated through its ability to inhibit cyclooxygenase-2 (COX-2), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS). COX-2, LOX, and iNOS are important enzymes that mediate inflammatory processes. Improper upregulation of COX-2 and/or iNOS has been associated with the pathophysiology of certain types of human cancer as well as inflammatory disorders. Because inflammation is closely linked to tumor promotion, curcumin with its potent anti-inflammatory property is anticipated to exert chemopreventive effects on carcinogenesis. Hence, the past few decades have witnessed intense research devoted to the antioxidant and anti-inflammatory properties of curcumin. In this review, we describe both antioxidant and anti-inflammatory properties of curcumin, the mode of action of curcumin, and its therapeutic usage against different pathological conditions.

Curcumin: The Indian Solid Gold


Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer’s disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal “Spice for Life”.

Curcumin decreases oxidative stress in mitochondria isolated from liver and kidneys of high-fat diet-induced obese mice


Oxidative stress plays a key role in obesity and diabetes-related mitochondrial dysfunction. Mitochondrial dysfunction is characterized by increased oxidative damage, nitric oxide (NO) synthesis, and a reduced ratio of adenosine-5′-triphosphate (ATP) production/oxygen consumption. Curcumin represents a potential antioxidant and anti-inflammatory agent. In this study, our objective was to determine the effect of curcumin treatment on oxidative stress and mitochondrial dysfunction in high-fat diet (HFD)-induced obese mice (OM). These results suggest that curcumin treatment increased oxygen consumption and significantly decreased lipid and protein oxidation levels in liver mitochondria isolated from HFD-induced OM compared with those in the untreated OM (UOM). In kidney mitochondria, curcumin treatment significantly increased oxygen consumption and decreased lipid and protein peroxidation levels in HFD-induced OM when compared with those in UOM. Curcumin treatment neither has any effect on body weight gain nor have any effects on mitochondrial NO synthesis. These findings suggest that obesity induces oxidative stress and mitochondrial dysfunction, whereas curcumin may have a protective role against obesity-induced oxidative stress and mitochondrial dysfunction.

Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients.

From: http://www.ncbi.nlm.nih.gov/pubmed/23745991


Radiation dermatitis occurs in approximately 95% of patients receiving radiotherapy (RT) for breast cancer. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the ability of curcumin to reduce radiation dermatitis severity in 30 breast cancer patients. Eligible patients were adult females with noninflammatory breast cancer or carcinoma in situ prescribed RT without concurrent chemotherapy. Randomized patients took 2.0 grams of curcumin or placebo orally three times per day (i.e., 6.0 grams daily) throughout their course of RT. Weekly assessments included Radiation Dermatitis Severity (RDS) score, presence of moist desquamation, redness measurement, McGill Pain Questionnaire-Short Form and Symptom Inventory questionnaire. The 30 evaluable patients were primarily white (90%) and had a mean age of 58.1 years. Standard pooled variances t test showed that curcumin reduced RDS at end of treatment compared to placebo (mean RDS = 2.6 vs. 3.4; P = 0.008). Fisher’s exact test revealed that fewer curcumin-treated patients had moist desquamation (28.6% vs. 87.5%; P = 0.002). No significant differences were observed between arms for demographics, compliance, radiation skin dose, redness, pain or symptoms. In conclusion, oral curcumin, 6.0 g daily during radiotherapy, reduced the severity of radiation dermatitis in breast cancer patients.

Curcumin attenuates insulin resistance in hepatocytes by inducing Nrf2 nuclear translocation

From: http://europepmc.org/abstract/med/22024084


BACKGROUND/AIMS: NF-E2-Related Factor-2 (Nrf2) is a transcription factor that plays a crucial role in the cellular protection against oxidative stress. Curcumin has been reported to induce Nrf2 nuclear translocation and upregulate the expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes in hepatocytes.This study was designed to investigate whether curcumin-induced Nrf2 nuclear translocation could reduce ROS-mediated insulin resistance in cultured LO2 hepatocytes. METHODOLOGY: Human LO2 hepatocytes were incubated with curcumin and glucose oxidase (GO) in the presence/absence of wortmannin (a phosphatidyinositol 3-kinase (PI3K) inhibitor). Oxidative stress, cellular damage, Nrf2 nuclear translocation and insulin resistance were measured. RESULTS: GO exposure significantly increased intracellular ROS, glutathione (GSH) depletion, malondialdehyde (MDA) formation, and increased activities of cellular lactate dehydrogenase (LDH) and aspartate amino transferase (AST), as well as causing insulin resistance. Curcumin pretreatment significantly attenuated these disturbances in intracellular ROS, liver enzyme activity and significantly antagonized the lipid peroxidation, GSH depletion and insulin resistance induced by GO in LO2 hepatocytes. These effects paralleled Nrf2 nuclear translocation induced by curcumin. Wortmannin partially blocked curcumin-induced Nrf2 nuclear translocation. In addition, wortmannin prevented curcumin-induced improvements in intracellular ROS, MDA formation, GSH depletion, liver enzyme activity and insulin resistance in cultured LO2 hepatocytes. CONCLUSIONS: These findings suggest that curcumin could reduce ROS-mediated insulin resistance in hepatocytes, at least in part through nuclear translocation of Nrf2.

Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer

From: http://www.greenmedinfo.com/article/curcumin-potentiated-significant-increase-nrf2-activation-it-restored-activityPLoS One.


Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated a significant role of curcumin during its long-term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. The present study was designed to investigate long-term effects of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated a significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.

Curcumin Activates the Heme Oxygenase-1 Gene via Regulation of Nrf2 and the Antioxidant Responsive Element

From: http://www.academia.edu/309816/Curcumin_Activates_the_Haem_Oxygenase-1_Gene_via_Regulation_of_Nrf2_and_the_Antioxidant-Responsive_Element


The transcription factor Nrf2, which normally exists in an inactive state as a consequenceof binding to a cytoskeleton-associated protein Keap1, can be activated by redox-dependent stimuli. Alteration of the Nrf2/Keap1 interaction enables Nrf2 to translocate to the nucleus, bind to the antioxidant responsive element (ARE) and initiates the transcription of genes encoding for detoxifying enzymes and cytoprotective proteins. This response is also triggered by a class of electrophilic compounds including polyphenols and plant-derived constituents. Recently, the natural antioxidants curcumin and caffeic acid phenethyl ester (CAPE) have been identified as potent inducers of heme oxygenase-1 (HO-1), a redox-sensitive inducible protein that provides protection against various forms of stress. Here, we show that in renal epithelial cells both curcumin and CAPE stimulate the expression of Nrf2 in a concentration- and time-dependent manner. This effect was associated with a significant increase in HO-1 protein expression and hemeoxygenase activity. From several lines of investigation we also report that curcumin (and, by inference, CAPE) stimulates HO-1 gene activity by promoting inactivation of the Nrf2/Keap1 complex leading to increased Nrf2 binding to the resident HO-1 AREs. Moreover, using antibodies and specific inhibitors of the mitogen-activated protein kinase (MAPK) pathways, we provide data implicating p38 MAPK in curcumin-mediated HO-1 induction. Taken together, these results demonstrate that induction of HO-1 by curcumin and CAPE requires the activation of the Nrf2/ARE pathway.

Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.


The medicinal properties of curcumin obtained from Curcuma longa L. cannot be utilised because of poor bioavailability due to its rapid metabolism in the liver and intestinal wall. In this study, the effect of combining piperine, a known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the bioavailability of curcumin in rats and healthy human volunteers. When curcumin was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg increased the serum concentration of curcumin for a short period of 1-2 h post drug. Time to maximum was significantly increased (P < 0.02) while elimination half life and clearance significantly decreased (P < 0.02), and the bioavailability was increased by 154%. On the other hand in humans after a dose of 2 g curcumin alone, serum levels were either undetectable or very low. Concomitant administration of piperine 20 mg produced much higher concentrations from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the increase in bioavailability was 2000%. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects.


Curcuminoids are important polyphenols, antioxidants, and Nrf2 activators that help make Ultimate Protector+ an outstanding nutritional supplement.