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ULTIMATE PROTECTOR+ INGREDIENTS – APPLE

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberry Ultimate Protector+ includes apple extract, as well as extracts from 12 different fruits, vegetables, and herbs. Each of these ingredients contain substances considered to be polyphenols, antioxidants, and Nrf2 activators. In this article, I explore the ingredient apple (Malus pumila mill.) extract, which is a component of SFB® – Standardized Fruit Blend from Ethical Naturals, Inc.

apple extract

Ultimate Protector+ Includes Apple

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, and quinic acid. With its diverse blend, SFB® offers over 40-50% polyphenols as well as >9,000 ORAC units in a single gram.

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

HEALTH BENEFITS OF APPLE

The Apple extract in Ultimate Protector+ has been extracted with non-GMO food grade ethanol and distilled water. Testing has indicated the product contains over 40% polyphenols. In numerous epidemiological studies, apples have been associated with a decreased risk of chronic diseases such as cardiovascular disease, cancer, and asthma.

When compared to many other commonly consumed fruits in the United States, apples had the second highest level of antioxidant activity. Apples also ranked the second for total concentration of phenolic compounds, and perhaps more importantly, apples had the highest portion of free phenolics when compared to other fruits.

APPLE PHYTOCHEMICALS

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

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

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

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

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

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

SCIENTIFIC STUDIES ON THE ANTIOXIDANT EFFECTS OF APPLE

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

Apple phytochemicals and their health benefits

Jeanelle Boyer1 and Rui Hai Liu1

Abstract

Evidence suggests that a diet high in fruits and vegetables may decrease the risk of chronic diseases, such as cardiovascular disease and cancer, and phytochemicals including phenolics, flavonoids and carotenoids from fruits and vegetables may play a key role in reducing chronic disease risk. Apples are a widely consumed, rich source of phytochemicals, and epidemiological studies have linked the consumption of apples with reduced risk of some cancers, cardiovascular disease, asthma, and diabetes. In the laboratory, apples have been found to have very strong antioxidant activity, inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol. Apples contain a variety of phytochemicals, including quercetin, catechin, phloridzin and chlorogenic acid, all of which are strong antioxidants. The phytochemical composition of apples varies greatly between different varieties of apples, and there are also small changes in phytochemicals during the maturation and ripening of the fruit. Storage has little to no effect on apple phytochemicals, but processing can greatly affect apple phytochemicals. While extensive research exists, a literature review of the health benefits of apples and their phytochemicals has not been compiled to summarize this work. The purpose of this paper is to review the most recent literature regarding the health benefits of apples and their phytochemicals, phytochemical bioavailability and antioxidant behavior, and the effects of variety, ripening, storage and processing on apple phytochemicals..

Cancer chemopreventive potential of apples, apple juice, and apple components.

 Gerhauser C1.

From: https://www.ncbi.nlm.nih.gov/pubmed/18855307

Abstract

Apples ( MALUS sp., Rosaceae) are a rich source of nutrient as well as non-nutrient components and contain high levels of polyphenols and other phytochemicals. Main structural classes of apple constituents include hydroxycinnamic acids, dihydrochalcones, flavonols (quercetin glycosides), catechins and oligomeric procyanidins, as well as triterpenoids in apple peel and anthocyanins in red apples. Several lines of evidence suggest that apples and apple products possess a wide range of biological activities which may contribute to health beneficial effects against cardiovascular disease, asthma and pulmonary dysfunction, diabetes, obesity, and cancer (reviewed by Boyer and Liu, Nutr J 2004). The present review will summarize the current knowledge on potential cancer preventive effects of apples, apple juice and apple extracts (jointly designated as apple products). In brief, apple extracts and components, especially oligomeric procyanidins, have been shown to influence multiple mechanisms relevant for cancer prevention in IN VITRO studies. These include antimutagenic activity, modulation of carcinogen metabolism, antioxidant activity, anti-inflammatory mechanisms, modulation of signal transduction pathways, antiproliferative and apoptosis-inducing activity, as well as novel mechanisms on epigenetic events and innate immunity. Apple products have been shown to prevent skin, mammary and colon carcinogenesis in animal models. Epidemiological observations indicate that regular consumption of one or more apples a day may reduce the risk for lung and colon cancer.

Apple Peel Polyphenols and Their Beneficial Actions on Oxidative Stress and Inflammation

. 2013; 8(1): e53725.
Marie Claude Denis, Alexandra Furtos, Stéphanie Dudonné, Alain Montoudis, Carole Garofalo, Yves Desjardins, Edgard Delvin, and Emile Levy
From: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553108/#

Abstract

Since gastrointestinal mucosa is constantly exposed to reactive oxygen species from various sources, the presence of antioxidants may contribute to the body’s natural defenses against inflammatory diseases.

Hypothesis

To define the polyphenols extracted from dried apple peels (DAPP) and determine their antioxidant and anti-inflammatory potential in the intestine. Caco-2/15 cells were used to study the role of DAPP preventive actions against oxidative stress (OxS) and inflammation induced by iron-ascorbate (Fe/Asc) and lipopolysaccharide (LPS), respectively.

Results

The combination of HPLC with fluorescence detection, HPLC-ESI-MS TOF and UPLC-ESI-MS/MS QQQ allowed us to characterize the phenolic compounds present in the DAPP (phenolic acids, flavonol glycosides, flavan-3-ols, procyanidins). The addition of Fe/Asc to Caco-2/15 cells induced OxS as demonstrated by the rise in malondialdehyde, depletion of n-3 polyunsaturated fatty acids, and alterations in the activity of endogenous antioxidants (SOD, GPx, G-Red). However, preincubation with DAPP prevented Fe/Asc-mediated lipid peroxidation and counteracted LPS-mediated inflammation as evidenced by the down-regulation of cytokines (TNF-α and IL-6), and prostaglandin E2. The mechanisms of action triggered by DAPP induced also a down-regulation of cyclooxygenase-2 and nuclear factor-κB, respectively. These actions were accompanied by the induction of Nrf2 (orchestrating cellular antioxidant defenses and maintaining redox homeostasis), and PGC-1α (the “master controller” of mitochondrial biogenesis).

Conclusion

Our findings provide evidence of the capacity of DAPP to reduce OxS and inflammation, two pivotal processes involved in inflammatory bowel diseases.

APPLE SUMMARY

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

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ULTIMATE PROTECTOR+ INGREDIENTS – CURCUMIN

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.

Abstract

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

Synopsis

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.

Abstract

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.

SUMMARY

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

ADDITIONAL RESOURCES

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OMEGA-3 ESSENTIAL FATS REMAIN “ESSENTIAL” – A REBUTTAL FROM OMNS

Fred Liers PhD omega-3 essential fats plus e EFA formulaOmega-3 essential fatty acids (EFA) are critically important for health. That is the reason we at HPDI include them in our foundational supplements system in the form of our Essential Fats Plus E formula. Essential Fats Plus E provides a balanced ratio of 4:1 omega-3 EPA to omega-6 GLA fatty acids proven to optimally support health.

As important as Omega-3 fats are in good health, various studies conclude they are of little value. In order to help clarity the fallacies found in such studies, this month we re-print the recent article “Omega 3 Fatty Acids and Cardiovascular Disease” from the Orthomolecular News Service (OMNS).

BACKGROUND

Essential fats including Omega-3 and Omega-6 are so important to health that we consider them as foundational or “core” to basic nutrition as multivitamins, antioxidants/vitamin C formulas, and high-RNA superfoods, like Rejuvenate! Plus.

Many of today’s health problems relate to deficiencies in Omega-3 essential fatty acids rather than overabundance of it. It makes sense for everyone to supplement their diets with at least a minimum amount of essential fats. This is addition to consuming foods high in Omega-3 (and Omega-6) essential fats, including leafy greens, nuts, seeds, and seed oils. Also, small amounts of wild-caught fish from clean waters. Preferably these fish would come from low on the food chain, such as sardines, herring, or young mackerel, for example.

In December 2107, my father Hank Liers, PhD, wrote “The Truth about Essential Fatty Acids.” In his article, he delves into detail about why essential fatty acids are critical for health.

The diagram below from Dr. Hank’s article shows in detail the pathways for the production and use of fatty acids in the body. In the figure the metabolic pathways (running left to right) for four fatty acids types are shown (top – Omega-3, second – Omega-6, third – Omega-9, bottom – Omega-7). Notice that only the omega-3 and omega-6 oils are considered to be essential fatty acids because they cannot be made in the body. This means they must come from food.

omega-3 fats omega-6 fats

Furthermore, an additional diagram from Dr. Hank’s article shown below provides details of the omega-6 and omega-3 pathways. Pathway specifics indicate key eicosanoids (series 1 prostaglandins [anti-inflammatory], series 2 prostaglandins [pro-inflammatory], and series 3 prostaglandins [anti-inflammatory]), oil sources, and important nutrient cofactors that are needed for the reactions to take place.

omega-3 fats omega-6 fats

In particular, Dr. Hank discusses how superior benefits to health result from a balanced 4:1 ratio between Omega-3 eicosapentanoic acid (EPA) fatty acids and Omega-6 gamma linoleic acid (GLA).

Below we list some of the functions and benefits obtained when by diet or supplementation the correct ratios and amounts of essential fatty acids are consumed.

• Regulate steroid production and hormone synthesis
• Regulate pressure in the eyes, joints, and blood vessels
• Regulate response to pain, inflammation, and swelling
• Mediate Immune Response
• Regulate bodily secretions and their viscosity
• Dilate or constrict blood vessels
• Regulate smooth muscle and autonomic reflexes
• Are primary constituents of cellular membranes
• Regulate the rate at which cells divide
• Necessary for the transport of oxygen from the red blood cells to tissues
• Necessary for proper kidney function and fluid balance
• Prevent red blood cells from clumping together
• Regulate nerve transmission

Dr. Hank also discusses the fallacy of thinking that supplemental Omega-3 fats alone are sufficient to produce health. That is, despite the relative lack of Omega-3 essential fats and the prevalence of Omega-6 fats in modern diets, it is nevertheless the forms (EPA and GLA)—and the critical 4:1 ratio between them—that makes the difference in how they act synergistically for health. The result of Hank’s scientific understanding of essential fatty acids has resulted in his formulation of a balanced EFA product, Essential Fats Plus E.

Orthomolecular Medicine News Service Article “Omega 3 Fatty Acids and Cardiovascular Disease”

Regarding the Orthomolecular Medicine News Service article “Omega 3 Fatty Acids and Cardiovascular Disease” (republished below) rebutting the “Cochrane Database of Systematic Reviews” which relies on so-called “Evidence Based Medicine” (EBM) to distort truth on Omega-3 essential fatty acids, the fact that Omega-3 fats are under such false attack represents a huge disservice to the public.

While essential fatty acids may not generate profits for corporations—and in fact may lead to improved health outcomes that threaten the use of chemicals and drugs—essential fats nevertheless remain foundational for health.

Above we have shown the important reasons Omega-3 fats and other essential fatty acids are scientifically termed “essential.” And why people continue taking essential fats, and giving them to their families and children, for supporting health and well-being. Primary among these reasons is that you cannot be healthy without them. Hence, they are essential. Why believe anyone who says otherwise?

The bottom line: Omega-3 essential fatty acids are critical for health. Supplementing the diet with them is a good idea for nearly everyone. This is especially true because typical diets are proven to be most deficient in Omega-3 among essential fats.

Below we re-print in full the recent article “Omega 3 Fatty Acids and Cardiovascular Disease” from the Orthomolecular News Service (OMNS) for the benefit of our HPDI blog readers. ~

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FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, Aug 6, 2018

Omega-3 Fatty Acids and Cardiovascular Disease

Commentary by Damien Downing, MBBS, MSB and Robert G. Smith, PhD

The Cochrane Database of Systematic Reviews has just updated its own review: Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease [1]. Here’s our take on it.

Michael Pollan, the brilliant food writer, reckoned you could sum up what to do about nutrition and diets in 7 words; “Eat food, not too much, mostly plants.” That sums up both what’s best for humans and what’s best for the planet.

We reckon you can sum up what’s wrong with evidence-based medicine (EBM) in 10 words; “Evidence is a waste of data; systematic reviews are palimpsests.” You can use that as a knife to quickly dissect this study.

There are many things wrong with this review. Somebody’s PR department has spun the review’s “no clear evidence of benefit” into “evidence of no benefit” – absence of evidence becoming evidence of absence. And clearly the media were entirely happy to take that one and run with it.

Systematic reviews are palimpsests

What’s a palimpsest? Back when things got written on vellum, an animal skin, not on paper, you didn’t throw it away; you recycled it and wrote over the original. It was called a palimpsest.

A systematic review gives an opportunity to write over the conclusions of a whole list of papers with your new version of the truth. You do that by the way that you select and exclude them.

For instance there was a meta-analysis (that’s a systematic review with more numbers) in 2005 that concluded that vitamin E supplements significantly increased the risk of death [2]. The way they did that was to rule out any study with less than 10 deaths – when fewer deaths was exactly the outcome they were supposed to be looking for.

The reason they gave for doing that was “because we anticipated that many small trials did not collect mortality data.” We’re not buying it; they used it as a trick to enable them to get the negative result they wanted – to over-write the findings of a long list of original studies.

And here we have authors doing the very same thing in this omega-3 study – and upping the ante slightly. Now the threshold is 50 deaths. Fewer than that and your study is ruled out of the final, supposedly least biased, analysis . . on the grounds that it’s more biased.

We don’t know how they could keep a straight face while saying (our interpretation); “The studies with fewer deaths showed more benefit from omega-3s, so we excluded them.” At least that’s what happened back in 2004 when the first version of this came out.[3]

But this is the 8th update (we think) and they no longer bother to tell you about what they included or excluded in detail, so we can only assume that if they had changed that exclusion they would have told us.

The weird thing is that they are allowed to do it. Nutrition researcher Dr. Steve Hickey has shown that in systematic reviews there is generally control for bias in the included studies, but none for bias in the actual review and its authors.[4,5]

They found not one example of adequate blinding among 100 Cochrane reviews (like this one); they could all be palimpsests. Do we know that they are fake? No, but it doesn’t matter: what we do know is that we can’t trust them. Nor can we trust this Cochrane review. Things haven’t changed since 2004.

Evidence is a waste of data

Evidence is what lawyers and courts use to find someone Guilty or Not Guilty, and we all know how that can go wrong. It’s a binary system: you’re either one or the other. But at least if you’re on trial all the evidence should be about you and whether you did the crime.

In EBM the evidence is all about populations, not about individuals. When a doctor tells you “There’s a 1 in 3 chance this treatment will work” he is required to base that on big studies, or even systematic reviews. You don’t, and you can’t, know what that means for you because very likely you don’t fit the population profile.

As Steve Hickey (again) said, the statistical fallacy underlying all this states that you have one testicle and one ovary – because that’s the population average! The authors of this study update started off with about 2100 papers that looked relevant. They then excluded 90 per cent of them for various reasons – some of them good reasons, some not.

A smarter way to work would be to data-mine them and look for useful information about sub-groups and sub-effects in all the papers. Is there a particular reason omega-3s might work for you and not for others? Perhaps you can’t stand fish, or are allergic to them, and so are deficient in omega-3s.

But the review system doesn’t allow it, it insists on overall conclusions (about populations), and that’s a colossal waste of data. It also confounds the overall finding of the review – it biases it in fact.

Here’s an example: while most subgroups that made it to the final analysis showed a small reduction in risk from taking omega-3s in one form or another (pills, food, whatever), those who got it from supplemented foods, which we understand means stuff like margarine with added omega-3, showed a 4.3-fold death risk increase!

The problem here is that the effects of omega-3 fatty acids cannot be studied alone as if they were a drug. What counts are all the other components of the diet that affect a person’s health.

Processed foods and drinks that contain many unhealthy ingredients can’t be made healthy by adding small doses of vitamins, minerals, and omega-3 fatty acids. In fact, many processed foods that contain small doses of vitamins and other essential nutrients are unhealthy because they contain large doses of sugar, salt, and harmful ingredients such as preservatives, dyes, and other non-food items.

Why lipids are so important

Part of the problem is that lipids are truly complicated, and not many people, patients, doctors or even scientists, understand them well. You need a good understanding of lipid metabolism to appreciate the difference in metabolism and impact between alpha-linolenic acid (ALA, in food such as oily fish) and extracted oils such as EPA and DHA that are only found at high levels in omega-3 supplements.

At these levels they are effectively new to nature; nobody, indeed no mammal, was exposed to really high doses of DHA until we invented fish oil supplements [6]. Miss that fact and you miss the difference between having people eat fresh oily fish or just using omega-3 margarine!

We know from a variety of studies that a diet containing generous portions of green leafy and colorful vegetables and fruits, moderate portions of eggs, fish, and meat, and supplements of adequate doses of essential nutrients (vitamins and minerals) is effective at lowering the risk for cardiovascular disease.

Adequate doses of both omega-3 (in flax oil, walnuts, fish) and omega-6 (in seed oils such as canola, soybean, peanut) fatty acids are essential for health. Although essential, omega-6 fatty acids are thought to contribute to inflammation throughout the body whereas omega-3 fatty acids are anti-inflammatory.

Omega-3 fatty acids are essential for most body organs including the brain but are found in lower levels than omega-6 fatty acids in most vegetables. Risk for cardiovascular disease can be lowered by adequate doses of vitamins C (3,000-10,000mg/d), D (2,000-10,000 IU/d), E (400-1,200 IU/d), and magnesium (300-600 mg/d) in addition to an excellent diet that includes an adequate dose of omega-3 fatty acids.[7]

(Dr. Damien Downing is a specialist physician practicing in London, and President of the British Society for Ecological Medicine. Robert G. Smith is a physiologist and Research Associate Professor at the University of Pennsylvania Perelman School Of Medicine.)

 

References:

1. Abdelhamid, A, Brown TJ, Brainard JS, et al., (2018) Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Syst Rev. 7:CD003177. https://www.ncbi.nlm.nih.gov/pubmed/30019766
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003177.pub3/abstract

2. Miller ER, Pastor-Barriuso R, Dalal D, et al., (2005) Review Meta-Analysis?: High-Dosage Vitamin E Supplementation May Increase. Annals of Internal Medicine, 142(1), pp.37-46. Available at: http://annals.org/article.aspx?articleid=718049.

3. Hooper L, Thompson RL, Harrison RA, et al.. (2004) Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev. (4):CD003177. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003177.pub2/abstract

4. Hickey S, Noriega LA. Implications and insights for human adaptive mechatronics from developments in algebraic probability theory, IEEE, UK Workshop on Human Adaptive Mechatronics (HAM), Staffs, 15-16 Jan 2009.

5. Hickey S, Hickey A, Noriega LA, (2013) The failure of evidence-based medicine? Eur J Pers Centered Healthcare 1: 69-79. http://ubplj.org/index.php/ejpch/article/view/636

6. Cortie CH, Else, PL, (2012) Dietary docosahexaenoic acid (22:6) incorporates into cardiolipin at the expense of linoleic acid (18:2): Analysis and potential implications. International Journal of Molecular Sciences, 13(11): 15447-15463. http://www.mdpi.com/1422-0067/13/11/15447

7. Case HS (2017) Orthomolecular Nutrition for Everyone. Turner Publication Co., Nashville, TN. ISBN-13: 978-1681626574

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WONDERS OF MOLECULAR HYDROGEN

Fred Liers PhD molecular hydrogen H2I drink hydrogen-infused water. You should, too. Why? Because the age of hydrogen is here. Molecular hydrogen, that is. We now know that molecular hydrogen has therapeutic potential for nearly every organ in the human body, as well as for 150 different human disease models! And it’s extremely safe.

MOLECULAR HYDROGEN: BACKGROUND

Molecular hydrogen, also known as “diatomic hydrogen,” is a colorless, tasteless, and odorless gas.

Elemental hydrogen (H) is the most abundant element in the universe constituting 75% of its mass. Yet, it is absent on earth in its monoatomic form, being present in water, and inorganic and organic compounds. Molecular hydrogen is found in the earth’s atmosphere at less than one part per million.

molecular hydrogen H2 water

Hydrogen-infused water is a simple means to consume molecular hydrogen.

The science regarding benefits to health of molecular hydrogen (H2) has advanced rapidly in recent years thanks to the pioneering efforts of research scientists around the globe.

Now hydrogen science is moving quickly beyond theory to practical applications. Moreover, new products exist allowing medical professionals and consumers to leverage the health benefits of hydrogen.

For decades, diatomic molecular hydrogen was generally considered an “inert” gas. That is perhaps the primary reason that molecular hydrogen has been recognized as a therapeutic molecule only recently.

Indeed, science has known about the health benefits of molecular hydrogen as early as 1798. Yet, as noted, for most of modern history the belief persisted that hydrogen was inert in the body. It was only in the late 20th century (ca. 1975) that it gained the attention of medical researchers, and only in the past 10 years has evidence for the health effects of molecular hydrogen gained critical mass in the scientific literature.

There are now more than 500 peer-reviewed articles demonstrating the therapeutic potential of hydrogen for nearly every organ in the human body, as well as in 150 different human disease models, according to the Molecular Hydrogen Foundation.

HEALTH BENEFITS OF MOLECULAR HYDROGEN (H2)

• Molecular hydrogen reduces oxidative stress as a selective antioxidant and by maintaining homeostatic levels of glutathione, superoxide dismutase, catalase,  and other free-radical scavenging nutrients.

• The antioxidant capacities of molecular hydrogen are such that it is beneficial for persistent and acute oxidative stress.

• Acute oxidative stress arises from a multitude of causes, including inflammation, cardiac or cerebral infarction, organ transplantation, heavy exercise, cessation of operative bleeding, and many other causes.

• Persistent oxidative stress relates to reactive oxygen species (ROS) generated in the body throughout life. For example, during exercise, exposure to pollutants and toxins or UV light, as well as physical and psychological stresses, and the aging process itself. As aerobic organisms, we generate ROS when breathing consumes oxygen.

• Molecular hydrogen is effective against hydroxyl radicals (OH). The hydroxyl radical is the radical species that causes much of the oxidative damage in the body. While vitamin C, glutathione, and certain plant-based antioxidants are somewhat effective against this radical, there is no Nrf2-induced enzyme that effectively quenches the hydroxl radical.

• This positions molecular hydrogen as a uniquely effective antioxidant against the hydroxyl radical. Notably, when molecular hydrogen quenches the hydroxyl radical, it produces water, which is non-toxic in the body.

• Beyond this, molecular hydrogen, like other gaseous signaling molecules such as NO, CO, H2S, appears to exhibit cell signal-modulating activity that confers it with anti-inflammatory, anti-obesity, anti-allergy, and many other benefits.

MOLECULAR HYDROGEN MEDICINE

The scientific literature discusses the use of molecular hydrogen for many clinical applications, including the following:

• METABOLIC SYNDROME including diabetes, hyperlipidemia, arteriosclerosis, hypertension, and obesity

• ISCHEMIA / REPERFUSION injuries including cerebral and myocardial infarctions, organ transplants, post-cardiac arrest

• NEUROPROTECTION including applications for dementia, Parkinson’s disease, depression, and anesthesia

• INFLAMMATION including applications for polymicrobial sepsis, rheumatoid arthritis, wound healing, and bowel diseases

• MITOCHONDRIAL DISEASES

• HEMODIALYSIS / VENTILATION

• AGING including cognitive decline

• EXERCISE including applications for fatigue, lactic acid, recovery, and oxidative stress related to heavy exercise

SIDE EFFECTS OF CANCER THERAPIES including radiotherapy and chemotherapy

• MANY OTHER BENEFITS

athlete molecular hydrogen performance race

Athletes benefit from molecular hydrogen. You can, too.

HOW MOLECULAR HYDROGEN WORKS

According to the Molecular Hydrogen Foundation, there are three ways molecular hydrogen exerts positive health effects.

1.  Molecular hydrogen easily diffuses into subcellular compartments where it scavenges cytotoxic oxygen radicals, thereby protecting DNA, RNA, and proteins against oxidative stress.

2.  Molecular hydrogen triggers activation or upregulation of additional antioxidant enzymes (e.g., glutathione, superoxide dismutase, catalase, and others) and/or cytoprotective proteins of the body.

3.  Molecular hydrogen may be a novel signaling molecule that alters cell signaling, cell metabolism, and gene expression. This may explain its apparent anti-inflammatory, anti-allergic, and anti-apoptotic (or anti-cell death) effects.

MOLECULAR HYDROGEN IS SAFE

Molecular hydrogen exhibits great safety, and it is regarded as safe for use in the body. It is shown no toxicity even in high concentrations.

Safety standards are already established for high concentrations of molecular hydrogen for inhalation because high-pressure H2 gas is used in deep-water diving gas mixtures to prevent decompression sickness.

Notably, H2 gas combusts only at temperatures higher than 527 °C, and it explodes by chain reaction with oxygen (O2) only in the range of Hconcentration (4–75%, vol/vol).

Molecular hydrogen can be used for medical applications safely by several ingestion methods including inhalation of 1–4% hydrogen gas, which exhibits great effectiveness.

All these factors mean that molecular hydrogen is safe, easy-to-use, and effective for therapeutic purposes.

molecular hydrogen H2 water

Hydrogen-infused water is safe, easy-to-consume, and cost effective.

USING MOLECULAR HYDROGEN

Methods for consuming molecular hydrogen include inhalation, oral ingestion of hydrogen-infused water, injection of hydrogen saline, and direct diffusion (eye drops, baths, cosmetics, etc.).

An advantage of inhaled H2 gas is that is acts rapidly. In this respect, may be suitable for defense against acute oxidative stress.

It has been shown that inhalation of 3–4% hydrogen (H2) gas reaches a plateau at approximately 10–20 μM in the arterial and venous blood in about 20 minutes. This is shown not to affect any physiological parameters (e.g., blood pressure), suggesting no adverse effects.

According to the Molecular Hydrogen Foundation, the consensus is that drinking H2-rich water is the easiest, and often the most effective, method for obtaining molecular hydrogen although it does not provide as many hydrogen molecules to the body as other methods.

Some studies show consuming H2-infused water to be more effective than inhalation or increasing intestinal H2 production via lactulose administration.

Another advantage of drinking hydrogen infused water is that it allows gastric induction of ghrelin, which is mediated via activation of beta 1 adrenergic receptors.

Above all, drinking hydrogen-infused water is easy to do, and convenient as you can drink it at home or while traveling.

HYDROGEN-INFUSED WATER

Inhalation of molecular hydrogen gas may be impractical for continuous H2 consumption in daily life. In contrast, solubilized H2 (hydrogen-infused water) is a portable, easily administered, and safe means to ingest H2.

H2 can be dissolved in water up to 0.8 mM (1.6 mg/L) under atmospheric pressure at room temperature without changing pH.

Hwater can be made by several methods: infusing H2 gas into water under pressure, electrolyzing water to producing H2, and reacting magnesium metal or its hydride with water.

Notably, H2 penetrates glass or plastic walls of vessels in a short time, yet aluminum containers retain hydrogen gas for a long time.

Water ionizers produce hydrogen gas via electrolysis. This method produces hydrogen concentrations from less than 0.05 ppm to more than 2.5 ppm. Typically 0.1 to 0.7 ppm hydrogen is produced, yet most companies manufacturing water ionizers neither know the concentration produced nor understand the significance of hydrogen for health.

In this regard, depending upon the production method much of the water containing molecular hydrogen exhibits a negative oxygen reduction potential (ORP). Yet, ORP is only a general indication of hydrogen production and is not a measurement of its concentration.

A second method of producing hydrogen-rich water by electrolysis is by infusion. In this method, hydrogen is directly infused into filtered water within a machine.

Another convenient method to generate molecular hydrogen is to add alkali-earth metals to water. Magnesium metal in commonly used for this purpose. This method allows for the production of high concentrations of molecular hydrogen that are generally near saturation (1.6 ppm), and therefore less water needs to be consumed by individuals drinking it.

Magnesium sticks and tablets/capsules are available (some of which are placed in water and others that can be consumed directly) that rapidly produce 2–4 ppm molecular hydrogen concentration. Like electrolysis, adding metals to water also increased the pH of water because they reduce the concentration of H+ ions.

Other methods exist that can produce supersaturated concentrations of molecular hydrogen with or without alteration of water pH. Advantages of these methods include having to drink a fraction of the amount of water in order to obtain an equal amount of molecular hydrogen.

Drinking water containing molecular hydrogen is probably the easiest and most cost-effective means for most persons to obtain hydrogen.

man drinks water infused with molecular hydrogen

Hydrogen-infused water can be consumed using tablets, prepared H2 beverages, or ionized water.

MOLECULAR HYDROGEN FROM YOUR MICROBIOME

Certain types bacteria in the intestinal tract produce hydrogen gas from non-digestible fibers, which may explain how fiber-rich diets reduce inflammation, and exert cardiovascular and other health benefits.

Diets low in dietary fiber from fruits and vegetables, or a decrease in microbiome diversity could potentially reduce production of molecular hydrogen. This could exert adverse effects on health.

The presence (or absence) of a diverse and robust microbiome may be one of the most significant factors in terms of how much hydrogen can be generated in the body. Most people today do not create the levels of molecular hydrogen in their digestive tracts that humans in earlier time periods generated largely because due to modern diets and less than optimal microbiome health.

Factors that influence or reduce microbiome health and diversity include antibiotic use, imbalanced diet, lack of certain fiber-rich vegetables in the diet, and consumption of herbicides, pesticides, and GMOs (that include glyphosate) that harm microbial populations and cause “leaky gut”.

As knowledge increases regarding ways we can support a healthy microbiome, the biological significance of hydrogen historically produced in our digestive tracts will be better understood.

BENEFIT TODAY FROM MOLECULAR HYDROGEN

The clinical applications of molecular hydrogen are impressive. One of the great advantages of molecular hydrogen infused water is that  it is easy to consume it, or make it in your own home or wherever you happen to be.

HPDI now sells a tablet hydrogen product from Purative known as Active H2.

Active H2 is a unique, patent-pending combination of all-natural minerals used to generate molecular hydrogen and electron-rich potential (-ORP). This distinguishes it from existing hydrogen formulas and electrolysis (water ionizers).

Active H2 is easy to use.  Simply place one tablet of in a 1/2 liter (16 oz) container of pure water (filled to the top) and close tightly. Wait at least 5–10 minutes for it to completely disintegrate (fizz), and then drink.

A one pint glass mason jar works well as a container for this purpose. However, you can use up to one liter (about 32 ounces) of water in a container, so a quart mason jar also works well. Consume the hydrogen-infused water ideally at least 30 minutes before food.

Active H2 formula consists of a proprietary blend of pure magnesium, malic acid, fumaric acid, and maltose that synergistically act to generate molecular hydrogen and electron-rich potential (-ORP).

Active H2 is the only all-natural add-in tablet providing molecular hydrogen in the amount of greater than 1.8 ppm, That is, one tablet typically generates molecular hydrogen in the concentration of about 2 ppm.

There are other molecular hydrogen products, including tablets, sticks, and pre-infused bottled products like H2Bev. H2Bev provides about 1.2–1.5 ppm of molecular hydrogen and comes in a 12 oz coated aluminum container for excellent H2 retention.

MOLECULAR HYDROGEN SUMMARY

Molecular hydrogen sits in the unique position of providing significant, wide-ranging benefits for health with an unmatched ease-of-use, and at relatively low cost for what it delivers.

We highly recommend the use of molecular hydrogen for its health benefits and for therapeutic applications. This includes the consumption of hydrogen-infused water whether from prepared H2 beverages, water ionizers, or highly effective Active H2 tablets.

Below we include important scientific abstracts you may find helpful in understanding the benefits and applications of molecular hydrogen.

 

SCIENTIFIC STUDIES ON MOLECULAR HYDROGEN

Beneficial biological effects and the underlying mechanisms of molecular hydrogen – comprehensive review of 321 original articles

From: http://www.ncbi.nlm.nih.gov/pubmed/26483953

Abstract
Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum. Hydrogen gas of less than 4% is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.

Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine

From: http://www.ncbi.nlm.nih.gov/pubmed/24769081

Abstract
Molecular hydrogen (H2) has been accepted to be an inert and nonfunctional molecule in our body. We have turned this concept by demonstrating that H2 reacts with strong oxidants such as hydroxyl radical in cells, and proposed its potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signaling reactive oxygen species; therefore, there should be no or little adverse effects of H2. There are several methods to ingest or consume H2; inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline into the eyes. The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.

Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.

From: http://www.ncbi.nlm.nih.gov/pubmed/25251220

Abstract
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.

The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance

From: http://www.ncbi.nlm.nih.gov/pubmed/23680032

Abstract
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums. There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.

Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases

From: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377272/

Abstract
Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson’s disease and three models of Alzheimer’s disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson’s disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease.

Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases

From: http://www.ncbi.nlm.nih.gov/pubmed/21621588

Abstract

BACKGROUND:
Mitochondria are the major source of oxidative stress. Acute oxidative stress causes serious damage to tissues, and persistent oxidative stress is one of the causes of many common diseases, cancer and the aging process; however, there has been little success in developing an effective antioxidant with no side effect. We have reported that molecular hydrogen has potential as an effective antioxidant for medical applications [Ohsawa et al., Nat. Med. 13 (2007) 688-694].

SCOPE OF REVIEW:
We review the recent progress toward therapeutic and preventive applications of hydrogen. Since we published the first paper in Nature Medicine, effects of hydrogen have been reported in more than 38 diseases, physiological states and clinical tests in leading biological/medical journals. Based on this cumulative knowledge, the beneficial biological effects of hydrogen have been confirmed. There are several ways to intake or consume hydrogen, including inhaling hydrogen gas, drinking hydrogen-dissolved water, taking a hydrogen bath, injecting hydrogen-dissolved saline, dropping hydrogen-dissolved saline into the eyes, and increasing the production of intestinal hydrogen by bacteria. Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.

MAJOR CONCLUSIONS:
Hydrogen has biological benefits toward preventive and therapeutic applications; however, the molecular mechanisms underlying the marked effects of small amounts of hydrogen remain elusive.

GENERAL SIGNIFICANCE:
Hydrogen is a novel antioxidant with great potential for actual medical applications. This article is part of a Special Issue entitled Biochemistry of Mitochondria.

Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications

From: http://www.ncbi.nlm.nih.gov/pubmed/21736547

Abstract
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H(2)) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H(2) has a number of advantages as a potential antioxidant: H(2) rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H(2). There are several methods to ingest or consume H(2), including inhaling hydrogen gas, drinking H(2)-dissolved water (hydrogen water), taking a hydrogen bath, injecting H(2)- dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H(2) by bacteria. Since the publication of the first H(2) paper in Nature Medicine in 2007, the biological effects of H(2) have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H(2) shows not only effects against oxidative stress, but also various anti-inflammatory and antiallergic effects. H(2) regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H(2) remain elusive.

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

From: http://www.ncbi.nlm.nih.gov/pubmed/17486089

Abstract
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.

ADDITIONAL RESOURCES

MOLECULAR HYDROGEN (H2) AT FOREFRONT OF HEALTH RESEARCH
by Hank Liers, PhD (from the HPDI blog)

ACTIVE H2 (tablet product)

Molecular Hydrogen Foundation (MHF)

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