Health Products Distributors

Enzyme Systems

  • METHYLATION CYCLE, GENETICS, B VITAMINS

    Dr. Hank Liers, PhD geneticsI previously published "Homocysteine Genetics – Coenzyme B Vitamins" in which I considered in-depth how homocysteine (an intermediate chemical in the Methylation Cycle) is formed from methionine, how genetics affects the metabolic pathways, and how B vitamins are used in metabolic pathways. I also wrote "Folate Ingredients – Folinic Acid & 5-MTHF" which discussed how coenzyme folate vitamins are far superior to the synthetic folic acid form. In today's article, I take a broader view of the topic that encompasses the Methylation Cycle, genetics, and B vitamins.

    THE METHYLATION CYCLE

    The Methylation Cycle is considered to be one of the most important metabolic pathways in the human body. Its most important function is to provide methyl groups via SAM (S-adenosyl methionine) to hundreds of different body substrates. Methylation is continually occurring in the body, transforming many millions of molecules throughout the body every second. Molecules receive methyl groups, then separate and recombine continuously, transforming and reforming constantly in the ongoing process of life!

    As a reminder of the pathways involved in the Methylation Cycle, the following figure provides a flow chart showing the details.

    Methylation Cycle

    Figure 1. Metabolic Pathways in Methylation Cycle

    A key purpose of this cycle is to provide methyl groups (CH3) needed by a broad range of of body functions (over 200 different functions). Examples include:

    1. Influences the genetic expression that parents give their children and helps guide the development of the embryo.
    2. Is needed by the nervous system to produce neurotransmitters and maintain the nerves.
    3. Mobilizes fats and cholesterol so they do not accumulate where they are harmful, such as the arteries and liver.
    4. Regulates hormones, including, estrogen, adrenaline, and melatonin.
    5. Detoxifies harmful chemicals and histamine a prime substance involved in inflammation.
    6. Helps repair damaged proteins in the cells so they can function properly.
    7. Protects the DNA in the genome (genetic code) to reduce the chances of mutation.
    8. Creates antioxidants used in the antioxidant defense system.

    DESCRIPTION OF PATHWAYS WITHIN THE METHYLATION CYCLE

    The overall flow of the Methylation Cycle begins with dietary methionine (an essential amino acid) which combines with ATP (adenosine triphosphate - body energy) to form SAM (S-adenosyl methionine) – the common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. When SAM transfers a methyl group to a body chemical the residue from this reaction leads to the production of homocysteine.

    Homocysteine can be converted in the transsulfuration pathway that requires coenzyme vitamin B6 to produce cysteine, glutathione, taurine, and sulfates. These sulfur containing substances provide important antioxidant protection and detoxification functions in the body.

    Homocysteine can be converted back to methionine through the betaine (trimethyl glycine) pathway which requires zinc and magnesium. This pathway also requires dietary betaine or choline which the body can convert into betaine.

    Also, homocysteine can be converted back to methionine via the remethylation pathway which requires 5-MTHF, coenzyme vitamin B2 and methylcobalamin (B12).

    GENETICS

    It is important to understand that each of the pathways described above are able to be executed only in the presence of enzymes (shown in blue boxes in the diagram) created by specific genes in your genetic code. For example, Betaine-Homocysteine S-Methyltransferase (BHMT) is the enzyme required in the betaine pathway, Cystathione Beta Synthase (CBS) is the enzyme required in the transsulfuration pathway, and Methylenetetrahydrofolate Reductase (MTHFR) and Methionine Synthase (MS) are enzymes required in the remethylation pathway.

    Assuming that you have perfect genetics (no mutations, SNPs, free radical damage, insertions/deletions, etc.), the proper functioning of these pathways are still subjected to the fact that the required vitamins and minerals (vitamin B6, vitamin B2, Folate, vitamin B12, zinc, magnesium, and betaine) need to be provided by your diet or from supplements for the body to function correctly.

    In addition, exposure to high levels of toxins from your environment and high levels of stress require that the nutritional needs will be even higher for the pathways to work properly. For example, exposure to high levels of toxins requires that the transsulfuration pathway be more active possibly reducing the amount of available methionine to support necessary methyl transfer reactions.

    For these reasons alone the consensus of knowledgeable practitioners is that you should be eating an organic whole foods diet, taking appropriate nutritional supplements, avoiding and eliminating toxins from food, water, and air (living in a clean environment), and avoiding an unduly stressful life. All of these actions fall into the category of Epigenetics which you generally have control over!! Doing these things alone could significantly balance the functioning of your Methylation Cycle and improve your health.

    Unfortunately, few people have perfect genetics which often causes the various pathways in the Methylation Cycle to become imbalanced and unable to correct the dysregulation imposed upon the body. For example, the enzyme MTHFR can have heterozygous (single chromosome) genetic variations in up to 50% of certain populations and homozygous genetic variations (both chromosomes) in 10% or more of certain populations.

    Some disorders that researchers have associated with MTHFR genetic variations include:

    • Alzheimer’s disease
    • Asthma
    • Atherosclerosis
    • Autism
    • Bipolar disorder
    • Bladder issues
    • Blood clots
    • Breast problems
    • Chemical sensitivity
    • Chronic fatigue syndrome
    • Down syndrome
    • Epilepsy
    • Fibromyalgia
    • Gastric problems
    • Glaucoma
    • Heart murmurs
    • High blood pressure
    • Irritable bowel syndrome
    • Leukemia
    • Male infertility
    • Methotrexate toxicity
    • Migraines with aura
    • Multiple sclerosis
    • Myocardial infarction
    • Nitrous oxide toxicity
    • Parkinson’s disease
    • Pulmonary embolisms
    • Schizophrenia
    • Stroke
    • Thyroid issues
    • Unexplained neurologic disease
    • Vascular dementia

    This extensive list is highly significant and tells us that it is very important to have  genetic testing done for the genes/enzymes in the Methylation Cycle pathway. I prefer the BodySync genetic test which evaluates the key Methylation Cycle genes plus many other important genes in a single test.

    B VITAMINS AND MINERALS

    We are strong believers that everyone should start their nutritional program by eating a balanced, organic, whole foods diet. We have been doing this ourselves for the past 30 years. Unfortunately, only a small percentage of people follow this advice and in most cases this leads to poor nutritional status that does not adequately support the body's needs. This is especially true with respect to obtaining the nutrients needed to support the Methylation Cycle.

    Nine of our family members and associates have taken the BodySync genetic test which evaluates the condition of 45 different enzymes including CBS, MTHFR (2 variations), MTR (related to B12 and 5-MTHF as they relate to methionine synthase - MS), and MTRR (related to maintaining B12 levels needed by the MTR enzyme). In every case the results showed at least 2 and up to 4 enzymes had genetic variations. These results indicate that the nutritional requirements for folate as 5-MTHF, vitamin B12 as methylcobalamin, vitamin B6, vitamin B2, magnesium and zinc will likely be significantly greater than normal.

    Given the above information, it seems essential for good health to take nutritional supplements that provide the important nutrients. Below I will discuss various formulas that I have developed and refined over many years that are useful especially for the Methylation Cycle.

    Please note that Health Products Distributors, Inc.  (HPDI) is the preferred supplier of nutritional supplements by the BodySync genetic testing company.

    MULTIVITAMINS

    When looking at the total needs the body has for nutrients that the body does not produce, including fat soluble vitamins (A, D (some), E, K1 and K2), vitamin C, B vitamins (B1, B2, B3, B5, B6, folate, B12, biotin, choline, and inositol), minerals (Ca, Mg, Zn, Se, Cu, Mn, Cr, Mo, K, boron, and vanadium), and betaine it only seems wise to include as a top priority a Multivitamin that includes all of these in what I term therapeutic amounts (carefully selected after evaluating thousands of research studies carried out over many years.)

    In this context, it is important to recognize that every enzymatic reaction in the body requires mineral cofactors in order to carry out its function. A good multivitamin provides many of these required minerals.

    Additionally, the multivitamin should contain ingredient forms that research has confirmed to be the most absorbable and usable by the body. These include coenzyme B vitamins, Krebs cycle (citrate, alpha-ketoglutarate, succinate, fumarate, & malate) minerals, and amino acid chelates.

    In the context of supporting the Methylation Cycle we are looking for specific forms and amounts of B vitamins that can adequately provide the body's needs. The means that there should be coenzyme folate as 5-MTHF of at least 400 mcg, coenzyme vitamin B-12 as methylcobalamin of at least 200 mcg, Vitamin B6 (including significant amounts of pyridoxal 5' phosphate) of at least 40 mg, and Vitamin B2 (including significant amounts of riboflavin 5' phosphate) of at least 25 mg. In addition, magnesium (100 mg) and zinc (at least 20 mg) should be provided.

    Please note that the body's requirements for magnesium is generally accepted by nutritional experts to be higher than 400 mg daily (and as high as 1,000 mg daily). For this reason we generally recommend that a person take supplemental magnesium (such as HPDI's MYO-MAG) at levels over 400 mg daily.

    The two multivitamin formulas Health Products Distributors provides for adults that meet these requirements (and more) are the Hank & Brian's Mighty Multi-Vite and Multi Two (in both capsule and tablet forms). Click on the bottles below for technical details.

    Hank & Brian's Mighty Multi-Vite multivitamin methylation cycle

    Multi Two Caps or Tablets methylation cycle

    B COMPLEX

    In situations where significant genetic variations are present it may be wise to add a B COMPLEX supplement to the MULTIVITAMIN to provide even larger amounts of the needed B vitamins. HPDI provides a B-Complex-50 product that includes significant amounts of coenzyme forms and contains 50 mg of Vitamin B1, 50 mg of Vitamin B2, 100 mg of Vitamin B3, 50 mg of Vitamin B6, 500 mcg of coenzyme folate (both folinic acid and 5-MTHF), 100 mcg of B12 (both methylcobalamin and hydroxocobalmin), 50 mg of Vitamin B5 (pantothenic acid), 500 mg of Biotin, 50 mg of choline, and 50 mg of inositol. Click on the bottle below for technical details.

    B-Complex-50 full spectrum B vitamins with coenzyme forms methylation cycle

    FOLATE AS 5-MTHF

    In situations where an inadequate diet is present and genetic testing indicates an MTHFR variation (especially a homozygous variation) Health Products Distributors provides a 5-MTHF folate supplement that easily absorbs into the body and can be directly used in combination with Vitamin B12 to convert homocysteine to methionine. Click on the bottle below for technical details.

    5-MTHF 1 mg in veggie cap methylation cycle 5-MTHF 1 mg in veggie cap

    B-12 as METHYLCOBALAMIN

    It is often the case for older patients and vegetarians that Vitamin B12 is deficient. In these cases it is wise to supplement with a significant amount of methylcobalamin to ensure that the Methylation Cycle has sufficient to effectively convert homocysteine into methionine. Health Products Distributors Vitamin B12 contains 5 mg of methylcobalamin in sublingual lozenge form that supports excellent absorption even if swallowed and absorbed by diffusion. Click on the bottle below for technical details.

    Vitamin B-12 5 mg methylcobalamin sublingual lozenge methylation cycle Vitamin B-12 – 5 mg Methylcobalamin sublingual lozenge.

    MINERALS

    Magnesium and zinc are two important minerals used in the betaine pathway of the Methylation Cycle in which homocysteine is converted back to methionine.

    In the body magnesium is involved in more than 400 essential metabolic reactions and is required by the adenosine triphosphate (ATP)-synthesizing protein in mitochondria. ATP, the molecule that provides energy for almost all metabolic processes, exists primarily as a complex with magnesium (MgATP). Therefore, it also is involved in converting methionine to SAM.

    Over 300 different enzymes depend on zinc for their ability to catalyze vital chemical reactions. Zinc-dependent enzymes can be found in all known classes of enzymes.

    Health Products Distributors provides 100 mg magnesium/vcap in its MYO-MAG supplement which is especially important in increasing ATP in the Krebs Cycle. This product also contains vitamin B1, vitamin B2, and vitamin B6 with substantial amounts of coenzyme forms and manganese. Click on the bottle below for technical details.

    MYO-MAG with 100 mg magnesium per serving key B vitamins methylation cycle MYO-MAG with 100 mg magnesium per serving and key B vitamins.

    Health Products Distributors provides 25 mg zinc/serving in its Double Zinc Plus supplement. This formula provides zinc in the picolinate and citrate forms as well as 3 mg of P5P (coenzyme B6). Click on the bottle below for technical details.

    Double Zinc Plus supplement with P5P and 25 mg zinc methylation cycle Double Zinc Plus supplement with P5P and 25 mg zinc

    SUMMARY

    The Methylation Cycle is recognized as one of the most important metabolic pathways in the human body. When not properly supported by key B vitamins and minerals, the Methylation Cycle can become severely imbalanced which can lead to a very wide range of poor health conditions. Furthermore, genetic variations in the genes that produce important enzymes allowing the Methylation Cycle to function correctly lead to even further imbalances and greater possibility for conditions of poor health.

    In this article, I have provided insight into how the Methylation Cycle works and how it can be significantly supported by lifestyle changes regarding diet and environment (Epigenetics) and by specific B vitamins and mineral supplements that I have developed over many years. In addition, we have shown that knowledge gained from genetic testing can further provide a critical understanding of your specific needs so that your health can be optimized.

    RELATED HPDI BLOG ARTICLES

    GENETICS, EPIGENETICS & HUMAN BIOLOGY

    Homocysteine Genetics – Coenzyme B Vitamins

     

  • HOMOCYSTEINE GENETICS – COENZYME B VITAMINS

    Dr. Hank Liers, PhD homocysteine coenzyme B vitaminsWe previously published an article titled FOLATE INGREDIENTS – FOLINIC ACID & 5-MTHF in which we discuss how coenzyme folate vitamins are far superior to the synthetic folic acid form. In today's article, I take a more in-depth look at how homocysteine is formed from methionine, how genetics affects the metabolic pathways, and how B vitamins are used in metabolic pathways.

    One way to look at the metabolic pathways of methionine (an essential amino acid) is that it provides a way for the body to convert this sulfur containing amino acid either to cysteine and its key by-products glutathione, taurine, and sulfates or allows remethylation back to methionine to occur using either the Folate Cycle or the Trimethyl glycine (betaine) pathways.

    Figure 1 shows these metabolic pathways including the vitamins required at each step including vitamin B6 (as P-5-P), methylcobalamin, and 5-methyltetrahydrofolate (5-MTHF). In addition, it shows the key enzymes produced by the body at each step. These enzymes include CBS (cystathione beta synthase), BHMT (betaine homocysteine methyltransferase), MS (methionine synthase), and MTHFR (methylene tetrahydrofolate reductase).

    homocysteine metabolism diagram Figure 1. Metabolic Pathways in Methionine and Homocysteine Metabolism

    HEALTH ISSUES ASSOCIATED WITH HIGH HOMOCYSTEINE LEVELS

    It is highly important that the various metabolic pathways function correctly to keep homocysteine at healthy levels (6–8 µmol/L). Unfortunately, high levels of homocysteine in the body (10–20 µmol/L) are a factor in a wide range of health issues, including:

    • Greater risk for heart problems, including coronary artery disease, heart attacks, stroke, high blood pressure, congestive heart failure, and abnormal cholesterol levels. This is due to increased inflammation, sometimes due to blood clotting spontaneously, and because of blockages of the major arteries.
    • Mental abnormalities such as depression, anxiety, bipolar disorder, and other mental problems are more common among people with high homocysteine
    • Migraines and headaches in a significant percentage of the population
    • In those who suffer from high homocysteine due to having nutritional deficiencies anemia, aches and pains, hearing loss, age-related macular degeneration (ARMD), slowed development, and birth defects might also be possible
    • Greater risk for dementia, Alzheimer’s disease, brain atrophy, and other cognitive problems
    • In children, skeletal and developmental abnormalities including having a curved spine or protruding chest and rib cage. Some patients appear very tall and thin, and some might also have very long, thin “spider-like” toes and fingers.
    • Behavioral problems, including ADHD, autism and other learning disabilities

    ROLE OF GENETICS IN HOMOCYSTEINE METABOLISM

    Ten or more years ago, questions of how genetics enters into homocysteine metabolism were unlikely to be asked. However, in recent years DNA testing has advanced and is now available to everyone (for example, see my article about Bodysync's genetic test, GET STARTED – NUTRIGENOMIC TESTING.

    You may have heard a great deal about MTHFR (methylene tetrahydrofolate reductase). This gene is involved in folate metabolism and has a central role in methylation processes like repair of and building new DNA in dividing cells.

    In the remethylation pathway for conversion of homocysteine to methionine, MTHFR plays a key role in converting folate into 5-MTHF which is needed along with B12 as methylcobalamin in order for the conversion to take place. Genetic variations in MTHFR have been studied in depth. Of the many variations studies the most significant ones appear to be variations of C677C such as C677T (referred to as heterozygous) or T677T (referred to as homozygous). The heterozygous variant appears in about 30–50% of the population and causes somewhat less efficiency in the conversion of folic acid to 5-MTHF. However, the homozygous variation occurs in about 10% of the population and can have serious effects due to converting little homocysteine back to methionine.

    Another variation in MTHFR is called A1298A. These variations are A1298C and C1298C and will have similar effects to the C677C variations. It was interesting to me when I recently analyzed my Bodysync genetic test results showing I carry the variation A1298C (heterozygous), which indicates I may not be effectively converting homocysteine back to methionine.

    Additionally, my Bodysync genetic test results also indicate that I have heterozygous variations in the CBS enzyme shown in Figure 1, as well as heterozygous variations in MTR and MTRR enzymes, which are involved with B12 levels in the  remethylation pathway. These results indicate that I need to take higher levels of methylcobalamin and 5-MTHF.

    IMPORTANCE OF COENZYME FORMS AND PROPER AMOUNTS OF B VITAMINS

    Many of the B vitamins on the market today unfortunately are in synthetic form. The body can only use the natural coenzyme forms effectively. For example, the body needs vitamin B6 in the form of P-5-P (pyridoxal-5-phosphate), folate in the form of L-5-MTHF, and B12 in the form of methylcobalamin for proper metabolism of methionine. In some cases the body can use the synthetic forms of pyridoxine HCl, folic acid, and cyanocobalamin but pays a cost (e.g., in time and energy) by having to convert synthetic forms to coenzyme forms.

    Add to the prevalence of synthetic B vitamins, the fact that genetic deficiencies are more common than previously assumed, and it becomes clear that the coenzyme forms of B vitamins in the proper amounts are extremely important.

    Fortunately, I have always believed it best to include as many coenzyme forms as possible in the nutritional supplements I formulate (over the past 27 years). For example, all HPDI multivitamins include coenzymes of B1, B2, B6, B12, and folate (as 5-MTHF and folinic acid). This is uncommon in most multivitamin formulas on the market. For this reason our supplements are ideally suited to the prevention or resolution of most genetic problems regarding homocysteine.

    In addition, I have always chosen to include higher amounts than most multivitamins on the market. We also make available 5-MTHF one milligram (1 mg) capsules and methylcobalamin five milligram (5 mg) sublingual tablets. When genetic variations are in play as discussed above, then providing relatively higher amounts of coenzyme B vitamins that support important requirements in the body seems necessary.

    Interestingly, several other nutrients are involved in the pathways involving methionine and homocysteine. These include zinc, magnesium, and Vitamin B2. Our multivitamin formulas and magnesium formulas, especially Myo-Mag with its coenzyme B1, B2, and B6, are recommended to support these nutrient needs. Finally, it has been found that N-Acetyl-L-Cysteine (NAC) can significantly lower homocysteine (by up to 50%), most likely because its gives the body an excellent source of cysteine without have to use methionine.

    SUMMARY

    In this article, I have shown the value of the use of genetic testing and high-quality coenzyme B vitamins in resolving health issues associated with high values of homocysteine in the body.

     

    SOURCES & RESOURCES

     GET STARTED – NUTRIGENOMIC TESTING.

    FOLATE INGREDIENTS – FOLINIC ACID & 5-MTHF

    The Homocysteine Revolution by Kilmer S. McCully, MD

    "Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease"
    (Cell Death and Differentiation 11, S56–S64)

    PRODUCTS

    5-MTHF
    (coenzyme folate)

    Methylcobalamin
    (vitamin B12)

    B-Complex-50

    HPDI Multivitamins

  • GET STARTED - NUTRIGENOMIC TESTING

    Dr. Hank Liers, PhDRecently, we published two articles titled Discovering Nutritional Needs Through Advanced Genetic Testing and Benefits of Nutrigenomic Testing for Health detailing the benefits of nutrigenomics testing.

    In addition, we provided details of HPDI's commitment to BodySync—a company dedicated to empowering individuals and organizations with key personal genetic data and information needed to make more informed nutrition and fitness decisions. In this article, I will provide details regarding how you can get started with nutrigenomics testing.

    Before making an enthusiastic commitment to BodySync's genetic testing program, we personally took the test (me, my son Fred, Fred's wife Stefanie, and Fred's son, Olin). In another article we will discuss the results in detail. However, suffice it to say that we have been extremely pleased with the program. I specifically am impressed with how the genetic test results can be used to make important recommendations regarding diet, exercise, and nutritional supplementation.

    A surprising (to me) simple test result example is the fact that regarding the VDR gene which produces a receptor that binds Vitamin D and helps regulate many functions in the body (bone formation, glucose balance, immune response, muscle formation, etc.) my test showed I had three different genetic variations that affected my bone integrity/mineral density. In view of this, it was recommended I supplement with higher levels of Vitamin D and calcium (which fortunately I already have done for a long time).

    Other surprising examples to me were the fact that my ability to detoxify chemicals in smoked meats and my ability to metabolize folic acid were genetically compromised. I have stopped eating smoked meats and have been taking folate in the form of coenzyme 5-MTHF and Folinic Acid for a long time (thank goodness!!).

    Developed by leading genetic scientists, genomic nutritionists, kinesiologists, and bioinformaticians, BodySync’s clinically tested DNA Nutrition and Fitness Systems are recognized and used by thousands of individuals, as well as health care professionals, physicians, and researchers around the world.

    Genetic nutrigenomic testing

    Based upon our personal results and recommendations from our tests, as well as the broad acceptance of the test by health care professionals, physicians, and researchers, HPDI has decided to offer the BodySync testing system to our professional clients on our reseller website (www.HealthProductsDistributors.com).

    In addition, we are supporting our professional clients during the process of getting started with nutrigenomics. Below we will review the potential benefits of nutritional genomics, and then walk you through the process of getting started.

    POTENTIAL BENEFITS OF NUTRIGENOMIC TESTING

    The first insights of how nutritional genomics will impact personal health have already begun to be appreciated. As research goes forward, we expect a continually expanding knowledge base that promises to have extensive benefits for health care in general and personal health in particular.

    Major anticipated contributions

    • Greater understanding of the role of genetics in health and disease (particularly chronic disease).
    • More effective therapeutic interventions for dealing with existing disease.
    • Early identification of disease susceptibility and initiation of risk reduction strategies.
    • A shift within health care from a disease management focus to one of health promotion and disease prevention.
    • Identification of the molecular mechanisms underpinning the interactions among genes and environmental factors, including components in food.
    • Individualization of dietary choices based on a person’s genotype.
    • A new dimension to food, one of genes being dietary targets with food having the ability to change gene expression.
    • Changes in food choices, including: a) increased selection of functional foods that scientific research has shown to reduce susceptibility to diet-related diseases and b) isolation and purification of bioactive food components for use in the development of new functional foods or for enrichment of commonly eaten foods and dietary supplements.
    • Public health messages conveying the role of genes and environment in health and disease and the ability of food to modify the outcome of these interactions, allowing diet and health to be tailored to an individual’s genetic variations.
    • Empowerment of consumers to take responsibility for their health through enhanced knowledge of appropriate food choices for their genotype.

    OFFERING BODYSYNC'S "GENETIC NUTRITION & FITNESS ASSESSMENT"

    Health care professionals can order test kits directly from HPDI, as well as ordering supplements matched to Bodysync test results.

    Health professionals must first register on the BodySync website where they are approved as an HPDI-related reseller. Be sure to mention "HPDI" in your application. I will discuss more about how to do that below.

    The next step is for you to recommend this test to your patients (or take it yourself). Alternatively patients may seek a health care professional—like you—who offers the test. Patients may request their health professional to offer the test.

    Health care professionals can obtain tests directly from HPDI or Bodysync. Before ordering tests, health professionals can learn more about the test and must register on the BodySync website.

    Having obtained a test through a health professional, patients register their test online and take a detailed questionnaire covering their diet, exercise and other lifestyle factors. Then they swab their cheeks, and submit their genetic material via prepaid FedEx mailer.

    Patients use two swabs (included in the test kit) to obtain genetic material by rubbing the swabs between the cheek and gum (one minute per swab for each cheek). Patients then seal the swabs in an envelope and send via prepaid FedEx mailer to Bodysync. The mailer can be taken to any FedEx pickup station or dropped in any FedEx box within 24 hours.

    The patient can complete the entire test at home. Registering the test and taking the online questionnaire can be completed in 20–30 minutes. Swabbing and sealing swabs takes just two or three minutes.

    Bodysync Nutrisync genetic assessment nutrigenomic testingTests include swabs and patient registration instructions.

    Health professionals who provide the test gain full access to their clients genetic test results and Action Plan. This way, approved health professionals can guide their clients in terms of diet, exercise, nutritional supplementation, and lifestyle factors so they can use their test as a means to improve their health.

    The genetic test is an ideal way for health professionals to develop and support a comprehensive plan for their clients that can help ensure compliance in diet, nutrition, exercise, and supplement use.

    Patients will readily see how they benefit from dietary and lifestyle recommendations based on genetics, and gain a clear action plan. Health professionals will find the test a useful tool for guiding their patients and for supporting their quest for better health.

    We at HPDI are excited to be working with Bodysync, Inc. to provide health professionals with test results and Action Plans that can help make a difference in their clients' health and lifestyle. We hope soon the test results will be matched to various HPDI products so that nutritional needs can more easily be met on a daily basis.

    HPDI highly recommends this test for health professionals who wish to leverage in-depth genetic analysis and a comprehensive action plan based on genetic science to help their patients achieve higher levels of health. Learn more about how you can provide the Bodysync genetic test to your patients.

    Purchase Bodysync test kits from HPDI for $249.95.

    INFORMATION FOR HEALTH PROFESSIONALS

    HPDI resellers wishing to purchase tests should first register as a health professional on Bodysync.com, and mention HPDI in the registration. Once approved by Bodysync to administer the test, you can purchase test kits from HPDI or from Bodysync. Below is a graphic illustrating the process:

    bodysync nutrisync nutrigenomic testing

    RESOURCES

    Articles

    DISCOVERING NUTRITIONAL NEEDS THROUGH ADVANCED GENETIC TESTING

    BENEFITS OF NUTRIGENOMIC TESTING FOR HEALTH

    Links

    HPDI Bodysync page for health professionals

    Purchase tests on HPDI reseller website

    Health professional registration and login page for Bodysync testing

    Bodysync homepage

    MyNutrisync (test kit registration for patients/clients/end-users)

  • MOLECULAR HYDROGEN (H2) AT FOREFRONT OF HEALTH RESEARCH

    Dr. Hank Liers, PhD molecular hydrogen H2Recently, I have been researching the healing potential and benefits of molecular hydrogen (H2). I was quite surprised to see the many studies carried out in the last 10 years regarding the healing abilities of H2. Below is an abstract of an article that summarizes much of the research that has been carried out. The entire article is available when you click the link.

    Molecular Hydrogen

    THE EVOLUTION OF MOLECULAR HYDROGEN: A NOTEWORTHY POTENTIAL THERAPY WITH CLINICAL SIGNIFICANCE

    From: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660246/

    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."

    BENEFITS OF MOLECULAR HYDROGEN (H2)

    Also, I have recently become aware of the testimonials of people consuming H2 infused water with powerful results. Several people have reported a great diminution of joint pains, improved breathing, clearer thinking, and better sleep shortly after consuming the water.

    HOW TO OBTAIN H2

    I have been investigating products on the market that contain H2 and these include 1) Tablets producing H2 when dropped into water, 2) Bottles of water that contain H2, and 3) Water ionizers that produce considerable amounts of H2. One of the advantages of molecular hydrogen-infused water is that it is easy to consume it, and convenient to make it wherever and whenever you like.

    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 preferably 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.

    Please look for additional information about molecular hydrogen and Active H2 tablets in forthcoming HPDI blog articles.

    ADDITIONAL RESOURCES

    WONDERS OF MOLECULAR HYDROGEN
    by Fred Liers, PhD (from the HPDI Blog)

    ACTIVE H2 (tablet product)

    Molecular Hydrogen Foundation (MHF)

     

  • ULTIMATE PROTECTOR INGREDIENTS - BLACK CURRANT EXTRACT

    Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberryUltimate Protector contains black currant extract, as well as components from 29 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I explore the ingredient black currant extract, which is a component of Anthocomplete™ from Futureceuticals.

    ANTHOCOMPLETE™

    AnthoComplete™ (N669) is a specially designed blend of anthocyanins derived from wild bilberry and wild blueberry, acai, black currant extract, sweet cherry, raspberry, elderberry, blackberry, aronia, black soybean hull extract, and blue corn. Anthocyanins are powerful plant polyphenols associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

    Carefully designed to maximize the amount of beneficial anthocyanins that can be available in a single source, AnthoComplete is a proprietary formula suitable for a wide-range of applications.

    With its diverse blend, AnthoComplete contains a minimum level of 10% anthocyanins, 3,000 ORAC μmole TE/g (typical), and 15% total phenolics (typical).

    Owing to the high levels of anthocyanins and Vitamin C, two types of important antioxidants, blackcurrants have been shown by scientific research to have many benefits in promoting health and preventing diseases. Vitamin C is an essential nutrient required for the body’s normal functions and the antioxidant polyphenols in black currants (particularly anthocyanins) may help in maintaining cardiovascular health, ageing and brain health, urinary tract health and healthy vision.

    Black Currant Black Currant Berries

    HEALTH BENEFITS OF BLACK CURRANT EXTRACT

    Black currants (Ribes nigrum) have been used in a wide variety of foods for many years. They contain a relatively large Vitamin C content, more than almost any other commonly consumed fruit. Ongoing research is further showing the benefits of black currants based largely on the polyphenolic content of the fruit and its related products.

    Black currants have anti-oxidant value (Oxygen radical absorbance capacity- ORAC) of 7950 Trolex Equivalents per 100g, which is one of the highest value for fruits after chokeberries, elderberry, and cranberries.

    The intensely dark color of blackcurrants is due to its high content of anthocyanin - primarily 3- glucosides and 3-rutinosides of cyanidin and delphinidin. It has been found that these components exhibit powerful hydroxyl radical scavenging abilities and protect endothelial cells in model systems.

    In addition, the anthocyanins have been shown to positively influence the α-glucosidase phase of starch digestion providing a reduction of sugar release during starch food digestion.

    Also, black currants are a good source of glycosylated flavonols such as quercetin, myrecetin and kaempferol. Scientific studies at the fundamental cellular level have indicated that these compounds can interact with the bodies own innate Antioxidant Response Elements (ARE), such as the transcription factor Nrf2, and more specifically stimulate expression of the detoxification enzymes such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes.

    Scientific Studies on the Antioxidant Effects of Black Currants

    Below, I provide a few relevant scientific studies on the antioxidant effects and potential health benefits of black currant extracts.

    Biological activity of blackcurrant Extracts (Ribes nigrum L.) in relation to erythrocyte membranes.
    From: http://www.ncbi.nlm.nih.gov/pubmed/24527456

    Abstract

    Compounds contained in fruits and leaves of blackcurrant (Ribes nigrum L.) are known as agents acting preventively and therapeutically on the organism. The HPLC analysis showed they are rich in polyphenol anthocyanins in fruits and flavonoids in leaves, that have antioxidant activity and are beneficial for health. The aim of the research was to determine the effect of blackcurrant fruit and leaf extracts on the physical properties of the erythrocyte membranes and assess their antioxidant properties. The effect of the extracts on osmotic resistance, shape of erythrocytes and hemolytic and antioxidant activity of the extracts were examined with spectrophotometric methods. The FTIR investigation showed that extracts modify the erythrocyte membrane and protect it against free radicals induced by UV radiation. The results show that the extracts do not induce hemolysis and even protect erythrocytes against the harmful action of UVC radiation, while slightly strengthening the membrane and inducing echinocytes. The compounds contained in the extracts do not penetrate into the hydrophobic region, but bind to the membrane surface inducing small changes in the packing arrangement of the polar head groups of membrane lipids. The extracts have a high antioxidant activity. Their presence on the surface of the erythrocyte membrane entails protection against free radicals.

    Anthocyanin-rich black currant extract suppresses the growth of human hepatocellular carcinoma cells.

    Abstract

    Dietary antioxidants, such as anthocyanins, are helpful in the prevention and control of various diseases by counteracting the imbalance of oxidative and antioxidative factors in the living systems. Black currant (Ribes nigrum L., Grossulariaceae) is known to contain high amounts of anthocyanins (250 mg/100 g fresh fruit). Black currant fruits have been used in Asian and European traditional medicine for the treatment of a variety of diseases. Black currant extract has recently been found to be the second most effective amongst nine different berry extracts studied for their free radical scavenging activity. Constituents present in black currant juice have been found to exert a number of health-promoting effects, including immunomodulatory, antimicrobial and antiinflammatory actions, inhibition of low-density lipoprotein, and reduction of cardiovascular diseases. Although antioxidant and antiinflammatory effects of black currant juice could be of value in preventing and treating oxidative stress- and inflammation-driven cancers, no experimental evidence is available to now. The objective of the present study was to evaluate the potential antiproliferative effects of black currant fruit skin extract against HepG2 human liver cancer cells. The aqueous extract yielded an anthocyanin-rich fraction with cyanidin-3-O-rutinoside as one of the major anthocyanins. This fraction exhibited a potent cytotoxic effect on HepG2 cells and this effect was more pronounced than that of delphinidin and cyanidin, two major aglycones of anthocyanins present in black currant. Our results indicate, for the first time, that black currant skin containing an anthocyanin-rich fraction inhibits the proliferation of liver cancer cells, possibly due to additive as well as synergistic effects. This product could be useful in the prevention and treatment of human hepatocellular carcinoma.

     

    Black currant anthocyanins abrogate oxidative stress through Nrf2- mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma.

    From:http://www.ncbi.nlm.nih.gov/pubmed/22873220

    Abstract

    Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost > 1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off potential cancer risks and mortality. A major predisposing condition, pertinent to the development and progression of HCC is oxidative stress. We previously reported a striking chemopreventive effect of anthocyanin-rich black currant skin extract (BCSE) against diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats. The current study aims to elucidate the underlying antioxidant mechanisms of black currant anthocyanins implicated in the previously observed chemopreventive effects against experimental hepatocarcinogenesis. Dietary BCSE (100 and 500 mg/kg) administered four weeks before and 18 weeks after DENA challenge decreased abnormal lipid peroxidation, protein oxidation, and expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in a dose-responsive fashion. Mechanistic studies revealed that BCSE upregulated the gene expression of a number of hepatic antioxidant and carcinogen detoxifying enzymes, such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes, in DENA-initiated animals. Protein and mRNA expressions of nuclear factor E2-related factor 2 (Nrf2) were substantially elevated with BCSE treatment, providing a direct evidence of a coordinated activation of the Nrf2-regulated antioxidant pathway, which led to the upregulation of a variety of housekeeping genes. The results of our study provide substantial evidence that black currant bioactive anthocyanins exert chemopreventive actions against DENA-inflicted hepatocarcinogenesis by attenuating oxidative stress through activation of Nrf2 signaling pathway.

     

    Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response.

    From: http://www.ncbi.nlm.nih.gov/pubmed/22213170

    Abstract

    Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti-inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis. Dietary BCSE (100 or 500 mg/kg) treatment for 22 wk afforded a striking inhibition of DENA-induced hepatic gamma-glutamyl transpeptidase-positive preneoplastic foci in a dose-responsive fashion. There was a significant increase in hepatic expression of heat shock proteins (HSP70 and HSP90), cyclooxygenase-2, and nuclear factor-κB (NF-κB) in DENA-exposed rat livers. Dietary BCSE dose-dependently abrogated all these elevated inflammatory markers. The possible cardiotoxicity of BCSE was assessed by monitoring cardiac functions using transthoracic echocardiography. BCSE-mediated anti-inflammatory effects during rat liver carcinogenesis have been achieved without any cardiotoxicity. Our results provide convincing evidence, for the very first time, that suppression of the inflammatory cascade through modulation of the NF-κB signaling pathway could be implicated, at least in part, in the chemopreventive effects of black currant bioactive phytoconstituents against experimental hepatocarcinogenesis. These results coupled with an excellent safety profile of BCSE support the development of black currant phytochemicals for the chemoprevention of inflammation-driven hepatocellular cancer.

     

    Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats.

    From: http://www.ncbi.nlm.nih.gov/pubmed/21216582

    Abstract

    Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) fruits have a high anthocyanin content. This "superfruit" is known to possess various pharmacological effects including alleviation of chronic oxidative stress and inflammation. In contrast to a large volume of literature on the health benefits of black currant, limited evidence on antitumor effects of black currant exists with virtually no data on the prevention of experimental carcinogenesis. In the current study, we have investigated the chemopreventive effects of an anthocyanin-rich black currant skin extract (BCSE) utilizing our well-characterized model of rat liver carcinogenesis. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary BCSE for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. BCSE dose-dependently decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was confirmed by histopathological examination of liver sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in DENA-induced rat liver tumorigenesis respectively. Mechanistic studies revealed that BCSE-mediated proapototic signal during experimental hepatocarcinogenesis may be propagated via the up-regulation of Bax and down-regulation of Bcl-2 expression at the translational level. These results along with a safety profile of BCSE encourage the development of black currant bioactive constituents as chemopreventive agents for human liver cancer.

     

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

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

    Abstract

    Abstract Image

    The berries of bilberry and black currant are a rich source of anthocyanins, which are thought to have favorable effects on nonalcoholic steatohepatitis (NASH). This study was designed to examine whether purified anthocyanins from bilberry and black currant are able to limit the disorders related to NASH induced by a methionine-choline-deficient (MCD) diet in mice. The results showed that treatment with anthocyanins not only alleviated inflammation, oxidative stress, steatosis, and even fibrosis but also improved depletion of mitochondrial content and damage of mitochondrial biogenesis and electron transfer chain developed concomitantly in the liver of mice fed the MCD diet. Furthermore, anthocyanins treatment promoted activation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α). These data provide evidence that anthocyanins possess significant protective effects against NASH and mitochondrial defects in response to a MCD diet, with a mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.

    SUMMARY

    Black currants are an important fruit full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.

     

  • ULTIMATE PROTECTOR INGREDIENTS – CURCUMINOIDS

     Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist curcuminoidsUltimate Protector contains curcuminoids (greater than 95% from turmeric), as well as components from 29 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I will explore the ingredient curcuminoids, which is added as a separate ingredient.

    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, very pretty! Turmeric plants are very pretty!

    Extensive research over the past 30 years has indicated 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 of scientific studies (like the National Institutes of Health (NIH) PubMed database) 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

1-6 of 12

Page:
  1. 1
  2. 2