Every month, we publish Vitamin Research News — a newsletter that brings you
the latest happenings from the world of nutritional science. You can read the
June
2009
newsletter below, or find the links to past issues in the
newsletter archive on the right side of this page.
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Customers Corner |
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The President’s Desk
Regulatory Insanity
Robert Watson, President/CEO
First, I’m happy to announce that our new software implementation went relatively smoothly. I sincerely appreciate the patience of those customers who were subjected to some breakdowns as we attempted to maintain the highest quality of service as we dealt with the normal bugs seen in a software integration of the magnitude we just experienced. We also experienced the frenzy of the H1N1 flu strain. This can be a serious disease, and we closely monitored the science and real issues and refused to take advantage of the hype surrounding this issue. Those individuals focused on maintaining a strong immune system with the recommendations we made in the past should weather the storm of this strain and most flu strains we face. We are closely monitoring the regulatory craziness happening as the FDA begins to take shape under the new administration. The absurdity of what is happening is best illustrated by the Cheerios fiasco. Many of you have heard that General Mills received an FDA warning letter because according to the regulatory agency the cholesterol-lowering claims made on Cheerios Toasted Whole Grain Oat Cereal implied the product was intended to treat or prevent a disease, moving it into the category of a drug. A harmless food substance called a drug? How ridiculous is that? What’s even more ludicrous is that the FDA says it agrees with the data that soluble fiber from whole grain oats can help reduce heart disease risk—yet it’s still preventing the cereal manufacturer from communicating the data because the science relating to cholesterol reduction was presented as a stand-alone claim rather than as part of the authorized health claim. Is this kind of regulatory absurdity really supporting our interests as consumers? The new Good Manufacturing Practices (GMP) regulations from the FDA are implemented this month for all companies with 20 to 499 employees. We’ve been fully prepared for some time and welcome the regulations to bring serious quality control to the industry. Let’s just hope the interpretation of the regulations are sane!
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Hyaluronic Acid
New Delivery System Provides Enhanced Absorption of Joint and Skin Nutrient
Karen Brown, PhD and Carol Cooper, PhD
Hyaluronic acid (HA or hyaluronan) is a naturally occurring biopolymer found in the extracellular matrix of all vertebrates, in the tissues and body fluids. It is a long unbranched chain comprised of two repeating disaccharide units, N-acetlyglucosamine and glucuronic acid, which can twist and fold back onto itself in a variety of three dimensional structures. Glucosamine is a raw material for the biosynthesis of hyaluronic acid. Glucosamine is also produced as a metabolite of HA. In fact, taking oral HA is like taking a time-release glucosamine. HA belongs to a family of endogenous polysaccharide polymers known as glycosaminoglycans, a class which also contains such molecules as heparin and chondroitin sulfate. While different repeating units distinguish these molecules, their overall physical structures are very similar. Although these molecules attach to the same cell-surface receptor, they do so at a much reduced efficiency (see below). Recently, HA has gained attention because it has been shown to impact numerous functions within the body. In its high molecular weight form, it is injected intra-articularly under the knee cap as a joint fluid replacement.1 It is also used in horses as an intravenous injection, where it works systemically to relieve inflammation of the joint.2 The scientific literature shows that high molecular weight (HMW) HA functions physiologically as an anti-inflammatory. The work of Ialenti and DiRosa examined both acute and chronic inflammation and showed that HA was able to resolve both.3 Capsules containing hyaluronic acid are now commonly available as nutritional supplements used for joint and skin health. However, high molecular weight oral liquids, as well as the new oral lozenge, are especially promising as delivery systems for hyaluronic acid because they are designed to be absorbed within the oral cavity. Oral Cavity Absorption The administration of active ingredients by way of the oral mucosa is becoming therapeutically more important. Delivery through the oral cavity is easy to administer and has the potential to provide efficient absorption because the oral mucosa is highly vascularized. Additionally, the “active” ingredient can bypass the acidic environment of the stomach, enzymatic activity of the intestine, and move directly into the bloodstream. Thus, the active ingredient can be effective in smaller, more controlled doses. Scientists have grappled with the problems of oral delivery mechanisms for decades. Designing biologically effective dosing forms that can be absorbed in the mouth is not easy due to the integrity of the lining of the oral cavity. Compatibility with the oral mucosa is key. Much can be learned from this research which is directly applicable to hyaluronic acid and reinforces the observation that oral absorption of liquid hyaluronic acid is the preferred delivery route. When designing medicines that will be absorbed via the oral cavity, scientists first look for high compatibility between the lining of the mouth and the active ingredient itself. Often a carrier molecule must be used to enhance compatibility. In this case, hyaluronic acid has a great advantage. The tissues that comprise the mucous membrane of the oral cavity are rich in high molecular weight (HMW) hyaluronic acid. When HMW liquid HA is put into the mouth, the lining can recognize the added HA and readily accept it into the membrane. HA is highly compatible with the oral mucosa. Hyaluronic acid has already been shown to be a good candidate for oral drug delivery systems because it is highly compatible with the tissues of the oral mucosa, which already contains large amounts of HA.4 Therefore, no carrier molecule needs to be added to HA to enhance its oral absorption. Pulling HA into the Membrane Scientists designing active ingredients to be absorbed via the oral mucosa also look for additional factors, like receptor sites, which can promote absorption. Such factors help to “pull” the actives into the mucosa so that the active can be delivered into the blood stream. In the case of hyaluronic acid, the receptor CD44 provides such an added advantage. The buccal cavity is highly vascularized and contains large quantities of CD44, a receptor molecule specific for hyaluronic acid.5 CD44 can attract and attach to the hyaluronic acid and move it into the blood stream where it can do its work. CD44 is a powerful cell-surface receptor, with a high affinity for HA. In fact, CD44 is specific for HA. It is a key player in the health of the immune system, and the primary driver for the anti-inflammatory properties of HA. The oral mucosa is rich in CD44. It can promote absorption of HA by pulling the molecule through the mucosa and into the blood stream. Advantage of a Lozenge It is well-known that only hyaluronic acid of high molecular weight (HMW) is active as an anti-inflammatory. For that reason, it is important to preserve the molecular weight, and thus the activity, of the HA molecule. When HA of high molecular weight of at least 2.4 million Daltons reaches the stomach, it is broken down into smaller, less effective fragments by the acidic environment. Chemically, it would be expected that the glycosidic bond present in hyaluronic acid would be broken down by stomach acid, rendering it less effective.6 Indeed acid hydrolysis (the breaking of the chemical bond) is often used to analyze biopolymers in analytical experiments.7-8 Capsules containing solid HA powder are designed to work in the stomach. The lining of the stomach, under normal conditions contains little CD44.9 Therefore, absorption of high molecular weight HA via the stomach is limited and HA administered via this route would be expected to be less effective. As indicated above, the most effective delivery of HA is via the mucous membranes, including the lining of the mouth, the tongue and the gums. Formulation of HA into a lozenge provides the necessary stabilization for the high molecular weight HA molecule. Additionally, the mild stickiness produced upon dissolution in the mouth and mixing with the saliva allows the HA to attach to the extensive surfaces that are available (lining of the mouth, tongue, gums). This produces a time-release effect. The mucous membranes of the mouth offer extensive numbers of CD44 receptors to attract and bind the HA, as well as the necessary vascularization to receive the HA molecule once it is pulled through the membranes via the receptors. Extending the time that the HA molecule remains in the mouth via formulation into a lozenge extends the time allowed for absorption and increases the effectiveness of the HA. Conclusion Hyaluronic Acid is commonly used to promote joint and skin health and to reduce inflammation. Now, a new high molecular weight HA lozenge provides a highly bioavailable form of this nutrient that is well absorbed through the oral mucosa. Karen Brown, PhD, received her BS from Washburn University, Topeka, KS in Chemistry and Biology, and her PhD from Oklahoma State University in Biochemistry and Microbiology. She has worked for 28 years in the area of hyaluronic acid. Carol Cooper, PhD, received her BS from Wayne State University, Detroit, MI, in Chemistry, and her PhD from Wayne State in Biochemistry. She has worked in the area of hyaluronic acid for more than 15 years. References 1. Wright KE, S.G. Maurer, P.E. DiCesare Viscosupplementation for osteoarthritis Am J Orthop 29(2)18-89 (2000). 2. Kawcak, CE, DD Frisbie, GW Trotter, CW McIlwraith, SM Gillette, BE Powerw, RM Walton Effects of intravenous administration of sodium hyaluronate on carpal joints in exercising horses after arthroscopic surgery and osteochondral fragmentation Am J Vet Res 58(10) 1132-40 (1997). 3. Ialenti, A. and M. Di Rosa Hyaluronic Acid Modulates Acute and Chronic Inflammation Agents Actions, 43, 44-47 (1994). 4. Andrews, GP, T P Laverty, D S Jones Mucoadhesive polymeric platforms for controlled drug delivery Eur. J. Pharmaceutics and Biopharmaceutics 71(3):505-518 (2009). 5. Aruffo, Alejandro, Ivan Stamenkovic, Michael Meinick, Charles B. Underhill and Brian Seed CD44 is the Principal Cell Surface Receptor for Hyaluronate Cell (61): 1303-1313 (1990). 6. Xiang, Qian, Y.Y.Lee, Par O. Petterson and Robert W. Torget Heterogeneous aspects of acid hydrolysis of a-cellulose in Applied Biochemistry and Biotechnology Humana Press, Inc. 107(1-3) pp 505-521 Spring, 2003. 7. Bosworth, TR and JE Scott A specific fluorometric assay for hexosamines in glycosaminoglycans, based on deaminative cleavage with nitrous acid Anal Biochem 223(2):266-73 (1994). 8. Sobocinski PZ, WJ Canterbury, KH Jurgens Improved continuous-flow method for determination of total serum hexosamines Clin Chem 22(8):1394-6 (1976). 9. Washington, K., MR Gottfried and MJ Telen Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas Hum Pathol 25(10):1043-9 (1994).
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Celiac Disease and Gluten Sensitivity
New Test Detects Condition Responsible for Common Health Concerns
Michael Joseph, HHC, AADP
Celiac disease is one of the most sinister and insidious of food allergies. It is estimated that as many as 3 million people in the US may have been diagnosed with the disease, and countless more, at least 97 percent, go undiagnosed and untreated.1 It should also be noted that as many as 30 million Americans or 10 percent of the American population have some kind of sensitivity to wheat or wheat gluten.2 Studies have shown that celiac disease is most prevalent in Ireland, Finland, and northern Italy. It is truly a pandemic of the 21st century, so much so that the Italian government has recently considered having all children under the age of six tested for celiac disease.3 | Statistics on the Prevalence of Celiac Disease14 | | 1 in 167 supposedly healthy school children 1 in 111 healthy, asymptomatic adults 1 in 39 adults with celiac disease are positively diagnosed | | Among those reported with gastrointestinal symptoms: | 1 in 40 children 1 in 30 adults | | According to a study published in the Lancet: | 19 out of 20 cases go undetected and untreated | | Prevalence in ethnicities: | 1 in 250 Italians 1 in 122 Irish 1 in 85 Finnish 1 in 70 Sardinians 1 in 18 Algerian Saharawi refugee children | | Among those with a parent, grandparent, or sibling diagnosed with celiac disease: | 1 in 11 people | Celiac disease (also known as CD or celiac sprue) is a permanent genetic syndrome of the small intestine caused by an extreme allergic reaction to the gluten protein found in wheat and wheat derivatives. It is the gluten sub-fraction gliadin that attacks the lining of the small intestine causing cellular deterioration. This then leads to the chronic inflammation of the small bowel, which results in poor absorption of nutrients, minerals, and vitamins. This chain reaction of events can cause a great deal of damage to not just the digestive system, but also the entire body, including the nervous system and the vital organs.4 Some of the symptoms and conditions associated with celiac disease are depression, overweight/underweight, rashes, diarrhea or constipation, abnormal elevation of liver enzymes, neuropathy, osteoporosis, diabetes, increased prevalence of autoimmune diseases, abdominal cancer, and thyroid conditions. It is important to note that some individuals with celiac disease will have very minor GI symptoms. Some health authorities state that clinical depression is the most commonly presenting symptom of undiagnosed celiac disease.5 This article will address a new celiac disease test available here as well as explain the recommended dietary changes one needs to undertake if the test results are returned as positive. | Commonly Reported Symptoms Presented with Celiac Disease and/or Gluten Allergy and Sensitivity14 | - Chronic Depression (some authorities say this is the most common presenting symptom of celiac disease, especially if the patient hasn’t responded well to medication or other treatments)
- Abnormal elevation of liver enzymes of unknown cause
- Permanent teeth with horizontal grooves and chalky whiteness
- Chronic nerve disease of unknown cause (such as ataxia and peripheral neuropathy)
- Osteoporosis in women not responding to conventional therapies
- Repeated low-impact bone fractures
- Intestinal Cancers
- Insulin Dependent Diabetes
- Thyroid disease, over and under active
| - Short stature in children
- Down Syndrome in children
- Chronic or recurring respiratory tract problems like ear infections and sinusitis
- Chronic fatigue caused by malabsorbtion of nutrients
- Chronic fatigue syndrome
- Mouth ulcers/canker sores
- Anemia, including, iron, folic acid, B12 and B6 deficiency anemia
- Osteoporosis
- Unintended weight loss
- Chronic diarrhea
- Constipation
- Abdominal bleeding
- Crohn’s disease
- Diverticulitis
- Depression
- ADD/ADHD and behavioral problems in children
- Autism
| Lifestyle Changes It takes less than a gram per day of gliadin, which is less than 2 percent of a single ounce, to cause a reaction.6 Consequently, the only way to alleviate the symptoms of celiac disease is the total elimination of all grains and foods containing gluten, like pastas, breads, sauces, cakes, pies, and crackers. This can be a daunting task, as much of the American and western diets are essentially based on the gluten cereals. The cereal grains that contain gluten include wheat, barley, rye, triticale, spelt, and kamut. Also note there is some controversy as to whether or not oats have an effect on celiac disease. Findings are inconclusive; however many times oats are stored in the same facility as wheat and flour, so there is the possibility of trace amounts of wheat gluten found in oats.7 Wheat isn’t just found in grain products. Wheat flour is used as a filler in cold cuts and deli meats, used to dust frozen vegetables, and is used as a thickener for soy sauce and many pharmaceutical medications use gluten as a filler or a binding agent. It is a common additive in soups, packaged products, and even found in sausages. It is important to keep in mind that if you have celiac disease, there is a risk every time you buy a packaged food.8 It is recommended that whole and unrefined foods are purchased and cooked to avoid any possibility of consuming a food containing hidden wheat gluten. Going to a restaurant can be challenging for those with celiac disease or wheat sensitivities, since wheat products make up much of most restaurants’ menus. Be sure to ask a lot of questions, and if there is any doubt, don’t order it. Some restaurants, such as the Italian chain Carabbas, have a gluten free menu, and Budweiser even makes a beer from a gluten free grain called sorghum. This may all seem very upsetting to those who like breads and pastas, but there are alternatives. There are many companies that make 100 percent wheat and gluten free pasta, bread, muffins, and other “wheat-type” items. A popular wheat-pasta alternative is rice pasta, which is a delicious change of pace for those even without gluten sensitivity. Also, a great way of circumventing all of this confusion is to buy and eat whole, unrefined, non-gluten grains, like brown rice, millet, quinoa, buckwheat, and many others. Not only are these grains all 100 percent gluten free, but you can make amazing pilafs and simple, tasty dishes that are quick and easy. The gluten free grains tend to cook quicker and are easier to digest then the gluten grains. | Celiac Disease Induces Mal-Absorption of the Following Nutrients14 | - Minerals
- Iron
- Zinc
- Calcium
- Magnesium
- Potassium
- Selenium
- Vitamins B1, B6, B12, Folic Acid, A, D, E, K
- Omega-3 and Omega-6 Fatty Acids
| Screening For Celiac Disease and Gluten Sensitivity The testing for celiac disease is somewhat obscure, but the “gold standard” is an intestinal biopsy. This biopsy examines to see if the villi, which are tiny finger-like protrusions in the walls of the small intestine that aid in nutrient absorption, have flattened and shriveled. Other testing includes the IgG ELISA test, which is a simple blood test that measures immune reactions mediated by the IgG antibody, and the very expensive and sophisticated IgA anti-endomysium test. It is recommended and encouraged to get some sort of testing done if you have any of the related symptoms listed here.9 There is, however, a blood test called the IgA Anti-Tissue Transglutaminase Test, or tTG for short, and also known as the TGA ELISA or Celiac Antibody Profile. This test measures anti-transglutaminase IgA antibodies in human serum, and a positive test means that a positive diagnosis for celiac disease is very likely. According to studies in the USA and in Europe, this test is as accurate as the IgA anti-endomysium test, but is much less expensive.10 This test is now available here. The importance of getting tested cannot be understated, even if obvious symptoms are not presented. Undiagnosed celiac disease or gluten sensitivity can increase one’s risk for abdominal cancer, lymphoma, and other diseases such as diabetes, especially if ones close relative has been diagnosed with celiac disease.11 A popular television personality was interviewed recently and she spoke about a more than ten-year struggle to find the source of her symptoms, and it wasn’t until a positive diagnosis for celiac disease, when she eliminated wheat gluten from her diet, that she was able to find relief.12 Because of the prevalence of gluten sensitivities and celiac disease that commonly goes undiagnosed or misdiagnosed, it is recommended that everyone have an IgG ELISA general food allergen panel done in addition to an anti-gliadin tTg test. These tests along with a food diary and a symptom scorecard can greatly assist a health care practitioner or nutrition consultant fine tune a non-allergic diet for the patient. Remember, the only cure for celiac disease is strict avoidance.13 Conclusion Reliable testing is the first step to identifying if wheat is the culprit behind ones symptoms. A new celiac test known as the IgA Anti-Tissue Transglutaminase Test (tTG) or Celiac Antibody Profile is now available here. The results of this test can be very enlightening and can help solve the mystery behind a variety of health concerns. If celiac disease or gluten sensitivity is detected, implementing lifestyle changes can have dramatic improvements in health. References 1. Celiac Disease Statistics Jefferson Adams Published 6/26/06; Celiac Disease facts and figures, University of Chicago Celiac Center. 2. James Braly MD & Patrick Holford. Hidden Food Allergies. Basic Health Publications, Inc. 2006. 3. Jefferson University Hospitals Division of gastroenterology and hepatology NIH Publication No. 98-4269. April 1998. 4. James Braly MD. Food Allergy Relief. 2000. 5. James Braly MD & Patrick Holford. Hidden Food Allergies. Basic Health Publications, Inc. 2006; Canadian Celiac Association “Celiac Disease” Dr. Mohsin Rashid. 6. James Braly MD & Patrick Holford. Hidden Food Allergies. Basic Health Publications, Inc. 2006 7. James Braly MD & Ron Hoggan MA. Dangerous Grains. Avery. 2002. 8. Dr James Braly’s Food Allergy and Nutrition Revolution 1992; Canadian Celiac Association “Celiac Disease” Dr. Mohsin Rashid. 9. James Braly MD & Patrick Holford. Hidden Food Allergies. Basic Health Publications, Inc. 2006; James Braly MD. Food Allergy Relief. 2000. 10. James Braly MD & Patrick Holford. Hidden Food Allergies. Basic Health Publications, Inc. 2006; James Braly MD. Food Allergy Relief. James Braly MD 2000. 11. Jefferson University Hospitals Division of gastroenterology and hepatology NIH Publication No. 98-4269 April 1998; James Braly MD & Ron Hoggan MA Dangerous Grains. Avery. 2002; James Braly MD & Patrick Holford. Hidden Food Allergies. 2006. 12. Daily News. “’The View’ co-host Elizabeth Hasselbeck dishes on celiac disease in the ’G Free Diet’” by Eloise Parker, Daily News staff writer 5/4/09. 13. Canadian Celiac Association “Celiac Disease” Dr. Mohsin Rashid; James Braly MD & Ron Hoggan MA. Dangerous Grains. Avery. 2002. 14. Celiac Disease facts and figures, University of Chicago Celiac Center; James Braly MD & Patrick Holford. Hidden Food Allergies. Basic Health Publications, Inc. 2006; Celiac Disease Statistics Jefferson Adams Published 6/26/06; Jefferson University Hospitals Division of gastroenterology and hepatology NIH Publication No. 98-4269 April 1998.
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New Dynammune™ Magnifies EpiCor®’s Immune-Enhancing Abilities in Great-Tasting Liquid Formula
Chris D. Meletis, ND
EpiCor®, when it was introduced, revolutionized the concept of immune support. Now, we’ve magnified the effects of this powerful immune-boosting supplement by introducing a new, great-tasting liquid formula called Dynammune™, which features ImmuneCE™, a proprietary blend of the premier immune enhancer EpiCor and a specially derived colostrum fraction that helps “educate” the immune system to target and rapidly respond to invading pathogens. With the new ImmuneCE blend, EpiCor’s actions become even more profound, helping EpiCor target its efforts by enhancing phagocytosis, the process whereby cells “digest” foreign intruders. ImmuneCE supports phagocytosis and makes cells more susceptible to the action of phagocytes, allowing for a faster response. Immunity Enhancement Times Two The delivery of EpiCor, as the key component of the ImmuneCE blend, stimulates the production of immune memory compounds that act as a sort of homing device to more specifically direct the activated natural killer (NK) cells, stimulated by EpiCor, to destroy foreign invaders such as viruses and bacteria. In other words, the components in Dynammune educate immune cells by teaching them where in the body they need to go to most effectively fight the invading pathogenic organisms. When EpiCor is blended with the other ingredient in ImmuneCE, it creates a synergistic interaction that promotes even more active immune response, causes faster phagocytosis, supports natural killer cell activation, and protects healthy cells from apoptosis (programmed cell suicide). EpiCor also provides antioxidant benefits that protect live cells from oxidative damage caused by the free radicals produced during the immune responses to the invading pathogens. In vitro testing suggests this powerful new partner of EpiCor prompts the innate immune system into action while simultaneously encouraging a “smarter” immune response. In order for the human body to recognize an invader as foreign, it must produce antibodies against the invading pathogen. The new fraction contained in ImmuneCE, helps “teach” the body to recognize and target foreign invaders, enhancing the antibody response. Immune cells known as phagocytes engulf or “eat” the foreign intruders and also educate the immune system as to what is foreign and what is normal. This helps the immune system to respond more rapidly to selectively neutralize pathogens. The “immune memory” enhancing factors contained in ImmuneCE bolsters EpiCor’s actions by priming and targeting the phagocytosis process, thus, making the invading pathogens more susceptible to the aggressive, protective action of the phagocytes. At this stage in the immune response process, cytokines are secreted to attract other white blood cells to migrate to the tissue area invaded by the foreign organism, in order to destroy it. Preliminary data has documented that the specially derived “immune memory” fraction in ImmuneCE was able to directly induce a number of cytokines that are known to support Th2 responses, which are involved in the humoral or B-lymphocyte immune response. The next important step in the coordinated immune response involves T-cell and B-cell communication, which leads to natural killer cell activation. T-cells help coordinate this phase of the immune response and help kill identified invaders, while B-cells seek out the targeted pathogenic organisms and produce antibodies against the invading pathogen, which inactivate the invaders and help to repel any future attacks. Both components in the ImmuneCE blend have shown an impressive ability to support activation of natural killer (NK) cells, which kill infected cells and are crucial to holding pathogens at bay until other immune cells can respond. Taking EpiCor One Step Farther ImmuneCE demonstrates an impressive ability to enhance the immune response. EpiCor has already been extensively studied for its immune stimulating, protective actions. One of the key ways that EpiCor enhances immunity is through its ability to increase secretory IgA (sIgA) levels. Researchers have demonstrated that subjects given EpiCor have higher levels of total salivary sIgA.1 This indicates that subjects taking EpiCor had the equivalent of an enhanced immunological envelope protecting the membranes in the eyes, nasal passages, mouth and all the exposed membrane surfaces where pathogenic organisms can enter the body. Studies also have shown that natural killer cells in EpiCor-exposed subjects had a much higher efficiency for killing of pathogen-infected and abnormal cells despite a significant decrease in the natural killer cells’ number, indicating EpiCor increased the natural killer cells’ efficiency. At the same time, subjects exposed to EpiCor experienced a significant inhibition of interferon gamma production and had significantly lower levels of immune complexes, plus produced higher levels of glutathione in their red blood cells, which indicates that EpiCor has anti-inflammatory abilities.2 EpiCor also recently received a Cap-e® bioavailable antioxidants certification. The CAP-e Assay (Cell-based Antioxidant Protection in erythrocytes) analyzes the antioxidant capabilities of natural products inside of cells. In order to claim a product has the potential to slow down or prevent oxidation, its antioxidants must be available at the cellular level. This new CAP-e method evaluates the bioavailability of the antioxidants in a product and documents that the antioxidant molecules have the ability to penetrate living cells and protect them. Emerging research indicates the other core ingredient in ImmuneCE has actions that are complementary to EpiCor. Cells that were exposed to this ingredient for three minutes experienced enhanced phagocytosis. Furthermore, the “immune-memory” fraction in ImmuneCE activated natural killer cells as indicated by this fraction’s ability to enhance activity of the natural killer cells’ activation marker, known as CD 69. Other actions included its ability to 1) provide protection from oxidative damage in a cell-based antioxidant test; 2) induce the production of the Th2 cytokines IL-4, IL-6 and IL-10, considered to be anti-inflammatory cytokines, that are known to support the humoral immune response toward antibody production and 3) protected live cells from oxidative damage, better than either whole colostrum or whey. The “immune memory” enhancing factors in ImmuneCE have also been shown to increase the reactive oxygen burst in immune cells known as polymorphic neutrophiles (PMN). The generation of reactive oxygen species (ROS) and free radicals by PMNs is essential to the destruction of the invading, foreign pathogens. Conclusion The new liquid Dynammune formula supports a balanced immune system with a proprietary blend of two powerful immune-enhancing substances. This new formula magnifies the power of EpiCor, producing an even more targeted immune response by supporting phagocytosis, activating natural killer (NK) cell activity and encouraging the production of “immune memory” stimulating factors that help educate the immune system. Individuals who want to build their immunity will appreciate the synergistic effects of the ImmuneCE components in Dynammune’s liquid formulation. References 1. Jensen GS, Patterson KM, Barnes J, et al. A Double-Blind Placebo-Controlled, Randomized Pilot Study: Consumption of a High-Metabolite Immunogen from Yeast Culture has Beneficial Effects on Erythrocyte Health and Mucosal Immune Protection in Healthy Subjects. The Open Nutrition Journal. 2008; 2:68-75. 2. Jensen GS, Hart AN, Schauss AG. An antiinflammatory immunogen from yeast culture induces activation and alters chemokine receptor expression on human natural killer cells and B lymphocytes in vitro. Nutrition Research. 2007 Jun;27(6):327-335.
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High Cholesterol and Arrhythmia
The Emerging Link Between Two Heart-Harming Conditions
Nieske Zabriskie, ND
High cholesterol and abnormal heart rhythm are often addressed as two separate topics. Individuals who are concerned about unbalanced lipid levels are not always concerned about arrhythmias and vice versa. However, research has uncovered a surprising direct-link between cholesterol levels and arrhythmias, indicating that maintaining healthy cholesterol levels and balancing heart rhythm are both equally essential to heart health. Electrical impulses follow a specific pathway through the heart and trigger the heart to beat. Arrhythmias occur when there is any kind of disruption to these electrical impulses. The impulses are under the control of the nervous system and specific cells in the heart, and are generated by electrically charged molecules called ions passing through ion channels in the heart cells (myocytes). Generally, a healthy heart beats 60-100 times per minute in a regular pattern. Arrhythmias include the heart beating too slowly (bradycardia), too quickly (tachycardia), or irregularly. Fibrillations, or chaotic electrical impulses causing the heart to not pump blood efficiently, can occur in the upper heart chambers (atrial fibrillation) or the lower heart chambers (ventricular fibrillation). Some arrhythmias increase the risk of heart disease, stroke, blood clot formation, cardiac arrest, and death. Atrial fibrillation is the most common sustained heart rhythm disorder and affects approximately 2.2 million adults in the United States.1 It is well established that elevated cholesterol contributes to the development of atherosclerosis, which is the accumulation of fatty deposits on the inner lining of arteries. When the arteries that supply blood to heart muscle become hardened and narrowed, it results in the development of coronary artery disease, which then may lead to angina, heart attack, and heart failure. Furthermore, an emerging body of research is beginning to establish a link between elevated cholesterol and arrythmias. Research has shown that animals fed a high-cholesterol diet had significantly increased abnormalities in the regular contraction of the heart and arrhythmias such as ventricular fibrillation.2 Evidence has also shown that low levels of the beneficial high-density lipoprotein (HDL)-cholesterol are associated with an increase in paroxysmal atrial fibrillation.3 Another study found that giving reconstituted HDL-cholesterol to rats decreased the duration of ventricular tachycardia or ventricular fibrillation after reperfusion (the return of blood flow—for example, after a heart attack), suggesting that sufficient levels of HDL-cholesterol is important in regulating normal heart rhythms.4 Statin drugs, used to lower cholesterol levels, have also shown benefit in regulating heart arrhythmias. Some evidence suggests that the lowering of low-density lipoprotein (LDL)-cholesterol by statins is one mechanism in which statins regulate heart rhythms.5 In one study, patients with acute heart attacks were evaluated for ventricular tachycardia/fibrillation and abnormal lipid levels. The study showed that during the acute stage, patients with ventricular tachycardia/fibrillation had higher levels of LDL-cholesterol. At a 3-month follow-up, patients with ventricular tachycardia/fibrillation showed higher levels of total cholesterol, LDL-cholesterol, and triglycerides. The study authors concluded that abnormal lipid levels increased the risk of tachycardia arrhythmias during a heart attack.6 More specifically, researchers have elucidated how cholesterol levels affect heart rate. Using chick heart cells, researchers showed that a specific type of ion channel, GIRK1, which plays an important role in the electrical stimulation of the heart, are increased in lipid-depleted cells resulting in an increase in electrical conductance. Additionally, a protein that helps regulate lipid levels, SREBPs, is increased in lipid-depleted cells. In mice lacking SREBPs, the heart was less responsive to parasympathetic stimulation, GIRK1 was decreased, and the mice were more likely to develop arrhythmias after a heart attack.7 Optimizing Normal Heart Rhythm Due to the connection between abnormal lipid levels and arrhythmia, it is essential to control both aspects of heart health. A number of natural substances, all contained in the formula CardioRhythm, have shown efficacy in supporting normal heart rhythm and improving cardiac function. Magnesium deficiency is associated with heart rhythm changes including atrial fibrillation and flutter.8 Correction of magnesium deficiency provides anti-hypertensive, anti-atherosclerotic, and anti-arrhythmic effects.9 Intravenous magnesium is used in conventional medicine to prevent and treat various types of cardiac arrhythmias.10 Taurine is an amino acid known to have anti-arrhythmic and blood pressure lowering effects. It also retards cholesterol-induced atherosclerosis, stabilizes platelets, and improves the ability of heart muscle tissue to contract.9,11 Taurine supplementation is reported to improve premature atrial and ventricular contractions by regulating the excitability of the heart tissue, and protecting against free radicals damage.12 Using animal models, researchers have shown that taurine supplementation significantly diminished the incidence of irreversible ventricular fibrillation, premature ventricular beats, and ventricular tachycardia during ischemia and reperfusion.13 Berberine is an alkaloid constituent found in several botanicals. Berberine has anti-arrhythmic activity, increases the strength of heart contractions, dilates blood vessels, and decreases heart rate.14 One study showed that in patients with congestive heart failure, berberine supplementation improved the ability of the heart to pump out blood, lessened the frequency of premature ventricular contractions, and decreased ventricular tachycardia.15 Another study showed that in subjects with ventricular tachycardic arrhythmias, berberine supplementation suppressed ventricular premature contractions (VPC) by 50 percent or greater in 62 percent of the subjects and suppressed VPC by 90 percent or greater in 38 percent of the subjects.16 Constituents from Panax notoginseng have also demonstrated anti-arrhythmia, antioxidant, and blood clot reducing activity.17 Studies indicate that this herb exerts anti-arrhythmic activity on ischemic and reperfusion arrhythmias in animal models, provides a protective effect for atrial fibrillation and/or flutter,18 and increases the ventricular fibrillation threshold.19 Another substance known to maintain a healthy heart rhythm is Sophora flavescens, which has been shown to reduce the incidence and delay the onset of experimentally-induced ventricular tachycardia.20 One of the constituents, oxymatrine, reduces both atrial and ventricular premature beats.21 In one study, Sophora flavescens demonstrated significant lowering of blood pressure, heart rate, left ventricular pressure, and increased the ventricular fibrillation threshold.22 In addition to directly regulating heart rhythm with the substances mentioned above, also using an indirect approach by regulating lipid levels can be highly effective in modulating the risk of arrhythmias. A number of natural substances (found in the formula LipiControl®) are used to regulate cholesterol levels. The mevinic acids in red yeast rice inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus blocking cholesterol synthesis. In patients with elevated lipid levels, red yeast rice supplementation maintains healthy levels of total cholesterol, LDL, and triglycerides. In one study, subjects were supplemented with red yeast rice for 8 weeks. The results showed a decrease in LDL cholesterol by 30.9 percent, an increase in HDL cholesterol by 19.9 percent, decreased triglycerides by 34.1 percent, and decreased total cholesterol by 22.7 percent.23 Commiphora mukul, also known as Guggul, contains the active constituents guggulsterones. Guggulsterones can inhibit the synthesis of cholesterol in the liver and modulate bile acid metabolism.24 In one study, guggulipid, containing a standardized dose of 50 mg of guggulsterones per day, was supplemented in subjects with elevated cholesterol for 24 weeks. The results showed that guggulipid supplementation reduced total cholesterol by 11.7 percent, LDL-cholesterol by 12.5 percent, triglycerides by 12 percent, and total cholesterol/ HDL ratio by 11.1 percent.25 Gamma-oryzanol, derived from rice bran oil, is another substance that can support healthy lipid levels. Evidence suggests that gamma-oryzanol acts by decreasing cholesterol absorption and increasing cholesterol excretion.26 Researchers have shown that supplementation with 50 grams per day rice bran oil for 4 weeks decreased the total plasma cholesterol by 6.3 percent and LDL-cholesterol by 10.5 percent, as well as lowered the LDL/HDL ratio by 18.9 percent.27 Other compounds known to play a role in lipid health include beta-sitosterol and niacin. Beta-sitosterol, a plant sterol similar in structure to cholesterol, inhibits cholesterol absorption and can lead on average to a 10 percent reduction in total cholesterol and 13 percent reduction in LDL-cholesterol levels.28 Niacin (vitamin B3) also often is used to help maintain healthy cholesterol levels.29 Inositol hexanicotinate, a non-flush form of niacin, consists of 6 molecules of nicotinic acid (niacin) chemically linked to an inositol molecule. This form of niacin causes less or no flushing seen with niacin or nicotinic acid supplementation and is therefore preferred by many people. Conclusion New research suggests that optimizing lipid levels is important to decrease the risk of cardiac arrhythmias and related adverse cardiac events. A number of vitamins and botanicals found in CardioRhythm and LipiControl can help support a normal heart rhythm while also balancing cholesterol levels. References 1. Centers for Disease Control and Prevention. Atrial Fibrillation Fact Sheet. Available at: http://www.cdc.gov/DHDSP/library/fs_atrial_fibrillation.htm. Accessed on: 05-04-09. 2. Liu YB, Wu CC, Lu LS, et al. Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits. Circ Res. 2003 May 30;92(10):1145-52. 3. Annoura M, Ogawa M, Kumagai K, et al. Cholesterol paradox in patients with paroxysmal atrial fibrillation. Cardiology.1999;92(1):21-7. 4. Imaizumi S, Miura S, Nakamura K, et al. Antiarrhythmogenic effect of reconstituted high-density lipoprotein against ischemia/reperfusion in rats. J Am Coll Cardiol. 2008 Apr 22;51(16):1604-12. 5. Tamargo J, Caballero R, Gómez R, et al. Lipid-lowering therapy with statins, a new approach to antiarrhythmic therapy. Pharmacol Ther. 2007 Apr;114(1):107-26. 6. Liu YB, Wu CC, Lee CM, et al. Dyslipidemia is associated with ventricular tachyarrhythmia in patients with acute ST-segment elevation myocardial infarction. J Formos Med Assoc. 2006 Jan;105(1):17-24. 7. Park HJ, Georgescu SP, Du C, et al. Parasympathetic response in chick myocytes and mouse heart is controlled by SREBP. J Clin Invest. 2008 Jan;118(1):259-71. 8. Nielsen FH, Milne DB, Klevay LM, et al. Dietary magnesium deficiency induces heart rhythm changes, impairs glucose tolerance, and decreases serum cholesterol in post menopausal women. J Am Coll Nutr. 2007 Apr;26(2):121-32. 9. McCarty MF. Complementary vascular-protective actions of magnesium and taurine: a rationale for magnesium taurate. Med Hypotheses. 1996 Feb;46(2):89-100. 10. Ho KM. Intravenous magnesium for cardiac arrhythmias: jack of all trades. Magnes Res. 2008 Mar;21(1):65-8. 11. Fujita T, Ando K, et al. Effects of increased adrenomedullary activity and taurine in young patients with borderline hypertension. Circulation.1987 Mar;75(3):525-32. 12. Eby G, Halcomb WW. Elimination of cardiac arrhythmias using oral taurine with l-arginine with case histories: Hypothesis for nitric oxide stabilization of the sinus node. Med Hypotheses. 2006;67(5):1200-4. 13. Chahine R, Feng J. Protective effects of taurine against reperfusion-induced arrhythmias in isolated ischemic rat heart. Arzneimittelforschung. 1998 Apr;48(4):360-4. 14. Lau CW, Yao XQ, Chen ZY, et al. Cardiovascular actions of berberine. Cardiovasc Drug Rev. 2001 Fall;19(3):234-44. 15. Zeng XH, Zeng XJ, Li YY. Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2003 Jul 15;92(2):173-6. 16. Huang W. Ventricular tachyarrhythmias treated with berberine. Chung Hua Hsin Hsueh Kuan Ping Tsa Chih. 1990;18:155-156,190. 17. Chan P, Thomas GN, Tomlinson B. Protective effects of trilinolein extracted from panax notoginseng against cardiovascular disease. Acta Pharmacol Sin. 2002 Dec;23(12):1157-62. 18. Gao BY, Li XJ, Liu L, et al. Effect of panaxatriol saponins isolated from Panax notoginseng (PTS) on myocardial ischemic arrhythmia in mice and rats. Yao Xue Xue Bao. 1992;27(9):641-4. 19. Wu W, Zhang XM, Liu PM, et al. Effects of Panax notoginseng saponin Rg1 on cardiac electrophysiological properties and ventricular fibrillation threshold in dogs. Zhongguo Yao Li Xue Bao. 1995 Sep;16(5):459-63. 20. Dai S, Chan MY, Lee SS, et al. The antiarrhythmic effects of Sophora flavescens Ait. in rats and mice. Am J Chin Med.1986;14(3-4):119-23. 21. Guo ZB, Fu JG, Zhao Y. Therapeutic efficacy of oxymatrine on arrhythmia and heart rate variability in patients with coronary heart disease. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006 Apr;26(4):311-5. 22. Dai S, Chan MY, Lee SS, et al. Effects of Sophora flavescens Ait. on haemodynamics and ventricular fibrillation threshold in anaesthetized dogs. Am J Chin Med.1987;15(1-2):53-7. 23. Wang J, Zongliang L, Chi J, et al. Multicenter clinical trial of the serum lipid-lowering effects of a Monascus Purpureus (Red Yeast) rice preparation from traditional Chinese medicine. Current Therapeutic Research. 1997; 58(12):964-78. 24. Wu J, Xia C, Meier J, et al. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol. 2002 Jul;16(7):1590-7. 25. Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther.1994;8:659–664. 26. Seetharamaiah GS, Chandrasekhara N. Effect of oryzanol on cholesterol absorption & biliary & fecal bile acids in rats. Indian J Med Res.1990 Dec;92:471-5. 27. Berger A, Rein D, Schäfer A, et al. Similar cholesterol-lowering properties of rice bran oil, with varied gamma-oryzanol, in mildly hypercholesterolemic men. Eur J Nutr. 2005 Mar;44(3):163-73. 28. Moghadasian MH, Frohlich JJ. Effects of dietary phytosterols on cholesterol metabolism and atherosclerosis: clinical and experimental evidence. Am J Med.1999 Dec;107(6):588-94. 29. Squires RW, Allison TG, Gau GT, et al. Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol. Mayo Clin Proc.1992 Sep;67(9):855-60.
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Pet Corner
Does Dementia Affect Dogs?
Gary L. Ailes, DVM
The simple answer to whether dogs can suffer from dementia is yes. However, sometimes there are different problems that look like dementia. An example of something that might mimic dementia could be a brain tumor or vestibular syndrome. Certainly those may not be the only conditions that could appear but may be some of the more common. Signs that your dog may have dementia can be changes in attitude, such as becoming more destructive, becoming more aggressive or more passive, atypical soiling inside the house, getting lost behind the couch or in corners and simply stopping and staring at nothing. These kinds of changes usually will not start until after the age of seven years and more commonly beyond ten years. If dementia is suspected, your pet should receive a full physical exam followed by full blood profile. X-rays are a good idea to evaluate for any possible masses in the chest or abdomen. MRI or CT scans can be used to rule out masses in the brain vault and some inflammatory lesions will show up. Dementia may be helped by treating with a product called Deprenyl, which is a MAO-B (monamine oxidase) inhibitor thereby sparing dopamine for use in the brain. Side effects that could occur include vomiting, diarrhea, restlessness, repetitive movements, lethargy, salivation and anorexia. Decreased hearing, pruritus (itching), licking and shivers or shakes have been reported less often. As with most medications, if we knew their side effects, we wouldn’t be likely to take them. There are several other agents that may be used, and they are like everything else used. That means they may help slow the progression or give some reversal of signs. In an interesting medical journal article, the authors addressed the subject of dementia in dogs and the nutritional supplements that can be used to support cognitive health in animals. (Araujo JA, Landsberg GM, Milgram NW, Miolo A. Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E and pyridoxine. Can Vet J. 2008 Apr;49(4):379-85.) The researchers gave nine aged beagles a supplement containing phosphatidylserine, ginkgo biloba, vitamin E, and pyridoxine to determine if it could improve cognitive function in the animals. The dogs were tested on performance on a neuropsychological test of short-term visuospatial memory. All subjects were tested on 5 baseline sessions; then, to assess the supplement, a crossover design was used in which 1 group received the supplement and the other a control substance in the 1st phase, with treatment conditions being reversed in the 2nd phase. In dogs given the nutritional supplement, performance accuracy was significantly improved compared with control dogs and the effect was long lasting. The researchers concluded, “Aged dogs demonstrate cognitive decline that is linked to brain aging. These findings suggest that the nutraceutical supplement can improve memory in aged dogs.” If my dog was to start to show signs of dementia, I would do a full work up as listed above then start on the supplements Phosphatidylserine 100 Plus and Neuron Growth Factors (NGF™) before I would consider using a prescription drug.
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Orthosiphon Stamineus
The Diverse Benefits of a Unique Natural Diuretic
VRP Staff
A diuretic is any substance that increases urination rate and therefore increases the excretion of water. Diuretics are often used clinically along with blood pressure medications in order to flush excess fluid and sodium from the body to decrease the amount of fluid pumped by the heart. Furthermore, diuretics are also used to reduce bloating and fluid retention. These effects make diuretics useful for individuals who are undergoing weight loss and for women who want to reduce the fluid build up that occurs during PMS. Diuretics also may be indicated in kidney stones and gout. Orthosiphon stamineus, otherwise known as java tea, has been used in traditional medicine for centuries to enhance the health of the urinary system. Orthosiphon stamineus is a popular traditional botanical extensively used in Southeast Asia for a wide range of conditions including rheumatism, diabetes, hypertension, tonsillitis, epilepsy, menstrual disorders, gonorrhea, syphilis, renal calculus (kidney stones), gallstones, edema, eruptive fever, hepatitis, and jaundice.1 In Japan, it is consumed as a healthy tea to facilitate body detoxification.1 Research confirms the traditional role of this botanical with studies showing it has diuretic properties. Rodent studies have indicated supplementation with Orthosiphon stamineus leads to an increase in urine flow and increased urinary sodium excretion.2 These properties indicate Orthosiphon stamineus can play a role in kidney health, but its effects appear to expand to other aspects as well. Kidney Stones and Gout Calcium oxalate stones are the most common type of kidney stones, which can be detected by routine x-ray studies. This type of stone is unlikely to be treated successfully with medical therapy but certain medications may help prevent calcium stones if they have a propensity to recur. Kidney stones can also be caused by disordered uric acid metabolism. Uric acid is a common constituent of urinary and renal calculi (kidney stones) and of gouty concretions. Diuretic action is an important factor in treatment of kidney stones of this type. An increase in the volume of fluid flowing through the kidney will help to dissolve the stones, assisting their passing to avoid further retention, and flushing out the deposits. Two recent studies provide a scientific foundation for the traditional use of Orthosiphon stamineus in kidney stones and gout. First, Orthosiphon stamineus appears to influence the activity of adenosine A (1) receptor antagonists, which can protect the kidney by increasing urine flow and sodium excretion.3 Additionally, an earlier study showed that Orthosiphon stamineus lowered levels of uric acid in rodents and acted as a diuretic.4 Fever Reduction A recent study indicates another interesting property of Orthosiphon stamineus. Researchers experimentally elevated body temperature in rodents then gave them Orthosiphon stamineus. The botanical significantly reduced the increased body temperature. The effect persisted up to four hours following the administration of the extract. Orthosiphon stamineus’ anti-pyretic (fever-reducing) effect was comparable with that of acetaminophen.5 Anti-inflammatory and Analgesic Effects Researchers also have studied Orthosiphon stamineus for its effects on inflammation and pain. Scientists induced edema in the hind paws of rodents. They then gave the animals Orthosiphon stamineus. The botanical significantly reduced the edema 3 and 5 hours after the swelling was induced. Furthermore, Orthosiphon stamineus also produced significant analgesic (pain-reducing) activity.6 According to the researchers, “The results of the present study support the proposal that O. stamineus has anti-inflammatory and non-narcotic analgesic activities. These findings justify the traditional use of the plant for treating pain and inflammation.” Liver Health A 2007 study suggests that Orthosiphon stamineus may be as protective to the liver as it is to the kidney. Researchers treated rats with Orthosiphon stamineus then induced liver toxicity in the rodents. The botanical dose-dependently reduced the necrotic changes in the liver and inhibited the increase of serum ALT and AST activities. Orthosiphon stamineus also acted as a powerful antioxidant and free radical scavenger.7 Maintaining Blood Sugar Unlike some pharmaceutical diuretics, which are thought to increase the risk of diabetes by promoting glucose intolerance, Orthosiphon stamineus can actually maintain blood sugar levels. When the extract was given to normal and diabetic rats, it significantly decreased plasma glucose concentration in a dose-dependent manner. After repeated daily oral administrations of the extract for 14 days, the extract significantly reduced plasma glucose concentration in diabetic rats at days 7 and 14. By the end of the study, plasma triglyceride concentration was lower in the extract-treated diabetic rats than untreated ones. Furthermore, plasma HDL-cholesterol concentration was significantly increased in diabetic rats treated with the extract.8 “Our findings suggested that Orthosiphon stamineus aqueous extract is effective for alleviating hyperglycemia and improving lipid profile in diabetic rats,” the researchers wrote. Balancing Nitric Oxide Levels Nitric oxide (NO) is an important molecule that signals the blood vessels to relax and acts in many tissues to regulate a diverse range of physiological processes. When certain cells are activated by specific proinflammatory agents such as endotoxins, tumor necrosis factor (TNF), interferon-gamma (IFN-g), and interleukin-1 (IL-1), NO is produced and protects the host by damaging pathogenic DNA. Balanced amounts of nitric oxide are essential to optimal health because just as normal amounts of NO promote health, the excessive production of NO that can occur during the inflammatory process can have detrimental effects on many organ systems of the body, which can lead to tissue damage. Therefore, inhibiting NO accumulation by inflammatory stimuli can result in overall benefits. Orthosiphon stamineus has been shown to inhibit levels of nitric oxide in macrophages that were stimulated with inflammatory endotoxins, indicating that the botanical can help support healthy levels of nitric oxide and reduce one of the harmful effects of inflammation.1 Safety of Orthosiphon stamineus The diuretic botanical Orthosiphon stamineus has been extensively studied in rodents with no signs of toxicity. In a 2008 study, researchers administered the botanical orally to rats for 14 days and compared it to a control group receiving distilled water. The four test groups were treated with 0.5 g/kg, 1 g/kg, 3 g/kg and 5 g/kg body weight of O. stamineus respectively. No lethality or adverse toxic signs were seen during the experimental period.9 According to the researchers, “In conclusion, methanol extract of O. stamineus within these range and treatment duration would not cause any severe toxic effects and organ damage in rats.” Individuals in Malaysia, Vietnam and Japan have consumed Orthosiphon stamineus for centuries, further supporting its safety. Conclusion Orthosiphon stamineus, which is found in the new product Herbal Diuretic along with 99 mg of potassium, is a natural diuretic supplement that can support kidney and liver health, reduce the excessive fluid retention that occurs during PMS, alleviate bloating, promote sodium excretion and act as an anti-inflammatory and analgesic agent. For individuals seeking diuretic support, it is an excellent choice that can also maintain liver health and blood sugar. References 1. Awale S, Tezuka Y, Banskota AH, Siphonols KS. Novel Nitric Oxide Inhibitors from Orthosiphon stamineus of Indonesia. Bioorganic & Medicinal Chemistry Letters. 2003;13:31–35. 2. Beaux D, Fleurentin J, Mortier F. Effect of extracts of Orthosiphon stamineus Benth, Hieracium pilosella L., Sambucus nigra L. and Arctostaphylos uva-ursi (L.) Spreng. in rats. Phytother Res. 1999 May;13(3):222-5. 3. .Yuliana ND, Khatib A, Link-Struensee AM, Ijzerman AP, Rungkat-Zakaria F, Choi YH, Verpoorte R. Adenosine A1 receptor binding activity of methoxy flavonoids from Orthosiphon stamineus. Planta Med. 2009 Feb;75(2):132-6. 4. Arafat OM, Tham SY, Sadikun A, Zhari I, Haughton PJ, Asmawi MZ. Studies on diuretic and hypouricemic effects of Orthosiphon stamineus methanol extracts in rats. J Ethnopharmacol. 2008 Aug 13;118(3):354-60. 5. Yam MF, Ang LF, Basir R, Salman IM, Ameer OZ, Asmawi MZ. Evaluation of the anti-pyretic potential of Orthosiphon stamineus Benth standardized extract. Inflammopharmacology. 2009 Feb;17(1):50-4. 6. Yam MF, Asmawi MZ, Basir R. An investigation of the anti-inflammatory and analgesic effects of Orthosiphon stamineus leaf extract. J Med Food. 2008. Jun;11(2):362-8. 7. Yam MF, Basir R, Asmawi MZ, Ismail Z. Antioxidant and hepatoprotective effects of Orthosiphon stamineus Benth. standardized extract. Am J Chin Med. 2007;35(1):115-26. 8. Sriplang K, Adisakwattana S, Rungsipipat A, Yibchok-Anun S. Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats. J Ethnopharmacol. 2007 Feb 12;109(3):510-4. 9. Chin JH, Abas HH, Sabariah I. Toxicity study of Orthosiphon stamineus Benth (Misai Kucing) on Sprague Dawley rats. Trop Biomed. 2008 Apr;25(1):9-16.
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Ribonucleic Acid Part One
A Highly Effective Anti-Aging Supplement
Ward Dean, MD
Durk Pearson and Sandy Shaw’s 1982 bestselling book, Life Extension— A Practical, Scientific Approach (more than 2.5 million copies sold), is generally recognized as the spark that ignited the currently popular field of anti-aging/life extension medicine. Pearson and Shaw’s blockbuster extolled the free radical theory of aging and introduced the terms free radicals and antioxidants to millions of non-scientist health enthusiasts. However, Pearson and Shaw’s success was partially due to another popular book that helped to pave the way, which preceded their publication by six years.  In 1976, a pioneering New York medical doctor named Benjamin Frank created a minor sensation with his book—Dr. Frank’s No-Aging Diet. Dr. Frank was unique. He was not only an MD, but also had a PhD in biochemistry. He was simultaneously a practicing physician and researcher, performing anti-aging experiments with mice and rats in addition to taking care of his patients. Dr. Frank was ahead of his time. He was an early advocate of high-dose vitamin therapy (especially Bs, C, & E), plus other nutrients not well known or available in the early ’60s through the mid-’70s when he did most of his research. For example, he recommended the use of carnosine, CoQ10, lipoic acid, DMG (then known as “Vitamin B15”), glycerol phosphate (magnesium glycerophosphate — he believed several grams per day promoted cell membrane integrity, and also restored receptors), vanadium, orotic acid, lecithin, choline, and inositol. A further indication of his foresight was his recommendation of the use of biguanide drugs like metformin, which is now becoming recognized as one of the most effective anti-aging drugs currently available (see my article, Metformin—An Effective and Underappreciated Life Extension Drug, in the November 1998 issue of Vitamin Research News). Dr. Frank’s Theory of Aging Dr. Frank theorized that aging and degenerative diseases are caused by the loss of cellular energy production (ATP) due to membrane damage and decreased efficiency of the Kreb’s cycle and the associated electron transport chain. He also believed that damage to cellular DNA from free radicals and crosslinkages could not be repaired due to inadequate cellular energy and availability of “raw materials” (i.e., nucleotides and nucleic acids [Fig.1.]) to repair the DNA. He believed that this decay of DNA further led to improper formation of messenger RNA and ribosomal RNA, which in turn led to abnormalities and structural defects in the cell. Frank’s theory is clearly related to the mitochondrial, free radical, crosslinkage, and membrane theories of aging, all previously discussed in Vitamin Research News. The key difference between Dr. Frank’s theory and the approach used by advocates of the other related theories is the specific anti-aging therapy that he recommended—high-dose nucleic acids, combined with high potency multivitamins. Dr. Frank did not discount the approaches recommended by other researchers—he believed, however, that their methods (i.e., antioxidants, cross-linkage inhibitors) would not be effective unless combined with adequate amounts of RNA. Dr. Frank believed that one cause of inadequate concentrations of RNA and nucleotides for repair and production of energy is an age-related increase in enzymes that destroy nucleic acids (i.e., nucleases—specifically, ribonuclease, which breaks down RNA). As people grow older, ribonuclease enzyme activity has been reported to increase. Consequently, just as the requirement to repair damaged cells increases, the substances required for this repair (nucleic acids) are being degraded by higher concentrations of destructive enzymes. Consequently, Dr. Frank believed older people have an even higher requirement for nucleic acids than younger people. Thus, the older we get, the greater our need for nucleic acids, both for replacement and for repair.  Nucleic Acids as Potential Life Extending, Disease-Preventing Nutrients Dr. Frank believed that exogenous RNA, especially when combined with associated B vitamins, minerals, amino acids, and sugars (like D-ribose) would enter the cell and aid in normal regeneration of the damaged cellular elements. This would, in turn, bring about normal enzyme synthesis and activation, and most importantly would increase cellular energy production. For this reason, Frank believed that providing RNA and associated compounds would aid in the repair of damaged DNA. He knew that ribonucleic acid is important in the initiation of DNA synthesis, acting in a coenzyme-like fashion. Dr. Frank stated, “The importance of nucleic acids in protein synthesis and in enzyme synthesis, as well as the importance of RNA in bringing about DNA synthesis, and the actually observed anti-aging effects of nucleic acids on whole man, support the claims regarding the value of increased intake of nucleic acids in the prevention and treatment of cellular degeneration.” Dr. Frank claimed that not only do nucleic acids (1) decrease overall oxygen utilization, but also (2) increase its inherent effectiveness, lessening potential oxidative damage to the cell. He believed that the “anti-anoxia effect” of nucleic acids (ability to do better work on less oxygen) was due to the increased synthesis of CoQ10 and enhancement of the efficiency of Kreb’s cycle and respiratory chain. He believed nucleic acids might even lead to increased synthesis of mitochondria. | Effects of Nucleic Acids | | Marked increase in “energy” or activity Anti-anoxia action (i.e., reduced shortness of breath) Increased ability to tolerate low temperatures Decreased skin wrinkling and increased skin elasticity Improved cognitive performance Immune enhancement | Dr. Frank described the dramatic results of his use of oral and injectable ribonucleic acid in the prevention and treatment of a wide variety of age-related illnesses. He used a nucleic acid-rich diet and nucleic acid extracts for a variety of ills including emphysema, heart disease, diabetic complications, arthritis, fading eyesight, memory loss, and other diseases of aging. He believed that nucleic acids should be considered as essential nutrients, along with fats, carbohydrates, proteins, vitamins and minerals. Dr. Frank reported that a common finding of those on a high nucleic acid diet was a normalization of blood lipid levels. This was reflected by a drop in total cholesterol and triglycerides, and an elevation of HDL. He believed that the cholesterol-lowering effect of nucleic acid-rich diets was due to increased ATP formation, enhanced electron transport chain activity, improved CoQ10 and cytochrome oxidase synthesis, and increased NADH oxidation. He also reported that some of the earliest noticeable effects of RNA therapy were increased energy, followed by improved skin tone, with increased elasticity and reduction in fine wrinkles. He frequently referred to the skin-tightening effect, causing folds to diminish and the skin to acquire a tighter and more youthful appearance. | Clinical Uses | | Arthritis Atherosclerosis Hyperlipidemia Cancer Diabetes and complications Emphysema Colds Glaucoma Poor vision Retinitis pigmentosa | Reduced skin wrinkles Acne Hair growth Psoriasis Diverticulitis Memory loss Parkinson’s Disease ALS Bell’s Palsy Lupus erythematosus | Frank’s dietary recommendations included: - Four days per week—eat one can of small sardines.
- Eat fish on the other three days.
- Calve’s liver once/week
- Lentils, peas, lima beans, or soybeans.
- Asparagus, radishes, onions, scallions, mushrooms, spinach, cauliflower, or celery.
- Seven glasses of fluid per day—4 of water, 2 milk, and 1 vegetable.
While most modern nutritionists attribute the benefits of a high fish diet to the concentration of omega 3 fatty acids, Dr. Frank was of the opinion that it was primarily due to the high content of nucleic acids in most fish, and especially in sardines. (He did not discount the possible benefit of the omega 3 fatty acids, but believed that they were merely a synergistic adjunct to the nucleic acids.) He reported that sardines contain 1.5 percent nucleic acid, liver approximately 0.5 percent, and muscle meat 0.05 percent. Consequently, Dr. Frank had many anti-aging activists in the mid-’70s eating sardines like crazy. (Frankly, I got sick of eating sardine sandwiches!) Dr. Frank recommended consuming a minimum of 1.5 gm daily of nucleic acid for general health and well being. However, he recommended much higher doses for those with specific health concerns. He cautioned, however, that when taking higher therapeutic doses of RNA, that urine pH be only slightly in the acid range. He found that highly acidic urine with a high RNA diet (more than 2 gm daily) may result in elevated levels of uric acid in the blood, which can cause kidney stones. This can be easily prevented by drinking plenty of water. Urine acid-base balance (pH) can be easily tested by using urine pH test strips. Clinically, Dr. Frank used dosages of RNA between 500 mg-20 gm. He usually recommended the higher doses (over 5 grams) be used several times per week. If dosages higher than 2 gm daily were taken, Dr. Frank recommended doing so under the care of a physician, where BUN, creatinine and uric acid levels could be monitored, and recommended that the urine pH be maintained near 6 (i.e., between 5.0-7.0). Dr. Frank stated that those with uric acid of 2-3 mg can take considerably larger amounts of nucleic acid than those with levels closer to 5, 6, or 7 mg. Higher amounts of uric acid can be better tolerated in near alkaline urine than in very acid urine. It should be noted that he never observed any problems in people with normal kidney function, who drank adequate fluids and maintained urine pH in the desired range. He recommended that additional protection could be gained by consuming adequate amounts (500-1,000 mg) of magnesium each day. Historical Basis of RNA as an Anti-Aging Supplement Dr. Frank was not the first to experiment with nucleic acids. In 1908, Dr. C.S. Minot first proposed that nucleic acids were vital for the health of cells and were essential for the longevity of the organism. However, the first evidence that nucleic acids might actually promote longevity was demonstrated by a series of experiments conducted by Dr. T. Brailsford Robertson in Australia in 1928. Dr. Robertson believed that the lifespan of organisms was determined by the ratio of nuclear (chromosomal) materials to the cytoplasm (protein) of the cells. He referred to this ratio as the “nucleocytoplasmic ratio”—and proposed that the way to optimize this ratio was to supply the nuclei of the organism with nutrients in “excessive abundance.” He tested his hypothesis in a series of experiments. He used 30-40 male and 30-40 female mice in each test group, with a similar group of controls in each experiment. The test groups received 25 mg of yeast nucleic acid each day throughout their lives. Robertson’s hypothesis was apparently confirmed, as the results were strikingly and uniformly positive. He reported an average lifespan extension of 12.5 percent for males, and 17 percent for females (Fig. 3).  Despite these positive, provocative results, almost twenty years elapsed before any further research was done in this area. In the mid-1940s, Dr. Thomas Gardner, an organic chemist in the scientific department of Hoffman-La Roche, picked up where Robertson had left off. Gardner agreed with Robertson’s hypothesis that the nucleocytoplasmic ratio decreased with aging, but was not convinced that correcting this ratio was the mechanism of RNA’s life-prolonging effects. He proposed several other possible mechanisms for these benefits. He suggested that nucleic acids might slow down the metabolism of the nucleus of the cell. He reasoned that if nucleic acids were provided to the cell in high amounts, they could be utilized in metabolism without destroying the nucleus or cytoplasm, and thereby enable the cells to live longer at a higher energy level. Alternatively, he theorized that the life-prolonging effect of yeast nucleic acid might be due to its ability to stimulate the immune system, since sodium yeast nucleinate was known to stimulate the growth and proliferation of white blood cells (leukocytes). He equated this to the proposed anti-aging effects of Anti-Reticulo Cytotoxic Serum (ARCS) then being used in Russia (Bogomolets). ARCS was briefly reviewed in the August, 2003 issue of Vitamin Research News. Whatever the mechanism, Gardner attempted to replicate Robertson’s work, with several modifications. First, he began his studies with mice that were 600 days old (instead of beginning treatment after weaning, as Robertson had done), because “mice are beginning to get old at that age.” Also, he believed that Robertson’s dosages were unrealistically high. He calculated that 25 mg per mouse per day would translate into a human dose of 55 gm per day. Gardner was apparently considering human use of RNA, and realized that few humans could consume such high doses. Consequently, Gardner administered 1/10th of the dosage used by Robertson, resulting in a daily RNA dosage of 2.5 mg per mouse per day. This corresponded to an equivalent human dosage of 5.5 grams per day, which Gardner believed could be practically consumed. Gardner used 72 female and 31 male albino mice, divided into test and control groups. Gardner reported that the treated mice retained vitality and vigor longer than the controls, fewer went blind, and the treated mice appeared healthier and exhibited greater activity than the controls. Although the lifespan extension of the mice receiving nucleic acids was not as great as reported by Robertson, there was an overall trend toward increased longevity in the nucleic acid-treated mice. Gardner attributed his less spectacular results to the fact that he started the experiment when the mice were already advanced in age, and that the dosage was so much less than that administered by Robertson. Interestingly, Gardner reported that Robertson and his staff had taken 15 gm yeast nucleic acid per day, and that Gardner himself (perhaps as a result of observing his healthy mice) had been taking 5 gm of yeast nucleic acid for weeks “without any ill effects.” He concluded that “As Robertson tested with three times the amounts I have suggested for [human] use, there is no reason known at the present time for fearing to use yeast nucleic acid freely for veterinary experimental purposes…and…for extending their life spans as well as for experimental therapy on aging men and women for the same purpose.” Nearly another twenty years were to elapse before further experiments with RNA were conducted—this time with even more spectacular results. Dr. Max Odens conducted a study with ten 750-day-old rats, of a species that had a normal lifespan of 800-900 days. Five rats were untreated controls. The other five received weekly injections of “DNA solution in water…plus ordinary RNA.” Unfortunately, details of the exact composition and dosage that was administered were not given. After twelve weeks of injections, Odens reported that the treated rats looked younger, were very lively, and had gained weight, in contrast to the untreated rats which “looked old, moved slowly, did not eat much, and had lost weight. The difference was remarkable.” Odens further reported that all of the untreated rats died before 900 days, while 4 of the treated rats survived between 1600 and 1900 days, and one rat lived 2250 days! Odens concluded that “with weekly injections of DNA and RNA, the life span of 4 rats was doubled on the average, and the life span of the fifth rat was more than trebled.” These results are frankly, hard to believe. But some credence must be given this report, considering the journal in which it was published—the prestigious Journal of the American Geriatrics Society. Conclusion The claims for the life-extending benefit of nucleic acid administration are supported by a diverse series of experiments that span nearly 50 years. Based on these findings and the reports by Dr. Frank of its widespread clinical benefits with human use, I consequently agree with Dr. Frank’s recommendation to add at least 1.5 grams per day of nucleic acids to an anti-aging nutritional supplement regimen. This recommendation is buttressed by the facts that two of the research teams admitted taking high dose nucleic acids themselves, after seeing the effects they had on their experimental animals, and that the third researcher also recommended consideration of nucleic acid supplementation for human and veterinary use. It is surprising that more researchers have not attempted to replicate these studies—especially when considering the high degree of safety and minimal cost of high quality yeast-derived nucleic acids that are available today. : References: 1. Minot, C.S., The Problem of Age, Growth and Death, G.P. Putnam’s Sons, 1908, New York.
2. Frank, G. Nucleic Acid Therapy in Aging and Degenerative Disease—A Metabolic Approach with DNA, RNA and Related Metabolites, Psychological Library, New York, 1968.
3. Frank, B. Dr. Frank’s No-Aging Diet. The Dial Press, New York, 1976.
4. Frank, B. Nucleic Acid & Antioxidant Therapy of Aging & Degeneration. Royal Health Books, Ltd, Long Island, NY 1977.
5. Robertson, T. Brailsford. On the influence of nucleic acids of various origin upon the growth and longevity of the white mouse. Australian J Exp Biol Med Sci, 1928, 5: 47-67.
6. Gardner, T. The effect of yeast nucleic acid on the survival time of 600 day old albino mice. J Gerontol, 1946, 1: 445-456.
7. Odens, M. Prolongation of the life span in rats. J American Geriatrics Soc, 1973, XXI: 450-451.
8. Bogomolets, A.A. Anti-reticular cytotoxic serum as a means of pathogenic therapy, Am Rev Soviet Med, 1943, 1: 101-112.
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Nutrition Review
Latest Research on Heart Health, Colon Health, Weight Loss and More
VRP Staff
Carotenoids Improve Measures of Physical Performance A recent study investigated the correlation between dietary factors and physical performance in older adults. In this study, 687 moderately to severely disabled women age 65 years or older were followed for 3 years. The researchers evaluated walking speed as a measure of physical performance, as it predicts both disability and mortality, and measured serum levels of carotenoids and selenium as indicators of fruit and vegetable intake. Serum carotenoids are considered the most valid indicators of fruit and vegetable intake. Serum carotenoid and selenium levels were measured at the beginning of the study and after 12 and 24 months. Walking speed was also evaluated at the beginning of the study and then every 6 months for a total of 36 months. The results showed that after adjusting for age, body mass index, and chronic diseases, both mean serum total carotenoids and mean serum selenium was associated with mean walking speed over the 3-year follow-up. Additionally, mean total serum carotenoids were associated with the rate of change of walking speed. The study authors concluded “a higher fruit and vegetable intake, as indicated by higher total serum carotenoid concentrations, may be protective against a decline in walking speed in older women.” These results confirmed a previous study performed by the same group of researchers. In this study, 554 women without severe walking disability at the beginning of the study were followed for 3 years. Total serum carotenoids were measured using the sum of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene. The results showed that 27.9 percent of the subjects developed severe walking disability during follow-up. The women with the lowest serum carotenoid levels had an increased risk of developing severe walking disability compared to the women with the highest levels. This study demonstrated that older women with low serum carotenoid concentrations are at a higher risk of developing severe walking disability. (Age and Ageing. 2007; 36(1):62-67.) Reference: Alipanah N, Varadhan R, Sun K, Ferrucci L, Fried LP, Semba RD. Low serum carotenoids are associated with a decline in walking speed in older women. J Nutr Health Aging. 2009 Mar;13(3):170-5. Individuals who want to increase their carotenoid intake can take CAROTeam™ and/or consume Primary Greens™ drink mix. Nattokinase Supports Cardiovascular Health Nattokinase is an enzyme derived from natto, a fermented soybean product that is popular in Japan. Nattokinase supports circulatory health by breaking down fibrin clots (fibrinolysis) formed during the process of coagulation and reduced or restricted blood flow that may also contribute to deep vein thrombosis and ischemia. In a recently published clinical trial, researchers evaluated the effects of nattokinase on several blood-clotting factors including fibrinogen, factor VII, and factor VIII. Elevated levels of these clotting factors have been associated with an increased risk of heart disease and atherosclerosis. Study subjects were categorized as healthy patients, patients with cardiovascular disease risk and patients undergoing dialysis. Subjects were supplemented with two capsules of nattokinase daily, totaling 4,000 fibrinolytic units (FU) per day, for 2 months. Fibrinogen, factor VII, and factor VIII were measured at the beginning of the study and periodically throughout the duration of this trial. The results showed that the levels of fibrinogen, factor VII, and factor VIII continuously decreased during the study for all 3 groups of subjects. In the healthy group, fibrinogen decreased by 9 percent, factor VII decreased by 14 percent, and factor VIII decreased by 17 percent after 2 months of supplementation. In the group with cardiovascular disease risk, fibrinogen decreased by 7 percent, factor VII decreased by 13 percent, and factor VIII decreased by 19 percent after 2 months of supplementation. In the dialysis group, fibrinogen decreased by 10 percent, factor VII by 7 percent, and factor VIII by 19 percent. Blood lipids did not change with nattokinase supplementation and no adverse events were reported. The study authors stated, “This study showed that oral administration of nattokinase could be considered as a cardiovascular disease nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.” Reference: Hsia CH, Shen MC, Lin JS, Wen YK, Hwang KL, Cham TM, Yang NC. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009 Mar;29(3):190-6. Select Antioxidants May Decrease the Risk of Metabolic Syndrome According to a recent study, certain antioxidants decrease the risk of developing metabolic syndrome. Metabolic syndrome is a condition presenting with central obesity, elevated cholesterol and blood pressure, and insulin resistance or glucose intolerance. In the United States, metabolic syndrome affects an astounding 34 percent of adults. In a new study, researchers investigated the relationship between dietary carotenoid intake and metabolic syndrome risk. Carotenoids are the brightly colored pigments found in plants and have significant antioxidant activity. In this study, 374 men between the ages of 40 and 80 were evaluated for intake of the carotenoids beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin by filling out a food frequency questionnaire. Next, the study subjects were evaluated for metabolic syndrome by measuring fasting serum glucose, blood pressure, triglyceride and high-density lipoprotein (HDL)-cholesterol concentrations, and waist circumference. Metabolic syndrome was present in 22 percent of the subjects. The results showed that increased total carotenoid and lycopene intake is associated with a decreased risk of metabolic syndrome, and conversely, decreased intake of carotenoids and lycopene increased the risk of metabolic syndrome. In fact, the men with highest intake of total carotenoids had a 58 percent lower risk of metabolic syndrome compared to the men with the lowest intake. In addition, the men with the highest intake of lycopene showed a 45 percent lower incidence of the syndrome, compared to men with the lowest average intakes. In addition, the researchers showed that higher total carotenoid, beta-carotene, alpha-carotene, and lycopene intakes are associated with lower waist circumference, as well as decreased fat deposition around the organs (visceral fat) and under the skin (subcutaneous fat). Also, the study found that higher lycopene intake is associated with lower serum triglyceride levels. The study authors concluded, “Higher total carotenoid intakes, mainly those of beta-carotene and lycopene, were associated with a lower prevalence of metabolic syndrome and with lower measures of adiposity and serum triglyceride concentrations in middle-aged and elderly men.” Reference: Sluijs I, Beulens JW, Grobbee DE, van der Schouw YT. Dietary carotenoid intake is associated with lower prevalence of metabolic syndrome in middle-aged and elderly men. J Nutr. 2009 May;139(5):987-92. Individuals wishing to increase their carotenoid intake can take CAROTeam™, which contains mixed carotenoids, beta carotene, lycopene and lutein. Vitamin B6 Supports Colon Health A new study investigated the relationship between vitamin B6 levels and the risk of developing colorectal cancer. Colorectal cancer, one of the most commonly diagnosed cancers, is the second leading cause of cancer-related deaths in the United States. In this large prospective study, 14,916 men were evaluated for plasma levels of pyridoxal 5’-phosphate, the active form of vitamin B6. Of the subjects, 197 men developed colorectal cancer. The study showed that plasma levels of pyridoxal 5’-phosphate also correlated with plasma levels of folate and vitamin B12. In addition, higher levels of pyridoxal 5’-phosphate was associated with lower levels of homocysteine, an amino acid associated with inflammation and cardiovascular disease, as well as decreased levels of the pro-inflammatory mediators C-reactive protein (CRP), tumor necrosis factor-alpha receptor 2, and interleukin-6. Most importantly, the study showed that higher levels of plasma pyridoxal 5’-phosphate were associated with lower risk of developing colorectal cancer. The men with the highest levels of pyridoxal 5’-phosphate showed a decreased risk ranging from 8-58 percent compared to men with the lowest pyridoxal 5’-phosphate levels. The study authors concluded, “Vitamin B6 may protect against colorectal cancer independent of other one-carbon metabolites and inflammatory biomarkers.” Reference: Lee JE, Li H, Giovannucci E, Lee IM, Selhub J, Stampfer M, Ma J. Prospective study of plasma vitamin B6 and risk of colorectal cancer in men. Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1197-202. Vitamin D Levels Important for Immune Function Numerous studies indicate that vitamin D plays a significant role in normal immune function. Bacterial vaginosis is the most common vaginal infection and is caused by an imbalance in the normal vaginal flora. Developing bacterial vaginosis during pregnancy increases the risk of pregnancy complications including pre-term delivery, delivering low birth-weight babies, and the development of pelvic inflammatory disease. In a recently published study, 469 pregnant women were evaluated for serum 25-hydroxyvitamin D levels. Measuring 25-hydroxyvitamin D is the most accurate way to measure vitamin D status in the body. The subjects also underwent pelvic examinations to determine the presence of bacterial vaginosis. The study found that 41 percent of the women had bacterial vaginosis. Additionally, 52 percent of the women had serum 25-hydroxyvitamin D levels less than 37.5 nmol/L. Also, the study showed that the women with bacterial vaginosis had lower mean serum 25-hydroxyvitamin D levels compared with women without bacterial vaginosis, and the prevalence of bacterial vaginosis decreased as vitamin D status increased. Furthermore, the study results revealed that of the women with serum 25-hydroxyvitamin D concentration of less than 20 nmol/L had approximately 57 percent more bacterial vaginosis, while only 23 percent of the women with serum 25-hydroxyvitamin D concentration greater than 80 nmol/L had the infection. In fact, women with serum 25-hydroxyvitamin D levels of 20 nmol/L had an increased risk of bacterial vaginosis by 1.65-fold, and women with serum 25-hydroxyvitamin D of 50 nmol/L had an increased risk of the infection of 1.26-fold, compared to the women with levels of serum 25-hydroxyvitamin D of 75 nmol/L. Thus, the authors concluded, “There was a dose-response association between 25(OH)D and the prevalence of BV. Vitamin D deficiency is associated with bacterial vaginosis and may contribute to the strong racial disparity in the prevalence of bacterial vaginosis.” Reference: Bodnar LM, Krohn MA, Simhan HN. Maternal Vitamin D Deficiency Is Associated with Bacterial Vaginosis in the First Trimester of Pregnancy. J Nutr. 2009 Apr 8. Published Online Ahead of Print. Popular Botanical Supports Brain Health A recent study investigated the effects of a popular herb in regards to cognitive deficits and oxidative damage in the brain. Curcumin is a potent antioxidant and the principle active constituent in turmeric (Curcuma longa). In a new study, rats were treated with a chemical called streptozotocin to induce oxidative damage within the brain, which is used as an experimental model for dementia. The rats then received either 80 mg per kg of curcumin or placebo for 3 weeks. After 2 weeks of streptozotocin treatment, the rats showed significant cognitive deficits as measured by passive avoidance and water maze tasks. The rats that received curcumin demonstrated significantly improved cognitive performance compared to the rats that did not. In addition, the group supplemented with curcumin also showed a significant decrease in markers for oxidative stress such as 4-hydroxynonenal, malonaldehyde, thiobarbituric reactive substances, hydrogen peroxide, protein carbonyl, and oxidized glutathione. Curcumin also augmented levels of the potent antioxidant glutathione and the enzymes responsible for the regeneration of glutathione in specific areas in the brain, including the hippocampus and cerebral cortex. Furthermore, curcumin increased the activity of the enzyme called choline acetyltransferase in the hippocampus, which is important in the synthesis of the neurotransmitter acetylcholine. Reduced levels of acetylcholine are believed to play a role in Alzheimer’s disease. The researchers concluded, “The study suggests that curcumin is effective in preventing cognitive deficits, and might be beneficial for the treatment of sporadic dementia of Alzheimer’s type.” Reference: Ishrat T, Hoda MN, Khan MB, Yousuf S, Ahmad M, Khan MM, Ahmad A, Islam F. Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer’s type (SDAT). Eur Neuropsychopharmacol. 2009 Mar 27. Published Online Ahead of Print. Nutrient May Improve Inflammation and Cardiovascular Health A new study suggests that an important nutrient may reduce an inflammatory marker associated with increased risk of cardiovascular disease. C-reactive protein (CRP) is an inflammatory marker and is used to evaluate and predict cardiovascular disease risk. Measuring high-sensitivity C-reactive protein (hsCRP) is useful as a potential warning sign for future disease, as elevated levels are associated with myocardial infarction (heart attack), thrombotic stroke, atherosclerosis, diabetes, and cardiovascular death. In the United States it is estimated that cardiovascular disease (CVD) affects one in three Americans. A recently published study examined the potential association between omega-3 fatty acids and CRP, as previous research indicates that omega-3 fatty acids exhibit anti-inflammatory activity and are associated with decreased cardiovascular disease risk. In this study, 124 subjects were evaluated for plasma levels of hsCRP and fatty acids including levels of eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA). The researchers found that high levels of hsCRP were correlated to low levels of total omega-3 fatty acids, EPA, and DPA. Furthermore, the group of subjects with the highest levels of hsCRP had significantly lower concentrations of total omega-3 fatty acids, EPA and DPA, when compared to the subjects with lower hsCRP. Thus, the researchers stated, “This study provides evidence that in healthy individuals, plasma n-3 fatty acid concentration is inversely related to hsCRP concentration, a surrogate marker of cardiovascular disease risk.” Reference: Micallef MA, Munro IA, Garg ML. An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur J Clin Nutr. 2009 Apr 8. Published Online Ahead of Print. Fish oil supplements and a test kit to measure levels of high sensitivity C-reactive protein are available here. Herb Studied for Potential to Lower Body Fat and Weight Gain A recently published study found that an herb well-known for antioxidant properties also modulated the metabolism of fat (adipose) cells. The Centers for Disease Control and Prevention report that 66 percent of adults in the United States are overweight or obese. A new study revealed that curcumin, the main constituent from turmeric (Curcuma longa), may be beneficial for decreasing body fat and weight gain. In this study, mice were fed a high-fat diet supplemented with curcumin 500 mg per kg for 12 weeks. The results indicated that curcumin supplementation affected adipose cell (adipocyte) metabolism by suppressing differentiation of the tissue, and inducing apoptosis (programmed cell death). Curcumin also decreased the growth of new blood vessels (angiogenesis), and suppressed vascular endothelial growth factor (VEGF) and its receptor VEGFR-2, which are important for blood vessel formation necessary for the growth of fat tissue. Furthermore, curcumin supplementation did not affect food intake, yet reduced body weight gain, adiposity, and blood vessel density in adipose tissue. In addition, curcumin supplementation modulated several enzymes involved in lipid and fat metabolism including 5’AMP-activated protein kinase phosphorylation, glycerol-3-phosphate acyl transferase-1, and carnitine palmitoyltransferase-1. The study also found that curcumin supplementation significantly lowered serum cholesterol levels, as well as decreased important transcription factors involved in fat and lipid metabolism. The researchers stated, “The curcumin suppression of angiogenesis in adipose tissue together with its effect on lipid metabolism in adipocytes may contribute to lower body fat and body weight gain. Our findings suggest that dietary curcumin may have a potential benefit in preventing obesity.” Reference: Ejaz A, Wu D, Kwan P, Meydani M. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr. 2009 May;139(5):919-25.
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Customers Corner |
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Polycystic Liver Disease
Question:
Dear Dr. Dean,
I have polycystic liver disease. Are there any specific vitamins etc. out there to help keep these cysts in check as they continue to grow and may require surgery in the future? Thank you.
Ms. K.
Response:
Dear Ms. K.,
Polycystic liver disease is a congenital condition that may or may not require any treatment. One potential complication that must be considered is the possible coexistence of polycystic kidney disease. I’d suggest HepatoGen™ to help maintain optimum liver function as well as N-Acetyl Cysteine (NAC) or Glutathione Plus to help protect both the liver and kidneys. NAC is a nutritional precursor of glutathione and glutathione is the principle antioxidant involved in the detoxification role of the liver and kidneys.
You may also wish to get your iodine levels measured, as iodine insufficiency can contribute to some cystic conditions. An Iodine Sufficiency Test is available here directly to consumers.
Sincerely,
Ward Dean, MD
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High Triglycerides
Question:
Dear Dr. Dean,
I have high triglycerides (721) and cholesterol (332). My doctor prescribed Gemfibrozil® (600 mg). I took it for two days and stopped as I felt terrible. I have taken Lipitor® in the past with no success. My doctor then suggested that I take LipiControl®, Policosanol, plus high-dose Niacin and Ethyl EPA™ fish oil. Do you have any ideas? I do not want to take any drugs. I do exercise with light weights and use a treadmill three times per week for 30 minutes per session. Please let me know if there is anything I can take to naturally reduce my triglycerides and cholesterol.
Thanks,
Mr. B.
Response:
Dear Mr. B.,
In my experience, such high triglycerides are usually diabetes (or pre-diabetes) related. Your doctor’s recommendations are sound and from experience work very well. I would recommend you take Coenzyme Q10 (CoQ10) or CoQ10-H2™ 100 mg/day with LipiControl. Also, Niacin, which is usually my first choice of lipid-lowering agents, may not work in your case since Niacin is sometimes contraindicated in diabetics due to its effects on glucose tolerance. Consequently, I suggest a low-carbohydrate diet (very important—don’t worry about fat in the diet), along with GluControl™, Optimum D, 500-1,000 mg of Alpha Lipoic Acid twice per day and Ethyl EPA™. As an alternative to Optimum D you could take a higher potency multi-nutrient formula like Optimum 6 plus three grams of Niacinamide (not Niacin), 150 mg. Vanadyl Sulfate and 1,000 mg Taurine. Keep up your current exercise routine.
Sincerely,
Ward Dean, MD
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Menopausal Symptoms and Anxiety
Question:
Dear Dr. Dean,
I am 55 years old and post-menopausal. I would like to know what vitamin I can take for anxiety, fear, occasional sleeplessness and a racing heart.
Ms. B.
Response:
Dear Ms. B.,
For post-menopausal women, I first suggest HerBalance II™ and HerBalance™ Cream with Pregnenolone. Melatonin, about an hour before bedtime, may help with the sleep. L-Theanine or Allay™ may help with the anxiety. Furthermore, the amino acid GABA is another important addition in regards to helping with anxiety.
Sincerely,
Ward Dean, MD
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Thyroid Health
Question:
Dear Dr. Meletis,
I’m 58, my TSH is 10.65 {(T3,T4)-in normal range}; A nurse practitioner suggests putting me on Synthroid®, but since I read Dr. Brownstein’s book, which spoke of advantages of Armour® thyroid (& others) over Synthroid, I’m thinking of maybe trying Armour. Also, I’ve been taking one 12.5 tablet(daily) of Iodoral® for six weeks prior to these thyroid tests. My question is: Would you recommend increasing the Iodoral? And how much Armour would you recommend starting off with?
I have been having significant hair loss, as well as urgency in bladder control. I also have been dealing with skin problems (rash). I’m visiting a nutritionist trying to get balances restored and toxins out of my system. (Both my mother and grandmother had goiters so there is indication of thyroid problems in the family). I tend to be cold-blooded. My hands and feet are cold, I have had some mild issues of stress or panic (addressed through Sublingual Vitamin B12). I had some infertility issues in the past, periods were always irregular until doctor finally put me on the pill to establish regularity. During a c-section, the surgeon did partial hysterectomy on me—24 years ago. Thank you in advance for addressing this issue.
Ms. C.
Response:
Dear Ms. C.,
Whenever working with the thyroid it is important to also look at the adrenal glands, in particular cortisol and DHEA. VRP offers Salivary Hormone Testing (the Adrenal Function Panel) if you are interested.
Armour thyroid common starting dose is 60 mg for a TSH in your range. Yet, a more conservative approach would be to start at 30 mg and retest your TSH and Free T4, Free T3 in 4 to 6 weeks. This way the thyroid will not be overtly suppressed.
Also, many individuals taking Iodoral will add ATP Cofactors, a special B vitamin combination, to help with the utilization of the iodine. Working with the Armour thyroid and ATP Cofactors would be the most concise approach and then re-evaluate in 4 to 6 weeks with blood work.
Prior to increasing Iodoral, getting a thyroid ultrasound and performing a 24-hour urinary Iodine Sufficiency Test would be strong considerations. The 24-hour Iodine Sufficiency Test available here is the one that Dr. Brownstein discusses in his excellent book.
Sincerely,
Chris D. Meletis, ND
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Timing of Glabrinex
Question:
Dear Dr. Meletis,
How important is it to take Glabrinex™ with dinner? I travel 90 percent of the time for work and frequently entertain clients at dinner and am reluctant to take Glabrinex or any other supplement or prescription in public. Would I still get full benefit if I take it at bedtime or on an empty stomach?
Ms. W.
Response:
Dear Ms. W.,
The current evidence is that Glabrinex was taken with food in the research, yet I would think clinically it should also work if taken prior to dinner or after dinner when you arrive back to your room. You may also consider incorporating Porangaba Tea as well into your clear fluid intake during the day, since it can nicely complement the use of Glabrinex.
Sincerely,
Chris D. Meletis, ND
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Blood Sugar Maintenance
Question:
Dear Dr. Meletis,
I am 34 years old with a family history of diabetes. My doctor said I am on the borderline so he put me on medication called metformin HCL 500 MG, 3 tablets per day, but my sugar level keeps going up. What can I do? Please help me. Thanks.
Ms. N.
Response:
Dear Ms. N.,
There are many factors that need to be taken into consideration; I will share a few considerations, although some of them may not directly apply to your circumstance. The first consideration is identifying the underlying trigger for the blood sugar imbalance at such a young age. Though there is a family history, there is a saying that often applies: “Genetics may predispose, yet diet and lifestyle manifest the genetic potential.” So, you are much more prone due to the family history; however, something triggered it in your early 30s opposed to 40s, 50s or older. Pregnancies can serve as a trigger due to weight gain and hormonal changes; so can weight gain itself.
Even more important than weight alone is the distribution of the weight; if it is in the mid-riff or waist line, even if one weighs within the normal range the hormonal impact of this weight leads to insulin resistance. Additionally, if by chance you snore this increases the likelihood that you may have sleep apnea that definitely will accelerate the potential for insulin resistance and diabetes. In the presence of any sleep disturbance it is essential to get evaluated by your physician. The most obvious considerations are also to dramatically cut back your carbs, increase lean body mass by building muscles and ensure that you are staying well hydrated. Some individuals on metformin actually find that they gain weight on this product, which is counterproductive to blood sugar management.
Catching blood sugar imbalances early and gaining control can actually prove to be a lifelong plan to maintain health and true wellness. Although it takes a fair amount of effort initially, once you create a personalized plan for yourself, of diet, exercise and supplementation, often the benefits can be significant.
You will also want to visit with your personal healthcare provider to ensure that your thyroid levels are fine. Asking for a TSH, Free T4 and Free T3 level test is a must. Also inquiring as to your Vitamin D3 levels via a 25-OH vitamin D test is critical especially in the Northern States. Low Vitamin D3 levels are associated with increased risk for many conditions.
From a supplement perspective, I would encourage you to read about the following on the website: GluControl™, Chromium, Glabrinex™, B vitamins (Extension B-Plex) for both stress and blood sugars and Gymnema Sylvestre.
Sincerely,
Chris D. Meletis, ND
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Skin Health
Question:
Dear Dr. Meletis,
I’ve had disseminated superficial actinic porokeratosis (DSAP), an inherited skin condition causing dry patches on the arms and legs, for many years and have tried everything available to dermatologists without success and wondered if you had any thoughts on alternatives. It’s when summer comes or any time it’s sunny that the little red spots turn up on my arms, but go away when I’m not in the sun. The condition is supposed to be inherited or genetically linked although the dermatologist said early age sun damage could have contributed to DSAP (I used to live in Corning, NY on upstate Finger Lakes and would visit my grandmother in St. Petersburg every spring break). But the condition is inherited.
Regards,
Mr. T.
Response:
Dear Mr. T.,
It sounds like you have tried lots of modalities to help with your condition. As you mentioned, there is a genetic link, with an increased prevalence among Europeans, yet there is also a specific chromosomal 12 association I believe according to some research. The question is what serves as the trigger for the gene expression?
Clinically, what I have used with my patients is year around Vitamin D3 supplementation 2,000 to 4,000 IU, along with Zinc Monomethione typically 25 mg per day, accompanied with 10,000 IU of Vitamin A, along with 2,000 to 3,000 mg of Ethyl EPA™. The goal is to address skin health and overall tissue integrity. Most patients have positive benefits. Starting in the early spring, by mid June-July, it should allow for some notable improvement. Of course individual results will vary, depending on previous skin damage, your personal skin quality and dermal/epidermal thickness. More recently I also now incorporate topical Hyaluronic Acid as well, such as Pure HA Serum to the most affected areas once per day after showering, while the skin is still slightly moist.
Sincerely,
Chris D. Meletis, ND
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Tremors in 22-Year-Old
Question:
Dear Dr. Meletis,
My 22-year-old son is showing perhaps early signs of Parkinson’s. His hands shake, which is quite pronounced, more than just a little. Have you heard of this and what supplements would you recommend please? Thanks very much.
Ms. Y.
Response:
Dear Ms. Y.,
If your son is showing signs of shaking and other symptoms, it will be very important to get him evaluated to make sure another process is not going on in his body. This evaluation may include either a CAT/CT scan or MRI. There are many potential causes for his condition and exploring each is important. For instance, thyroid conditions can cause tremors, so can adrenal issues, sleep apnea, medication and drugs and others factors.
If you live in the northern portion of North America, low Vitamin D3 levels are believed to be contributory to MS as well. From an overall nutritional perspective, a good multivitamin such as Extend Core or Extend Plus, a green drink such as Primary Greens™, Extension Resveratrol and liquid Vitamin B12 (methylcobalamin) along with Vitamin D3 are some considerations for nutritional wellness and to help create a health-promoting foundation. Also it is advisable to avoid caffeinated beverages. Having him thoroughly evaluated by a competent physician will be important, for both you and his peace of mind.
Sincerely,
Chris D. Meletis, ND
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Adrenaline
Question:
Dear Dr. Meletis,
I recently was told by my doctor after a blood test that I have no adrenaline level. He prescribed hydrocortisone 10 mg, twice daily. I was told I should start to feel better in 2 days. However, after 2 weeks I have experienced no improvement in my energy level or any other changes for that matter. What side effects are there with hydrocortisone (if any) and is there any supplement I can take for low adrenaline levels? Also, I have been taking 100 mg DHEA on an empty stomach upon rising in the morning and I have been taking DHEA on a regular basis for a long time.
Do you have any suggestions for what to take to increase my adrenaline level?
Mr. M.
Response:
Dear Mr. M.,
Thanks for the excellent question. If your adrenaline levels actually measured low, you will want to look at your adrenal function very closely and see what is going on. The typical way to measure adrenaline levels is test for the break down product in the urine. If that has not been done that would be a consideration for discussion with your doctor. Relative to hydrocortisone, typically my patients will begin to feel better within a couple of weeks. It depends on what other obstacles are also involved. If you have not already shared with your doctor the 100 mg DHEA dose, which is on the higher side of supplementation, this needs to be factored into your clinical picture. Also getting your DHEA levels measured would be prudent to see if you are within the acceptable range and how your overall adrenal picture is looking. A Salivary Hormone Test measuring adrenal function and DHEA levels is available here.
Relative to adrenaline, precursors like Tyrosine are often used. In terms of the cortisol pathway, a popular product is CortiTrophin®. You can read more about CortiTrophin on the website.
Sincerely,
Chris D. Meletis, ND
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Phlegm and Food Allergies
Question:
Dear Dr. Meletis,
My son has hacked up phlegm every morning since he was 3. He is now 18 and still has this problem. Some say it is sports-induced asthma. I would like to know how to help him. When he was born there was a green fluid. We had to have a pulmonologist help him through the first hours. What do you think?
Ms. F.
Response:
Dear Ms. F.,
Thanks for sharing your son’s history and challenge. With my patients with ongoing issues of this nature, they all are recommended to get a 96 item Food Allergy Test. This test is available here.
I would also strongly consider getting his phlegm cultured for bacteria, with an emphasis that the first morning sample is provided immediately after collection.
I would encourage you to also read about NAC (N-Acetyl-Cysteine), which is a mucolytic that helps get rid of mucus. Also EpiCor®. You can read about both on the website.
I will be interested in hearing how he feels after avoiding potential food triggers. Until he gets his results I would suggest he experiment with stopping all milk, peanuts, bananas and citrus fruit and juice for 3 weeks.
Sincerely,
Chris D. Meletis, ND
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Food Allergies, Bone Health
Question:
Dear Dr. Meletis,
I’m allergic to all dairy, egg, almond, peanut, yogurt, wheat, and garlic. I’ve got the beginning of osteoporosis—what calcium supplements would you suggest?
Ms. H.
Response:
Dear Ms. H.,
You appear to have some of the most challenging allergies relative to maintaining a healthy diet for optimal calcium intake. Over the last 16 years of clinical practice I have found that Calcium Citrate Malate is by far my favorite, along with Calcium Hydroxyapatite. I routinely have my patients take 500-750 mg of Calcium Hydroxyapatite in the AM and 500-750 mg of Calcium Citrate Malate in the evening prior to going to bed. In addition, I seek to optimize Vitamin D3 levels, as there is strong evidence that many women with osteoporosis have low Vitamin D3 levels. My personal goals for my patients are to have a minimum Vitamin D3 level of 55 for blood serum 25-OH. Your personal physician should be more than pleased to measure your levels, as not only is it helpful for bone health, but also mental health, heart health, and immune competence while being protective of the colon and breast tissues as well for women.
I would also encourage you to read about Strontium at www.vrp.com; 340 mg, 2 times per day over the course of 2 years was reported to improve bone density up to 15 percent over the course of 2 years, according to a 2002 study.
Relative to your food allergies, you may consider using probiotics, such as BioPro™ or Culturelle® and GI Cell Support to see if you can help lessen any possible leaky gut syndrome that may be present. Often after avoiding ones major food sensitivities for 3 to 6 months and working on GI health, retesting can show some improvement on the level of food reactivity. As you probably know, a Food Allergy Test, which tests for sensitivities to 96 different foods, is available here. Of course visiting with your personal healthcare provider is important.
Sincerely,
Chris D. Meletis, ND
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