In the News

VITAMIN K2 RECOMMENDED TO SUPPORT HEART HEALTH IN AORTIC VALVE CALCIFICATION

Sleep Apnea May Increase Risk of Developing Alzheimer's Disease

Biomarker May Predict Early Alzheimer's Disease

What Nurses Need to Know: Pain Research

NEW to the United States: Equelle®, a Non-Hormonal Supplement Clinically Shown to Help Ease Menopause Symptoms*

VITAMIN K2 RECOMMENDED TO SUPPORT HEART HEALTH IN AORTIC VALVE CALCIFICATION

The European Heart Journal has published an important review paper that highlights the potential of Vitamin K2 supplementation for calcific aortic valve stenosis (CAVS), a common cardiovascular condition in the aging population where no medical therapy currently exists.

According to researchers, once symptomatic severe CAVS has developed, the prognosis without intervention is dismal. Currently the only treatment for (symptomatic) severe CAVS is surgical or trans catheter aortic valve replacement (AVR), to which not all patients are suited. While multiple trials have attempted to repurpose commonly used pharmacological interventions to slow CAVS progression, pharmacological interventions have thus far failed to alter the course of CAVS. The review paper notes that studies have demonstrated that statins, widely used for lipid lowering in atherosclerosis and inflammation, have no effect on CAVS progression or clinical outcomes, and might actually exacerbate the condition.

However, the researchers noted promise with Vitamin K2, specifically the long-chain menaquinones (MK7), as they are transported efficiently beyond the liver. “Vitamin K supplementation is an attractive option to replenish vascular vitamin K stores to ensure optimal calcification inhibition,” the researchers wrote.

“This review is so very significant, “ says Dr. Hogne Vik, chief medical officer with NattoPharma ASA, world leaders in Vitamin K2 research and development. “Recognizing that medical therapies are proving ineffective, researchers are shining a light on efficacious supplemental alternatives, which leads them to the clinical research that NattoPharma has spearheaded. Specifically, our three-year cardiovascular study in healthy postmenopausal women taking just 180 mcg daily of Vitamin K2 as MK-7 (as MenaQ7), which demonstrated a cessation and even regression in arterial stiffness.

“The relevance of our three-year study has resulted in several studies by the medical community for patients with existing coronary artery calcification, aortic valve calcification, and peripheral artery calcification,” adds Dr. Vik.

The review paper concluded: “The pathophysiological mechanisms involved in CAVS initiation and progression are being rapidly elucidated and include inflammation, fibrosis, and calcification. With this advancing knowledge, we have identified novel therapeutic targets like vitamin K and new imaging techniques that can be used to test the efficacy of novel agents and further inform our pathophysiological understanding.”

References:

Peeters FECM, et al. Calcific aortic valve stenosis: hard disease in the heart. Euro Heart J (2017) 0,1-8.

Knapen MHJ, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: double-blind randomised clinical trial. Thrombosis and Haemostasis (2015) 19;113(5).

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About NattoPharma and MenaQ7®

NattoPharma ASA, based in Norway, is the world’s leader in vitamin K2 research and development. NattoPharma is the exclusive international supplier of MenaQ7® Vitamin K2 as MK-7, the best documented, vitamin K2 as menaquinone-7 (MK-7) with guaranteed actives and stability, clinical substantiation, and international patents granted and pending, and now the new MenaQ7® Full Spectrum, which delivers menaquinones 6, 7, 8, and 9. The company has a multi-year research and development program to substantiate and discover the health benefits of vitamin K2 for applications in the marketplace for functional food and dietary supplements. With a global presence, the company established its North American subsidiary, NattoPharma USA, Inc., in Edison, NJ, and NattoPharma R&D Ltd. in Cyprus. For more information, visit www.nattopharma.com or www.menaq7.com.

For more information, please contact:

Kate Quackenbush, NattoPharma Communications Director

Phone: 609-643-0749 x 220

E-mail: kate.quackenbush@nattopharma.com

Sleep Apnea May Increase Risk of Developing Alzheimer's Disease

?Obstructive sleep apnea (OSA) may put elderly people at greater risk of developing Alzheimer’s disease (AD), according to new research published online in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

In “Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly: A Longitudinal Study,” researchers report that biomarkers for amyloid beta (Ab), the plaque-building peptides associated with Alzheimer’s disease, increase over time in elderly adults with OSA in proportion to OSA severity. Thus, individuals with more apneas per hour had greater accumulation of brain amyloid over time.

According to the authors, AD is a neurodegenerative disorder that afflicts approximately five million older Americans. OSA is even more common, afflicting from 30 to 80 percent of the elderly, depending on how OSA is defined.

“Several studies have suggested that sleep disturbances might contribute to amyloid deposits and accelerate cognitive decline in those at risk for AD,” said Ricardo S. Osorio, MD, senior study author and assistant professor of psychiatry at New York University School of Medicine. “However, so far it has been challenging to verify causality for these associations because OSA and AD share risk factors and commonly coexist.”

He added that the purpose of this study was to investigate the associations between OSA severity and changes in AD biomarkers longitudinally, specifically whether amyloid deposits increase over time in healthy elderly participants with OSA.

The study included 208 participants, age 55 to 90, with normal cognition as measured by standardized tests and clinical evaluations. None of the participants was referred by a sleep center, used continuous positive airway pressure (CPAP) to treat sleep apnea, was depressed, or had a medical condition that might affect their brain function. The researchers performed lumbar punctures (LPs) to obtain participants’ cerebrospinal fluid (CSF) soluble Ab levels, and then used positron emission tomography, or PET, to measure Ab deposits directly in the brain in a subset of participants.

The study found that more than half the participants had OSA, including 36.5 percent with mild OSA and 16.8 percent with moderate to severe OSA. From the total study sample, 104 participated in a two-year longitudinal study that found a correlation between OSA severity and a decrease in CSF Ab42 levels over time. The authors said this finding is compatible with an increase in amyloid deposits in the brain; the finding was confirmed in the subset of participants who underwent amyloid PET, which showed an increase in amyloid burden in those with OSA.

Surprisingly, the study did not find that OSA severity predicted cognitive deterioration in these healthy elderly adults. Andrew Varga, MD, PhD, study coauthor and a physician specializing in sleep medicine and neurology at the Icahn School of Medicine at Mount Sinai in New York, said this finding suggests that these changes were occurring in the preclinical stages of AD.

“The relationship between amyloid burden and cognition is probably nonlinear and dependent on additional factors,” he added. This study finding may also be attributable to the study’s relatively short duration, highly educated participants and use of tests that fail to discern changes in cognitive abilities that are subtle or sleep-dependent, the authors wrote.

The high prevalence of OSA the study found in these cognitively normal elderly participants and the link between OSA and amyloid burden in these very early stages of AD pathology, the researchers believe, suggest the CPAP, dental appliances, positional therapy and other treatments for sleep apnea could delay cognitive impairment and dementia in many older adults.

“Results from this study, and the growing literature suggesting that OSA, cognitive decline and AD are related, may mean that age tips the known consequences of OSA from sleepiness, cardiovascular, and metabolic dysfunction to brain impairment,” Dr. Osorio said. “If this is the case, then the potential benefit of developing better screening tools to diagnose OSA in the elderly who are often asymptomatic is enormous.”

The National Institutes of Health, Foundation for Research in Sleep Disorders, the American Sleep Medicine Foundation and Friedman Brain Institute supported this research.

Contact for Article 
Ricardo Osorio, MD
ricardo.osorio@nyumc.org

Biomarker May Predict Early Alzheimer's Disease

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified a peptide that could lead to the early detection of Alzheimer’s disease (AD). The discovery, published in Nature Communications, may also provide a means of homing drugs to diseased areas of the brain to treat AD, Parkinson’s disease, as well as glioblastoma, brain injuries and stroke.

“Our goal was to find a new biomarker for AD,” says Aman Mann, Ph.D., research assistant professor at SBP who shares the lead authorship of the study with Pablo Scodeller, Ph.D., a postdoctoral researcher at SBP. “We have identified a peptide (DAG) that recognizes a protein that is elevated in the brain blood vessels of AD mice and human patients. The DAG target, connective tissue growth factor (CTGF) appears in the AD brain before amyloid plaques, the pathological hallmark of AD.”

“CTGF is a protein that is made in the brain in response to inflammation and tissue repair,” explains Mann. “Our finding that connects elevated levels of CTGF with AD is consistent with the growing body of evidence suggesting that inflammation plays an important role in the development of AD.”

The research team identified the DAG peptide using in vivo phage display screening at different stages of AD development in a mouse model. In young AD mice, DAG detected the earliest stage of the disease. If the early appearance of the DAG target holds true in humans, it would mean that DAG could be used as a tool to identify patients at early, pre-symptomatic stages of the disease when treatments already available may still be effective.

“Importantly, we showed that DAG binds to cells and brain from AD human patients in a CTGF-dependent manner” says Mann. “This is consistent with an earlier report of high CTGF expression in the brains of AD patients.”

“Our findings show that endothelial cells, the cells that form the inner lining of blood vessels, bind our DAG peptide in the parts of the mouse brain affected by the disease,” says Erkki Ruoslahti, M.D., Ph.D., distinguished professor at SBP and senior author of the paper. “This is very significant because the endothelial cells are readily accessible for probes injected into the blood stream, whereas other types of cells in the brain are behind a protective wall called the blood-brain barrier. The change in AD blood vessels gives us an opportunity to create a diagnostic method that can detect AD at the earliest stage possible.

“But first we need to develop an imaging platform for the technology, using MRI or PET scans to differentiate live AD mice from normal mice. Once that’s done successfully, we can focus on humans,” adds Ruoslahti.

“As our research progresses we also foresee CTGF as a potential therapeutic target that is unrelated to amyloid beta (Aβ), the toxic protein that creates brain plaques,” says Ruoslahti. “Given the number of failed clinical studies that have sought to treat AD patients by targeting Aβ, it’s clear that treatments will need to be given earlier—before amyloid plaques appear—or have to target entirely different pathways.

“DAG has the potential to fill both roles—identifying at risk individuals prior to overt signs of AD and targeted delivery of drugs to diseased areas of the brain. Perhaps CTGF itself can be a drug target in AD and other brain disorders linked to inflammation. We’ll just have to learn more about its role in these diseases”.

Co-authors of the study include: Sazid Hussain, Gary Braun, SBP; Tarmo Mölder, Kadri Toome, Tambet Teesalu, University of Tartu; Rajesh Ambasudhan, Scintillon Institute; and Stuart A. Lipton, Scintillon Institute and UC San Diego.

Funding sources for this research came, in part, from the Defense Advanced Research Projects Agency (DARPA), the European Research Council, the Wellcome Trust International Fellowship (WT095077MA), the European Regional Development Fund, the National Institutes of Health (P01 HD29587, R01 NS086890, DPI DA041722, and P30 NS076411), and a Distinguished Investigator Award of the Brain & Behavior Research Foundation.

This technology has been licensed to a startup company, AivoCode Inc.

What Nurses Need to Know: Pain Research

Assistant Professor Janiece Taylor, PhD, RN, thinks back to the clinical nurse who she once was, who loved caregiving but wrestled with doubt and struggled to treat pain at a nursing home. She wishes she could have been there in spirit to reassure that nurse, “Don’t give up.”

Something good was coming.

“One summer I wanted to get out of New Mexico—I was just young and wanted to travel,” and the University of Texas-Austin had a program teaching undergraduate students about nursing research. She was hooked. Staying at UT-Austin for the PhD program, she began to fall for teaching as well. She says watching students grow, “and knowing I had something to do with that … it’s pretty amazing.”

Today, as a developing researcher (“I consider myself so new in the area of pain research”), Taylor lets frustration drive her instead of holding her back. And once again, she feels something good is on the way in the form of her pilot project “working with people in their homes to tailor strategies to help them address their pain above and beyond pharmacology.” She’s got footsteps to follow.

“Hopkins is so much a team effort,” Taylor explains, pointing to colleagues Sarah Szanton, PhD, ANP, FAAN, and Laura Gitlin, PhD, and their success on aging in place and non-pharmaceutical treatment of dementia, respectively. “They address things with that different lens. There is so much room for that in pain research as well. … Because pain really is outside the box.”

NEW to the United States: Equelle®, a Non-Hormonal Supplement Clinically Shown to Help Ease Menopause Symptoms*

MANCHESTER, N.H., Oct. 30, 2017 /PRNewswire/ -- INNATE Response, a brand of FoodState^®, manufacturer of naturally-inspired supplements that support and strengthen the body's innate healing response, today announced the United States launch of Equelle, a non-hormonal dietary supplement clinically shown to help ease the symptoms commonly experienced during menopause, such as hot flashes and muscle discomfort*. The supplement will be available to integrative healthcare professionals exclusively through Emerson Ecologics^® beginning October 30, 2017.

"Menopause is a normal, transitionary period of life that all women will eventually experience," said Tieraona Low Dog, M.D., an integrative medical doctor and expert in integrative medicine, women's health, herbal medicine and dietary supplements. "In the United States alone, there are 53 million women between the menopause ages of 40 to 64, and increasingly, these women want and use complementary therapies to manage symptoms of menopause. I'm delighted that clinicians now have the opportunity to recommend Equelle as a part of a total approach in the management of menopause."

The active ingredient in Equelle is S-equol, a metabolite of the soy isoflavone daidzein, which can be naturally produced in the intestinal tract. Clinical studies have shown that incorporating the regular use of a S-equol supplement like Equelle can ease menopausal symptoms in as few as four weeks, with optimal results shown after eight to 12 weeks of consistent use.* Since only 20 to 30 percent of women in the U.S. have the ability to naturally produce S-equol in their bodies, those seeking to benefit from S-equol to manage menopausal symptoms may find supplementation essential.

Equelle is the product of fermentation of whole, non-GMO soy germ using a patented and proprietary process by the Otsuka Pharmaceutical Co., Ltd. The process results in the conversion of the daidzein to S-equol. Equelle tablets, created under current Good Manufacturing Practices, are clear coated and free of gluten, dairy, magnesium stearate and talc. Suggested patient use is two Equelle tablets daily, one tablet taken in the morning and one tablet at night, which provide the standardized dose of 10 mg of S-equol.

Clinicians interested in ordering Equelle may do so via emersonecologics.com, or by calling Emerson Ecologics directly at 800.654.4432. In addition, INNATE Response's customer support team is available at 800.634.6342 or questions@innateresponse.com for questions and assistance with product ordering. Interested patients should ask their healthcare practitioner about how Equelle can help with their menopause symptoms. To learn more about Equelle, visit equelle.com.

©FoodState, Inc. 2017.

About INNATE Response

At INNATE Response, we share the belief that nothing is more important than restoring the body's innate ability to heal. To that end, we develop nutrient-rich supplements that embrace the wholism of nature and help people achieve optimal health.* We are committed to supporting wholistic healthcare professionals who understand that the body always seeks wellness, and who appreciate the wisdom of nature in their protocols. For more information, please visit innateresponse.com and innate-edu.com.

About Otsuka Pharmaceutical Co., Ltd.

Otsuka researches, develops, manufactures and markets innovative products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

Otsuka Pharmaceutical is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 45,000 people worldwide and had consolidated sales of approximately USD 11 billion in 2016.

Otsuka Pharmaceutical welcomes you to visit its global website at https://www.otsuka.co.jp/en.

*This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Media Contact:
Curt Finckler, INNATE Response
curt.finckler@innateresponse.com / 617-304-3988

SOURCE FoodState