Physician's Seal, LLC® (PS) today announced favorable results from its REMfresh® Safety Update at 24 Months (REMSU24) for REMfresh® continuous release and absorption melatonin (CRA-melatonin™), a real-world surveillance study reporting on the safety and tolerability profile of REMfresh. It is estimated that 320,255 individual patients used the product during the two-year surveillance period. No serious adverse events were reported. Additionally, the self-reporting rates and patterns of non-serious adverse events were very low with only 51 events received. The three most commonly reported, non-serious adverse events were headache (6), nightmares (4) and dizziness (3). The robust scientific literature on melatonin does not show that REMfresh is known to cause any of these non-serious adverse events and, in fact, these reported non-serious adverse events are often co-morbid conditions for people suffering from chronic sleeplessness.3,4,5
REMSU24 captured and analyzed serious and non-serious adverse event reports for REMfresh over a 24-month period from March 9, 2017 to March 9, 2019. "The findings from REMSU24 are consistent with the outcome observed from REMSU12, which reaffirms the safety and tolerability profile of REMfresh in an extended and comprehensive real-world setting," said David C. Brodner, M.D., a leading sleep specialist who is Double Board-Certified in Otolaryngology -- Head and Neck Surgery and Sleep Medicine, Founder and Principle Physician at The Center for Sinus, Allergy, and Sleep Wellness, in Palm Beach County, Florida, and Senior Medical Advisor for Physician's Seal, LLC®. "This calculation results in an estimated 0.016 percent adverse event reporting rate for REMfresh, which is remarkably low. The outcome does not cause any concern for the safety profile of the product. This confirms the benign safety and tolerability profile of REMfresh seen in prior studies and especially in the landmark REMAKT study2 where REMfresh showed superiority over the leading marketed, conventional melatonin product. In fact, the scatter of these non-serious adverse events in REMSU24 probably cannot be separated from what could be expected in the general population. More importantly, no pattern of next-morning drug hangover was seen."
REMfresh is the first and only, continuous release and absorption melatonin, designed to mimic the body's own 7-hour Mesa Wave®, the natural pattern of melatonin blood levels during a normal night's sleep cycle. This helps induce sleep onset and provides lasting and restorative sleep support for up to 7 hours. Since REMfresh is not a drug, there is no drug hangover.
"REMfresh has been shown to be an effective drug-free solution that is now available to the millions of Americans in need of a good night's sleep, many of whom seek alternative therapies that will help induce sleep and keep them asleep until the morning, without causing residual effects they'll feel the next day. Delivered with its patented Ion Powered Pump® (IPP ® ) technology, that imitates the body's own natural sleep pattern, REMfresh is revolutionizing the role of melatonin. It is no longer just for jet lag, but the 99% ultrapure, CRA-melatonin found in REMfresh has been shown to provide substantial benefit to individuals having nightly sleep challenges," said Dr. Brodner.
Chronic disorders of sleep and wakefulness affect an estimated 50-70 million adults in the United States.6 The cumulative long term effects of sleep loss have been associated with a wide range of damaging health consequences, including obesity, diabetes, impaired glucose tolerance, cardiovascular disease, hypertension, anxiety and depression.7 In terms of preventing health consequences, sleeping 6-8 hours per night consistently may provide optimal health outcomes.8
Melatonin: The Body's Natural Sleep Ingredient
Melatonin is produced by the pineal gland in the brain and is the body's natural sleep ingredient. Melatonin levels normally begin to rise in the mid-to late evening and remain high for the majority of the night. Levels begin to decline towards early morning, as the body's wake cycle is triggered. As people age, melatonin levels can drop by as much as 70 percent9 and their bodies may no longer produce enough melatonin to ensure adequate sleep.
Other available products, such as immediate-release melatonin, help initiate the onset of sleep but often are unable to sustain prolonged sleep maintenance. An explanation for this is that after the initial absorption in the stomach, the absorption of conventional melatonin may not be sustainable in the low acidity environment beyond the stomach. Additionally, the melatonin absorbed from the stomach is quickly degraded due to melatonin's relatively short half-life (60 minutes). Continuous absorption in the lower digestive tract is limited by melatonin's limited ability to be absorbed in the low acidity or close to neutral pH environment beyond the stomach. This fundamental challenge for melatonin absorption is overcome in the case of patented REMfresh, which has a built-in low pH pump to keep ion-powered absorption going for seven hours.
The REMfresh® Safety Update at 24 Months (REMSU24) report for REMfresh® is a real-world surveillance study reporting on the safety and tolerability profile of REMfresh® among the estimated 320,255 individual patients who used the product.
An independent call center with pharmacovigilance-trained health care personnel in accordance with U.S. Food and Drug Administration (FDA) and global regulatory guidelines on properly reporting events was retained to receive and record REMfresh customer questions, product issues and adverse events. In addition, a 24-month cluster analysis and trend analysis of adverse events reports received for REMfresh (CRA-melatonin) was conducted by the same personnel.
About Nonprescription REMfresh ®
REMfresh® (CRA-melatonin™) is the first and only, continuous release and absorption formulation of 0.5mg (Lite), 2 mg and 5mg (Extra Strength) UltraMel ® melatonin. UltraMel® melatonin is a high-quality, 99 percent ultrapure melatonin sourced from Western Europe, exclusively for Physician's Seal.
REMfresh caplets continuously release bioavailable, 99 percent ultrapure melatonin over 7 hours, which may help a person fall asleep faster, stay asleep longer and experience quality sleep, such as deep sleep and REM sleep, and wake up refreshed in the morning.
REMfresh was designed as a hydrogel matrix tablet with its patented, scientifically advanced Ion-Powered Pump ® (IPP® ) technology, pioneered by Physician's Seal. Initially, there is a rapid release of the melatonin from the surface of the tablet in the acidic environment of the stomach. As the tablet moves into the higher pH of the small intestine, where conventional melatonin is unlikely to dissolve and be absorbed, acidic factors built inside the tablet maintain a lower pH within the tablet over 7 hours, to allow for continuous release and absorption of active melatonin into the intestines.
Primary Care Companion for CNS Disorders , a peer-reviewed and well-regarded medical journal, has published important results of a U.S.-based randomized, crossover pharmacokinetic (PK) evaluation study in healthy, non-smoking adults, called REMAKT (REM A bsorption Kinetics Trial), that compared REMfresh® continuous release and absorption melatonin (CRA-melatonin™) with a market-leading, immediate-release melatonin (IR-melatonin).
The published study, entitled "A Randomized, Crossover, Pharmacokinetics Evaluation of a Novel Continuous Release and Absorption Melatonin Formulation,"2 demonstrated that melatonin levels with REMfresh exceeded the targeted sleep maintenance threshold for a median of 6.7 hours, compared with 3.7 hours for IR-melatonin. Conversely, the levels of the IR-melatonin formulation dramatically increased 23 times greater than the targeted sleep maintenance threshold level, and then had a rapid decline in serum levels that did not allow melatonin levels to be maintained beyond 4 hours.
The 7-hour action of REMfresh together with its benign tolerability profile, has been validated by two real-world, patient-reported outcomes (PRO) studies, REM f resh® Patient Reported Outcomes DURation (REMDUR) and REMfresh Duration Validation (REMVAL). Both of these studies, involving a total of over 1,600 patients, have been peer reviewed, accepted and presented at SLEEP 2018 and SLEEP 2019, respectively, the Annual Meetings of the Associated Professional Sleep Societies (APSS), and a joint meeting of the American Academy of Sleep Medicine (AASM) and the Sleep Research Society (SRS). Both of these studies demonstrated significant user benefit in sleep onset, sleep duration and sleep quality when taking REMfresh.10,11
REMfresh is a dietary supplement and is regulated under the Federal Dietary Supplement Health and Education Act, which does not require pre-approval. Melatonin has been in common use for over two decades and has a well-established profile of safe use by millions of people around the world. As with all supplements, individual results may vary.
REMfresh is non-habit forming and does not contain narcotics, hypnotics, barbiturates, sedatives, antihistamines, alcohol or other harsh additive chemicals. The usual adult recommended dose is 1-2 tablets 30-90 minutes before bedtime. Specific dosing instructions found on the back of the box should be followed for proper use of supplements. REMfresh is available in 0.5mg (Lite), 2mg and 5mg (Extra Strength) versions.
REMfresh is available at Walgreens, CVS, Rite Aid, Amazon.com and www.REMfresh.com.
About Physician's Seal®
Physician's Seal® is the Innovator of REMfresh®, the first and only continuous release and absorption, 99 percent ultrapure melatonin (CRA-melatonin™), that mimics the way the body naturally releases and takes up melatonin over a 7-hour period. Physician's Seal (PS), founded in 2015, is a privately held company based in Boca Raton, Florida. It is committed to bringing cutting-edge life science applications to doctors and their patients. For more information, visit www.REMfresh.com.
Physician's Seal's sister subsidiary, IM HealthScience® (IMH), is the innovator of the two medical foods IBgard® and FDgard® for the dietary management of Irritable Bowel Syndrome (IBS) and Functional Dyspepsia (FD or recurring indigestion), respectively. IMH rounds out its line of digestive products with Fiber Choice®, a well-known, natural prebiotic chewable daily fiber that helps with regularity. IMH® is a privately held company based in Boca Raton, Florida. It was founded in 2010 by a team of highly experienced pharmaceutical executives. Both PS and IMH are dedicated to developing products to address overall health and wellness in digestive health and sleep. The Physician's Seal and IM HealthScience advantage comes from developing products based on patented, targeted-delivery technologies, including IPP® (Ion-Powered Pump®) and SST® (Site Specific Targeting®) technologies. For more information, visit www.imhealthscience.com to learn about the company, or www.IBgard.com, www.FDgard.com and www.FiberChoice.com.
1 Among primary care physicians with a certification in sleep disorders who recommended a brand of melatonin. IQVIA ProVoice Jan-.Feb.2019 survey.
2 Seiden, D.J., & Shah, S.M. A Randomized, Crossover, Pharmacokinetics Evaluation of a Novel Continuous Release and Absorption Melatonin Formulation. Primary Care Companion for CNS Disorders 2019. doi: https://doi.org/10.4088/PCC.19m02450
3 Tran D.P and Spierings E.L.; Headache and insomnia: their relation reviewed; Cranio. 2013 Jul; 31(3): 165-70.
4 Schlarb A.S. et.al. Nightmares and Associations with Sleep Quality and Self-Efficacy among University Students; J. Sleep Disorders and Management 2015; 1:1.
5 Kim S.K. et. al. Relationship between sleep quality and dizziness; PLoS One. 2018; 13(3): e0192705.
6 Colten, H.R., & Altevogt, B.M. (Eds). Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Institute of Medicine (US) Committee on Sleep Medicine and Research. Washington, DC: National Academies Press (US). 2006.doi: https://doi.org/10.17226/11617.
7 Cappuccio, F.P., D'Elia, L., Strazzullo, P., & Miller, M.A. Sleep duration and all-cause mortality: A systemic review and meta-analysis of prospective studies. 2010. Sleep, 33(5):585-592.
8 Watson, N.F., Badr, M.S., Belenky, G., et al. Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society on the Recommended Amount of Sleep for the Healthy Adult, Methodology and Discussion. Journal of Clinical Sleep Medicine. 2015. 11(6); 591-592.
9 Zisapel, N. Melatonin and sleep. The Open Neuroendocrinology Journal. 2010. 3: 85-95.
10 Brodner, D.C., Seiden, D.J., & Shah, S.M. (2019). Observed Hypnotic Effects with a Continuous-Release Ion Powered Pump Melatonin Delivery System: Self-Reported Patient Outcomes Study Results Demonstrating Improvement in Sleep Duration and Quality. (Abstract 0399). Poster Presented at SLEEP 2019, San Antonio, Texas.
11 Seiden, D.J., Brodner, D.C., & Shah, S.M. (2018). Improvement in Sleep Maintenance and Sleep Quality with Ion Powered Pump Continuous Release and Absorption Melatonin: Results from a Self-Reported Patient Outcomes Study. (Abstract0419). Poster Presented at SLEEP 2018, Baltimore, Maryland.
Copyright © 2019 REMfresh ® This information is for educational purposes only and is not meant to be a substitute for the advice of a physician or other health care professional. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. You should not use this information for diagnosing a health problem or disease. REMfresh is intended to relieve occasional sleeplessness. Statements made in this release rely upon reviews of literature, input from PS's advisors and PS's own expertise. There may always be other opinions or emphasis points. Some of the statements from different sources may not mesh with each other. There may be inadvertent inaccuracies that PS is not aware of. Space limitations in this release only allow limited reference to some guidelines or practices which may, or may not, be fully agreed to by all scientific, medical or regulatory experts. For any of PS's products this release does not make or have any intent to make drug claims or any comparison or implied claims against FDA approved interventions for sleep disorders. Any comments on any products are based on literature reviews and input from PS's own advisors. There may be others who have other points of view. Pre-clinical findings do not always correlate with clinical or real-world findings. The reader is urged to check all current information, including the latest website disclosures and/or package inserts, of any of the medical products mentionedhere, as information, including government regulations, changes all the time. The statements of individual opinions are those of the individuals quoted and do not necessarily reflect opinions of PS. Please fully read all disclaimers/clarifications/explanations. PS disclaims any injury or alleged injury resulting from any ideas, methods, instructions or products referred to here. Health care practitioners should use their independent, professional judgment in helping their patients best manage their sleep conditions. The company will strive to keep information current and consistent but may not be able to do so at any specific time. Generally, the most current information can be found on www.REMfresh.com. Individual results may vary.
REMfresh is protected by U.S. Patents No.: 8,691,275; 9,186,351; 9,241,926; 9,549,900. Keep out of reach of children. Store at room temperature. Individual results may vary. Do not use if blister is torn or ripped or if there is any other evidence of tampering. Consult a physician if using any supplement for the first time. Please read package insert and the website for more information.