MedicalResearch.com Interview with:
David C. Brodner, M.D.
Founder and Principle Physician, The Center for Sinus, Allergy, and Sleep Wellness
Double Board-Certified in Otolaryngology (Head and Neck Surgery) and Sleep Medicine
Assistant Clinical Professor
Florida Atlantic University College of Medicine
Medical Director, Good Samaritan Hospital Sleep Laboratory
Senior Medical Advisor, Physician’s Seal, LLC®
MedicalResearch.com: What is the background for this study?
Response: Chronic sleep and wakefulness disorders affect an estimated 50 to 70 million Americans, and long-term sleep deprivation has been associated with negative health consequences, including an increased risk of diabetes, hypertension, heart attack, stroke, obesity and depression.
Sleep/wake cycles are regulated by melatonin, levels of which 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 in triggered. Melatonin levels typically decline with age, with a significant decrease after age 40.
And as people age, their bodies may no longer produce enough melatonin to ensure adequate sleep. In addition to difficulties falling asleep, sleep in older populations can include fragmented and sustained sleep problems. Melatonin supplementation has been shown to promote and maintain sleep in older populations.
In this study, we compared the pharmacokinetics (PK) profile of REMfresh®, a continuous release and absorption melatonin (CRA-melatonin), with that of a leading immediate-release melatonin (IR-melatonin) formulation.
MedicalResearch.com: What are the main findings?
Response: Our research has shown that REMfresh® (CRA-melatonin) is a scientific breakthrough in the management of sleep. As a drug-free, non-prescription sleep product, REMfresh® (CRA-melatonin) mimics the body’s own 7-hour Mesa Wave™, a natural pattern of melatonin blood levels during a normal night’s sleep cycle.
The study demonstrated the continuous release and absorption of 99 percent ultra-pure melatonin in REMfresh® (CRA-melatonin) was designed to induce sleep onset and provide continuous, lasting restorative sleep over 7 hours. The scientifically advanced, patented formulation, called Ion Powered Pump (IPP™) technology, replicates the way in which the body naturally releases and absorbs melatonin, unlike conventional melatonin sleep products. Since REMfresh® (CRA-melatonin) is not a drug, there is no drug hangover.
The findings are based on REMAKT® (REM Absorption Kinetics Trial), a U.S.-based randomized, crossover, pharmacokinetics (PK) evaluation study.
Analysis of the data showed that use of REMfresh® (CRA-melatonin) resulted in:
• Melatonin levels exceeding the target sleep maintenance threshold of 1,000 pg/mL for a median of 6.7 hours, compared with 3.7 hours for immediate-release melatonin (IR-melatonin).
• A burst of release and absorption of approximately 50 percent of the melatonin within the first 3 hours, facilitating sleep onset.
• Sustained release and absorption of approximately 50 percent of the remaining melatonin within the next 4 hours to help with sleep maintenance.
• Median maximum concentrations of 5 mg doses was 4,690 pg/mL for REMfresh® (CRA-melatonin) versus 23,352 pg/mL for the IR-melatonin formulation (23-fold higher than the targeted levels for sleep onset). Median time to maximum concentration was 1.5 hours.
REMfresh® (CRA-melatonin) builds upon the body of evidence from prolonged-release melatonin (PR-M), which demonstrated in well-conducted, placebo-controlled studies, statistically significant improvement in sleep quality, morning alertness, sleep latency and quality of life in patients aged 55 years and older compared with placebo.
Additional clinical findings of REMfresh® (CRA-melatonin) data included an analysis of several modified-release formulations of melatonin, which have had difficulties overcoming the challenges of release and absorption of melatonin in the higher pH environments in the small and large intestines. This may explain why other melatonin products have difficulties with continuous absorption through the night, and conventional melatonin products have had challenges at mimicking the profile of a Mesa Wave™.
Our data was presented in three posters at the recent American Academy of Sleep Medicine and the Sleep Research Society. The research abstracts are published in the online supplement of the journal, Sleep, which is available at
MedicalResearch.com: What should readers take away from your report?
Response: These results represent an unparalleled breakthrough in drug-free sleep maintenance therapy that physicians and their patients have been waiting for in a sleep product. Melatonin products have been used primarily as a chronobiotic to address sleep disorders associated with abnormal timing of the circadian system, such as jet lag and shift work, but that has now changed. With its patented Ion Powered Pump™ delivery system that mimics the body’s own natural sleep pattern, REMfresh® (CRA-melatonin) may allow more individuals having trouble sleeping to experience drug-free, consistent, restorative sleep and have an improved quality of life.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Larger studies on the effect of REMfresh® (CRA-melatonin) in adults will add additional information to our body of knowledge.
MedicalResearch.com: Any disclosures?
Response: Dr. Brodner is Senior Medical Advisor to Physician’s Seal®, the company that markets REMfresh® (CRA-melatonin). Their web site is www.remfresh.com for further information on the product.
• (Abstract 0385) A Continuous Release Ion Powered Pump Melatonin Delivery System that Overcomes Challenges of Release and Absorption in the Intestines.
• (Abstract 0388) Clinical Evaluation of the Ion Powered Pump Melatonin Delivery System.
• (Abstract 0396) REM Absorption Kinetics Trial: A Randomized, Crossover,
Pharmacokinetics Evaluation of a Novel Continuous Release and Absorption Melatonin formulation versus a Same Strength Immediate Release Formulation, in Healthy Adults
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.
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