Researchers in Iraq have published an important paper this October, on a full randomized trial, which will hit home for many of us in our community, who have watched one courageous local doctor use melatonin to battle covid-19 for the past year and a half, although it has not been accepted as part of standard Covid-19 treatment (more on that later). The purpose of this trial conducted in Iraq, which included 158 severely-ill hospitalized Covid-19 patients, was to determine the effect of melatonin on thrombosis, sepsis, and mortality rate.
The results are clear, especially given the huge benefit shown even with only 10mg of melatonin added to daily standard treatment. The randomized study results showed a 17% mortality rate of participants who were only taking standard treatments, compared to a 1% mortality rate for patients who were taking melatonin along with standard treatments together. (1)
For added perspective, that’s 1 out of 82 patients, who died in the melatonin group, whereas 13 of 76 patients died in the control group that was not taking melatonin.
The patients given melatonin were also significantly less likely to develop sepsis (35.5% control group, and 8.5% melatonin group) and thrombosis (23.7% in control group, and 11% in melatonin group).
This prospective, randomized clinical trial was conducted from 1 December 2020 to 1 June 2021 at Al-Shifaa hospital in Mosul, Iraq, and published this October 2021.
There were 158 patients with severe COVID-19 included in the study, 82 patiens in the melatonin group (who received 10 mg melatonin in addition to standard therapeutic care), and 76 in the control group (given standard therapeutic care only). The physician then evaluated and recorded the incidence of thrombosis, sepsis, and mortality rate on days 5, 11, and 17 of symptoms.
All patients of the control group received standard therapy ((Oxygen therapy, Antiviral agents: Remdesevir (day one 200 mg intravenously infusion during 1 hour, then in day 2, 3, 4 & 5 the patients given 100 mg intravenously infusion during 1 hour), Antibacterial agents: levofloxacin 500 mg intravenously per day was used empirically for secondary bacterial infections, Corticosteroid: (dexamethasone 24 mg intravenously per day), Anticoagulant: enoxaparin 6000 unit once daily for prophylaxis and twice daily for therapeutic treatment of thrombosis). Whereas All the intervention group patients received standard therapy plus 10 mg melatonin (Natrol®) once daily 20-30 minutes before bed time for 14 days following diagnosis.
A research paper titled “Implications for Systemic Approaches to COVID-19”, also showed that markers are impacted so greatly by melatonin. (2)
The authors of this paper note, “Many of the pharmacological interventions that are capable of significant system-wide effects, such as the leading COVID-19 medications Remdesivir and Tocilizumab, are often accompanied by negative side-effects. Therefore, it is imperative to establish adjunctive interventions that can address the broader, holistic factors behind COVID-19 and do not result in dangerous side effects or numerous contraindications.”
“Some individuals who have fully cleared the virus still exhibit significantly impaired cardiopulmonary, central nervous, and peripheral nervous systems. This suggests an eventual potential spike in pulmonary fibrosis, cardiopulmonary events, neuronal damage, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis,” the researchers state, showing all the more need for something to control the cytokine storm that is capable of doing so much long-term damage to the body during a Covid infection, even those who have “recovered”.
The authors note that adjunctive therapy using Vitamin D3 and melatonin both affected multiple markers in Covid-19 patients.
“Vitamin D3 demonstrated very large reductions in TNF-a and IL-6 trans levels, moderate effects on increasing IL-6 classic levels, and small dysregulation of IL-10,” the authors state.
However, researchers found that Melatonin, “had the greatest number of very large effects of any intervention or medication, with major improvements in C-reactive protein, IL-6 trans, and TNF-a,” even compared to standards of care such as Remdesivir and Tocilizumab.
“Melatonin, vitamin D3, and meditation had very large or large effects on 7 inflammatory markers, Remdesivir and Tocilizumab had very large or large effects on 1 inflammatory marker, though that single effect was extremely large,” the authors noted.
Looking back on what seemed “impossible”
It was over a year and a half ago, on March 20, 2020, that local doctor Richard Neel, MD, MPH called The Devine News to share his ideas on this very topic….covid-19 versus melatonin.
On that chilly, gloomy day as the pandemic loomed, he acknowledged that randomized, controlled studies needed to be done, but he noted that they would take a year or more to complete and put simply– “people are dying right now.”
As new studies like the one in Iraq come out, garnering attention, it is fun to reflect back on that day in March when my Google search of the world wide web literally turned up little to nothing in regards to Covid-19 versus melatonin…nothing but one pre-print paper which was written by one of Dr. Neel’s old medical professors (more on that later) and a short radio clip interview that Neel had done earlier that morning.
It was certainly an out-of-the-box, very new idea, and Dr. Neel wanted us to share it with the world. However, there was plenty of evidence of melatonin affecting other diseases such as sepsis, ebola, neurodegenerative diseases, cancer, and various infections (10,11,12, 13), and importantly for Covid-19, melatonin’s powerful ability to reduce inflammation and prevent deadly cytokine storms.
At that time, physicians in Italy were warning that they were making “war time” like decisions, treating patients with the best chance of survival, unable to treat them all. New York soon began seeing 400 deaths a day. It was unreal.
During that first interview (4), I was both honored and terrified. Honored because this awesome doctor who I have so much respect for, had chosen us to help his put his idea into words; terrified because it was experimental, and because it was kind of unbelievable that our little newspaper would be the first to publish and print an article that could literally affect the whole world.
I did the interview on a Saturday, using my home computer, and presented a rough draft to my mom/publisher at my kitchen table. She put on her glasses, and read every word carefully, more closely than any other article I’ve ever written. She nodded her head and said, “Let’s do this.”
It was history in the making. We didn’t know it then, but those articles would eventually be read in every single state of the United States, and by people on every single continent of the world.
If Dr. Neel was willing the put his name and reputation on the line for this, we were too. We published the article that day on our website and printed it on the front page the following Tuesday. To our knowledge, the first printed article on the topic, at least in the United States.
It was just an idea, at that point, that he wanted to share with other physicians, hoping the hospitals would try it. He was very clear that it should be done only under the direction of a doctor. However, he soon put his idea into action, treating Covid patients in our community, who read the article and went to him for help.
Dr. Neel called us on press day to let us know he had begun treating covid patients, and I will never forget it. It worked. We stopped what we were doing and rearranged the whole front page.
The week after our first article was published, Covid-19 began to hit Medina County. Calls poured into the news office, giving nothing but good feedback. Throughout the following weeks and months in 2020, we interviewed Dr. Neel and several of his patients, as well as many other scientists, researchers, and doctors from across the world who believed in this treatment.(5,6,7,8,9)
The series of articles we reported on this topic are the most meaningful, impactful stories that we have ever published.
As I always say, the Covid-19 pandemic was a war, and the retired Air Force Colonel and Chief Flight Surgeon was no stranger to war time, having flown many fighter jet missions in his younger days. He also worked as a subject matter expert in chemical and biological weapons at the Pentagon during the 2001 Anthrax and Terrorist attacks. Along with his MD, Dr. Neel also held a Master’s in Public Health from Harvard. If anyone was qualified to come up with an idea like this, it was him.
Through our interviews, Neel actively pushed for someone to do a randomized, double blind studies. Researchers from all over started calling his clinic to learn more, and discussed doing studies –including some from New York, Canada, California, Florida, Brazil, Italy, and more. A few courageous doctors began using the high dose melatonin on their patients, and reported the same success. Many hospitals have also started using melatonin in smaller doses.
While melatonin v Covid-19 may be still considered experimental, studies done in Thailand, New York, Iraq, and more have now suggested it helps significantly. Some studies like the one done by the Cleveland Clinic and the one being done by Dr. Rafael Castillo in Thailand have made national headlines.
The work and research of Dr. Russell Retier, Phd, who we have also interviewed, is at the heart of many of these studies….for he has researched and published papers on the many mechanisms and applications of melatonin for years. In fact, when Dr. Neel was going to medical school, he was in Dr. Reiter’s class.
Dr. Neel has now treated thousands of patients with high dose melatonin and a specific regimen, many from right here in our community. He believed in it so strongly and observed it working so well that he felt it would be unethical for him to conduct a controlled, randomized study (where some patients get melatonin, and some don’t).
One of the many patients from our hometown, who called and shared her story with us, broke down into tears as we talked. “That article saved my life,” she said, “And there’s no telling how many others.”
Comments from Dr. Richard Neel this week
“The study in Iraq adds to the growing body of evidence that melatonin works as well as myself and many extremely reputable scientists have been saying it does,” Dr. Neel said. “The second study highlights that melatonin reduces the markers associated with the cytokine storm even better than Remdesivir.”
Neel adds, “It is encouraging that they obtained the results they did with such low dosing. I have no doubt the results would have been even more dramatic if they had used a higher therapeutic dose.”
New research could lead to a “whole new ball game” in medicine
There is even more breakthrough research starting to come out, showing why and how melatonin could possibly have such an effect on so many DIFFERENT diseases and conditions. Look for a future article on melatonin’s ability to regulate biomolecular condesates and molecular phase separation. (14)
The authors state that the novel theoretical review was “presented with the intention to spur further research interest and exploration in the full, multi-faceted potential of melatonin in the regulation of biomolecular condensates that could provide solutions and answers to existing and future challenges and questions in this exciting and promising field of study.”
“Phase separation is quietly going to change science and medicine,” said one of the authors, Doris Loh. Loh recently co-authored the research paper with a local professor Russell Reiter, on the topic that brings “a whole new ball game” to the table for researchers, scientists, and physicians trying to understand the pathology of diseases and how to combat them.
By Kayleen Holder, Editor & Kathleen Calame, Publisher
1-Hasan, Z. T., Atrakji, D., & Mehuaiden, D. (2021). The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, S1201-9712(21)00798-0. Advance online publication. https://doi.org/10.1016/j.ijid.2021.10.012
2- Castle, R. D., Williams, M. A., Bushell, W. C., Rindfleisch, J. A., Peterson, C. T., Marzolf, J., Brouwer, K., & Mills, P. J. (2021). Implications for Systemic Approaches to COVID-19: Effect Sizes of Remdesivir, Tocilizumab, Melatonin, Vitamin D3, and Meditation. Journal of inflammation research, 14, 4859–4876. https://doi.org/10.2147/JIR.S323356
10- (Beneficial effect of melatonin in treatment of neonatal sepsis, 2018)
El-Gendy, F. M., El-Hawy, M. A., & Hassan, M. G. (2018). Beneficial effect of melatonin in the treatment of neonatal sepsis. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 31(17), 2299–2303. https://doi.org/10.1080/14767058.2017.1342794
11- Effects of Melatonin Treatment in Septic Newborns, 2001)
Gitto, E., Karbownik, M., Reiter, R. J., Tan, D. X., Cuzzocrea, S., Chiurazzi, P., Cordaro, S., Corona, G., Trimarchi, G., & Barberi, I. (2001). Effects of melatonin treatment in septic newborns. Pediatric research, 50(6), 756–760. https://doi.org/10.1203/00006450-200112000-00021
12- (Melatonin on oxidative stress resistance to bacterial, parasitic and viral infections: a review, published in a journal called Acta Tropica/Elsevier, 2014).
Vielma, José & Bonilla, Ernesto & Chacín-Bonilla, Leonor & Mora, Marylú & Medina-Leendertz, Shirley & Bravo, Yanauri. (2014). Effects of melatonin on oxidative stress, and resistance to bacterial, parasitic, and viral infections: A review. Acta tropica. 137. 10.1016/j.actatropica.2014.04.021.
13- Melatonin and viral infections, published by Journal of Pineal Research, 2004).
Bonilla, Ernesto & Valero, Nereida & Chacín-Bonilla, Leonor & Medina-Leendertz, Shirley. (2004). Melatonin and viral infections. Journal of pineal research. 36. 73-9. 10.1046/j.1600-079X.2003.00105.x.
14-Loh, D., & Reiter, R. J. (2021). Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders. Antioxidants (Basel, Switzerland), 10(9), 1483. https://doi.org/10.3390/antiox10091483