Looking at Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3with or without Intravenous Vit C: An International, Multicenter, Randomized Trial
Since the emergence of the Covid pandemic, various combinations of drugs and nutraceuticals have been used in attempt to decrease hospitalizations and help millions of people suffering worldwide. One of these combinations, consists of hydroxychloroquine (HCQ), azithromycin (AZM) and Zinc, also known as the Zelenko protocol.
The question raised with regularity by many is “Are these medications being used “off label” to treat Covid-19 disease valid or are they unfounded? Where is the research?”
This is one study with supportive references to many other studies around the world demonstrating efficacy of early treatment for Covid 19 with a combination protocol of medications, minerals, and vitamins.
What does ‘off-label’ mean? Is it legal? “Off-label prescribing is when a physician gives you a drug that the U.S. Food and Drug Administration (FDA) has approved to treat a condition different than your condition. This practice is legal and common. In fact, one in five prescriptions written today are for off-label use.”0 It is not uncommon today to hear the use of these medications being described as “unproven therapies” rather than “off-label”. This study is an example of medications being used “off-label” in a hospital setting to prevent the progression of Covid-19.
This study published November 25, 2021, in Cureus Journal of Medical Science, is a 237 patient, peer-reviewed, randomized controlled, prospective trial conducted in Australia and Turkey at seven participating hospitals.
The study aimed to determine the effectiveness of HCQ, AZM, zinc, and vitamin D with or without IV vitamin C (IVC) among hospitalized patients with Covid infection.1
Why this Treatment Combination?
Chloroquine was found to block viral infection in vitro (in the lab). HCQ has been shown to have a higher potency against SARS-CoV-2 in vitro and carries a more desirable safety profile than chloroquine. A meta-analysis of over 290 worldwide trials in more than 412,000 patientsfound a significant decrease in morbidity and mortality in Covid patients treated with HCQ. A separate meta-analysis of 32 studies in more than 54,600 patients showed early treatment to improve symptoms and prevent death by 64-75%.1
AZM, a commonly used antibiotic, has antiviral and anti-inflammatory properties. It has demonstrated activity against SARS-CoV-2 in vitro when used in combination with HCQ. When used as early treatment, the combination of HCQ with AZM shortened hospital length of stay and reduced recovery time in a clinical study of 83 patients. 1
Zinc boosts immunity and has antiviral properties though needs to get into a virus-infected cell in order to exhibit effects. To increase intracellular zinc, a zinc ionophore is necessary such as HCQ. Quercetin and Green Tea are also examples of ionophores… In vitro studies demonstrated the anti-viral properties of zinc by inhibiting SARS-CoV RNA polymerase and ACE2 expression.2 Low zinc levels have been linked with severe Covid disease and zinc supplementation has been found to reduce severity of Covid symptoms.3,4
Vitamin C is a known antioxidant, immune booster with antiviral properties. It has shown benefit in the treatment of pneumonia and acute respiratory syndrome. Vitamin C deficiency is relatively common and is the fourth leading nutrient deficiency in the US. There is an increased demand for vitamin C when fighting infections and adequate levels are required for proper immune response.5
Vitamin D is critical to immune function and the importance of adequate levels to protect against viruses, pathogens and respiratory infections has been demonstrated in studies. Low vitamin D levels have been shown to be a risk factor for severe Covid disease leading to hospitalization and increased mortality.6
A total of 237 Covid hospitalized patients aged 22-99 years were enrolled in the study. The participants were randomly selected for group 1 or group 2.
73% had at least one comorbidity including lung disease, heart disease, diabetes, cancer, autoimmune disease, history of heavy smoking.
70% had difficulty breathing; 7% severe and 21% moderate
60% headache, 48% cough, 46% fever
5 vaccinated at the time of the study.
6% admitted to ICU, 40% required oxygen
55% severely deficient in vitamin D, 42% deficient, and 3% insufficient. No study participants had optimal vitamin D levels.
Group 1 received HCQ, AZM, Vit D and zinc
Group 2 received HCQ, AZM, Vit D and zinc plus IV vitamin C
Dosing was as follows:
HCQ 400 mg daily x 1 day, followed by 200 mg daily x 6 days
AZM 500 mg daily x 1 day, followed by 250 mg daily x 4 days
Zinc citrate 30 mg elemental zinc daily x 14 days
Vitamin D3 5000 IU daily x 14 days
IVC (sodium ascorbate) 50 mg/kg every 6 hours on day 1, followed by 100 mg/kg every 6 hours x 7 days (max dose of 50 g/24 hours)
The primary outcome was assessed by mortality and need for invasive mechanical ventilation at any point in the first 15 days.
The secondary outcome was measured at 15 days and 45 days. Outcomes assessed were mortality, need for humidified high-flow oxygen, invasive mechanical ventilation, admission to ICU, days in the ICU, days in the hospital, extracorporeal support and renal replacement therapy.
Safety outcomes were determined by closely monitoring for serious cardiac events and unexpected death 24 hours after receiving the study therapeutics. Adverse events such as nausea, vomiting and diarrhea were monitored for the first 10 days.
236 of the 237 participants fully recovered.
51% of all participants fully recovered after 15 days and the other 49% at 45 days.
Addition of vitamin C led to a significantly quicker recovery, at day 15 ( 57% vs 39%)
Low vitamin D status strongly correlated with ICU admission and longer hospital stay.
One 70 year old female patient died. She had a history of heart disease, lung disease, and severe vitamin D deficiency. The authors propose the severely low vitamin D (level of 6) greatly contributed to this outcome.
No cardiac adverse events were identified in any study patients. A proportion of patients experienced mild to moderate transient side effects (diarrhea, nausea, vomiting).
99.6% of study participants reached a full recovery with this protocol.
This study demonstrates HCQ, AZM, vitamin D3, and zinc with or without vitamin C as an effective and safe therapeutic combination for the treatment of Covid by reducing mortality and aiding full recovery.
With such a prevalence of vitamin D deficiency among the patients, this study suggests a link between low vitamin D status and more severe Covid disease which is in agreement with other studies. Further trials to assess the efficacy of adjunct treatment with high dose vitamin D3 are warranted.
Author: Dr. Valerie Donaldson is the Founder and Medical Director of Regenerative Medicine Center (RMC). She graduated from Rush Medical College and is Board Certified in Internal Medicine, Emergency Medicine, and certified in Anti-Aging Medicine, Functional Medicine, and Stem Cell Therapy. As an attending physician at UPMC Presbyterian Hospital Emergency Department, she authored research papers on the effects of Incubation Techniques on the Traumatic Cervical Spine and the use of lab results in the Emergency Room.