Advanced Mediterranean Diet

Melatonin is a commonly-available over-the-counter sleep aid. In 2020, the Cleveland Clinic did epidemiological study that linked melatonin usage with a 30% reduced risk of contracting COVID-19. Clinical psychologist Michael J Breus, Ph D has an article at Psychology Today on the use of melatonin as a preventative or treatment for COVID-19.

Melatonin, of course, is best known as a sleep regulator. But melatonin also plays an important role in regulating the immune system. One way it does so is by influencing the production of small proteins known as cytokines, which act as signalers from the immune system to cells around the body. Cytokines can be inflammation producing (pro-inflammatory cytokines) or inflammation restricting (anti-inflammatory cytokines). Melatonin has been shown to reduce the production of pro-inflammatory cytokines. Melatonin also is well known to be an antioxidant, neutralizing free radical cells and limiting oxidative stress and damage, which contribute inflammation.

Pro-inflammatory cytokines serve an important purpose, in marshaling the inflammatory response that fights off viruses, bacteria, and other pathogens. That’s the protective mechanism of inflammation at work. But for the pro-inflammatory cytokine response to be beneficial, it must be proportional to the threat. A too vigorous response of pro-inflammatory cytokines creates a dangerous amount of inflammation—and can actually serve to spread the viral infection, rather than tamping it down. It is this inflammatory overreaction and viral spread that appears to take place in the most serious cases of COVID-19.

I spent 10 minutes on the Internet trying to find the appropriate dose of melatonin for its possible preventative and treatment powers. But no luck. It’s likely in the range of 1 to 10 mg/day, typically taken at night or bedtime. For insomnia in my hospitalized patients, I start at 1.5 mg. Most of my colleagues use a much higher dose. Dr Josh Farkas at emcrit.org suggests that the treatment dose is 5 mg/day.

As always, check with your personal physician first.

Steve Parker, M.D.

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Remdesivir and hydroxychloroquine don’t do much good for hospitalized COVID-19 patients, according to this abstract of the SOLIDARITY trial:

BACKGROUND

World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19).

METHODS

We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.

RESULTS

At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.

CONCLUSIONS

These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.

Steve Parker, M.D.

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