August 15, 2020
Disclaimer: None of this is medical advice. See the more detailed disclaimer at the bottom of this page.
I was an early advocate for zinc in the context of COVID-19, having first recommended it on March 17 in The Food and Supplement Guide for the Coronavirus and providing detailed justifications for zinc dosing in the April 10 issue of this newsletter.
On May 8, I covered a report from New York City physicians that suggested that adding 50 mg of zinc to their hydroxychloroquine and azithromycin protocol lowered the risk of either being transferred to hospice or dying by 49%, decreased the chance of requiring invasive ventilation by 44%, and increased the likelihood of being discharged from the hospital and released to home care by 56%, when compared to using the two drugs without the zinc. This study simply compared their results before and after they added zinc to the protocol, so it was an observation suggesting the zinc may have been responsible for the improvement of outcomes rather than showing this to be the case.
While no one has yet reported a randomized controlled trial testing different doses of zinc in different contexts for the treatment of COVID-19, based on mechanistic considerations I believe the following are likely to be true:
- Zinc will be effective on its own, without needing hydroxychloroquine or anything argued to be a zinc ionophore.
- The optimal dose of zinc required is likely to be between 40 and 150 mg per day.
- The ideal way to target it to the upper respiratory tract (nose and throat) would be to obtain a portion of it as zinc acetate lozenges.
A colleague recently drew my attention to a peer-reviewed report of four cases of treatment with high-dose zinc lozenges. As anecdotal evidence, this still doesn't provide the smoking gun that the zinc is effective, but the cases are interesting and consistent with the three bulleted points above.
The first case was a 63-year-old man who never had a COVID-19 test, but got sick five days after contact with a household member who had direct exposure to a laboratory-confirmed COVID-19 case. He developed painful muscle aches, a headache, shaking chills, and a fever. He took three 23-mg zinc citrate lozenges right away, and took a total of nine lozenges over the first 24 hours, equaling 207 mg of zinc. He then continued taking 184 mg zinc per day over the next ten days. His symptoms improved starting on day 2 and his fever was gone by day 3.
The second case was the first case's 57-year-old female partner. She developed mild diarrhea, fatigue, and low-grade fever seven days after contact with the same household member who got case 1 sick. She took only one or two lozenges per day, providing 23-46 mg/d. This didn't help. She continued to get worse, and on day 5 of symptoms she developed a sore throat, dry cough, tight chest, and, while walking, difficulty breathing. On day 10 of symptoms, she developed a severe dry cough, intense pains in her chest and neck muscles, headache, more intense fever, and developed shortness of breath even while at rest.
She then increased her dose of zinc, consuming 7 23-mg lozenges within 5-7 hours, reaching a total of 161 mg of zinc. By the last of those seven lozenges, her cough and shortness of breath already started to improve. The next day, she reduced her zinc dose to two lozenges per day, and her symptoms began getting worse again. She increased it, taking three lozenges in a short period of time, and started improving again. She then took five lozenges (115 mg zinc) per day for the next ten days and gradually improved.
The third case was a 41-year-old female healthcare worker who developed body aches, cough, and sinus pain. By day 3 of symptoms, she had a fever, tested positive for COVID-19, and her other symptoms continued to worsen. She self-tested and documented her oxygen saturation and temperature during this time. By day 4, her oxygen saturation dropped to 94%. On day 6 she developed shortness of breath and started on hydroxychloroquine at 200 mg twice a day. She kept getting worse for the next three days.
The evening of day 9 of symptoms, she started taking 23-mg zinc citrate/gluconate lozenges every four hours for a total of 138 mg/d. Her oxygen saturation bottomed out in the two days before she started the zinc, and once she started the zinc it increased linearly until it had returned to normal after 5 days. Her fever didn't change, and by the data provided may have even increased, in the days between starting hydroxychloroquine and starting zinc, but it disappeared within two days of starting zinc. She continued the zinc at the same dose until fully recovered on day 19.
The fourth case was a 26-year-old female who never got tested, but got sick with COVID-19 symptoms after direct contact with an infected health care worker. She got progressively more sick over the first three weeks. The first week she developed fever, cough, and body aches. The next week she developed shortness of breath and became fatigued. The third week her fever got better but she still had a cough, fatigue, and body aches, and was sleeping more than 14 hours per day. After three weeks she started taking 15-mg zinc acetate lozenges every two hours for a total of ten lozenges or 150 mg of zinc per day. She took this dose of zinc for the next two weeks. Within one day, her symptoms began improving, and within two weeks she was fully recovered.
Only one person had a positive COVID-19 test, but the other three had symptoms consistent with COVID-19 and a plausible chain of transmission from known cases, so these are all reasonably interpreted as COVID-19.
Case reports are anecdotal and cannot show cause-and-effect. However, case three provides excellent timecourse data showing that two objective measures, oxygen saturation and temperature, were strongly associated in time with zinc dosing, and were not as closely associated with the use of hydroxychloroquine, which had been started earlier. Case 2 provides start-and-stop timecourse data where symptoms improved only during the use of high-dose zinc and not during the use of low-dose zinc. Across the four cases, cases improved most rapidly when they started the zinc most rapidly, and took the longest to improve when they started the zinc late.
The fact that only one of the four cases had used hydroxychloroquine, and that even in this case her improvement is more clearly tied in time to the zinc than to the hydroxychoroquine, is consistent with high-dose zinc being effective without the need for any zinc ionophores or drugs.
These cases do not offer a means of comparing the effectiveness of different zinc salts, but they are consistent with zinc citrate, gluconate, and acetate all being effective.
Case 2 is very consistent with 46 mg/d of zinc being insufficient and 115 mg of zinc being sufficient. These two values are very similar to the lower and upper bounds of my estimate of the optimal dose, which I suggested would be at least 40 mg and possibly as high as 114 mg/d, when used as prevention and continued through the course of illness. It is possible she would have needed only 46 mg/d if she had started it weeks in advance of getting sick, but it is very clear that, when starting it after becoming sick, 115 mg/d proved to be superior and 46 mg/d simply didn't work. We don't know if there is a dose lower than 115, but higher than 46, that would have achieved maximal effectiveness. We also don't know if she would have gotten better faster had she used an even higher dose, such as the 184 mg/d used by case 1, the 138 mg/d used by case 3, or the 150 mg/d used by case 4.
These doses are consistent with my recommendations in The Food and Supplement Guide for the Coronavirus, which supplies 46-78 milligrams of zinc per day, depending on how it's implemented, with an extra 36 milligrams of zinc around each potential exposure to the virus, and then additional zinc added for anyone experiencing any symptoms of cold, flu, or COVID-19. Someone who uses a typical zinc supplement and the recommended zinc lozenges, and goes out to the store once a day, would wind up getting 114 milligrams per day of zinc for prevention. During illness the guide steps up the use of lozenges to 8 per day, which would bring the total zinc to 190-222 mg/d for a short period of time.
The Bottom Line
We still don't have evidence showing that zinc works, but these cases add to evidence suggesting it might, and I am personally very bullish on zinc for COVID-19.
I personally would shoot for something closer to 15 mg/d zinc when in a low-risk environment (such as living in an area with low case loads that are not increasing and working remotely), but I would aim for 40-115 mg/d for prevention if living in an area with a high case load or if in a high-risk line of work, and I would increase this to 115-222 mg/d during suspected or known COVID-19 (if you suspect or know you have COVID-19, please seek the advice of a health care practitioner before acting on any of this information).
It is important to balance zinc with copper by getting an extra 1 mg of copper for every 15 mg extra zinc, and if one is at risk of iron deficiency anemia it would be wise to supplement with an extra 18 mg iron bisglycinate per day while using high-dose zinc.
The Food and Supplement Guide for the Coronavirus provides a detailed protocol that combines zinc with the other components I believe are likely to be effective, and I have lots of free, practical advice on zinc supplementation on my web site.
Stay safe and healthy,
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I am not a medical doctor and this is not medical advice. I have a PhD in Nutritional Sciences and my expertise is in conducting and interpreting research related to my field. Please consult your physician before doing anything for prevention or treatment of COVID-19, and please seek the help of a physician immediately if you believe you may have COVID-19.
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* The term “preprint” is often used in these updates. Preprints are studies destined for peer-reviewed journals that have yet to be peer-reviewed. Because COVID-19 is such a rapidly evolving disease and peer-review takes so long, most of the information circulating about the disease comes from preprints.