12 Natural Alternatives to Oral Ivermectin Evidence based Review (2024) Part 2 of 4
This practical guide on natural alternatives has more than 200 supporting studies that represent the best of science-backed strategies for nutritional interventions in the prevention and treatment of
By: Dr Frank Yap, M.D. - November 12, 2024
3. Zinc - Anti-viral
Zinc is another powerful immune nutrient known for its benefits for providing immune health support and inflammation reduction as well as for improving cold and respiratory symptoms, wound healing, acne reduction, and lowering the risk of age-related diseases. This trace element is essential to to cell function and involved in over 100 enzymes. Research on atherosclerosis and diabetes mellitus suggests that zinc deficiency may contribute to low-grade systemic inflammation.
Aging is associated with compromised immunity, that just means that your immune response to pathogens and infections starts to slow and is less robust, including a reduced vaccine immune response/efficacy.
Improving zinc intake/zinc status improves/modulates/enhances immune function. The flip side is, while some aspects of immunity slow, others increase. Uncontrolled immune responses drive excess inflammation. Zinc helps to balance all of this.
The National Institutes of Health (NIH) states:
“Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of approximately 100 enzymes and it plays a role in immune function, protein synthesis, wound healing, DNA synthesis, and cell division. Zinc also supports normal growth and development during pregnancy, childhood, and adolescence and is required for proper sense of taste and smell.”
Foods that are high in zinc include oysters, crab, lobster, mussels, red meat, and poultry. Cereals are often fortified with zinc. Most multivitamin and nutritional supplements contain zinc.
Zinc and COVID-19
The use of zinc for SARS-CoV-2 was a topic routinely flagged by COVID fact checkers as “misinformation,” so word didn’t really get out about its potential as an anti-COVID agent. However, there are more than 35 studies that provided evidence on zinc’s promise for keeping people healthy if they get COVID.
Zinc gluconate (R), zinc acetate (R) and zinc sulphate (R) have all been shown to reduce the severity and duration of viral infections such as the common cold. Zinc also appears to be the key ingredient in treatment protocols using hydroxychloroquine (HCQ).
The reason for this is because HCQ is a zinc ionophore (zinc transport molecule), meaning it’s a drug that improves your cells’ uptake of zinc. Once inside your cells, zinc prevents viral replication. This is also why zinc and zinc ionophores need to be taken very early in the illness, or as a prophylactic.
The problem is that zinc is largely insoluble and cannot easily enter through the fatty wall of your cells. Getting all the way into the cell is crucial, as this is where the viral replication occurs. This is why zinc ionophores are so important.
Aside from hydroxychloroquine, other natural, and safer, zinc ionophores include quercetin and epigallocatechin-gallate (EGCG). If given early, zinc along with a zinc ionophore should, at least theoretically, help lower the viral load and prevent the immune system from becoming overloaded.
Check out the evidence tracker on zinc and COVID-19 from c19zinc.com (constantly updated).
Safety: Taking zinc long term is typically safe for healthy adults, as long as the daily dose is under the set upper limit of 40 mg of elemental zinc (PubMed). Be aware that typical daily doses of zinc provided by zinc lozenges generally exceed tolerable upper limits for zinc, and for this reason, they should not be used for longer than about a week.
Excessive doses may interfere with copper absorption, which could negatively affect your immune system as it can cause copper deficiencies, blood disorders and potentially permanent nerve damage. Zinc can also impair the absorption of antibiotics, and use of zinc nasal gels or swabs has been linked to temporary or permanent loss of smell.
When it comes to zinc supplementation, more is not necessarily better. In fact, it can frequently backfire is you do not also maintain a healthy zinc-to-copper ratio. As explained by Chris Masterjohn, who has a Ph.D. in nutritional sciences, in an article and series of Twitter posts:
“In one study, 300mg/day of zinc as two divided doses of 150 mg zinc sulfate decreased important markers of immune function, such as the ability of immune cells known as polymorphonuclear leukocytes to migrate toward and consume bacteria.
The most concerning effect in the context of COVID-19 is that it lowered the lymphocyte stimulation index 3 fold. This is a measure of the ability of T cells to increase their numbers in response to a perceived threat. The reason this is so concerning in the context of COVID-19 is that poor outcomes are associated with low lymphocytes …
The negative effect on lymphocyte proliferation found with 300 mg/day and the apparent safety in this regard of 150 mg/d suggests that the potential for hurting the immune system may begin somewhere between 150-300 mg/d …
It is quite possible that the harmful effect of 300 mg/d zinc on the lymphocyte stimulation index is mediated mostly or completely by induction of copper deficiency …
The negative effect of zinc on copper status has been shown with as little as 60 mg/d zinc. This intake lowers the activity of superoxide dismutase, an enzyme important to antioxidant defense and immune function that depends both on zinc and copper …
A study done with relatively low intakes of zinc suggested that acceptable ratios of zinc to copper range from 2:1 to 15:1 in favor of zinc. Copper appears safe to consume up to a maximum of 10 mg/d.
Notably, the maximum amount of zinc one could consume while staying in the acceptable range of zinc-to-copper ratios and also staying within the upper limit for copper is 150 mg/d.”
Another factor to keep in mind is that certain additives can inhibit zinc absorption, which is the complete opposite of what you’re looking for. For instance, research has shown citric acid, glycine, mannitol and sorbitol can reduce zinc absorption,48 so zinc lozenges containing these ingredients may be less useful.
Zinc Form and Dosage
There are several types of zinc supplements. Supplements contain several forms of zinc, including zinc gluconate, zinc citrate and zinc picolinate. The percentage of elemental zinc varies by form. To find out the percentage of elemental zinc in each form, check out elemental zinc percentage.
Chelated zinc is a general form of supplementary zinc in which the zinc is chelated — or bound — to a compound to make it easier for the body to absorb. Zinc picolinate or zinc gluconate are formed when zinc is chelated to picolinic acid or gluconic acid, so the main difference between zinc gluconate and picolinate is what compound it is bound to.
To find out which zinc supplement to consider, check out best zinc supplement.
Most people do not lack an intake of zinc, but in disease state, there might be an increase in demand by the body. The FLCCC I-Prevent protocol recommends 20 - 50 mg a day for prevention and the FLCCC I-Care protocol recommends 75 - 100 mg a day for early treatment of COVID-19. This should not be taken long term without evaluation of your zinc/copper ratios.
The ideal zinc form should come from zinc lozenges to spread the zinc through the tissues of the nose, mouth and throat. It should be accompanied by at least 1 mg copper from food and supplements for every 15 mg zinc.
Do take note that you should keep the dosage back to within 40 mg/d once the exposure risk is back to normal.
Related: Best Anti Inflammatory Supplements 2024
4. Nigella Sativa (Black Seed Oil) and Cytokine Storm - Anti-inflammatory
Nigella sativa (N. sativa) is a small flowering plant that grows in Southwest Asia, the Middle East, and Southern Europe (Source). This shrub produces fruit with tiny black seeds. Commonly referred to as black seed, N. sativa seeds go by many other names, such as black cumin, black caraway, nigella, fennel flower, and Roman coriander (Source).
Black seed oil is extracted from N. sativa seeds and has been used in traditional medicine for over 2,000 years due to its many therapeutic benefits.
Thymoquinone which is the active ingredient in N. sativa seeds has demonstrated effects in significantly reducing the cytokine storm chances and consequent mortalities (Source).
Summary results of more than 10 published clinical studies are available on this dedicated webpage: c19ns.com.
Geneva here: Nigella Sativa does have anticoagulant properties. It’s thymoquinone, a compound that has been shown to inhibit platelet aggregation, is a key factor to be considered in blood clotting prevention. Nigella Sativa could potentially help prevent the formation of harmful blood clots.
5. Melatonin- Anti-inflammatory and anti-viral
Melatonin is a hormone produced by the pineal gland in the brain, mainly during the night, that helps regulate circadian rhythms [Source]. Its levels decrease with aging. Most melatonin supplementation studies have evaluated its ability to control sleep and wake cycles, promote sleep, and reduce jet lag.
The potential utility of melatonin in treating COVID patients has not gone unnoticed, with a PubMed search combining melatonin and COVID producing more than 50 citations.
Check out the evidence tracker on melatonin and COVID-19 from c19melatonin.com (constantly updated). As of January 2023, there are more than 15 published clinical studies of melatonin for treatment and prevention in COVID-19 and the results are promising even when it's given as a late treatment.
Melatonin is a hormone synthesized in your pineal gland and many other organs. While it is most well-known as a natural sleep regulator, it also has many other important functions. For example, melatonin is a potent antioxidant (Antioxidants, 2020) with the rare ability to enter your mitochondria, where it helps “prevent mitochondrial impairment, energy failure and apoptosis of mitochondria damaged by oxidation.” It also helps recharge glutathione and glutathione deficiency has been linked to COVID-19 severity.
Production of melatonin diminishes with age, contributing to immune dysfunction and increasing oxidative stress, inflammation, and infection susceptibility (Ref). In addition, infectious viruses can suppress melatonin production, disrupting circadian controls and impairing immune function (Ref).
According to a review (Cardinali et al. 2020), melatonin might counteract the consequences of COVID-19 via salutary effects on the sleep/wake cycle and more generally on chronobiology, as well as through its antioxidant and anti-inflammatory effects.
Based on melatonin’s therapeutic potential and well-established safety profile, it has been suggested those at higher risk for severe illness and complications from viral respiratory infection, including the elderly and those with chronic medical conditions, may benefit most from regular use of 3–10 mg melatonin at bedtime (Ref).
Fluvoxamine (Selective Serotonin Reuptake Inhibitor) might also exert beneficial effects in COVID patients through its well-characterized ability to substantially increase (~ 2–3-fold) night-time plasma levels of melatonin. This increase appears to result from fluvoxamine’s inhibition of the melatonin-metabolizing liver enzymes (von Bahr et al. 2000).
An Iranian randomised controlled trial (Arch Med Res 2021), studied 74 mild to moderate hospitalized patients. The study showed that adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.
Some researchers have suggested high doses of melatonin, ranging from 50 to 200 mg twice daily, might help treat patients hospitalized for severe acute respiratory illness (Ref).
In a small Philippine case series study of 10 hospitalised COVID-19 patients, high dose melatonin (hdM) was given in addition (adjuvant) to standard therapy. According to the authors:
"High dose melatonin may have a beneficial role in patients treated for COVID19 pneumonia, in terms of shorter time to clinical improvement, less need for MV, shorter hospital stay, and possibly lower mortality."
Safety: If you take a melatonin supplement, be careful: Too much can cause daytime sleepiness. There is no federal RDA nor any formal advice on supplement dose ranges. Based on an on-going Spanish study, a 2 mg daily dose protocol is being investigated for prevention of COVID-19. Do take note that the dosage for 'prevention' and 'treatment' is different, For prevention or maintenance, a lower dosage is normally recommended whereas a 'treatment' or 'therapeutic' dosage is normally higher.
Typical doses of 1–10 mg/day melatonin appear to be safe for short-term use (Source). Reported side effects, which are usually minor, include dizziness, headache, nausea, upset stomach, rash, and sleepiness. However, some reports have linked high blood levels of melatonin with delayed puberty and hypogonadism.
Studies have not evaluated melatonin supplementation during pregnancy and breastfeeding, but some research suggests that these supplements might inhibit ovarian function (Source). Therefore, some experts recommend that women who are pregnant or breastfeeding avoid taking melatonin.
By: Dr Frank Yap, M.D.