10 Natural Alternatives for Paxlovid (2022) - Evidence based Review
In March 2022, the Biden administration launched the Test to Treat initiative. The initiative’s goal was to allow people to be tested for COVID-19 at
pharmacies or health centers that have an on-site clinic, like CVS
MinuteClinic. If you had a positive test, you’d then receive an antiviral
prescription at the pharmacy before leaving the building.
While well-intentioned, there were many roadblocks that made the Test to Treat initiative difficult to roll out. One big barrier was the fact that most pharmacies don’t have clinics in the same building. In late May 2022, there were only about 2,500 Test to Treat locations in the entire U.S. This left many Americans still struggling to get a prescription from their healthcare providers in enough time to benefit from Paxlovid.
In response to this, the FDA updated Paxlovid’s EUA in July 2022. This change allows pharmacists to prescribe Paxlovid directly to people who have tested positive for COVID-19. This means that you might be able to head over to your local pharmacy for the medication without having to make other stops along the way. Keep in mind that not all pharmacies may offer this service.
- Your current health records, which must be less than a year old (either electronic or printed records are fine)
- Your most recent liver and kidney function tests, which must be less than a year old
- A complete list of all medications that you take, including any over-the-counter (OTC) medications, vitamins, and supplements
How much will Paxlovid cost?
New Paxlovid Dose Pack Authorized by FDA
- The standard packaging that is currently in distribution: 300 mg nirmatrelvir;100 mg ritonavir - Each carton contains 30 tablets divided in 5 daily-dose blister cards. Each blister card contains 4 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.
- The new packaging option that will be in distribution later this month: 150 mg nirmatrelvir; 100 mg ritonavir - Each carton contains 20 tablets divided in 5 daily-dose blister cards. Each blister card contains 2 nirmatrelvir tablets (150 mg each) and 2 ritonavir tablets (100 mg each). Nirmatrelvir tablets and ritonavir tablets are supplied in separate blister cavities within the same child-resistant blister card.
The COVID-19 Treatment Guidelines Panel’s Statement on Therapies for High-Risk, Non-hospitalized Patients With Mild to Moderate COVID-19 (Last Updated: Sept. 26, 2022)
Preferred therapies. Listed in order of preference:
- Ritonavir-boosted nirmatrelvir (Paxlovid)
At the same time, the CDC wrote, “a brief return of symptoms may be part of the natural history of [coronavirus] infection in some persons, independent of treatment with Paxlovid and regardless of vaccination status.”
The CDC said there is no evidence for more treatment in rebound cases, though people should isolate again for at least 5 days so they won’t pass COVID-19 to others.
People who have a rebound after taking Paxlovid can report their cases to Pfizer’s adverse event reporting page.
Researchers found that when patients received a placebo instead of treatment, a portion of them still experienced a rebound of their symptoms after they had initially improved.
“Symptom return is common,” said Dr. Davey Smith, the chief of infectious diseases and global public health at the University of California, San Diego School of Medicine, who led the study. “It doesn’t mean that things are going south. It’s just the natural way the disease goes.” What is surprising, however, is how many people may experience a rebound, he said. (Read More)
Paxlovid for long COVIDA report from the Veterans Affairs health system (now in preprint), the largest in the United States, is the first study to look at longer term effects. Dr. Ziyad Al -Aly and colleagues, who have published many of the important papers on Long Covid in leading peer review journals, now studied over 9,000 paxlovid treated patients (within 5 days of symptom onset; in March-June 2022 during Omicron and subvariant waves) and compared the results to ~47,000 controls. Their mean age was 65 years and 12% were female.
The complex medical condition involves more than 200 symptoms ranging from exhaustion and cognitive impairment to pain, fever and heart palpitations that can last for months and even years following a COVID-19 infection.
According to details of the study, posted on Clinicaltrials.gov, the randomized, placebo-controlled trial will test Pfizer's treatment or a placebo in 1,700 volunteers aged 18 and older.
The Duke Clinical Research Institute is supervising the study, which is scheduled to start on Jan. 1, 2023.
The trial will investigate a leading theory of the cause of long COVID, which holds that fragments of the virus persist in the tissues of some individuals, causing prolonged symptoms.
Patients in several case studies have reported improvements in their symptoms after taking Pfizer's antiviral treatment, and several physicians have called for the drug to be studied in a large, scientifically rigorous study in patients with long COVID.
Paxlovid, which combines a new Pfizer pill with the old antiviral ritonavir, is currently authorized for use in the first days of a COVID infection to prevent severe disease in high-risk patients.
Estimates of long COVID prevalence range from 5 to 50% of people who have had a COVID-19 infection. It affects people who have had both mild and severe COVID-19, including children, and can be severe enough to keep people out of work.
Paxlovid's Contraindications and Drug Interactions
Pfizer anti-COVID pill's interaction with common drugs will narrow its benefit, experts say | National Post:
The buzz around PAXLOVID™ has largely obscured one major downside of this treatment. Ritonavir can interact dangerously with a slew of commonly used medications, pumping up the potency of blood thinners, heart-arrhythmia therapies, epilepsy drugs and others. And the patients targeted for its use – those most at risk of serious COVID disease because of age and other health issues – are also the people most likely to be taking those “contraindicated” medications.
In some cases, the interactions could be managed, but it’s clear the problem will limit the pool of potential recipients, experts say. “It has a utility, it has a use,” said Dr. Gerald Evans, head of the Infectious Diseases Division of the Queen’s University medical school. “(But) I certainly would not call it a game-changer.” “A patient on blood thinners could end up with spontaneous bleeding in the gastrointestinal tract or brain”, noted Evans.
“Someone taking pills for hypertension might see their blood pressure fall so much they pass out”, said Dr. Andrew Hill, a pharmacology researcher at the U.K.’s Liverpool University. “There are all kinds of ways that PAXLOVID™ could cause serious harm,” he said.
Ritonavir is also used in HIV treatments, so there is a wealth of knowledge about those potential drug interactions. The U.S. Food and Drug Administration (FDA) product monograph for PAXLOVID™ lists over 100 drugs that it says should not be taken with the COVID pills, or whose use ought to be carefully monitored. The figure below lists a few of these drugs as well as liver enzymes whose functions are impacted by Ritonavir.
See Sections 4 and 7 of the FACT SHEET FOR HEALTHCARE PROVIDERS and a publication on JAMA by Ross et al. Pharmacists as prescribers may be a problem since they are not authorized to manage, deprescribe and be responsible for the OTHER drugs.There are many Paxlovid drug-interaction checkers, but the one we find most useful is from the University of Liverpool summarized in the Table below. For most, the interactions can be avoided by holding the 'medication of concern' until the 5-day treatment course is completed.
Natural Alternatives to PaxlovidPAXLOVID is not recommended in patients with severe kidney impairment or severe liver impairment (See sections 2 of the FACT SHEET FOR HEALTHCARE PROVIDERS). In the event that you simply cannot get Paxlovid, there are viable natural alternatives.
There is more than one way to manage COVID-19. Nutrients are natural alternatives that will benefit your body for optimal health.
We know there’s an ocean of information out there to navigate, so we’ve compiled and covered 10 best natural alternatives for Paxlovid.
We have perused hundreds of studies and identified multiple nutritional supplements that can be a game-changer in the alleviation and prevention of severe COVID-19.
This practical guide on nutritional supplements has more than 200 supporting studies that represent the best of science-backed strategies for nutritional interventions in the prevention and treatment of COVID-19. Various dietary supplements can be used in combination with other treatments of COVID-19. All these featured supplements have scientific studies to back up their claims. These natural alternatives can easily be purchased over the counter in most countries.
Nutrients and nutraceuticals tend to be agnostic to the COVID-19 virus i.e. it doesn't matter if the patient is down with the Indian, European, Delta, Omicron or Deltacron variants. The mode of actions tend to be multiple and do not have a specific target like targeting the spike protein alone.
Nutrients and supplements are also safer alternatives especially if your risk is low e.g. age below 50 and no other chronic illness. Discuss with your doctor on the benefit vs risk for each treatment. If you are on multiple medications, be aware of supplement-drug interactions that might enhance the possibilities of adverse effects.
The important key takeaway is that you should never attempt to self medicate without the guidance of a licensed medical provider. If you are not a medical doctor, you are likely to find the information below overwhelming. The aim of this article is to empower you with a better understanding of the options available and to discuss the options with your medical doctor as an informed patient.
We have provided the list below as a summary and followed by a summary explanation and references for each option/nutrient:
1. Vitamin D3 - Anti-inflammatory and Anti-coagulantAt this point, there is simply no question that vitamin D optimization is a crucial component of COVID-19 prevention and treatment. In addition to the many studies published during 2020 and 2021, since December 2021, four large systematic meta-analyses (R, R, R, R) have been published, looking at either vitamin D levels, supplementation or both.
In all cases, the data consistently show that low vitamin D levels raises your risk of COVID while higher baseline levels and/or supplementation lowers all risks by 1.5 to three times.
“Each 10 ng/mL increase in vitamin D levels was associated with a 45 % and 26 % lower risk of 45-day mortality (HR: 0.55, 95 % CI: 0.40–0.74) and ICU mortality due to COVID-19 (HR: 0.74, 95 % CI: 0.60–0.92), respectively.”
Almost all studies consider a vitamin D blood serum level of >30 ng/mL ‘adequate/good’. Several studies have shown that people with a blood serum level of >50 ng/mL hardly get sick at all. Results of a systematic review and meta-analysis (Nutrients 2021) suggested that COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3.
2. Quercetin - Anti-inflammatory, anti-coagulant, zinc ionophore and anti-viral
3. Zinc - Anti-viral
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.
“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.”
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, research once again shows zinc’s promise for keeping people healthy if they get COVID.
They conducted a randomized, double-blind, placebo-controlled trial, during which patients who tested positive for COVID-19 — including 190 outpatients and 280 hospitalized patients (R) — received either oral zinc or a placebo twice daily for 15 days. Those taking zinc had a nearly 40% lower rate of death and admission to the intensive care unit (ICU). They also had shorter hospital stays and cut the number of days needed for their symptoms to resolve. (R)
Specifically, mortality after 30 days was 6.5% in the zinc group compared to 9.2% in the placebo group. ICU admission rate was 5.2% in the zinc group and 11.3% in the placebo group. Further, those in the zinc group had, on average, a 3.5-day shorter hospital stay while their symptoms resolved 1.9 days sooner than those who received a placebo. (R)
The beneficial effects of zinc were seen even in subgroups of patients, including those under 65, people with comorbidities and those who needed oxygen therapy at the start of the study. No severe adverse effects were seen. In fact, more minor adverse events occurred in the placebo group (7.1%) than in those taking zinc (3.9%). (R) The researchers concluded: (R)
When administered orally to patients hospitalized with COVID-19 without end-organ failure, zinc demonstrated its efficacy to prevent ICU admission and to reduce hospital length of stay; for outpatients, zinc reduced symptom duration. Zinc should be considered for the treatment of patients with COVID-19.”
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.
4. Nigella Sativa (Black Seed Oil) and Cytokine Storm - Anti-inflammatoryNigella 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.
5. Melatonin- Anti-inflammatory and anti-viral
Check out the evidence tracker on melatonin and COVID-19 from c19melatonin.com (constantly updated).
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.
6. Vitamin A
Based on this early treatment mortality studies drug league table below, vitamin A might even out-perform vitamin D, ivermectin and hydroxychloroquine:
7. Curcumin and Turmeric - Anti-inflammatory and anti-viral
Curcumin, a yellow carotenoid from turmeric, is a
nutritional therapeutic recommended as part of the FLCCC
I-CARE early treatment protocol, and has antiviral,
anti-inflammatory, antioxidant and immune modulating
There are more than 20 completed studies of curcumin in COVID-19 that suggest that it
improves clinical outcome of patients.
Curcumin also acts as natural zinc ionophores and can
promote the cellular uptake of zinc and can be used with
zinc to increase the effectiveness of these compounds in
the inhibition of the virus (Ref).
Curcumin has been demonstrated (Ref) to suppress several inflammatory cytokines and
mediators of their release such as tumor necrosis
factor-alpha (TNF-alpha), IL-1, IL-8 and nitric oxide
8. Vitamin C - Anti-inflammatory
Vitamin C, which most of us reach for with any cold or
flu, was used in high doses to great effect by COVID-19
early treatment doctors.
Vitamin C may be one of the most well-known immune
nutrients that protect against immune deficiencies and
which supports the prevention and recovery from the
common cold and upper-respiratory issues, and also
protects your cardiovascular system, eyes, skin, and
other parts of your body. Research has found that
vitamin C may help to optimize the immune system.
Do take note that the vitamin C dosages given in the
hospitals intravenously are different from those over
the counter vitamin C supplements. Therefore, when you
come across studies on vitamin C, you need to
differentiate those that are given intravenously vs oral
Vitamin C and COVID-19
Check out the evidence tracker on vitamin C and COVID-19
from c19vitaminc.com (constantly updated).
Safety: The U.S. Recommended Dietary
Allowance (RDA) for vitamin C is 75 to 120 milligrams
per day. Taking large doses of vitamin C (ascorbic
acid) on a regular basis lowers your level of copper,
so if you are already deficient in copper and take
high doses of vitamin C, you can compromise your
While generally considered safe even in high doses,
way too much vitamin C — anything above 2,000
milligrams daily—can cause headaches, insomnia,
diarrhea, heartburn, and other issues.
Temporarily taking megadoses of vitamin C
supplements to combat a case of the cold or flu is
likely not going to cause a problem.
Many vitamin C supplements that are above the US RDA are
sold in the market. It’s important to seek a physician’s
advice if you intend to take high dose vitamin C on a
long term basis. To be on the safe side, you may also
request for your kidney functions to be monitored.
For long-term, daily use, your best bet is to eat a diet
that is full of high quality organic vegetables and
fruits that are minimally processed. Not only will you
get vitamin C, but you will get all the other accessory
nutrients and micronutrients that are needed to optimize
Vitamin C, Omicron and Deltacron
Will Vitamin C Work Against Omicron or Deltracron?
Vitamin C is not variant specific because it's primary
mode of action is to support the body’s immune system
which reacts in a variety of ways against viral
attack, not just in a specific antibody reaction to a
specific spike protein.
Related: Best Vitamin C Supplement
Temporarily taking megadoses of vitamin C supplements to combat a case of the cold or flu is likely not going to cause a problem.
9. NAC, Glutathione and COVID-19 - Anti-inflammatory and anti-coagulant
Much of the research on NAC has used an inhaled, liquid form of this compound. This form—which is classified as a drug, not a dietary supplement—is approved by the U.S. Food and Drug Administration (FDA) as a mucolytic agent and for decreasing respiratory secretion viscosity (Source). Products containing NAC are also sold as dietary supplements.
Consider taking around 500 milligrams/day of NAC, as it helps prevent blood clots and is a precursor for your body to produce the important antioxidant glutathione.
Different types of exercise can influence your levels as well. In one study, researchers enrolled 80 healthy but sedentary volunteers to measure the type of exercise that may have the greatest effect. They found that aerobic training in combination with circuit weight training showed the greatest benefit.
10. B Vitamins and COVID-19 - Anti-inflammatory
It follows that anything that improves immune system function and decreases the chances that an infected person will have a catastrophic cytokine storm may improve the outcome of COVID-19 cases and decrease the overall death rate. Therefore, it’s quite feasible that B-vitamin supplementation could contribute to preventing the worst COVID outcomes.”
Structurally, the closest molecule to NAD+ is NMN, requiring only one enzymatic step to be converted to NAD+. NR, which is two enzymatic steps away from NAD+, is also being studied clinically (David Sinclair. Trends Immunol. 2022).
B12, also known as cobalamin, is a powerful cold- and flu-fighting nutrient in your system, as is vitamin B6, another important, germ-combating vitamin that naturally benefits and strengthens your immune system and even protects against the damaging effects of air pollution.
Adequate amounts of folate, vitamin B6 and vitamin B12 are also needed for your body to make the amino acid cysteine. N-acetyl cysteine (NAC) is a supplement form of cysteine. Consuming adequate cysteine and NAC is important for a variety of health reasons — including replenishing the most powerful antioxidant in your body, glutathione.