Ivermectin, an anti-parasitic drug used in both animals and humans, has jumped to the forefront as an alternative therapeutic for COVID-19. Exaggerated media reports portray ivermectin as being as effective as vaccines or as a dangerous veterinary medicine. These overblown claims, unsupported by data — particularly since the emergence of the Delta variant — have driven some people to seek out unsafe treatments and steered some scientists away from conducting further research. Small, inadequately designed clinical trials suggest that ivermectin, possibly in combination with other therapeutics might enhance viral clearance in some populations. However, more data is required before a drug can be repurposed and safely prescribed. On the other hand, real-world data encompassing billions of people indicate that vaccines confer protection against severe disease. In this clip, Dr. Roger Seheult and Dr. Rhonda Patrick discuss whether medical alternatives such as ivermectin are as effective against COVID-19 as vaccines.
Kyle: Dr. Patrick, what are your thoughts on this question?
Dr. Patrick: Well, I do have many thoughts particularly with the ivermectin being as good as vaccines statement that is very sensationalized and I think is doing a lot of harm because, as Dr. Seheult pointed out, you know, we should study any type of therapeutic that is repurposed, anything we know is safe in humans, and anything that could have even the slightest positive effect on the SARS-CoV-2 virus and COVID-19 illness because we need everything that we can to fight this. We need multiple therapeutics. We need vaccines. We need everything. And so, I think, when you sensationalize something more than the data suggests it deserves, then you have a couple of problems. One, you're misleading people, and that's a big problem. And two, you're getting a sort of knee-jerk reaction from researchers, scientists, from physicians that are going, "Whoa, wait a minute. Something feels a little, you know, off." And so you kind of put off those people that otherwise may be more open to looking at that therapeutic if they otherwise didn't hear a very sensationalistic claim like ivermectin is just as good as vaccines at protecting against COVID-19. And so meta-analysis, Dr. Seheult mentioned a very popular one that was a systematic review and did show some conclusions that were positive generally speaking. But when you actually go down and look at the individual studies within that meta-analysis and other types of analysis that are aggregating a bunch of data, what you'll often find is a common set of problems. And these problems are manifold. One, they include the co-treatments, and the treatments are very different with each of these studies. So, for example, sometimes you'll have ivermectin alone. Sometimes you'll have ivermectin plus azithromycin. Sometimes you'll have ivermectin plus some kind of nose spray. Sometimes you'll have ivermectin plus vitamin C and zinc and blood thinners and azithromycin in the kitchen sink basically. Then you'll compare that to sometimes placebo, sometimes hydroxychloroquine, sometimes hydroxychloroquine and azithromycin, sometimes doxycycline. There's so many variables here that you can't look at just one of the variables and say ivermectin is doing this when you have ivermectin plus the kitchen sink, or you have ivermectin plus something else compared to the kitchen sink or compared to...you know, so there's a lot of variables that are just being aggregated together that are very different.
The second major problem with a lot of these studies is that they are small sample sizes, and so at the end of the day, when you're looking at a clinical endpoint, for example, hospitalization, when you have 50 people in a group, you know, then if 2 people end up in the hospital, so you have 2 people in the control group end up in the hospital, but out of the other 50 people, you have zero end up in the hospital, so let's say in the ivermectin group because you'll find studies like this, it's such a low sample size that the risk of that event happening, the certainty of that event happening being actually, you know, causal by that treatment is so low. Like you can't make a definitive statement about that. And so what you'll see happening is that more and more studies will be pulled together so that you now have larger sample sizes when you pull them all together, and then your certainty becomes a little bit better. But then you have to ask yourself, well, is that really true? When you have such a low sample size within that individual study, pulling them together is kind of a statistical way of manipulating the data in a way saying, well, look, there's statistical significance when you pull it all together. I think that's really important to keep in mind when you're looking at some of these meta-analysis with ivermectin.
And then you also have the clinical endpoints varying. So you have people looking at hospitalization. You'll have research groups looking at deaths. You'll have research groups looking at viral clearance time to a negative PCR. And in some cases, they're all being aggregated together, and it's like clinical benefit is the end point. And it's like, well, geez, these are vastly different clinical endpoints. So, you really need to be careful when looking at aggregated data. Certainly, there's a number of websites out there that are doing this. And I can tell you that I've looked at these individual studies, and in many cases, I mean, it's everything I just mentioned and worse. It's where you can't even find the numbers that they're coming up with.
But sticking to just the scientific literature, you know, even that systematic meta-analysis that Dr. Seheult mentioned, you know, if you look at all the different studies, and a lot of them were pre-prints that they included, the only real consistent finding that was found, consistent meaning every study showed it, was basically time to a negative PCR, in other words, an ivermectin plus the kitchen sink or ivermectin plus whatever, it seemed to lead to a faster viral clearance to some degree. And again, it might be that it takes ivermectin plus the kitchen sink to do it, but that ivermectin plays a small role. We don't really know. And when you take ivermectin plus the kitchen sink, you can't pinpoint it and say it's ivermectin doing it. You just can't do that unless you give the kitchen sink without ivermectin to the control group. And then you can say, well, look, they were given the exact other, you know, array of therapeutics, and they didn't have the same improvement as the other group with the array of therapeutic treatments plus the ivermectin. So, there's a lot of nuance to this. And I think that at the end of the day, there is a little bit of a signal. There is something that seems to be going on with ivermectin, whether or not it's in combination with all these other things or by itself. It's unclear. What is clear is that we definitely do need more data. We need more high quality data. We need more data from, you know, states that...or from countries that don't have a really high background of parasitic disease as Dr. Seheult pointed out. It's a very big confounding factor. But also we need to not sensationalize something and, you know, speak about things that are not true. Like there's just no evidence that ivermectin is going to protect you from infection and from severe disease as well as a vaccine. There's no evidence of that, and so don't make that claim. Make the claim for what the data speaks to. There may be an effect. There may be an effect particularly on viral clearance. If people would tone it down and not make these grandiose claims, there would be a lot more interest in ivermectin and studying ivermectin.
And, you know, the other thing to keep in mind is that there's been a lot of people that have now sought out a veterinary form of it because it is something that in addition to being used in humans for parasitic diseases and helminths and also scabies and lice and things like that, it's also used in like...you know, people are calling it horse dewormer, which, you know, it's just...it's not a good idea to go and get a veterinary type of medication and try to treat yourself because there's vastly, you know, different doses involved. I mean, you know, horses are much larger than humans. It's very dangerous to do something like that. And I think people have sort of heard these sensational claims and sort of taking their own action trying to get some form of ivermectin, and really, that could be quite dangerous. I agree with Dr. Seheult that we should be studying these repurposed therapeutics. There is a potential for ivermectin. At least in my opinion at the very least, it seems as though it's pretty consistently involved in speeding up the viral clearance to some degree. It's not like a huge, huge effect, but there is an effect, and it's consistent with pretty much all the studies that I've personally looked at. So, I think that, you know, we should really go after that and try to see if that's real. That's pretty much my thought.
Kyle: Excellent. And speaking of those studies that you both talked about and these meta-analyses, one argument I've heard for ivermectin is some of these population-based studies where certain countries have decided to give ivermectin on a large scale. And you can understand, you know, potentially their motivation. They want to protect their population and prevent COVID-19 if they can, and they're going to use whatever resources they think they have to do that. What are some problems with these population-based studies for people who aren't familiar with what those are?
Dr. Patrick: So basically, they're known as ecological studies. They're great to look at. They're hypothesis generating. You don't rely on hypothesis generating studies to determine whether or not somebody gets a medication. So first off, you know, all the disclaimers, don't take this as medical advice, talk to your doctor, see if it's right for you, and don't get your ivermectin from the feed store are some reasonable advice to take. But in terms of the studies, what you need to be able to reach the point where you're able to prescribe someone something is what the FDA requires, which is a randomized placebo-controlled trial that's usually multi-centered, and it's very large. And that's what you have to do to be able to say this is the medicine that's indicated for this condition. And we just haven't had that yet here in the United States.
Dr. Patrick: And to sort of add to that, Dr. Seheult, I mean, you know, even going back to the original clinical trials with our mRNA vaccines, there were 75,000 people originally in that randomized controlled trial where, you know, half the population was getting the treatment, which were the vaccines, and the other half was getting the placebo. And then on top of that...so that's a large number of people. The sample sizes with this ivermectin is a fraction of that, I mean, a fraction. And on top of that, we now have all this real world data where we've got billions of people worldwide who have had a COVID-19 vaccine, and they are protecting from severe disease, and to some degree they're also protecting against even getting infected depending on which, you know, vaccine a person has gotten. So, we know they're effective. We know from large, large, large numbers. And to sort of even add on to that, everything has changed since the Delta variant. We have had to sort of start again and look at...aggregate new data because this is a new variant where our vaccines are not as effective at preventing infection. And, you know, the reality is, is all these meta-analysis and all this data we just talked about with ivermectin, this was not when Delta was the dominant variant. We don't really know what ivermectin even does with, you know, the Delta variant. I haven't seen data really showing how ivermectin, you know, affects Delta variant. So I think that's also something to consider as well.
Dr. Seheult: Yeah. That's a great point. And, you know, FoundMyFitness even more than MedCram, we've been talking about things that you can do, things that are easy for you to do like sleep. We talked about vitamin D. We're not opposed...I mean, look at our video histories, our respective video histories, we are all in for trying to take control of your health care, take control of your life, and to do this. So let's just take the 3,000 foot level here or the 30,000 foot level. This vaccine is indicated for this particular virus. I mean, I'm not naive to believe that this is the only pandemic that we're ever going to see in our lifetime. It's not the only illness that we're ever going to have to deal with. Some of those other things that we talked about with vitamin D, with sleep, with exercise, stress reduction, fresh air, sunlight, these things have enormous benefits, not just with COVID-19, but every other aspect of our life. And so again, it's the Swiss cheese model. The more slices you have in there, the better.
Dr. Patrick: 100%. I mean, the low hanging fruit is obviously the things that you can do to improve your lifestyle, making sure your vitamin D levels are high enough, you know, trying to be metabolically healthy, you know, eating the best diet or losing weight if you're overweight or obese, getting good enough sleep. All these things are hugely important for overall health and certainly for immunity.
A medication used to prevent and to treat malaria. It is also occasionally used for amebiasis that is occurring outside of the intestines, rheumatoid arthritis, and lupus erythematosus. Currently it is being researched as an antiretroviral in humans with HIV-1/AIDS, an agent in chemotherapy for cancer, and its ability to inhibit lysosomal degradation of protein products during autophagy.
In statistics, a confounder (also confounding variable or confounding factor) is a variable that is correlated (directly or inversely) to both the dependent variable and independent variable.
A variable that is related to one or more of the other variables in a study. A confounding factor can mask an association that exists between variables or demonstrate an association that does not exist. If confounding factors are not measured and considered, the findings of the study may be biased.
An infectious disease caused by the novel coronavirus SARS-CoV-2. COVID-19, or coronavirus disease 2019, was first identified in Wuhan, China, in late 2019. The disease manifests primarily as a lower respiratory illness, but it can affect multiple organ systems, including the cardiovascular, neurological, gastrointestinal, and renal systems. Symptoms include fever, cough, fatigue, shortness of breath, and loss of smell and taste. Some infected persons, especially children, are asymptomatic. Severe complications of COVID-19 include pneumonia, sepsis, acute respiratory distress syndrome, kidney failure, multiple organ dysfunction syndrome, and cytokine storm. Treatments currently involve symptom management and supportive care. Mortality varies by country and region, but approximately 6 percent of people living in the United States who are diagnosed with COVID-19 expire. 1
A broad-spectrum antibiotic used in the treatment of bacterial infections. Doxycycline, commonly called “doxy,” is a bacteriostatic drug that slows bacterial growth by inhibiting protein production. The World Health Organization considers doxycycline an essential medicine because of its widespread applications and its use as a treatment against biothreats such as anthrax, tularemia, and plague.
Important for the endocrine enhancing properties of exercise. Exerkines are exercise-induced hormonal-like factors which mediate the systemic benefits of exercise through autocrine, paracrine, and/or endocrine properties.
A common antimalarial drug that is also used to treat rheumatoid arthritis and lupus. Hydroxychloroquine is relatively safe with a few side effects. In 2017, it was the 128th most prescribed medication in the United States with more than five million prescriptions. It was used to treat COVID-19 early in the pandemic, but multiple high-quality studies subsequently showed no benefit from the drug.
An essential mineral present in many foods. Iron participates in many physiological functions and is a critical component of hemoglobin. Iron deficiency can cause anemia, fatigue, shortness of breath, and heart arrhythmias.
An antiparasitic drug used to treat round worm infections. Ivermectin exerts both anti-viral and anti-inflammatory properties. It has been proposed as an adjunct treatment for COVID-19.
A type of study that analyzes the data derived from multiple studies. Meta-analyses apply objective, statistical formulas to identify a common effect.
A respiratory illness caused by the MERS-CoV coronavirus. MERS is a zoonotic illness, first isolated in bats and then transferred to camels and humans. Symptoms may be mild, moderate, or severe, and include fever, cough, diarrhea, and difficulty breathing.
A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.
A type of vaccine that contains the genetic material to encode a single viral protein that, when injected into the body, induces antibody production against the target protein. Because mRNA degrades easily, it must be encapsulated in lipid nanoparticles in order to be absorbed by cells and often must be delivered in multiple injections to promote optimal immune response.
A chemical reaction in which an atom, molecule, or ion gains one or more electrons.
The virus that causes severe acute respiratory syndrome, or SARS. First identified in China in 2002, SARS-CoV-2 is a type of coronavirus. It was responsible for an epidemic that killed nearly 800 people worldwide.
The virus that causes COVID-19. SARS-CoV-2 is one of seven coronaviruses known to infect humans. Others include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). SARS-CoV2 exploits the angiotensin-converting enzyme 2, or ACE2, receptor to gain entry into cells. The ACE2 receptor is widely distributed among the body's tissues but is particularly abundant in lung alveolar epithelial cells and small intestine enterocytes. SARS-CoV-2 binds to a cell's ACE2 receptor and injects its genetic material (RNA) into the cytosol. Once inside, the viral RNA molecules are translated to produce RNA-dependent RNA polymerase, also known as replicase, the enzyme critical for the reproduction of RNA viruses. The viral RNA is then packaged into infective virion particles and released from the cell to infect neighboring cells.
The highest level of intake of a given nutrient likely to pose no adverse health effects for nearly all healthy people. As intake increases above the upper intake level, the risk of adverse effects increases.
A potent water-soluble antioxidant found in citrus fruits. Vitamin C is an essential nutrient involved in tissue repair, neurotransmission, and immune system function. Also known as ascorbic acid.
A fat-soluble vitamin stored in the liver and fatty tissues. Vitamin D plays key roles in several physiological processes, such as the regulation of blood pressure, calcium homeostasis, immune function, and the regulation of cell growth. In the skin, vitamin D decreases proliferation and enhances differentiation. Vitamin D synthesis begins when 7-dehydrocholesterol, which is found primarily in the skin’s epidermal layer, reacts to ultraviolet light and converts to vitamin D. Subsequent processes convert D to calcitriol, the active form of the vitamin. Vitamin D can be obtained from dietary sources, too, such as salmon, mushrooms, and many fortified foods.
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