I am not a physician and this posting does not constitute medical advice.
One of the oddest aspects of the coronavirus epidemic is that the Chinese are using traditional Chinese medicine (TCM) in addition to modern medicine. And I don’t mean, people are buying folk remedies. That may well be happening. What I mean is, TCM is being used in the hospital setting. By report, on-order-of 85% of diagnosed cases have received some form of TCM in addition to standard medical treatment (per this reference).
I’m sure that most people scoff at any use of folk medicine/traditional medicine in this context. And the Chinese government apparently aims for some sort of propaganda angle in the use of TCM. And any benefits, if real, appear to be quite modest. And, frankly, if you read what TCM practitioners actually do, it does in fact sound wildly unscientific. And, finally, there is little evidence basis for use of TCM here, in the sense that western medicine recognizes it — in terms of controlled clinical trials.
And yet, I’m not one of those scoffing at the use of folk medicine in this context. In this post I try to explain why.
A definition of folk medicine
If you look up any definition of folk medicine, you’re likely to run across words like “superstition” and “unscientific”. But, at root, most folk medicine consists of using (mostly) plant-derived chemicals to treat diseases, in the absence of an acceptable evidence basis for doing so.
So, think of folk medicine as a set of drugs whose effectiveness for a given disease has never been formally tested. And yet they are used. Typically, the reason for using a particular drug for a given disease is “lore”, or “tradition”. That is, somebody, somewhere, at some time, thought that a folk remedy did some good. And that observation got passed down through some oral (or, rarely) written tradition.
Even when effectiveness is known, folk remedies typically offer only weak, low-dose drugs of unknown strenth. Willow bark tea for pain is a classic example. It does work, it contains more-or-less the same ingredient as aspirin (reference). Just at a low dose, with a lot of impurities. And its use, in this context, goes back to the ancient Greeks.
Tamiflu as folk medicine
Under the definition above, physicians practice folk medicine all the time. Although I am sure most would bristle at that statement. Most commonly, I’d say that much off-label use of drugs constitutes a form of folk medicine. An off-label use of a drug is a use that (typically) has not been formally subjected to a standard clinical trial for the proposed use, and which does not have formal FDA approval. So, just like folk medicine, off-label use means the use of a drug whose effectiveness for a given disease has never been formally tested.
And yet, physicians will use drugs off-label. In some cases, there is some reasonably firm evidence basis, it’s just that the drug manufacturer never bothered to get FDA approval for the use. In other cases, there is some weaker evidence basis, such as a collection of case reports (individual patients). Sometimes physicians resort to off-label use if there is no known effective treatment for a disease, where the off-label use of the drug makes some kind of sense. And sometimes, off-label use can be driven by something like the perception that the efficacy of a drug in a given situation is common knowledge.
And that seems to be the case with Tamiflu and coronavirus.
Tamiflu is one of few anti-viral drugs available. The on-label use of Tamiflu is for cases with Type A or B influenza. Even then, the effect of Tamiflu is modest, and in some cases its questionable whether it has any material effect at all. Given at the right time, to the right population, it reduces the duration of a bout with the flu by about a day, and appears to reduce the likelihood than an individual will be hospitalized for the flu. But evidence is weak, at best, for those major effects (reference Wikipedia, and another reference). They aren’t even entirely certain as to why it works at all (reference).
So, this is a drug that has been shown to have a modest impact on the course of two major strains of influenza, when taken early in the course of the disease. Near as I can tell, it has never been evaluated for coronavirus, though it’s a good bet clinical trials are underway now, along with a handful of other anti-virals (reference).
And yet, fully one-third of hospitalized patients in China were given Tamiflu (per this New England Journal of Medicine article.) And it’s a good bet that patients in other countries will get it as well. Because — well, this is a serious disease, there’s no known effective treatment, and it seems plausible that it might help some.
In that context, if a practitioner of TCM cooks up some broth using herbs with some demonstrated anti-viral efficacy (against swine flu, reference), containing herbs with known anti-viral properties in vitro (licorice root, per this reference), traditionally used for lung ailments — and says, drink this, it might help — you know, I wouldn’t turn it down. As long as it wasn’t outright poisonous. Honestly does not strike me as markedly different from providing Tamiflu. Likely to have a modest effect, at best. Evidence basis is weak. But better than nothing.
Scientific folk medicine.
Going back to the example of willow bark and aspirin, that’s far from the only example of a chemical that made the transition from folk medicine to mainstream medicine.
One important example is the use of the active component of wormwood (artemesinin) to treat malaria. A Chinese physician was awarded the Nobel prize in medicine (reference) for that.
That was discovered by what I would term scientific folk medicine. She and her team looked at hundreds of folk remedies for fevers, looking for any plant or substance that came up frequently. (With the logic being that if many different traditions arrived at using the same plant, the odds that they all made the same mistake are slim, and likely the plant has some effect.) And once they systematically identified candidate plants, they then they developed a proper evidence basis as recognized by mainstream medicine, including controlled clinical trials.
And here’s where this post goes off the rails.
At this point, I got the idea of doing my own bit of scientific folk medicine. I mean, absent a known effective medication, there wouldn’t seem to be any harm in it.
Here are the rules.
First, you rely on mainstream medicine to the greatest extent possible. This means you only go down this path if a) there’s no effective mainstream medical treatment, or b) there is a treatment, but the disease is vague or rare enough that your odds of being properly diagnosed are slim-to-none. Finally, any “natural” substance that it more-or-less just a naturally-occurring version of a mainstream medication is ignored (e.g., willow bark is out in favor of aspirin for pain; red rice yeast is out in favor of statins for cholesterol; wormwood is out in favor of artemesinin extracts for malaria, and so on.)
So, in no way, shape, or form would I use this process to displace any known effective mainstream treatment. The only use that I see, for this, is in areas where mainstream medicine either has no effective treatment, or is unlikely to provide a diagnosis of some specific, treatable illness.
Second, you do a systematic literature review. Figure out a couple of reasonable search terms, go to a standard source (in my case, the National Library of Medicine PubMed interface), and search for the topic of interest. In this case, I looked for substances with anti-viral properties against coronaviruses. (Figuring, if they work on some member of that family, there’s a chance they’ll work on COVID-19).
Third, you look at every study and establish a “strength of inference” hierarchy. And that is:
- Controlled clinical trials on humans.
- Controlled clinical trials on animals.
- Case reports and other anecdotal data on humans.
- Compatibility with/use as a traditional (folk) medicine.
- In vitro (test-tube) studies of human cell lines.
I have found that in vitro studies are not-quite-totally worthless. The number of chemical substances that show some biological activity in the test tube vastly exceeds the number that will actually work inside the human body. And you need at least one clinical trial in humans or animals to get some guess as to the relevant dose rate, typically expressed as migs-per-kig (mg/kg, milligrams of the substance in question per kilogram of body weight).
Fourth, you restrict your search to a) things you can buy that b) probably won’t kill you, and that c) you can in fact absorb by eating or drinking them. At this stage, you realize that you can get damned near anything on Amazon, and many of the substances offered for sale as herbals on Amazon are are just downright dangerous. (For example, the licorice root that is in the TCM broth is toxic if taken in large amounts. And raw wormwood contains toxic chemicals called thujones.) So due diligence on toxicity is required.
From the toxicity standpoint, it is always best if what you end up with is something commonly (or at least sometimes) found in food. That’s not always a guarantee against toxicity. (For example, lectins found in most beans are quite toxic in their raw state.) And, almost without exception, in order to achieve the dosages used in the literature, you’re going to have to take some concentrated extract of whatever-it-is. But even then, I’d rather take something that is at least vaguely recognized as food, as opposed to (e.g.) chewing on the bark of a tree (as with willow bark.)
The gold standard is when you find a substance that is classed as “generally recognized as safe” (GRAS). If it’s that, then you’re probably good to go from the standpoint of toxicity for any plausible dosage.
Finally, you look to see if some substance or group of substances appears frequently. Especially if that substance was discovered independently by several different research efforts. This is the analog of the scientific folklore approach, where repeated independent discovery of a particular treatment provides some indication that the treatment is efficacious.
When I shake that all out, the group of chemicals that appears most frequently is flavonoids. Like so:
myricetin and scutellarein — these are flavonoids, and the first can be bought: https://www.ncbi.nlm.nih.gov/pubmed/22578462
Hesperetin which is also hesperidin (as a food), a citrus flavonoid: https://www.ncbi.nlm.nih.gov/pubmed/16597209
flavonoids generally: https://www.ncbi.nlm.nih.gov/pubmed/2981979 ; https://www.ncbi.nlm.nih.gov/pubmed/29233744
Prunin, a naringen precursor, and other flavonoid: https://www.ncbi.nlm.nih.gov/pubmed/31666401
licorice root: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629407/ again, flavonoids, but note that there can be health problems from excess consumption of glycyrrhizin glycoside
houttuynia cordata extract, arguably flavonoids. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032839/
Weirdly, there have already been foreign patents applied for, for specific components of that last one, flavonoids from houttuynia cordata, in the context of coronavirus. But those patents are already more than a decade old, so any actual efficacy from that is probably pretty modest (reference).
Flavonoids are commonly found in foods including fruits, berries, onions and some others. You can get the complete USDA listing from this page.
One problem with foods alone is that the dose is too low. Merely eating apples and berries won’t give you anything like the dosage rate that, per the literature review, appears to show some antiviral effect. For apples, for example, for me to achieve 5 mg/kg of total flavonoids from apples, I’d have to eat 11 pounds per day.
A second problem is that flavonoids are a large and diverse class of molecules, so it’s not clear that any one food substance will give you the “right” ones.
These problems can be mitigated to some degree by buying flavonoids sold as health supplements. (Yeah, I know, it’s an unregulated market, you don’t really know what you’re getting, and so on. That’s never been a problem for me. When in doubt, buy from a German company, because they are far more serious about herbal supplements there than we are here (reference).
And so I arrive at a strategy of: eat your fruits and vegetables. Good advice under any circumstances, and hardly anything radical. This just emphasizes those high in flavonoids. I plan to eat maybe a gram of flavonoids per day, from a variety of sources including both food and supplements. It’s probably harmless, it’s cheap, arguably it’s actually good for your health regardless (if you get them from food sources, for sure), and it might provide some slight anti-viral resistance that you would not otherwise have.
Think of it as analogous to TCM. That doesn’t replace hand-washing, avoiding crowds, and so on. It in no way replaces any part of the advice and treatment offered by mainstream medicine. But, you know, if it’s cheap, non-toxic, and maybe gives you a little bit of an edge in resistance — what the heck, why not.
