Conquering COVID Part 1.7:
“Now over 900 clinical studies - including a Gout pill?!”
(aka a few weeks ago it was 100 clinical studies - the pros & cons of a “natural” medicine)
April 24, 2020
by Mark A. Moyad, MD, MPH
“I am concerned, of course, but I am also incredibly optimistic.”
Okay, this is getting somewhat remarkable! A few weeks ago, I wrote about the approximately 100 clinical studies setting up, actively recruiting, or ongoing with COVID-19 all over the planet and now the number is well over 900 and growing daily! Wow! Only a few weeks ago there were a little more than 100! This is an impressive and diverse list, but there tends to be a focus out there on several interventions that have been adequately covered by countless sources (including this column).
However, what about other unique studies going on that are not getting enough awareness? Why not give many other interesting products a platform here?! Of course, we will, but first I have to give my disclaimer that the point of this article is to demonstrate the diversity of studies beginning or ongoing, and not to think for a minute these products will definitely work better, worse or even the same versus any other product out there. This column is about objective or non-biased education, so it is for this reason we will cover the well-covered and the less well-covered potential COVID-19 preventive options and treatments. Additionally, this column is about overall education and personal health/knowledge-empowerment, which means that by covering some of these products we learn more about what they do and do not offer
and this could help some of you in a future dialogue with the doctor(s) and other health care professionals you trust with your overall health. Okay, now I will step off my EPA approved disinfected soapbox (I know I like to use that line). Here is an intervention being tested widely against COVID-19 that is interesting or different and not receiving much attention:
Gout, Lifestyle Changes & Colchicine (Old & New Gout Drug)
Gout is a well-recognized metabolic issue, or a type of “inflammatory arthritis.” It is caused, in general, by higher body levels of uric acid, which is a compound created when the body breaks down substances known as “purines” that are normally produced by the human body, and also found in some food and beverage sources (Dalbeth N, et al.
Lancet 2016;388:2039-2052). Basically, many different things can impact uric acid levels from genetics to medications and lifestyle factors.
In other words, it is not unusual for a person to carry a certain “normal amount” of uric acid in the blood and urine (levels can be measured by your doctor), but abnormally high amounts anywhere in the human body can be problematic for SOME folks. Uric acid crystals or a buildup of this compound can get into the joints causing painful inflammatory arthritis and, when abnormally high in the urinary tract, it can cause a type of kidney stone (another ouch!). In fact,
gout is NOW the most common type of inflammatory arthritis that impacts adults and it has become a common source of kidney stones. Still, if high levels of uric acid can cause inflammation in various parts of the body then it may also cause more widespread body inflammation (a theory being tested) leading to other problems from head-to-toe, such as cardiovascular issues (Gupta MK, Singh JA.
Drugs 2019; 79:531-541).
Gout has been on the increase due to a variety of factors including the obesity epidemic. Interestingly, weight loss can reduce uric acid, and even some studies of bariatric surgery have demonstrated an impact on reducing the risk of gout (Maglio C, et al.
Ann Rheum Dis 2017;76:688-693).
Lifestyle changes are considered an important part of gout prevention and management and major rheumatology guidelines from the American College of Rheumatology (ACR) to EULAR (European League Against Rheumatism) recommend a variety of anti-gout tips including reducing the following: weight, alcohol, fructose-containing beverages (aka sugar-sweetened drinks), heavy meals, excessive intake of meat, and encouraging exercise. (Richette P, et al.
Ann Rheum Dis 2017;76:29-42). In reality, these clinical recommendations suggest more studies are needed in the area of lifestyle changes to prevent gout or gout flares. There are also suggestions to reduce certain types of seafood (a source of purines) or increase low-fat dairy intake but, again, the studies are preliminary. It is for this reason it appears general weight loss (when needed), consuming less calories overall - including from red meat and alcohol, and engaging in regular exercise appears to have the greatest consistent benefits for overall health and gout prevention. In fact, the majority of the higher quality observational studies have found a benefit with weight loss (when needed) for patients with gout (Nielsen SM, et al.
Ann Rheum Dis 2017;76:1870-1882; & Nielsen SM, et al.
Autoimmun Rev 2018; 17:1090-1096.). Now, with that as a background, including another surreptitiously placed Dr. Moyad reason to become
more heart healthy because it can reduce gout risk and gout flares in many people, it is time to talk about one of the oldest “natural” drugs in the history of medicine.
The prescription drug colchicine is one well-known option utilized in some individuals for the prevention and treatment of gout flares/attacks. (Webb CA, et al.
Pharmacotherapy 2020; 10.1002/phar.2401). Still, this anti-gout medication is a so-called “ancient natural drug” derived from a member of the lily family and, in reality, was utilized in one form or another for 1000’s of years (Pascart T, Richette P.
Curr Pharm Des 2018;24:684-689.). Ancient Greeks apparently used the plant source of this medication as a laxative, and even Hippocrates (460-375 BC) recommended it for the treatment of gout flares. Apparently, Hippocrates called gout “the unwalkable disease” (anyone that has had a flare is nodding their head in agreement right now), and the “arthritis of the rich,” and suggested it was the result of an excess of wine, food, and sex (Hudson B.
The Pharmaceutical Journal 2009; December 11.). So, Hippocrates clearly had some understanding of SOME (not all) of the potential causes of gout and he also attributed some factors to gout that were NOT associated with this condition (you can guess which one from his list above…I am staying out of that mouse trap).
The anti-gout benefit derived from the plant source of colchicine was incorrectly believed by many of the ancient experts to be the result of the diarrhea that would occur when it was ingested, but this is actually one of the side effects. Nausea, vomiting, abdominal pain, and especially diarrhea were, and still are, just some of the more common symptoms of colchicine toxicity. In fact, the toxicity of colchicine is part of the reason it fell in and out of favor throughout history. Fast forward to 1763 and it was recognized again for its benefit by Austrian researchers and in the 1800s, French chemists discovered the actual specific compound colchicine as the principal active component of the colchicum plants. In fact, colchicine is actually derived from the autumn crocus (meadow saffron) or
Colchicum autumnale (Nerlekar N, et al.
Med J Aust 2014;201:687-688.).
Interestingly, even though colchicine is utilized for many gout patients today it has minimal effects on uric acid levels (unlike other common gout drugs such as allopurinol), so its different known and unknown anti-inflammatory mechanisms has many researchers excited. For example, colchicine is known to impact a type of white blood cell known as the “neutrophil”, which normally likes to show up where crystals of uric acid are located. Neutrophils help to amplify the inflammatory response, but colchicine likes to modify or turn down this response. In fact, in past COVID studies some patients have been found to have an excessive number of neutrophils, also known as
“neutrophilia” (Ye G, et al.
J Infect 2020; 80:e14-e17; & Wu C, et al.
JAMA Intern Med 2020; doi: 10.1001/jamainternmed.2020.0994), which some researchers hypothesize is part of the problem that makes people more sick.
This is an interesting theory, but the key is determining if this problem with the neutrophils is an ASSOCIATION OR CAUSATION when it comes to COVID-19. So, it is for this and many other reasons mentioned that colchicine is now being utilized in multiple clinical studies against COVID-19 around the world, despite receiving minimal-to-no attention.
Currently, multiple study sites around the planet are testing whether or not it can reduce the risk of COVID-19 from progressing/causing an exaggeration of the immune response that we have talked about in this and previous columns. Still, and I cannot emphasize this enough, this drug has a
narrow therapeutic window, which also means side effects are common as dosages are even slightly increased,
so even though colchicine is a “natural drug,” please keep in mind that POISON IVY AND ARSENIC ARE ALSO CONSIDERED “NATURAL." In other words, natural drugs are always interesting to discuss, but the side effects are not necessarily less, and can be more than other drugs utilized for the same indication.
Multiple clinical studies are registered to begin colchicine testing soon against a variety of COVID-19 situations including the following (
clinicaltrials.gov):
- Colchicine to reduce injury to the heart (UCLA)
- Colchicine for hospitalized patients to reduce inflammation and inflammatory markers (Spain)
- Colchicine in addition to standard of care (University of Athens, Greece)
- Colchicine alone or with other antivirals (South America and other sites)
- Colchicine with standard of care for those with pneumonia (Parma, Italy)
- Colchicine phase 3 trial to recruit approximately 6,000 non-hospitalized patients or those in outpatient setting, but at high-risk for complications or progression of the condition such as the elderly, diabetics, respiratory disease, heart disease, uncontrolled hypertension, etc.(University of California-San Francisco, New York University School of Medicine, and Montreal Heart Institute-Montreal, Canada).
Thus, colchicine is quietly being utilized in multiple clinical trials around the world. This not only demonstrates the potential diverse power of naturally derived medications, but also drug repurposing and, of course, the potential for toxicity with anything considered “natural.” Again, colchicine comes with a good deal of toxicity, especially as the dosage is increased, and it also has the potential for multiple drug-drug interactions, which is why NO ONE SHOULD TOUCH THIS DRUG WITHOUT YOUR DOCTOR APPROVING IT FOR UTILIZATION FOR GOUT OR ANOTHER APPROVED MEDICAL CONDITION (NOT for COVID now because it is completely unproven in this setting, but more will be learned very soon). Research also suggests it has drug-food interactions, for example it should not to be used with grapefruit or grapefruit juice (
mayoclinic.org).
In conclusion, aspirin was first derived from willow bark, statins were first derived from a fungus, metformin from the French Lilac, the chemotherapy drug Taxol came from the bark of the Pacific yew tree, and the list of naturally derived drugs goes on and on. And, now you know about some of the pros and cons of an amazing compound derived from the autumn crocus! Nature provides us with countless amazing and powerful medicines, but determining where they actually fit within medicine takes more time.
But with more research the potential for any of a number of medicines to potentially kick COVID-19 in the gluteus maximus becomes more plausible.
Thank you for reading my latest installment and I wish you and your family the best of health.
I am concerned, of course, but I am also incredibly optimistic! I look forward to modern day science and you of course, kicking COVID-19 and cancer in the gluteus maximus!
All of my best always,
Mark A. Moyad MD, MPH
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