Last month I wrote about a proposed treatment for COVID-19 – an extract (oleandrin) from a plant known to be highly poisonous, Oleandra. This was news because the CEO of MyPillow (Mike Lindell) was pushing this new snake oil to President Trump through HUD secretary Ben Carson. Trump assured him that “We will look into it”. This is a perfect representation of what is wrong with supplement regulation in this country, I argued, because Lindell was simultaneously asking for approval as an investigational drug and, failing that, as a dietary supplement. It brazenly revealed how our lax supplement regulation is used to essentially market untested drugs, without any assurance of safety or efficacy.
Phoenix Biotechnology, the company that produces oleandrin (and in which Lindell now has a stake) recently received a letter from the FDA (clicking on this link will automatically download a PDF of the letter) on their decision regarding their disclosure of a potential new ingredient. For dietary supplements, manufacturers only need to inform the FDA at least 75 days before putting the new ingredient on the market. The FDA reviews the new ingredient on two criteria – does it meet the definition of a dietary supplement, and can it be generally regarded as safe (GRAS) based on prior use. Dietary supplements, in other words, are treated as if they were food.
However the regulations also allow companies to make pseudo-medical claims for their supplement ingredients, so-called structure-function claims. As long as they don’t mention a disease by name, they can make or imply claims that the supplement can be used to improve certain health conditions or symptoms. Of course, outside of direct company marketing, people (who may or may not be connected to the company) can make direct medical claims, creating a market for the supplement with health claims that have not been reviewed by the FDA.
The FDA letter to Phoenix Biotechnology has rejected their filing of oleandrin as a new dietary ingredient. The primary reason they cite is that oleandrin does not meet the definition of a dietary ingredient, because it contains:
…an article authorized for investigation as a new drug, antibiotic, or biological for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public
This is where the Phoenix Biotechnology strategy of hedging their bets has bit them in the backside. Because they are also asking to investigate oleandrin as an FDA approved drug, this excludes the substance from being considered a dietary supplement. That is the one thing you can’t put into your nutritional supplement – an actual drug. The FDA considers such products as “adulterated”. This is still a common occurrence. The FDA’s response when it discovers that a product is adulterated with a drug is to send them a strongly worded warning letter.
For example, a recent review found:
The authors found that between 2007 and 2016 the FDA identified 746 brands of supplements adulterated with pharmaceutical agents. The adulterants included prescription medications such as sildenafil and fluoxetine, withdrawn medications including sibutramine and phenolphthalein, and unapproved drugs including dapoxetine and designer steroids. Twenty percent of the adulterated supplements contained 2 or more undeclared drugs, for example, weight loss supplements containing both an anorectic and a laxative.
The FDA essentially asks the company for a voluntary recall. However:
Despite their limited effectiveness, voluntary recalls are the most common approach used by the FDA to remove adulterated supplements from commerce. In the current study, the agency discovered 746 distinct supplements to be adulterated but announced voluntary recalls for only 360. Only 360 of 746 (48%) were recalled, leaving the majority of adulterated supplements, more than 350 products, available for sale.
In the case of oleandrin, however, the FDA is preemptively rejecting approval as a new dietary ingredient on the grounds that it meets the definition of a drug.
FDA has concluded that the “Oleandrin” has been authorized for investigation as a new drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public. Further, FDA has carefully reviewed the information provided in your submission and other available information and has not identified any evidence to demonstrate that “Oleandrin” was marketed as a dietary supplement or as a food prior to such authorization.
This implies that if oleandrin were marketed as a supplement prior to being studied as a drug, it would be OK. Again this shows the blurry distinction between the two, and how the regulations are essentially just a way to market drugs without having to prove safety or efficacy.
Not only is oleandrin being tested as a potential drug, it is failing so far. The U.S. Army Institute of Infectious Diseases halted a neutralization test of oleandrin against COVID-19 because the results were “inconclusive”. So it did not even look promising on a preliminary study of potential effectiveness, and was abandoned to focus on other potential agents.
Finally, the FDA points out in the letter that, even if oleandrin could be considered a dietary ingredient:
…the agency has significant concerns about the evidence included in your submission as a basis for concluding that a dietary supplement containing “Oleandrin” will reasonably be expected to be safe under the conditions of use described in your notification.
They could not even meet the low bar of showing that the ingredient is probably safe, based on prior usage (as opposed to controlled clinical trials).
While this is a good decision from the FDA, it does also reflect the weakness of our current regulatory scheme. A company could, for example register as a new ingredient a substance that is not toxic and is not already being studied as a potential drug. If approved as a dietary ingredient (even though it is actually a pharmacological agent), the company could then market it as a way to help fight off COVID-19, by “boosting the immune system” or some other vague language. This is not the FDA’s fault, it’s Congress’s. They passed DSHEA, and have failed to revise it despite its blatant problems.