Let us start by stating that the FDA’s Office of Dietary Supplement Programs (ODSP) told the Commission On Responsible Nutrition (CRN) that they are still investigating the use of n-acetyl cysteine as a dietary supplement, as opposed to as a regulated drug. What Amazon, and pretty much just Amazon, has done, is to pre-emptively remove a dietary supplement that sells very well from their website, without prior notice, declaring that it is a drug according to the FDA.
The wording in seven warning letters, which were sent to makers of supplements in August of last year by the Food and Drug Administration , was ambiguous and far-reaching. The letters start off by talking about how the supplements make multiple claims about their product, such as that it cures hangover, which has been determined to be a disease. The supplements targeted were for hangover medicines and contained NAC as an active ingredient.
However, the FDA went even further, and stated that even if the drug-claims category was resolved, there was still another issue. The FDA stated that they have determined that NAC is actually a drug, and cannot be marketed as a supplement. These letters are very important to understanding why NAC is no longer available for sale on Amazon.
From the letter sent to one of the manufacturers of hangover supplements, Vita Heaven, “FDA has concluded that NAC products are excluded from the dietary supplement definition under section 201(ff)(3)(B)(i) of the Act [21 U.S.C. § 321(ff)(3)(B)(i)]. Under this provision, if an article (such as NAC) has been approved as a new drug under section 505 of the Act [21 U.S.C. § 355], then products containing that article are outside the definition of a dietary supplement, unless before such approval that article was marketed as a dietary supplement or as a food. NAC was approved as a new drug under section 505 of the Act [21 U.S.C. § 355] on September 14, 1963. FDA is not aware of any evidence that NAC was marketed as a dietary supplement or as a food prior to that date.”
As such, Amazon de-listed all of the supplements on their site containing NAC as the main or any ingredient, citing the fact that the FDA has declared them as a drug.
What the FDA has done by essentially rule-making through a warning letter instead of through the usual required legal channels, is cause retailers to have to choose whether to pre-emptively remove the supplement, or risk that the FDA will follow through and send them warning letters as well.
In light of the statement from the ODSP, which is the arm of the FDA who would be responsible for actually making this type of decision, this was a bit premature, and to our knowledge, only Amazon has removed the supplement. Manufacturers are still making more product, and other retailers are still selling it.
It should be noted, though, that this has caused something to happen among those who consume vitamins and supplements: a run on NAC. Most manufacturers are seeing unprecedented demand for the supplement, and they have continued to manufacture it to meet the demand. Eventually, one can certainly assume that the demand will soon outstrip supply if the FDA does not actually clarify their position.
Council For Responsible Nutrition Writes A Citizen’s Petition To FDA Demanding Clarification
The Council on Responsible Nutrition is not waiting for the FDA to come around on its own. They have issued a Citizen’s Petition to the FDA demanding that it clarify its position on NAC immediately. Of course, for the FDA, “immediately” can be a very long time. However, the FDA is legally required to answer within 180 days, which would give retailers further clarification. However, these petitions are often ignored by FDA, or responded to in vague and unhelpful ways.
In their letter, they bring up several very important points. Please note the following statements: “…we urge FDA to reverse its recently adopted position that the Federal Food, Drug, and Cosmetic Act (FDCA) prohibits manufacturers from marketing products containing N-acetyl-L-cysteine (NAC) as dietary supplements. This policy—which represents a sudden and drastic departure from past Agency practice—is legally invalid. As such, FDA should revert to its longstanding policy of allowing manufacturers to market products containing NAC as dietary supplements.”
The Dietary Supplement Label Database lists over 1,500 supplements containing NAC, and they have been manufactured and safely used for decades. The letter continues, “But, in July 2020, FDA enacted a sudden policy change by issuing multiple warning letters asserting that products containing NAC cannot be marketed as dietary supplements under section 201(ff)(3)(B)(i) of the FDCA. Section 201(ff)(3)(B)(i) prohibits manufacturers from marketing…products as dietary supplements if they contain an article that FDA has approved as a new drug…”
Further, “FDA’s sudden policy change is legally invalid on multiple grounds. First, it is not even clear, from FDA records, whether section 201(ff)(3)(B)(i) applies to NAC as a dietary supplement. The decades-old records for NAC drug approval contain unreliable information, such as handwritten dates, and unverifiable information. Second, NAC drugs approved prior to 2016 appear to be comprised of different forms of NAC from that which is found in a dietary supplement. Third, interpreting FDCA section 201(ff)(3)(B)(i) to prohibit the marketing of dietary supplements containing NAC violates the well-established presumption against statutory retroactivity.”
NAC has been marketed as a supplement for over 57 years. According to the FDA, NAC was approved as a drug back in 1963, and they are not aware of its existence as a supplement prior to that date. However, as stated in the above letter, the 1963 date could have easily been written in later, as it is handwritten and thus unreliable. Since 1963, there have been many dietary supplements made of single formulations as well as multi formulations containing NAC. It is in fact quite an old supplement.
What Is NAC?
Now that we are talking about NAC, many of our readers may not know what it is or why it is important. So, what is n-acetyl cysteine? According to the Wikipedia page for the chemical, “Acetylcysteine, also known as N-acetylcysteine (NAC), is a medication that is used to treat paracetamol (acetaminophen) overdose, and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It can be taken intravenously, by mouth, or inhaled as a mist. Some people use it as a dietary supplement.”
The semi-essential amino acid cysteine is normally taken supplementally as NAC. While it is not considered an essential amino acid, a study titled (.)“Crosstalk between cystine and glutathione is critical for the regulation of amino acid signaling pathways and ferroptosis“ showed that cysteine (which is broken down into cystine) is the most essential ingredient to the synthesis of glutathione (GSH).
Glutathione is a super-antioxidant, and is very important for many body functions. According to the University of Maryland Medical Center (https://web.archive.org/web/20170701184417/http://www.umm.edu/health/medical/altmed/supplement/cysteine), “The body makes [NAC] into cysteine and then into glutathione, a powerful antioxidant.
Antioxidants fight free radicals, which are harmful compounds in the body that damage cell membranes and DNA. Researchers think free radicals play a role in aging as well as the development of a number of health problems, including heart disease and cancer.” There are multiple studies which have been undertaken in order to attempt to prove this.
When the body absorbs NAC, it converts it into the amino acid component of cystine, and uses that to make glutathione. Glutathione is known as a super antioxidant, as it fights harmful compounds in the body known as free radicals, which can cause DNA and cell damage.
In addition, according to WebMD, the authority on medical information, “There aren’t many studies on NAC and the immune system, but current research suggests that it and glutathione may help to improve your immune function. Most of the studies focus on NAC and people with human immunodeficiency virus (HIV).” Considering the fact that the body produces glutathione from NAC, it would seem that taking NAC is very important for your immune system.
Covid Research Relating To NAC
During the time of Covid, six studies were conducted in order to determine the effects of N-acetylcysteine on Covid, and their effectiveness in preventing severe illness.
According to one review of the evidence, titled “N-Acetylcysteine to Combat COVID-19: An Evidence Review,“ “As a dietary supplement, NAC has been used increasingly worldwide. During this COVID-19 pandemic, NAC can potentially prevent development of critical pneumonia for the people sensitive to SARS-CoV-2 infections.
“It also provides the potential references of how to use NAC for ongoing clinical trials. In addition, NAC features and its successful application for treating COVID-19 may encourage patients to enroll into the clinical trials using NAC.”
The same review listed above concludes: “N-acetylcysteine (NAC) is inexpensive, has very low toxicity, has been FDA approved for many years, and has the potential to improve therapeutic strategies for COVID-19. NAC administered intravenously, orally, or inhaled, may suppress SARS-CoV-2 replication and may improve outcomes if used timely. Potential therapeutic benefits of NAC include, extracellularly scavenging ROS radicals, replenishing intracellular GSH, suppression of cytokine storm, and T cell protection, thus mitigating inflammation and tissue injury. NAC administration in combination with other antiviral agents may dramatically reduce hospital admission rate, mechanical ventilation and mortality.”
It should be noted their statement that it has been FDA approved for many years. It has, in fact, been FDA approved under many different drug trade names, and most importantly, in multiple forms. However, one form that has never been FDA approved, but has been marketed as a supplement, is the simple oral tablet form. A search of the “Orange Book,” published by the FDA and listing all drugs that have been approved for manufacture in the United States, shows many different forms of NAC.
A review of the same information page noted above, by the University of Maryland Medical Center, lists a number of approved uses for NAC. These include its use in acetaminophen poisoning (liver toxicity caused by Tylenol, either overdose or use with other substances); conditions with abnormal mucus secretion such as pneumonia, bronchitis, and others; as well as a number of off-label uses such as in the treatment of angina, influenza, acute respiratory distress syndrome, boosting levels of glutathione in HIV (research is ongoing), along with many others.
The Orange Book shows the manufacturers, forms, strength, route of administration, and proprietary names of all approved drugs. If you want to know if a drug has been approved by the FDA, this is where you would look. This author searched for Acetyl, and all the results came up for Acetylcysteine, which is the accepted form that the FDA uses, and is the same chemical as NAC.
There are multiple forms available for the approved forms of the drug, such as inhalation, mist, injection, and effervescent tablets (like Alka-Seltzer). But the only oral use is as an effervescent, no tablets have apparently ever been approved. Whether this is because the absorption rate is inconsistent or if they are less cost-effective to make, is unknown, and are not the only two possibilities for why no pharmaceutical company has every tried to get them approved. It may also be due to the status of oral pills as a supplement.
In addition to the alternative forms that are approved, there is also the reality that there are many over the counter drugs, as well as vitamins, that can be used in a hospital setting, by a prescription in the hospital. This does not make them a drug requiring a prescription, but a supplement or drug for which a prescription is available but not required. Two obvious examples that come to mind are Acetaminophen and Vitamin C (ascorbic acid injection), and Ibuprofen and Aleve can both be added to this list.
Dietary Supplements As Drugs, and NAC As A Vitamin
As far as the use of a dietary supplement as a drug, Vitamin C would be an excellent example of a case-in-point. In the Orange Book, you can find Vitamin C under its listing as ascorbic acid. (https://www.accessdata.fda.gov/scripts/cder/ob/search_product.cfm) This is a bit of a misnomer, as straight ascorbic acid is never injected, and all of the listed approved drugs are injectable forms.
However, under no circumstances would the FDA ever try to say that just because Vitamin C is approved as a drug (in some form or other, just as NAC is) it cannot be sold as a supplement. As far as why, this is because it is a vitamin. If you have a deficiency of Vitamin C, especially a severe one, it can be life threatening, causing scurvy in mild to severe cases. There are many manifestations of scurvy, but humans cannot manufacture it themselves, which is why it is a vitamin.
It is unclear why NAC is not considered a vitamin. Some sources have stated that NAC is produced in the body, and that is why it’s not a vitamin. Others have said that it isn’t essential, as the amino acid, while a building block, is not one of the twelve essential amino acids.
According to Very Well Health, “Cysteine is both naturally produced in the body and obtained from animal- and plant-based foods. Because of this, cysteine is considered a semi-essential amino acid (unlike essential amino acids that must be obtained externally).“
This statement does not appear anywhere else online, and does in fact contradict statements on WebMD’s website, so it may or may not be the case. Their statement may simply be a reference to the fact that your body can produce it from other amino acids that are essential, which is why WebMD and the medical community also considers it semi-essential.
But taking this valuable supplement is a good thing, and is known to have many beneficial effects. Even so, since it is essential to the production of glutathione, and GSH is necessary to many body functions, including as an antioxidant, it should be classified as a vitamin. NAC is the usual form of cysteine that most people take, since it is less subject to oxidation.
According to a study titled, “N-acetylcysteine – a safe antidote for cysteine/glutathione deficiency,” published on the NIH website, “Chemically NAC is similar to cysteine. However, the presence of the acetyl moiety reduces the reactivity of the thiol as compared to cysteine. Thus as compared to cysteine, NAC is less toxic, less susceptible to oxidation (and dimerization) and is more soluble in water, making it a better source of cysteine than parenteral administration of cysteine itself” So, while you can find L-Cysteine in the stores, a much more stable, non-reactive, more absorbable form of cysteine is NAC.
Role In Virus Therapy
One of the lesser known effects, as discussed above, is as a possible treatment for the Covid-19 virus, along with other viral infections. This is all due to its role as a producer of glutathione.
According to a study published in May of 2020 in the Journal American Chemical Society Infectious Disease, titled “Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients” by Alexey Polonikov, the more glutathione there was in the bloodstream, the better the prognosis from Covid.
This paper was based on several women who had their blood drawn the month prior to the start of the study, and then developed Covid infection. Those with high levels of glutathione in their blood had a much better outcome, where the disease resolved in a matter of days. Participants who had low levels of glutathione had long-term unresolved symptoms for longer than the duration of the study.
There has also been research, conducted with Dr Fauci, in fact, that have shown its anti-viral effects, especially with regard to HIV. The paper, titled, “Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine” credited to several researchers including Dr. Fauci, concluded that the use of NAC, and its derivative glutathione had many beneficial effects in the treatment of AIDs.
The paper showed that reverse transcriptase activity was significantly decreased. Reverse Transcriptase is where the HIV virus converts its RNA into viral DNA. Inhibiting this process is a goal of many of the drugs currently used to treat AIDs. Retrovir, Epivir, Ziagen, and a host of other HIV drugs attack this very process of the HIV virus, though not as effectively as 80-90%, which was the result of administration of NAC in patients with HIV/AIDs.
From the abstract, “Reverse transcriptase activity,… was decreased by 80-90% after pretreatment with GSH, GSE, or NAC. The induction of total HIV protein synthesis was also decreased appreciably after pretreatment with GSH, GSE, or NAC. The accumulation of HIV mRNA was substantially suppressed after pretreatment with NAC but to a lesser extent after pretreatment with GSH or GSE….The present findings,… suggest that therapy with thiols may be of value in the treatment of HIV infection.“
This is incredible, and every HIV and AIDs patient should be treated with this valuable chemical, either as a drug or as a supplement. If a pharmaceutical drug had a 80-90% effect on the reverse transcriptase activity, it would be fast-tracked to approval by the FDA. But wide-scale implementation of administration to AIDs patients did not happen. Most AIDs patients have no idea that these studies were even conducted, or that such a valuable treatment option, with no or low side-effects, exists.
Any such patients who keep up with medical research, especially from alternative sources, were probably aware of the antiviral uses of NAC, both for Covid and for HIV. In fact, it was a best-seller last year, as it was reported in several non-mainstream publications, such as What Doctors Don’t Tell You and the Orthomolecular News Service.
As a result, they were likely already taking this supplement. For the FDA to step in and claim that they have already concluded that NAC is a drug and cannot be marketed as a dietary supplement, at a time when such supplement are crucial, is completely ridiculous, unscientific, and legally tenuous.
Where Do We Go From Here
Many of our readers are likely asking this question. Unfortunately, it would seem that Amazon is unlikely to reverse their decision any time soon. This gives consumers an opportunity to demand the attention of the behemoth with their pocket books. This is a very effective way to gain attention of giant companies.
If you want to try the supplement yourself, you can buy it from many other retailers. Walmart, Lucky Vitamin, VitaCost, and many others still have the supplement in stock. Source Naturals is still manufacturing this supplement, and with incredible demand, they are shipping it to distributors all over the country. This may, in fact, be an opportunity for you to discover new retailers that you can use for other vitamin supplements, instead of the giant Amazon. Even eBay has not removed this supplement from its website, so you can purchase from them too.
Something else you might want to do: write a letter to Amazon. A letter from a consumer will have much more impact than a review or an email. Express your disappointment that they have removed this supplement from their site, which they are not required to do, and without any argument. Other companies have, thankfully, not followed their example.
You can also write a letter to the FDA. Explain your frustration with their ambiguity and overreach. Letters from consumers can also have an impact on their future decision when it finally does come. Since there has been no response from the FDA other than the one noted above, that they are investigating the matter and will let them know soon, this is an issue that is languishing. Without additional warning letters to other retailers or manufacturers, nothing more is happening on this issue, and the market for NAC supplements is still strong.
However, consumer input is very important on this matter. Since the FDA has made a statement that is contrary to both law and practice (that NAC cannot be sold, and that supplements are generally left along by FDA), it is up to consumers to vote with their wallets and to take their complaints directly to the source.
In addition, if you do not have a supply of NAC, or if you are concerned that it may become completely unavailable in the future, buy a supply for yourself. VitaCost has a limit of 8 bottles, and they appear to have recently replenished their stock. Walmart was selling NAC through DailyVita, and they were still in stock. If the major retailers are out, then just search on Google, and purchase from the shopping links. Source Naturals and Now Foods are high quality and inexpensive, and have lately been available. These are very shelf stable supplements, with a three to four year expiration date, and they would likely last even longer without any additional ingredients that can go rancid (check the labels before you buy).
One final thing you can do is to sign a petition online, posted by Meghan Walker at change.org. They are close to their goal of 2,500 signatures, and it should be even higher than that. Thousands of people are helped by this supplement, and they need to continue to be helped by it.
Other than that, all that we can do is wait. Do your own research, take responsibility for your own health, and do what is best for you and your family.