The FDA’s Targeting of NAC is a target on Over the Counter Therapies
The reversal to ban the supplement may have Overarching Consequences
Note that this newsletter is intended to be informative and not prescriptive. Please seek out medical professionals to consult/discuss this topic with.
On Steven Crowder’s podcast “Louder with Crowder” he mentioned the FDA targeting the over the counter supplement N-Acetyl Cysteine (NAC). This target includes warning supplement companies about the selling of NAC. It seems the FDA has used an arbitrary rule that the supplement’s designation as a drug during the 1980’s means that it cannot be sold over the counter or online, even though it was widely available for purchase for several decades.
This targeting of the supplement is not new; it seems to have started around the summer of 2020. Strangely (or not so strangely) enough this is around the same time that hydroxychloroquine was targeted and had it’s EUA approval removed, so there may be some link to its effectiveness in treating COVID-19.
N-Acetyl Cysteine is an L-Cysteine residue with an additional acetyl group added to the nitrogen atom (ergo N-acetyl).
Taken from PubChem:
Acetylcysteine is a synthetic N-acetyl derivative and prodrug of the endogenous amino acid L-cysteine, a precursor of the antioxidant glutathione (GSH), with mucolytic, antioxidant, and potential cytoprotective, cancer-preventive, and anti-inflammatory activities. Upon administration, acetylcysteine exerts its mucolytic activity by reducing disulfide bonds in mucoproteins, resulting in liquification of mucus and reducing its viscosity. It is also used for the treatment of acetaminophen overdose as it can restore the depleted GSH reserves in the hepatocytes during the process of detoxification. The antioxidant activity is attributed to the ability of GSH to scavenge reactive oxygen species (ROS), thereby preventing ROS-mediated cell damage, decreasing oxidative stress, protecting cells against the damaging effects of free radicals and preventing apoptosis in these cells. In addition, this may inhibit tumor cell proliferation, progression and survival, in susceptible tumor cells that rely on ROS-mediated signaling for their proliferation and malignant behavior. Under certain circumstances, acetylcysteine is able to induce apoptosis in susceptible cells, including certain tumor cells, via the intrinsic mitochondria-dependent pathway but not involving endoplasmic reticulum stress. Also, acetylcysteine may also be able to degrade Notch2, thereby preventing proliferation, migration, and invasion in Notch2-overexpressing glioblastoma cells. In addition, acetylcysteine may inhibit viral stimulation by reactive oxygen intermediates, thereby producing antiviral activity in HIV patients. Acetylcysteine also possesses anti-inflammatory activity through modulation of the nuclear factor-kappa B (NF-kB) pathway and the modulation of cytokine synthesis.
NAC has an extremely broad range of uses, so no wonder many see it as a miracle supplement. Many people have indicated online about using it for mobility, depression, fatigue, and to help with symptoms of COPD. Note that this does not mean NAC is effective against the listed symptoms, nor does it mean I condone it’s usage. However, it does indicate a cheap, over the counter supplement with a possibly large variety of uses. In a time when many people would like to take better care of themselves it seems like having a cheap option may go against the interests of certain corporations.
Here is another list of other possible clinical uses for NAC taken from Dominari et. al. 2021:
Respiratory Diseases
A study by Cotgreave et al[61] observed the levels of NAC in the bronchoalveolar lavage of six healthy volunteers following administration of 600 mg of NAC orally for four weeks. Although the levels of NAC, cysteine, and glutathione in the bronchoalveolar lavage fluid did not increase, the levels of protein-bound NAC and both free and total plasma glutathione were shown to rise significantly[62]. On the other hand, a study by Rodenstein et al[62] demonstrated that NAC given orally to people with respiratory disorders led to a similar NAC level in the plasma and lung tissue. NAC has been used as a mucolytic agent in chronic bronchitis. Although initial studies like the one by Millar et al[63] showed no significant effect in patients with chronic bronchitis, a study by Parr et al[64] showed that there is a substantial decrease in the number of incapacitated days in the individuals suffering from chronic bronchitis.
Additionally, Rasmussen et al[65] conducted a double-blind, placebo-controlled, six-month comparison study, which showed that the NAC treatment group had a lower number of sick-leave days and exacerbation days. Jackson et al[66] conducted a multicenter, double-blind, placebo-controlled study that found that the difficulty in expectoration and cough severity improved and was more evident in patients using NAC. Behr et al[67] studied the effect of NAC administration for 12 wk on 18 patients suffering from fibrosing alveolitis, a disease known for the uncontrolled activation of the oxidative stress response, as well as for the reduced levels of GSH in the lower respiratory tract. This treatment led to improved pulmonary function tests and an increase in total and reduced glutathione[68]. NAC has shown some preventive effect of microembolism in a rat model having acute respiratory distress syndrome by decreasing alveolar edema, fibrin deposition, and plasma viscosity.
Cancer
NAC has been proven to have some beneficial effects on cancer and its management. Though evidence is still preliminary, a few studies have shown its efficacy when combined with chemotherapeutic agents. De Flora et al[69] have studied NAC's effect on GSH metabolism and the biotransformation of carcinogenic compounds. In vitro and in vivo studies have shown that NAC counteracted the mutagenicity of direct-acting compounds and, at high concentrations, inhibited procarcinogens' mutagenicity[70]. This study has also combined NAC with doxorubicin and found that, under certain experimental conditions, it can be highly effective by working synergistically with doxorubicin to reduce tumor formation and prevent metastases. Pre-treatment with NAC increased the non-protein content of P388 Leukemia cells nearly threefold, without negatively affecting the chemotherapeutic activity of doxorubicin against this tumor.
Heart Disease
NAC is also useful in heart disease. It affects the levels of homocysteine and possibly even the levels of lipoprotein A. Moreover, it protects against ischemic and reperfusion damage and increases the efficacy of nitroglycerine. Gavish and Breslow et al[71] proved that NAC administration to patients with increased lipoprotein levels had reduced plasma lipoprotein levels by 70%. Wiklund et al[72] postulated that NAC administration reduces plasma homocysteine levels by 45% but did not show any effect on lipoprotein levels. Bostom et al[73] reported that even in dialysis patients who have high homocysteine levels and are refractory to vitamin B supplementation, oral NAC supplementation resulted in a 16% decrease in non-fasting pre-hemodialysis total plasma homocysteine[74]. In combination with nitroglycerin and streptokinase, NAC decreased the oxidative stress and preserved left ventricular function in patients with evolving acute myocardial infarction[75]. In combination with nitroglycerin, NAC should be used with caution because of the adverse effects[76].
Cigarette Smoking
Oral supplementation with NAC is necessary for smokers and people exposed to second-hand smoke, as NAC has been proven to decrease smoking-induced mucus cell hyperplasia, epithelial hypertrophy, and the time required for the secretory cells to return to normal[77].
HIV
HIV-positive individuals have low cysteine and GSH levels. Supplementation of NAC in these individuals has been studied, and the results are still unclear. Wu et al[76] observed that NAC administration had increased the ability of cells to form T-cell colonies in people with AIDS[78]. Herzenberg et al[77] noted that the oral administration of NAC in HIV-infected individuals improves GSH levels and aids in the improvement of survival rates in this population[79]. Sandilands et al[80] suggested that NAC administration to HIV-infected individuals prevented the progression to AIDS. Though further evidence is needed to determine NAC's efficacy in HIV-positive individuals, based on the available evidence, NAC supplementation can be considered an essential component of anti-HIV treatment in individuals with low GSH levels[81].
And when it comes to COVID-19 NAC may have many different clinical routes. Here’s a quick list from Shi et. al. 2020 summarized below:
NAC may have immunomodulating abilities by replacing depleted glutathione reservoirs.
NAC may target NF-ϰB pathways to reduce viral replication.
NAC may target SARS-COV2’s main protease and cause inhibition.
NAC can reduce severity and incidence of pneumonia.
NAC’s antioxidant properties can reduce Reactive Oxygen Species (ROS) and help improve lung function.
As of now there seems to be 19 Clinical Trials utilizing NAC as well as 58 publications that mention the supplement.
So why target NAC and ban its use as a supplement? Maybe social media’s influence may cause people to overdose on NAC. However, that position won’t hold up, considering that NAC helps with acetaminophen overdose, which may indicate it’s very difficult to overdose on the supplement.
I have outlined in previous newsletters that many cheap, over the counter therapeutics that have been used worldwide have gained recent stigmatization and have undergone severe scrutiny. In this case we actually have the targeting of a widely used supplement.
This step is an even larger step towards encroachment; not only does it indicate that supplements that may have some benefit against SARS-COV2 may become a target by regulatory bodies such as the FDA or CDC, it also provides validation to target other supplements as well.
One of the new supplements being looked into for anti-aging properties is nicotinamide (NAD+), which is also being looked into for COVID as well. It wouldn’t be hard to see that something such as NAD may become a target if it may indicate some usefulness against COVID or other diseases.
In fact, this sets the precedence that any widely available supplement may become a target by the FDA if they indicate any effects that would make it difficult for pharmaceutical companies to patent or charge exorbitant prices on. This assertion is speculative, but it also would fit with what we have been seeing over the past 18 months.
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In-Text Citations:
Dominari et. al. 2021. Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19. Taken from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995409/
Shi et. al. 2020. N-Acetylcysteine to Combat COVID-19: An Evidence Review. Taken from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649937/
Additional Info:
Thiols for COVID-19: https://link.springer.com/article/10.1007%2Fs00408-021-00465-3
NAC Substack- This is another person’s Substack I came across who made a post a month prior about this topic if you would like to check it out:
Editor’s Note: I added 2 extra images taken from Pubchem indicating the difference in fatal doses between NAC and Acetaminophen.