N-acetylcysteine (NAC), a precursor for glutathione biosynthesis, is a common dietary supplement that may hold the secret to treating tumors resistant to conventional cancer drugs. Researchers at the Department of Biomedicine at the University of Basel in Switzerland found that NAC restores the sensitivity of breast cancer cells to treatment.1:
NAC is already valued in the medical field for helping to increase glutathione in the body, which prevents liver damage from acetaminophen (Tylenol) overdose. It also reduces the toxicity of acetaldehyde,2: which causes many hangover symptoms. But it appears that NAC is living up to its reputation as an “old drug with new tricks,” as a recent study shows that it can significantly improve breast cancer treatment.
NAC may help fight persistent breast cancer
Breast cancer is the most common cancer in women, with more than 2.2 million cases developing annually.3: Survival rates among women with recurrent disease have barely improved over the past two decades. “Most recurrent metastatic cancers are either drug-resistant or will become resistant to therapy,” the researchers write in Cell Reports Medicine. “Thus, drug resistance is a significant obstacle in the long-term treatment of patients.”4:
About 70% of breast cancers have mutations in genes that affect the PI3K signaling pathway.5:00 Overactivation of PI3K promotes tumor development, which is why the drug alpelicib (brand name Piqray), a PI3Kα-selective inhibitor, is often used to treat it. Drug resistance, however, is a serious problem.
“Unfortunately, it turned out that the drug’s success is severely limited by resistance,” researcher Mohamed Bentires-Alj said in a news release from the University of Basel. “Therefore, we urgently need to learn more about how resistance occurs.”6:00
The team found mutations that shut down the production of a protein called NF1, which suppresses tumor growth, are involved in alpelicib-resistant cancers. “The absence of NF1 is the elephant in the room. it messes things up in the cell and prevents successful treatment,” Bentires-Alge said.7:00
When NF1 was lost, the team found that cells produced less energy through their mitochondria and relied more on other energy-producing pathways. NAC, an antioxidant, affects energy metabolism in a similar way, so the researchers expected it to have the same effect on cancer cells as the loss of NF1. Instead, the opposite happened.
NAC unexpectedly restored and enhanced the efficacy of alpelisib in previously resistant cancer cells. Loss of NF1 is also frequently implicated in other drug resistance cases, including skin, ovarian, endometrial, lung, and bladder cancers, so it is possible that NAC may be useful in the treatment of many drug-resistant cancers.8 o’clock
“Since N-acetylcysteine is a safe and common supplement, this result is very important for clinical research,” says Bentires-Alge. The team plans to conduct further trials in breast cancer patients to see if NAC improves treatment in resistant cases.9:00 The study concluded:10:00
“NF1 loss is a resistance-enhancing event in PI3Kα inhibition. This suggests that patients with tumors lacking NF1 are likely to develop resistance to PI3Kα inhibition. Furthermore, we found that NAC treatment circumvents resistance to PI3Kα inhibition, possibly by attenuating glycolytic activity and mTOR signaling, and may be an attractive strategy to test in patients with resistant NF1 loss.”
Anticancer effects of NAC
NAC, a form of the amino acid cysteine, has long been considered a preventative and therapeutic agent for conditions involving glutathione depletion. It was found to be safe “even at very high doses and for long-term treatment,” according to researchers at the University of Genoa in a review of Carcinogenesis.11:00
The study points out that NAC has the potential to prevent DNA damage, cancer, and other mutation-related diseases, noting its “impressive array of mechanisms and protective effects against DNA damage and carcinogenesis.” This includes:12:00
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Nucleophilicity |
Antioxidant activity |
Modulation of metabolism |
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Effects in mitochondria |
Reducing the biologically effective dose of cancer |
Modulation of DNA repair |
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Inhibition of genotoxicity and cell transformation |
Modulation of gene expression and signal transduction pathways |
Regulation of cell survival and apoptosis |
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Anti-inflammatory activity |
Antiangiogenic activity |
Immunological effects |
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Inhibition of malignant tumor progression |
Effect on cell cycle progression |
Inhibition of preneoplastic and neoplastic lesions |
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Inhibition of invasion and metastasis |
Protection against adverse effects of other chemopreventive agents or chemotherapeutic agents |
A number of studies support the anticancer potential of NAC. In a mouse study, combining ketogenic with NAC significantly reduced tumor growth in anaplastic thyroid cancer, an aggressive and often fatal form of the disease.13:00 Another study showed that NAC inhibited the growth, adhesion, migration, and invasion of human bladder cancer cells.14:00
Similar effects were observed in breast cancer cells, where NAC reduced proliferation and increased apoptosis, or cell death.15:00 When combined with bromelain, NAC also significantly inhibited the proliferation and survival of gastrointestinal cancer cells.16:00
Is NAC a fountain of youth?
In addition to its anti-cancer role, NAC may help prevent premature aging through its longevity-enhancing effects. Specifically, a combination of NAC and glycine, known as GlyNAC, improved “deficits associated with premature aging” in people with HIV.17:00 This included improvements in oxidative stress, mitochondrial dysfunction, inflammation, endothelial dysfunction, insulin resistance, genotoxicity, strength and cognition.18:00
A subsequent pilot trial in older adults found similar results, with GlyNAC supplementation for 24 weeks correcting glutathione deficiency and improving multiple measures of health, including:19:00
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Mitochondrial dysfunction |
Oxidative stress |
Inflammation |
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Endothelial dysfunction |
Insulin resistance |
Genomic damage |
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Cognition |
Power |
Walking speed |
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Exercise capacity |
Body fat level |
Waist circumference |
The researchers concluded that “GlyNAC supplementation in aging individuals may be a simple and viable method for health promotion and warrants further investigation.”20:00 GlyNAC supplementation also improved four of the nine hallmarks of aging known to contribute to age-related disorders. This includes:21:00
- Mitochondrial dysfunction
- Inflammation
- Insulin resistance
- Genomic damage
Neuroprotective effects of NAC and stroke benefits
People with hereditary cystatin C amyloid angiopathy (HCCAA), a rare genetic disorder,22:00 their average life expectancy is only 30 years, and most die within five years of their first stroke.23:00 Thus, reducing their incidence may be important to increase survival.
NAC may help prevent strokes in the population by preventing the formation of amyloid-producing proteins that contribute to the build-up of amyloid associated with strokes.24:00
Researchers at the Children’s Hospital of Philadelphia (CHOP) conducted a study indicating that NAC may also have potential for Alzheimer’s disease, as the protein aggregation process that occurs in HCCAA is similar to Alzheimer’s, albeit at an accelerated rate in HCCAA. :
NAC shows promise for psychiatric and neurological disorders
NAC also shows particular promise in the treatment of mental health disorders, including post-traumatic stress disorder.25:00 depression26:00 and substance use disorders.27:00
It is known to modulate pathophysiological processes such as oxidative stress, neuroinflammation, and dysregulation of glutamate and dopamine neurotransmitter systems that contribute to psychiatric and neurological disorders.28:00 According to a systematic review published in Neuroscience & Behavioral Reviews,29:00
“In this systematic review, we find favorable evidence for the use of NAC in a number of psychiatric and neurological disorders, particularly autism, Alzheimer’s disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder. : schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy.
Disorders such as anxiety, attention deficit hyperactivity disorder, and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies… Overall, NAC treatment appears to be safe and tolerable.”
Was NAC targeted as it fights COVID-19?
Among the many benefits of NAC is its ability to reduce viral replication of certain viruses, including the influenza virus.30:00 During the pandemic, NAC emerged as a tool to prevent and treat COVID-19, including hypercoagulation, which can lead to stroke and/or blood clots.31:00 which impair the ability of the lungs to exchange oxygen. As mentioned in the FASEB magazine in 2020.32:00
“Based on a wide range of antioxidant and anti-inflammatory mechanisms… oral administration of NAC is likely to reduce the risk of developing COVID-19, as has been previously shown for influenza and influenza-like illnesses.
Furthermore, high-dose intravenous NAC can be expected to play an adjunctive role in the treatment of severe COVID-19 cases and the control of its fatal complications… including pulmonary and cardiovascular adverse events.”
Another literature review33: concluded that glutathione deficiency may be associated with the severity of COVID-19, leading the author to conclude that NAC may be useful for both its prevention and treatment.
Not long after several scientists pointed to NAC’s benefits against COVID, the US Food and Drug Administration (FDA) suddenly clamped down on the supplement, claiming it was exempt from the definition of a dietary supplement because it had been approved as a new remedy: 196334: — before it is sold as a dietary supplement or as a food.
Retailers, including Amazon, responded by pulling supplements containing NAC from their shelves because the FDA’s move meant that NAC could no longer be legally sold as a supplement, even though the National Institutes of Health’s Dietary Supplement contained no less than 1,170 Products containing NAC. Fill the Label database then.35:00
The draft guidance issued by the FDA in April 2022,36: However, there have been rumors suggesting that the FDA would not enforce its policy that NAC could not be marketed as a dietary supplement, even though it was still technically illegal to do so. In August 2022, after the FDA issued its final guidance, Amazon “quietly notified” supplement manufacturers that it was resuming sales of NAC dietary supplements.37:
Fortunately, research into NAC’s potential anti-cancer and other disease-reducing effects is ongoing. And if you’re curious about NAC’s health-promoting potential and are interested in supplementing with NAC, it’s inexpensive and, for now, widely available.
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