One Intervention, Many Effects

Last week, I started my review of the famous antioxidant, N-acetylcysteine (NAC). I discussed how it is used in conventional medicine to prevent the toxic effects of acetaminophen overdose on the liver. I also highlighted its role in oxidative stress by protecting the body from cellular damage that can occur from hungry free radicals.

However, NAC is more than just a precursor to the “master antioxidant”, glutathione. It has many other uses and has been shown to support respiratory, reproductive, immune, and emotional health. I did a quick review of its many applications in this week’s blog, which you can read here.

What has recently piqued my interest in NAC is the research on its use in psychiatric disorders. Although I know that you cannot  medicate away any brain disorder or emotion with a pill, I was intrigued with NAC’s promising preliminary evidence as a low cost and low risk intervention. This is particularly appealing to me because of the current mental health crisis.

According to recent statistics, one in five adults suffer yearly from a mental health issue and many are not seeking treatment. To complicate matters, this area in healthcare is fraught with high degrees of stigmatization, misperceptions, and controversies in treatment. (source, source, source, source)

A major plus of a natural substance is that it has the potential to impact more than just one area of wellness. This may provide an advantage over, or additional support to, a chemical which only manipulates one biochemical pathway and can result in unwanted side effects. (This is similar to the concept of synergy with essential oils.) (source, source, source)

So, How Does NAC Work?

Several mechanisms have been suggested on how NAC may modulate brain health and are listed below: (source, source, source, source, source)

  • Down-regulation of the part of the brain that is associated with “addiction,” the nucleus accumbens. This is via the cystine-glutamate exchange system which results in increasing extracellular glutamate and the regulation of dopamine (DA) release, two brain signaling molecules.
  • Modulation of glutathione and oxidative stress. (see above)
  • Decreasing inflammatory mediators.

In a 2009 review article, the authors reiterate my belief that there are many positive implications to the fact that NAC may be targeting various pathways common across psychiatric disorders. They also discuss the limitations of the current classification of mental illnesses, which tries to fit one diagnosis into a single, neatly fit category:

The apparent lack of specificity of NAC in initial studies is intriguing and suggests that it may be targeting pathways that are common across disorders; oxidative stress appears to be a fairly nonspecific finding in a range of psychopathologies, and dysregulation of glutamate, inflammatory pathways and DA are similarly widely reported. Given that the current diagnostic systems are phenomenologically based, and that in no other branch of medicine are phenomenology and pathophysiology linearly linked, this may reflect an intrinsic limitation of our classification system. This is high-lighted by the fact that there is extensive overlap of other treatments and biomarkers across disorders. As the body of evidence is currently provisional for many disorders, as the evidence base expands, it is possible that the efficacy will appear to be greater in some areas than others.


More on NAC’s Efficacy for Brain Health

The bottom line on NAC for brain health is that it has a lot of potential, some impressive and clinically meaningful results, and overall is very safe. (source, source, source).

Still, there are some limitations in trials with NAC to take into consideration, including:

  • individual variations in oxidative stress may impact appropriateness of treatment. For example, this review on the use of NAC for schizophrenia found that those with depleted GSH were the subtype of patients that responded favorably. There was no effect in those who already had sufficient glutathione levels.
  • variations in duration of treatment and dosages used across studies make it hard to standardize prescriptive strength.
  • co-administration of other therapies, i.e., antidepressants, may have impacted effectiveness.
  • intrinsic biases in supplement studies as outlined in Box 2 in my previous blog.
  • higher than needed dosage may cause more oxidative stress vs. helping to decrease it. (i.e, the hormesis effect or the “goldilocks” U-shaped optimal dose range)
  • need for more long-term studies, as with everything! (source, source)

Regarding the last point, one doctor who spoke on the topic of PANDAs (Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal Infections) stated that NAC may run out of efficacy long-term in this population due to the fact that it can become easily oxidized. (Those hungry free radicals are chomping on the NAC every time the bottle is opened and exposed to oxygen.) Due to this factor, it was suggested to take NAC in liposomal form, or, if not available, to refresh the bottle consistently.

For those who wish for a more detailed summary of the current literature on the evidence for NAC, I found this overview that assesses various clinical trials.

Cautions with NAC

There are some specific precautions to consider before using NAC. Below are a few of them.

1. Sulfur Utilization Issues and/or Genetic Variations in Efficacy of Sulfur Metabolism

Some individuals have an issue with sulfur utilization. An example of this is those with a variation in an enzyme known as cystathionine-beta-synthase (CBS). Other causes of sulfur sensitivity can be suboptimal methylation, bacterial overgrowth in the small bowel, and issues with detoxification. They may experience side effects when eating certain foods or taking certain supplements with cysteine and sources of sulfur. More information can be found here and here.

WARNING: PLEASE DON’T GO SPASTIC OVER a SNP (Single Nucleotide Polymorphism)!

Please, please (TWO PLEASES) note that no single nucleotide polymorphism, or genetic variation found within a population, alone determines an intervention.

Considering bioindividuality and the context of the gene and how it interplays with one’s lifestyle, emotions, and environment are keys to determine if it is even significant!

2. Even with NAC hitting more than one mechanism, most often more than one intervention will be needed, and nothing can replace psychological support.

For example, Exposure and Response Prevention (a form of cognitive behavior therapy) is the gold-standard treatment for OCD (obsessive compulsive disorder). There are many factors involved in brain health and these all need to be considered (see below).

3. Safety First!

Please check with your primary care provider before implementing any change to your health care regimen.

The Bottom Line with NAC and When You May Consider Using It

Just to reiterate what I stated in the previous section, I am not implying that any one intervention is the “cure” for any psychological issue. The complexity of factors linked to brain function is enough to make any head spin and they are listed in Box 1 below.

Therefore, you may be wondering, “Then when do you use NAC for psychological issues?”

The skill of a practitioner that looks at the whole person can help determine appropriateness of its use.

Coming Up- Essential Oils Return



Although I’ve written many articles on essential oils as a tool for emotional, physical, and spiritual support, diving deep into NAC’s mechanisms made me curious to explore in more detail how essential oils work at the biochemical level of the brain via neurotransmitters.

Coming up, I will decode in common language how one of my favorite holistic modalities impact brain signaling mechanisms.

Stay tuned!


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This material is for information purposes only and is not intended to diagnose, treat, or prescribe for any illness. You should check with your doctor regarding implementing any new strategies into your wellness regime. These statements have not been evaluated by the FDA. (Affiliation link.)

Disclaimer: This information is applicable ONLY for therapeutic quality essential oils. This information DOES NOT apply to essential oils that have not been tested for purity and standardized constituents. There is no quality control in the United States, and oils labeled as “100% pure” need only to contain 5% of the actual oil. The rest of the bottle can be filled with fillers and sometimes toxic ingredients that can irritate the skin. The studies are not based solely on a specific brand of an essential oil, unless stated. Please read the full study for more information.

Thanks Pixabay.

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