Name: N-acetylcysteine, NAC, acetylcysteine
Number of scientific references: 38
Level of Evidence: Level II What is this?
Note: N-acetylcysteine is proven to improve antioxidant defences and reduce depressive symptoms. Though there are limited studies on Major Depressive Disorder with this compound, NAC is proven to reduce depression and improve mental health in various conditions. Thus it is likely to benefit as an add-on to conventional therapy in depression.
Dr Dean and colleagues have referred to N-acetylcysteine as ‘a useful agent in the treatment of psychiatric disorders’. And some reviews on the internet have confirmed this by stating that it is helpful for depression and other mood disorders.
N-acetylcysteine or NAC is a derivative of the non-essential amino acid, L-cysteine. It’s usage in the field of medicine, is primarily for detoxifying in case of drug overdose. Apparently, it has been used for 30 years or more for treating paracetamol overdose.
Apart from that, it has been used to reduce mucus in chronic obstructive pulmonary disease, to protect kidney health in contrast-induced nephropathy and for treating HIV.
N-acetylcysteine’s use in mental health conditions is attributed to its antioxidant property. It is a precursor to a powerful antioxidant present in our body- glutathione.
Consuming oral glutathione or oral l-cysteine does not boost glutathione levels. But oral NAC consumption increases cysteine levels in the blood and results in increased levels of glutathione.
Oxidative stress and reduced natural antioxidant defences are some of the important factors that worsen depressive disorder. NAC helps in depression by boosting the brain’s natural antioxidant defense agent-glutathione.
Let’s explore some evidence-based ways by which NAC can help in depression.
Suggested NAC Supplements For Depression
Please consult a health practitioner before taking any health supplements.
There are many NAC supplements available online, but I have selected the ones that have only NAC (no additional minerals).
Also, there is a buzz about pharmaceutical grade NAC and I have listed two of those as well. Pharmaceutical grade NAC are those that are used in research studies and are packaged in a way to decrease their chance of oxidation.
There is not much data to comment whether pharmaceutical grade is better than dietary supplement, but those using regular dietary supplement form have also experienced relief from depressive symptoms.
A few things to note about NAC use:
- NAC is a sulphur containing compound and hence may emit a rotten egg odour. This happens when the supplements are exposed to air so please ensure that you store them appropriately.
- NAC is a powerful antioxidant; avoid using any other antioxidant (herbal/natural) along with it or reduce the dosage.
- NAC aids in detoxing; to avoid distressing detoxing symptoms start with small doses and increase gradually over weeks.
N-AcetylCysteine Dietary Supplements
|Jarrow Formulas NAC Sustain TM||Life Extension NAC|
Image Credit: Jarrows Formula
Image Credit:Life Extension
|Dietary supplement containing 600mg NAC in patented optimised release technology in veg capsules||Dietary supplement containing 600mg NAC in veg capsules|
|Buy from Amazon
Buy from iHerb (Global)
|Buy from Amazon
Buy from iHerb (Global)
Pharmaceutical Grade N-AcetylCysteine Supplements
|BioAdvantex PharmaNAC||Swanson Ultra AjiPure NAC|
Image Credit:BioAdvantex Pharma Inc.
Image Credit: Swansons Vitamins
|Pharmaceutical grade 900mg NAC (Thiolex TM) effervescent tablets||Pharmaceutical grade 600mg NAC (AjiPure) in veg capsules|
|Buy from Amazon (US, Canada)
Buy from iHerb (Global)
|Buy from Amazon (US, UK)|
6 Potential Benefits of N-Acetyl Cysteine For Depression
Here are a few scientific studies that suggest the possible therapeutic benefits of NAC in depression.
1. It reduces depressive symptoms as an add-on therapy to conventional antidepressants
Taking N-acetylcysteine alone may boost antioxidant defences in the brain, but most studies have investigated it’s benefits as an add-on to conventional therapy in depression.
Table of Contents
- 1 Suggested NAC Supplements For Depression
- 2 6 Potential Benefits of N-Acetyl Cysteine For Depression
- 2.1 1. It reduces depressive symptoms as an add-on therapy to conventional antidepressants
- 2.2 2. It can help reduce depressive symptoms in other mental health conditions
- 2.3 3. It reduces oxidative stress in the brain
- 2.4 4. NAC may reduce inflammation in the brain
- 2.5 5. It regulates brain chemistry and relieves anxiety
- 2.6 6. It can protect cognition and brain health
- 3 Dosage of N-acetylcysteine For Depression
- 4 Precautions with N-acetylcysteine use
- 5 Conclusion
Researchers from The University of Melbourne examined the effect of NAC as a maintenance therapy for bipolar depression. Individuals with moderate depression were asked to take 1g NAC twice a day for 2months.
An 8 point reduction in depressive score was observed at the end of 8 weeks with improvement in functioning and quality of life.
Researchers have also found this amino acid derivative beneficial for treatment resistant depression. Carvalho et al. (2013) reported that NAC benefits as an add-on therapy in treatment-resistant depression (in this case patients who do not respond to MAOI or monoamine oxidase inhibitors).
Now there has been one study that evaluated NAC’s effect in major depressive disorder. This study was published in The Journal of Clinical Psychiatry, 2014.
Patients were given NAC or placebo in addition to conventional treatment for 12 weeks. The follow up lasted till 16 weeks.
Till 12 weeks, no significant differences were observed between NAC and placebo. In patients with high depressive scores, treatment differences were observed from week 6. At week 12, improvement in ‘impaired functioning’ scores was observed with NAC treatment.
Interestingly a significant improvement was observed at week 16. This was observed regarding improvement in function and reduction of clinically observed symptoms.
Remission and response to therapy were greater in NAC group at week 16.
Adverse events in the form of gastric symptoms and muscle health-related issues were observed in NAC group.
Since benefits were not observed till week 12, researchers concluded that NAC has limited benefits as an add-on therapy for the major depressive disorder.
Despite these mixed findings, a review study published in 2016 concluded that NAC helps reduce depressive symptoms, improves functionality and is well tolerated.
Scientific literature suggests that NAC may interact with certain antidepressants if taken concomitantly. It may help reduce the dose of certain antidepressants to deliver the same therapeutic effect.
Quick Gist: One study demonstrated that NAC does have limited benefits in major depressive disorder which are evident at week 12-16 of the therapy.
Overall NAC can improve therapeutic outcomes of conventional therapy for depression, but more studies are required to investigate its effect specifically in unipolar depression.
2. It can help reduce depressive symptoms in other mental health conditions
This review study ,that found NAC effective in depression, investigated five studies with data on 574 patients with depressive symptoms as a part of various mental health conditions. It also included a study on major depressive disorder.
NAC has shown decent improvement in behavioural conditions, addictive patterns and mental health conditions like bipolar disorder and schizophrenia. Self-harm, at times, is observed as a part of depressive behaviour.
A recent case study reported in 2017 described how N-acetylcysteine treatment helped reduced frequency of self-harm cutting in a 17-year-old girl. It also helped reduced ADHD and depressive symptoms.
Quick Gist: Review of currently available literature suggests that N-acetylcysteine can reduce depressive symptoms in mental health conditions apart from unipolar depression.
It may reduce the frequency of self-harm. Also NAC interacts with antidepressants and this may help reduce the therapeutic dose of these medications; but these findings need to be corroborated.
3. It reduces oxidative stress in the brain
As I told you previously, NAC is used to improve antioxidant defences in depression and other mental health disorders. Oxidative stress is the imbalance between prooxidants and antioxidants in the body.
Now this is a bit geeky part that will give you an idea of how N-acetylcysteine boosts antioxidant defences of the brain. You can skip this point if you wish and check the Quick gist for this section.
NAC is the N-acetyl derivative of amino acid L-cysteine. Once consumed it is rapidly absorbed and converted to L-cysteine. L-cysteine is then, oxidised to cystine.
Glutamate is a neurotransmitter or chemical found in the brain. If present in excess, it causes toxicity to the brain cells and contributes to oxidative stress. In a state of oxidative stress in depression, glutamate toxicity is observed.
Cystine forces excess glutamate out of the cell and enters the cell in its place. Here in the cell, cystine is reduced to cysteine. Cysteine serves as a precursor for antioxidant glutathione and boosts antioxidant defences in the brain.
Smaga et al. have proven via an animal study that NAC exerts an anti-depressant effect by boosting the brain’s antioxidant defences.
However, some researchers feel that NAC by itself is not a powerful antioxidant. They say it is beneficial only in cells that are deficient in the antioxidant glutathione.
And it may be ineffective in cells that still retain the capacity to restore glutathione naturally. This study was discussing the antioxidant property of NAC in general and not about depression.
Quick Gist: N-acetylcysteine’s antioxidant nature helps restore the levels of antioxidant enzymes in the brain and also reduces toxicity and oxidative damage. As a result, a reduction in depressive symptoms are observed.
4. NAC may reduce inflammation in the brain
Inflammation and oxidative stress go hand in hand: the presence of one can give rise to the other. Neuroinflammation or inflammation in the brain is one of the causative factors that worsen depression.
A recent study published in Experimental Biology and Medicine (Maywood, N.J.) demonstrated that NAC along with an antidepressant (fluoxetine) inhibited inflammatory pathways to ameliorate depressive symptoms.
Contrary to expectations, a study in humans did not find definite evidence on this aspect. This study was published in Acta Neuropsychiatrica, 2017.
2000mg of NAC per day was provided in addition to antidepressants for 12 weeks. The patients were followed up four weeks after the study was completed.
A significant reduction in depressive symptoms was observed. Interleukin-6 is one of the agents in our body that is involved in inflammation.
No improvement in inflammatory parameters was observed with N-acetylcysteine treatment. But Interleukin-6 levels were associated with the reduction in depressive symptoms irrespective of whether the patient did or did not respond to the treatment.
Quick Gist: N-acetylcysteine is proven to reduce neuroinflammation. Some studies also suggest that its anti-inflammatory action may benefit in depression, but more research is required to confirm this.
5. It regulates brain chemistry and relieves anxiety
Linck et al. conducted an animal study where they observed that NAC exerts an antidepressant effect by regulating neurotransmitters other than glutamate. It was found to influence norepinephrine and serotonin pathways indirectly.
This ability to regulate brain chemistry may contribute to NAC’s anti-anxiety property.
Data from a recent study published in Brain Behavioural Research, 2017 suggests that NAC’s anti-anxiety activity may be comparable to that of diazepam. Also, it is safer than diazepam.
Certain antidepressants contribute to sleep disturbances. Preliminary findings suggest that the amino acid derivative may help relieve such sleep disturbances induced anxiety.
Quick Gist: Findings from animal studies suggest that N-acetylcysteine can help regulate the brain chemistry which is said to be impaired in depression. This property may be responsible for its anti-anxiety and stress relieving effect.
6. It can protect cognition and brain health
Dodd et al. have identified N-acetylcysteine as a promising neuroprotective agent.
It’s antioxidant, anti-inflammatory properties and ability to regulate brain chemistry protect the brain from neurodegenerative diseases, neurotoxicity and other conditions like traumatic brain injury.
Cognitive dysfunction in major depressive disorder is evidenced by reduced ability to think and concentrate, poor memory and attention, inability to plan tasks, reduced verbal fluency etc.
NAC is identified as one of the agents that can help restore cognition (or thinking) in depression.
Well-planned review studies give us a good idea of the overall efficacy of a particular therapy in a given condition.
A recent review study published in Neuroscience and Biobehavioural Reviews, 2017 highlights that NAC therapy leads to ‘statistically significant improvement in cognition’ but the data on this is limited.
Quick Gist: Apart from reducing depressive symptoms, N-acetylcysteine can help protect cognition in major depressive disorder. Depression may impair our ability to think, concentrate, plan and affect our memory.
But NAC therapy in addition to conventional treatment may help mitigate these effects. Also, it protects brain health from toxicity and other brain disorders.
Dosage of N-acetylcysteine For Depression
NAC has been studied in a dose range of 0.6g to 6g/day. However, most studies have used a dose of 2-2.4g/day, and this dose range is found to safe and well tolerated.
2g NAC per day is effective for depression. Start with a small dose and scale up gradually to identify a dose that suits you. Also it aids in detoxing; to avoid distressing detoxing symptoms start with small doses and increase gradually over weeks.
It is beneficial as an add-on therapy for depression. It may reduce the effective dose of antidepressants and also mitigate the side effects associated with them.
It may interact with antidepressants, so please take a doctor’s advice on the same. Also, maintain a 3-4 hour gap between consuming the two.
Please consult a health practitioner before taking NAC supplements.
Precautions with N-acetylcysteine use
Oral NAC is well tolerated if taken within recommended doses. Gastric symptoms are the most common side effects, and these include mild abdominal pain, heartburn, flatulence, cramps, nausea, vomiting and diarrhoea.
NAC is a sulphur containing compound and hence may emit a rotten egg odour when the supplements are exposed to air. Please ensure that you store them appropriately. Also if a new bottle already has a rotten egg smell, then the supplement may have oxidised and degraded.
It is a powerful antioxidant; avoid using any other antioxidant (herbal/natural) along with it or reduce the dosage.
High dose N-acetylcysteine may have troublesome and some serious side effects as evidenced by the studies reported below.
One study has reported the occurrence of cold sores, neutropenia with a high dose of NAC (6g/day) and this was reversed by reducing the dose.
A case of sensorineural hearing loss was reported with 3g of NAC per day. This could be due to the presence of additives or fillers in the supplements.
One animal study has reported pulmonary hypertension as an adverse effect of chronic NAC administration.
High dose intravenous NAC was found to cause seizures in a child being treated for paracetamol overdose. Serious allergic reactions have been noted with intravenous NAC but not oral.
Please consult a health practitioner before using NAC as an add-on therapy in depression.
The brain engages in high metabolic activity; thus it is important to maintain the organ’s antioxidant defences at normal levels. N-acetylcysteine is a precursor to one of the brain’s important antioxidant glutathione.
Additionally, it regulates glutamate and other neurotransmitters in the brain, reduces brain inflammation, protects the brain from toxicity and other neurodegenerative conditions. This makes it a viable brain protective and antidepressant agent.
Addition of NAC to conventional antidepressant therapy helps boost therapeutic outcomes and can be of benefit to individuals who experience treatment-resistant depression.
But there are a few limitations to the current available literature on this topic.
NAC’s benefits in depression have been studied as an add-on therapy and not in drug naive patients.
Also, it would be interesting to compare it’s antioxidant and antidepressant action with plant-based compounds that show dual action as well (e.g.: curcumin).
It benefits in reducing depressive symptoms in other mental health conditions and addiction-related disorders. More research is required to examine its effect on unipolar depression alone.
NAC may help you in depression when you are taking conventional therapy, and if antidepressants are not delivering the desired effect and also if your diet is deficient in antioxidants ( if it is missing out on fruits, veggies and herbs).
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