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Name: N-acetylcysteine, NAC, acetylcysteine
Goes well with: Curcumin
Number of scientific references: 47
Level of Evidence: Level II What is this?
Note: N-acetylcysteine is proven to improve antioxidant defences and regulates brain-chemistry to relieve addiction. No study to date has explored the effect of NAC on alcoholism alone; several studies have found NAC beneficial for treating substance use disorders or mental health conditions that may involve alcohol abuse.
It can also help reduce depressive symptoms and help manage co-existing mental health conditions in alcoholism. N-acetylcysteine can help in alcohol addiction and withdrawal, but it is advisable to consult a doctor before taking NAC to avoid drug interactions.
N-acetylcysteine (NAC) is a derivative of amino acid L-cysteine. It is a mucus-reducing agent that is used in cystic fibrosis treatment and for treating paracetamol overdose.
It is also beneficial for conditions like ulcerative colitis, PCOS, infertility, neurodegenerative conditions etc.
It benefits in mental health disorders by raising antioxidant defences and regulating brain chemistry. Glutathione is our primary antioxidant that is produced naturally in our body.
It maintains redox status of the cell, scavenges free radical species and curbs oxidative stress, regulates immune responses and activity of inflammatory mediators. NAC serves as a precursor to glutathione and helps maintain cellular glutathione status.
N-acetylcysteine benefits in alcoholism by restoring the function of neurotransmitter glutamine to normal; dysfunction of glutamine contributes to alcohol addiction and withdrawal. It also boosts antioxidant defences, protects from alcohol toxicity and relieves mental health related symptoms.
No study till date has examined the effect of NAC on alcohol addiction exclusively but there are a few studies on substance abuse and compensatory alcohol use which can shed some light on this topic.
Suggested NAC Supplements For Alcoholism
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 benefits for mental health.
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|
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|
6 Evidence-Based Benefits Of NAC For Alcoholism
Very few studies have investigated the role of NAC in alcohol addiction. Nevertheless, let’s go over other research studies that can help us draw a parallel between substance abuse and alcoholism.
Table of Contents
- 1 Suggested NAC Supplements For Alcoholism
- 2 6 Evidence-Based Benefits Of NAC For Alcoholism
- 2.1 1.N-acetylcysteine can reduce alcohol addiction
- 2.2 2.It can help reduce alcohol withdrawal symptoms
- 2.3 3.It protects from alcohol-induced toxicity
- 2.4 4.It helps as an antioxidant and anti-inflammatory agent
- 2.5 5.N-acetylcysteine can protect mental health and cognition in alcohol addiction
- 2.6 6.It can benefit in alcohol-induced peripheral neuropathy
- 3 Dosage of N-acetylcysteine For Alcoholism
- 4 Precautions with N-acetylcysteine Use
- 5 Conclusion
1.N-acetylcysteine can reduce alcohol addiction
N-acetylcysteine provides our system with the amino acid cysteine. NAC and Cysteine have two major roles:
- Boosting antioxidant defences
- Regulating neurotransmitter glutamate levels
NAC is broken down to cysteine which along with L-glutamate and L-glycine helps in producing glutathione. Cysteine levels control the amount of glutathione produced.
Now glutamate and its related glutaminergic system are actively involved in repetitive reward-seeking behaviour. Disturbance of glutaminergic system can cause toxicity to the brain cells, and this disturbance is observed in substance use disorders, OCD etc.
Acute alcohol exposure reduces the activity of these receptors, but chronic alcohol exposure followed by its withdrawal leads to hyperactivity of the receptors.
Cysteine derived from NAC enters astrocytes (a type of brain cells) and is exchanged for glutamate present in the cell. The glutamate moves out of the cell and participates in the communication between neurons.
The level of cysteine and glutathione regulates the amount of glutamate released out of the cells. Also, glutathione activates the NMDA receptors response to glutamate.
The total of these reactions is that NAC reduces the decline in cysteine-glutamate exchange and restores the function of the glutaminergic system in addiction.
Restoration of glutaminergic function by NAC can reduce addiction and relapse. There haven’t been many studies investigating the effects of NAC in alcohol addiction, but researchers have explored its effect on substance abuse.
Let’s go through those studies.
A recent study published in Addiction Biology, 2018 revealed the benefits of N-acetylcysteine for alcohol addiction via an animal model.
NAC was found to reduce motivation and reduce alcohol-induced reinforcement (the feelings of high after consuming alcohol that motivates an individual to consume more) by 35-81%.
It reduced alcohol-seeking behaviour by 77% and reduced relapse after short-term abstinence. Researchers concluded that N-acetylcysteine could be a potential treatment for maintaining alcohol abstinence.
Mocelin and colleagues have found (in an animal model) that NAC reduces behavioural changes and oxidative stress caused by excess alcohol intake and can be used to prevent hangovers.
DeltaFosB is a transcription factor- a protein that controls gene expression. It contributes to addiction by regulating genes that affect the brain reward pathways. Brain rewarding system is a part of the brain that elicits a rewarding feeling in response to addictive drugs.
N-acetylcysteine is found to regulate DeltaFosB levels in the brain to block alcohol-induced behavioural changes and abort alcohol abuse.
Review of studies exploring the effect of N-acetylcysteine on substance abuse disorders reported that ‘NAC is superior to placebo for reducing craving in substance abuse. It’s safety profile, tolerability and easy availability as OTC medication makes it a potential therapeutic agent for addictive disorders.’ (The American Journal on Addictions, 2017)
Researchers from Medical University of South Carolina, US have demonstrated via an fMRI study (an imaging technique used to scan the brain), that NAC treatment actually restructures the brain’s reward processing pathways and promotes smoking abstinence in humans.
Squeglia et al. state that this ‘anti-addiction’ activity of N-acetylcysteine may not be limited to substance abuse alone; it may reduce dependence on other addictive substances. In their study, marijuana-dependent adolescents were treated with 1200mg NAC twice daily for eight weeks.
During marijuana cessation, the patient may develop a compensatory mechanism and hence consume excess alcohol.
Interestingly, NAC prevented compensatory alcohol use during marijuana treatment. NAC lowered use of both marijuana and alcohol.
Recently they confirmed that NAC treatment reduces alcohol consumption by 30% in individuals seeking treatment for cannabis use disorder. Individuals treated with NAC had increased chances of remaining abstinent, consumed fewer drinks per week and had fewer drinking days per week.
These findings are suggesting that N-acetylcysteine can help in reducing alcohol addiction. Further research in a population that is only seeking treatment for Alcohol use disorder (without including other substance use disorders) is needed to understand the dosage and effects.
Quick Gist: Animal studies have confirmed that N-acetylcysteine prevents hangovers, reduces alcohol addiction and maintains abstinence.
Studies investigating its action in substance use disorders have confirmed that NAC can reduce cravings in alcohol-dependent individuals. Also it reduces compensatory alcohol use in patients being treated for cannabis and marijuana use disorders.
The evidence is promising, and further research focused exclusively on NAC’s benefits on alcohol use disorders is warranted.
2.It can help reduce alcohol withdrawal symptoms
Alcohol withdrawal syndrome is a group of symptoms occurring as a result of sudden alcohol cessation. Symptoms include anxiety, hallucinations, tremors, seizures and delirium tremens.
A few animal studies have explored the effect of NAC on alcohol withdrawal symptoms. Schneider et al. demonstrated that NAC treatment after alcohol cessation helps reduce both behavioural and biochemical changes occurring during alcohol withdrawal.
Excessive alcohol intake can affect fat metabolism and cause dyslipidemia (abnormal levels of lipid in the blood) and liver dysfunction. Alcohol abstinence helps restore these parameters back to normal but adding N-acetylcysteine to the treatment regime helps potentiate this effect.
N-acetylcysteine rectifies abnormalities in fat metabolism caused by alcoholism and relieves oxidative damage in the liver.
Researchers are exploring the influence of genetic factors on alcohol dependence and withdrawal. Walter and colleagues conducted the first ‘Weighted Gene Co-expression Network Analysis using reciprocal congenic models’ to study genetic influences on alcohol withdrawal.
This is a systems biology method that studies molecular networks or pathway to understand genomic data. The researchers detected genetic patterns that were limited to one or common in two genetic backgrounds (those who prefer and those who avoid alcohol) and tried to understand how these patterns could predict alcohol withdrawal severity.
The patterns contained genes related to oxidative phosphorylation which a process involved in the production of ATP or cellular energy. It is involved in maintaining the prooxidant/antioxidant balance in the body. Oxidative phosphorylation takes place in the mitochondria -powerhouse of our cells.
This implied that disturbances in oxidative phosphorylation are linked with alcohol use disorders and alcohol withdrawals.
The researchers decided to test these findings by treating animal models with NAC, a strong antioxidant that targets mitochondrial activity. NAC successfully reduced convulsions and alcohol withdrawal symptoms in the animal model.
This suggests that oxidative stress caused by alcohol consumption and cessation can have significant adverse effects on health and contribute to alcohol withdrawal symptoms. NAC’s antioxidant activity can help mitigate these symptoms.
Quick Gist: Studies in animal models suggest that NAC can help treat alcohol withdrawal symptoms. Genetic studies reveal that high levels of oxidative stress can influence the severity of alcohol withdrawal and treatment with NAC can help fight oxidative damage.
Also, NAC treats alcohol-induced abnormalities in lipid levels and restores liver function and antioxidant status.
3.It protects from alcohol-induced toxicity
Accumulation of metabolites derived from alcohol and oxidative stress contributes to alcohol-induced toxicity. Excessive alcohol consumption is highly associated with liver dysfunction and can lead to fatty liver disease, alcoholic hepatitis and alcoholic cirrhosis.
Excessive alcohol intake can cause oxidative stress in the heart tissue and impact its energy metabolism. N-acetylcysteine prevents such negative changes occurring in heart-related energy metabolism and can protect from alcoholic heart disease in both alcoholic and abstinent conditions.
N-acetylcysteine also protects from alcohol-induced gastric injury.
Alcohol exposure can impair bone metabolism and weaken bone health, thus increasing the risk of bone fractures. In an animal model, N-acetylcysteine treatment is found to improve bone strength and accelerate repair under conditions similar to that of binge drinking.
Excessive alcohol intake can have negative effects on the respiratory system as well. Acute respiratory distress syndrome is a severe lung condition, and alcohol abuse increases the risk of developing ARDS by 3.6-fold. There is a high risk of developing sepsis in ARDS.
Tang et al. have shown that dietary NAC attenuates acute lung injury and fights lung infections. Similarly, N-acetylcysteine also protects from alcohol-induced ciliary dysfunction (a condition where hair like structure (cilia) present in the respiratory tract are damaged by excess alcohol) by exerting its antioxidant action.
Quick Gist: N-acetylcysteine’s antioxidant property, ability to scavenge free radical species and restore antioxidant status makes it a potential detoxifying agent.
Pre-clinical studies demonstrate that it can protect various organs from alcohol-induced toxicity.
4.It helps as an antioxidant and anti-inflammatory agent
Animal studies suggest that N-acetylcysteine protects from alcohol-induced oxidative damage by serving as a free radical scavenger and influencing antioxidant enzymes and liver enzymes.
Consumption of oxidised polyunsaturated fatty acids (thermally oxidised dietary fats) with alcohol can increase alcohol-induced oxidative damage and NAC is found to combat such oxidative damage.
Rushworth and Megson state that N-acetylcysteine should not be considered as a strong antioxidant by itself as it only replete glutathione in cells deficient in the enzyme and not cells that already have glutathione. What they intend to say is that certain pre-requisites predict NAC’s effectiveness as an antioxidant.
Nevertheless, NAC serves as an antioxidant precursor and helps fight oxidative damage caused by excess alcohol consumption.
Inflammation in the brain caused by excess alcohol intake is found to influence craving and relapse in alcohol-dependent individuals. A recent study published in Neurochemical Research, 2017 revealed that NAC treatment along with alcohol abstinence counteracts neuroinflammation induced by chronic alcohol intake.
NAC lowered pro-inflammatory agents and increased anti-inflammatory agents in parts of the brain; this may help during alcohol detoxification and withdrawal.
Curcumin is one of the active ingredients present in turmeric and turmeric helps in alcohol detoxification. Research suggests that the combination of curcumin and NAC helps lower the levels of pro-inflammatory agents which were induced by alcohol toxicity.
Quick Gist: N-acetylcysteine serves as an antioxidant precursor and anti-inflammatory agent. It helps lower oxidative damage and brain inflammation caused by excess alcohol intake. It may assist in alcohol detoxification and withdrawal.
5.N-acetylcysteine can protect mental health and cognition in alcohol addiction
NAC’s ability to regulate brain chemistry and strengthen antioxidant defences in the brain makes it a potential neuroprotective agent.
The co-occurrence of psychiatric or mental health conditions can complicate alcohol addiction treatment. Rarely do individuals with mental health issues tell the doctor that they also have a drinking problem.
Current research highlights that indeed NAC is rising as a potential therapeutic agent for psychiatric conditions.
Back and colleagues have found NAC and psychotherapy useful for treating individuals with co-occurring post-traumatic stress disorder and substance use disorder. An 8-week therapy with NAC and cognitive behavioural therapy helped relieve PTSD symptoms, depressive symptoms and reduced cravings.
Bernado et al. also reported that NAC had ‘little effect’ on reducing substance use in bipolar disorder patients. These studies demonstrate the potential of NAC for treating alcohol use disorder co-occurring with other mental health conditions but more research is required to corroborate these findings.
Patients with alcohol addiction frequently report depressive symptoms, especially during withdrawal. One reason for this is that the precursor to happy hormone serotonin-tryptophan metabolism is disturbed in alcoholism.
N-acetylcysteine is proven to reduced depressive symptoms and is well tolerated in individuals with mental health conditions (The Journal of Clinical Psychiatry, 2016).
N-acetylcysteine’s cognition modulating effect may also help protect from and prevent alcohol-induced cognitive deficits.
Quick Gist: Alcohol addiction can severely impair mental health. Mental health conditions may coexist with active alcohol dependence, and this can complicate the treatment.
N-acetylcysteine may be useful in treating co-occurring psychiatric conditions and alcohol use disorder. It may help reduce depressive symptoms in patients and protect cognition.
6.It can benefit in alcohol-induced peripheral neuropathy
One preliminary study shows that NAC can help relieve nerve pain and protect mental health in patients experiencing chronic neuropathic pain.
To explore this therapeutic action in detail, please check my post on potential benefits of N-acetylcysteine for neuropathy.
Quick Gist: N-acetylcysteine benefits in peripheral neuropathy as a unique antioxidant. It increases the level of glutathione, a vital antioxidant that protects the nervous system.
It regulates neurotransmitter levels, reduces inflammation and exerts an antioxidant action to reduce nerve pain. It may help as add-on therapy, but further research in humans is required.
Dosage of N-acetylcysteine For Alcoholism
Two human studies have used a dose of 1200mg N-acetylcysteine 1-2 times a day for substance abuse disorders and simultaneous alcohol use.  Further research is required to confirm the safe and effective dose of NAC for alcohol addiction alone.
High dose NAC can have side effects; the dose range of 2-2.4g/day is safe and effective in most conditions.
Start with a small dose and increase gradually to identify a dose that suits you. NAC aids in detoxing; to avoid distressing detoxing symptoms start with small doses and increase gradually over weeks.
Please consult a health practitioner before taking N-acetylcysteine supplements to ascertain the dosage, duration of therapy and to mitigate possible drug interactions.
Precautions with N-acetylcysteine Use
Oral NAC is safe for use within recommended doses. The most common side effects are gastric side effects like abdominal pain, heartburn, flatulence, cramps, nausea, vomiting and diarrhoea. Individuals with peptic ulcer should avoid it.
- A headache
- Tingling sensations in the hand
- Body rash
- Elevated blood pressure
- dry mouth
- vivid dreams
- running nose, nasal congestion
- muscle pain
- The occurrence of cold sores, neutropenia with a high dose of NAC (6g/day)
- A case of sensorineural hearing loss (3g NAC per day)
- Pulmonary hypertension
- Seizures and allergic reactions with intravenous NAC not oral
NAC may have drug interactions with anti-cancer agents, paracetamol, nitroglycerin and related medicines and should be taken with caution in such cases.
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. Also if a new unopened bottle already emits the odour, it is quite likely that the supplement has oxidised or degraded.
It is a powerful antioxidant; avoid using any other antioxidant (herbal/natural) along with it or reduce the dosage.
Please consult a health practitioner before taking N-acetylcysteine supplements.
Dysfunction of the glutaminergic system (glutamine is a neurotransmitter) plays an important role in alcohol addiction, withdrawal and relapse. N-acetylcysteine helps restore the function of the glutaminergic system back to normal.
Thus it is found to be useful in treating substance use disorders, and this property can be applied to alcoholism treatment.
Additionally, NAC serves as an antioxidant precursor to the primary antioxidant- glutathione. This helps fight alcohol-induced toxicity and may also aid in mitigating alcohol withdrawal symptoms.
It can also help lower depressive symptoms and cognitive deficits in alcohol-dependent individuals.
Most studies have explored the therapeutic action of NAC in substance use disorders or in comorbid conditions that involve alcohol abuse. An exclusive study that focuses on NAC treatment solely for alcohol addiction and withdrawal is still awaited.
Based on the evidence available to date, it is safe to say that N-acetylcysteine helps in alcoholism treatment. Since alcohol addiction and withdrawal is a complicated process, please consult your doctor before taking NAC supplements.