NAC Side Effects: Who Should Avoid It and What Not to Mix With It

In studies giving NAC for more than six weeks, abdominal pain, nausea and vomiting, diarrhoea and joint pain were 1.4 to 2.2 times more frequent with NAC; the allergy-like reactions a review describes belong to the hospital drip. NICE lists asthma and a history of stomach ulcers as cautions, nitrate angina medicines interact, and Dutch assessors advise against adding a supplement to a NAC medicine.^{1, 2, 3, 4, 5, 6, 7} NAC (N-acetylcysteine) is acetylcysteine, a licensed UK medicine that the NHS lists as a second mucolytic for COPD, and it is also sold as a food supplement.⁸ For the background, see what NAC is and the Wellgard glutathione guide.

Evidence at a glance

• Trials: 83 studies longer than six weeks (9,988 people) pooled for side effects; a review of 41 respiratory studies at 600 to 3,000 mg a day.
• Largest trial: 1,006 people with COPD, 600 mg twice a day for a year, manufacturer-funded; adverse events 29% on NAC, 26% on placebo.
• Strongest measured outcome: abdominal pain, nausea and vomiting, diarrhoea and joint pain 1.4 to 2.2 times more frequent with NAC, pooled.
• Not tested: NAC in an ordinary pregnancy or in breastfeeding; tumour growth in people; morning against evening doses.

Sources checked on 13 October 2026.

What are the side effects of NAC?

Pooled across 83 studies in which 9,988 people took NAC for more than six weeks, abdominal pain, nausea and vomiting, diarrhoea and joint pain were 1.4 to 2.2 times more frequent.¹ A manufacturer-sponsored review of 41 respiratory studies at 600 to 3,000 mg a day read it differently: stomach symptoms were "no more common than in the control group".⁹

The NICE formulary lists the uncommon side effects of acetylcysteine by mouth as diarrhoea, fever, stomach discomfort, headache, low blood pressure, nausea, a sore mouth, tinnitus and vomiting; bleeding is rare, and face swelling has no known frequency.³ Constipation and sleep problems are not on the list. The hospital drip, given for paracetamol overdose, is a different question: its reactions resemble allergy, with rash, itching, swelling and wheeze, and women and people with asthma or allergies are "particularly susceptible".²

Is it safe to take NAC every day?

The longest trial cited here gave 523 people with COPD 600 mg a day for three years; its abstract reports effectiveness, not side effects.¹⁰ In a one-year, manufacturer-funded trial of 1,006 people on 600 mg twice a day, 29% on NAC and 26% on placebo reported adverse events.¹¹ The manufacturer-sponsored review found the safety profile "similar at both the high and standard doses", and the licensed long-term dose by mouth is 600 mg a day.⁹ These were patients, not supplement users: a pharmacist can check daily use against your medicines.

Who should not take NAC?

NICE lists two cautions for acetylcysteine by mouth: "Asthma; history of peptic ulceration".³ The 2009 review's asthma signal comes from the drip.²

• Pregnancy and breastfeeding. Three small trials gave NAC in pregnancy, to 22 to 51 women with an infection around the baby, pre-eclampsia or a risk of early birth, under specialist care; none studied an ordinary pregnancy or breastfeeding, and a 1991 review found no data on placenta or breast milk.^{12, 13, 14, 15} Ask a midwife, GP or pharmacist.
• Children under two. Dutch assessors advise against NAC supplements; the medicine is contraindicated at this age.⁷
• Anyone prescribed acetylcysteine. The same assessors advise against adding a supplement, "as people may take too much".⁷
• Severe liver or kidney disease, histamine intolerance or cystinuria. The assessment notes side effects may be more likely with the first two and advises caution or a doctor's advice for the others.⁷
• Anyone with cancer, or in cancer care. Mouse studies found that NAC sped the growth or spread of tumours; this has not been studied in people, so ask your cancer team first.^{16, 17, 18}

What should you not mix with NAC?

Nitrate angina medicines are the interaction with trial evidence. In 11 healthy volunteers, NAC raised the median headache score after a nitrate infusion from 1 to 3; in a four-month trial of 200 people with unstable angina, intolerable headache on the combination was almost twice as frequent as on the nitrate alone; and with both given by drip, 7 of 24 patients had symptomatic low blood pressure against none of 22.^{4, 5, 6} If you use a nitrate spray, tablet or patch, ask a pharmacist first.

We found no trial reporting a problem when NAC was taken with vitamin C, vitamin D, zinc, magnesium or coffee. For glutathione itself, see glutathione side effects.

Does NAC deplete minerals?

In the one small study we found, 10 healthy volunteers took 200 mg three times a day for two weeks, and blood levels and urine losses of calcium, magnesium, iron, zinc and copper did not change.¹⁹

Is NAC hard on the liver?

Its liver uses are hospital treatments by drip: acetylcysteine is the antidote for paracetamol overdose.³ By mouth, in an eight-week trial of 69 people with fatty liver taking 600 mg three times a day, liver enzymes did not differ from placebo.²⁰ None of the trials cited here reported liver harm from NAC by mouth, and a liver condition is a GP question. If you have taken more paracetamol than the packet says, the NHS says to "get help from NHS 111".²¹ How NAC relates to glutathione is on NAC vs glutathione.

How much NAC is too much?

Trials used 600 to 3,000 mg a day as a medicine; ask a pharmacist, especially if you take a NAC medicine.⁹ In a three-month lupus trial of 36 people, everyone tolerated up to 2.4 g a day, while a third of those on 4.8 g had nausea that cleared.²² A 2024 Dutch government safety assessment set the upper level for adults at 1,200 mg of NAC a day from supplements, with gut symptoms possible above it, and notes that in many EU countries NAC has "dual status", medicine and food supplement.⁷ We found no UK upper level. Most deaths on record followed dosing errors with the medicine.²

What we don't know

• How NAC affects an ordinary pregnancy or breastfeeding: the trials enrolled women with complications.^{12, 13, 14}
• Whether the mouse tumour findings apply to people: we found no human study.¹⁶
• Whether timing matters: the long trials gave NAC once or twice a day and none compared morning with evening.^{10, 11}
• How NAC behaves with most medicines: we found no trial with carbamazepine, antibiotics or blood thinners.⁷
• Whether women react differently to NAC by mouth, as the drip review found for the drip.²

Frequently asked questions

What happens if you take NAC every day?

People with COPD have taken it daily for up to three years in trials.¹⁰ In the one-year trial, 29% on NAC and 26% on placebo reported adverse events; pooled across 83 longer studies, stomach effects and joint pain were more frequent with NAC.^{11, 1}

Does NAC cause cancer?

Mouse studies found that NAC sped the growth or spread of existing tumours, and in one, lung tumours appeared in 10% of older mice given it long term; this has not been studied in people.^{16, 17, 18} The studies tested NAC, not glutathione. Anyone with cancer, or in cancer care, should ask their cancer team first.

Can you take NAC in pregnancy or when breastfeeding?

We found no trial of NAC in an ordinary pregnancy or in breastfeeding; the three small pregnancy trials enrolled women with complications under specialist care.^{12, 13, 14} Ask a midwife, GP or pharmacist first.

When is the best time to take NAC, morning or night?

We found no trial comparing morning with evening doses; the medicine trials gave it once or twice a day.^{10, 11} Sleep problems are not on the NICE side-effect list.³

Can NAC cause headaches or low blood pressure?

Both are uncommon side effects of acetylcysteine by mouth in the NICE list.³ Both were also seen when NAC was combined with nitrate angina medicines, so anyone using a nitrate should ask a pharmacist first.^{4, 5, 6}

Sources

1. Kranzer K et al. Thorax 2015. Pooled analysis, 83 studies, 9,988 people. PubMed 26347391
2. Sandilands EA, Bateman DN. Clinical Toxicology 2009. Systematic review. PubMed 19280424
3. NICE British National Formulary. Acetylcysteine. No review date shown; read 13 October 2026. nice.org.uk
4. Iversen HK. Clinical Pharmacology and Therapeutics 1992. Crossover trial, 11 volunteers; funding not checked. PubMed 1505148
5. Ardissino D et al. Journal of the American College of Cardiology 1997. Randomised trial, 200 people, four months. PubMed 9120179
6. Horowitz JD et al. Circulation 1988. Double-blind trial, 46 people; funding not checked. PubMed 3127076
7. RIVM. Risk assessment of food supplements containing N-acetylcysteine (NAC). Dutch government safety assessment, 2024. doi.org
8. NHS. COPD: treatment. Page last reviewed 11 April 2023 (review overdue). nhs.uk
9. Calverley P et al. Drug Safety 2021. Review of 41 studies; sponsored by a NAC manufacturer. PubMed 33326056
10. Decramer M et al. Lancet 2005. Randomised trial, 523 people, three years. PubMed 15866309
11. Zheng JP et al. Lancet Respiratory Medicine 2014. Randomised trial, 1,006 people, one year; manufacturer-funded. PubMed 24621680
12. Küster A et al. Pediatric Research 2026. Randomised pilot trial, 39 women. PubMed 42177307
13. Silva DAVD et al. Pharmaceuticals 2026. Randomised pilot trial, 51 women. PubMed 42797390
14. Jenkins DD et al. Journal of Pediatrics 2016. Randomised trial, 22 women. PubMed 26545726
15. Holdiness MR. Clinical Pharmacokinetics 1991. Pharmacokinetic review. PubMed 2029805
16. Sayin VI et al. Science Translational Medicine 2014. Mouse study. PubMed 24477002
17. Le Gal K et al. Science Translational Medicine 2015. Mouse study. PubMed 26446958
18. Breau M et al. JCI Insight 2019. Mouse study. PubMed 31578304
19. Hjortsø E et al. European Journal of Clinical Pharmacology 1990. Uncontrolled study, 10 volunteers, two weeks; funding not checked. PubMed 2276385
20. Sinaeinejad M et al. Addiction and Health 2025. Randomised trial, 69 people, eight weeks; no funding declared. PubMed 41431629
21. NHS. How and when to take paracetamol for adults. Page last reviewed 24 March 2026. nhs.uk
22. Lai ZW et al. Arthritis and Rheumatism 2012. Randomised trial, 36 people, three months; government and charity funded. PubMed 22549432

Spotted something out of date? Email support@wellgard.co.uk with the page address and the sentence.