Can N-acetylcysteine (NAC) cause fatigue?

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Last updated: April 2, 2025View editorial policy

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From the Guidelines

N-acetylcysteine (NAC) can cause fatigue or tiredness in some individuals, although the provided evidence does not directly address this side effect. The studies focused on the use of NAC in patients with chronic obstructive pulmonary disease (COPD) and its effectiveness in reducing exacerbations 1. However, it is essential to consider that NAC is generally well-tolerated, with rare adverse effects, mostly gastrointestinal in nature 1. When considering the potential for NAC to cause tiredness, it is crucial to weigh this against the benefits of NAC in reducing COPD exacerbations, as demonstrated in studies such as the one by Zheng et al, which showed a significant reduction in exacerbation rates 1. Key points to consider:

  • NAC is used for its mucolytic properties in COPD patients.
  • The provided studies do not directly mention fatigue as a side effect but highlight the drug's tolerability.
  • Typical considerations for managing potential side effects like fatigue include adjusting dosage or timing of supplementation.
  • The mechanism of potential NAC-induced fatigue is not well understood but may relate to its effects on glutathione and neurotransmitter activity.
  • If significant tiredness occurs, consulting a healthcare provider is recommended to assess the appropriateness of NAC supplementation or the need for dosage adjustments.

From the FDA Drug Label

ADVERSE REACTIONS Adverse effects have included ... drowsiness...

  • Drowsiness is listed as an adverse effect of N-Acetylcysteine (NAC).
  • Tiredness is not explicitly mentioned, but drowsiness can be related to feeling tired. NAC can potentially make you feel tired, as it can cause drowsiness 2.

From the Research

NAC and Fatigue

  • The effect of NAC on fatigue is not consistently reported across studies.
  • One study found that oral NAC can extend time to fatigue (TTF) at 80% of peak power output, but not at higher work rates 3.
  • Another study reviewed the clinical usefulness of NAC as a treatment or adjunctive therapy in various medical conditions, including chronic diseases, but did not specifically address fatigue 4.
  • A narrative review of vitamins and minerals for energy, fatigue, and cognition discussed the importance of micronutrients in energy-yielding metabolism and neuronal functions, but did not focus on NAC specifically 5.
  • There is no direct evidence from the provided studies that NAC can cause tiredness, but the relationship between NAC and fatigue may depend on the specific context, such as exercise intensity or medical condition 6, 3, 4, 7.

Safety Profile of NAC

  • A review of the safety profile of NAC at high doses in chronic respiratory diseases found that the safety profile was similar to that of standard doses, with gastrointestinal symptoms reported but no more common than in the control group 6.
  • Another study discussed the medical and dietary uses of NAC, noting that it is considered a safe substance, but results among clinical trials can be controversial or incomplete 7.

Potential Mechanisms of Action

  • NAC may have various mechanisms of action, including antioxidant effects, which could influence its impact on fatigue and other conditions 4, 7.
  • However, the exact relationship between NAC and fatigue is not fully understood and may require further research to elucidate 3, 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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