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NAC

N-acetylated derivative of L-cysteine. Serves as a glutathione precursor. Half-life approximately 5.6 hours.

Strong Evidence
~5.6 h
Half-Life
9%
Bioavailability
600–1200 mg/day
Typical Dose
Oral
Routes

Overview

NAC is tracked as a supplement in Milligram's compound library. N-acetylated derivative of L-cysteine.

With a half-life of ~5.6 hours, NAC requires daily administration in most observed protocols. Taken orally, it has a bioavailability of approximately 9% via its primary route.

Serves as a glutathione precursor. Half-life approximately 5.6 hours. Low oral bioavailability (~9%) due to extensive first-pass metabolism. One-compartment model.

Mechanism of Action

NAC's pharmacological activity involves the following key pathways:

Primary Mechanism

NAC exerts its effects through its established pharmacological pathway. Its mechanism has been characterized in published research.

Antioxidant Activity

NAC supports the body's antioxidant defense systems, contributing to cellular protection from oxidative stress.

Pharmacokinetics

Parameter Value
Half-Life ~5.6 hours
Bioavailability ~9%
Time to Peak ~2 hours
Duration of Activity ~12 hours
Routes Oral

Dosing Protocols

The following protocols represent commonly observed dosing patterns. These are observational summaries, not recommendations.

Standard Protocol
Dose 600 mg/day
Route Oral
Frequency 2-3 times daily
Duration Ongoing
Higher-Dose Protocol
Dose 1200 mg/day
Route Oral
Frequency 2-3 times daily
Duration Ongoing

Frequently Asked Questions

What is NAC and how does it work?
NAC (N-Acetyl Cysteine) is a semi-essential amino acid derivative that serves as the rate-limiting precursor to glutathione, the body's most abundant intracellular antioxidant. Once absorbed, NAC is deacetylated to L-cysteine, which combines with glutamate and glycine to form glutathione (GSH). It also directly scavenges reactive oxygen species and modulates inflammatory pathways via NF-kB regulation.
What is the half-life and bioavailability of NAC?
Oral NAC has a terminal half-life of approximately 6.25 hours. Absolute oral bioavailability is low, ranging from 6–10% due to extensive first-pass metabolism in the gut wall and liver. Peak plasma concentrations are typically reached within 1–2 hours after ingestion. Despite the low bioavailability, oral dosing is sufficient to significantly elevate intracellular glutathione levels.
Is NAC good for liver support?
NAC is the standard clinical treatment for acetaminophen (paracetamol) overdose due to its ability to rapidly replenish hepatic glutathione stores. At supplemental doses of 600–1200 mg/day, NAC supports glutathione synthesis in the liver, which is central to phase II detoxification pathways. It is commonly used alongside hepatotoxic compounds in community protocols to support liver enzyme markers.
Can NAC be taken on an empty stomach?
NAC is commonly taken on an empty stomach as food can reduce its absorption. However, some individuals report mild nausea or gastrointestinal discomfort when taking NAC without food, particularly at higher doses. In clinical studies, doses of 600–1200 mg/day were generally well-tolerated regardless of timing. Starting with a lower dose taken with food and gradually increasing is a commonly observed approach.
How long does it take for NAC to raise glutathione levels?
Intracellular glutathione levels begin increasing within hours of the first dose, reflecting NAC's role as a direct cysteine donor. However, measurable improvements in oxidative stress biomarkers and liver enzyme panels are typically observed over 4–8 weeks of consistent supplementation. The relatively short 6-hour half-life means daily dosing is important for sustained glutathione support.
What are the side effects of NAC?
The most commonly reported effects at supplemental doses include mild nausea, diarrhea, and a sulfurous taste or odor due to the compound's thiol group. These are generally dose-dependent and more common above 1200 mg/day. NAC has a strong safety profile across decades of clinical use at doses up to 1800 mg/day. Splitting the daily dose into two administrations is commonly observed to reduce GI effects.

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