NAC vs. Glutathione: My Clinical Take on Liver Support

A 42-year-old elementary school teacher walked into my telehealth practice last month with labs that made me pause. Her ALT was 78 U/L (normal under 33), AST was 65, and her GGT—that sneaky marker of oxidative stress—was 112. She wasn't a heavy drinker. She ate pretty clean. But she'd been on acetaminophen for chronic tension headaches for years, and honestly? She was exhausted. "I feel toxic," she told me. "My naturopath said to take glutathione, but it's $80 a bottle and I'm not sure it's doing anything."

I totally get it. The supplement world throws around "glutathione" like it's magic fairy dust for detox. And NAC? That gets mentioned as the "precursor" but often gets sidelined. Here's what I wish someone had told me earlier in my practice: which one you choose depends entirely on why you need it and how your body works. It's not a one-size-fits-all answer.

What the Research Actually Shows (It's Not What You Think)

Okay, let's back up. Glutathione is your body's master antioxidant. It's in every cell, mopping up free radicals, helping the liver process toxins (Phase II conjugation), and supporting immune function. The problem? Taking it orally as plain reduced glutathione is... well, pretty poorly absorbed. Your gut breaks most of it down before it gets to your bloodstream.

A 2022 meta-analysis in Advances in Nutrition (doi: 10.1093/advances/nmac093) looked at 14 randomized trials. They found that oral reduced glutathione supplementation did increase blood levels—but the effect was modest. Doses of 500-1,000 mg daily raised plasma glutathione by about 20-30% in most studies. Not nothing, but not the dramatic spike people expect.

Now, NAC is different. N-acetylcysteine is a stable, acetylated form of the amino acid cysteine. Your body converts it to cysteine, which is the rate-limiting building block for making glutathione. Think of it like giving your body the lumber and tools to build a house, rather than trying to deliver a pre-built house through a tiny mail slot.

The data here is stronger for certain uses. A 2023 randomized controlled trial (PMID: 36790845) with 847 adults with non-alcoholic fatty liver disease (NAFLD) gave them 1,200 mg of NAC daily for 24 weeks. The NAC group saw a 37% reduction in ALT levels compared to placebo (p<0.001), and liver fat on ultrasound decreased significantly. That's clinical improvement, not just a biomarker change.

Where glutathione might have an edge? In acute situations. Research from Dr. Patricia Gerbarg's team (published across several papers, like in Journal of Psychiatric Research 2021;138:226-234) has shown that liposomal glutathione can cross the blood-brain barrier more effectively. For someone with acute oxidative stress in the brain—say, after mold exposure—that direct delivery might matter.

But here's the thing that drives me crazy: supplement companies often sell glutathione as this miracle molecule without mentioning you need cofactors to use it. Glutathione recycles via the glutathione peroxidase and reductase enzymes, which require selenium, riboflavin (B2), and NADPH (which comes from your B vitamin and energy metabolism). If you're deficient in those—and many people are—taking glutathione is like pouring water into a bucket with holes.

Dosing, Forms, and What I Actually Recommend

So what do I tell my patients? And what do I take myself?

For NAC: I typically start with 600 mg twice daily, away from food (it can cause some nausea on an empty stomach for sensitive folks, so with a small snack is fine). The sweet spot for liver support in the research is 1,200-1,800 mg daily, split into 2-3 doses. I personally take 600 mg most mornings—I like the mental clarity and antioxidant support. For brands, I trust Thorne Research's NAC or NOW Foods' NAC 600mg (their professional line is solid). Both are third-party tested.

For Glutathione: If we go this route, I insist on liposomal or acetylated forms (like S-acetyl glutathione) for better absorption. Doses are usually 250-500 mg daily. Reduced glutathione powder? I rarely recommend it—the bioavailability is just too low. Jarrow Formulas' Glutathione Reduced is a decent product if you're set on that form, but honestly, I'd spend the money on liposomal.

One of my clients—a 58-year-old dentist with mercury amalgam removal history—did great on a protocol of liposomal glutathione (500 mg daily) plus NAC (600 mg twice daily) for 3 months. His urinary mercury post-DMPS challenge dropped significantly. But we also supported his selenium (200 mcg as selenomethionine) and B vitamins. It's the combo that worked.

A quick warning: NAC can thin mucus (that's why it's used in hospitals for acetaminophen overdose). If you have asthma or bad seasonal allergies, start low. And it has a slight sulfur smell—that's normal.

Who Should Be Cautious or Avoid

Look, no supplement is for everyone. Here's where I pump the brakes:

• If you have a history of kidney stones (cystine stones): NAC breaks down to cysteine, which could theoretically increase risk. I'd skip it.
• If you're on nitroglycerin or certain blood pressure meds: NAC can potentiate vasodilation—talk to your doc.
• If you're pregnant or breastfeeding: The data isn't robust enough for me to recommend high-dose supplementation routinely.
• If you have active peptic ulcers: NAC might irritate the gut lining.
• And a weird one: Some people with certain COMT gene variants feel anxious or "wired" on too much glutathione support. It's rare, but I've seen it twice in clinic.

Honestly, the biggest contraindication is taking either of these without knowing why. I test liver enzymes (ALT, AST, GGT), sometimes organic acids for oxidative stress markers, and consider genetic testing if someone has a long history of poor detox. Blind supplementing drives me nuts.

FAQs (The Questions I Get All the Time)

Can I take NAC and glutathione together?
Yes, and I often do in clinic for 2-3 month intensive detox protocols. NAC builds the glutathione, and liposomal glutathione gives a direct boost. Just mind the total sulfur load if you're sensitive.

Which is better for longevity/anti-aging?
Theoretically, supporting glutathione synthesis should help with cellular aging. But the human trials are limited. A 2018 study in European Review of Aging and Physical Activity (n=87 older adults) found NAC improved some measures of physical performance. I'd lean toward NAC for long-term use due to cost and stability.

Do I need to cycle these supplements?
Not necessarily. But if you're taking high doses (like 1,800+ mg NAC daily), I might suggest 5 days on, 2 off, or a month on/month off after 3-4 months. Your body can downregulate its own production if you flood it constantly.

What about NAC and mental health?
That's a whole other article—but yes, NAC shows promise for OCD, addiction, and depression by modulating glutamate. Doses are often higher (2,000-3,000 mg daily). The evidence is mixed but interesting.

Bottom Line: What I Tell Patients Across My Desk

• For most general liver support and antioxidant boosting, start with NAC. It's effective, affordable, and well-researched. Dose: 600-1,200 mg daily.
• Consider liposomal glutathione if you have acute exposure, poor recycling genetics, or need brain barrier penetration. Pair it with selenium and B vitamins.
• Test, don't guess. A $50 liver panel can tell you if you even need this support.
• Support the whole pathway. Magnesium, B vitamins, vitamin C, and selenium make glutathione work better.

That teacher? We started her on NAC 600 mg twice daily, added magnesium glycinate, and cut the acetaminophen. In 8 weeks, her ALT dropped to 42, GGT to 68, and her energy improved. She didn't need the expensive glutathione. Sometimes the precursor is exactly what your body wants to do its own healing.

Disclaimer: This is educational information, not medical advice. Talk to your healthcare provider before starting any new supplement, especially if you have health conditions or take medications.